Ofev 100 mg mehke kapsule, Ofev 150 mg mehke kapsule Kakovostna in kolicinska sestava: Ena kapsula vsebuje 100 mg (150 mg) nintedaniba (v obliki esilata). Vsebuje sojin lecitin. Terapevtske indikacije: Za zdravljenje odraslih bolnikov z idiopatsko pljucno . brozo (IPF). Za zdravljenje odraslih bolnikov z drugimi kronicnimi .brozirajocimi intersticijskimi pljucnimi boleznimi (ILD) s progresivnim fenotipom. Za zdravljenje odraslih bolnikov z intersticijsko pljucno boleznijo, povezano s sistemsko sklerozo (SSc-ILD). Odmerjanje in nacin uporabe: Zdravljenje mora uvesti zdravnik, ki ima izkušnje z obvladovanjem bolezni, za katere je zdravilo odobreno. Odmerjanje: Priporoceni odmerek je 150 mg nintedaniba dvakrat na dan, ki ga je treba jemati v približno 12urnem razmiku. Odmerek po 100 mg 2x/ dan se priporoca samo za uporabo pri bolnikih, ki ne prenašajo odmerka po 150 mg 2x/ dan. Najvecji priporoceni dnevni odmerek je 300 mg. Prilagajanja odmerka: Poleg simptomatskega zdravljenja, ce je potrebno, lahko obravnava neželenih ucinkov pri zdravilu Ofev vkljucuje zmanjšanje odmerka in zacasno prekinitev, dokler speci.cni neželeni ucinek ne bo izzvenel do ravni, ki omogoca nadaljevanje zdravljenja. Zdravljenje lahko nadaljujete s polnim odmerkom (150 mg 2x/ dan) ali z zmanjšanim odmerkom (100 mg 2x/ dan). Ce bolnik ne prenaša odmerka po 100 mg 2x/ dan, je treba zdravljenje z zdravilom Ofev ukiniti. Ce so driska, navzea in/ali bruhanje še vedno prisotni kljub ustrezni podporni oskrbi (vkljucno z antiemeticnim zdravljenjem), je morda treba odmerek zmanjšati ali zdravljenje prekiniti. Zdravljenje lahko nadaljujete z zmanjšanim odmerkom (100 mg dvakrat na dan) ali s polnim odmerkom (150 mg dvakrat na dan). V primeru, da huda driska, navzea in/ali bruhanje kljub simptomatskemu zdravljenju vztrajajo, je treba zdravljenje z zdravilom Ofev ukiniti. V primeru prekinitev zaradi zvišanja vrednosti AST ali ALT na > 3x zgornjo mejo normalnih vrednosti (ULN), se lahko zdravljenje po vrnitvi vrednosti aminotransferaz na izhodišcno raven nadaljuje z zmanjšanim odmerkom, nato pa se lahko poveca na polni odmerek. Starejši: Verjetneje je, da bodo bolniki, stari 75 let ali vec, potrebovali zmanjšanje odmerka za obvladovanje neželenih ucinkov. Ledvicna okvara: Varnosti, ucinkovitosti in farmakokinetike nintedaniba pri bolnikih s hudo ledvicno okvaro (ocistek kreatinina < 30 ml/min) niso proucevali. Jetrna okvara: Izpostavljenost se je povecala pri bolnikih z jetrno okvaro (Child Pugh A, Child Pugh B). Pri bolnikih z blago jetrno okvaro (Child Pugh A) je priporoceni odmerek 100 mg dvakrat na dan. Zdravljenja bolnikov z zmerno (Child Pugh B) in hudo (Child Pugh C) jetrno okvaro se ne priporoca. Pediatricna populacija: Varnost in ucinkovitost zdravila Ofev pri otrocih, starih 0 do 18 let, nista bili dokazani. Podatkov ni na voljo. Nacin uporabe: Zdravilo Ofev je namenjeno peroralni uporabi. Kapsule je treba zaužiti s hrano, pogoltniti cele z vodo; ne sme se jih žveciti ali drobiti. Kontraindikacije: Nosecnost. Preobcutljivost na nintedanib, arašide ali sojo ali katero koli pomožno snov. Posebna opozorila in previdnostni ukrepi: Driska: V klinicnih preskušanjih je bila driska najpogostejši neželeni ucinek prebavil, o katerem so porocali. Pri vecini bolnikov je bil neželen ucinek blag do zmeren in se je pojavil v prvih 3 mesecih zdravljenja. V obdobju trženja zdravila so porocali o resnih primerih driske s posledicno dehidracijo in elektrolitskimi motnjami. Bolnike je treba zdraviti takoj, ko se pojavijo prvi znaki, vcasih je treba zmanjšati odmerek ali zdravljenje prekiniti. Zdravljenje lahko nadaljujete z zmanjšanim odmerkom ali s polnim odmerkom. Pri trdovratni hudi driski, je treba zdravljenje ukiniti. Navzea in bruhanje: Pogosta neželena ucinka prebavil sta bila navzea in bruhanje. Pri vecini bolnikov z navzeo in bruhanjem je bil dogodek blag do zmeren. Pri trdovratnih simptomih, ki kljub podporni oskrbi ne izginejo, je morda treba odmerek zmanjšati ali zdravljenje prekiniti. Zdravljenje se lahko nadaljuje z zmanjšanim odmerkom ali s polnim odmerkom. Pri trdovratnih simptomih je treba zdravljenje z zdravilom Ofev ukiniti. Delovanje jeter: Zdravljenje za bolnike z zmerno (Child Pugh B) ali hudo (Child Pugh C) jetrno okvaro ni priporocljivo. Na podlagi vecje izpostavljenosti se lahko Literatura: 1. Povzetek glavnih znacilnosti zdravila Ofev® julij 2020 SKRAJŠAN POVZETEK GLAVNIH ZNACILNOSTI ZDRAVILA poveca tudi tveganje za neželene dogodke pri bolnikih z blago jetrno okvaro (Child Pugh A). Bolnike z blago jetrno okvaro je treba zdraviti z nižjim odmerkom. Pri zdravljenju z nintedanibom so opazili poškodbe jeter, povzrocene z zdravilom, vkljucno s hudo poškodbo jeter s smrtnim izidom. Zato je treba pred uvedbo zdravljenja in v prvem mesecu zdravljenja dolociti raven jetrnih aminotransferaz in bilirubina. Bolnike je treba v naslednjih dveh me-secih zdravljenja spremljati v rednih intervalih, nato pa periodicno ali kot je klinicno indicirano. Ce so izmerjene vrednosti aminotransferaz (AST ali ALT) > 3 x ULN, se priporoca zmanjšanje odmerka ali prekinitev zdravljenja, bolnika pa je treba natancno spremljati. Ko se aminotransferaze vrnejo na izhodišcne vrednosti, se lahko zdravljenje nadaljuje s polnim odmerkom ali z zmanjšanim odmerkom, nato pa postopoma zvišuje do polnega odmerka. Ce so zvišane vrednosti jetrnih testov povezane s klinicnimi znaki ali simptomi poškodbe jeter, je treba zdravljenje trajno ukiniti. Raziskati je treba alternativne vzroke za zvecanje jetrnih encimov. Pri bolnikih z majhno telesno maso (<65 kg), bolnikih azijske rase in ženskah obstaja vecje tveganje za povecanje ravni jetrnih encimov. Izpostavljenost nintedanibu se linearno veca z bolnikovo starostjo, kar lahko povzroci vecje tveganje za povecanje ravni jetrnih encimov. Priporocljivo je skrbno spremljanje bolnikov s temi dejavniki tveganja. Delovanje ledvic: pri uporabi nintedaniba so porocali o primerih ledvicne okvare/odpovedi, v nekaterih primerih s smrtnim izidom. Med zdravljenjem je treba bolnike spremljati, posebna pozornost pa je potrebna pri tistih bolnikih, ki imajo dejavnike tveganja za ledvicno okvaro/odpoved. V primeru ledvicne okvare/odpovedi je treba razmisliti o prilagoditvi odmerka. Krvavitev: Zaviranje receptorja vaskularnega endotelijskega rastnega faktorja VEGFR lahko poveca tveganje za krvavitev. V obdobju trženja zdravila so porocali o neresnih in resnih krvavitvah, od katerih je bilo nekaj s smrtnim izidom (vkljucno pri bolnikih, ki niso zdravljeni z antikoagulanti, in tistih, ki so zdravljeni z antikoagulanti ali drugimi zdravili, ki bi lahko povzrocili krvavitve). Bolniki z znanim tveganjem za krvavitve, vkljucno z bolniki z dedno nagnjenostjo h krvavitvam ali tisti, ki so pred zacetkom zdravljenja z zdravilom prejemali polne odmerke antikoagulantov, niso bili vkljuceni v klinicna preskušanja. Ti bolniki se lahko zdravijo le, ce so pricakovane koristi vecje od možnih tveganj. Arterijski trombembolicni dogodki: Bolniki z miokardnim infarktom ali možgansko kapjo v nedavni anamnezi so bili iz klinicnih preskušanj izkljuceni. Pri zdravljenju bolnikov z vecjim srcnožilnim tveganjem, vkljucno z znano koronarno arterijsko boleznijo, je potrebna previdnost. Ce se pri njih pojavijo znaki ali simptomi akutne miokardne ishemije, je treba razmisliti o prekinitvi zdravljenja. Anevrizme in disekcije arterij: Uporaba zaviralcev poti VEGF pri bolnikih s hipertenzijo ali brez nje lahko spodbudi nastanek anevrizem in/ali disekcij arterij. Pred uvedbo zdravila Ofev je treba to tveganje skrbno preuciti pri bolnikih z dejavniki tveganja, kot sta hipertenzija ali anamneza anevrizme. Venska trombembolija: Zaradi mehanizma delovanja nintedaniba je lahko pri bolnikih tveganje za trombembolicne dogodke vecje. Predrtje prebavil: Zaradi mehanizma delovanja nintedaniba je lahko pri bolnikih tveganje za predrtje prebavil vecje. V obdobju trženja zdravila so porocali o primerih predrtja prebavil, od katerih jih je bilo nekaj s smrtnim izidom. Posebno pozornost je treba name-niti zdravljenju bolnikov s predhodno abdominalno operacijo, pepticno razjedo, divertikular-no boleznijo v anamnezi ali bolnikom, ki socasno jemljejo kortikosteroide ali nesteroidna protivnetna zdravila. Zdravilo Ofev se lahko uvede najmanj 4 tedne po abdominalni opera-ciji. Zdravljenje je treba trajno ukiniti pri bolnikih, pri katerih se pojavi predrtje prebavil. Hipertenzija: Dajanje zdravila Ofev lahko zviša krvni tlak. Sistemski krvni tlak je treba me-riti periodicno in kot je klinicno indicirano. Pljucna hipertenzija: Podatkov o uporabi zdravi-la Ofev pri bolnikih s pljucno hipertenzijo je malo. Bolniki z resno pljucno hipertenzijo (srcni indeks = 2 l/min/m˛ ali parenteralni epoprostenol/treprostinil ali resna odpoved desnega prekata) so bili izkljuceni iz preskušanjINBUILD in SENSCIS. Zdravila Ofev se ne sme uporabljati pri bolnikih s hudo pljucno hipertenzijo. Pri bolnikih z blago do zmerno pljucno hi-pertenzijo se priporoca pozorno spremljanje. Zapleti s celjenjem rane: Zaradi mehanizma delovanja lahko nintedanib poslabša celjenje ran. Zdravilo Ofev je dovoljeno uvesti ali v primeru perioperativne prekinitve nadaljevati njegovo jemanje le na podlagi klinicne ocene ustreznega celjenja rane. Socasno dajanje s pirfenidonom: zaradi podobnosti varnostnega pro.la obeh zdravil lahko pricakujemo kombinirane neželene ucinke, vkljucno z neželenimi ucinki prebavil in jetrnimi neželenimi ucinki. Razmerje med koristjo in tveganjem pri socasni uporabi s pirfenidonom ni bilo ugotovljeno. Ucinek na interval QT: Previdnost je potrebna pri dajanju nintedaniba bolnikom, pri katerih se lahko razvije podaljšanje interva-la QTc. Alergijska reakcija: Pri bolnikih z znano alergijo na arašidove beljakovine je tveganje za resne reakcije na izdelke s sojo povecano. Vožnja: Zdravilo ima blag vpliv na sposobnost vožnje in upravljanja s stroji. Interakcije: Pglikoprotein (Pgp): Socasno dajanje z mocnim zaviralcem Pgp, je povecalo izpostavljenost nintedanibu. Mocni induktorji Pgp lahko zmanjšajo izpostavljenost nintedanibu. Encimi citokroma (CYP): Na podlagi presnove s CYP velja, da je verjetnost medsebojnega delovanja zdravil z nintedanibom majhna. Socasno dajanje nintedaniba z bosentanom ni spremenilo farmakokinetike nintedaniba. Plodnost, nosecnost in dojenje: Nintedanib lahko povzroci poškodbe ploda pri ljudeh.Ženskam v rodni dobi je treba svetovati, naj med zdravljenjem z zdravilom Ofev ne zanosijo. Svetovati jim je treba, naj med zdravljenjem z zdravilom Ofev in še najmanj 3 mesece po zadnjem odmerku uporabljajo visokoucinkovite metode kontracepcije. Trenutno ni znano, ali lahko nintedanib zmanjša ucinkovitost hormonskih kontracepcijskih sredstev, zato morajo ženske, ki uporabljajo hormonska kontracepcijska sredstva, dodatno uporabiti tudi pregradno metodo kontracepcije. Ker lahko nintedanib pri ljudeh poškoduje plod, se ga med nosecnostjo ne sme uporabljati, pred zdravljenjem z zdravilom Ofev in med zdravljenjem, kot je ustrezno, pa je treba opraviti test nosecnosti. Ce bolnica med uporabo zdravila Ofev zanosi, je treba zdravljenje ukiniti in bolnico seznaniti z možno nevarnostjo za plod. Med zdravljenjem z zdravilom Ofev je treba prenehati z dojenjem. Ni znakov vpliva na plodnost pri moških. Neželeni ucinki 1) IPF: Zelo pogosti: driska, navzea, bolecine v trebuhu, zvecana vrednost jetrnih encimov. Pogosti: zmanjšana telesna masa, zmanjšan tek, krvavitev, bruhanje, zvecana vrednost ALT, AST in GGT, izpušcaj in glavobol. Obcasni: trombocitopenija, dehidracija, miokardni infarkt, hipertenzija, pankreatitis, kolitis, poškodba jeter zaradi zdravila, hiperbilirubinemija, zvecana vrednost ALKP v krvi, pruritus in alopecija. Neznana pogostnost: anevrizme, disekcije arterij in ledvicna odpoved. 2) ILD: Zelo pogosti: zmanjšan tek, driska, navzea, bolecine v trebuhu, bruhanje, zvecana vrednost jetrnih encimov in zvecana vrednost ALT. Pogosti: zmanjšana telesna masa, krvavitev, hipertenzija, poškodba jeter zaradi zdravila, zvecana vrednost AST in GGT, zvecana vrednost ALKP v krvi, izpušcaj in glavobol. Obcasni: trombocitopenija, dehidracija, miokardni infarkt, pankreatitis, kolitis, hiperbilirubinemija, pruritus, alopecija in ledvicna odpoved. Neznana pogostnost: anevrizme in disekcije arterij. 3) SSc-ILD: Zelo pogosti: driska, navzea, bolecine v trebuhu, bruhanje, zvecana vrednost jetrnih encimov. Pogosti: zmanjšana telesna masa, zmanjšan tek, krvavitev, hipertenzija, zvecana vrednost ALT, AST in GGT, zvecana vrednost ALKP v krvi in glavobol. Obcasni: trombocitopenija, kolitis, poškodba jeter zaradi zdravila, izpušcaj, pruritus in ledvicna odpoved. Neznana pogostnost: dehidracija, miokardni infarkt, anevriz-me, disekcije arterij, pankreatitis, hiperbilirubinemija in alopecija. Preveliko odmerjanje: Zdravljenje je treba prekiniti in takoj uvesti ustrezne splošne podporne ukrepe. Nacin in režim izdaje: Rp/ Spec. Imetnik dovoljenja za promet z zdravilom: Boehringer Ingelheim International GmbH, Binger Strasse 173, D-55216 Ingelheim am Rhein, Nemcija. Za podrobnejše informacije o zdravilu glejte Povzetek glavnih znacilnosti zdravila 07/2020. V kolikor imate medicinsko vprašanje v povezavi z zdravilom podjetja Boehringer Ingelheim, Podružnica Ljubljana, vas prosimo, da poklicete na telefonsko številko 01/5864-000 ali pošljete vaše vprašanje na elektronski naslov: medinfo@boehringer-ingelheim.com. Informacijsko gradivo za strokovno javnost. Datum priprave informacije november 2020. PC-SL-100353 Boehringer Ingelheim RCV, Podružnica Ljubljana, Šlandrova 4b, 1231 Ljubljana Crnuce The congress was supported by: AstraZeneca Betamed Boehringer Ingelheim Chiesi Ewopharma MSD Sanofi Swixx Biopharma Takeda Berlin Chemie Biomedica IRIS LKB Medicopharmacia Medis Novartis Pfizer Pharming Group Pliva Teva Providens CIP - Kataložni zapis o publikaciji Narodna in univerzitetna knjižnica, Ljubljana 616.24(082) 616-097(082) SLOVENIAN Pneumology, Allergology and Immunology Congress (7 ; 2020 ; online) 7th Slovenian Pneumology, Allergology and Immunology Congress : 10th - 12th of December 2020, online : [book of abstracts] / [editor Mitja Košnik ; organisers Slovenian Respiratory Society ... et al.]. - Golnik : Slovenian Respiratory Society, 2020 ISBN 978-961-95041-1-6 1. Košnik, Mitja COBISS.SI-ID 42448643 ISBN 978-961-95041-1-6 789619 504116 Book of Abstracts 7th Slovenian Pneumology Congress joined with Allergology and Immunology Congress Editor Mitja Košnik Published by Slovenian Respiratory Society Year of Issue 2020 Circulation 600 copies Design Zala Košnik Technical Editor Zdravko Topolnjak Printed by Tisk Žnidaric, Kranj 7th Slovenian Pneumology Congress joined with Allergology and Immunology Congress DECEMBER 10-12 2020 Web based event ORGANISERS Slovenian Respiratory Society together with Slovenian Association of Allergy and Clinical Immunology Immunology Society of Slovenia Professional group of nurses and health technicians in pulmology in association with University Clinic of Respiratory and Allergic Diseases Golnik University Clinical Centre Ljubljana University Clinical Centre Maribor Organising Committee: Robert Marcun, Mitja Košnik, Matevž Harlander, Vladka Curin Šerbec, Maruša Ahacic, Aleš Rozman, Marjeta Tercelj, Duška Vidovic, Veronika Podlogar Programme Committee: Mitja Košnik, Matevž Harlander, Aleš Rozman, Marjeta Tercelj, Robert Marcun, Matija Rijavec, Sabina Škrgat, Kristina Ziherl, Irena Šarc, Jure Šorli, Matjaž Fležar, Petra Svetina, Katarina Osolnik, Mateja Marc Malovrh, Katja Mohorcic, Igor Požek, Izidor Kern, Viktorija Tomic, Vojka Gorjup, Uroš Krivec, Marko Bitenc, Tanja Cufer, Tina Vesel, Peter Korošec, Alojz Ihan, Tadej Avcin, Vojko Berce, Maja Benko, Klemen Jenko, Alojz Ihan, Borut Božic, Maja Cemažar, Roman Jerala, Matija Tomšic, Maruša Ahacic, Katja Vrankar, Saša Kadivec ALLERGY Thursday, 10th December Allergy diagnostics 9:00 AM - 10:30 AM Moderator: Peter Korošec, Mitja Košnik Edward Knol: Clinical implementation of Basophils Activation Testing in allergy diagnostics Bernadette Eberlein: Diagnostics of alpha-gal syndrome Ana Koren: Mast cell activation test in the diagnosis of allergic disease Immune deficiencies 10:45 AM - 12:15 PM Moderator: Tade Avcin, Alojz Ihan Anna Sediva: Lungs in Primary Immmunodeficiencies Natasa Toplak: Recent advances on management of autoinflammatory diseases Maruša Debeljak: Genetics of inborn errors of immunity Brigita Koren: Selective IgA defficiency – our experience Gašper Markelj: PID and covid-19 Drug allergy / anaphylaxis 12:30 PM - 2:00 PM Moderator: Peter Kopac, Lenka Sedlackova Lenka Sedlackova: Radiocontrast media hypersensitivity Grzegorz Porebski: MRGPRX2 in immediate drug hypersensitivity reactions - tips or tricks Tina Vesel Tajnšek: Myths and truths in drug allergy in children Peter Kopac: Perioperative anaphylaxis Satellite symposium Swixx Biopharma 2:00 PM - 3:00 PM Eike Wüstenberg: Grazax: clinical data and practical recommendations Anja Koren Jeverica: Grazax Asthma Prevention (GAP) trial Immunotherapy 3:00 PM - 4:30 PM Moderator: Renato Eržen, Asja Stipic Markovic Mirjana Turkalj: Immunotherapy of food allergy: does it work? Sinisa Savic: Autoinflammation Satellite symposium Ewopharma 4:30 PM - 4:50 PM Renato Eržen: The benefits of early intervention with allergen immunotherapy Urticaria/angioedem / AD 7:00 PM - 8:30 PM Moderator: Emek Kocaturk Frank Siebenhaar: Why omalizumab (usually) works in CU? Matija Rijavec: Predictive factors of response to omalizumab treatment in chronic spontaneous urticaria Edward Knol: Implementing biomarkers in immunophenotyping and severity scoring of atopic dermatitis Sladana Andrejevic: Hereditary angioedema and systemic autoimmune diseases IMMUNOLOGY Friday, 11th December Innate immunity 9:00 AM - 10:30 AM Moderator: Roman Jerala Iva Hafner Bratkovic: Regulation of NLRP3 inflammasome activation Petra Sušjan: Inhibition of NLRP3 inflammasome by peptide inhibitors Nataša Kopitar Jerala: Cystatins in non-canonical inflammasome activation and sepsis Žiga Jakopin: Development of NOD2 agonists as vaccine adjuvants Mateja Mancek Keber: Extracellular vesicles as modulators of innate immune response Peter Pecan: Cardioprotection against simulated ischemia/reperfusion injury mediated by calcium ionophore-induced extracellular vesicles Cancer immunotherapy 11:15 AM - 12:55 PM Moderator: Maja Cemažar Gregor Serša: Interleukin-12 gene therapy for treament of cutaneous tumors Urška Kamenšek: Gene electrotransfer for cancer immunotherapy Martina Reberšek: Retrospective analysis of treatment-naive Slovenian patients with metastatic melanoma treated with pembrolizumab – real-world experience Damijan Valentinuzzi: Radiomic analysis of lung cancer immunotherapy Marija Ivanovic: Real-world efficacy of immunotherapy in advanced non-small cell lung cancer: a single centre experience Marina Mencinger: Outcomes and safety in patients with metastatic urothelial cancer receiving atezolizumab at the Institute of Oncology Ljubljana Autoimmunity I 1:45 PM - 3:30 PM Moderator: Mojca Frank Bertoncelj, Saša Cucnik Katja Perdan Pirkmajer: Systemic sclerosis – where do we stand? Katja Lakota: Integrative approaches in systemic sclerosis Blaž Burja: A role of dimethyl-a-ketoglutarate in TGFß-driven profibrotic responses of dermal fibroblasts Alojzija Hocevar: Can we predict gastrointestinal and/or renal complication in IgA vasculitis? Tadeja Kuret: Serum microRNA profile in adult patients with IgA vasculitis Tina Kamhi Trop, Rok Orel: Autoimmunity and Coeliac disease Frank Bertoncelj: Integrative epigenomic atlas of synovial fibroblasts provides new insights into heritability of rheumatoid arthritis Autoimmunity II 3:45 PM - 5:15 PM Moderator: Borut Božic, Saša Cucnik Yehuda Shoenfeld: Hyper stimulation of the immune system as a major role in Autoimmunity; CPI and Silicone breast implants as proofs of concepts Polona Žigon: Extracellular vesicles in antiphospholipid syndrome Manca Ogric: Detection of anti-drug antibodies improves therapeutic drug monitoring in patients created with TNF-a inhibitors Blaž Krhin: Autoimmune thyroiditis Genetics in pulmonology 5:30 PM - 7:00 PM Moderator: Matija Rijavec Anastasios E. Germenis: Rare Diseases: From Therapeutic Orphans to Pioneers of Precision Medicine Katarina Osolnik: Clinical characteristics and lung function of our patients with genetically confirmed alpha-1 antitrypsin deficiency Julij Šelb: Genetics of pulmonary diseases – single centre experience Anton Lopert: Genetic variants and clinical parameters of asthma treatment outcome in adults Katja Lakota: Fibrotic Processes in Lungs – Meta-analysis of the Transcriptome Data Transition between pediatric and adult pneumology 7:30 PM - 9:00 PM Moderator: Uroš Krivec, Vojko Berce Andreja Kukec: The prevalence of respiratory diseases in schoolchildren in Ljubljana health region area due to public health perspectives Vojko Berce: Ultrasound in diagnostics and etiologic definition of pneumonias in children Erika Jerele: Comparison of efficacy between penicillin and broad spectrum beta-lactam antibiotics in the treatment of community-acquired pneumonia in children Ana Kotnik Pirš: CFTR modulator therapy in children and adolescents with cystic fibrosis Barbara Salobir: Transition from pediatric to adult CF care in era before CFTR modulators – our experience Saturday, 12th December Development of advanced therapies 9:00 AM - 11:00 AM Moderator: Jelka Pohar, Vladka Curin Šerbec Uroš Rajcevic: Adoptive Cell Therapy and Chimeric Antigen Receptor - T cells Duško Lainšcek: Nobel prize in Chemistry 2020 Duško Lainšcek: CRISPR method modification for enhanced genome editing Jelka Pohar: Regulatory T cells for immunotherapy of autoimmune diseases Anže Smole: Next generation Chimeric Antigen Receptor (CAR) T cells Antigen presenting cells and T cell response 12:00 PM - 2:00 PM Moderator: Alojz Ihan Maša Bizjak: Safety and immunogenicity of varicella vaccine in children with juvenile idiopathic arthritis treated with anti-cytokine therapy Larisa Janžic: Optimization of thp-1 cell line differentiation to macrophages for in vitro studies of macrophage immune response to infection with different strains of group B Streptococcus Andreja Nataša Kopitar: Difference in the dendritic cell function in intestinal immunity and inflammation Mojca Pavlin: Immunometabolism - targeting metabolism of antigen presenting cells PNEUMOLOGY Thursday, 10th December Pleural diseases: Infections 12:30 PM - 2:00 PM Moderator: Mateja Marc Malovrh Mateja Marc Malovrh: Conservative treatment of pleural space infection Boris Greif: When is the right time for surgical treatment? Katja Adamic, Iztok Fošnaric, Jasna Fuerst: Our experience in the treatment of pleural infection Rehabilitation and COPD 3:00 PM - 4:30 PM Moderator: Irena Šarc Tomaž Hafner: Rehabilitation in times of covid-19 Irena Šarc: COPD – what can we measure and what it means Satellite symposium Ewopharma 4:30 PM - 5:00 PM Renato Eržen: The benefits of early intervention with allergen immunotherapy Imaging 5:00 PM - 6:30 PM Moderator: Igor Požek Ante Marušic: Lung cancer screening in Croatia Igor Požek: Imaging in covid-19 Satellite symposium Boehringer Ingelheim 6:30 PM - 7:00 PM Katarina Osolnik: IPF and key insights from the INBUILD trial for PF-ILDs Mislav Cerovec: Treatment of SSc-ILD Rare pulmonary diseases 7:00 PM - 8:40 PM Moderator: Marjeta Tercelj, Katarina Osolnik Marco Confalonieri: Pulmonary fibrosis Nadja Koren: PET-CT in sarcoidosis Katarina Osolnik: IPF – our experience Klara Svenšek, Majda Kocar, David Lestan: IPF – our experience Julij Šelb: Genetics in IPF Friday, 11th December Satellite symposium Takeda 8:30 AM - 8:50 AM Tanja Cufer: Navigating an evolving ALK+ NSCLC landscape to optimize patient outcomes Lung cancer 9:00 AM - 10:30 AM Moderator: Tanja Cufer, Katja Mohorcic Maximilian Hochmair: Novel lung cancer drugs and how to optimize access to them Bojan Zaric: Novel lung cancer drugs– experience from Novi Sad Marko Jakopovic: Novel lung cancer drugs- experience from Zagreb Jelena Spasic: Novel lung cancer drugs – experience from Beograd Urška Janžic: Access to novel lung cancer drugs in Slovenia Katja Mohorcic: Real world data on treatment with novel lung cancer drugs at UC Golnik Satellite symposium Boehringer Ingelheim 10:30 AM - 11:15 AM Maximilian Hochmair: Treatment of advance NSCLC patients Sequencing approach in treatment of EGFR – positive NSCLC Possibilities of treatment advance NSCLC adenocarcinoma patients after immunotherapy Intensive medicine 11:15 AM - 12:55 PM Moderator: Vojka Gorjup Giacomo Bellani: Spontaneous breathing in critically ill patients: opportunities and challenges Dušanka Obradovic: Recognizing a critically ill patients-do we need scoring systems? Jovan Matijaševic: Direct catheter interventions in acute PTE Rihard Knafelj: Use of volatile sedation in ICU covid-19 patients Alenka Golicnik: Ventilation monitoring in intubated patients - basic principles Satelitski simpozij MSD 1:00 PM - 1:35 PM Tanja Cufer: Kako je imunoterapija izboljšala preživetja bolnikov z NDRP Paliative care 3:45 PM - 5:15 PM Moderator: Urška Lunder Urška Lunder: Kvaliteta življenja in moteci simptomi slovenskih bolnikov v zadnjih dveh mesecih življenja - izsledki primerjave z drugimi državami v EU projektu ACTION Hana Kodba Ceh: Kaj pomeni upanje za bolnike z napredovalo neozdravljivo boleznijo Pulmonary hypertension – novel invasive procedures and novel risk factors 5:30 PM - 7:00 PM Moderator: Barbara Salobir Irene Lang: Novelities in managment of pulmonary hypertension – focus on invasive procedures Arsen Ristic: Pulmonary endarterectomy in CTEPH – our experiences Polona Mlakar: Treatment of multiple peripheral pulmonary artery stenoses with balloon pulmonary angioplasty and stent implantation in a young adult Nika Škoro-Sajer: Role of infalmmation in CTEPH Marko Miklic: Pulmonary hypertension in intermediate risk patients with acute pulmonary embolism, patient outcomes – our single center results Sleep disordered breathing 7:30 PM - 9:00 PM Moderator: Kristina Ziherl Stefan Mihaicuta: OSAS phenotypes might tailor different treatment strategies Kristina Ziherl: OSAS and women – different clinical presentation and different consequences Jasmina Gabrijelcic: Noncardiovascular complications of untreated OSAS Irena Šarc: CPAP or NIV in treatment of OHS Saturday, 12th December Lung infection / Tuberculosis 9:00 AM - 11:00 AM Moderator: Petra Svetina Dušan Popadic: Tuberculosis and immune response; Sponzorirano predavanje Betamed Sanja Grm Zupan: How successful we are in LTBI detection in TB contacts? Manca Žolnir-Dovc, Eva Sodja: Tuberculosis and laboratory work - are we at a breaking point? Petra Svetina: Timeline and factors influencing sputum conversion in TB patients Azra Jusufovic: Diagnosis and management Endobronchial Tuberculosis Jelica Videnovic-Ivanov: COPD and infections with nontuberculosis M.Xenopi Satellite symposium Sanofi 11:00 AM - 11:30 AM Sabina Škrgat: Vloga vnetja tipa 2 pri astmi Satellite symposium Boehringer Ingelheim 11:30 AM - 12:00 PM Marija Vukoja: Inhaler – the most important part of inhalation treatment Obstructive lung diseases I 12:00 PM - 12:40 PM Moderator: Sabina Škrgat Ratko Djukanovic: Insight into the mechanisms of asthma through transcriptomic analysis Matija Rijavec: T2-high asthma, classified by sputum mRNA expression of IL4, IL5 and IL13, is characterized by eosinophilia and severe phenotype Satellite symposium Astra 12:40 PM - 1:00 PM Neven Tudoric: Benralizumab - from clinical trials to clinical practice (moderator: Sabina Škrgat) Obstructive lung diseases II 1:00 PM - 2:00 PM Moderator: Sabina Škrgat Ratko Djukanovic: SHARP – three years old but already running strong Jusufovic Edin: Vitamin D and COPD: missed opportunities Matevž Harlander: The role of biomarkers in COPD: do they really matter in the complexity of the disease Satellite symposium Chiesi 2:00 PM - 2:30 PM Sylvia Hartl: Triple Therapy the new treatment standard Closing of the congress 2:30 PM - 3:00 PM COVID POKONGRESNI SIMPOZIJ 3:00 PM - 7:00 PM (Slovenski jezik) Moderator: Mitja Košnik, Matevž Harlander Alojz Ihan: V cem je ta virus drugacen? Miroslav Petrovec: Kateri testi so za kateri namen? Robert Marcun: UZ pri obravnavi bolnika s covidom-19 Matjaž Fležar: Patofiziologija covid-19 pljucnice in zdravljenje s kisikom Franc Šifrer: Neinvazivna ventilacjja covid-19 pljucnice Matej Furlan: Posebnosti invazivne ventilacije covid-19 bolnikov Vojka Gorjup: Kaj narediti, ko niti invazivna ventilacija vec ne pomaga Katarina Osolnik, Igor Požek: Ali covid-19 pušca trajne posledice na pljucih? Urška Lunder: Kako izvajati paliativno oskrbo v covid-19 casih Roman Jerala: Kako se naredi cepivo proti covidu-19 Tatjana Lejko: Kako bomo živeli s covidom-19, ko ne bo vec epidemije? ZDRAVSTVENA NEGA (NURSING) Friday, 11th December Zdravstvena nega: Kronicne pljucne bolezni 8:00 AM - 10:30 AM Moderator: Ditka Benedicic Saša Kadivec: Kultura varnosti na Kliniki Golnik Sanela Pivac: Zavedanje medicinskih sester o vlogi na podrocju nadzora nad tobakom Irena Šarc: Neinvazivna ventilacija na domu: kdaj in kako? Ditka Benedicic: Kaj mora medicinska sestra vedeti o neinvazivni ventilaciji? Tatjana Kosten: Prehranska podpora bolnika s pljucno boleznijo Alenka Smukavec: Aplikacija pospeševalca izdihanega zraka (free aspire) ali izkašljevanje s pozitivnim tlakom (cough assist) v respiratorni fizioterapiji pri pljucnem bolniku Zdravstvena nega: Astma 10:45 AM - 12:20 PM Moderator: Maruša Ahacic Maja Zrnic: Samonadzor bolnikov z astmo Mariana Paula Rezelj: SAQ – vprašalnik za težko astmo – multidisciplinarni pristop za validacijo prevoda Mariana Paula Rezelj: Uporaba olajševalcev pri bolnikih s težko astmo na biološki terapiji Jana Tršan: Multidisciplinarna obravnava bolnika s težko astmo v ambulanti za biološko terapijo v Kliniki Golnik Zdravstvena nega: Alergijske bolezni 12:30 PM - 2:05 PM Moderator: Saša Kadivec Tea Mocnik: Timsko sodelovanje in predaja pacienta z anafilaksijo iz Alergo enote v Enoto za intenzivno terapijo – klinicni primer Renato Eržen: Imunoterapija v zdravljenju alergijskih bolezni Tea Mocnik: Vloga multidisciplinarnega tima pri izvajanju intravenozne desenzibilizacije za zdravila Saša Kadivec: Kako znajo epipen uporabljati bolniki, ki dobijo predpis na urgenci Zdravstvena nega: Pljucni rak 2:30 PM - 4:25 PM Moderator: Ivanka Kržišnik Nataša Grahovec: Diagnostika pljucnega raka Urška Janžic: Sodobni pristopi v sistemskem zdravljenju pljucnega raka Shpresa Mazreku: Organizacijski vidik zdravstvene oskrbe bolnika s pljucnim rakom Ivanka Kržišnik: Obvladovanje neželenih ucinkov pri bolniku na sistemskem zdravljenju pljucnega raka Marija Petrinec Primožic: Zdravstvena nega bolnika s trajnim plevralnim drenažnim katetrom – šola praznjenja plevralnega izliva Zdravstvena nega: Bolnik s covidom-19 – 1. del 4:45 PM - 6:40 PM Moderator: Tanja Žontar Barbara Bitežnik: Bolnik s covidom-19 Nika Kokl, Sasa Kociper: Doživljanje in izkušnje medicinskih sester urgentne ambulante med epidemijo covida-19 Tina Remškar: Izzivi zdravstvene nege pri obravnavi pacienta s covidom-19 Matjaž Fležar: Kako spoznati bolnika s covidom-19, ki potrebuje intenzivno obravnavo Zdravstvena nega: Bolnik s covidom-19 – 2. del 6:45 PM - 9:00 PM Moderator: Tatjana Kosten Viktorija Tomic: Diagnostika okužb s SARS-CoV-2 Irena Grmek Košnik: Izkušnje epidemiologov z virusom covid-19 Tatjana Kosten: Prehranska podpora pri bolniku s covidom-19 Matic Jerman: Izzivi medicinskih sester pri delu z bolniki okuženimi s SARS-CoV-2 v enoti intenzivne terapije Zrnic Maja, Mocnik Tea, Kopac Peter: Doživljanje stresa zaposlenih v zdravstvu s covid-19 obolelimi pacienti CONTENTS PLENARY SESSIONS Pneumology 19 Rare Pulmonary Diseases 21 Pleural Diseases: Infections 22 Genetics in Pneumology 23 Transition between Pediatric and Adult Pneumology 27 Pulmonary Hypertension – Novel Invasive Procedures and Novel Risk Factors 30 Lung Infections / Tuberculosis 33 Obstructive Lung Diseases 35 Allergy 39 Drug Allergy 41 Skin Allergy 42 Immunology 42 Immune Deficiencies 45 Innate Immunity 46 Cancer Immunotherapy 53 Autoimmunity 59 Development of Advanced Therapies 66 Antigen Presenting Cells and T Cell Response 72 Zdravstvena nega 77 Kronicne pljucne bolezni 79 Astma 86 Alergijske bolezni 91 Pljucni rak 99 Bolnik s covidom-19 108 POSTERS Allergy 123 Diagnostics 123 Food Allergy 129 Drug Allergy and Anaphylaxis 135 Skin Allergy 137 Immunology 141 Tumour Immunity 141 Miscellaneous 144 Pneumology 146 Genetics 146 Rare Lung Diseases 147 Lung Cancer 153 Lung Vessel Diseases 154 Obstructive Lung Diseases 164 Infection / Tuberculosis 172 Miscellaneous 183 Rare Pulmonary Diseases Pleural Diseases: Infections Genetics in Pneumology Pulmonary Hypertension – Novel Invasive Procedures and Novel Risk Factors Nadja Koren Pucelj, Marko Grmek, Marjeta Tercelj University Medical Centre Ljubljana, Ljubljana, Slovenia nadja.koren@gmail.com Background: We tried to find out if 18F-FDG PET/CT (PET/CT) has a role in assessment of activity of sarcoidosis, in assessment of different organ involvement and in follow up of sarcoidosis, compared to other established methods. Methods: We studied 104 sarcoidosis patients who underwent PET/CT scan at time of diagnosis between March 2010 and February 2018. 54 of them also had PET/CT at follow up. We aimed to assess the presence of inflammatory activity using PET/CT. Correlations between PET/CT findings (MAXSUV at any location, in lymph nodes and in parenchymal organs), different biomarkers (CTO, ACE, sIL2R, TNF-alpha), radiological evaluation (XrayScore, Scadding stage) and pulmonary function at the time of diagnosis (1) and at follow-up (2) were calculated. Results: PET/CT more often showed involvement of mediastinal lymph nodes and lung than X-ray (XrayScore, Scadding stage). In addition PET/CT showed possible involvement of extra thoracic organs (whole body CT) and it provided possibility for robust quantitative assessment of metabolic activity of specific lesions. No correlations were found between PET/CT and pulmonary function tests. PET/CT findings at the time of diagnosis significantly correlated with X-ray score, ACE, CTO, sIL2R and TNF-alpha at time of diagnosis and only with CTO at follow up. Conclusion: PET/CT is better diagnostic method for assessment of activity of sarcoidosis, assessment of different organ involvement and for monitoring of the effects of therapeutic interventions. As more frequent use of PET/CT is limited due to its availability, cost and radiation exposure, CTO has a place in follow up of patients with sarcoidosis. Boris Greif Clinical Department for Thoracic Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia boris.greif@kclj.si Background: Main principles of acute stage (I and II) empyema treatment are appropriate antibiotic therapy, evacuation of pleural fluid and full lung reexpansion. If later two cannot be achieved by conservative means, surgical intervention is mandatory. VATS debridement is standard surgical procedure before the onset of organizing stage (III) empyema, when open decortication is mostly necessary. Therefore timely recognition of emypema is a keypoint of an effective surgical treatment of empyema that avoids thoracotomy. Methods: We retrospectively analyzed patients who underwent surgery for empyema between January 2020 and November 2020 in our institution. All patients with stage II eympema were submitted to VATS approach. Primary goal of the study was to evaluate effectivness and complication rate of VATS debridement for parapneumonic empyema. Results: Out of 51 patients, 37 (72,5 %) underwent surgery for parapneumonic empyema. Among them, 26 (70,2 %) underwent VATS debridement. Conversion rate was 3 (11,5 %), 1 for bleeding and 2 due to technical difficulties. There were 6 reoperations, 4 for bleeding, 1 for failed debridement and 1 for prolonged airleak. Among all revisions only 1 was performed through thoracotomy. The average ICU stay and hospital stay were 2,8 days (1-23) and 9,0 days (2-25), respectively. Average chest tube duration was 7,4 days (1-29). Postoperative complication rate was 8 (34,8%), the most common was bleeding (4). In-hospital mortality and readmission rate were 0. Conclusions: Our VATS debridement program for empyema revealed to be effective and safe with only 1 procedure failure, low conversion rate and 0 in-hospital mortality. However, bleeding rate was not negligible and could have impact on the outcome. Therefore it is of utmost importance to employ early and effective reoperation that can be in expert hands mostly performed by minimally invasive VATS as shown in our study. Julij Šelb, Peter Korošec, Katarina Osolnik, Matija Rijavec University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia julij.selb@klinika-golnik.si Introduction: In pulmonology, as well as in other diseases, genetic testing is being increasingly used to identify the cause of different diseases. Aim: To describe the experience with genetic testing in different disease settings in patients being referred to testing to Laboratory for Clinical Immunology and Molecular Genetics Golnik. Methods and results: Genetic tests in our laboratory were performed in the context of alpha 1 antitrypsin deficiency (AATD) and in the context of Clinical Exome sequencing for different diagnoses. Six hundred and fifty eight patients had genetic test for AATD performed. In 398 (60.5%) Pi*MM, 189 (28.7%) Pi*MZ, 36 (5.5%) Pi*MS, 31 (4.7%) Pi*ZZ and 4 (0.6%) Pi*SZ genotypes were discovered respectively. Furthermore, we tested 68 patients using NGS with pulmonary disease as indication. In 13 patients (20 %) we found a causative variant namely i.) in 2 patients with Hermansky-Pudlak syndrome (HPS1, HPS4) ii.) in 1 patient with non Z/S AATD iii.) in 4 patients with primary ciliary deficiency (DNAH11, DNAH5, DNAI1, SPAG1) iv.) in 4 patients with idiopathic pulmonary fibrosis (TERC, 2*TERT, RTEL1) and v.) in 2 patients with Birt-Hogg-Dube (FLCN). In two patients with idiopathic pulmonary fibrosis we found rare missense variants (absent from GNOMAD control population) in genes associated with IPF (namely RTEL1 and PARN), however we were not able to classify them as pathogenic/likely pathogenic, therefore they were classified as variants of unknown significance (VUS). Conclusions: Our single centre experience shows that molecular genetic testing is a valuable tool for establishing/confirming diagnosis in patients with pulmonary diseases. High rate of positive diagnoses in NGS testing (roughly 20%) in an adult population shows that clinical suspicion to consider a genetic test is too high and should be lowered (to achieve 10% rate of positive diagnoses). Anton Lopert1, Matija Rijavec2, Mateja Žavbi2, Peter Korošec2, Matjaž Fležar2 1Outpatient clinic for pulmonary diseases and allergy, Murska Sobota, Slovenia 2University clinic of pulmonary and allergic diseases Golnik, Golnik, Slovenia anton.lopert@siol.net Background: The aim of our study was to evaluate the success of long-term inhaled corticosteroids (ICS) controller therapy in adult asthmatics. Genetic variants important for the biologic action of corticosteroids might be responsible for different treatment response. Patients and methods: A prospective study involved 208 adult patients with newly diagnosed (“glucocorticoid naďve”) mild to moderate asthma. The chosen treatment outcome parameters were: changes in FEV1, PD20 for methacholine, Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) scores. We wanted to evaluate correlations between changes in all four parameters after at least 3 years of treatment with ICS. In the genetic part of the study, variants rs9910408 in TBX21, rs37973 in GLCCI1, rs242941 and rs1876828 in CRHR1 gene, identified in previous studies to predict the therapeutic response to ICS, were genotyped in all 208 patients. Genotypic distribution and allelic frequencies in »good« and »poor« responders were compared. Results: Despite the fact that all four parameters of asthma treatment outcome showed a significant improvement, we only found significant correlation between the two ”subjective” outcome parameters: change in asthma control and change in asthma-related quality of life. Variant rs9910408 in TBX21 gene was associated with response to ICS treatment. In good responders, assessed by increase in PD20, the frequency of AA genotype was significantly higher than in poor responders. With regard to changes in PD20 and in FEV1 this genotype related response was even more evident in the subgroups of nonsmokers and in non-atopic patients. Furthermore in non-atopic patients AA genotype was overrepresented among good responders regarding changes in AQLQ score. Genotype dependent difference in FEV1 improvement for variant rs37973 in GLCCI1 gene was highly influenced by smoking and atopy. We were unable to confirm the association of variants rs242941 and rs1876828 in CRHR1 gene with therapeutic reponse to ICS. Conclusion: There is only weak correlation between changes in subjective and objective treatment outcome parameters after long-term treatment with ICS in adult asthmatics. Our results suggest that genotyping for rs9910408 in TBX21 gene and rs37973 in GLCCI1 gene may allow the identification of patients that are more or less likely to respond to ICS therapy. Nika Testen1, Peter Juvan1,2, Katja Lakota1,3 1Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Koper, Slovenia 2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 3Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia nikatesten2@gmail.com Introduction: Pulmonary fibrosis occurs when excessive deposition of extracellular matrix appears in lungs. It is characteristic for idiopathic pulmonary fibrosis (IPF), but it can also happen as complication of systemic sclerosis (SSc) and progressive fibrotic sarcoidosis. Our goal was to identify common mechanisms of these diseases and propose novel candidates for therapeutic targets, as well as disease-specific mechanisms possibly explaining different course of the studied diseases. Methods: The study included transcriptome data on primary lung fibroblasts from patients with SSc, IPF and normal donors(1) and from patients with progressive fibrotic sarcoidosis and self-limiting sarcoidosis(2). Using bioinformatics tools BRB-ArrayTools, String and BioVenn we performed a differential gene expression analysis and gene set enrichment analysis based on KEGG and BioCarta pathways and transcription factors (TF) target genes. Results: We found 7 differentially expressed (DE) genes, leukocyte transendothelial migration KEGG pathway and 2 TF (CEBPA, JUN) in all studied diseases. SSc and IPF shared 541 (53 %) of all identified DE genes including various proteins of extracellular matrix and matrix metaloproteinases. Steroid biosynthesis was the most significantly changed KEGG pathway and Cell cycle G1/S checkpoint was common perturbed pathway of SSc and IPF according to BioCarta. On the contrary, sarcoidosis showed lesser, but more interconnected number of DE genes, as observed by high number of enriched pathways and involved TF. Only there HLA genes and T cell surface proteins were noticed. Enriched pathways belonged to cytokine-receptor, Jak-STAT signaling pathway by KEGG and to 18 different B and T cell signaling and polarization pathways by BioCarta. Additionally, we showed that TF RARG/RARA and Oct-1/Oct-2 are involved in expression of DE genes at intersections of different combinations of studied diseases, resulting in covering of DE genes in all three. Conclusion: Findings suggest that the number of mutual DE genes and enriched pathways between SSc and IPF is markedly larger than if comparing them to sarcoidosis. Changes in sarcoidosis transcriptomics expectedly confirm predominant involvement of immune cells in disease pathology. While RARG/RARA were already examined in different models of fibrosis, our further experiments will examine role of until now non-described Oct-1/Oct-2 in development of fibrotic disease pathology. Funding: This study was supported by Slovenian research agency (Systemic autoimmune diseases P3- 0314 and Z3-9261 to KL). References: (1) Hsu et al. Arthritis Rheum 201;63(3) (2) Lockstone et al. Am J Respir Crit Care Med 2010;181(12) Jasmina Bošnjic, Suvad Dedic, Dženan Halilovic Clinic for Pulmonary Diseases, University Clinical Centre Tuzla, Tuzla, Bosnia and Hercegovina jasmina.bosnjic@gmail.com Background: Metabolic syndrome is a new worldwide epidemic and leading cause of the cardiovascular disease, including pulmonary embolism. Previously described as a degenerative disease, atherosclerosis is now described as inflammatory immunological disease. The mechanisms of pulmonary embolism in patients with metabolic syndrome have not been fully established. The aim of the study is to determine the incidence of pulmonary embolism in patients with metabolic syndrome in our conditions and to evaluate the values and significance of atherogenesis and inflamamation biomarkers (CRP, fibrinogen, uric acid, lipid profile) in patients with pulmonary embolism in metabolic syndrome. Method: A retrospective study enrolled 30 patients with pulmonary embolism in metabolic syndrome selected by the International Diabetes Federation (IDF) criteria who were hospitalized at the Clinic for Pulmonary Disease UKC Tuzla from January to December 2019. The patients included in the study were determined the following parameters: history and physical examination, anthropometric parameters (age, sex, weight, height, body mass index, waist circumference), pulmonary artery CT angiography and biochemical parameters (CRP, fibrinogen, uric acid, total serum cholesterol, serum HDL cholesterol, serum LDL cholesterol, serum triglycerides). Results: Standard methods of descriptive statistics were used in the statistical processing of results. The results showed significantly higher incidence of metabolic abnormalities, elevated CRP, fibrinogen, uric acid and more frequent lipid profile disorders in patients with pulmonary embolism in the metabolic syndrome compared to the general population. Conclusion: The effects of metabolic syndrome on the respiratory system are often underestimated. Metabolic syndrome may play a key role in the pathogenesis of pulmonary embolism. Significant proportion of patients who show an increased risk of pulmonary embolism in metabolic syndrome remain unrecognized. Very often there is no clinical suspicion of pulmonary embolism in patients with metabolic syndrome. The results of this study will contribute to the identification of individuals at increased risk for pulmonary embolism in the metabolic syndrome. Marko Miklic Clinical Department for Vascular Diseases, UMC Ljubljana, Ljubljana, Slovenija marko.miklic@gmail.com Introduction: Although pulmonary embolism (PE) is quite common, there is limited information about the prevalence, management and outcomes of intermediate-high risk patients with PE in routine clinical practise. The incidence of chronic thromboembolic pulmonary hypertension (CTEPH) in this group of patients is expected to be low, but due to unstructured ambulatory follow-up the true number of patients is unknown. Methods: Intermediate-risk PE is characterized by initially normal hemodynamics and evidence of right ventricle dysfunction on echocardiography or CTPA and/or positive cardiac biomarkers. In UMC Ljubljana these patients are admitted to our level 2 intensive care unit for monitoring and further treatment. A retrospective analysis was performed of all these patients treated in the year 2018 and a thorough review of all available electronic medical records until November 2020 was then used to check for dedicated outcomes. Results: In the year 2018 we treated 95 intermediate risk PE patients with a wide age range of 25 to 95 years (average 67 years). 45% of patients were female. Most were overweight, with a mean body weight of 85 kg (min 54 kg, max 160 kg). 61% of patients presented with hypoxia, 50% with tachycardia, 25% with hypotension and 17% with syncope. D-dimer levels (ref. < 500 µg/L) were measured at admittance in 79% of patients, all were elevated with values ranging between 1480 and 41105 (average 12490). Troponin I values were negative (<100) in 36% of patients. NTproBNP values were measured in 70% of patients, out of those 15% were negative (below 500 ng/L). All PE were confirmed by CTPA, 94% had radiologic evidence of right ventricle overload, and 67% had dilated pulmonary arteries. 86% of patients had an echocardiographic assessment, out of those 62% had signs of right ventricular strain. The average peak systolic pulmonary pressure was 45 mmHg and ranged between 25 and 105 mmHg. 76% of patients were assessed for concomitant lower limb deep vein thrombosis, of which only 20% had none. 17% of patients had a prior venous thromboembolic event (VTE), 13% had active cancer, 15% had a history of malignancy, 9% were hospitalized in the prior 3 months, 8% had prior surgery and 5% were immobilized due to prior trauma. 10% of patients were treated with systemic intravenous thrombolysis and 7% received an IVC filter. Patients received different forms of anticoagulant treatment according to their underlying medical conditions. 19% were prescribed LMWH, 27% VKA, 31% apixaban, 11% dabigatran and 10% rivaroxaban. 64% of patients were advised to receive indefinitive anticoagulant treatment. Out of the group of patients treated with NOACs 19% continued with the lower dose of NOAC after 6-12 months of treatment. During hospitalization and follow up 12% of patients experienced a major bleeding event and a further 10 % a clinical relevant non-major bleed. 9,5% of patients had a recurrent VTE, all after anticoagulant discontinuation. 10% died in the first 30 days and a further 14% during follow up. Most common cause of death was malignant disease and sepsis. 38% of patients had an echocardiographic follow up and 36% of these patients had evidence of pulmonary hypertension. 7 of the 95 patients after intermediate high risk PE had signs compatible with CTEPH on echo and further lung imaging, 2 of those died of malignancy and the remaining 5 patients were evaluated at a specialist ambulatory clinic for pulmonary hypertension. All were deemed unsuitable for pulmonary endarterectomy or pulmonary artery balloon dilatation, three are receiving riociguat, one has not received specific vasodilatator treatment and one is still awaiting further evaluation. 5 of the 7 CTEPH patients had an echocardiographic estimated sPAP values over 60 mmHg on admittance and 3 out of 7 had a history of prior VTE. None received thrombolytic therapy. Conclusions: Patients with intermediate risk pulmonary embolism are a heterogenous group with a higher than expected rate of diagnosed CTEPH on follow-up. Improving education of PE caretakers, higher awareness for CTEPH and further evaluation, validation and implementation of clinical/radiological algorithms for earlier CTEPH diagnosis will likely help ensure earlier referral to expert centres and improved prognosis. Literature: 1. Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jiménez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ní Áinle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020 Jan 21;41(4):543-603. doi: 10.1093/eurheartj/ ehz405. 2. Mirambeaux R, León F, Bikdeli B, Morillo R, Barrios D, Mercedes E, Moores L, Tapson V, Yusen RD, Jiménez D. Intermediate-High Risk Pulmonary Embolism. TH Open. 2019 Dec 4;3(4):e356-e363. doi: 10.1055/s-0039-3401003. 3. Klok FA, Couturaud F, Delcroix M, Humbert M. Diagnosis of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Eur Respir J. 2020 Jun 25;55(6):2000189. doi: 10.1183/13993003.00189-2020. 4. Kim NH, Delcroix M, Jais X, Madani MM, Matsubara H, Mayer E, Ogo T, Tapson VF, Ghofrani HA, Jenkins DP. Chronic thromboembolic pulmonary hypertension. Eur Respir J. 2019 Jan 24;53(1):1801915. doi: 10.1183/13993003.01915-2018. 5. Konstantinides SV, Vicaut E, Danays T, Becattini C, Bertoletti L, Beyer-Westendorf J, Bouvaist H, Couturaud F, Dellas C, Duerschmied D, Empen K, Ferrari E, Galič N, Jiménez D, Kostrubiec M, Kozak M, Kupatt C, Lang IM, Lankeit M, Meneveau N, Palazzini M, Pruszczyk P, Rugolotto M, Salvi A, Sanchez O, Schellong S, Sobkowicz B, Meyer G. Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism. J Am Coll Cardiol. 2017 Mar 28;69(12):1536-1544. doi: 10.1016/j.jacc.2016.12.039. 6. Pesavento R, Prandoni P. Prevention and treatment of the chronic thromboembolic pulmonary hypertension. Thromb Res. 2018 Apr;164:150-156. doi: 10.1016/j.thromres.2018.02.149 TRANSITION BETWEEN PEDIATRIC AND ADULT PNEUMOLOGY The prevalence of respiratory diseases in schoolchildren in Ljubljana health region area Andreja Kukec1,2, Matjaž Krošel2, Tanja Carli2, Lijana Zaletel-Kragelj1,2, Peter Otorepec2 1Centre of Public Health, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 2National Institute of Public Health, Ljubljana, Slovenia andreja.kukec@mf.uni-lj.si Background: There is a mixture of different pollutants present in indoor and outdoor air, which may have adverse effects on health. Children are the most vulnerable population group due to their behavioral and pathophysiological characteristics in relation to the effects of air pollution on health. The purpose of the study is to examine the association between air quality in the school environment and diseases of respiratory system including allergic diseases considering confounding factors. Methods: In the period between September and December 2017 there was HIS-type cross-sectional study conducted in Ljubljana health region area. Considering the protocol of InAirQ project, which was implemented across Europe, there were 12 elementary schools enrolled in the study. The observed population group is represented by third grade pupils, age interval of 7 to 9 years. The data regarding the characteristics of school building, school surrounding and school happening were assessed by interview with school officials. Completing the questionnaire by parents the data about health status regarding the diseases of respiratory system, about pre-, peri-, postnatal period and home environment of the child were assessed. Association between explanatory factors and observed health outcome was analyzed with univariate and multivariate logistic regression models. The study was approved by Medical Ethics Authority of Slovenia. Results: Results of univariate association analysis for observed population group yielded statistically significant influence of respiratory illness in the first year of life on respiratory system diseases in last 12 months (p=0.017). The frequency of allergic respiratory diseases using the same methods is statistically significantly associated with the use of carpet in the child bedroom (p=0.025) and with the presence of moisture and mold in the child bedroom (p=0.050). Multivariate logistic regression model yielded statistically significant influence of settlement type (p=0.017) and respiratory illness in the first year of life (p=0.009) on respiratory disease. Considering allergic respiratory disease, the use of carpet in child bedroom (p=0.032) appeared as statistically significant variable. The total responsiveness of the study was 83.75%. Conclusions: There were numerous methodological public health challenges identified in the study, which offer good foundation for more comprehensive data analysis. Vojko Berce1, Maja Tomazin1, Mario Gorenjak2, Barbara Lovrencic1 1Pediatric Clinic, UMC Maribor, Maribor, Slovenia 2Faculty of Medicine, University of Maribor, Maribor, Slovenia vojko.berce@guest.arnes.si Background: Community-acquired pneumonia (CAP) still represents an important cause of morbidity. The aetiology of community-acquired pneumonia (CAP) is not easy to establish. Respiratory viruses are the most common cause of CAP in preschool children, followed by bacteria (especially Streptococcus pneumoniae). Atypical bacteria Mycoplasma pneumoniae and Chlamydiophila pneumoniae prevail in schoolchildren and adolescents. Lung ultrasound (LUS) has only recently been considered as an alternative to the chest x-ray (CXR) for diagnosing CAP. Less is known about the usefulness of LUS for the establishment of the etiological diagnosis of CAP. Therefore, we first compared the sensitivity of chest x-ray (CXR) and LUS for the diagnosis of CAP. In addition, we analyzed and compared the LUS characteristics of different etiological types of CAP in children. Methods: We performed a prospective study and included 166 children with CAP, who were admitted to hospital. LUS and CXR were performed in all patients at admission. Nasopharyngeal swab was taken for the detection of respiratory viruses and atypical bacteria with the polymerase chain reaction (PCR). Blood tests and sputum analysis were done for further stratification of patients. Results: Subjects were stratified into bacterial (n = 80), atypical bacterial (n = 32) and viral (n = 54) CAP subgroups. Pneumonia was detected with LUS in 161 (97.0 %) patients and with CXR in 137 (82.5 %) patients (p < 0.01). Sensitivity of LUS was calculated as 97.0% and sensitivity of CXR as 82.5% (p < 0.01). LUS-detected consolidations in viral CAP were significantly smaller, with a median diameter of 15 mm, compared to 20 mm in atypical bacterial CAP (p = 0.05) and 30 mm in bacterial CAP (p < 0.01). Multiple consolidations were detected in 65.4 % of patients with viral CAP and in 17.3 % of patients with bacterial CAP (p < 0.01). Bilateral consolidations were also more common in viral CAP than in bacterial CAP (51.9 % vs. 8.0 %, p < 0.01). At follow-up, a regression of consolidations was observed in 96.6 % of patients with bacterial CAP and in 33.3 % of patients with viral CAP (p < 0.01). Conclusion: We determined that LUS is an excellent tool for diagnosing the CAP in children. We found LUS to be especially suitable for differentiating bacterial CAP from CAP due to other aetiologies. However, LUS must be interpreted in the light of clinical and laboratory findings. Erika Jerele1, Maša Cugmas1, Maja Tomazin2, Mario Gorenjak1, Vojko Berce2 1Faculty of Medicine, University of Maribor, Maribor, Slovenia 2Pediatric Clinic, UMC Maribor, Maribor, Slovenia vojko.berce@guest.arnes.si Background: Bacterial community-acquired pneumonia (CAP) is still a common cause of morbidity in children in the developed world. Bacterial CAP is mostly caused by Streptococcus pneumoniae. The resistance of pneumococci against penicillin is increasing in Slovenia and worldwide. However, most guidelines still prefer treatment with narrow-spectrum antibiotics. Therefore, we compared the effect of intravenous treatment with penicillin and broad-spectrum beta lactam antibiotics in children with CAP. Methods: We performed a prospective study and included 136 children hospitalized because of bacterial CAP, diagnosed with lung ultrasound (LUS). Patients were treated intravenously either with penicillin G or broad-spectrum beta lactam antibiotic monotherapy. The size of lung consolidations was measured with LUS. White blood cell (WBC) count and C-reactive protein (CRP) were determined in venous blood at admission and after two days of treatment. Follow-up LUS was performed after two days of treatment in 64 (47.1 %) of patients. The time interval from the application of antibiotic to the permanent defervescence was recorded. Results: 87 (64.0 %) of patients were treated with penicillin G, and 49 (36.0 %) with broad spectrum beta-lactam antibiotics. The median time to the persistent defervescence was 5 hours in penicillin-treated patients and 8 hours in broad-spectrum group (p = 0.18). There were no significant differences between both treatment regimens regarding the effect on the consolidation size and CRP decrease. However, the decrease of WBC count was greater in the penicillin treatment group (p < 0.01). Conclusions: We have shown that penicillin is at least as effective as broad-spectrum antibiotics in the treatment of bacterial CAP in children. Despite the resistance of bacteria (including pneumococci) to antibiotics is increasing, clinicians should still adhere to national guidelines, which promote the use of penicillin and other narrow-spectrum beta lactams in the treatment of bacterial CAP in children. Azra Jusufovic Clinic for Pulmonary Diseases, University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina azraokanovic_1987@yahoo.com The diagnose of endobronchial tuberculosis is still challenging. In February 2018 28-year-old female pharmacist due to pneumonia was treated with antibiotic, when good chest X ray resolution was noticed. In July 2018 an occasional, dry cough was still present. Lungs’ CT lung was done in December 2018, and showed sequel of pneumonic infiltration in the right lower lobe. In July 2019 sputum smear microscopy for acid-fast bacilli was negative, but her Quantiferon TB test was positive. In September 2019 the culture on Mycobacterium tuberculosis from July 2019 was was positive. Bronchoscopy was done in October 2019 and revealed the fine-grained changes of distal part of trachea and right main bronchus together with necrotic changes of bronchus for right basal lobe. Bronchoaspirate was negative for acid-fast bacilli, but positive for culture on Mycobacterium tuberculosis and TB-polymerase chain reaction. Standard TB treatment was prescribed due to endobronchial tuberculosis. In December 2019, control chest X ray showed very significant regression of the shading in right lung. In April 2020 the patients was asymptomatic. Last chest X ray was normal. Control sputum smear microscopy for acid-fast bacilli and the culture on Mycobacterium tuberculosis from December 2020 were negative. TB therapy was finished after 6 months (from October 2019 to April 2020). The diagnosis of endobronchial tuberculosis is still complicated because of nonspecific respiratory symptoms, often normal chest X ray and variable diagnostic yield with sputum microscopy. However, endobronchial tuberculosis should be considered as differential diagnosis in cases of long-term nonspecific respiratory symptoms, particularly in the countries with high and middle TB incidence. This should be considered even in low risk patients. On the end the bronchoscopy is the most reliable method for confirmation of endobronchial tuberculosis. Jelica Videnovic-Ivanov Clinic for Lung Diseases, Clinical Centre Serbia, Belgrade, Serbia jelicavi@gmail.com Introduction: The manifestation of respiratory infection involves a series of diagnostic procedures to determine the cause of cough change and / or insite cough, fever, shortness of breath. Results: in 4 persons / 2 M, 2 F, mean age 52.4 years and chronic obstructive pulmonary disease accompanuing with smoking habits /. HIV infection was not determined. Extensive changes and destruction/ veryfied billateral patterns as centrilobular emphysema, cavities, consolidations / of the lung parenchyma and airways were presented radiographically - chest CT scans M.xenopi were isolated from the sputum in 4 persons during the analysis. Treatment controlled according to ATS / IDSA recommendations, were performed during the 12 months. Satisfactory clinical and radiographic responses achieved. Conclusion: Nowadays, clinical doubts can be confirmed by modern technology in the aim of healthy population. Matija Rijavec1,2, Tomaž Krumpestar1, Izidor Kern1, Sabina Škrgat1,3, Peter Korošec1 1University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 2Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia 3Medical Faculty, University of Ljubljana, Ljubljana, Slovenia Asthma is a common, highly heterogeneous inflammatory disease. Identification of asthma endotypes, that reflect highly variable response to conventional treatment, will lead to a more precise asthma management. T2 asthma is characterized by airway inflammation driven by T2 cytokines including interleukins IL-4, IL-5 and IL-13. The aim of this study was to determine whether induced sputum samples can be used for gene expression profiling and if T2-high endotype can be classified based on IL4, IL5 and IL13 profiling. Induced sputum samples were obtained from 44 subjects, among them 36 asthmatic patients and 8 controls. Immediately after collection, samples were processed with Sputolysin and cell pellets were stored in Qiazol reagent. Following total RNA extraction, RNA quantity and quality measurement, mRNA expression levels of IL4, IL5, IL13, were quantified by RT-qPCR. Gene expression levels of IL4, IL5, and IL13 were significantly increased in asthmatic patients’ samples compared to controls. High correlation between IL4, IL5 and IL13 expression was also observed. We calculated T2 gene mean by combining the expression levels of IL4, IL5 and IL13 and set the T2-high/T2-low asthma cutoff value based on the expression of T2 gene mean in controls. Twenty four (67%) asthmatic patients had T2-high asthma. T2 gene mean inversely correlated with FEV1, and positively correlated with blood and sputum eosinophils. Patients with T2-high asthma had significantly higher eosinophil blood and sputum counts, as well as lower albeit not statistically significantly FEV1. Furthermore, T2-high asthma was characterized as a more severe, difficult-to-treat asthma, and T2-high asthma patients more often received biological therapy to control their asthma symptoms/exacerbations. In this study we found that interleukins transcripts can be easily detected in sputum from asthmatic patients. mRNA expression levels of IL4, IL5 and IL13 are increased in sputum cells from asthmatic patients and can be used as molecular biomarkers to categorize patients into T2-high endotype, characterized by eosinophilia, and severe, difficult-to-treat asthma, often requiring biological treatment. Edin Jusufovic Medical Faculty of University Tuzla and Center for Pulmonary Diseases of Public Health and Educational Institution Tuzla, Bosnia and Herzegovina edin.jusufovic@bih.net.ba A male, aged 70 years, patient was presented due to 9 moderate/severe COPD exacerbations with 3 hospitalizations during last year. He was treated with triple inhaled therapy (Salmeterol/Fluticasone proprionate 100/1000 mcg BID + Aclidinium bromide 800 mcg, BID), together with long-term oxygen therapy (5L/min.; 14 hours/ day). After addition of Roflumilast (500 mg/day, orally; for 2 months) and later of Azithromycin (500 mg/day, orally; for 5 months) exacerbations were still present. At presentation oxygen saturation on room air was 88% and he was with respiratory insufficiency type II. Hematocrit was 61%. Diffusion capacity for carbon monoxide was 62%. High resolution computed tomography revealed centrilobular and paraseptal emphysema with traction adhesions and borderline bronchiectasis. Additional diagnostics excluded asthma, alpha 1 antitrypsin deficiency, tuberculosis and severe cardiac disease. Vitamin D concentration was 7.2 nmol/L (range: 36.8 - 171.0). After 6 months with vitamin D3 (4000 I.U. per day) supplementation mMRC and CAT score, as well as FEV1 improved. The therapy was de-escalated to Aclidinium (800 mcg, BID) + Indacaterol (150 mcg, once daily). He experienced only one mild egzacerbation in next one year. The clinical outcomes in COPD are markedly heterogeneous. Identification of reliable, predictive biomarkers of COPD outcomes is imperative. Some studies have shown that vitamin D deficiency was associated with increased risk of COPD and severe COPD. Systematic reviews and meta-analysis from randomised controlled trials (RCT) showed that vitamin D supplementation protected against acute respiratory tract infection and may reduce inflammation in hospitalized COPD patients, but also, increase the quality of life. 8 cohort, 5 case-control, and 5 RCTs showed that vitamin D supplementation may prevent COPD exacerbations. But, it has been shown that vitamin D3 supplementation reduced the rate of moderate/severe COPD exacerbations, only when baseline levels were <25 nmol/L or <50 nmol/L. Although, some meta-analysis found certain evidence for the association between low serum vitamin D levels and COPD, the association between serum vitamin D and COPD is not well studied and further research is warranted. Matevž Harlander1,2, David Lestan1, Matjaž Turel1 1Department of Pulmonary Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia matevz.harlander@gmail.com Introduction: This study aimed to determine the association between peripheral blood cell counts and exacerbations of COPD. Methods: This observational prospective study comprised 97 patients (44 females) with COPD. Their clinical characteristics and a history of exacerbations in the last 12 months were noted. Upon inclusion, all patients had to be in a stable state, at least 4 weeks after the last COPD exacerbation and not receiving systemic corticosteroids. Peripheral blood cell counts were determined upon the first visit. Patients were followed up for 12 months, and the number of moderate and severe exacerbations during this period was recorded. Results: Patients who had at least one moderate or severe exacerbation during the observational period had lower BMI (24.5 [4.0] vs. 26.4 [4.8], p = 0.046), lower age (65 [9] vs. 68 [7] years, p = 0.037), worse lung function (FEV1: 45 [17] vs. 63 [21] %, p < 0.001 and FVC: 75 [16] vs. 86 [20] %, p = 0.005) and more frequent history of at least one exacerbation in previous 12 months (50.0 vs. 26.2 %, p = 0.027), while there was no difference in sex, smoking history or CAT. Peripheral blood cell counts showed higher relative and absolute eosinophil counts in patients with at least one exacerbation as compared to patients without exacerbations (3.01 [2.60] vs. 1.91 [1.27] %, p = 0.006 and 225 (190) vs. 154 (99) cells/µL, p = 0.017) but there were no significant differences in other parameters. Multivariate analysis using Cox regression model identified lung function (FEV1) as the only independent predictor of future exacerbations (HR [95% CI]: 0.976 [0.956 - 0.996], p = 0.019). Conclusion: In our cohort of patients with COPD, higher relative and absolute eosinophil counts were seen in patients with at least one observed moderate or severe exacerbation. However, the multivariate analysis confirmed only lung function as an independent predictor of exacerbations. Lenka Sedlácková Nemocnice Na Homolce, Prague, Czech Republic sedlackova.len@email.cz Introduction: Many patients are prevented from radiocontrast examination due to so called „iodine allergy “. Only a minority of them rightfully. True radiocontrast hypersensitivity can be confirmed or ruled out by allergy work up. Clinical manifestation: Hypersensitivity reactions (HR) to radiocontrast media (RCM) are classified as immediate or nonimmediate. Immediate reactions start within one hour from RCM application while nonimmediate reactions start usually within several hours or days. Urticaria, angioedema, bronchospasm and anaphylaxis are typical clinical pictures of immediate reactions. Maculopapular exanthema is the most frequent nonimmediate manifestation. Diagnosis and management: The most significant risk factor of HR is a past reaction to RCM. Contact or irritant dermatitis after iodine disinfection or fish/seafood allergy is not considered a risk factor of RCM hypersensitivity anymore. Laboratory tests can confirm the diagnosis of anaphylaxis (acute and basal tryptase) or detect an immediate type of allergy mediated by IgE to the respective RCM (basophil activation tests). Skin tests (ST) can confirm an immediate allergy (prick and intradermal tests with evaluation in 20 minutes) as well as a nonimmediate allergy (intradermal or patch tests with evaluation in 24-96 hours). Negative results of ST do not predict tolerance as approximately half of HR to RCM are mediated by direct mast cell degranulation without specific immune response. Some centres use drug provocation tests (DPT) to confirm allergy or tolerance to the respective RCM, in appropriate settings due to a risk of inducing HR. The current approach to the management of RCM HR is based on risk stratification, according to the type and severity of index reaction. Main measures are a change of RCM with respect to allergy test results and a premedication. Conclusion: Proper allergy evaluation helps to de-label false diagnosis of iodine allergy and find safe RCM for future use. Total avoidance of all RCM is necessary in a very low proportion of patients. Matija Rijavec1,2, Mitja Košnik1,3, Ana Koren1, Peter Kopac1,3, Julij Šelb1, Romana Vantur1, Žan Kogovšek1, Mojca Bizjak1, Nissera Bajrovic1, Mihaela Zidarn1,3, Peter Korošec1 1University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 2Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia 3Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia matija.rijavec@klinika-golnik.si Omalizumab represents an effective treatment for chronic spontaneous urticaria (CSU). However, the response to treatment is variable, as some CSU patients respond to treatment within days of their first omalizumab injection, others respond within weeks, and a subgroup of patients do not respond to omalizumab at all. Currently, it is difficult to predict which patients will benefit most from omalizumab treatment. The aim of this study was to evaluate the predictive value of different markers, measured before starting omalizumab treatment, for the response to omalizumab in patients with CSU. We enrolled 43 patients with active CSU, whose symptoms were not controlled with high doses of H1 antihistamines and were consequently treated with omalizumab. The rate of clinical response to omalizumab treatment (CSU-R) was 84% (36/43). Seven (16%) patients were nonresponders (CSU-NR). CSU-NR had significantly lower absolute numbers of circulating basophils and basophil CD63 activation, higher CD63 activation of donor basophils after incubation with sera of CSU patients, lower FceRI and IgE densities on the basophils, and lower whole-blood relative gene expression of FCER1A and HDC, and a lower basophil gene mean (calculated as the mean of standardized gene expression variables of FCER1A, CPA3 and HDC). As indicated by the estimated area under the ROC curve, the absolute blood basophil count (AUC = 0.99), followed by the FceRI density per basophil (AUC = 0.95), FCER1A gene expression (AUC = 0.95) and the basophil gene mean (AUC = 0.95), showed the highest accuracy in discriminating between CSU-R and CSU-NR. Similarly, the number of circulating basophils was the most significant predictor of CSU-NR (The optimal cut-off was 1.7 basophils/µL with the OR of 144. In conclusion, the most important finding of our study is that a very low number of circulating basophils, in addition to the corresponding low whole blood gene expression of basophil related markers, especially FCER1A and the basophil gene mean, showed the highest accuracy in discriminating between CSU-R and CSU-NR, and in predicting the response to omalizumab therapy. Therefore, we speculate that the baseline absolute basophil count represents a promising and feasible laboratory approach for predicting the clinical response to omalizumab. Brigita Koren, Maja Tomazin, Vojko Berce Pediatric Clinic, University Medical Centre Maribor, Maribor, Slovenia gitakoren@yahoo.com Background: Selective IgA deficiency (sIgAD) is defined as an isolated deficiency of serum IgA in an individual older than four years of age in whom other causes of hypogammaglobulinemia have been excluded. It is the most common primary immunodeficiency. Methods: The clinical manifestations of pediatric patients seen at our clinic in the last 5 years were retrospectively analyzed. Results: 45 patients were enrolled. The results are presented in table. Clinical manifestation, n (%) Partial deficiency, n=9 Complete deficiency, n=36 Total, n=45 P -value Recurrent otitis media 5 (55.5) 7 (19.4) 12 (26.7) 0.043 Pneumonia 3 (33.3) 6 (16.6) 9 (20) 0.354 Sinusitis 0 2 (5.5) 2 (4.4) 1.000 Gastrointestinal infections 3 (33.3) 6 (16.6) 9 (20) 0.354 Urinary infections 1 (11.1) 2 (5.5) 3 (6.7) 0.497 Autoimmune diseases 2 (22.2) 5 (13.8) 7 (15.6) 0.614 Food allergy 3 (33.3) 7 (19.4) 10 (22.2) 0.393 Asthma 3 (33.3) 8 (22.2) 11 (24.4) 0.666 Atopic dermatitis 1 (11.1) 3 (8.3) 4 (8.9) 1.000 Celiac disease 0 4 (11.1) 4 (8.9) 0.569 Positive autoantibodies 0 10 (27.7) 10 (22.2) 0.173 Asymptomatic 2 (22.2) 4 (11.1) 6 (13.3) 1.000 Average age was 6.4 years. 23 patients (51%) were male. 36 patients (80%) had complete sIgAD. The most common infections were recurrent otitis media. Asthma and autoimmune diseases were also common. Mostly, there were no significant differences between patients with partial and complete IgA deficiency. None of our patients had serious invasive infection and none progressed to common variable immunodeficiency. In most patients sIgAD was persistent, whereas in 1 patient severe deficiency resolved over time. In 1 patient partial deficiency progressed to severe deficiency. Most of our patients were symptomatic, even those with partial deficiency which is probably due the fact that we included only patients who were examined in our clinic because of health problems. Conclusion: Children with sIgAD are at risk of recurrent infections, allergic, autoimmune and other diseases. Therefore, they should be followed up regularly. Iva Hafner Bratkovic, Petra Sušjan, Duško Lainšcek, Roman Jerala National Institute of Chemistry, Ljubljana, Slovenia iva.hafner@KI.si NLRP3 inflammasome is a multiprotein complex mediating inflammatory response in a variety of autoinflammatory, metabolic and degenerative diseases. Upon activation with diverse triggers NLRP3 oligomerizes, recruits adaptor protein ASC and procaspase-1. Active caspase-1 processes IL-1ß and IL-18 cytokines to their mature form and gasdermin D to a pore-forming protein that induces pyroptotic cell death. Although the role of NLRP3 in various pathologies has been described, not much is known about the molecular mechanism of NLRP3 inflammasome activation. In order to define the role of particular domains of NLRP3 in inflammasome trigger sensing, assembly and autoregulation systematic truncation of NLRP3 and reconstitution of NLRP3 variants in NLRP3-deficient macrophages was performed. We demonstrate that LRR domain is dispensable for NLRP3 activation and self-regulation. A minimal NLRP3 truncation variant was found fully responsive to various canonical NLRP3 activators. Substitution of the pyrin domain of NLRP3 with the CARD domain of NLRC4 or ASC led to a constitutive activation, demonstrating that the pyrin domain restricts NLRP3 in an inactive conformation. NLRC4 inflammasome is formed by self-catalytic polymerization of NLRC4 initiated with bacterial ligand/NAIP complex. We were interested whether similar process is involved in NLRP3 activation. We show that pathological mutations of NLRP3 failed to engage wild-type NLRP3 in a self-catalytic oligomerization, demonstrating that the activating signal is not enhanced at the level of NLRP3 oligomerization, representing an additional level of NLRP3 regulation. These results contribute to the understanding of the molecular basis of NLRP3 inflammasome activation and demonstrate the versatility of recognition and regulation mechanisms of the innate immune receptors. Reference: Hafner-Bratkovic et al. (2018) Nature Communications 9, article no. 5182 Petra Sušjan1,2, Duško Lainšcek1,5, Žiga Strmšek1,2, Vesna Hodnik3,4, Gregor Anderluh3, Iva Hafner- Bratkovic1,5 1Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia 2Graduate School of Biomedicine, University of Ljubljana, Ljubljana, Slovenia 3Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, Slovenia 4Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia 5EN-FIST Centre of Excellence, Ljubljana, Slovenia petra.susjan@ki.si NLRP3 inflammasome is a multiprotein complex which forms within cells in response to various microbial and self-derived stress-associated triggers in order to activate the production of pro-inflammatory cytokines such as IL-1ß and pyroptotic cell death. Mutations in the gene encoding NLRP3 cause rare cryopyrin-associated periodic syndromes (CAPS) and growing evidence links NLRP3 inflammasome to common diseases such as Alzheimer´s disease. The mechanism of NLRP3 inflammasome activation is not fully understood, which hinders the design of effective and specific NLRP3 inflammasome inhibitors. In order to modulate different stages of NLRP3 inflammasome assembly we selected a set of peptides whose sequences correspond to segments of the inflammasome proteins NLRP3 and ASC. The design was based on the crystal structures of the PYD and CARD interaction domains and on the pathological mutation hotspots in the NLRP3 NACHT domain. We identified peptides that were inhibiting the activation of caspase-1, the release of IL-1ß and ASC oligomerization in response to soluble and particulate NLRP3 triggers. Modulatory peptides also attenuated IL-1ß release from the cell lines with NLRP3 mutations linked to CAPS. One of the peptide inhibitors selectively inhibited NLRP3 inflammasome and also effectively dampened neutrophil infiltration in the mouse model of silica-induced peritonitis. When equipped with peptide sequence which allows transfer through the blood-brain barrier the peptide localised inside the cells as well as within the brain of mice after intravenous injection showing its potential as an NLRP3 inflammasome inhibitor in a neurological setting. Designed peptides provide an insight into the mechanism of NLRP3 inflammasome assembly and the basis for the development of novel anti-inflammatory strategies. M. Trstenjak Prebanda1, M. Biasizzo1,2, J. Završnik1, V. Brault3, Y. Herault3, B. Turk1,4, N. Kopitar Jerala 1Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana, Slovenia 2Jožef Stefan International Postgraduate School, Ljubljana, Slovenia 3IGBMC, University of Strasbourg, Strasbourg, France 4Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia natasa.kopitar@ijs.si Progressive myoclonus epilepsy of Unverricht–Lundborg type (EPM1) is an autosomal recessively inherited neurodegenerative disease, characterized by the cerebellar granule neurons apoptosis, progressive ataxia and myoclonic epilepsy. Mutations in the cysteine proteinase inhibitor stefin B/cystatin B (CTSB) are found in patients with EPMI. A mouse model of the EPM1 disease, stefin B deficient mice, recapitulates the principal symptoms of EPM1, myoclonic seizures and progressive ataxia. Stefin B deficient mice were found more sensitive to lipopolysaccharide (LPS) induced sepsis as a consequence of increased expression of caspase 11 and nucleotidebinding oligomerization domainlike receptor 3 (NLRP3) inflammasome activation and higher levels of mitochondrial reactive oxygen species (ROS). In addition we determined that the lack of stefin B leads to a significant increase in the expression of the mitochondrial antioxidant proteins to LPS challenge [3]. In our study we used stefin B deficient mice (StB KO), as well as mice with an additional copy of stefin B gene, stefin B trisomic mice (StB 3n). In macrophages from stefin B trisomic mice we determined lower caspase 11 expression and non canonical inflammasome activation. Stefin B suppressed mammalian target of rapamycin (mTOR) activity and induced autophagic activity for mitophagy by increase of unc51 like autophagy activating kinase 1 (Ulk1) phosphorylation. As a conclusion, we propose that stefin B plays an important role in regulation of autophagy and non canonical inflammasome activation. REFERENCES: Maher K et al. Biol Chem. 2014;289(46):31736-50. Kopitar-Jerala N. Front Cell Neurosci. 2015 Dec 8;9:458. Trstenjak Prebanda M et al. Cells. 2019 Nov 21;8(12):1476. Žiga Jakopin Faculty of Pharmacy, University of Ljubljana, Slovenia ziga.jakopin@ffa.uni-lj.si Muramyl dipeptide, a fragment of bacterial peptidoglycan, has long been known as the smallest fragment possessing adjuvant activity, on the basis of its agonistic action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). There is a pressing need for novel adjuvants and NOD2 agonists provide an untapped source of potential candidates. Here, we present the design, synthesis and characterization of a series of novel acyl tripeptides. A pivotal structural element for molecular recognition by NOD2 has been identified, culminating in the discovery of the most potent desmuramylpeptide NOD2 agonist to date, albeit solely in in vitro conditions. Further pharmacokinetic optimization afforded an in vivo active compound, which was able to significantly induce ovalbumin-specific IgG titers in a mouse model of adjuvancy. Our findings provided deeper insights into the structural requirements of desmuramylpeptides for NOD2-activation and highlight the potential use of NOD2 agonists as adjuvants for vaccines. ACKNOWLEDGMENTS This work was supported by the Slovenian Research Agency grant (No. 0787-P208) and the Croatian Science Foundation (HrZZ) (Project No. 7387). REFERENCES [1] Jakopin et al., J Med Chem 2012, 55, 6478–6488. [2] Gobec et al., Eur J Med Chem 2016, 116, 1–12. [3] Gobec et al., J Med Chem 2018, 61, 2707–2724. Mateja Mancek Keber Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia mateja.mancek@ki.si Extracellular vesicles (EVs) are submicron membrane-contained vesicles that are released from cells. The significance of EVs lies in their capacity to transmit the information from donor to recipient cells thus influencing their function. The information can be proteins, nucleic acids, lipids or sugars. The amount of released EVs increases under stressful conditions and increased concentrations of EVs are detected in the peripheral blood of patients with chronic inflammatory diseases, cancer or infection. Atherosclerosis and RA are chronic diseases with inflammatory characteristics involving oxidative stress, where lipids with unsaturated fatty acids chains are particularly prone to oxidation with reactive oxygen species and might be released from cells with EVs. These oxidized species represent endogenous damage associated endogenous ligands (DAMPs), which can be recognized by innate immune receptors. We showed that EVs from patients with RA or produced under oxidative stress in cell cultures activated Toll-like receptor 4 (TLR4/MD-2) receptor complex. The activity of EVs was oxidation related. 15-lipoxygenase oxidized lysoPLs were identified as TLR4 ligands. Their generation was dependent on 15-LO and sPLA2 activity, which we detected in the synovial fluid from patients. Injection of sPLA2-IIA into mice promoted K/BxN serum induced arthritis in TLR4-dependent manner. As both 15-LO and sPLA2 are induced during inflammation, therefore these results imply the role of oxidized lysoPLs in stressEVs in promoting sterile inflammation through TLR4 signaling. Link between activation of inflammatory signaling pathways and cancer is particularly evident in Waldenström macroglobulinaemia (WM), where more than 90% of patients harbor a mutant of MyD88. MyD88 is a signaling adapter protein involved in TLR signaling through myddosome formation. MyD88L265P constitutively activates the signaling pathway and provides a survival signal to cancer cells, thus chronic inflammation may contribute to the tumor` microenvironment. We identified an alternative mechanism to the transmission of inflammatory mediators by transfer of the myddosome via EVs. Constitutively active MyD88L265P was transferred to other recipient cells, where MyD88L265P recruited the endogenous MyD88wt to trigger cell activation without receptor activation. In vivo internalization of EVs containing MyD88 occurred and the changes to the bone marrow microenvironment were observed. MyD88-containing EVs were detected in the bone marrow aspirates of WM patients. This process may play an important role in WM cancer development by triggering inflammation in the nontransformed cells independently of the membrane receptors. The work was financially supported by the H2020-MSC-ETN-642157 project TOLLerant and the Slovenian Research Agency (project no. J3-9257, J3-8196, J7-2379; research core no. P4-0176). Peter Pecan1,2, Szabolcs Hambalkó3, Van Thai Ha1,2, Csilla T. Nagy3, Csilla Pelyhe3, Duško Lainšcek1,4, Bence Kenyeres3, Gábor B. Brenner3, Anikó Görbe3,5, Ágnes Kittel6, Monika Barteková7,8, Péter Ferdinandy3,5, Mateja Mancek-Keber1,4, Zoltán Giricz3,5 1Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia 2Graduate School of Biomedicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 3Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary 4Centre of Excelence EN-FIST, Ljubljana, Slovenia 5Pharmahungary Group, Szeged, Hungary 6Institute of Experimental Medicine, ELRN, Budapest, Hungary 7Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia 8Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia peter.pecan@ki.si Introduction: Adaptive response is an important defense function, which helps cells to fight against oxidative stress. Studies showed that low levels of oxidized species (among them also oxidized phospholipids) enhance defense capacity of cells by inducing the expression of antioxidant enzymes such as heme oxygenase 1 (HO-1) as well as by triggering transient activation of Toll-like receptors (TLRs). We investigated the capability of extracellular vesicles (EVs), released after oxidative stress (stressEVs), to induce TLR dependent signaling in H9c2 and AC16 heat-derived proliferating cell lines. We wanted to assess if such EVs are capable of inducing cardioprotection against acute ischemia/reperfusion injury. Methods: StressEVs were produced in HEK293 cells exposed to 10 µM calcium ionophore A23187 and isolated using ultracentrifugation. StressEVs were characterized by DLS, NTA, WB and electron microscopy. Changes in gene expression and signaling after stressEV stimulation were determined by dual luciferase assay, qPCR, WB and ELISA. Cytotoxicity after hypoxia/reoxygenation was assessed by LDH activity assay and by calcein staining. Results and discussion: Our results show that EVs released from cells cultured in vitro as a consequence of calcium ionophore treatment can be utilized as a treatment option against simulated I/R injury in cardiac myocytes. Even though stressEVs were capable of activating TLR dependent signaling, the cardioprotection resulted from induction of antioxidant pathways, which were triggered in a TLR-independent manner. Based on these results, we suggest that calcium ionophore-induced stressEVs may reveal novel avenues for cardioprotective treatments against ischemic cardiac disease such as myocardial infarction. Funding: Slovenian research was funded by the Slovenian Research Agency (research project no. J3-8196 and J3-9257 to M.M.-K.; bilateral project BI-HU/17-18-010 to M.M.-K and Z.G.) and by the H2020-MSC- ETN-642157 project TOLLerant. Hungarian research was funded by the National Research, Development and Innovation Office of Hungary (NKFIH; VEKOP-2.3.2-16-2016-00002, TÉT_16-1-20160057, National Heart Program NVKP, Grant/Award Number: NVKP_16-1-2016-0017), EU COST Action BM1203 EU-ROS, the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the Therapeutic development thematic programme of Semmelweis University, grant H2020-SMEInst-2018-2020-1 / SME-1 Project Number: 856235 and by Research Excellence Programme of the National Research, Development and InnovationOffice of the Ministry of Innovation and Technology in Hungary (TKP/ITM/NKFIH. Gregor Serša, Maja Cemažar Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia gsersa@onko-i.si Interleukin-12 (IL-12) is cytokine with potent antitumor effectiveness. Its action is mediated by cellular and humoral immune system stimulation and antiangiogenic action. The first clinical studies with recombinant proteins were terminated due to its high toxicity, although the good antitumor effectiveness was evident in some patients. New technologies, though, enable sustained and controlled local or systemic release of IL-12 by gene therapy approach. Transfection of cells, tumor or normal in the skin enable local release of the transgene (IL-12) and direct antitumor effectiveness on targeted tumors. Specific delivery system, by electroporation enables also plasmid DNA transfer, with no side effects. Thus, naked plasmid coding for IL-12 transfection by electroporation is feasible and effective as demonstrated on preclinical level and on clinical level. Studies on mouse tumors demonstrated its effectiveness on various tumors, in veterinary oncology on mast cell tumors and oral malignant melanoma, and in the clinical study conducted in USA on melanoma metastases. We tested this system on various levels and want to further develop it into use in clinical oncology. Our aim is to develop combined treatment of electrochemotherapy with adjuvant intratumoral IL-12 gene electrotransfer. With such approach, we anticipate to transform the local effectiveness of either of the approaches into the locoregional and systemic effect. This is also the purpose of the SmarGene.Si project that will be developing this treatment approach from the bench to bedside. Acknowledgement: This research was funded by the Slovenian Research Agency, grant number P3-0003. The investment was co-financed by the Republic of Slovenia and the European Regional Development Fund within the scope of SmartGene.Si. Urška Kamenšek, Katja Uršic, Maja Cemažar, Gregor Serša Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia ukamensek@onko-i.si Gene electrotransfer (GET) is one of the most efficient non-viral gene therapy approaches for localized gene transfer into tumors in vivo. It is especially promising for delivering different cytokines that are toxic if administered systemically. Currently, GET of plasmids encoding the cytokine interleukin 12 (IL-12) is approaching clinical use for treatment of various superficial solid tumors. Plasmids used in ongoing IL-12 GET clinical trials in the USA, contain antibiotic resistance genes and are, thus, according to safety recommendations of the European Medicines Agency, not suitable for clinical trials in the EU. Hence, in our group we are striving to prepare plasmids without antibiotic resistance genes. Moreover, we are investigating different immunological capacities of GET: from using GET as an adjuvant to local ablative therapies or tumor-based vaccines, to investigating the adjuvant effect of plasmid DNA itself. In one of the immunological GET based approaches, we are utilizing concomitant intratumoral GET of two plasmids: a plasmid encoding a cytotoxic cytokine tumor necrosis factor alpha (TNFa) to induce in situ vaccination and a plasmid encoding an immunostimulatory cytokine IL-12 to boost the primed local antitumor immune response into a systemic one. Our initial results confirmed the feasibility and effectiveness of the approach in eliciting a potent and durable antitumor response in a mouse melanoma tumor model. In furthers studies, our aim was to prove the systemic, i.e., abscopal, effectiveness of the approach. Furthermore, we tested the approach in two additional tumor models, since in situ vaccination has the potential to be effective in different cancer types, considering it utilizes the tumors own antigens. It turned out that both local and abscopal effectiveness of in situ vaccination by intratumoral GET of TNFa and IL-12 very much depend on the immune status of the tumor. While the abscopal effectiveness was higher in more immunogenic tumor model, local was lover. Currently, we are investigating the mechanisms of observed differences in the effectiveness of the described and similar approaches. Acknowledgement: This research was funded by the Slovenian Research Agency, grant number P3-0003. The investment was co-financed by the Republic of Slovenia and the European Regional Development Fund within the scope of SmartGene.Si. Martina Rebersek Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia mrebersek@onko-i.si Background: Based on recent data from clinical trials, the immune checkpoint inhibitor pembrolizumab prolongs survival and has a good toxicity profile in patients with advanced or metastatic melanoma: However, the question remains whether these results are transmitted into daily clinical practice: The aim of this study was to assess the efficacy and toxicity of pembrolizumab in treatment-naive patients with metastatic melanoma in everyday clinical practice in Slovenia and compare it to the results from clinical trials. Patients and methods: From January 2016 to December 2018, 138 metastatic treatment-naive melanoma patients treated with pembrolizumab at the Institute of Oncology Ljubljana in Slovenia were included in our observational retrospective study: Patient and treatment characteristics were retrospectively collected from hospital data base: Statistical data was obtained using the SPSS software version 22: Survival rate was calculated with the Kaplan-Meier method: Observation period took place between January 2016 and the end of June 2019. Results: The estimated median overall survival (OS) was 25.1 months (95% CI, 14.6 35.6) and the median progression-free survival (PFS) was 10.7 months (95% CI, 5.915.4): Among all patients, 29 (21.0%) achieved complete response, 31 (22.5%) partial response and 23 (16.7%) reached stable disease: The number of organs with metastatic involvement and the level of baseline lactate dehydrogenase (LDH) concentration had significant influence on survival rates: Immune-related adverse events (irAE) were reported in 88 (63%) patients, while grade 3-4 irAE occurred in 12 (8.7%): Due to toxicity, 16 (11.6%) patients discontinued the treatment. Conclusions: Our real-world data from single centre retrospective analysis of treatment-naive metastatic melanoma patients treated with pembrolizumab showed inferior median OS and similar median PFS, compared to the results from clinical trials: However, patients with normal serum levels of LDH and a small number of organs with metastatic involvement had comparable survival outcomes: Toxicity rates of pembrolizumab were quite similar: These results further support the use of pembrolizumab for metastatic treatment-naive melanoma patients. Funding: The research was financially supported by The Slovenian Research Agency (ARRS), grant number P3-0321. Damijan Valentinuzzi1,2, Martina Vrankar3, Nina Boc3,Valentina Ahac3, Žiga Zupancic3, Mojca Unk3, Katja Škalic3, Ivana Žagar3, Andrej Studen1,2, Urban Simoncic1,2, Jens Eickhoff4, Robert Jeraj1,2,5 1Jožef Stefan Institute, Ljubljana, Slovenia 2Faculty of Mathematics and Physics, University of Ljubljana, Ljubljana, Slovenia 3Institute of Oncology Ljubljana, Ljubljana, Slovenia 4Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA 5Department of Medical Physics, University of Wisconsin, Madison, WI, USA damijan.valentinuzzi@ijs.si Background: Immune checkpoint inhibitors have shown impressive results in patients with various malignancies. However, non-invasive biomarkers of response are still needed to identify candidates for non-responders. We investigated whether immunotherapy 18F-FDG PET radiomics signature (iRADIOMICS) predicts response of non-small-cell lung cancer patients better than the current clinical standards. Methods: Thirty patients were treated with pembrolizumab and scanned with 18F-FDG PET/CT at baseline, month 1 and month 4. Six robust radiomics features of primary tumours were analysed. The Mann-Whitney U-test (MWU), Cox proportional hazards regression analysis, and receiver operating characteristic (ROC) curve analysis were used to study the impact of radiomics features on overall survival (OS). The iRADIOMICS signature was constructed using univariate and multivariate logistic models of the most promising radiomics feature(s). Its predictive power was compared to PD-L1 tumour proportion score (TPS) and iRECIST signatures using ROC curve analysis. Accuracy of predictions were assessed with repeated 5-fold cross validation. Results: The most predictive were baseline radiomics features, e.g. Small Run Emphasis (MWU, p = 0.001; Hazard Ratio (HR) = 0.46, p = 0.007; area under the ROC curve (AUC) = 0.85 (95% Confidence Interval 0.69-1.00)). Multivariate iRADIOMICS signature was found superior to the current standards, both in terms of predictive power, as well as timewise: iRADIOMICS (baseline), AUC = 0.90 (0.78-1.00), accuracy = 78% (standard deviation 18%); PD-L1 TPS (baseline), AUC = 0.60 (0.37-0.83), accuracy = 53% (18%); iRECIST (month 1), AUC = 0.79 (0.62-0.95), accuracy = 76% (16%); iRECIST (month 4), AUC =0.86 (0.72-1.00), accuracy = 76% (17%). Conclusions: Pre-treatment multivariate iRADIOMICS signature was identified as a promising imaging biomarker of response to anti-PD-1 immunotherapy. iRADIOMICS signature could improve the management of patients on immunotherapy considerably. For example, patients identified as non-responders could receive additional therapy besides immunotherapy (e.g. chemotherapy) to improve their OS. M. Ivanovic1, A. Herzog2, L. Knez3,4, I. Kern3, M. Kovacevic3, T. Cufer3,5 1Department of Oncology, University Medical Centre Maribor, Maribor, Slovenia 2Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia 3University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 4Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia 5Medical Faculty Ljubljana, University of Ljubljana, Ljubljana, Slovenia marija.ivanovic@ukc-mb.si Background: Immunotherapy with checkpoint inhibitors (CPIs) changed the standard of treatment for advanced non-small cell lung cancer (NSCLC). In the clinical trials, monotherapy with CPIs resulted in incredibly high 1-year OS rates of up to 55% - 70% in second-line (SL) and first-line (FL) setting. Our study aimed to evaluate the efficacy of monotherapy with CPIs in advanced NSCLC. Methods: This was a retrospective observational study of 66 consecutive patients (pts) treated at a single academic centre, from August 2015 to November 2018. Clinical, pathological, treatment and survival characteristics were retrieved from the hospital registry, with prospective data collection. By Kaplan-Meier estimator progression-free survival (PFS) was calculated from the start of treatment until progression (according to RECIST 1.1 criteria), death or last follow-up, while overall survival (OS) was calculated until death or last follow-up date. Results: The main characteristics were: median age 63 (42 – 77), 55% male, 82 % current or former smokers, 83% adenocarcinoma, 94% with performance status (PS) 0 – 1. Six percent had PS = 2 and 33% had controlled CNS metastases at baseline. The characteristics did not differ between the SL cohort of 40 pts treated with atezolizumab, nivolumab or pembrolizumab (PD-L1 expression 0%-100%) and the FL cohort of 26 pts (PD-L1 = 50 %) treated with pembrolizumab. Median PFS was 3.5 months (95% CI: 1.9 – 6.6) in the SL cohort and 9.3 months (95% CI:3.5 – 8) in the FL cohort. Median OS was 9. 9 months (95% CI: 4.9 – 16.2) in the SL cohort, and has not yet been reached (95% CI: 7.1 – 8) in the FL cohort. Of note, 1-year OS was 38% (95% CI: 25 – 56%) and 62% (95% CI: 45 – 83%) in the SL and FL cohorts, respectively. Conclusion: In our real-world study, mono-immunotherapy with CPIs demonstrated very similar PFS and OS rates to those observed in the pivotal clinical trials, despite including some patients with PS = 2. Even though our cohort was small, these data support the efficacy of CPIs in a real-world setting. Marina Mencinger, Dusan Mangaroski, Urska Bokal Institute of Oncology Ljubljana, Ljubljana, Slovenia mmencinger@onko-i.si Introduction: Data from non-randomized and randomized studies show that atezolizumab (AT), a PD-L1 inhibitor, improves prognosis of chemotherapy-naive (CTn) patients whose tumors are PDL-1 positive and of chemotherapy pre-exposed (CTe) patients with metastatic urothelial cancer (mUC). The response rates, survival outcomes and safety of patients with mUC treated with AT in real-world practice were investigated. Methods: 62 patients with mUC, who received at least one cycle of AT at the Institute of Oncology Ljubljana between May 8, 2018, and Dec 31, 2019, were included. The best overall response rates as defined by RECIST and immune-related adverse events (irAE) as assessed by treating oncologists were obtained from patient’s data charts. Median overall survival (mOS) times using the Kaplan–Meier method are reported for the cohort of CTn versus CTe patients. Results: Of 62 patients, 5 (8.1%) have not been evaluated yet and 20 (32%) died prior to first radiologic evaluation. Clinical benefit was obtained in 15 (26%) cases, objective response in 12 (21%) and complete response in 5 (11%). Of all patients, 18 (29%) were CTn and 44 (71%) were CTe. PDL-1 testing was not performed in 6 (33%) CTn patients and all of them, but one, died or had progressive disease. At 5.2 months median follow-up, the mOS was 8.7 months for CTn (CI 95%:0.8-16.5) and 6.8 months for CTe (CI 95%:3.7-10). For patients with clinical benefit the mOS was 23.1 months. IrAE occurred in 20 (32 %) patients, of those 7 (11%) had grade 3-4 by CTCAE version 5.0. Systemic corticosteroids for irAE were used in 5 (8%) patients. AT was discontinued because of irAE in 7 (11%) patients. One patient suffered presumably autoimmune encephalitis that caused severe functional impairment. Conclusions: Patients with clinical benefit on AT have long disease remission. However, the mOS of all CTn and CTe patients was shorter than the mOS of similar patient groups reported in prospective studies. Noteworthy, not all of our CTn patients have been tested for PDL-1 as this was not initially required. More than 40% of patients had ECOG PS 2 or more and a significant percentage of our patients received AT near the end of life. The types and the frequency of irAE were as expected. Disclaimer: Financial support for the statistical analysis was provided by Roche Farmacevtska Družba d.o.o., Ljubljana, Slovenia. The interpretation of the results and the content of this publication expresses the author's independent professional opinion and was not influenced by Roche. Katja Perdan Pirkmajer Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia katja.perdan@mf.uni-lj.si Background: Systemic sclerosis (SSc) is a chronic autoimmune disease, currently still considered incurable. It is characterized by widespread vascular dysfunction, immune dysregulation and progressive fibrosis of the skin and internal organs. The diagnosis is based primarily upon the presence of characteristic clinical findings and supported by specific serologic abnormalities. SSc still carries the highest mortality of all the rheumatic diseases. Methods: A systematic PubMed search for papers regarding systemic sclerosis between 1st January 2010 and 1st January 2020 with search terms “systemic sclerosis”, “diagnosis” and “treatment “ was performed. Eleven articles corresponded to the pre-specified search terms. Results: SSc is classified into two subsets based on the extent of skin involvement: 1) limited cutaneous SSc with skin involvement restricted to distal limbs below elbow and knees with or without facial involvement and 2) diffuse cutaneous SSc occurring proximally to the elbows and knees. Diffuse SSc is usually characterized by more rapid onset of skin and internal organ involvement. In addition to puffy fingers or skin thickening, systemic manifestations of SSc are myopathy, joint involvement and contractures, interstitial lung disease, gastro-intestinal dysmotility and cardiac involvement. Vascular manifestations of SSc include Raynaud's phenomenon, digital ulcers, scleroderma renal crisis and pulmonary hypertension. SSc has the highest mortality, mainly due to the development of lung complications. The two most important lung complications in SSc are lung fibrosis (50-70 % of patients with interstitial lung disease) and pulmonary arterial hypertension (9-12% SSc patients). Current therapeutic options mainly manage vascular disease and fibrotic manifestations (skin disease and ILD). None of the therapies is curative, and treatment response rates vary. Conclusions: Diagnosis and follow-up of patients with systemic sclerosis has to be systematic, while treatment must be adapted to organ manifestations. Although specific therapies for gastrointestinal, pulmonary or vascular complications exist, patients respond only partly to these and new therapeutic approaches are still needed. Acknowledgements: KPP is supported by Slovenian Research Agency Grants P3-0314 and J7-8276. Katjuša Mrak Poljšak1, Neža Brezovec1,2, Katja Lakota1,3 1Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia 3FAMNIT, University of Primorska, Koper, Slovenia katja.lakota@guest.arnes.si Gene expression microarrays and RNA-Seq data of transcriptomic profiling are published in public repositories, such as Array Express or Gene Expression Omnibus, containing 2.5 and 3.5 million assays respectively. This is in line with open science policy of EU Commission and FAIR (Findable, Accessible, Interoperable and Reusable) open access data policy recommendation for publicly funded research. Accessibility of transcriptomic data allows secondary analyses to answer novel questions, test reproducibility of published data, perform meta-analyses and compare gene expression profiles across different studies and to stratify clinical responses retrospectively. Integrative analysis of skin biopsy molecular signatures divided systemic sclerosis (SSc) patients into four subgroups with divergent mechanistic features. Peripheral blood mononuclear cell gene expression re-analysis suggested that the fibroproliferative subgroup of SSc patients benefits most from autologous hematopoietic stem cell transplantation (1), while modified Rodnan skin score improves most in inflammatory subgroup of patients after mycophenolate mofetil therapy (2). No such studies are published on SSc lung tissue datasets, although pulmonary fibrosis is life threatening complication of SSc. We used deposited lung fibroblasts dataset of SSc patients with interstitial lung disease vs. controls (GSE40839) and lung tissue vs. control (GSE76808) to analyze differentially expressed gens, processes, transcription factors and miRNA importantly implicated in development of lung fibrosis in fibroblasts, the main effector cells and the rest of lung cell populations. We found 843 differentially expressed genes in fibroblasts and 549 in lung tissue, with 66 overlapping genes. Apoptosis and response to cytokines were shared in both groups, while growth factors, cell cycle and proliferation pathways were only upregulated in fibroblasts. Only in lung tissue, but not in fibroblasts 42 immunoglobulin genes were increased, pointing towards B cell involvement. Other upregulated genes only in tissue showed central involvement of insulin growth factor (IGF), complement and DNA damage pathways. PI3K/Akt pathway and FOXO1 transcription factors, already known therapeutic targets in some metabolic diseases, were suggested to regulate perturbed genes and mir-132 was suggested as regulator of their expression. Leveraging existing datasets offered us a convenient and cost-effective avenue to identify novel hypotheses for further experimental work. Funding: This study was supported by Slovenian research agency (Systemic autoimmune diseases P3- 0314 and Z3-9261 to KL). Resources: 1) J.Franks et al., Machine Learning Classification of Peripheral Blood Gene Expression Identifies a Subset of Patients with Systemic Sclerosis Most Likely to Show Clinical Improvement in Response to Hematopoietic Stem Cell Transplant, Arthritis Rheumatol. 2018; 70 (suppl 10). 2) M. Hinchcliff et al, Mycophenolate Mofetil Treatment of Systemic Sclerosis Reduces My-eloid Cell Numbers and Attenuates the Inflammatory Gene Signature in Skin, J Invest Der-matol. 2018 Jun; 138(6): 1301–1310. Alojzija Hocevar Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia alojzija.hocevar@gmail.com Background: IgA vasculitis (IgAV) is an immune complex vasculitis, characterized by deposition of immunoglobulin A in vessel wall, and clinically by skin, joint, gastrointestinal (GI) and renal involvement. It is still poorly defined disease in the adult population, particularly markers, predicting visceral involvement have not been extensively. The aim of our study was to determine the predictors of GI or renal involvement in adult IgAV. Methods: The prospective study included histologically proven adult IgAV cases diagnosed between January 2013 and July 2019 at Department of Rheumatology, UMC Ljubljana. We evaluated the role of several clinical and the laboratory parameters as markers predicting the GI or renal involvement in IgAV, using the multiple logistic regression analysis. Results: During the observation period, we identified 214 incipient adult IgAV cases (59.3% males, median (interquartile range) age 64 (57–76) years). Skin involvement was present in all patients (necrotic lesions developed in 98 (45.8%) patients and vasculitic lesions above the waistline (i.e. generalized purpura) were observed in 109 (50.9%) patients). Seventy-two (33.6%) patients reported arthralgia, and 29 (13.6%) patients had arthritis. The GI tract and renal involvement developed in 58 (27.1%) and 83 (38.8%) cases, respectively (concurrently in 26 cases). In the multivariate logistic regression analysis, generalized purpura (OR 6.74 (95%CI 3.18–14.31)), the pretreatment neutrophil to lymphocyte ratio (NLR) >3.5 (OR 2.78 (95%CI 1.34–5.75)), and elevated serum IgA levels (OR 0.40 (95%CI 0.20–0.79)) emerged as factors associated with GI involvement, whereas current smoking (OR 3.23 (95%CI 1.50–6.98)), generalized purpura (OR 1.98 (95%CI 1.08–3.61)), elevated serum IgA (OR 2.25 (95%CI 1.21–4.18)), NLR >3.5 (OR 1.96 (95%CI 1.02–3.77)), and age (1.02 (95%CI 1.01–1.04)) emerged as factors associated with renal involvement. Conclusion: Generalized purpura and pre-treatment NLR predicted both GI and renal involvement, and active smoking was associated with renal involvement. The serum IgA level had a divergent effect on renal and GI involvement in adult IgAV. The presented findings could help clinicians to identify patients, who need a vigilant monitoring during the acute IgAV. T. Kuret1,2,3, A. Hocevar1,4, K. Lakota1,2, T. Grentzinger5, O. Distler6, S. Cucnik1,3, O. Voinnet5, M. Tomšic1,4, S. Sodin-Šemrl1,2, M. Frank-Bertoncelj6 1Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia 2FAMNIT, University of Primorska, Koper, Slovenia 3Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia 4Medical Faculty, University of Ljubljana, Ljubljana, Slovenia 5Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland 6Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich, Zurich, Switzerland tadejakuret@gmail.com Background: Immunoglobulin A vasculitis (IgAV) is a small vessel, immune complex vasculitis, involving skin, joints, gastrointestinal tract and kidney. Currently, no serum diagnostic or prognostic biomarkers exist for IgAV. Circulating microRNAs (miRNAs) can be used as noninvasive biomarkers of various diseases, since they are stable in serum and their expression signatures can reflect the disease-specific pathology. Our aim was to investigate the serum miRNA profile in IgAV patients and healthy blood donors (HBDs), as well as explore in silico their gene targets and biological pathways. Methods: Small RNAs were isolated from sera of therapy-naive IgAV patients and from age- and sex-matched HBDs (n=6 each) using the novel TRAPR method. Small RNA libraries, prepared with Lexogen kit, were sequenced (Illumina4000) and reads mapped onto human genome (GRCh38). We used the miRror database to predict target genes of differentially expressed miRNAs (log2 fold change = |1| and padj < 0.05) between IgAV patients and HBDs and the enrichment of target genes in biological pathways was analysed using the STRING protein networks platform. Results: In total, 88 miRNAs were identified as differentially expressed (log2 fold change = |1| and padj < 0.05) between IgAV patients and HBDs. Specifically, 28 miRNAs were elevated in the serum of IgAV patients (e.g. miRNA-128, -937, -30c, -328, -26a, padj < 0.005), whereas 60 miRNAs were decreased (e.g. miRNA-22, -146a, -185, -320a/b/c, -378a, -423, -3184; padj < 10-10). These miRNAs thus represented the IgAV-associated serum miRNA signature. miRror analysis identified 426 protein-coding genes as predicted targets of IgAV-associated miRNAs. These genes, as analyzed by STRING, were enriched in distinct molecular networks including “Regulation of actin cytoskeleton” (FDR 0.008), “Fcgamma receptor dependent phagocytosis” (FDR 0.01) and “Proteoglycans in cancer” (FDR 0.009). Additionally, three distinct molecular clusters were identified as enriched in miRNA-target genes, specifically “Chemokines and their receptors”, “Ubiquitination process” and “Vesicle, endocytosis, lysosomes and their trafficking”. Conclusions: An IgAV-associated serum miRNA signature was identified in adult IgAV patients that clearly discriminated IgAV patients from HBDs, and might play a key role in the pathogenesis of IgAV. Our study sets the basis for the identification of novel, serum-based disease biomarkers in IgAV. Funding: The study was supported by Slovenian research agency (Systemic autoimmune diseases P3-0314). M. Ogric1,2, P. Žigon1,3, K. Lakota1,3, K. Mrak Poljšak1, S. Praprotnik1, D. Drobne4,5, B. Štabuc4,5, S. Sodin-Semrl1,3, S. Cucnik1,2 1Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia 3FAMNIT, University of Primorska, Koper, Slovenia 4Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia 5Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia manca.ogric@gmail.com Background and aim: The treatment of inflammatory bowel and chronic rheumatic diseases has changed dramatically since the development of TNF-a inhibitors. However, despite evidences of high efficacy, many patients do not respond or fail to respond to the treatment, and the immunogenicity, formation of anti-drug antibodies (ADA), could be the major reason. Therefore, the importance of therapeutic drug monitoring of TNF-a inhibitors, such as infliximab (IFX) and adalimumab (ADL) has been increasingly recognized in the recent years, thus also establishing a demand for developing appropriate assays. Many different assays used in routine analysis of ADA differ in their reported levels and types of the detected antibodies. We aimed to investigate which method for ADA detection best improves the therapeutic drug monitoring of IFX and ADL. Methods: 134 samples of patients on IFX therapy (IFX group) and 68 samples of patients on ADL therapy (ADL group) from the Departments of Rheumatology and Gastroenterology, University Medical Centre Ljubljana, with undetectable drug levels were tested for ADA with in-house competitive ELISA (cELISA), in-house bridging ELISA (bELI-SA) and Reporter Gene Assay (RGA). Samples were collected between August 2016 and October 2019. Agreement between assay results was quantified with Kappa coefficient. Results: In IFX group 22/134 (16%) and in ADL group 12/68 (18%) samples negative in bELISA tested positive in cELISA. The Kappa coefficients between bELISA and cELISA were 0.597 (95%CI 0.466–0.728) for anti-IFX assays and 0.597 (95%CI 0.416–0.777) for anti-ADL assays. The results of cELISA were confirmed with RGA. In IFX group we have samples of 28 patients and in ADL group samples of 17 patients available at different time points. In samples of 10/28 (IFX group) and 6/17 (ADL group) patients cELISA could detect ADA earlier than bELISA. In samples of 18 (IFX group) and 11 (ADL group) patients cELISA and bELISA yielded the same result, negative or positive. Conclusions: Our results show that cELISA could be superior in clinical practice because it detects ADA earlier and in up to 18% more samples than routinely used bELISA. Polona Žigon1,2 1Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Koper, Slovenia polona.zigon@guest.arnes.si Antiphospholipid syndrome (APS) is a systemic autoimmune disease, characterized by thromboses and/or obstetric complications and persistence presence of antiphospholipid antibodies (aPL) (1). aPL, cause activation of vascular cells (endothelial cells, platelets, monocytes) and release of extracellular vesicles (EVs). EVs are submicron particles constitutively released from all cells. Increased numbers of EVs are released in response to stimuli such as cellular activation and/or apoptosis. EVs circulate in plasma at concentrations approaching 109/mL. Frequencies of plasma EVs of different cellular origin may be altered in disease states. The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field (2). According MISEV2018 guidelines EVs can be divided into subsets according to their a) physical characteristics, such as size (“small EVs” (sEVs) and “medium/large EVs” (m/lEVs), with ranges < 100nm or < 200nm for sEV and > 200nm as m/lEV) and density (low, middle, high); b) biochemical composition (protein marker positivity) or c) descriptions of conditions or cell of origin. EVs, particularly endothelial m/lEVs, have been studied in antiphospholipid syndrome (APS) (3). Compared with healthy controls, patients with aPL have significantly higher levels of circulating endothelial and platelet m/lEVs. On the other hand, no data till now has been provided for exosomes or sEVs (<100nm), secreted vesicles of endosomal origin. Our research group first determined plasma levels of sEVs in APS patients and investigate their surface protein profiles. Altered sEVs levels as well as different exosomal surface marker profile between APS and healthy controls were found. These findings show that a complex systemic network existing in the form of cell-cell communication via sEVs is altered in APS patients. 1. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, et al. 2006. J Thromb Haemost 4: 295-306 2. Théry C, Witwer KW. 2018. 7: 1535750 3. Chaturvedi S, Alluri R, McCrae KR. 2017. Semin Thromb Hemost Uroš Rajcevic1, Valerija Kovac1, Anja Golob Urbanc2 1Blood Transfusion Centre of Slovenia, R&D, Ljubljana, Slovenia 2Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia uros.rajcevic@ztm.si Adoptive T-cell therapy can be divided mostly to therapies with tumor-infiltrating lymphocytes (TIL) and to therapies using T-cells genetically modified with transgenic T-cell receptors (TCR) or chimeric antigen receptors (CAR). All of these therapies are exclusively personalized and are at the moment based on the autologous transplant of the patient’s own cells. Therapeutic cells are prepared for each patient individually, which carries a great impact on the processes of their development and production, as well as the logistics and costs involved. The new mode of therapies with CAR-T, for specific diseases at the moment the only registered mode of ATC, causes revolutionary breakthroughs in the development of such advanced therapeutics and, consequently in clinical oncology. CAR-T therapy is achieving an incredible success in clinical practice especially in combat against hematological cancers, while the treatment of patients with solid tumors it has not been as successful. Along with that, due to great complexity of the CAR-T therapy, it is accompanied by frequent and severe side effects, which can be fatal in worst cases. By adopting adequate measures, these effects can be controlled and partially mitigated. CAR-T therapy is being introduced to Slovenia through registered, commercially accessible therapeutics of this kind, while the access to other ATC is still pending. At the same time, in Slovenia in this field, we are developing our own knowledge and technology, hoping that new, efficient treatment modalities become accessible to a wider population of patients as soon as possible. Duško Lainšcek1,2 1Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia 2EN-FIST Centre of Excellence, Ljubljana, Slovenia dusko.lainscek@ki.si In Year 2020, Nobel Prize Committee awarded 12 laureates a Nobel Prize for different discoveries with important benefit for humankind. Their findings range from the formation of black holes to important tools for genome editing. The Nobel Committee awarded The Nobel Prize in Chemistry 2020 two scientists, which pioneered the revolutionary genome editing technology CRISPR/Cas9. Emmanuelle Charpentier, born in 1968 in France and Jennifer Doudna, born in 1964 in USA, share the prize for their important work on developing a powerful gene-editing tool CRISPR/Cas that derives from majority of species of archaea and bacteria. Emmanuelle Charpentier who works at Max Planck Unit for the Science of Pathogens in Germany discovered that CRISPR/Cas system constitute a variety of immune systems that offers bacteria and archaea protection against invading phages and plasmids. Key feature of her finding, which was published in year 2011 in Nature, is tracrRNA mediated maturation of short CRISPR RNA (crRNA) that silence foreign nucleic acid in a sequence specific manner, therefore offering RNA-mediated immunity against invaders. Shortly after this discovery, she began her collaboration with Jennifer Doudna from University of California, Berkeley in USA. Their joint effort led to the rise of CRISPR/ Cas9 system, which comprises a dual base-paired small RNAs (crRNA+tracrRNA) and an endonuclease Cas9. Pairing of crRNA to tracrRNA forms a two-RNA structure that directs CRISPR-associated protein Cas9 to introduce a site-specific DNA double-stranded break. This latter can be exploited for programmable genome editing via intrinsic cell repair mechanism. Repair mechanisms are exploited to introduce the desired changes. Using CRISPR/Cas9 system, knockout models by introducing indel mutations can be made or knock in models by codelivery of a donor DNA can be established. Work describing the discovery of CRISPR/Cas system was published in 2012 in Science. CRISPR/Cas technology allows a precise way to alter genome and influence gene expression. Although the genome-wide specific CRISPR/Cas9 system has some possible disadvantages regarding off-target effects, the wide range of applicability offers tremendous progress in time and efficiency in development of various cell lines, animal models for human illnesses and gives a possible treatment choice for human genetic-derived diseases and that represents a revolution in personalized medicine. Duško Lainšcek1,2, Vida Forstneric1, Veronika Mikolic3, Špela Malenšek1,6, Mojca Bencina1,2, Matjaž Sever3,4, Helena Podgornik3,5, Roman Jerala1,2 1Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia 2EN-FIST Centre of Excellence, Ljubljana, Slovenia 3Department of Hematology, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia 4Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 5Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia dusko.lainscek@ki.si Background: The CRISPR/Cas system is a highly potent tool, which has revolutionized genome engineering and regulation of gene transcription in various cells and organisms. This gene-editing tool consists of a guide RNA (gRNA), which targets the Cas9 endonuclease to the desired genomic site. Cas9 catalyzes the formation of double-strand DNA breaks, which are then repaired by different cell mechanisms. Depending on the size (tens of base pairs) of indel mutations, higher rates of “knock-out” can be achieved. To achieve greater indel mutations, CRISPR system can be coexpressed in cells with DNA exonucleases, which cause increased recessions of DNA following DNA breaks. We show that joint action of the CRISPR system with different exonucleases significantly increases the percentage of indel mutations at various targeted genes. Of the different exonucleases tested, the E.coli-derived exonuclease III (EXOIII) exhibited the best performance in terms of indel formation. Material and methods: K562 cells, model for Philadelphia chromosome positive cells and chronic myelogenous leukemia (CML) patient cells were used. Constructs, expressing BCR- ABL1 targeting gRNA and Cas9, tethered via coiled-coil forming peptides to E.coli exonuclease EXOIII, were nucleofected into target cells. T7E1 assay to detect genome modifications was carried out. TUNEL assay, FACS analysis with bioluminescence measurement were used for cell death determination. SCID mice were used for a subcutaneous K562 cancer model. Results: Of the different exonucleases tested, the EXOIII exhibited the best performance in terms of indel formation. To improve the rate of indel mutations, we connected Cas9 and EXOIII via coiled-coil forming peptides, bringing the two enzymes into close proximity. This resulted in increased indel formation compared to the classical CRISPR/ Cas system. We performed a case study for the use of our novel CRISPR system as a potential anti-cancer therapeutic tool. In the case of our new system, we showed significant increase in cell death due to higher genome modification in BCR-ABL1 region. Later, these findings were confirmed also in animal cancer model, where animals with tumors, electroporated with CRISPR-EXO system showed 100% survival and drastic reduction in tumor size. Conclusion: Our de novo upgraded CRISPR system by tethering Cas9 protein to exonuclease EXOIII by heterodimeric coiled-coil forming peptides, resulted in higher editing of BCR- ABL1 fusion gene, leading to enhanced death of CML cancer cells. Jelka Pohar1,4, Luc Jouneau2, Pierre Boudinot2, Wolfgang Uckert3, Simon Fillatreau4 1National Institute of Biology, Ljubljana, Slovenia 2Université Paris-Saclay, Espace Technologique Bat. Discovery, Saint-Aubin, France 3MDC, Berlin, Germany 4Institut Necker-Enfants Malades (INEM) INSERM U1151-CNRS UMR 8253, Paris, France jelka.pohar@nib.si Background: Autoimmune diseases affect people of all ages often greatly aggravating their quality of life. Regulatory T cells (Treg) are crucial for the maintenance of homeostasis and the prevention of immune responses against self-antigens. They can employ direct and indirect mechanisms such as the expression of anti-inflammatory cytokines or via co-inhibitory receptors. They can even promote tissue repair. Clinical trials demonstrated that polyclonal Tregs can control autoimmune responses following adoptive transfer. In preclinical models, antigen-specific Tregs were superior to polyclonal ones, which has driven the field towards the development of antigen-specific Tregs for cell-based therapies. However, such cells are rare end difficult to isolate. This could be overcome by engineering the polyclonal Tregs into antigen-specific ones by T cell receptor (TCR) gene transfer. Methods:We used a preclinical model of experimental autoimmune encephalomyelitis (EAE), which is an animal model for demyelinating diseases of the central nervous system (CNS) including multiple sclerosis. The EAE is triggered by immunization with encephalitogenic peptides like peptide from myelin oligodendrocyte glycoprotein (MOG). Tregs engineered to express TCR that recognizes MOG peptide protect mice from the development of EAE. To understand molecular mechanisms involved in the protective function of engineered autoreactive Tregs we silenced or overexpressed several proteins shown to be overexpressed in the CNS of EAE mice. Results: We have shown that engineered antigen-specific Tregs employ IL-10, LAG3, and CTLA-4 to inhibit disease in recipient mice while the expression of the tissue repair factor AREG has no effect. Antigen-specific Tregs can intercept EAE progression when administered at the disease onset but not at the peak of the disease. Engineered cells also persist in the animals and, compared to endogenous Tregs, display activated phenotype. Conclusions: This study greatly contributes to the understanding of the features that control the efficacy of Treg cell therapy. Engineered autoreactive Tregs protect from CNS autoimmunity via multiple immune mechanisms and they block disease progression upon administration at clinical onset underscoring their immense potential for intercepting autoimmune responses and the development of cell-based therapies. Grant support: ANR - Agence nationale de la recherché, AXA and Université Paris Descartes. Anze Smole1,2, Monika Eiva1, Mathilde Poussin1, Alexander Benton1, Prannda Sharma1, Nicholas Minutolo1, Falon Gray1, Tatiana Blanchard1, Alba Rodriguez-Garcia1, Michael Klichinsky1, Beatriz M. Carreno1,2, Gerald P Linette1,2, Avery D. Posey1,2, Carl H. June1,2, Daniel J. Powell Jr1,2 1Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 2Parker Institute for Cancer Immunotherapy, San Francisco, California anzes@pennmedicine.upenn.edu Background: T cell-intrinsic dysfunctions and immunosuppressive tumor microenvironment (TME) influence clinical efficacy of CAR T cells. We recently discovered that inducible expression of transcription factors or immunostimulatory molecules improved functional qualities and augmented anti-tumor activity of CAR T cells in preclinical in vivo models. Methods: We have developed genetic approach that combines autonomous antigen-triggered production of an accessory molecule, along with constitutive CAR expression in a single lentiviral vector - Uni-Vect. By knocking out the endogenous TCR we render CAR signaling an exclusive activator of the system. To modulate CAR T cell-intrinsic features we implemented Uni-Vect for transient, activation-inducible transcription factor expression (iTF-CAR T). In a second model, we introduced inducible expression of IL-12 (iIL-12-CAR T) to overcome immunosuppressive TME. We analyzed phenotype, expansion, and anti-tumor activity of “upgraded” CAR T cells in vitro and in vivo. Results: iTF-CAR T cells demonstrated enhanced antigen-dependent proliferation and a less differentiated phenotype following repeated stimulations with cancer cells in vitro. CyTOF analysis of iTF-CAR T cells showed that antigen-inducible expression of a single TF favorably affected T cell markers of efficacy. Finally, we tested activity in vivo in tumor xenografts models where iTF-CAR T cells demonstrated significantly increased expansion in the blood compared to control CAR T cells. Importantly, T cells expansion was transient and ultimately contracted to the normal levels after tumor was cleared. iTF- CAR T approach addresses challenges related to intrinsic CAR T cell dysfunctions, however, it may not directly counteract immunosuppressive TME. Therefore, we have developed an iIL-12-CAR T system and demonstrated that only iIL-12- secreting, and not conventional CAR T cells, were capable of eradicating solid tumors in vivo. Conclusions: First, we demonstrated that inducible TF expression equips CAR T cells with improved therapeutically relevant T cell states, which translates into improved in vivo T cell expansion. Second, iIL-12 expression remarkably enhanced anti-tumor responses in established solid tumors in vivo. With these contributions, we have established a foundation for more effective next- generation cellular immunotherapies. Disclosure of relevant financial relationships: AS, ADP, CHJ and DJP are co-inventors on a PCT International Patent Applications by The Trustees of the University of Pennsylvania, which incorporate discoveries described here. Funding: Perelman School of Medicine at the University of Pennsylvania, Parker Institute for Cancer Immunotherapy. Maša Bizjak1, Eva Breznikar2, Alojz Ihan2,3, Andreja Nataša Kopitar2,3, Nataša Toplak1,3 1Department of Allergology, Rheumatology and Clinical Immunology, University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 3Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia bizjakm89@gmail.com Background: Children with juvenile idiopathic arthritis (JIA) on immunosuppressive therapy are at risk for more severe course of varicella infection. Vaccination against Varicella zoster virus (VZV) is the most effective method for protection against varicella, but data on live attenuated vaccines in patients treated with anti-cytokine therapy are scarce. The aim of this study is to evaluate long-term safety and immunogenicity of varicella vaccine in children with JIA, treated with anti-cytokine therapy. Methods: VZV-naive patients with JIA on anti-cytokine therapy, who were at risk for contracting varicella, had stable disease and normal values of immunoglobulins and lymphocyte populations, were vaccinated against VZV. Adverse events and disease activity after vaccination were followed. One month and then every 6-12 months after second vaccination VZV-specific humoral and cellular immunity were measured by ELISA and intracellular cytokine staining, respectively. Control group includes children with JIA who had varicella, healthy children who had varicella and healthy children after varicella vaccination. Results: To date, 15 patients were vaccinated. At the time of vaccination, 11 patients were treated with anti-TNFa therapy, 3 with anti-IL6 therapy and 1 with anti-IL1 therapy. There were no serious adverse events, no increase in disease activity and no varicella infection after vaccination. Twelve patients developed VZV-specific humoral immunity and 10/12 patients VZV-specific cellular immunity following vaccination. Cellular immunity persisted for longer time than humoral. Three patients had a mild case of varicella 4 months – 4.5 years after vaccination. Further 5 patients had a documented contact with varicella but did not contract it. Conclusion: Vaccination against varicella appears to be safe, but not always immunogenic and also not effective in some children with JIA, treated with anti-cytokine therapy. VZV-specific cellular immunity could offer additional insight into immunogenicity of the vaccine. Larisa Janžic1, Andreja Nataša Kopitar1, Mojca Pavlin2,3, Alojz Ihan1, Špela Zemljic Jokhadar3 1Department of Immunology, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 2Nano and Biotechnological Applications Group, Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia 3Institute of Biophysics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia larisa.janzic@mf.uni-lj.si Macrophages are mononuclear phagocyte cells that are part of innate immunity and the first line of defence against pathogenic microbes. They also play a key role in the maintenance of tissue homeostasis and repair and are as such extremely heterogeneous. In order to fulfil all of their functions they are capable to adopt different activation states by polarization from basic M0 state, which differ in metabolic phenotype. The so-called M1 macrophages are associated with inflammatory responses and acquire ATP by aerobic glycolysis while M2 macrophages produce anti-inflammatory mediators and depends mainly on oxidative phosphorylation. Studies show that infection with pathogens induce specific M1 or M2 programs in macrophages and therefore indicate that their immune functions are directly related to metabolic reprogramming. We have therefore set to determine immune response of macrophages following infection with different Group B Streptococcy strains on the level of macrophage immunometabolism. Streptococcus agalactiae is a Gram-positive pathobiont that can thrive and live in a healthy host without causing any problems but due to many virulence factors that allow him to avoid host immune responses it remains one of the most invasive pathogens that can cause serious illnesses such as sepsis, pneumonia, meningitis and death in newborns and immunocompromised elderly people. THP-1 monocytic cell line has been shown to be a good model for in vitro studies of macrophages. As part of our study we first optimized the process of differentiation of THP-1 monocytes into macrophages. For this purpose, cells were treated with 3 different concentrations of mitogen PMA (30 nM, 100 nM, 162 nM) and allowed to differentiate for 24 and 72 hours, followed by 1 or 5-days rest in medium without PMA. Using the flow cytometry, we sought to determine the viability of the cells and the presence of surface markers CD14, CD16, CD163, CD11c and intracellular CD68. Differentiation lasting for 72 hours with 100 nM PMA and 5-day rest resulted in significantly higher cell viability, while the expression of markers was comparable between the treated cells. Successful differentiation into macrophages was confirmed by bright-field microscopy and confocal microscopy. Funding: This research was founded by ARRS under postgraduate program and P3-0083. Andreja Nataša Kopitar1, Maja Jakopic1, Nataša Smrekar2, Alojz Ihan1 1Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 2Department of Gastroenterology and Hepatology, University Medical Centre, Ljubljana, Slovenia andreja-natasa.kopitar@mf.uni-lj.si The intestine is a complex environment that is constantly exposed to antigens derived from food, microbiota, and metabolites. Intestinal dendritic cells (DC) have the responsibility of establishing oral tolerance against these antigens while initiating immune responses against mucosal pathogens. In the intestine, DC are a heterogeneous population of innate immune cells composed of conventional cDC (classical and monocyte-derived DC, Langerhans cells), and plasmacytoid pDC. We were studying function of gut DC and T lymphocytes in the context of intestinal homeostasis and inflammation. Breakdown of tolerance against the commensal micro-flora is believed to be a major factor in the pathogenesis of inflammatory bowel disease. Dendritic cell (DC) function is believed to be of critical importance for the pathogenesis of IBD. Intestinal biopsies (inflamed and uninflamed areas) were obtained from 30 patients with IBD before and after the treatment with TNF inhibitors (infliximab 13 patients, adalimumab 17 patients) and 10 healthy controls. Intestinal lamina propria cDCs were identified as lineage (CD3, CD19, CD56 and CD14)negative cells that express CD11c and plasmocytoid pDCs that express CD123 and CD303. Conventional DCs were further analysed on the expression of costimulatory molecules CD80, CD86, and HLA-DR, CD83, CD103. To determine the proportions of different subtypes of T lymphocytes cells were stained with CD103/CD28/CD3/CD8 and FoxP3/CD127/CD4/CD25/CD3. The analysis was performed on BD FACS Canto II using FlowJo software. Disease activity was endoscopically assessed at baseline and after treatment induction. We found a significantly higher frequency of plasmacytoid DCs and conventional DCs in the inflamed colonic mucosa compared with uninflamed mucosa. Moreover, the proportion of CD80+, CD83 and HLA-DR expressing myeloid DCs were significantly higher in inflamed mucosal tissue compared to a uninflamed mucosal tissue. IBD patients compared to control group had higher expression of costimulatory CD28 molecules on cytotoxic T lymphocytes and they had more activation molecules HLA-DR+. Helper T cells expressed more IL-2RA (CD25+) receptor and had regulatory properties (FoxP3+CD25hiCD127low/-). 18/30 (60%) patients responded to treatment at week 12. Responders had significantly higher proportion of cDCs with higher expression of HLA-DR in inflamed mucosa before treatment compared with non-responders. After the treatment, the responders to showed lower frequency of cytotoxic T lymphocytes expressing CD28 molecules and HLA-DR+, as well as lower frequencies of cytotoxic T lymphocytes expressing integrin aEß7 (CD103+). Understanding these processes should help target individual subsets for ‘fine tuning’ immunological responses within the intestine, a process that may be of relevance for the treatment of inflammatory bowel disease (IBD). Mojca Pavlin1,2, Jernej Repas1, Andreja Nataša Kopitar3, Alojz Ihan3 1Institute of Biophysics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 2Nano and Biotechnological Applications Group, Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia 3Department of Immunology, Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia mojca.pavlin@mf.uni-lj.si Warburg presented the first evidence that cancer cells produce lactate from glucose under normoxic conditions, a phenomenon known as the ‘Warburg effect.’ Recently, many studies have explored the modulation of cancer cell metabolism as a therapeutic strategy. Similarly as cancer cells, immune cells use different metabolic pathways to support their differentiation and specific functions. The metabolic pathways change depending on the differentiation and activation of the immune cells and at the same time, they are critically dependent on the microenvironment. For example, naive T cells in quiescence are fueled by fatty acid oxidation (FAO), cytotoxic CD 8+ T lymphocytes mainly depend on glycolysis while regulatory T lymphocytes (Treg cells) rely on FAO and oxidative phosphorylation (OXPHOS). Recently, metabolic reprogramming of antigen presenting cells (APC) has been also implicated in regulating their phenotype and function and the studies show that metabolism of monocytes, macrophages and dendritic cells (DC) is altered in case of different autoimmune diseases and cancer. Studies suggested that DC activation also requires an increase in glycolysis, while FAO is important in tolerogenic DCs. The reduction of glycolytic capability significantly impairs DC effector functions including antigen presentation, co-stimulatory molecule expression, cytokine secretion, and T lymphocyte stimulatory capacity. For macrophages, it was demonstrated that the metabolic profile of M1 macrophages shift to glycolysis, which is crucial for production of mediators such as NO, whereas M2 macrophages rely on mitochondrial OXPHOS. Importantly, glycolysis itself drives inflammatory macrophage responses, while OXPHOS supports M2 activation. Altogether, the mechanisms behind metabolic regulation of macrophages polarisation and DC activity are still being explored and only very recently, unexpected non-metabolic functions for metabolic enzymes were identified in the context of inflammation. Specifically, there are several open questions of metabolic alterations of different types and subtypes of APC cells because of pathological changes in autoimmune diseases. Metabolic phenotype of APC cells could for example present a potential biomarker for predicting the response to specific treatments in autoimmune diseases such as rheumatoid arthritis. This research was funded by ARRS under program P1-0055. Astma Saša Kadivec University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia sasa.kadivec@klinika-golnik.si Between 2005 and 2019, a total of 1,001 reports of medication-related adverse events and near misses were collected at the University Clinic Golnik. In 2005, 5 medication-related adverse events were reported (5,436 hospitalizations). In 2014, the number rose to 52 events, 15 of which were near misses (6,843 hospitalizations); and in 2015, there were 112 reports, 20 of which were those of near misses (7,271 hospitalizations). Reports were mostly submitted by nurses. In 2015, only a few reports were submitted by physicians, but in 2018, there were 19 physicians and 10 pharmacists who reported of adverse events and/or near misses. There were 152 adverse events (9,203 hospitalizations) in 2016. In 2017, we collected reports of 128 adverse events (8,844 hospitalizations). There were 197 adverse events (9,095 hospitalizations) in 2018. In 2019, we collected reports of 229 adverse events, most of which (108 adverse events) were medication-related, and the least adverse events occurred in the area of work organization (16). The number of adverse events is increasing each year. We believe that this is due to the increased commitment to report such events. The main two goals of adverse event reporting and control are to analyze causes and to implement corrective measures. We follow the PDCA cycle and evaluate the outcome of implemented changes. This is also where the staff get their chance to be active in implementing the necessary changes. It is our goal for the employees to realize that making a mistake does not result in a punishment, but rather that correct steps will reduce damage to the patient or the staff, and prevent future recurrence of such mistakes by finding the appropriate solution to the problem. An experimental e-registry of adverse event reporting has been set up in 2020. Its emphasis is on following up analyses of causes and corrective measures. Each person who is assigned tasks receives these by email. Only up-to-date contents that regularly follow the analysis of adverse events in practice enable continuous development of the staff, case-based learning and problem solving. Sanela Pivac Fakulteta za zdravstvo Angele Boškin Jesenice, Jesenice, Slovenija spivac@fzab.si Uvod: Povecati znanje, odgovornost in zavedanje medicinskih sester o nekadilskem vedenju ter izobraževanju pacientov o opušcanju kajenja predstavlja pomembno podrocje v okviru promocije nekajenja med medicinskimi sestrami. Nekadilski status zdravstvenih delavcev je kljucni element za zagotavljanje ucinkovite pomoci pri opušcanju kajenja. Glavni namen raziskave je bil ugotoviti mnenje medicinskih sester o zavedanju lastnega pomena nekadilskega vedenja. Metode: Uporabljena je bila kvantitativna metoda dela, kot instrument smo uporabili strukturiran vprašalnik. Raziskava je bila izvedena med medicinskimi sestrami na vseh treh nivojih zdravstvenega varstva, ki so se udeležile delavnic v okviru mednarodnega projekta Tobacco Control v obdobju od leta 2017 - 2018. Uporabljen je bil prirocni vzorec. V raziskavo je bilo vkljucenih 79 medicinskih sester, ki so se udeležile delavnic. Anketo je izpolnilo 66 medicinskih sester. Podatki so analizirani s pomocjo programa SPSS 20.00. Rezultati: Statisticno pomembnih razlik o vplivu lastnega kajenja in zglednega delovanja glede na starost in delovno dobo nismo ugotovili. Rezultati so pokazali na enotno, stabilno in pozitivno mnenje o vplivu lastnega kajenja in zglednega delovanja (PV = 1,4; SO = 0,7), o vlogi medicinskih sester pri aktivni pomoci pacientom pri opušcanju kajenja (PV = 1,4; S= 0,8) ter o potrebi po dodatnem znanju na podrocju nadzora nad tobakom (PV = 1,5; SO = 0,8). Diskusija in zakljucek: Ugotovitve raziskave kažejo nato, da se anketiranci v veliki meri zavedajo, da lastno kajenje vpliva na poslanstvo in delo na podrocju promocije zdravja, promocijo nekajenja in pomoc pri opušcanju kajenja, kar vsekakor lahko predstavlja oviro za ucinkovito izvajanje nadzora nad tobakom. Glede na rezultate raziskave o pridobivanju znanja, menimo, da je potrebno medicinske sestra opolnomociti na podrocju opušcanja kajenja z uvedbo razlicnih metod dela ter krepiti programe promocije nekadilskega vedenja med zdravstvenimi delavci. Razlicne iniciative po vzorih iz tujine (npr. “Medicinske sestre proti kajenju”) bi lahko delovale s ciljem zmanjševanja kajenja v tej skupini zdravstvenih delavcev. Ditka Benedicic Katona Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija ditka.benedicic@klinika-golnik.si Neinvazivna mehanska ventilacija (NIMV) je temeljni del obravnave pri pacientih s poslabšanjem kronicne obstruktivne pljucne bolezni (KOPB), saj zmanjša število intubacij, hospitalizacij in smrti (Fisher, 2018), hkrati pa kot kronicna NIMV dokazano ucinkuje pri hiperkapnicnih pacientih s KOPB (Duiverman, 2019). Študije primerov akutne uporabe NIMV so pokazale, da rezultati doseženi v klinicnem okolju pogosto ne dosegajo rezultatov pridobljenih z raziskavami. Dejavniki vkljucujejo neprimerno izbiro pacientov in neucinkovito uporabo NIMV. (Elliott, 2018). Pri obravnavi pacientov na NIMV je potreben multidisciplinarni pristop in formalno izobraževanje zaposlenih, ki ga dopolnjuje usposabljanje na delovnem mestu. Uspešen NIMV team mora imeti posameznike z veliko razlicnimi znanji (Elliott, 2018), zlasti s profesionalnimi in tehnicnimi vešcinami (Escarrabill, 2015). Eni osebi ni potrebno storiti vsega, toda tim zahteva vodjo, ki prevzame odgovornost. Predvsem se mora znati odlocati kateri pacienti morajo prejemati zdravljenje z NIMV in kako hitro je potrebno ukrepati (Elliott, 2018). Kljucni dejavniki, ki jih je potrebno upoštevati za uspešno NIMV (British Thoracic Society Reports- BTS, 2018): 1. Zdravljenje pravih pacientov: Ali je indicirana NIMV? Študija NCEPOD (National Confidential Enquiry into Patient Outcome and Death) je pokazala, da zdravljenje z NIMV ni bilo primerno ali ni bilo indicirano pri skoraj 20% pacientih. Razlogi za to so bili zdravljenje hipoksemije namesto hiperkapnije ali zdravljenje metabolicne acidoze. Skoraj dve tretjini pacientov, pri katerih NIMV ni bila indiciran ali je bil neustrezna, je umrlo. Zato je zdravljenje pravih pacientov z ustrezno indikacijo nujno. 2. Nacrt in potek zdravljenja z NIMV. Pomembno je nacrtovanje zdravljenja, saj NIMV uspe v dveh tretjinah primerov. Ko z NIMV ne izboljšamo hiperkapnije, je tveganje za smrt veliko. Vnaprejšnje nacrtovanje ukrepov, ki jih je treba sprejeti, ce je NIMV neuspešna, lahko izboljša izid zdravljenja. 3. Dokumentiranje in prilagajanje nastavitev NIMV kot odziv na nove informacije (npr. izvid plinske analize arterielne krvi). Študije so pokazale, da tam, kjer so bile nastavitve NIMV ustrezno dokumentirane, je bila umrljivost nižja. Dokumentacija nastavitev je bila v 50% primerov slaba, kljub temu da je vec kot dve tretjini bolnišnic imelo nacrt za izvajanje NIMV in vec kot 80% z doloceno NIMV kontrolnim obrazcem. 4. Zacetek NIMV v 60 minutah po odlocitvi za zdravljenje z NIMV. Klinicno poslabšanje zaradi zamujenega zdravljenja lahko povzroci poslabšanje acidoze. Pri meritvah plinov v krvi pred NIMV je poslabšanje acidoze povezano s povecano umrljivostjo. 5. Neprekinjeno spremljanje pacienta v prvih 24 urah ali dokler zacetna respirator-na acidoza ne izzveni. Študije so pokazale, da pacienti, ki so bili zdravljeni z akutno NIMV, v prvih 24 urah niso bili dovolj pozorno spremljani, kar bi lahko povzrocilo zapoznelo prepoznavanje poslabšanja ali prekinitve NIMV. BTS in NCEPOD priporocata neprekinjeno spremljanje pulzne oksimetrije, frekvenco dihanja in pulza v prvih 24 urah ali do razrešitve acidoze. 6. Usposabljanje in usposobljenost osebja. Vsi zgoraj navedeni ukrepi se do neke mere opirajo na dobro klinicno znanje, razumevanje NIMV in usposobljenost za vodenje pacientov na NIMV. To velja za vse clane tima NIMV. Za zagotavljanje visokokakovostne in ucinkovite storitve standardi kakovosti BTS od bolnišnic zahtevajo, da lahko dokažejo stopnjo us-posobljenosti osebja. Literatura: 1. Duiverman, M. L., Vonk, J. M. eds. (2019). Home initiation of chronic non-invasive ventilatio in COPD patients with chronic hypercapnic respiratory failure: a randomised controlled trial. Thorax, 2019 BMJ. 1-9. 2. Elliott, M. W., (2018). Non-invasive ventilation: Essential requirements and clinical skills for successful practice. Offical Journal of the Asian Pacific Society of Respirology. 1-8. 3. Escarrabill, J. (2015). Setting up and staffing your NIV unit. In: Simonds, K. A. eds. Noninvasive Ventilation. 2015 European Respiratory Society, 289-294. 4. Fisher, K. A., Mazor, K. M., eds. (2017). Successful Use of Noninvasive Ventilation in Chronic Obstructive Pulmonary Disease. Ann Am Thorac soc, 2017 (Vol 14, No 11), pp 1674-1681. 5. Quality Improvement Tool- Non- Invasive Ventilation. (2018). British Thoracic Society Reports, (Vol 9, Issue 4). 8-16. Tatjana Kosten Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija tatjana.kosten@klinika-golnik.si Bolniki z razlicnimi respiratornimi obolenji: s kronicno obstruktivno pljucno boleznijo, s cisticno fibrozo, s tuberkulozo, s pljucnim rakom, z idiopatsko pljucno fibrozo in bolniki po transplantaciji pljuc so v veliki meri podhranjeni. Izjema so bolniki z motnjami dihanja v spanju, ki se obicajno spopadajo s morbidno debelostjo in tudi potrebujejo prehransko obravnavo. Izguba telesne mase, predvsem puste telesne mase je pogost spremljevalec kronicnih respiratornih bolezni. Pljucna bolezen s svojimi simptomi povzroci zmanjšan vnos hrane na drugi strani pa povecane energijske in beljakovinske potrebe, kot posledica same bolezni, vodijo v podhranjenost. Pljucni bolniki s podhranjenostjo imajo daljšo ležalno dobo, slabši izid zdravljenja in slabšo prognozo, zato je pomembno, da podhranjenost prepoznamo cim prej in jo poskušamo obravnavati individualno. Samo ITM ni zadosten kriterij za diagnosticiranje podhranjenosti, zato uporabimo vprašalnike za presejanje. Prehranska obravnava obsega oceno prehranskega stanja, pomembna je meritev telesne sestave in s tem dolocitev indeksa puste telesne mase. Prehranski ukrepi, ki sledijo, so individualno prilagojeni posameznemu bolniku. Timski pristop z vkljucitvijo razlicnih strokovnjakov v obravnavo je za uspešnost zdravljenja zelo pomemben. Z rednim spremljanjem prehranskega stanja in presnove nadzorujemo uspešnost prehranskih ukrepov in po potrebi prilagajamo ukrepe. Prehranska podpora pozitivno vpliva na uspešnost zdravljenja in kakovost življenja bolnika s pljucno boleznijo. Alenka Smukavec Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija alenka.smukavec@klinika-golnik.si Uvod: Respiratorna fizioterapija velik poudarek namenja cišcenju in predihavanju pljuc. Pri vseh bolnikih z oteženim ali onemogocenim izkašljevanjem je respiratorna fizioterapija kljucnega pomena. Poznamo mnogo tehnik za pomoc pri izkašljevanju, zato je odlocanje o pravilni zelo pomembno. Namen: je predstaviti in primerjati novo tehniko izkašljevanja s pomocjo pospeševalca ekspiratornega tlaka - Free Aspire, z že veljavno tehniko izkašljevanja – Cough Assist glede na izkušnje na Univerzitetni Kliniki Golnik. Metode dela: Free Aspire je pospeševalec ekspiratornega pretoka, ki omogoca bolniku lažje izkašljevanje. Prilagojena je glede na bolnikov naravni vzorec dihanja. Bolniki se med terapijo pocutijo prijetno in udobno. Gre za popolnoma varno tehniko brez znanih kontraindikacij. Tehnika neinvazivno odstranjuje sluz, kjer ni pritiska na pljuca, tlak pa je minimalen. Nacin odstranjevanja izlockov s tehnologijo Free Aspire se doseže povecanim pretokom med izdihom. V ustniku pretok zraka zaokroži in se nato prenese v pljuca, kjer seže za sluzni cep in ga pomakne proti velikim dihalom. Postopek deluje v fazi izdiha ter sledi naravnem ritmu dihanja bolnika, zato to tehniko uporabljamo tudi pri nesodelujocemu bolniku, ki samostojno diha vsaj eno uro. Ucinkovit je za drenažo spodnjih dihalnih poti. Free Aspire uporabljamo pri bolnikih s KOPB, z bronhiektazijami, po OP pljuc, s pljucnico itd. Uporaba Cough Assist-a za pomoc pri izkašljevanju je že zelo uveljavljena. Temelji na uporabi pozitivnega tlaka. V dihalnih poteh bolnika spodbudi vdih (insuflacija), nato omogoci hiter vklop in prehod na negativen tlak (eksuflacija). Prisilni tlak izdiha je tolikšen, da omogoca odstranjevanje izlockov, ki so v dihalnih poteh bolnika. Za predpis se odlocamo na podlagi meritev moci kašlja (PCF) in/ali moci dihalnih mišic (MIP/MEP). Indikacije: živcno mišicna obolenja, pljucna obolenja, bolniki s traheostomo, huda izcrpanost in slaba ucinkovitost kašlja. Kontraindikacije: povišan intrakranialni tlak, nedreniran pnevmotoraks, bulozni emfizem, nesodelujoci bolniki, slaba toleranca bolnika ali odklonilnost, aktivne hemoptize,… Zakljucek: Free Aspire je nova tehnika za pomoc pri izkašljevanju, kjer zaenkrat še primanjkuje število kvalitetnih raziskav z velikim vzorcem preiskovancev. Kaže se, da dela podobno kot že uveljavljen Cough Assist. Zaenkrat še ne obstaja študija, ki bi primerjala obe tehniki. Glede na pregled študij obeh pripomockov zgleda, da je Free Aspire varnejša tehnika za izkašljevanje, saj še zaenkrat nima znanih kontraindikacij, prav tako pa je manj utrujajoca za bolnika, saj ne deluje na spremembi tlaka. Predvidevamo, da je kombinacija obeh tehnik najboljša. Free Aspire se izvaja pri šibkih, slabo sodelujocih bolnikih, ki imajo KOPB, pljucnico, bronhiektazije, in so po operaciji pljuc. Cough Assist se uporablja pri tistih bolnikih, kjer je zelo zmanjšana moc kašlja in so dobro sodelujoci. To so bolniki z živcno mišicnimi obolenji (Auger et al., 2017) in pljucnimi obolenji. Obe tehniki se lahko dopolnjujeta, saj Free Aspire cisti male dihalne poti, medtem ko Cough Assist ocisti centralno dihalno pot. Aparat Kalos združuje obe tehniki izkašljevanja. Uporaba je v dolocenih primerih zelo dobrodošla. Literatura: 1. Auger C, Hernando P, Galmiche H (2017). Use of Mechanichal Insufflation – Exufflation Devices for Airway Clearance in Subjects With Neuromuscular Disease. Respir. Care 62 (2): 236 – 45. 2. Benditt O.J (2018). Mechanichal Insufflation-Exsuflation: More Than just Cough Assist. Respir. Care 63 (8): 1076 – 7. 3. Partizio G., DAndria M., DAbrosca F., Cabiaglia A., Tanzi F., Garuti G., et al. (2018) Airway Clearance with Expiratory Flow Accelerator Technology: Effectiveness of the »Free Aspire« Device in Patients with Severe COPD. TurkThoracJ. 4. Ferreira de Camillis M. L., Savi A., Goulard Rosa R., Figueiredo M., Wickert R., Alegretti Borges L. G., et al (2018). Effects of Mechanical Insufflation – Exsufflation on Airway mucus Clearance Among Mechanically Ventilated ICU Subjects. Respir. Care 63 (12): 1471 – 7. 5. Philips Respironics, Cough assist E70. Prirocnik za uporabnike. 6. Bach JR (1993). Mechanical insufflation – exsufflation: a comparision of peak expiratory flows with manually assisted coughing techniqes. Chest 104: 1553 – 62. 7. Bach JR (1994). Update and perspective on noninvasive respiratory muscle aids. Part 2: the expiratory aids. Chest 105: 1538 – 44. 8. Kalos. Prirocnik za uporabnike. 9. Free Aspire advanced. https://www.mpr-italy.it/ 10. Garuti G., Verucchi E., Fanelli I., Giovannini M., Winck J.C., Lusuardi M (2016). Manegement of bronchial secretions with Free Aspire in children with cerebral palsy: impact on clinical outcomes and healthcare resources. Italian Journal of Pediatrics 42:7. 11. Belli S., Masocco F., Cataneo D., Savio G., Balbi B., Maugeri F.S (2017). The Kalos device: experimental protocol for airway clearance in patients with ineffective cough. ERCA. 12. Manatellini E., Bacchetta C., Caputo F., Defilippi D, Pizzorno M (2018). Consecutive use of Flow Accelator and Cough Assist in patients with Neuro – muscular pathology: 2 clinical cases. ERCA. Maja Zrnic Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija maja.zrnic@klinika-golnik.si Uvod: Pravilen samonadzor bolezni izboljšuje kakovost življenja pacienta z astmo. Z ustrezno zdravstveno vzgojo se omogoci njihovo samostojnost in boljši nadzor nad boleznijo. Cilj raziskave je bil ugotoviti kako pacienti vodijo samonadzor astme doma. Metode: Kvantitativna raziskava je bila izvedena na prirocnem vzorcu 58 pacientov, ki so bili obravnavani v pulmološki ambulanti v Kliniki Golnik zaradi astme, od zacetka maja do konca aprila . Podatki so bili zbrani s pomocjo strukturiranega vprašalnika. Za obdelavo rezultatov je bila uporabljena statisticna analiza (t-test, Hi-kvadrat in korelacijsko analizo). Rezultati: Pacienti ocenjujejo, da delno obvladujejo svojo bolezen (75,86%). Ustrezno uporabo inhalacijskih zdravil ocenjujejo kot dobro (84,48%), ampak so neodlocni glede uporabe PEF-a (81,03%). Nekadilci bolje poznajo dejavnike, ki poslabšajo astmo (51,72%) v primerjavi s kadilci (31,03%). Pacienti ocenjujejo, da je zdravljenje astme zamudno (87,93%), vendar zaupajo inhalacijskim zdravilom (89,66%) in so pripravljeni spremeniti življenjski stil (86,21%). Vecina je je spremenilo življenjske navade zaradi astme (85,96%). Menijo, da je zdravstvena vzgoja pomembna in ocenjujejo, da imajo dovolj znanja, da se astma ne poslabša (82,76%). Ugotavljali smo moc povezanosti med znanjem o astmi, obvladovanjem bolezni ter merjenjem PEF-a doma. Ugotovili smo statisticno znacilno povezanost med meritvami PEF-a doma in razumevanjem namena merjenja PEF-A vsak dan Povezava je pozitivna (r = 0,898, p < 0,001), kar pomeni, da pacienti, ki si doma merijo PEF tudi bolj razumejo namen merjenja PEF-a. Prav tako smo ugotovili statisticno znacilno povezanost med dejavniki, ki poslabšajo astmo in meritvami PEF-a (r = 0,300, p = 0.041). Povezava je srednje visoka in pozitivna, kar pomeni da pacienti, ki si doma merijo PEF bolj poznajo dejavnike, ki poslabšajo astmo. Zakljucek: Rezultati so primerljivi podobnim raziskavam drugih avtorjev. Za nadaljnjo natancnejšo obdelavo bi bila priporocljiva raziskava, v katero bi bil zajet obsežnejši vzorec pacientov z astmo. Mariana Paula Rezelj, Peter Kopac, Anja Simonic, Tina Remškar, Tea Mocnik, Sabina Škrgat Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija mariana.paula-rezelj@klinika-golnik.si Uvod: Trenutni vprašalniki, ki jih uporabljamo za oceno urejenosti astme, kot so na primer ACT (Asthma Control Test), so bili razviti predvsem za bolnike z blago do srednje težko astmo. Bolniki s težko astmo predstavljajo najmanjši delež (4-10%) vseh pacientov z astmo, vendar pa imajo nesorazmerno najvišjo stopnjo obolevnosti, komorbidnosti in tudi najvišje stroške zdravljenja. Na kakovost življenja bolnikov s težko astmo ne vplivajo samo vsakodnevne omejitve zaradi respiratornih simptomov, imajo tudi vec in težja poslabšanja, vec in pogostejše hospitalizacije, ki motijo življenje bolnikov in njihovih svojcev. Kakovost življenja zniža tudi breme sistemskih steroidov. Neželeni ucinki steroidov so povezani s številnimi težavami, vkljucno s spremembami razpoloženja, samopodobe, težavami s prehranjevanjem, motnjo spanja in spremembami videza. Te neželene ucinke lahko izboljšamo z zmanjšanjem peroralnih kortikosteroidov, kar lahko dosežemo, ko bolniki zacnejo biološko zdravljenje. Posege, ki izboljšujejo kakovost življenja, povezanih z zdravjem, je mogoce natancno oceniti le, ce se uporabijo ustrezna orodja za oceno specificnih zdravstvenih težav, ki jih imajo ljudje težko astmo. Vprašalnik za težko astmo SAQ (Severe Asthma Questionary) je bil zasnovan s perspektive bolnika, tako, da odkrije vpliv simptomov astme in stranskih ucinkov zdravil, breme jemanja sistemskih steroidov, na kakovost življenja. Zajema vsa podrocja življenja od težav v službi do zasebnega življenja, spolnosti, prostega casa, vpliva bolezni na odnose s svojci in na lastno samopodobo. Potek validacije: Za prevod SAQ v slovenski jezik smo se držali protokola skupine Plymouth SAQ. Potreben je bil dvostopenjski postopek, ki je vseboval prevode in kvalitativno analizo razumevanja vprašalnika s strani bolnikov. Sodelovala je interdisciplinarna ekipa medicinskih sester, zdravnikov in klinicnega psihologa. Udeleženi sta bili dve fokusni skupini bolnikov, ki so bili izbrani tako, da so predstavljali obravnavano populacijo, tj. Bolniki s hudo astmo v skladu s smernicami GINA. Zaželeno je bilo ravnovesje med moškimi in ženskami, starostjo. Povprecna starost udeležencev fokusnih skupin je bila 54,4 let. Sodelovalo je 7 moških in 6 žensk. Moderator je pridobil soglasje bolnikov. Seja smo zvocno posneli in anonimizirano prepisali. Bolniki so bili seznanjeni s ciljem seje, to je izboljšanje besedila vprašalnika. Prebrali so in izpolnili vprašalnik. Na vsako vprašanje je moderator sprožil razpravo o tem, kako bolniki razumejo, kaj je napisano. Spodbujal jih je, da so opisali, kaj mislijo. Opis vsakega bolnika je postal osnova za razpravo z drugimi udeleženci. Moderator je popisal vse predloge. Postopek se je nato ponovil z drugo fokusno skupino. Moderator je pripravil priporocilo o koncnem besedilu vprašalnika. Skupne predloge smo upoštevali in vprašalnik popravili, dopolnili. Koncno prevedena razlicica s potrditvijo izvedenih postopkov in kratkim povzetkom vseh vprašanj, ki so jih postavili bolniki je bila predstavljena skupini Plymouth SAQ, ki je prevod odobrila in objavila na svoji spletni strani. SAQ vprašalnik lahko sedaj uporabljamo za sledenje uspeha zdravljenja težke astme z biološkimi zdravili in tudi za primerjavo z drugimi državami. Mariana Paula Rezelj, Peter Kopac, Irena Pocvavšek, Jana Tršan, Tina Morgan, Sabina Škrgat Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija mariana.paula-rezelj@klinika-golnik.si Uvod: Zdravljenje bolnikov s težko astmo je namenjeno nadzoru astme. GINA (Globalna iviciativa za astmo) prepoznava visoko porabo SABA in nepravilne tehnike vdihavanja, kot pomembne dejavnike tveganja za poslabšanje astme. Cilj: Cilj naše raziskave je bil preuciti tehniko vdihavanja olajševalca pri bolnikih s težko astmo. Preverili smo, ali je bila velika poraba olajševalca povezana z neprimernimi tehnikami vdihavanja. Metode: Multidisciplinarna skupina (medicinska sestra, farmacevt in zdravnik) je analizirala in ocenila tehniko vdihavanja pri 80 bolnikih s težko astmo na bioloških zdravilih. Vprašali smo bolnika o uporabi olajševalcev in izmerili inspiratorni pretok pri vdihavanju z napravo In-Check Dial®. Primerjali smo podatke bolnikov, ki porabijo 1 do 3 kanistre na leto, s tistimi, ki so porabili 5 ali vec. Rezultati: Med 80 bolniki (30 moških, mediana starosti 55 let) jih je bilo 26 (11 moških, mediana starosti 55,5), ki so porabili 5 ali vec kanistrov/leto in 17 (5 moških, mediana starosti 53) z do 3 kanistrov/leto. Samo pri 12 bolnikih smo ugotovili klinicno ucinkovit pretok (razpon od 30 do 60 l/min). Bolniki z visoko porabo SABA so imeli slabšo inhalacijsko tehniko v primerjavi s tistimi z nizko porabo (pravilno le pri 31 % oziroma 53 %), zavrgli so pol prazen kanister pogosteje (31% v primerjavi z 24 % ) in so po nepotrebnem uporabljali vdihovalnik (53% v primerjavi s 35 %). Zakljucki: Vec kot polovica bolnikov s težko astmo, olajševalcev ne uporablja pravilno. Visoka poraba olajševalca je povezana z neustrezno tehniko vdihavanja, prezgodaj zavrženimi kanistri in pogosto nepotrebno uporabo zdravila. Izboljšanje tehnike vdihavanja in multidisciplinarni pristop pri obravnavi bolnika, privede do boljšega nadzora nad astmo. Jana Tršan Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija jana.trsan@klinika-golnik.si Astma je bolezen, ki jo spremlja poslabšanje simptomov. Bolnikom s težko obliko astme je namenjeno podporno zdravljenje z biološkimi zdravili. Za zdravljenje težke astme so trenutno v Sloveniji na voljo štiri biološka zdravila. Bolnik s težko astmo je najprej napoten na ambulantni pregled na Kliniko Golnik s strani podrocnega pulmologa. Na podlagi pregleda se bolnika predstavi na zdravniškem obstruktivnem konziliju za pljucne bolezni, ki tudi sprejme indikacijo za samo zdravljenje ter se doloci, katero biološko zdravilo bi bilo za bolnika najbolj primerno. Ob prvi aplikaciji biološkega zdravila je bolnik obvezno hospitaliziran, nato pa zdravljenje nadaljuje ambulantno. Kontinuirana in koordinirana ambulantna obravnava je osnova za zagotavljanje varne in kakovostne oskrbe. Na Univerzitetni Kliniki Golnik poteka ambulantno zdravljenje bolnikov s težko astmo v ambulanti za biološko terapijo. Namen te ambulante je najboljša možna ambulantna oskrba in vodenje te skupine bolnikov, ki imajo lahko pridružene tudi druge kronicne bolezni. V zadnjih letih smo reorganizirali nacin dela v biološki ambulanti in razširili tim poklicnih strokovnjakov z namenom ucinkovitejšega vodenja bolnikov s težko astmo. Poleg zdravnika in diplomirane medicinske sestre se v multidisciplinarno obravnavo aktivno vkljucujejo tudi respiratorni fizioterapevt, dietetik, klinicni farmacevt in psiholog. Vsi izvajalci delujejo povezano z ucinkovito medsebojno komunikacijo. Diplomirana medicinska sestra ima pomembno vlogo tako pri narocanju bolnikov, izvaja zdravstveno vzgojno delo in samostojno pripravi ter aplicira zdravilo. Bolnika napoti predhodno k zdravniku samo v primeru odstopanj. Respiratorni fizioterapevt bolnika po potrebi nauci ali preveri pravilno tehniko izvajanja dihalnih vaj ter cišcenja dihalnih poti. Prav tako je pomembna tudi prehranska obravnava s strani dietetika pri bolnikih, ki so prepoznani kot prehransko ogroženi. Klinicni farmacevt se vkljuci takrat, ko je potrebno preverjati, koliko zdravil je bolnik dejansko prevzel v lekarni in preveri razumevanje vloge posameznih zdravil. V primeru, da se pri bolnikih opazi izguba motivacije, brezvoljnost in znaki depresije, se vkljuci tudi psihologa. Naše izkušnje potrjujejo, da se vecina vseh bolnikov zelo dobro vkljucuje in aktivno sodeluje v timskem procesu zdravljenja v biološki ambulanti in imajo bolj urejeno osnovno bolezen ter izboljšano kvaliteto življenja. Tea Mocnik, Lidija Oštir, Anton Justin Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija tea.mocnik@klinika-golnik.si Specificna imunoterapija (VIT) s strupi žuželk je edino ucinkovito vzrocno zdravljenje za paciente, ki so preobcutljivi za pik kožekrilca. VIT izvajamo po konvencionalni (angl. convencional), hitri (angl. rush) ali zelo hitri (angl. ultra-rush) shemi, zdravljenje pa traja približno 5 let. Med zdravljenjem se lahko pojavi približno 12 do 30 odstotkov sistemskih preobcutljivostnih reakcij (Kolaczek et al., 2017; Ludman in Boyle, 2015). Med najpogostejše dejavnike, ki lahko vplivajo na vecjo verjetnost in težji potek sistemske preobcutljivostne reakcija spada mastocitoza (Przybilla et al., 2011). Pomembna naloga diplomirane medicinske sestre med zdravljenjem z VIT je zagotavljanje varnosti pacientov, zgodnje prepoznavanje prvih znakov preobcutljivostne reakcije in hitro ukrepanje po smernicah za obravnavo anafilaksije (Košnik et al., 2015; Rezelj, 2012). Predstavitev primera: 54-letni pacient je septembra 2018 po piku sršena utrpel sistemsko preobcutljivostno reakcijo z dolgotrajno hipotenzijo in izgubo zavesti. V diagnosticnem postopku smo pri pacientu potrdili senzibilizacijo s stupom ose in cebele in glede težo sistemske reakcije ocenili, da potrebuje zdravljenje s specificno imunoterapijo z obema strupoma. Pacient ima potrjeno indolentno mastocitozo, zdravi pa se zaradi arterijske hipertenzije. Do sistemske preobcutljivostne reakcije IV. stopnje je prišlo 20 minut po aplikaciji vzdrževalnega odmerka strupa cebele. Pacient je oba strupa prejemal v intervalu 30 minut. Pacient je kolabiral, bil poten in slabo odziven. Prvi krvni tlak 84/70 je bil izmerjen po aplikaciji adrenalina 0.5mg intramuskularno. Pacient je v skupnem odmerku prejel 2mg adrenalina (4x 0.5mg) intramuskularno, v vmesnih fazah tlak obcasno ni bil merljiv. Aplicirali smo tudi 0.2 mg adrenalina subkutano na mesto, kjer je prejel injekcijo specificne imunoterapije, inhalacije adrenalina zaradi pokašljevanja in intravenozno 1000ml fiziološke raztopine. Vmes je prehodno prihajal k zavesti, vendar ni komuniciral. Pacienta smo nato premestili v intenzivni oddelek. Pred premestitvijo je prejel tudi 0.1 ml razredcenega adrenalina intravenozno, nato je adrenalin prejemal v kontinuirani infuziji. Ob sprejemu Na Oddelek za intenzivno nego in terapijo je bil pacient normotenziven, normokarden, prejemal je infuzijo Adrenalina v 100 ml FR s hitrostjo 30 ml/h, kasneje se je pretok znižal na 15 ml/h, nato smo do vecera infuzijo postopoma prekinili. Sprva je imel 2l kisika apliciranega preko nosnega katetra, postopoma smo kisik odstranili. Tekom dneva je bil vitalno stabilen, zaradi hemodinamskega nadzora je bil izvajan neinvazivni monitoring. Vzorec triptaze (20.9) je bil odvzet 120 minut po zacetku sistemske preobcutljivostne reakcije, kar potrjuje, da je šlo za anafilaksijo. Pacient je bil zaradi sistemske preobcutljivostne reakcije 24 ur zadržan v intenzivni enoti. Predpisan ima recept za dva avtoinjektorja adrenalina Epipen. Ob odpustu je prejel natancna navodila o izogibanju kožekrilcem in navodila kako ukrepati ob morebitnem ponovnem piku. O nacinu uporabe avtoinjektorja adrenalina smo poucili tudi pacientove svojce. Literatura: 1. Kolaczek, A., Skorupa, D., Antczak-Marczak, M., Kuna, P., & Kupczyk, M. (2017). Safety and efficacy of venom immunotherapy: a real life study. Advances in Dermatology and Allergology/Postepy Dermatologii i Alergologii, 34(2), 159. 2. Košnik, M., Zidarn, M., Glavnik, V., Vesel, T., Avcin, T., Rotar Pavlic, D., Kokalj Kokot, M., Vajd, R., Zelinka, M., Jereb, M., Mežnar, M., Novak Jankovic, V., Mušic, P. (2015). V M. Košnik in R. Marcun (ur.), Dogovor o obravnavi anafilaksije. Consensus on management of anaphylaxis. Golnik. 3. Ludman, S. W., & Boyle, R. J. (2015). Stinging insect allergy: current perspectives on venom immunotherapy. Journal of asthma and allergy, 8, 75. 4. Przybilla, B., Ruëff, F., Walker, A., Räwer, H. C., Aberer, W., Bauer, C. P., ... in Fuchs, T. (2011). Diagnose und Therapie der Bienen-und Wespengiftallergie. Allergo Journal, 20(6), 318 – 339. 5. Rezelj, M. P. (2012). Izvajanje specificne imunoterapije (novosti) in pomen zdravstvene vzgoje. V L. Prestor, M. Bratkovic (ur.), Zbornik predavanj z recenzijo: Zdravstvena nega pa-cienta z astmo in alergijo (str. 129 – 137). Ljubljana: Zbornica zdravstvene in babiške nege Slovenije - Zveza strokovnih društev medicinskih sester, babic in zdravstvenih tehnikov Slovenije, Sekcija medicinskih sester in zdravstvenih tehnikov v pulmologiji. Renato Eržen Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija renato.erzen@klinika-golnik.si Specificna imunoterapija z alergeni je metoda zdravljenja, pri kateri pri alergicnih osebah z aplikacijo ponavljajocih odmerkov alergena skušamo vzpostaviti imunsko toleranco. Gre za etiološko zdravljenje alergijskih bolezni. Z imunoterapijo zdravimo tiste alergijske bolezni, ki jih posredujejo IgE. Odlocitev o IT sprejmemo po prepricljivi anamnezi, dokazani senzibilizaciji (kožni testi alergije, serološki testi, celicni testi) in jasni povezavi med simptomi alergijske bolezni in izpostavitvijo. Natancni imunski mehanizmi specificne imunoterapije niso poznani. Med imunoterapijo se zmanjša koncentracija sIgE, poveca koncentracija sIgG4, poveca koncentracija Tr1 celic s posledicnim povecanjem koncentracije IL-10. Indikacije za zdravljenje s specificno imunoterapijo so: alergijski rinokonjunktivitis z ali brez astme, alergijska astma, anafilaksija po piku kožekrilcev, redko tudi atopijski dermatitis in alergija na hrano. Kontraindikacije za zdravljenje s specificno imunoterapijo so slabo nadzorovana astma in resne kardiovaskularne bolezni (težka ishemicna bolezen srca, nestabilna AP, nezdravljena AH), slaba komplianca bolnika. Relativne kontraindikacije so zdravljenje z beta-blokerji, avtoimune in maligne bolezni, nosecnost. Alergen lahko apliciramo subkutano (subkutana IT) ali sublingvalno (sublingvalna IT). Subkutano IT izvajamo z inhalacijskimi alergeni (pršica, pelodi) in strupom kožekrilcev, subkutano IT pa samo z inhalacijskimi alergeni. Med subkutano IT bolniku s podkožnimi injekcijami vbrizgamo alergen, na katerega je preobcutljiv. Na zacetku je kolicina alergena majhna, postopno jo vecamo do vzdrževalnega odmerka. Sprva je razmak med aplikacijami kratek, postopno ga daljšamo. Obdobje vecanja odmerka imenujemo uvodna faza, obdobje aplikacije vzdraževalnega odmerka pa vzdrževalna faza. Med vzdrževalno fazo bolniku vbrizgamo vzdrževalni odmerek vsake 4 tedne, nato razmak postopno daljšemo na 8-12 tednov. Specificno imunoterapijo z inhalacijskimi alergeni izvajamo 3 leta, s strupom kožekrilcev pa 5 let. Zapleti med zdravljenjem z inhalacijsko IT so zelo redki. Med IT s strupom kožekrilcev približno 20% bolnikov doživi zaplet v obliki sistemske preobcutljivostne reakcije. IT zato poteka v ustrezno opremljenih prostorih, s pripravljenimi zdravili za zdravljenje sistemskih zapletov, v bližini EIT. Pri sublingvalni IT bolnik kapljice ali tablete alergena na tešce aplicira sublingvalno, zadrži 2 minuti in preostanek pogoltne. Uvodna faza, med katero odmerek alergena postopno vecamo do vzdrževalnega odmerka, poteka v ambulanti pod zdravniškim nadzorom, nato si bolnik aplicira alergen dnevno v domacem okolju. Bolnik s perzistentnim rinokonjunktivitisom prejema alergen vsak dan tri leta. Bolniki z intermitentnim rinokonjunktivitisom pricnejo z jemanjem alergena 12-16 tednov pred sezono polinacije in z jemanjem nadaljujejo do konca sezone, nato prekinejo in po enaki shemi nadaljujejo 3 sezone. Pri sublingvalni IT so lokalni zapleti zelo pogosti, praviloma so blagi in ne potrebujejo zdravljenja, sistemski zapleti pa izjemno redki. Za uspešno vodenje IT je pomembno, da pravi bolnik prejme pravi alergen v pravem odmerku. Bolniku pred aplikacijo preverimo identiteto, ga pregledamo, povprašamo o spremembi terapije, zdravstvenem stanju, cepljenju, težavah ob predhodni aplikaciji alergena, morebitnih pikih, preverimo obdobje od zadnje aplikacije. Nato preverimo alergenski produkt, koncentracijo, odmerek, rok uporabe. Po vsaki aplikaciji bolnika opazujemo 30 minut. Bolniki morajo biti obvešceni, da med opazovanjem ne zapušcajo oddelka in takoj obvestijo osebje o pojavu zapletov. Bolnik mora dobiti tudi navodila o ukrepih ob poslabšanju po odhodu iz bolnišnice. S specificno imunoterapijo dosežemo izboljšanje klinicne slike, manjšo porabo zdravil in izboljšanje kakovosti življenja. Specificna imunoterapija je pri preobcutljivih za strup kožekrilcev edina ucinkovita profilaksa pred ponovnimi težkimi sistemskimi preobcutljivostnimi reakcijami po piku. Tea Mocnik, Karmen Perko, Tina Remškar, Maja Jošt, Peter Kopac Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija tea.mocnik@klinika-golnik.si V zadnjih letih je povecanje uporabe novih zdravil za zdravljenje raka in sistemskih vezivnotkivnih bolezni ter zdravljenje z uporabo monoklonskih protiteles povezano s povecanjem preobcutljivostnih reakcij za tovrstna zdravila (3). Desenzibilizacija je postopek, ki spremeni imunski odziv in povzroci zacasno toleranco na doloceno zdravilo. Razlicni desenzibilizacijski protokoli omogocajo bolnikom, da prejmejo celoten odmerek zdravila, za katerega so imeli predhodno preobcutljivostno reakcijo. V kolikor zdravljenje z zdravilom prekinemo, se bolnikova preobcutljivost za zdravilo vrne (2). Za aplikacijo zdravil po desenzibilizacijskem postopku se odlocimo, ko za izboljšanje zdravstvenega stanja nimamo no voljo boljših nadomestnih zdravil oziroma, ko je ucinkovitost zdravljenja z dolocenim zdravilom po postopku desenzibilizacije bistveno vecja od tveganja za poslabšanje bolnikovega zdravstvenega stanja (1; 5). Desenzibilizacijski postopek izvaja multidisciplinarni tim, ki vkljucuje zdravnika specialista alergologa, diplomirano medicinsko sestro s specialnimi znanji iz podrocja alergologije ter klinicnega farmacevta. Na Univerzitetni kliniki za pljucne bolezni in alergijo Golnik je bilo od leta 2014 do 2020 po protokolu intravenoznih desenzibilizacij zdravljenih 18 bolnikov. Približno 73 odstotokov je bilo izvedenih po 12 ali 16 - stopenjskemu desenzibilizacijskem protokolu, 27 odstotkov pa je bilo izvedenih po protokolu pocasne intravenozne aplikacije. Od vseh izvedenih desenzibilizacij jih je 66 odstotkov potekalo brez zapletov, pri 22 odstotkih (n=4) smo zabeležili SR z generalizirano urtikarijo ter 11 odstotkov (n=2) SR s padcem krvnega tlaka. Prekinjenih zdravljenj s postopkom desenzibilizacije smo zabeležili 22 odstotkov. Dva bolnika sta se na lastno željo odlocila za prekinitev zdravljenja, dva bolnika pa sta zdravljenje prekinila zaradi spremembe nacina zdravljenja po posvetu z lececim revmatologom oziroma onkologom. Od vseh izvedenih desenzibilizacij je bilo 78% uspešno zakljucenih. Dobro medsebojno sodelovanje in prizadevanje razlicnih strokovnjakov pripomore k ucinkovitemu izvajanju desenzibilizacij, izboljša pa tudi psihicno pocutje bolnika, da se ob samem izvajanju zdravljenja pocuti varno. Razvoj ekipe, ki skrbi za natancno ter kakovostno zdravljenje po desenzibilizacijskh protokolih in ob tem zagotavlja najsodobnejšo oskrbo bolnikov, pa je možno le z usklajenim multidisciplinarnim timskim delom (4). Literatura: 1. Bonamichi-Santos, R., & Castells, M. (2016). Desensitization for drug hypersensitivity to chemotherapy and monoclonal antibodies. Current pharmaceutical design, 22(45), 6870-80. 2. De las Vecillas Sánchez, L., Alenazy, L. A., Garcia-Neuer, M., & Castells, M. C. (2017). Drug hypersensitivity and desensitizations: mechanisms and new approaches. International journal of molecular sciences, 18(6), 1316. 3. Isabwe, G. A. C., Neuer, M. G., de Las Vecillas Sanchez, L., Lynch, D. M., Marquis, K., & Castells, M. (2018). Hypersensitivity reactions to therapeutic monoclonal antibodies: phenotypes and endotypes. Journal of Allergy and Clinical Immunology, 142(1), 159-170. 4. Mezzano, V., Giavina-Bianchi, P., Picard, M., Caiado, J., & Castells, M. (2014). Drug desensitization in the management of hypersensitivity reactions to monoclonal antibodies and chemotherapy. BioDrugs, 28(2), 133-144. 5. Silvia, C., Carlo, C., Francesca, S., Lucia, L., Giuseppe, C., Fabio, C., ... & Gian, L. M. (2019). Drug desensitization in allergic children. Acta bio-medica: Atenei Parmensis, 90(Suppl 3), 20. Saša Kadivec Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija sasa.kadivec@klinika-golnik.si Uvod: Uporaba samoinjektorja adrenalina je prva linija zdravljenja anafilaksije. Zgodnja in pravilna raba izboljša klinicne izide, kot sta obolevnost in umrljivost. Samoinjektor se predpiše pacientu z anamnezo anafilakticne reakcije in tveganjem, da se anafilaksija ponovi ob ponovnem kontaktu z alergenom. Za pravilno uporabo samoinjektorja je pomembno, da je pristop k edukaciji bolnikov celovit, kar pomeni, da vkljucuje vsa starostna obdobja od otroka naprej, družino, šolo, športne dejavnosti in da izobraževanje vkljucuje tudi nadzor bolnikov glede prepoznavanja anafilaksije in ukrepanja v primeru pojava. V raziskavi smo želeli ugotoviti, kako so uporabe samoinjektorja adrenalina vešci bolniki, ki so dobili prvi predpis recepta v okviru urgentne obravnave anafilakticne reakcije oziroma pri svojem osebnem zdravniku. Želeli smo ugotoviti dejavnike, ki vplivajo na sposobnost pravilno uporabiti samoinjektor in ugotoviti v katerih korakih najveckrat storijo napako. Metode: Raziskava je bila izvedena v specialisticni ambulantni dejavnosti terciarne ustanove. V raziskavo so bili vkljuceni bolniki z anamnezo anafilaksije, ki so bili napoteni na prvi alergološki pregled v specialisticno alergološko ambulanto zaradi anafilaksije in so že v urgentnem centru ali pri osebnem zdravniku dobili predpis samoinjektorja adrenalina. Zaprošeni so bili, naj pokažejo uporabo samoinjektorja z uporabo vadbenega pripomocka. Medicinska sestra je bolnika opazovala 1 minuto in po tem casu presodila, ali si je bolnik uspel ucinkovito aplicirati zdravilo. Uporabniki, ki so kljucne korake (odstranjevanje modrega varnostnega pokrova, postavitev konice za injiciranje stegno in držanje injekcijskega peresa nekaj sekund) izvedli pravilno, so bili oznaceni kot kompetentni pri uporabi samoinjektorja. Bolnike smo razdelili v dve skupini; skupina, ki zna uporabiti samoinjektor in skupina, ki ga ne zna. Za statisticno analizo obdelave podatkov smo uporabili program Microsoft Excel 2013. Rezultati: Vkljucili smo 41 bolnikov (24% žensk), ki so na pregled prišli 116 ± 145 dni po tem, ko so dobili predpis recepta za samoinjektor adrenalina. Ob predpisu recepta sta 26 bolnikom (63,4 %) zdravnik ali medicinska sestra razložila navodila o uporabi samoinjektorja, 13 bolnikov (31,7%) je uporabo samoinjektorja vadilo z uporabo vadbenega pripomocka. V lekarni je bilo devetim bolnikom (22,0%) razloženo glede uporabe samoinjektorja, trije od njih so vadili z uporabo vadbenega pripomocka. V casu obiska v alergološki specialisticni ambulanti je imelo 25 bolnikov (61%) samoinjektor pri sebi. Bolniki z višjo izobrazbo so pogosteje znali uporabiti samoinjektor (p= 0,02564). Razprava: Glavna ugotovitev raziskave je, da kljub temu, da so bolniki dobili samoinjektor adrenalina, velik delež ni bil deležen pouka glede njegove uporabe. Le dobra polovica (54%) bolnikov je ob obisku specialisticne alergološke ambulante ucinkovito izvedlo kljucne faze uporabe samoinjektorja. Ukrep: predlagamo redno spremljanje in ponavljanje usposabljanja bolnikov, pošiljanje opomnika, ce pozabijo na obisk, in ob obisku preverjanje pravilne rabe samoinjektorja. Nataša Grahovec Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija natasa.grahovec@klinika-golnik.si Uvod: Pljucni rak je najpogostejši rak, za katerim ljudje po svetu in pri nas zbolevajo in umirajo. Vecja obolevnost sledi predvsem spremenjenim kadilskim navadam, izpostavljenosti škodljivim snovem na delovnih mestih in bivanju v onesnaženem okolju. Prav poznavanje teh dejavnikov tveganja in preventivni ukrepi lahko pripomorejo k manjši obolevnosti v prihodnosti. Pomemben del izboljšanja in vzdrževanja zdravja nasploh je v zadnjih desetletjih pripisati tudi uspešni realizaciji preventivnih zdravniških pregledov in pa izobraženosti ljudi, da v primeru zdravstvenih težav cimprej obišcejo osebnega zdravnika. Možnost hitre diagnosticne obravnave in sodobne terapevtske sheme pa omogocajo zgodnjo postavitev diagnoze, uspešnejše zdravljenje in obvladovanje bolezni. Najpogostejše invazivne preiskave: V Univerzitetni kliniki za pljucne bolezni in alergijo Golnik, je dokaj pogosta pot diagnostike pljucnega raka, najprej pregled v ambulanti za pljucne infiltrate, kamor so napoteni s strani triažnega pulmologa znotraj klinike, kjer opravijo osnovne preiskave (biokemicne preiskave krvi, elektrokardiogram, preiskava pljucne funkcije, rentgen pljuc, ev. tudi globinsko slikanje prsnega koša, trebuha, glave, nato pa so pacienti v nekaj dneh s strani oddelcnega koordinatorja klicani za sprejem na oddelek za interventno pulmologijo, kjer se jih obravnava za nadaljnjo diagnostiko. Pacient ob tem prejme tudi navodila glede jemanja nizko molekularnega heparina, antikoagulantne, antiagregacijske ter diabeticne terapije Spremljajoce bolezni pacienta in njegova telesna kondicija sta osnovna podatka za opredelitev ocene tveganja za zaplete med invazivnimi preiskavami in poznejšim kirurškim ali ne kirurškim zdravljenjem, še pomembneje pa je oceniti funkcionalno stanje bolnika po koncanem zdravljenju (Boc, idr., 2019). Diagnosticni postopki si sledijo v jasnem in enostavnem zaporedju od manj invazivnih do bolj invazivnih, vse do jasne histopatološke diagnoze in natancne ugotovitve razširjenosti bolezni. Diagnosticni postopek indicira zdravnik glede na splošno stanje pacienta, vrsto in lego tumorja ali morebitnih drugih sumljivih sprememb. (Kržišnik & Koren, 2012). Plevralna punkcija: je prva invazivna diagnosticna metoda v diagnostiki plevralnega izliva. Namen je pridobitev plevralnega izliva za nadaljne preiskave. Pri plevralni punkciji zdravnik po predhodno ultrazvocno dolocenemu mestu punkcije, z iglo in brizgo zabode skozi prsno steno in aspirira plevralni izliv. Plevralni izliv po narocilu zdravnika pošljemo na razlicne analize, kot so biokemicna, citološka in mikrobiološka analiza ter laboratorij za tuberkulozo (Kržišnik & Koren, 2012). Gre za izkljucitev ali potrditev malignega plevralnega izliva. Ugotavlja se, ali gre za eksudat ali transudat. Eksudat je tekocina s serumskimi proteini in nastane zaradi povecane prepustnosti plevre ali kapilar. Najpogostejši vzrok eksudata v plevralnem prostoru je vnetje in maligna bolezen. Transudat pa je tekocina, ki jo najdemo v telesnih votlinah in nastane zaradi spremenjenih hidrostatskih sil v plevralnem prostoru, medtem ko prepustnost plevre in kapilar nista bistveno spremenjeni. Diagnozo transudat najveckrat postavimo že na podlagi klinicne slike in izvidov drugih preiskav (Štupnik, 2013). Bronhoskopija: osnovna invazivna preiskava za biopsijski odvzem tkiva je bronhoskopija, ki jo opravimo brez ali v sedaciji. Material je navadno odvzet z biopsijskimi klešcami in igelno punkcijo, ker kombinacija obeh metod poveca možnost za postavitev diagnoze. Pljucna punkcija je preiskava pri kateri po predhodni lokalni anesteziji kože, podkožja in parietalne plevre punktiramo spremembe v prsnem košu. Preiskava poteka pod nadzorom rentgena, racunalniške tomografije ali ultrazvoka. Vzorce za citološke oz. histološke preiskave dobimo z iglami razlicnih dimenzij. Indikacije za preiskavo so sumljive, rentgensko vidne spremembe v pljucih, mediastinumu, plevralnem prostoru in prsni steni (Triller, 2013). Torakoskopija je endoskopski pregled prsne votline oziroma plevralnega prostora. Izvede se v lokalni anesteziji z dodatkom intravenske sedacije, medtem ko pacient spontano diha. Navadno se uporablja le eno, najvec dve vstopni mesti (Rozman, et al., 2011). Indikacije za poseg so: plevralni izliv – eksudat, ki ni bil diagnosticiran z manj invazivnimi metodami, spremembe po plevri, plevrodeza, delno septiran plevralni izliv, pnevmotoraks itd. (Rozman, 2013). Torakoskopija je pogosta invazivna preiskava za potrditev ali izkljucitev mezotelioma. Vloga medicinske sestre: Pacienti s pljucnim rakom so posebna skupina pacientov, ter imajo navadno posebna, z zdravjem povezana vprašanja. So ranljivi in tudi obcutljivi. Zdravstvena nega takšnih pacientov zahteva veliko strokovnega znanja in izkušenj medicinskih sester (Bishop, 2009). Pomembna vloga medicinske sestre je spremljanje pacienta skozi diagnostiko pljucnega raka. S svojim strokovnim znanjem in izvedenimi diagnosticno medicinsko-tehnicnimi posegi zagotavlja varno in hitro obravnavo, preprecuje in prepozna morebitne zaplete ter mu nudi celostno psihosocialno oporo ob soocenju s strahom, ki ga prinaša sum na maligno bolezen ter kasneje tudi samo soocenje z boleznijo. Medicinska sestra mora poleg strokovnega znanja s podrocja diagnosticno-terapevtskih postopkov obvladovati tudi znanja s podrocja komunikacije, custvene inteligence in empatije (Kržišnik & Koren, 2012). Pacientu je vedno treba dati možnost, da opiše obcutke v zgodbi, kot jo doživlja le on. Zelo pomembno je, da pacientovo stisko prepoznamo in se nanjo odzovemo. Izražajo jo na razlicne nacine, nekateri z verbalno, drugo z neverbalno komunikacijo, nekateri z jezo, besom, drugi z jokom. Ob tem je pomembno vkljucevanje psihologinje, ce se pacient s tem strinja. Ena od pomembnih vlog medicinske sestre pa je tudi prepoznavanje zapletov po invazivnih posegih. Zakljucek: Pri obravnavi bolnika s pljucnim rakom je kljucnega pomena hitra diagnostika. Bolniki s pljucnim rakom, odkritim v zgodnjem stadiju, imajo boljšo prognozo in boljše možnosti zdravljenja. S tem namenom nacrtujemo invazivne preiskave na nacin, da biopsijski material dosežemo na najlažje dostopnem mestu in, ce je možno z isto preiskavo potrdimo tako bolezen kot tudi njen stadij. Za izboljšanje odkrivanja bolezni bo potrebno v prihodnosti izobraževati zdravstveno osebje ter ozavešcati in opozarjati prebivalstvo na škodljivost in posledice kajenja ter simptome te zahrbtne bolezni. Smiselna pa bi bila tudi uvedba presajalnega programa. Literatura: 1. Boc, N., Kern, I., Rozman, A., Stanic, K., Štupnik, T., Unk, M., idr. (2019). Priporocila za obravnavo bolnikov s pljucnim rakom. V M. Vrankar (ured.). Ljubljana: Onkološki inštitut: Sloven-sko zdravniško društvo. 2. Kržišnik, I. & Koren, P. (2012). Medicinska sestra spremlja pacienta med diagnostiko pljucnih tumorjev. V M. Matkovic (ured.), Pacienti in pljucni rak – trendi in novosti / 39. strokovni seminar, Zrece 23. marec 2012 (str. 65-74). Ljubljana: Sekcija medicinskih sester in zdravstvenih tehnikov v onkologiji pri Zbornici zdravstvene in babiške nege – zveza strokovnih društev medicinskih sester, babic in zdravstvenih tehnikov Slovenije. 3. Marc Malovrh, M., 2019. Organizacijski vidik obravnave bolnikov s pljucnim infiltratomvloga ambulantne obravnave. Zbornik sestanka Jesensko srecanje ZPS 2019, november 2019 Portorož: Združenje pnevmologov Slovenije, pp.12-14. 4. Rozman, A., Debeljak, A. & Kern, I., 2011. Torakoskopija – analiza 129 posegov. Zdravniški vestnik, 80:546-52. 5. Rozman, A., 2013. Malignom plevre, torakoskopija in plevrodeza. In: Prestor, L. ed. Zbornik predavanj z recenzijo - Obravnava pacientov s pljucnim rakom, Debeli rtic, 24.-25. maj 2013. Ljubljana: Zbornica zdravstvene in babiške nege Slovenije – Zveza društev medicinskih sester, babic in zdravstvenih tehnikov Slovenije, Sekcija medicinskih sester in zdravstvenih tehnikov v pulmologiji, pp. 35- 40. 6. Štupnik T. (2013). Torakalna punkcija & torakalna drenaža. Ucbenik za zdravnike in medicinske sestre. Ljubljana: samozaložba. Urška Janžic Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija urska.janzic@klinika-golnik.si V zadnjem desetletju smo prica ogromnemu napredku v sistemskem zdravljenju pljucnega raka, predvsem pri bolnikih z napredovalo boleznijo – zdravljenje gre v smeri personalizirane medicine, ko za vsakega bolnika poišcemo najbolj optimalen nacin zdravljenja. Pri omejeni bolezni, ko je še možno radikalno zdravljenje, to poteka z operacijo in nato glede na znacilnosti in stadij tumorja še s pooperativno kemoterapijo in/ali radioterapijo. Vedno vec pa je podatkov tudi glede uporabe imunoterapije ali tarcne terapije tudi pooperativno. Pri razsejani bolezni, ki je praviloma neozdravljiva, je cilj onkološkega zdravljenja podaljšanje bolnikovega življenja, ki naj bo cimbolj kvalitetno. Torej je cilj tako zmanjšanje simptomov raka, kot tudi cim manj neželenih ucinkov s terapijo, ki jo uporabljamo. Še pred dobrim desetletjem smo lahko bolnikom z napredovalim pljucnim rakom ponudili le zdravljenje s kemoterapijo na bazi platine, ob kateri je bilo povprecno preživetje bolnikov okoli 12 mesecev, ob tem pa so imeli bolniki kar nekaj neželenih ucinkov kot posledica citostatskega zdravljenja. Danes se kemoterapija kot samostojno zdravljenje pri napredovalem raku pljuc umika drugim, bolniku bolj prijaznim možnostim zdravljenja. Ena od teh je tarcna terapija in je usmerjena proti tocno doloceni tarci (izraz, ki se za ta zdravila pogosto uporablja, so biološka zdravila, vendar biološka nakazuje samo na nacin njihove izdelave, ne pa na nacin ucinkovanja). Poleg že rutinsko dostopnih zdravil, usmerjenih proti EGFR, ALK in ROS-1, imamo preko posebnih programov na voljo tudi zdravila, usmerjena proti BRAF, MET, NTRK, RET, HER-2 itn. Tarcna terapija je uperjena proti tocno doloceni tarci – deluje na sistemu kljuc - kljucavnica. Zato je tarcna terapija tudi zelo ucinkovita in ima bistveno manj neželenih ucinkov, saj deluje vecinoma samo na rakavo spremenjene celice in ne na ostale celice organizma. Taka terapija torej omogoca bolnikom dobro kvaliteto življenja z malo neželenimi ucinki in bistveno daljšimi preživetji – tudi do 5 - 7 let. Še veliko bolj revolucionarna je bila uvedba zdravljenja z inhibitorji nadzornih tock (angl. immune checkpoint inhibitors) ali na kratko imunoterapije za zdravljenje raka pljuc. Onkologija se je že od nekdaj spogledovala tudi z imunoterapijo oz. terapijo, ki bi uspešno aktivirala imunski sistem z namenom unicevanja rakavih celic. Imunoterapija ne ucinkuje direktno na tumorske celice, ampak omogoca bolnikovim lastnim limfocitom, da prepoznajo tumorsko celico in jo unicijo. Pricakovano ima zdravljenje z zaviralci imunskih nadzornih tock vecinoma neželene ucinke, ki posnemajo avtoimunska dogajanja in posnemajo kakršnokoli vnetje kjerkoli v telesu. V tem primeru je razpoznava in hitro ukrepanje kljucnega pomena, saj so sicer lahko taki neželeni ucinki tudi smrtno nevarni. V kolikor rakava bolezen dobro reagira na zdravljenje z imunoterapijo, lahko pricakujemo zelo dolge zazdravitve bolezni; tudi do te mere, da bolnik ne potrebuje vec nobene terapije in ga lahko samo spremljamo. Vsekakor so možnosti zdravljenja raka pljuc danes veliko bolj obetavne kot še samo desetletje nazaj in kot kaže, bo v prihodnosti teh možnosti še veliko vec, saj gre razvoj v pravi smeri z neverjetno hitrostjo. Shpresa Mazreku Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija shpresa.mazreku@klinika-golnik.si Na Univerzitetni kliniki za pljucne bolezni in alergijo Golnik(Klinika Golnik) vsako leto odkrijemo 600-700 novih bolnikov s tumorji torakalnih organov, najpogosteje je to pljucni rak, redkeje pa mezoteliom in rak priželjca. Vecino novo-odkritih bolnikov po postavitvi diagnoze nadaljuje obravnavo na Kliniki Golnik. V Enoti za internisticno onkologijo (EIO) zdravimo bolnike, ki potrebujejo sistemsko terapijo, bodisi kot dopolnilno zdravljenje po operaciji, ali v okviru zdravljenja razsejane bolezni. Za optimalno obravnavo bolnikov s pljucnim rakom, je potrebno sodelovanje strokovnjakov razlicnih podrocij. Delo, ki ga opravijo zdravniki, se prepleta z delom medicinskih sester, socialnih delavcev ter psihologov in drugih služb. Na Kliniki Golnik smo po vzoru onkoloških centrov v tujini, razvili organizacijski model, ki zajema sodelovanje vseh omenjenih služb. Ob sumu na raka poskušamo ugotoviti izvor in vrsto rakave bolezni, razširjenost in morebitne molekularne oznacevalce, saj so vsi ti podatki pomembni za odlocitev o zdravljenju. Po zakljucku diagnosticnih postopkov dokumentacijo predstavimo na multidisciplinarnem Konziliju za torakalne tumorje, kjer so prisotni pulmologi, internisti onkologi, kirurgi, patologi, radiologi in radioterapevti. Bolnike, ki potrebujejo zdravljenje v EIO, kontaktira koordinator EIO. Obvesti jih o manjkajoci dokumentaciji, napotnici in da osnovne informacije o poteku prvega pregleda pri onkologu. Ob prvem pregledu je priporocljivo, da je prisoten nekdo od svojcev, ker se pogovorimo o nacinu in poteku zdravljena v naši enoti. Vsakemu bolniku, damo pisna in ustna navodila o poteku zdravljenja, ucinkih in stranskih ucinkih ter telefonsko številko, na katero lahko poklice za informacije. Bolniki izpolnijo vprašalnik o psihološkem stanju na osnovi katerega jim svetujemo glede obravnave pri psihologu. Prejmejo tudi informacije o možnosti vkljucitve v obravnavo socialne službe. Pri uvedbi kemoterapije diplomirana medicinska sestra (DMS) izvede zdravstveno vzgojno šolo. Pri naslednjem pregledu pa oceni koliko bolnik podana navodila razume in oceno pisno zabeleži. Pri zdravljenju z imunoterapijo po prvem pregledu, bolnike napotimo na pregled k tirologu. , Po potrebnih preiskavah in prejetih izvidih bolniki pridejo na ponovno kontrolo in pricnejo z imunoterapijo. Pri prvi aplikaciji so bolniki še dve uri po koncani terapiji na monitorju in opazovanju. Med aplikacijo terapije DMS opravi zdravstveno vzgojno šolo in po potrebi vkljuci klinicnega farmacevta. Pri imunoterapiji ki jo apliciramo na 6 tednov, po 3 tednih DMS poklice pacienta in povpraša o splošnem stanju in neželenih ucinkih in glede na to tudi dalje ukrepa, poda nasvete ali ce je potrebno obvesti tudi lececega onkologa. Pri zdravljenju s tarcnimi zdravili, poleg omenjenih navodil zdravnika in DMS, ob prvem pregledu vkljucimo klinicnega farmacevta, ki se z bolnikom pogovori o socasni terapiji, alternativi in prehranskih dodatkih. Vloga koordinatorja in skupnih sestankov: Koordinator poklice za prvi pregled, sprejema klice in bolnikove težave skupaj z zdravnikom rešuje. Svetuje kako ukrepati ob pojavu neželenih ucinkov. Vse klice zabeleži. Vsak cetrtek je skupni sestanek EIO, kjer poteka predaja bolnikov. V te sestanke so vkljuceni farmacevti, klinicni psiholog, socialna delavka. S takim nacinom dela bolnike spremljamo v celotnem procesu zdravljenja. Delo je bolje organizirano, s telefonskimi svetovanjem o neželenih ucinkih, le te pravocasno prepoznamo, uspešno in hitro rešujemo ter zmanjšujemo število obiskov v bolnišnici. Poleg boljših rezultatov zdravljenja, se bolniki pocutijo varno, saj v vsakem trenutku vedo kam se za nasvet lahko obrnejo. Diagnostika in zdravljenje bolnikov s pljucnim rakom morata biti hitra, ucinkovita in varna. Da bi to dosegli, bolnike cim bolj celostno obravnavamo. Ivanka Kržišnik Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija ivanka.krzisnik@klinika-golnik.si Zdravljenje raka pljuc je v zadnjem desetletju mocno napredovalo. Na voljo imamo vec zdravil, ki so bolj ucinkovita. Pojav neželenih ucinkov je nemogoce napovedati. Vendar pa pri posameznih zdravilih poznamo možne neželene ucinke. Ti podatki so nam v pomoc, ko poucujemo bolnika, ki mu uvajamo sistemsko zdravljenje raka pljuc. Pri obravnavi bolnika z pljucnim rakom se med seboj mocno prepletajo vloge zdravnika, farmacevta in medicinske sestre. Nujno je, da smo pri obravnavi bolnikov usklajeni o vsebini nasvetov, ki jih dajemo bolnikom. Sistemsko zdravljenje pljucnega raka obsega kemoterapijo, imunoterapijo, kemoimunoterapijo in zdravljenje s tarcnimi zdravili. Vsako od naštetih zdravljenj ima lahko specificne neželene ucinke, ki jih moramo pri delu z bolniki dobro poznati. Zelo pomembno je pravocasno prepoznavanje neželenih ucinkov in pravilno ukrepanje ob njihovi pojavitvi. Neželene ucinke delimo na pogoste, manj pogoste in redke. Glede na jakost jih ocenjujemo s pomocjo poenotenih kriterijev: Common Terminology Criteria for Adverse Events (CTCAE). Neželeni ucinki se lahko pojavijo kadarkoli med zdravljenjem ali pa tudi po že zakljucenem zdravljenju. Ob uvedbi sistemske terapije ocenimo bolnikovo sposobnost razumevanja navodil, sposobnost samooskrbe, socialno okolje, potrebo po psihološki pomoci ter prepoznamo vecja tveganja za neželene ucinke (denimo že prizadeta ustna sluznica/ nevarnost stomatitisa). Ob uvedbi sistemske terapije mediciska sestra pouci bolnika glede splošnih navodil za preprecevanje neželenih ucinkov, ki zajemajo skrb za sluznice, kožo, prehrano, gibanje, izogibanje okužbam ipd. ter predstavi najpogostejše neželene ucinke posamezne sistemske terapije in ukrepanje ob njihovi pojavitvi. Bolnik se mora nauciti, kako mora v casu zdravljenja skrbeti sam zase, da prepreci tiste neželene ucinke, na katere lahko vpliva. Poucen mora biti, kdaj mora k zdravniku. Poleg ustnega informiranja dobi bolnik tudi pisna navodila. Ob vsakem obisku v ambulanti preverimo neželene ucinke in jih tudi zabeležimo. Kadar so neželeni ucinki zdravljenja resni, je pogosto potreben sprejem bolnika v bolnišnico. Resni neželeni ucinki pogosto vodijo v prekinitev trenutnega onkološkega zdravljenja. Poucitev bolnika o preprecavanju neželenih ucinkov in ukrepanje ob njihovi pojavitvi je kljucno za varno obravnavo onkoloških bolnikov. Marija Petrinec Primožic Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija marija.petrinec@klinika-golnik.si Bolniki z malignim plevralnim izlivom v napredovalem stadiju bolezni potrebujejo celostno paliativno obravnavo. Vstavitev trajnega plevralnega drenažnega katetra (TPDK) je ena izmed možnosti paliativnega zdravljenja malignega plevralnega izliva. TPDK kateter se bolnikom lahko uvede ambulantno v lokalni anesteziji. Bolnikom z malignim plevralnim izlivom (MPI) posredno lajša dihalno stisko in izboljšuje kakovost življenja. Ne posega v bolnikove obicajne dnevne aktivnosti. Bolniku omogoca, da kljub svoji osnovni bolezni, vecino casa preživi v svojem domacem okolju. Medicinske sestre imajo kljucno vlogo pri izobraževanju bolnikov, njihovih svojcev in patronažnih medicinskih sester o praznjenju plevralnega izliva preko trajnega plevralnega drenažnega katetra. Prvi TPDK je bil v Univerzitetni kliniki za pljucne bolezni in alergijo Golnik (Klinika Golnik) vstavljen leta 2009. Od aprila 2010 do konca oktobra 2020 smo vstavili 201 TPDK. V Kliniki Golnik na Oddelku za endoskopijo dihal in prebavil, kjer ustavljamo bolnikom z MPI TPDK, redno od decembra 2013 izvajamo individualno šolo ucenja rokovanja in praznjenje plevralnega izliva preko TPDK za bolnike in njihove svojce. Za patronažne medicinske sestre pa izvajamo Šolo zdravstvene oskrbe bolnika s trajnim plevralnim drenažnim katetrom. Medicinske sestre imajo kljucno vlogo pri izobraževanju bolnikov in svojcev o uporabi TPDK in izpraznitvi MPI. Medicinske sestre, ki educirajo bolnike z vstavljenim TPDK in njihove svojce si postavijo vzgojni cilj: usposobiti bolnika oziroma njegove svojce za aktivno praznjenja MPI preko TPDK na bolnikovem domu in s tem izboljšati kakovost bolnikovega življenja. V šoli ucenja rokovanja in praznjenje plevralnega izliva preko TPDK se bolnik, svojci, patronažna medicinska skozi šest faz ucenja seznanijo: kaj je TPDK in kakšen je njegov namen, poznajo set z vakuumsko bucko za praznjenje plevralnega izliva, so sposobni izvesti in prikazati praznjenje plevralnega izliva, znajo namestiti novo obvezo, znajo odstraniti uporabljeno vakuumsko bucko in ostali obvezilni material, dokumentirajo datum, kolicino in barvo izpraznjenega izliva in vedo kdaj poklicati medicinsko sestro ali zdravnika. Barbara Bitežnik Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija barbara.biteznik@klinika-golnik.si Uvod: SARS-CoV-2 je nov koronavirus, ki so ga prvic identificirali v kitajski provinci Vuhan decembra 2019, ko so zaznali vec primerov pljucnic, ki niso bile povzrocene z obicajnimi povzrocitelji pljucnic oz. respiratornih okužb. Bolezen, ki jo virus povzroca, so poimenovali covid-19. Bolezen se kaže s slabim pocutjem, utrujenostjo, bolecinami v mišicah in sklepih, glavobolom, nahodom, z vrocino, kašljem, drisko in pri težjih oblikah z obcutkom težke sape. V lažji obliki poteka pri približno 80 % okuženih. Težji potek, za katerega je znacilna pljucnica, naj bi imelo približno 20 % zbolelih. Smrtnost po okužbi z novim koronavirusom je približno 2-4%. Vecina umrlih je starejših s pridruženimi kronicnimi boleznimi srca, pljuc, sladkorno boleznijo,… Okužbo z novim koronavirusom potrdimo ali izkljucimo z mikrobiološkim testiranjem. Okužbe z novim koronavirusom zaradi podobne klinicne slike namrec ne moremo lociti od okužb z ostalimi povzrocitelji akutnih okužb dihal. Koronavirus lahko dokažemo v brisu nosno-žrelnega prostora, v brisu žrela, izmecku dihal in še v drugih kužninah. Zdravljenje je v vecji meri simptomatsko. Od specificnih zdravil uporabljamo protivirusno ucinkovino remdesivir, kot ucinkovito pa se je izkazalo tudi protivnetno zdravilo deksametazon, še posebno pri težko bolnih intubiranih bolnikih in bolnikih na ECMO. Podatkov o ucinkovitosti D vitamina ter cinkovih preparatov zaenkrat še ni. Naše izkušnje s covid-19 bolniki v 1. valu: Od marca do junija je bilo v naši bolnišnici hospitaliziranih 48 bolnikov, razlike med spoloma v številu ni bilo. Povprecna starost hospitaliziranih bolnikov je bila 67,9 let, najstarejši bolnik je imel 95 let, najmlajši 35 let. 15 bolnikov je bilo oskrbovancev DSO. Bolniki so imeli pridružene bolezni (arterijsko hipertenzijo, srcno popušcanje, sladkorno bolezen, astmo/KOPB), le 7 bolnikov je bilo brez znanih kronicnih bolezni. 36 bolnikov je bilo sprejetih zaradi virusne pljucnice, dodatek kisika je potrebovalo 31 bolnikov. 23 bolnikov je bilo zdravljenih s takrat uveljavljeno eksperimentalno terapijo (hidroksiklorokin/azitromicin/ lopinavir+ritonavir), ostali so bili zdravljeni simptomatsko. Sekundarno bakterijsko pljucnico smo ugotavljali pri 16 bolnikih. 7 bolnikov je potrebovalo intenzivno zdravljenje. 11 bolnikov je umrlo. Obdukcija je bila opravljena pri 6 bolnikih, pri vecini bolnikov je bila vzrok smrti respiratorna odpoved, ki je posledica covid-19 pljucnice z razvojem difuzne alveolarne okvare. Prisotnost IgG protiteles proti SARS-CoV-2 smo dokazali pri 32 bolnikih. Jolanda Munih Klinika za infekcijske bolezni in vrocinska stanja, Univerzitetni klinicni center Ljubljana, Ljubljana, Slovenija jolanda.munih@kclj.si V obdobju vsakoletnih priprav na obvladovanje vecjega števila obolelih zaradi gripe in respiratornih okužb se v zdravstvenih ustanovah vedno soocimo z dejstvom, da se lahko pojavi okužba, ki bo imel epidemicne razsežnosti kot se je to zgodilo v casu španske gripe leta 1918. V casu od 1918 smo se soocali z manjšimi izbruhi gripe in nekaterih drugih nalezljivih bolezni za katere je na zacetku kazalo, da bi lahko šlo za okužbe širših razsežnosti, vendar so se zadeve ali omejile na dolocena podrocja ali pa precej hitro umirile in za zdravstveni sistem in širšo skupnost niso imela hujših posledic. Leta 2003 so veliko pozornosti vzbudile okužbe s koronavirusi na Kitajskem. Okužba, ki so jo kasneje poimenovali SARS se je razširila v 29 držav. Na možnost pojava smo se pripravljal tudi v Sloveniji. Spomladi leta 2009 se je v svetu pojavil podtip virusa prašicje gripe H1N1, ki je dobil ime nova gripa. Zaradi hitrega širjenja je Svetovna zdravstvena organizacija junija 2009 uradno razglasila, da gre po njenih kriterijih za pandemijo, ki se je koncala dobro leto kasneje. V letu 2013 se je na obmocju nekaterih zahodno afriških držav pojavilo vecje število oseb obolelih za Ebola virusno boleznijo. Z vecanjem števila okuženih, obolelih in tudi umrlih se je bojazen pred možnim stikom z okužbo razširila tudi na evropske države. V skladu s priporocili mednarodnih organizacij smo tudi v Sloveniji zaceli s pripravami na možnost pojava primerov s to zelo kužno nalezljivo. Koordinacijska skupine za obvladovanje nalezljivih bolezni pri Ministrstvu za zdravje Republike slovenije je aktivno spremljala dogajanje v svetu in pripravila priporocila za obvladovanje okužbe v Sloveniji. Pri Nacionalnem inštitutu za javno zdravje je bila imenovana posvetovalna skupina, ki je pripravila krovni dokument: Smernice pripravljenosti in odzivanja ob sumu na nalezljivo bolezen, ki lahko predstavlja tveganje za javno zdravje. Klinika za infekcijske bolezni in vrocinska stanja v Ljubljani je pricela z usposabljanjem kadra in zagotavljanjem prostorov in opreme za namestitve bolnika z ZNB. Izdelani protokoli, smernice in izvedena uposabljanja so predstavljala pomembno izhodišce za obvladovanje razmer v casu pojava SARS-COV-2 v zacetku leta 2020. Nika Kokl, Saša Kociper Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija nika.kokl@klinika-golnik.si Uvod: Proti koncu leta 2019 pa se je v mestu Wuhan na Kitajskem pojavila nova vrsta virusne okužbe katere podatki o genomskem zaporedju tega virusa kažejo na nov sev koronavirusa imenovan SARS-CoV-2 (covid-19). Zaradi hitrega prenosa iz cloveka na cloveka preko tesnih stikov, govorjenjem ter kihanjem in kašljanjem je bolezen privedla do pandemije v letu 2020. S pojavom okužb v svetu v kratkem casu je bilo potrebno za obvladovanje bolezni in preprecitve prenosa le-te narediti veliko sprememb pri obravnavi pacientov v bolnišnicah in ambulantah. Zaradi visoke kužnosti obravnava pacienta poteka v posebej opremljenih izolacijskih sobah, zdravstveno osebje pa ves cas uporablja popolno osebno varovalno opremo. Namen naše raziskave je bil ugotoviti, kako se medicinske sestre v urgentni ambulanti srecujejo z izzivi epidemije covida-19, ter kako je le-ta spremenila delo v urgentni ambulanti. Metode: Naša raziskava temelji na empiricno kvalitativni metodologiji s tehniko intervjuja. Intervju je vkljuceval pet osrednjih tematskih vprašanj in pet podvprašanj s podrocja proucevane teme. V raziskavi smo uporabili neslucajnostni namenski vzorec, ki je zajemal 10 diplomiranih medicinskih sester in zdravstvenikov urgentne ambulante Klinike za pljucne bolezni in alergijo Golnik. Po pridobitvi podatkov in transkripciji intervjujev je sledila kvalitativna vsebinska analiza podatkov s kategoriziranjem, kodiranjem in oblikovanjem osrednjih tem. Rezultati: Bolezni covid-19 ter dela z okuženimi pacienti se naši intervjuvanci ne bojijo, po vecini pa je prisoten strah, da bi okužbo nehote prinesli v domace okolje. Njihovo delo se je zelo spremenilo. Z vsakim pacinetom v urgentni ambulanti se obnašajo kot potencialno kužnim in obravnavo pacienta opravijo v posebej urejenih izolacijskih sobah, obleceni v osebno varovalno opremo. Zaposleni so mnenja, da se za paciente obravnava od prejšnih razmer najbolj razlikuje v vecurnem cakanju na PCR test na covid-19. Z nastopom epidemije je bila potrebna reorganizacija dela znotraj zdravstvenega tima in na splošno. Prav tako se je prilagodila namembnost prostorov v sami urgentni ambulanti. Poleg novosti pri samem neposrednem delu s pacienti, pa je epidemija prinesla veliko nepricakovanega tudi našim sodelujocim. Tudi sami so se srecevali z lastnimi okužbami in obolevnostjo svojih najbljižnjih, karantenami in prigoditvami v domacem okolju. Razprava in zakljucek: Epidemija covida-19 je prinesla v svet veliko novega. Zdravstveni delavci so izpostavljeni vsakodnevnim izzivom in morajo biti pri svojem delu zelo organizirani in biti voljni improvizacije novim razmeram. Naši intervjuvaci iz urgentne ambulante so mnenja, da je epidemija prinesla veliko slabega, saj imajo vsakodnevno stik s pacienti s hudimi poslabšanji, prav tako pa so izpostavili, da je izredno stanje pripomoglo k vecji povezanosti kolektiva njihove urgentne ambulante. Zelo veseli so tudi hvaležnosti svojih sodelavcev, družine in širše javnosti, ki v teh kriznih casih zacenja razumeti kako pomembni in nezamenljivi so zdravstveni delavci v kriznih razmerah. Kljucne besede: Coronavirus Disease, symptoms covid-19, epidemic, Emergency nursing. Judita Slak, Tina Remškar Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija judita.slak@klinika-golnik.si Z epidemijo covida-19 smo bili zdravstveni delavci postavljeni pred veliko izzivov. Zaradi reorganizacije dela in pomanjkanja medicinskih sester na Kliniki Golnik smo morali sprejeti 12-urni delavnik. Zaposleni v zdravstveni negi smo se morali na hitro prilagoditi novim, izrednim razmeram, se poglobiti v nove specialnosti ter nehote prilagoditi standarde za izvajanje zdravstvene nege, na katerih smo v zadnjih letih gradili sistem za zagotavljanje varne in kakovostne obravnave pacientov. Glede na reorganizacijo dela smo primorani delati z na novo sestavljenimi timi. Nadvse spodbudno je, da nam je priskocilo na pomoc veliko študentov zdravstvene nege, medicine in prostovoljcev Rdecega križa, ki so zelo motivirani za delo, ceprav so povecini še brez izkušenj. Zagotovo pa je izziv za prihodnost zdravstvene nege, kako mlade motivirati, da bi se odlocili za poklice v zdravstveni negi in v njih tudi vztrajali. V casu epidemije covida-19 se je pod vprašajem znašla tudi varnost medicinskih sester na delovnem mestu, strah pred pomanjkanjem osebne varovalne opreme ter zaskrbljenost pred okužbo ter posledicno prenos le te na družinske clane in sodelavce. Ko smo vzpostavili izolacijske enote, cisto obmocje (bela cona); obmocje, kjer so namešceni pacienti s sumom na covid-19 (siva cona) in obmocje, kjer so pacienti s covidom-19 (rdeca cona), smo se srecali z vrsto težav v komunikaciji, ki se dogajajo med pacienti in zaposlenimi, med zaposlenimi, ki delajo v razlicnih izolacijskih conah ter med pacienti, ki so izolirani in njihovimi bližnjimi. Vecina pacientov, ki so hospitalizirani zaradi okužbe s covidom-19, je v slabem zdravstvenem stanju, tako je pogostejši slab izid zdravljenja, nekateri tudi umrejo. Posledicno smo medicinske sestre pogosteje v stiku z umirajocimi in umrlimi in njihovimi bližnjimi, kar zagotovo vpliva na pocutje zaposlenih in negativno doživljanje svojega dela. Prav gotovo je izziv za prihodnost uvedba supervizije, ki bi bila v podporo zaposlenim v zdravstveni negi, da bi lahko prepoznavali osebne in custvene odzive na delo in jih opremili z znanjem za premagovanje stresa. Poseben izziv pri obravnavi pacientov s covidom-19 predstavlja zdravstvena dokumentacija, ki medicinski sestri v coni izolacije ni dostopna. Tako je pri sprejemanju informacij o zdravljenju pacienta, pri sporocanju informacij o pacientu, o negovalnih intervencijah in pri dokumentiranju odvisna od sodelavcev v beli coni. Z namenom tocnosti in dostopnosti informacij, sprotnega dokumentiranja narocenih in izvedenih intervencij se oblikujejo vedno novi dokumenti, ki pa zaradi že obstojecega velikega števila dokumentov bolj povecujejo obseg dela, kot pa zagotavljajo varnost in informiranost. V dobi digitalizacije, ki se je izkazala kot zelo koristna še posebno v casu epidemije, bi bila edina dobra rešitev obstojecega problema digitalna dokumentacija. Matjaž Fležar Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija Medicinska fakulteta, Univerza v Ljubljani, Ljubljana, Slovenija matjaz.flezar@klinika-golnik.si Uvod: Infekcija z novim koronavirusom povzroci pri 80 % okuženih blago bolezen, med njimi jih je od 20 do 40 % takih, ki so »asimptomatski« torej niti ne pomislijo na okužbo. Do 10 % okuženih potebuje bolnišnicno obravnavo in od teh 25 % intenzivno zdravljenje. V prispevku se bomo osredotocili na slednje. Sprejem bolnika v bolnišnico: Sprejem je indiciran takrat, ko ima bolnik potrebo po zdravljenju s kisikom, ima RTG potrjeno covid-19 pljucnico ali je zaradi prizadetosti ostalih organov (srca, prebavil, metabolnih bolezni) potreben sprejem. Ob sprejemu se pomerijo vitalni znaki in takoj doda kisik v takem odmerku, da se saturacija popravi na 90 %. Pomemben podatek je, koliko casa je bolnik bolan oziroma kdaj je bil bris pozitiven, to pa zato, ker se vecina poslabšanj covid-19 pljucnice zgodi v prvih 10. dneh poteka bolezni. Ker moramo z bolnikom, ki je sum na covid-19 in pozitivnim delati v polni OVO opremi in bolnika imeti v izolaciji (siva cona ali covid-19 oddelek), je pomembno, da že v tem izolacijskem prostoru lahko zacnemo z vsem zdravljenjem (kisik, nadzor vitalnih funkcij, parenteralna terapija, video nadzor). Dobra praksa je tudi taka, da se ob sprejemu pozitivnega bolnika v bolnišnico le-tega ne namešca v prostore sprejemne ambulante ali sive cone, pac pa se takoj naredi RTG PC, pomeri vitalne funkcije (saturacija, tlak, pulz, temperatura) kar na transportnem vozicku in se pred prelaganja bolnika takoj odpelje na covid-19 izolacijski oddelek, kjer ga pregleda zdravnik in se odvzame kri ter zacne zdravljenje. S tem se verjetnost kontaminacije in prenosa okužbe v sprejemni ambulanti, kjer se sprejemajo tudi ne-covid-19 bolniki, obcutno zmanjša. Zdravljenje na oddelku (ali v sivi coni) – kateri je tvegan bolnik? Potreba po kisiku je v dobri korelaciji s težo pljucnice, še posebej, ce potreba nastane zgodaj v razvoju bolezni (prve dni do enega tedna). Primer: bolnik, ki že ob sprejemu potrebuje vec kot 35 % kisikovo masko ali se mu v osmih urah od sprejema potreba po kisiku podvoji in doseže vrednosti vec kot 50 % maska, so ZELO ogroženi. Potrebno se je odlociti, ali je bolnik v svojem splošnem telesnem stanju primeren za intenzivno zdravljenje (to je odlocitev lececega zdravnika in ob odgovoru NE tudi konzilija treh zdravnikov, seznanitev svojcev in bolnika). Za bolnika, pri katerem pridejo v poštev vsi ukrepi, je primeren konstantni monitoring vitalnih funkcij (npr. Midray monitorji). Ce tega ni na voljo, pa meritve vitalnih funkcij na 3 ure. Podporno zdravljenje s kisikom (bolezen povzroca HIPOKSEMICNO respiracijsko odpoved, brez hiperkapnije) omogoca, da bolnik prebrodi najbolj aktivno fazo bolezni in jo tako premaga; sam kisik pa ne zdravi virusa ali pljucnice. Najbolj pogosti spremljajoci zapleti pri teh bolnikih so metabolna iztirjenost (acidoze in alkaloze) in pljucni embolizmi. Manj je ob okužbi sproženih srcnih popušcanj. Bolniki s preeksistentnimi pljucnimi boleznimi so še posebej ogroženi, ker imajo manjšo rezervo v delovanju pljuc. Sem spada predvsem KOPB in intersticijske pljucne bolezni. Covid-19 okužba NE poslabšuje astme in pri astmatikih potek ni slabši kot pri zdravih. Trajanje potrebe po zdravljenju s kisikom je pri takih bolnikih daljša. Bolnikom, ki akutno fazo bolezni preživijo in zaradi covid-19 pljucnice vsaj tri dni hospitalizacije potrebujejo konstantno 1 do 3 litre kisika za vzdrževanje saturacije na 90 %, imajo možnost predpisa in zdravljenja s koncentratorjem kisika na domu do trajanja treh mesecev. S tem skrajšujemo hospitalizacijo, organizem potrebuje vsaj dva meseca, da se stanje povsem normalizira. Podatov o trajnih posledicah prebolele covid-19 pljucnice pa še ni zadosti. Literatura: 1. Kakodkar P, Kaka N, Baig MN. A Comprehensive Literature Review on the Clinical Presentation, and Management of the Pandemic Coronavirus Disease 2019 (COVID-19). Cureus. 2020 Apr 6;12(4):e7560. 2. Miller R, Englund K. Clinical presentation and course of COVID-19. Cleve Clin J Med. 2020 Jun 30;87(7):384-388. Viktorija Tomic Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija viktorija.tomic@klinika-golnik.si Od decembra 2019 se cloveštvo ponovno spopada s pandemijo, ki jo tokrat povzroca beta-koronavirus, SARS-CoV-2. SARS-CoV-2 je respiratorni virus, ki povzroca gripipodobno bolezen, lahko pa tudi težko obliko bolezni, kjer virus ne prizadene le pljuca, ampak tudi druge organe. Bolezen, ki jo povzroca SARS-CoV-2 so poimenovali covid-19 (ang. Coronavirus disease 2019). Ob vsaki pandemiji je kljucnega pomena hitra identifikacija povzrocitelja, tako biološka kot genetska in ugotovitev, kakšen imunski odziv sproži okužba. Za diagnostiko covida-19 imamo na voljo teste, ki neposredno dokazujejo prisotnost (delckov) virusa. To lahko izvedemo s pomocjo kultivacije virusa na celicnih kulturah, z dokazovanjem razlicnih površinskih beljakovin virusa, kar nam omogocajo hitri antigenski testi in z najpogosteje uporabljenimi metodami molekularne biologije in sicer direktnim dokazovanjem virusnih nukleinskih kislin ali detekcijo s pomnoževanjem nukleinskih kislin virusa. Druga možna diagnosticna pot je ugotavljanje imunskega odgovora gostitelja na okužbo z virusom s pomocjo detekcije specificnih protiteles proti SARS-CoV-2. Diagnostiko covida-19 lahko izvajamo za razlicne namene kot so: - triaža simptomatskih oseb, - triaža presimptomatskih in simptomatskih oseb z dejavniki tveganja za, - diagnostika simptomatskih oseb, - diferencialna diagnostika, - potrditveno testiranje, - testiranje oseb s predhodno izpostavljenostjo virusu, - presejanje dolocenih skupin ali okolij, - pojasnjevanje preteklih ali potencialnih izbruhov, - okoljski (epidemiološki) monitoring. Glede na naš diagnosticni cilj uporabimo teste oz. kombinacijo testov, od katerih pricakujemo optimalen diagnosticni izplen. Da bi znali optimalno izbirati teste, moramo poznati njihove tehnicne prednosti in pomanjkljivosti, optimalno casovno okno, v katerem so najbolj uporabni ter njihovo odvisnost od prevalence bolezni v populaciji. Irena Grmek Košnik Nacionalni inštitut za javno zdravje in Nacionalni laboratorij za zdravje, okolje in hrano, Slovenija irena.grmek.kosnik@nlzoh.si Uvod: Koronavirusi zavzemajo pomembno mesto v zgodovini 21. stoletja. V tem stoletju so izolirali pet od sedmih cloveških koronavirusov. Zadnji trije so v naše življenje prinesli strah pred izbruhom, pandemijo in smrtjo. Najnovejši cloveški koronaviruski je izšel iz Kitajske Wuhan, imenuje se SARS CoV-2 in povzroca bolezen covid-19. Epidemiologija bolezni covid-19 ima nekatere svoje znacilnosti širjenja in obnašanja, kar do sedaj nismo poznali. Prenaša se kapljicno in kontaktno s cloveka na cloveka. Prenos preko zraka še ni popolnoma dokazan. Bolezen je zelo kužna. Paleta bolezni covid-19 je opredeljena kot asimptomatska, blaga, zmerna, huda in kriticna. Ceprav so o covidu-19 porocali od bolnikov vseh starosti, se starejši pacienti zdijo bolj dovzetni za okužbo. Pri otrocih bolezen ponavadi poteka brez simptomov, pri ostalih v blagi obliki. V Sloveniji smo prvi val epidemije uspešno obvladali. Dejavnosti smo zaceli sprošcati že po 7 tednih od prvega pozitivnega primera. S hitrimi ukrepi smo preprecili prekomerno širjenje epidemije in s tem povecano smrtnost. Konec maja je število okuženih znova narašcalo zaradi primerov vnesenih iz tujine, in sicer iz Bosne in Hercegovine, Srbije in Kosova. V zacetku avgusta smo zaznali povecano število obolelih predvsem mladih, ki so se vrnili iz Hrvaške. Kako se bo dogajanje odvijalo v prihodnosti je ugibanje. Epidemija sama in ukrepi za njeno zajezitev so povzrocili gospodarsko škodo, škodo na zdravju številnih pacientov zaradi odlaganja zdravljenja, psihicne stiske prebivalstva. Kljub omenjenim težavam je bilo obvladovanje prvega vala epidemije covida-19 v Sloveniji uspešno. Sedaj v zacetku novembra smo v sredini drugega vala, ki je po številu obolelih in umrlih veckratnik prvega. Zakljucek: Kako se bo dogajanje odvijalo v prihodnosti je ugibanje. Epidemija sama in ukrepi za njeno zajezitev so povzrocili gospodarsko škodo, škodo na zdravju številnih pacientov zaradi odlaganja zdravljenja, psihicne stiske prebivalstva. Tatjana Kosten Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija tatjana.kosten@klinika-golnik.si Bolniki z okužbo covidom-19 SARS imajo lahko blage, srednje ali hude respiratorne simptome in veliko jih potrebuje tudi specialno zdravljenje in zdravstveno nego v bolnišnici zaradi respiratorne odpovedi. Covid-19 je nova bolezen, zato so bile smernice za prehransko podporo povzete po priporocilih, ki se uporabljajo za bolnike, ki imajo težko respiratorno obolenje. Simptomi in znaki okužbe z virusom SARS-COV-2 pripomorejo k slabšemu apetitu in posledicno k nezadostnemu vnosu energije in posameznih hranil. Nezadostna prehrana v casu okužbe pripomore k izgubi funkcionalne telesne mase in vpliva na razvoj vnetnih procesov pri okužbi, kar še dodatno vpliva na podhranjenost, ki lahko povzroci dodatne zaplete. Energijske potrebe bolnikov s covidom-19 se doloca individualno, cilj je nekje 30 kcal/kg telesne mase za podhranjene bolnike in starostnike. Ta cilj je potrebno doseci postopno. Potrebe po beljakovinah so 1-1,2 g na kg telesne mase. V primeru nezadostnega energijskega vnosa (manj kot 60% potreb) in pri podhranjenih bolnikih, se svetuje uporaba oralnih prehranskih dodatkov, ki naj bi jih bolniki jemali vsaj en mesec. V primeru da tudi to ne zadošca, se uvede enteralna prehrana preko sonde. Zgodnja uvedba enteralne prehrane lahko zavira vnetje in pripomore k zmanjšanju zapletov. Sondna hrana se uporablja tudi v primeru disfagije, ko tudi hrana ustrezne/ modificirane teksture ni vec primerna. Dopolnilno parenteralno prehrano uvedemo, ce z enteralno ne zagotovimo zadostnega vnosa. Pomembo je preprecevati in zdraviti pomanjkanje mikronutrientov, medtem ko ni dokazov, da bi rutinsko dodajanje le teh imelo vpliv na izid zdravljenja. Za bolnike s covid-19 pljucnico, ki so mehansko ventilirani in se zdravijo v enoti intenzivne terapije, se najprej, ce se le da, uporabi enteralna prehrana, šele nato, ce to ne gre, zacnemo s parenteralno prehrano. Bolnike hranimo po nasogastricni ali nasojejunalni sondi. Tekom zdravljenja na intenzivni enoti se priporoca višji vnos beljakovin: 1,3 g/kg beljakovin na dan, pri bolnikih z debelostjo se upošteva prilagojena telesna masa. Raziskave navajajo, da je dolgotrajna hospitalizacija v ICU enoti vzrok za podhranjenost z izgubo puste telesne mase in funkcionalnosti in vodi v slabšo kakovost življenja, nefunkcionalnost in številne polimorbidnosti. Pomembna je tudi prehranska podpora v casu okrevanja in rehabilitacije bolnikov po odpustu iz bolnišnice v domace okolje. Zagotavljanje ustrezne prehranske podpore je pomembno v vseh korakih zdravljenja, kjer je potrebno upoštevati individualne posebnosti starostnikov, njihovo krhkost in polimorbidnost. Dobra prehranjenost in hidracija sta pomemben del zdravljenja bolnikov s covid-19 boleznijo. Matic Jerman Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenia matic.jerman@klinika-golnik.si Uvod: V zacetku leta 2020 se je bolezen covid-19 pricela nenadzorovano širiti iz Kitajske. Tako velikega navala bolnikov ni pricakoval noben zdravstveni sistem, zato je obremenitev le-tega postala zelo velika. Posledicno so obremenjeni tudi zdravstveni delavci. Metode: Raziskava temelji na metodi kvantitativnega raziskovanja, s pregledom strokovne literature. Pregled literature je bil opravljen s pomocjo podatkovnih baz. Kljucne iskalne besedne zveze po katerih smo iskali zadetke so bile: “Nursing in ICU while covid-19 pandemic”, “Nursing workload in ICU”, “Nursing workload in covid-19 ICU’s”, “Obremenitev medicinskih sester v EIT”. Za izkljucitvene kriterije smo dolocili: vsi viri, ki niso strokovni, nestrokovni spletni viri, neeticne raziskave, zastareli viri, ki so potrjeni z novimi spoznanji, nepopolna besedila oziroma izvlecki. Dobljene rezultate pregleda literature smo nato primerjali z rezultati prikaza ocenjevalnega seznama TISS – 28, ki smo ga vodili tekom epidemije. Rezultati: Rezultati so nam prikazali, da se vecina medicinskih sester, ki so jih zajele raziskave po svetu, srecuje z nekaj osnovnimi problemi oziroma vprašanji. Velika vecina medicinskih sester opozarja na to, da obcutijo strah in nemoc zaradi nepoznavanja delovnega okolja in procesov, ki so nastali tekom sprejemanja bolnikov okuženih z virusom SARS-CoV-2. Anksioznost, ki jo obcutijo medicinske sestre izvira predvsem iz nepoznavanja in neizkušenosti pri delu z bolniki, ki imajo nalezljive oblike bolezni. Prav tako je prisotna skrb, da se nebi okužile z virusom SARS-CoV-2 ali le-tega iz delovnega okolja prenesle domov oziroma bližnjim. Veliko avtorjev pri tem doda, da medicinske sestre navajajo veliko delovno obremenitev in posledicno dolgorocno izcrpanost zaradi preobilice dela. Nekateri avtorji dodajajo, da so medicinske sestre v enotah intenzivne terapije, kjer so hospitalizirani bolniki okuženi s SARS-CoV-2 virusom, skrbele tudi za 9 bolnikov naenkrat, kar je privedlo do zelo velikih delovnih obremenitev ter posledicno slabše obravnave bolnikov. Dobljene rezultate avtorjev smo nato primerjali z rezultati, ki jih prikazuje orodje TISS - 28 za vrednotenje težavnosti obravnave zdravstvene nege bolnikov v enoti intenzivne terapije, ki prav tako prikaže veliko delovno obremenitev medicinskih sester. Zakljucek in diskusija: Velika delovna obremenitev in novosti pri obravnavi bolnikov okuženih z SARS-CoV-2 virusom medicinskim sestram prinašajo veliko novih izzivov. Vsekakor je pomembno, da v teh casih velikih delovnih naporov in nemalokrat osebnih stisk ustrezno poskrbimo za zdravje medicinskih sester in ostalih zdravstvenih delavcev. Maja Zrnic, Tea Mocnik, Peter Kopac Univerzitetna klinika za pljucne bolezni in alergijo Golnik, Golnik, Slovenija majazr21@gmail.com Uvod: Stres je vsako dejanje, ki cloveku postavlja posebne psihološke zahteve in mu poruši njegovo ravnovesje. Stres povezan z delom je zaskrbljujoc pri zdravstvenih delavcih. Povezan je z zmanjšanim zadovoljstvom z delom, tesnobo, depresijo, strokovnimi napakami in nesrecnimi dogodki. Izbruh covida-19 je povzrocil veliko breme ter psihološki stres za zdravstvene delavce. Cilj raziskave je bil ugotoviti kako so doživljali stres zdravstveni delavci pri delu s covid-19 pacienti. Metode: Za izvedbo raziskave smo uporabili prevedeni vprašalnik DASS-21 (cronbach alfa=0.88). V raziskavi je bilo skupno udeleženih 99 anketirancev zaposlenih na Univerzitetni kliniki za pljucne bolezni in alergijo Golnik. Za analizo smo uporabili 93 pravilno izpolnjenih anketnih vprašalnikov. Za statisticno obdelavo podatkov smo uporabili program Excel in GraphPad Prism. Srednje vrednosti oziroma povprecja nenormalno razporejenih spremenljivk smo med skupinami primerjali z uporabo Mann-Whitney U testa. Kot statisticno znacilno smo uporabili p vrednost nižjo od 0.0001. Rezultati: Raziskava je pokazala statisticno pomembne razlike (p<0.0001) v doživljanju stresa, tesnobe in depresije med izpostavljeno skupino (povprecje=10.33) in ne izpostavljeno skupino (povprecje=5.71) ter statisticno pomembne razlike glede na cas izvajanja aktivnosti pri pacientih s covidom-19. Statisticno visoko pomembne razlike (p<0.0001) smo dokazali med skupino, ki je bila izpostavljena do 2 uri (povprecje=6.93) in skupino, ki je bila izpostavljena 5 ur ali vec (povprecje=13.96). Ravno tako smo dokazali statisticno pomembne razlike (p=0.0013) med skupino, ki je bila izpostavljena od 3 do 5 ur (povprecje=7.84) ter skupino, ki je bila izpostavljena 5 ur ali vec. Na vprašanja o trenutnih epidemioloških delovnih razmerah 61 odstotkov udeleženih meni, da so v službi bolj pod stresom, kot obicajno, 84 odstotkov udeleženih skrbi, da bi okužili druge, 63 odstotkov jih navaja, da njihove svojce in znance skrbi, da bi se okužili preko njih in 53 odstotkov udeleženih navaja, da se jih zaradi trenutnega podrocja dela ljudje izogibajo. Zakljucek: Rezultati so dokazali, da je casovna izpostavljenost pri delu s covid-19 obolelimi pacienti pomemben dejavnik, ki vpliva na obcutek stresa, tesnobe in depresije. Udeleženci skupin, ki so bili izpostavljeni dlje casa, so ocenjevali višjo stopnjo obcutka stresa, tesnobe in depresije v primerjavi z udeleženci, ki je bili izpostavljeni manj casa. Po mnenju anketirancev je delo v trenutnih epidemioloških razmerah vplivalo na njihovo socialno življenje. Skoraj vecina se jih je soocala s skrbjo, da bi okužili druge, vec kot polovica pa je navajala, da se jih je zaradi narave dela širša družba izogibala. Urška Bidovec-Stojkovic1, Martina Vachová2, Žiga Košnik1, Mitja Košnik1, Petr Panzner2, Jasna Volfand3, Matjaž Homšak4, Vojko Berce5, Ines Hasanovic1, Monika Šohar1, Peter Korošec1 1University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 2Department of Immunology and Allergology, Faculty of Medicine in Pilsen, Charles University, Czech Republic 3Diagnostic Center Bled, Bled, Slovenia 4Private paediatric practice, Lenart, Slovenia 5University Medical Centre Maribor, Maribor, Slovenia Urska.Bidovec-Stojkovic@klinika-golnik.si Background: ImmunoCAP ISAC (ISAC, Phadia, Uppsala, Sweden) is a multiplex allergen test that enables the measurement of IgE antibodies to a fixed panel of 112 components from 51 allergen sources in a single step, including two major venom components, honeybee rApi m1 and yellow jacket rVes v5 and two additional marker allergens, Api m4 and Pol d5. Both components are markers of genuine (species-specific) sensitization and are important for molecular diagnosis, which may permit the identification of bees and/or yellow jackets as culprit insects in venom-sensitized subjects. We conducted a multicentre study and the first methodological comparison of IgE measurements for rApi m1 and rVes v5 between ImmunoCAP singleplex (CAP, Phadia, Uppsala, Sweden) and ISAC testing, and evaluated the possible clinical utility of ISAC in Hymenoptera venom allergy. Methods and results: We included 3001 subjects, who were routinely tested with ISAC from 2012 to 2017 at University Clinic Golnik, Slovenia, or at Charles University Faculty of Medicine, Pilsen, Czech Republic (801 subjects from Golnik, Slovenia, and 2200 subjects from Pilsen, Czech Republic). Positive ISAC results (=0.30 ISU-E; ISAC Standardized Units) for rApi m1 and/or rVes v5 were observed in 342 (11.4%) subjects; 83 (24.3%) were sensitized to rApi m1, 232 (67.8%) to rVes v5, and 27 (7.9%) to both components. Of those 342 subjects, 93 subjects were methodologically and clinically analysed in detail. By ISAC, 8 (8.6%) of those subjects were positive for rApi m1, 74 (79.6%) for rVes v5 and 11 (11.8%) for both components. The ISAC results showed a high concordance with standard quantitative CAP testing, 90.3% for rApi m1 and 96.8% for rVes v5. Furthermore, there was a significant positive correlation between semiquantitative ISAC and quantitative CAP values, both for rApi m1 (R=0.79, p<0.0001) and for rVes v5 (R=0.69, p<0.0001). Discordant results were observed in 12 subjects; nine for rApi m1 and three for rVes v5. Eight subjects showed negative ISAC and positive CAP rApi m1 results, and only one subject showed positive ISAC and negative CAP rApi m1 results. Three subjects had positive ISAC and negative CAP rVes v5 results. A detailed clinical evaluation showed that 29 of 93 subjects (31.2%) had a positive history of Hymenoptera venom allergy. For honeybee allergy, one (1.1%) subject had a systemic reaction and five (5.4%, 5/93) subjects had LLR. For Vespula allergy, 9 (10.3%) subjects had systemic reactions, 10 (10.8%) had LLRs after yellow jackets sting, two (2.2%) had a history of double-positive systemic reactions to both honeybee and yellow jacket stings, one subject had a systemic reaction after honeybee sting and LLR after yellow jacket sting, and one subject had LLRs after both stings. In the other 64 (68.8%) subjects, rApi m1 and rVes v5 sensitization seemed to be asymptomatic. According to the clinical data, ISAC and CAP rApi m1 were positive in 5 of 6 (83%) honeybee-allergic subjects. For rVes v5, ISAC and CAP were positive in all (100%, 19/19) yellow jacket–allergic subjects. In subjects allergic to both honeybee and yellow jacket venom, rApi m1 was positive by ISAC in one (25%) and CAP in 3 (75%) subjects; for rVes v5, both ISAC and CAP were positive in all 4 (100%) subjects. Conclusions: With this study, we showed that, for measuring specific IgEs for rApi m1 and rVes v5, ISAC and CAP are methodologically comparable methods. Additionally, a high correlation between the measured values was observed, although the ISAC system measures semiquantitatively. ISAC displayed lower sensitivity regarding rApi m1, whereas the correlation for rVes v5 was optimal. ISAC is a diagnostic test that is generally not used for the detection of sensitization to Hymenoptera venom in routine practice. Nevertheless, patients, regardless of the clinical indication, needs to have their positive results precisely interpreted regarding the Hymenoptera allergy. Ines Hasanovic, Urška Bidovec-Stojkovic, Monika Šohar, Peter Korošec University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia ines.hasanovic@klinika-golnik.si Background: The introduction of ImmunoCAP ISAC (ISAC) in 2009 was a major breakthrough in allergy diagnostic since the multiplex enables to determine specific IgE to 112 different allergen components. Recently another multiplex platform Allergy Explorer (ALEX) became available. It can detect specific IgE against 157 allergen extracts and 125 allergen components, based on a nano-bead technology. The objective of this study was to compare the methodological concordance between ISAC and ALEX assay. Method: We included 20 patients in the analysis and we compared the results for 69 allergen components present in both assays. When discordant result between ISAC and ALEX was found sample was tested with singleplex ImmunoCAP test. Positive cutt-off values for ISAC was 0.30 ISU-E, for ALEX 0.30 kUA/L and for ImmunoCAP 0.35 kUA/L. Results: Out of 1380 measurements for sIgE (20 patients x 69 components), concordant result for both multiplex systems was found in 96% (1327/1380) cases. The discordance was demonstrated for 34 allergen components. For nOle e 1 the discordance was 25% (5/20) and for rPol d 5, rAra h 8 and nJug r 2 15% (3/20). For 9 allergens discordance was 10% (2/20) and for 21 allergens 5% (1/20). Total agreement between both results were found among all patients for 35 (51%) allergens. 15 discordant measurements for 9 allergens (rApi m 1, rVes v 5, rPol d 5, rAra h 8, rAra h 9, nCor a 9, rBet v 1, rDer p 10 and rHev b 5) were additionally tested with ImmunoCAP singleplex assay. ISAC result was confirmed with ImmunoCAP in 9 cases (60%) and ALEX in 6 (40%). On the level of single patient, concordance of sIgE results are varying from 85.5% to 100.0%. Total agreement was observed in four (20%) patients, one patient had discordant result in 10 allergens (85.5%), one patient in 6 (91.3%), one patient in 5 (92.8%), three patients in 4 (94.2%), four patients in 3 (95.7%), two patients in 2 (97.1%) and four patients had discordant result in one allergen (98.6%). Conclusion: There is a high level of concordance between ISAC and ALEX multiplex assay. When comparing results of both multiplexes with singleplex ImmunoCAP, ISAC showed slightly higher correlation in contrast to ALEX. Nevertheless, before starting using novel multiplex assay in a diagnostic routine setting, larger studies are needed and results should be interpreted carefully according to the clinical data. Ana Koren1, Mojca Lunder2, Peter Molek2, Peter Kopac1,3, Abida Zahirovic2, Pia Gattinger4, Irene Mittermann4, Rudolf Valenta4,5,6, Peter Korošec1 1University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 2Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia 3Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 4Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria 5NRC Institute of Immunology FMBA of Russia, Moscow, Russian Federation 6Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, Moscow, Russian Federation Ana.Koren@klinika-golnik.si Introduction: Basophil activation test (BAT) represents a useful tool to detect immediate hypersensitivity reactions, whereas the labelling of allergens with fluorescent probes may represent a major step in development of multiplex BAT, which would enable analysis of the basophil activation by various allergens with a significantly smaller number of test probes. In this study we undertook initial validation and assessment of multiplex BAT, by using two major bee venom allergens Api m 1 and Api m 2 labelled with Quantum dot (Qdot) nanocrystals of two different sizes and surface chemistries. Methods: nApi m 1 and rApi m 2 were conjugated to Qdot® ITK™ quantum dots (705 nm and 800 nm) with an amino (PEG) or carboxyl functionalized polymer coating. The IgE reactivity of the Qdot-labeled allergens was assessed by an immunodot assay. The allergenic activity was determined with BAT using CD123-PE/HLA-DR-APC/CD63-FITC labelled antibodies. Usefulness of Qdot-labelled allergens for multiplex BAT analysis was tested in 17 bee venom-allergic patients and in 6 controls. Results: The amino and carboxyl Qdot-labeled Api m 1 (NQ705-Api m 1 and CQ705Api m 1) and Api m 2 (NQ800-Api m 2 and CQ800-Api m 2) allergens bound IgE in patient samples in the immunodot assay regardless of their conjugation and size, whereas the unconjugated Qdots showed no interaction with serum IgE. The amino but not the carboxyl Qdot-labeled Api m 1 and Api m 2 were able to activate basophils, as reflected in the dose-response curves of basophil CD63 in the presence of NQ705Api m 1 and NQ800-Api m 2, which were comparable to the responses to Api m 1 and Api m 2. We further tested the NQ705-Api m 1 and the NQ800-Api m 2 in the multiplex BAT by analyzing CD63 expression in a subpopulation of basophils according to the binding of the fluorescent allergen. We found a strong positive correlation between native and NQ-labeled Api m 1 or 2 (r=0.88, P<0.0001). Considering the threshold value of 15% for CD63-positive basophils, 15 out of 17 patients and 6 out of 6 controls had matching results for the multiplex BAT and BAT. Conclusion: This is the first study describing the labeling of allergens with fluorescent probes, the evaluation of their IgE reactivity and their performance in the BAT. This approach will provide novel diagnostic possibilities and enable further studies of the role of the surface distribution of allergen-specific IgEs in the responses of effector cells. Asja Stipic Markovic1, Iva Topalušic2 1Special Hospital for Pulmonary Diseases, Zagreb, Croatia 2University Children's Hospital Zagreb, Zagreb, Croatia asjastipic90@gmail.com Background: Urbanisation delays postnatal maturation of adaptive immunity. Interplaying with genetical determinants it is drammatically increasing the risk for all types of allergy, especially among children. Rural living comprises protective (not fully understood) immunomodulatory factors inducing immunotolerance. The main aim of our study was to investigate prevalence differences in asthma (A), rhinitis (AR) and atopic dermatitis (AD) symptoms between three age groups of children living in the city of Zagreb and children living in Natural Park Lonjsko Polje, complex of lowland riparian forests with 1500 species living there. Second, we intend to get insight into differences of some urban/rural early-life environmental exposures assessed from ISAAC questionnaires. Patients and methods: In the schoolyear 2017/2018 total of 1745 schoolchildren aged 6-14 years (6-7 yrs, 10-11 yrs and 13-14 yrs age groups), from 39 randomly selected elementary schools, were included. Questionnaires were answered by parents. The results were compared with the study in Zagreb in year 2002. Results: Regarding allergic rhinitis, children from rural setting showed lower risk for current AR (last 12-months symptoms) (OR 0,373; 0,563; 0,172 for all age groups respectivelly) in comparison to the children from the urban area who reported more drugs usage for current AR (X2 Yates corect 0,46, p <0,0001), and more often pharmacies visits (p<0,046). The responses for asthma are different from the data seen in rhinitis. There was no difference between rural and urban three-age-groups-children current and ever in lifetime asthma. However, the meaning of more frequent urban wheezing ever in a lifetime in the oldest, 13-14 years old age group, is not clear. There are literature evidences of strong genetic relationship in AD. Our study showed different environmental influences on current AD symptoms which are strongly associated with urban life-style and medication consumption. That is opposite in children living in rural area of Lonjsko Polje for all age groups. History of allergic diseases in both parents (mother´s AR and father´s AD) are risk factors for current AD in the city while cooked green vegetables were protective. Conclusion: Comparisson of rural/urban risks for AR, A and AD symptoms has shown complex and different patterns of environmental associations with distinct type of allergic disease. Klara Cvenkel1, Mitja Košnik2,3 1Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Division of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 3University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia klara.cvenkel@gmail.com Background: Alpha-gal syndrome or. mammalian meat allergy, is an allergy to galactose-a-1,3-galactose. Alpha-gal is an oligosaccharide in the saliva of ticks and meat of four-legged non-primate animals. Allergic sensitization with alpha-gal appears to occur through a tick bite. Sensitization to this allergen is common (10% of rural individuals), but fortunately most sensitized individuals are asymptomatic. The characteristic clinical picture of this allergy is late anaphylaxis after eating red meat, especially offal. In patients with sIgE against alpha-gal, allergic reactions may also occur when using medicines containing gelatin (certain vaccines, antivenoms, cetuximab). Alpha-gal may be present in recombinant proteins derived from mammals, heparin, bioprosthetic heart valves. Methods: The data refers to patients who are in the hospital information system of clinic Golnik. We looked for patients who, based on their anamnesis, the presence of sIgE against alphaGAL and a good response to diet, had a diagnosis of red meat allergy in a two year period from 2018 to 2020. Results: Over a two-year period, the diagnosis was made in 15 patients (8 women), at the age of 44 (17-69). The concentration of sIgE alphaGAL was 16.8 (0.74-100) kIU / L. 11 had anaphylaxis, 3 had urticaria, and 1 had gastrointestinal symptoms. It took 12 (3 300) months from the first symptoms to the diagnosis. Patients had 6 (1-600) episodes. The problems started 3 (1-14) hours after eating meat. Only 4 patients suspected that the cause of anaphylaxis was meat. 6 patients had episodes that started overnight. In addition to eating red meat, 4 patients needed cofactors (effort, NSAIDs, alcohol) for symptoms. 11 patients follow a strict diet and 10 have no problems, one has less, two patients need to avoid offal, two patients are not strict in the diet. Conclusion: The diagnosis of anaphylaxis due to allergy to alpha-gal is often missed because, unlike typical anaphylaxis, symptoms appear after several hours, often in the middle of the night. The allergen is quite weak, so patients do not always have problems when eating red meat. This allergy was discovered only a few years ago, so it is still quite unknown among doctors. As a result, these patients are often initially diagnosed with idiopathic anaphylaxis. Laura Haidar1,2, Saskia Schömann1, Tudor-Paul Tama.1, Marius Georgescu1,2, Carmen Panaitescu1,2 1Discipline of Physiology, Department III Functional Sciences, “Victor Babes” University of Medicine and Pharmacy Timisoara, Timisoara, Romania 2Center of Immuno-Physiology and Biotechnologies “Victor Babes” University of Medicine and Pharmacy Timisoara, Timisoara, Romania haidar.laura@umft.ro Background: The goal of this study was to establish a pattern of sensitization in food allergy, as well as to prove that serum eosinophilic cationic protein (ECP) can be used as a clinical marker for chronic inflammation and could assist in diagnosing food allergies. Methods: The study group consisted of 150 subjects with skin manifestations, which were selected according to specific criteria and were examined clinically (skin prick test, clinical score) and paraclinically (complete blood count, inflammation markers, total serum IgE, specific food IgEs, ECP, diamine oxidase activity, nasal- and pharyngeal samples, anti-Helicobacter pylori IgG, anti-Toxocara IgG, and stool ova). Criteria for exclusion were patients that did not have specific IgE measured, and cases where 2 out of 3 paraclinical blood investigations as for total serum IgE, blood eosinophil count or serum ECP were missing. Results: 54% of the patients had a final diagnosis of urticaria, 26% atopic dermatitis, 16% angioedema, and 14% dermographism. 38% of the study group also had infections. Regarding the patterns of sensitization in food allergy, the most common allergies in the age group 0-5 years and 5-17 years were due to milk and egg, whereas the most common in >17 years were due to flour, nuts, legumes and fish. With increasing age, food allergy prevalence decreased. 38% of the study group also had infections. We found a strong positive correlation between food allergy and allergy to inhaled allergens. Furthermore, serum ECP does not only reflect chronic inflammation, but also the severity of the ongoing inflammation. Conclusion: Our findings suggest that the patterns of food allergy change with age and they are also less the cause of urticaria in older children. Serum ECP may be used as a biomarker in skin manifestations showing a possible chronic progression. Thereby, information about the severity of the chronic inflammation can be gathered, which can then be treated accordingly. Grant support: This work was supported through the project “INnovative Strategies for Prevention, diagnosis and therapy of ragweed pollen Induced REspiratory Diseases” (INSPIRED), MySMIS 103663. Selma Mutevelic1, Jusuf Mehic2, Emir Hondo2, Nejra Džananovic1, Lamija Zecevic Pašic1, Amir Fazlagic1, Suzana Tihic-Kapidžic1, Besim Prnjavorac2, Rifat Sejdinovic2 1Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina 2General Hospital Tešanj, Tešanj, Bosnia and Herzegovina semutevelic@gmail.com Objective: The aim of the study was to compare two diagnostic methods, with three ways of detection of anti tTG IgA antibodies, for 45 consecutive samples (analysed in the order they were recived by the laboratory) of adult patients, and to observe what is the correlation of results between these two diagnostic methods. Introduction: Celiac disease is a serious autoimmune disease that occurs in genetically predisposed people, where the ingestion of gluten leads to inflamatory damage in the small intestine with villous atrophy. The disease occurs in 1 in 100 individuals with symptoms similar to diarrhoea, abdominal pain, and malabsorption, loss of appetite and growth retardation. In the event of delayed diagnosis, it may present with other autoimmune diseases such as neuropathies and multiple sclerosis. The diagnosis is established on a biopsy of the small intestinal mucosa, which is found to be damaged before the patient is put on a gluten free diet, and control biopsy of the regenerated mucosa after the introduction of the strict implemented diet. Determination of anti-DG, anti-tTg IgG and IgA antibodies by ELISA as well as detection of endomysial IgA with immunofluorescence has proven to be the most sensitive serological method in the diagnosis of this disease. Materials and methods: We analysed serum samples from 45 patients (27 females and 18 males) who we screened for celiac disease. Each serum sample underwent both tests: the CytoBead CeliAK ( GA Generic Assays GmbH) multiplex indirect immunofluorescence method and the ALEGRIA ( ORGENTEC diagnostika Gmbh ) ELISA assay. After qualitative analysis of each individual sample, the test was determined to be either positive or negative by the indirect immunofluorescence method on monkey oesophageal tissue + bead (purified tTG fixed antigen).The same serum sample was analysed by an ELISA method for anti-tTG IgA quantitative, with a positive or a negative result according to the »CUT OFF« specified by the reagent manufacturer. Results: We made three types of comparisons: 1.) Bead anti tTG IgA - Endomysium IgA ( EmA ) and found a 100% test match, 2.) Bead anti tTG IgA - ELISA anti tTG IgA whose test match was 100%, 3.) Endomysium IgA ( EmA ) - ELISA anti tTG IgA whose test match was 100%, Conclusion: The compared diagnostic methods for screening of Celiac disease demonstrate a perfect agreement between their respective results. Ecaterina Stasii, Tatiana Gorelco, Olesea Nicu, Olga Gustiuc, Irina Taranet Chisinau, Moldova ecaterina_stasii@yahoo.com Background: Food allergies have increased substantially over the past decade. The success of the clinical management is depending on early diagnostic and determining the whole spectrum of sensitization to food allergens. The scope of the study was to determine the indexes of sensitivity(ISS) and specificity(ISC) of different diagnostic tests to detect food sensitization in children with atopic dermatitis. Method: There were analyzed the results of the data of the allergic history(AH), of food diary register(FDR), skin test(ST), detection of Ig E specific allergens, oral food challenge(OFC) and reaction of inhibition of leukocyte migration(RIML) at 315 patients aged 1 month up to 18 years suffered with atopic dermatitis. The research results were processed by methods of mathematical statistics the distribution of the frequencies of the variation series depending on the value of the studied feature. Results: The ISC of AH method was 84.2% and ISS 68%. False positive data were noted in 15.7%, and false negative in 31.3% of patients. AH is most informative for detecting sensitization to most obligate allergens (fish, honey, egg white, citrus) and the least to everyday foods (wheat flour, beef, milk ). ST revealed sensitization to the allergen of eggs (32%), egg white (32%), fish (30%), chicken meat (28%), lemon (25%), oranges (23%), tomatoes ( 23%), milk (22%), grapes (21%).The false negative results ST were most often observed with allergies to milk, eggs, meat, buckwheat, rice, barley, and less often to fish, strawberries, oranges, and raspberries. It was established, that the ISS of the detection of Ig E antibodies has value of 95% with ISC of 86% and respectively the TILM 100% and 90%, DFR 95% and 86%, ST 41% and 71%, OFC 45% and 97%. Conclusion: In early detection of food sensitivity in vitro tests have advantages with higher ISS and ISC in comparison with diagnostic tests in vivo with possibility to use them in different age periods, in any period of the disease and also allows to obtain the most complete information for a faster preparation of elimination diets, which underlie the complex therapy of food allergies in children. Mirjana Živanovic1, Marina Atanaskovic-Markovic2,3, 1Special Hospital „ Sokobanja “, Sokobanja, Serbia 2University Children Hospital, Belgrade, Serbia 3Faculty of Medicine, University of Belgrade, Belgrade, Serbia sveda1@ptt.rs Introduction: Nutrition allergy is an unfavorable immune response to food proteins. The most common food allergens in children are cow’s milk proteins, eggs, fish, nuts, peanuts, wheat flour and soy. The testing begins with the standard, known concentration, nutrition comercial allergens skin prick testing. A more selective test is a skin prick test performed using a fresh food allergen. A skin prick test analyzes the size of wheal diameter, whereas an in vitro test measures the value of specific IgE. So far neither of these tests has had a priority, which means that it is most useful to do both in vivo and in vitro tests in practice and either confirm or exclude the suspicion of a nutrition allergy. However, gold standard for nutrition allergy diagnosis is a provocation test, but it takes lot of time and there is certain risk for patient. Objectives: The objective of this study is to determine the concordance between in vitro and in vivo testing. Material and methods: This study has involved a group of 571 respondents, 142 out of which are sensitized to cow’s milk proteins, 137 to eggs, 98 to peanuts, 76 to soy, 74 to wheat flour and 44 to kiwi. Skin prick testing has been performed using both standard commercial nutrition allergens and fresh food allergens. Specific IgE is measured using UniCAP Pharmacia Upsala method. Results: This study examines diagnostic procedures and their interrelations for the purpose of proving nutrition allergies. Sensitization and the specificity of the response have been determined for all the three tests, as well as the odds ratio. For cow’s milk protein allergen SPT sensitization of 0.77 is high, with the lower specificity of 0.21, and the odds ratio of 0.85 with CI (confidence interval) from 0.55 to 1.32. PPT sensitization at 0.92 is high, but the specificity of 0.06 is low, with the odds ratio of 0.67 and CI between 0.34 and 1.34. Specific IgE has the lowest sensitization of 0.62, but it has the highest specificity of 0.41, with the odds ratio of 1.11 and CI of 0.76-1.62. For egg white allergen SPT sensitization of 0.93 is high, with the lower specificity of 0.25, and the odds ratio of 4.62 with CI from 2.29 to 9.32. PPT sensitization at 0.99 is high, but the specificity of 0.08 is low and the odds ratio is 11.36 with higher CI – 1.55 - 83.15, which means that we must be very cautious when using only this test to confirm the existence of allergy. Specific IgE sensitization is 0.69, but the specificity is 0.42, and the odds ratio is 1.65 with CI of 1.11- 2.46. For wheat flour allergen SPT sensitization is 0.69 and specificity is 0.20, whereas the odds ratio is 0.55 with CI of 0.32-0.93. PPT sensitization at 0.96 is high, but the specificity of 0.07 is low with the odds ratio of 1.68 and CI of 0.51-5.56. Specific IgE sensitization is 0.64 and the specificity is 0.40, with the odds ratio of 1.18 and CI of 0.72- 1.94. For peanuts allergen SPT sensitization is 0.70, and the specificity is 0.20, with the odds ratio of 0.58 and CI from 0.36 to 0.94. PPT sensitization is 0.88, and the specificity of 0.05 is really low, with the lowest odds ratio of 0.41 (compared to other tested allergens) and the lowest CI of 0.20-0.82. Specific IgE sensitization is 0.49, and the specificity has similar value of 0.38, whereas the odds ratio is 0.59 with CI of 0.39-0.91. For soy allergen SPT sensitization is 0.70, and the specificity is 0.20, with the odds ratio of 0.57 and CI from 0.34 to 0.97. PPT sensitization is 0.86, with the low specificity of 0.06, and the odds ratio of 0.53 with CI of 0.24-1.18. Specific IgE sensitization is 0.45, and the specificity is 0.38, with the odds ratio of 0.50, which is the lowest odds ratio value for all the tested allergens, and CI of 0.31-0.81. For kiwi allergen SPT sensitization of 0.59 was the lowest, whereas the specificity of 0.20 was the same as for other tested allergens, with the lowest odds ratio for positive response 0,20 and CI from 0.19 to 0.67. PPT sensitization of 0.93 was high, with the low specificity of 0.06, and the odds ratio of 0.92 with CI of 0.27-3.11. Specific IgE sensitization was 0.57, and the specificity was 0.40, with the odds ratio of 0.87 and CI of0.47-1.61. Conclusion: Tests with higher specificity values are more required in the situations when the false positive test results are less desirable than the false negative test results, i.e. with the diseases that are not life threatening. However, a false positive test result could bring about an unnecessary medical intervention. In our study SPT has good sensitization and slightly low specificity; PPT has excellent sensitization, but it has low specificity, whereas specific IgE has the best specificity values with the moderate sensitization. With this study we confirmed that it is often really necessary to do all the three tests and therefore triple-check test results, commercial extract values and test concordance. That way any potentially dangerous oral challenge, performed in order to prove a nutrition allergy, can be avoided. Peter Kopac1,2, Ana Koren1, Maja Jošt1, Dušan Mangaroski3, Peter Korošec1 1University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 2Medical Faculty, University of Ljubljana, Ljubljana, Slovenia 3Institute of Oncology, Ljubljana, Slovenia peter.kopac@klinika-golnik.si Introduction: Basophil activation test (BAT) represents a useful tool to detect IgE mediated reactions and predict the severity and threshold of allergic reactions to food and venom allergens, but experiences in drug allergy are limited. Herein we report the first case of positive BAT to paclitaxel. Case report: A 50-year-old female with estrogen receptor-positive and HER2-positive breast cancer was treated with adjuvant trastuzumab,pertuzumab and paclitaxel. The first two 3-weekly applications of both anti HER-2 drugs were uneventful. During the first 5 minutes of the second infusion of paclitaxel the patient developed a reaction with abdominal cramps, dyspnea, generalized erythema, hypotension (RR 70/40 mmHg) and desaturation (80%). She was treated with methylprednisolone, clemastine, saline, and oxygen. Next day she had again reaction after infusion of 15 ml of paclitaxel with abdominal cramps, dyspnea, heart rate 120/min and was treated with methylprednisolone and clemastine. No tryptase was taken during reactions. Skin prick test with paclitaxel (1 mg/ml) and IDT (0.001 mg/ml) were negative, but IDT (0.01 mg/ml) was positive. . Basal tryptase was normal (5.1 ug/l). To confirm allergenic activity of paclitaxel sensibilization we performed BAT which was highly positive even at low allergen concentrations. Thus, we showed 80%, 69%, 62%, 67% and 2% of CD63 positive basophils for stimulation with paclitaxel (5 to 0.0005 µg/ml). BAT response to paclitaxel in all three healthy controls was negative (<5%; 5 to 0.0005 µg/ml). After premedication with antihistamines and steroids a 12 step (3 bags) desensitization protocol was performed. By cumulative dose of 0.022 mg paclitaxel patient had reacted with generalized erythema and pruritus. Shewas treated with adrenaline, clemastine and desensitization was stopped. Next day 16 step protocol was performed and after 0.010 mg paclitaxel generalized urticarial occurred. The infusion was paused, the patient was treated with adrenaline and clemastine. After 30 minutes desensitization was continued but the patent again reacted with generalized urticaria after a cumulative dose of 0.023 mg paclitaxel and treatment was stopped. Conclusion: High basophil sensitivity at low concentrations of paclitaxel may be associated with the severity of the reaction, a lower threshold of allergic reactions to the allergen could consequently, predict severe side effects during desensitization and even failure to desensitize. Simona Percic1, Mitja Košnik2,3, Andreja Kukec4 1Centre for Environmental Health, National Institute of Public Health, Ljubljana, Slovenia 2University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 3Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 4Department for Public Health, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia simona.percic@gmail.com Background: In the past five decades the interest in hypersensitivity reactions caused by stings of Hymenoptera has increased noticablly. Allergic reactions to Hymenoptera stings can be more or less severe. Current criteria to diagnose Hymenoptera venom allergy, can not accurately predict the occurrence or severity of the systemic reaction or even anaphylaxis symptoms, after a sting either with bee or vespid. Our aim was to elucidate some of the possible markers, identified by different researchers, which could play an important role in determining the predictive factor for severe systemic reaction or local reaction in sensitized patients after a bee or vespid sting. The quality of life for the affected persons can be severely dimenished, since many of them are frightened what will happen after being re-stung. Methods: A systematic literature review was conducted for the period to 31 December 2017 in the bibliographic database PubMed. In the systematic review we included all types of epidemiological studies, most of them were observational prospective and retrospective epidemiological studies, in which researchers identified some possible predictive markers that could be used to identify allergic patients’ response to a bee or vespid sting with either local or severe systemic reaction. Results: In the final analysis of the systematic review 16 original articles were included. The analysis elucidated the prevalence for large local reactions and severe systemic reaction after a bee or vespid sting. We identified the following risk factors that could play an important role to react with severe systemic reaction: the etiology of the Hymenoptera sting, sex, age, history and severity of previous systemic reaction, to be re-stung in the interval of two months, the frequency of the re-stings, atopy, genetic predisposition and mastocytosis. Conclusions: There are few studies concerning predictive factors for determining the severity of allergic reaction after bee or vespid stings. Also, a verified predictive factor for prognosis still remains unidentified. Further studies in this field are needed. Public health activities could support promotion of awareness for the sensitized patients about proper behavior and eventual treatment with immunotherapy to improve quality of life for the affected. Mojca Bizjak, Mitja Košnik Urticaria Center of Reference and Excellence (UCARE), University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia mojca.bizjak@klinika-golnik.si Background: Urticaria patients represent a large proportion of referrals to allergy clinics, but the distribution of urticaria types and subtypes is not well known. Objective: To perform statistical analysis of chronic urticaria (CU) diagnoses assigned to consecutive patients in an outpatient setting of our urticaria center. Methods: We performed a retrospective study of electronic medical records of CU patients evaluated by the same dermatologist in 12 consecutive months. We searched for urticaria ICD-10 codes. Chronic inducible urticaria (CIndU) was diagnosed by established provocation protocols and instruments. FricTest® was used in all patients and other tests were done only based on patient history. Results: A total of 233 adult CU patients were found in the records and analyzed (64% female, 36% male; age 43.4 ± 15.0 years). Eighty-two percent had at least one follow up and 18% were seen for the first time only. 55% of patients (127/233) had only chronic spontaneous urticaria (CSU), 42% (99/233) had only CIndU, and 3% (7/233) had both forms. The most common CIndUs were symptomatic dermographism (SD), cold urticaria (ColdU), and cholinergic urticaria (CholU). CIndU was diagnosed in 106 (45%) patients: 38 SD only, 32 ColdU only, 11 CholU only, 7 delayed pressure urticaria (DPU) only, 8 SD-CholU, 3 SD-ColdU, 4 CSU-ColdU, 2 CSU-SD, and one CSU-ColdU-DPU. Thirty-six patients (64% CSU only, 28% CIndU only, and 8% CSU-CIndU) were not well controlled even with a regular daily fourfold dose of 2nd-generation H1-antihistamines and 3rd line treatment was required. Conclusion: Our findings demonstrate a heterogeneous clinical picture of CU. There is a need to diagnose and treat all urticaria types in order to achieve disease control. Mojca Bizjak1, Marcus Maurer2, Dorothea Terhorst-Molawi2, Mitja Košnik1 1Urticaria Center of Reference and Excellence (UCARE), University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 2Urticaria Center of Reference and Excellence (UCARE), Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany mojca.bizjak@klinika-golnik.si Background: Cold urticaria (ColdU) phenotypes are not well known. Cold agglutinins (CA) are immunoglobulins that reversibely bind with red blood cells at reduced temperatures causing them to agglutinate. They have been well researched in hematology since they can cause autoimmune hemolytic anemia. They have also been mentioned in publications as factors possibly associated with ColdU, but there are no reports of CA-studies in ColdU and no definitive causative relationships have been determined so far. Objective: To determine the rate of CA-positive ColdU patients and to analyze clinical characteristics of ColdU patients with and without CA. Methods: A total of 35 adult patients (66% female, 34% male; age 41.4 ± 13.4 years, disease duration 96.1 ± 103.7 months) with ColdU were prospectively investigated at University Clinic Golnik. Detailed patient history was obtained according to the COLDCE (comprehensive evaluation of cold urticaria) GA2LEN UCARE project protocol. Blood withdrawal and the CA test with titration at 4.C was performed at the Blood Transfusion Centre. Results: CA were found in 30% of patients (14 female, 2 male). CA titer ranged from 1 to 16 (1.4 ± 2.9). The presence of CA was linked to: female gender (p=0.030); itch, wheals or angioedema induced by < 20°C ambient air (p=0.009); local skin contact with cold liquids (p=0.018); < 25°C total body water exposure (p=0.045); angioedema induced by cold foods/beverages (p=0.043); and disease deteriorations during increased humidity in summer months (p=0.007). CA positive patients also had lower disease control based on UCT (Urticaria Control Test) scores (U=83.5, p=0.023). The following correlations were found for CA titers: weak negative with UCT scores (r s =0.359, p=0.034), moderate positive with mean daily temperature of blood withdrawal (r s=0.456, p=0.006), and moderate negative with weight (r s=-0.478, p=0.004). Conclusion: CA titers in our patients are below the ones clinically significant in hematology and low titers are known to occur in normal beings as well, but our findings demonstrate that CA, in patients with ColdU, may be linked to specific clinical features of ColdU. Further studies will aim to characterize, in more detail, the relevance of CA in ColdU and their potential role in the pathogenesis of ColdU. Ajda Demšar1, Peter Korošec1, Mitja Košnik1,3, Peter Kopac1,3, Mojca Bizjak1, Matija Rijavec1,2 1University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 2Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia 3Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia ajda.demsar@klinika-golnik.si Background: Chronic spontaneous urticaria [CSU] is characterized by appearance of wheals and/or angioedema. It persists for at least six weeks. Even though the exact underlying pathophysiology remains unknown, release of histamine and other mediators from activated cutaneous mast cells has a key role in the development of clinical signs and symptoms. Omalizumab, a monoclonal antibody that selectively binds to free human IgE, represents a valuable treatment for CSU patients that remain symptomatic despite treatment with high doses of H1 – antihistamines. However, the mechanisms of action that result in reduction of inflammation remain unknown. The aim of our study was to analyse transcriptional differences between responders [CSU-R] and non-responders [CSU-NR] to omalizumab treatment. Methods: RNAseq based whole transcriptome characterization of total RNA from whole blood samples was performed at different time points in 11 CSU patients - before the omalizumab treatment and after 14 days/3 months of treatment. Eight patients were classified as CSU-R, while three patients as CSU-NR. Characterization of differentially expressed genes [DEGs; cut off was set to FC > 5 and p-value < 0.05] and pathway analysis was made with CLC Genomics Workbench and Ingenuity Pathway Analysis, respectively. Results: At baseline, before starting omalizumab treatment, 140 genes were differentially expressed between CSU-R and CSU-NR, where cellular movement, chemotaxis and inflammatory response were identified as the most important events that differentiate CSU-R from CSU-NR. Comparison of DEGs before and after treatment in CSU-R contains 18 entities, 17 with lower expression and one (FCER1A) with higher expression after successful treatment. Functional analysis of these genes suggests that omalizumab treatment represses inflammatory response and affects the quantity of cells. No statistically significant differences in gene expression before and after omalizumab treatment were found in the CSU-NR group. Conclusion: The potential of whole blood transcriptional signature for prediction of response to omalizumab in CSU is shown. These findings further improve our understanding of CSU pathophysiology and mechanism of omalizumab action. Ana Kovac1, Zeljka Kardum1,2, Ana Marija Lukinac1,2, Visnja Prus1,2 1Department of Rheumatology, Clinical Immunology and allergology UH Osijek, Osijek, Croatia 2Faculty of Medicine Josip Juraj Strossmayer University of Osijek, Osijek, Croatia ana.kovac.dr@gmail.com Amyloidosis is usually a multisystem disease in which abnormal proteins, known as amyloid fibrils, accumulate in a variety of tissues, resulting in a wide spectrum of clinical presentations. We present a case of amyloidosis occurred in 65-year-old woman with massive macroglossia misinterpreted as angioedema. The patient was first examined at the University Hospital Center Emergency Department and was admitted to the Otorhinolaryngology and Maxillofacial Surgery Clinic. Due to suspected angioedema patient was treated with high doses of corticosteroids, antihistamines and C1-esterase inhibitor. Considering that edema of the tongue did not completely regress due to therapy, immunology specialist was consulted and after clinical examination suspicion of amyloidosis, sarcoidosis or myxedema was set. After the extensive laboratory workup and biopsy of the tongue, the diagnosis of primary AL amyloidosis was established. We present this case of rare and unusual presentation of systemic amyloidosis in order to point up a differential diagnosis of macroglossia. Tim Božic1,2, Simona Kranjc Brezar1, Maja Cemažar1,3, Gregor Serša1,4, Boštjan Markelc1,4 1Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia 2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 3Faculty of Health Sciences, University of Primorska, Izola, Slovenia 4Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia tbozic@onko-i.si The tumor microenvironment represents a primary location in which tumor and immune cells interact. Different subpopulations of immune cells are guided to tumors through interactions between various proinflammatory chemokines secreted by tumor cells and their corresponding receptors of immune cells. The degree of infiltration and activation status of effector immune cells is usually associated with a positive outcome in cancer immunotherapies. Therefore, chemokines in combination with immune activation inducing therapy such as irradiation represent potential immunotherapeutic strategy. To elucidate the effect of overexpression of two proinflammatory chemokines CCL5 and CCL17 on tumor microenvironment we transferred the plasmid DNA encoding each chemokine to tumor cells in vitro and in vivo by utilizing two delivery methods – lipofection and gene electrotransfer (GET). Two murine breast (4T1 and E0771) and two murine colon (CT26 and MC38) cancer cell lines were transfected in vitro with plasmids encoding either CCL5 or CCL17. The viability of 4T1, CT26 and MC38 48 h after lipofection was 90% while the viability of E0771 remained above 80%. Concurrent expression analysis of CCL5, CCL17 and 9 other cytokines 48 h after lipofection showed significantly increased expression of both transfected transgenes, while levels of IL-6 and CXCL10 in the surviving cells were also increased. For in vivo study GET after intratumoral injection of plasmids encoding either CCL5 or CCL17 in murine CT26 and 4T1 tumor model (animal license: U34401-1/2015/43) resulted in minor tumor growth delay. Expression analysis at day 3 and day 7 after GET to CT26 tumors showed increased expression of both transgenes. Moreover, concurrent expression analysis of 5 other cytokines revealed increased expression of proinflammatory cytokines IL-6, IL-12 and IFN.. Overexpression of CCL5 and CCL17 both in vitro and in vivo resulted in a modified cytokine expression profile associated with inflammation, but did not translate into pronounced antitumor effect. However, GET of plasmids encoding CCL5 or CCL17 followed by irradiation in CT26 and 4T1 tumor model resulted in significant tumor growth delay. Based on the modified tumor microenvironment the scope of future experiments will be focused towards elucidating the type of immune cells present in the tumors after treatment. Furthermore, the optimal time window to combine this therapy with irradiation will be determined. This research was funded by ARRS under the postgraduate program and P3-0003. Tinkara Remic1,2, Gregor Sersa1,3, Katja Ursic1, Maja Cemazar1,4, Urska Kamensek1 1Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia 2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 3Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia 4Faculty of Health Sciences, University of Primorska, Izola, Slovenia ukamensek@onko-i.si Background: Tumor cells can be used as the source of tumor-associated antigens to make tumor cell-based vaccines. Our aim was to develop a tumor cell-based vaccine and test its therapeutic and preventative effect in two immunologically different tumor models: less immunogenic B16F10 malignant melanoma and more immunogenic CT26 colorectal carcinoma. Methods: The vaccine was constructed by mixing cell lysates containing 0.5 or 1 mg of proteins from irradiation killed tumor cells with 50 µg of plasmid DNA encoding interleukin-12 (IL-12). Vaccination was performed by injection of vaccine in the mouse skin, followed by gene electrotransfer of IL-12 using a contact hexagonal multielectrode array (electric pulse parameters were: 170 V/cm, 5.64 Hz, pulse length 150 ms). In the therapeutic setting, the vaccine was applied in the skin distant from the tumor, the tumor was irradiated with 15 Gy concomitantly and tumor growth delay was followed. Histological samples were harvested and stained for the presence of granzyme B positive cells. In the preventative setting, the vaccine was applied in the skin before tumor inoculation and tumor outgrowth and growth delay was followed. All experimental procedures were done in accordance with the national guidelines (U34401–1/2015/16) and EU directive (2010/63/EU). Results: A synergistic effect between vaccination and tumor irradiation was observed in the B16F10 tumor model, but no contribution of vaccination to tumor irradiation was observed in the CT26 tumor model. In the B16F10 tumor model, the elevated levels of granzyme B positive cells in the skin and tumor samples after the therapy coincided with the higher antitumor efficacy. No such trend was observed in the CT26 tumor model. Interestingly, a preventative vaccination effect was observed in the CT26 tumor model (up to 56% protection), but not in the B16F10 tumor model. Conclusion: The results suggest a greater contribution of the vaccination to tumor irradiation in the less immunogenic tumor model, while, in a preventative setting, a greater contribution of the vaccination was indicated in the more immunogenic tumor model. In future studies, we will consider these results when investigating the vaccination effects and its mechanism of actions. Funding: This research was funded by the SLOVENIAN RESEARCH AGENCY, grant number P3-0003. The investment was co-financed by THE REPUBLIC OF SLOVENIA and THE EUROPEAN REGIONAL DEVELOPMENT FUND within the scope of SmartGene.SI. Katja Ursic1, Spela Kos1, Urska Kamensek1, Maja Cemazar1,2, Gregor Sersa1,3 1Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia 2Faculty of Health Sciences, University of Primorska, Izola, Slovenia 3Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia gsersa@onko-i.si Background: The therapeutic effectiveness of electrochemotherapy (ECT) in the clinics is up to 90% of local tumor control; however, a systemic antitumor effect (abscopal effect) has not yet been observed. The aim of the study was to test a new combined therapy including ECT with cisplatin, bleomycin or oxaliplatin and gene electrotransfer (GET) of plasmid encoding interleukin-12 (IL-12) in three immunologically different tumors. We hypothesized that in the combination, IL-12 boosts the in situ vaccination effect of ECT by recruiting effector immune cells. Methods: A malignant melanoma (B16F10), mammary carcinoma (4T1) and colon carcinoma (CT26) were treated. The combined therapy included intratumoral ECT with bleomycin, cisplatin or oxaliplatin (plate electrodes, 8 pulses, 1300 V/cm, 100 µs, 1 Hz) and peritumoral GET of plasmid pORF-mIL-12-ORT encoding murine IL-12 (pin non-invasive multi-electrode array, 12 pulses, 170 V/cm, 150 ms, 2.82 Hz). Growth of primary treated tumors and distant untreated tumors in a dual-flank model mimicking systemic disease was followed. After the therapy, cytometric and immunohistochemical analyses were performed to detect immunologically important biomarkers. Results: In poorly immunogenic B16F10 melanoma, IL-12 potentiated the antitumor effect of ECT using equally effective low doses of cisplatin, oxaliplatin or bleomycin. However, we observed the most pronounced potentiation after ECT with cisplatin, resulting in 38% of complete responses as well as an abscopal effect. The antitumor effectiveness of this treatment combination could be ascribed to the induction of the local and systemic immune responses. Namely, infiltration of granzyme B positive effector immune cells was observed in both, primary and distant tumors. In comparison to B16F10 melanoma, better responsiveness to ECT was observed in more immunogenic 4T1 and CT26 tumors. In both, the GET of IL-12 did not significantly improve the therapeutic outcome of ECT using either of the chemotherapeutic drugs. Conclusion: We showed that IL-12 boosts the in situ vaccination effect of ECT by recruiting effector immune cells in poorly immunogenic melanoma. Effectiveness of the tested treatment combinations depended on the tumor immune status; ECT was more effective in more immunogenic tumors but the contribution of peritumoral GET was higher in less immunogenic tumors. Funding: This research was funded by the Slovenian Research Agency (Program No. P3-0003). The Investment was co-financed by the Republic of Slovenia and the European Regional Development Fund (SmartGene.Si). Mijanovic Radovan1,2 1Clinic of Allergy and Immunology, Clinical Center of Serbia, Belgrade, Serbia 2Medical Faculty, University of Belgrade, Belgrade, Serbia rmijanovic@yahoo.com Background: Etiopathogenesis of ulcerative colitis (UC) has not been fully elucidated. Characteristic changes in the number of circulating immune cells in this disease, which are thought to be due to the disease itself, have been established previously. Here we present the case of a patient with a serious disorder in lymphocyte subpopulations that had been present for three years before the clinical onset of the disease. Case report: A healthy female respondent, 40 years of age, participated in a clinical trial as a healthy control. Blood analysis with a leukocyte formula and immunophenotyping of peripheral leukocytes were done. She had not suffered from chronic illnesses and had no frequent viral and bacterial infections. Her family history was negative for autoimmune and malignant diseases. There was a mild lymphopenia (1116 cells/µL of blood), CD4 + mild lymphopenia (446 cells/µL), a limit-CD4/CD8 ratio (0.89) and notably reduced number of CD3-CD16++56+ natural killer (NK) cells (45 cells/µL) found in the tests performed. In the further course she had no new complaints nor infections and was feeling well. Three years later, after the stressful event, she first noticed difficulty in controlling intestinal emptying, and soon afterwards, frequent bloody mucoid stools, up to 8 per day. A total colonoscopy with terminal ileoscopy was performed which indicated the existence of chronic ulcerative proctitis with a pronounced degree of activity. Peroral and topical treatment with mesalazine and probiotics resulted in clinical, laboratory and histopathological remissions of the disease. Lymphopenia (1000 cells/µL) persisted during the active phase of the disease. Two years later, during the remission, control immunophenotyping of peripheral leukocytes was performed, which showed the following values: the lymphocyte count was within the reference, but with sustained reduce in a number of CD4+ lymphocytes (464 cells/µL), CD4/CD8 ratio (0.71) and considerable reduce in a number of NK cells (69/µL). B cell lymphocyte count marginally reduced (77 cells/µL). Conclusion: Changes in lymphocyte subpopulation number not only occur in the active phase of the UC, but may precede the onset of the disease years in advance. Lymphopenia, and in particular NK cell lymphopenia, may participate in the pathogenesis of this disease, and further research on this topic is needed. Sara Bertok1, Marina Praprotnik2, Gašper Markelj3, Mirjana Maslar4, Maruša Debeljak5, Malena Aldeco2 1Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children’s Hospital, UMC Ljubljana, Ljubljana, Slovenia 2Unit for Pulmonary Diseases, University Children’s Hospital, UMC Ljubljana, Ljubljana, Slovenia 3Department of Allergology, Rheumatology and Clinical Immunology, University Children’s Hospital, UMC Ljubljana, Ljubljana, Slovenia 4Developmental Pediatrics, Pediatric Primary Health Care, Celje, Slovenia 5Clinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, UMC Ljubljana, Ljubljana, Slovenia sara.bertok@kclj.si Background: Pigmentary disorder, reticulate, with systemic manifestations, X-linked (PDR) is a X-linked recessive disorder characterized by recurrent infections and sterile inflammation in various organs. Skin hyperpigmentation with a distinctive reticulate pattern is evident by early childhood. This is followed by hypohidrosis, corneal inflammation and scarring, enterocolitis that resembles inflammatory bowel disease, and recurrent urethral strictures. Case report: We present the first family with PDR diagnosed in Slovenia. The index case is an 8 years old boy with a history of prolonged coughing, recurrent bronchitis and ear infections. From the age of 2 years, both hypopigmented and hyperpigmented spots on the skin were observed. Born with urgent cesarian section because of preeclampsia and small fetus for gestational age on the 38th week. In the first month, allergic proctocolitis due to milk hipersensitivity, which later resolved. In the first three years he had recurrent lower respiratory infections which required several hospitalisations. Episodes of productive coughing was seen. HRCT excluded bronchiectasis but tree in bud sign was found. Ophtalmologic evaluation was normal. He has lactose intollerance and is hypersensitive to azitromycine. His imunologic function was thourougly evaluated and didn't revealed specific abnormalities. 50 frequent mutations for cystic fibrosis revealed no mutation. Sweat test was not possible to interprete because of absent sweating. His brother and mother have similar, but less evident skin pigmentations and history of recurrent bronchiolitis, ear infections, obstipation and allergy to nuts and grass pollens. The mother has got oligodontia and had repeated bronchitises during childhood. Sequencing of the gene POLA1 (DNA polymerase alpha 1) in the index case and his brother revealed a hemizygous variant c.1375-354A>G in intron 13, which is very likely involved in the splicing process. The variant was described in the literature (Starokadomsky, 2016) in 11 families with X-linked reticulate pigmentary disease. The mother is heterozygous for the same mutation. Conclusion: according to clinical manifestations and genetic testing performed, we diagnosed a family (mother and two siblings) with X-linked pigmentary disease. Thus far, a couple of families affected by this rare disorder have been described in the literature. By our knowledge this is the first family described in Slovenia. Jerneja Debeljak1, Peter Korošec1, Anton Lopert2, Maja Skerbinjek Kavalar3, Matija Rijavec1 1University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 2Outpatient Practice for Pulmonary Diseases and Allergy, Murska Sobota, Slovenia 3University Clinical Centre Maribor, Maribor, Slovenia jerneja.debeljak@klinika-golnik.si Background: Asthma is a common chronic disease, characterized by airway inflammation and structural remodelling. Vascular endothelial growth factor (VEGFA) is a major regulator of angiogenesis and vascular permeability and is elevated in asthma patients. Inhaled corticosteroids (ICS) have been shown to decrease VEGF levels and suppress airway inflammation. Since inhibition of VEGFA also diminishes asthma symptoms in mice, it is predicted that variants in VEGFA gene could be associated with asthma treatment response. Materials and methods: We genotyped variant rs2146323, in VEGFA gene in 208 adult and 40 children asthma patients treated with ICSs. The percentage change in % predicted FEV1 was analysed after short-term treatment (3 months) and long-term treatment (at least 3 years) in adults, and after 6 and 12 months in children. Changes in Asthma Control Test (ACT) were followed after at least 3 years of treatment in adults and after 12 months in children. Results: Variant rs2146323 in VEGFA was associated with response to ICS treatment. Both, adult and children asthmatics showed improvement in average lung function according to an increase of average FEV1, % predicted. Children asthmatics with the AA genotype show higher improvement in % predicted FEV1 after 3 months and after 12 months. While, adult patients with genotypes CC and AC have higher improvement in % predicted FEV1 and in ACT scores after 3 months and after at least 3 years. In adult asthmatics genotype-dependent differences in treatment response were evident when analysing entire group of patients and in non-atopic patients, suggesting that treatment response was influenced by the atopic status. No association was found between rs2146323 and asthma control after 12 months of ICS therapy in children. Conclusion: Our study showed that variant rs2146323 in VEGFA is associated with treatment response to ICS, assessed as changes in % predicted FEV1, and ACT scores. In adults the difference in treatment response is highly influenced by atopy and only evident in non-atopic patients. Interestingly, in children asthmatic patients AA genotype is associated with better response, whereas in adults, patients with CC or AC genotypes responded better to ICS treatment. D. Buklioska Ilievska, C. Volkanovska Ilijevska, M. Kuzmanovska Dimitrovska City General Hospital ,,8-th September“, Skopje, Macedonia dbuklioska@yahoo.com Background: Wegener granulomatosis (WG) is a rare multisystem autoimmune disease characterized by necrotizing granulomatous inflammation, tissue necrosis, and vasculitis in small and medium-sized blood vessels. The classic clinical pattern is a triad involving the upper airways, lungs and kidneys. Case presentation: A 33-year-old woman was admitted to our hospital with a history of progressively worsening dry cough, shortness of breath, polyarthralgia, fever, epistaxis and hemoptysis. Two months before admission, she had episodes of nasal bleeding, dry cough, fever not more than 38.2°C. Her primary physician did not detect any abnormal findings in the chest radiographs at that time. Two months later, she consulted the doctor again due to the symptoms and because of the chest X-ray with multiple small infiltrates in both lungs, high sedimentation rate she was admitted to our hospital. Lungs were clear to auscultation bilaterally. Laboratory results revealed anemia with Hgb 90g/L, hematocrit 30%, erythrocytes 3600/L, leucocytes 13800/L, CRP 110mg/L, sedimentation rate 70mm/h. Urine sediment – erythrocytes 16-18, proteins +, epithelial cells ++. 24hour proteinuria 0,5g/L (upper limit 0,2). Rheumatoid antibodies: positive c-ANCA 95U/ml, RF 158IU/ml, ASO 88U/ml. ECG with sinus tachycardia of 120 beats/min. Gas analyses in partial respiratory failure with hypoxemia 7,5kPa and hypocapnia 3,6kPa, oxygen saturation 91%. Chest radiography and lung CT showed multiple infiltrates in the bilateral upper lobes. Bronchoscopy finding of intranasal coagulum without changes of nasal mucosa, transoral intubation revealed diffuse erythema and edema of the vulnerable tracheobronchial mucosa without any ulcerous lesions or infiltrative changes. Chest ultrasound with many apical bilateral, subpleural, hypoechogenic changes with zones of central necrosis with maximal diameter 20mm. Ophthalmology examination - punctiform conjunctival bleeding. Transbronchial biopsy was performed and revealed necrotic granulomas with multinucleated giant cells in the bronchial/bronchiolar and parenchymal lesions. Bronchial alveolar lavage (BAL) was performed and showed the small increase of neutrophils (total cell counts: 320/µL, neutrophils: 19.2%, macrophages: 85.0%, lymphocytes: 7.4%, eosinophils: 0.0%) and no growth of bacterial culture. According to the results the diagnosis granulomatosis with polyangiitis, Wegener’s granulomatosis. She was successfully treated by rheumatologist with high-dose steroids and cyclophosphamide. Conclusion: The recognition of multisystem disease involving joints, kidney, eye and lung is critical for diagnosing Wegener's vasculitis. Zeljka Kardum1,2, Jasminka Milas Ahic1,2, Ana Kovac1, Ana Marija Lukinac1,2, Visnja Prus1,2 1Department of Rheumatology, Clinical Immunology and Allergology UH Osijek, Osijek, Croatia 2Faculty of Medicine Josip Juraj Strossmayer University of Osijek, Osijek, Croatia zeljkakardum@gmail.com Background: Small vessel vasculitis (SVV), according to Chapel Hill Consensus, is vasculitis predominantly affecting small vessels, defined as small intraparenchymal arteries, arterioles, capillaries, and venules, but medium arteries and veins may also be affected. Patients affected with vasculitis have a risk of premature death, especially if the disease is not recognized and treated properly. Poor survival rates are reported in patients with higher BVAS score and the Five Factor Score (FFS). Methods: Retrospective analysis of clinical records of patients with small vessel vasculitis treated from 2017. – 2019. at the Department of Rheumatology, Clinical Immunology and Allergology, University Hospital Osijek. Results: 34 patients with small vessel vasculitis (6 EGPA patients, 14 GPA, 7 MPA patients and 7 patients with IgA vasculitis) were included in the study. Age, sex and Birmingham vasculitis activity score (BVAS) were used to asses poor outcome (death in the analyzed period), which was reported in five patients. Conclusion: Poor outcome was associated in patients with higher BVAS score. There were no differences in survival rate regarding sex, age or type of vasculitis. Ana Marija Lukinac1,2, Željka Kardum1,2, Ana Kovac1, Višnja Prus1,2 1Department of Rheumatology, Clinical Immunology and Allergology, Osijek University Hospital, Osijek, Croatia 2Faculty of Medicine, University J. J. Strossmayer in Osijek, Osijek, Croatia lukinac28@gmail.com Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare small-vessel vasculitis that commonly occurs in patients with bronchial asthma and is characterized by a prodromal, eosinophilic, and vascular phase of the disease. We present a patient who was diagnosed with bronchial asthma and allergic rhinitis at the age of 46, and was treated with inhaled glucocorticoids and a ß2 agonist, antihistamines and montelukast. Five months after the introduction of therapy, she becomes febrile, loses weight, has palpable purpura and oligoarthritis. Laboratory analysis showed leukocytosis with eosinophilia, high levels of acute phase reactants and total IgE. Antineutrophil cytoplasmic antibodies (ANCA) were negative, as were other immunological tests. The pathohistological findings of skin bioptates revealed infiltration of eosinophils. On the second day of hospitalization, she develops muscle weakness in the upper and lower extremities and a lesion of the upper and lower motoneurons was confirmed by electromioneurography. Montelukast was omitted from therapy, and pulse doses glucocorticoid (GK) were administered intravenously (i.v.) with clinical improvement and normalization of eosinophils. The finding of cytologic bone marrow puncture raises suspicion of hypereosinophilic syndrome. Infectious analysis excluded other causes of eosinophilia. Given the nephritic syndrome done by the kidney biopsy, the rapid progressive pauci-immune type of glomerulonephritis was confirmed and EGPA was diagnosed. According to the vasculitis protocol, she received cyclophosphamide i.v., with reducing doses of GK. She then developed a pulmonary embolism, which is why she is on anticoagulant therapy. In further controls, a positive finding of perinuclear antibodies (p-ANCA) is coming, and azathioprine is included in therapy with GK, after which the disease went into remission. It is a patient with a markedly progressive course of EGPA, who has predominantly presented with neurogenic damage, with no changes in the lungs characteristic of the vasculitic stage of the disease. In view of the above, it is possible that the eosinophilic phase of EGPA was already at the diagnosis of asthma, and the severity of the clinical picture was further enhanced by the use of montelukast, which has already been described in the available literature. Frosina Markoska1, David Lestan1, Matjaž Turel1, Matevž Harlander1,2 1Department of Pulmonary Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia markoskafrosina@gmail.com Introduction: Acute interstitial pneumonia (AIP) is a rare and severe form of idiopathic interstitial lung disease. The disease is identified by the acute onset of respiratory failure, bilateral lung infiltrates, diffuse alveolar damage on lung histopathology and the absence of an identifiable cause or predisposing condition. We present a case report of a patient with AIP seemingly triggered by strenuous physical exercise. Case report: A 48-years-old female without chronic diseases with a documented normal chest radiograph was admitted to the hospital due to acute shortness of breath, respiratory failure and suspected pneumonia. First symptoms included fever, chills and muscle pain that started seven days before admission. Three days before she ran a Ljubljana half-marathon. Initially, she received azithromycin, after which there was no improvement. Moreover, a dry cough appeared. Upon admission, we noted bilateral opacities on chest radiograph, increased CRP (155 mg/L) and a normal level of procalcitonin. Her condition quickly deteriorated. CT showed extensive bilateral infiltrates. Bronchoscopically obtained microbiological samples were negative. The transbronchial biopsy was not attempted. Immuno-serological investigations were negative. After further respiratory deterioration pulses of methylprednisolone (1000 mg for five days) were given, followed by gradual tapering. There was a partial improvement, but respiratory failure persisted. A therapeutic trial with mycophenolatemofetil (MMF) in the initial dose of 500 mg twice daily with an increase to 1000 mg twice daily was started. After that, her clinical and radiological picture started to improve gradually. A follow-up 12 months after the beginning of the disease showed significant regression of infiltrates on chest radiograph and CT. Lung function tests showed normal FVC and FEV1 (84 % and 89 %, respectively) and mild to moderate impairment of DLco (59 %). Discussion: We presented a case of a previously healthy patient who was admitted due to rapidly progressive interstitial pulmonary disease after running a half-marathon. A presumptive diagnosis of AIP was made given that lung biopsy was not considered safe. The patient was successfully treated with corticosteroids and MMF. Although we found no previous reports of the use of MMF in AIP, it could be considered as a treatment option. Saša Rink1, Barbara Salobir1,2, Dašmir Nuredini3, Matjaž Turel1, Matevž Harlander1,2 1Department of Pulmonary Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 3Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia sasa.rink@kclj.si Introduction: Osler-Weber-Rendu syndrome or hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder of vascular development. Its clinical features, that develop with age, are mucocutaneous telangiectasia, arteriovenous malformations, epistaxis and GI bleeding. With the incidence 1 in 5000 it is the main cause of pulmonary arteriovenous malformations (PAVMs), which can lead to haemoptysis, paradoxical embolisms to the central nervous system and brain abscess. PAVMs normally start occurring in puberty and continuously develop in adult life as a result of the pressure the vessels are subjected to over time. Case Report: A 28-years-old female with diagnosed HHT, sideropenic anaemia and epilepsy after cerebral abscess was admitted to our department from another hospital for further treatment after 3x2x1,5 cm PAVM was discovered in the right superior lobe with CTA of pulmonary arteries. Head MRI showed no signs of AVMs, neither did gastroscopy and colonoscopy that were performed later on. Six years ago, she had embolization of 4 PAVMs. Since then she had occasional haemoptysis that started occurring on daily bases in the last 3 months and caused severe anaemia. She also reported decrease in physical performance especially when walking uphill and being constantly tired. Upon admission she received 3 units of concentrated erythrocytes and tranexamic acid after which bronchoscopy was done but showed no traces of bleeding. Echocardiogram indicated important pulmonary arteriovenous shunt. A repeated CTA of pulmonary arteries showed several additional PAVMs in almost all lobes, the biggest being the one in right superior lobe that we successfully embolized. After the procedure the patient’s clinical signs improved. Due to the great extent of the embolization of the largest PAVM, smaller ones were planned to be embolised later. With no recurrent haemoptysis, she was discharged from the hospital with advice to avoid any kind of physical or emotional stress including house chores and pregnancy. In case of further deterioration, lung transplantation could be considered. Consequently, four remaining PAVMs were embolised. In 3 years of followup she reported stable condition with no further bleeding. With haemoptysis ceased, satisfactory life quality was achieved and referral for lung transplantation was not needed. Conclusions: We presented a case of a patient with HHT with several PAVMs on both sides of the lungs with recurring potentially life-threatening haemoptysis and severe anaemia. Her condition was successfully managed by a combination of gradual embolization of PAVMs and non-pharmacological measures including major lifestyle changes. Furthermore, this case illustrates the need for a regular follow-up of patients with HHT with PAVMs in an expert centre as PAVMs may recur and additional intervention may be needed. Tatjana Vujic, Snezana Cvetkovic, Aleksandra Todorovic, Ljudmila Nagorni Obradovic Clinic for Pulmology, Clinical Centre of Serbia, Belgrade, Serbia tvujic@vektor.net Introduction: Sjogren Syndome (SS) and sarcoidosis are multisystemic autoimmune diseases of unknown etiology which share certain clinical features. Case report: A 72-year-old woman presented with a several months history of dry mouth, dry eyes and fatigue. She was admitted to the department of immunology where the diagnosis of primary SS was established (based on the existence of xerostomia, xerophthalmia, verified keratoconjunctivitis sicca, low unstimulated salivary flow, abnormal salivary gland scintigraphy, positive antinuclear antibodies). Chest radiograph and computed tomography scan showed bilateral hilar and mediastinal lymphadenopathy with diffuse reticulonodular densities in lungs, so patient continued examination in the department of pulmology. Sedimentation rate, levels of angiotensin converting enzyme and chitotriosidase were elevated. The hemogram and biochemical tests including calcium were normal. Lung function test showed restrictive pattern and carbon monoxide diffusing capacity was lowered. Bronchoscopy with biopsy was performed and histopathologic examination revealed non-caseating granuloma consistent with sarcoidosis. The patient was diagnosed with coexisting SS and sarcoidosis. Treatment for sicca symptoms, hydroxychloroquine and corticosteroids were recommended. Conclusion: This case shows that possibility of simultaneous presentation of SS and sarcoidosis should not be excluded in clinical practice. Loredana Mrak1, Robert Marcun2, Tanja Cufer1, Matej Podbregar3 1Department of Medical Oncology, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 2Department of Cardiology, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 3Department of Intensive Care, General Hospital Celje, Celje, Slovenia Background: Novel systemic therapies in treating non-small-cell lung cancer (NSCLC) enable longer survival of patients (pts) with advanced NSCLC than ever before. With prolonged survival, quality of life, and treatment's side effects are brought more to our attention. Although we have some information about the cardiotoxicity of novel systemic therapies from clinical studies, real-world data on this topic are scarce. This study aimed to monitor the development of cardiac toxicity in pts treated for advanced NSCLC with either immunotherapy or targeted therapy in routine clinical practice. Methods: This was a prospective, observational study conducted at a single academic center. We followed NSCLC pts treated with either immune checkpoint inhibitor (CPI) or endothelial growth factor receptor tyrosine kinase inhibitor (EGFR TKI) who consented to additional monitoring. During their routine treatment, they had a directed clinical examination, echocardiogram recording, proBNP and troponin T sampling at treatment initiation, months 2 and 4, and then every four months until the end of treatment. Only pts with normal baseline cardiac function were included in the study. Results: We included 61 pts with advanced NSCLC and a mean age of 63,7±9 years, 34 of them female (56%). 48% of pts (29 pts) were treated with monotherapy with CPI (atezolizumab, nivolumab, or pembrolizumab), while 52% of pts (32 pts) received EGFR TKI (afatinib, gefitinib, erlotinib, or osimertinib). We analyzed recorded data for up to 24 months of treatment; at 4, 12, and 24 months, there were 59, 29, and 15 pts still included, respectively. No pts on either CPI or EGFR TKI developed signs of heart failure during their treatment. In a joint study cohort, left ventricular ejection fraction stayed normal at all time points (p=0.71), the values of troponin T and NTproBNP stayed stable throughout treatment (p=0,45 and p=0,85, respectively). Conclusion: Our observational study has shown no cardiac toxicity in pts treated for advanced NSCLC with either immunotherapy or targeted therapy in routine clinical practice. Analysis of more sensitive parameters and longer observation times are needed. Srdan Lukic1, Veronika Podlogar2, Robert Marcun3 1General Hospital Izola, Izola, Slovenia 2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 3University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia srdjann@gmail.com Background: Pulmonary hypertension (PH) is defined by mean pulmonary arterial pressure (mPAP) equal or greater than 25 mmHg at rest, measured with right heart catheterisation. The diagnosis of pulmonary hypertension is obtained gradually, while simultaneously searching for its etiology. Pulmonary hypertension is classified into five subgroups based on their clinical presentation, pathophysiological findings, haemodynamic characteristics and treatment. In the last years there has been immense progress in treatment strategies for PH. Therapy is multifaceted and beside the symptomatic treatment it focuses on treatment of the underlying disease. The initial approach consists of several steps; it comprises general measurements (physical therapy and supervised rehabilitation, avoidance and elimination of the risk factors that could exacerbate the disease and provoke it’s progression), non-specific supportive therapy (oxygen, diuretics, oral anticoagulant treatment, cardiovascular drugs) and PH-specific treatment (calcium channel blockers, prostanoids, endothelin receptor antagonists, phosphodiesterase type-5 inhibitors. For chronic thromboembolic pulmonary hypertension, pulmonary endarterectomy is the treatment of choice for operable patients. If no adequate response is achieved the therapy with combination of approved drugs should be implemented and the patient should be evaluated for lung transplantation. Specific pulmonary hypertension treatments and advanced surgical techniques offer a chance to improve not only the quality of patients’ life but also increase their survival. Case presentation: Female patient J.M, born in 1929, non-smoker, a retired professor, admitted to University Clinic Golnik in 2005 for further evaluation of dispnea on exertion, lasting 5 years. In the past month the patient noticed progressive decline in daily physical activities, with her walking distance on a flat surface being reduced to only few steps. Beforehand she was diagnosed with arterial hypertension and hyperlipidemia and was receiving simvastatin (Sinvacor), nicergolin (Adavin) and irbesartan (Aprovel). Physical examination did not reveal any clinically relevant abnormalities. ECG showed sinus rhythm with frequency of 65/min without signs of right heart overload. Laboratory findings were normal, D-dimer negative (109 mcg/l). Arterial blood gasses analysis revealed moderate hypoxemia (pO2 8.0 kPa, SAT 89 %) and no acid-base abnormalities (pH 7.43, pCO2 4.8 kPa, HCO3 23.5 mmol/l). Pulmonary function tests were normal, (VC 2500 ml (90 %), FEV 1780 ml (96 %), Tiff. 71 %). On transthoracic echocardiography right ventricular pressure was significantly elevated (67 mmHg + CVP). Chest CT showed signs of chronic pulmonary thromboembolism with most of the thrombi partially organised. The patient underwent right heart catheterisation in April 2007, where precapillary pulmonary hypertension was confirmed (right atrium 3 mmHg, right ventricle 55/0 mmHg, pulmonary artery 55/14 mmHg, mPAP 31 mmHg, PCWP 3 mmHg). The patient was classified into group 4 – chronic thromboembolic pulmonary hypertension. Warfarin therapy with a target INR 2-3 was initiated. The patient was a responder for tested substances and therapy with calcium channel blocker (diltiazem 3x90 mg/day) was implemented after catheterisation. Her previous therapy with Nicergolin (Adavin) and irbesartan (Aprovel) was discontinued. NYHA functional class of the patient improved on therapy from NYHA 3 to NYHA 2. Patient has been followed up closely and in 13 years after the initial diagnosis (od 2007 do 2020) she has remained stable and has not been hospitalised due to pulmonary hypertension. She is now 91 years old and continues to live a fully functional life. Table 1: Long term follow up of a patient with chronic thromboembolic pulmonary hypertension 6-minute walking test 6.2008 6.2009 6.2012 1.2013 7.2013 7.2014 6.2015 6-minute walking distance 410 406 325 375 340 350 255 SAT%/mean heart rate at begining of test (0') 94%/72 93%/84 93%/87 92%/81 94%/89 93%/98 94%/91 SAT%/mean heart rate at end of test (6') 89%/107 90%/111 89%/109 89%/103 89%/112 86%/119 92%/97 SAT%/mean heart rate after the test (+1') 95%/88 93%/95 92%/95 92%/85 93%/100 89%/105 94%/89 Figure 1: Right ventricle pressure at examination Discussion: Non-adequately treated pulmonary hypertension is associated with poor prognosis. Until recently treatment consisted of only supportive therapy, but in the last decade immense progress was made in the treatment of individual groups of PH. Before the therapy is introduced a comprehensive diagnostics should be performed to determine the underlying etiology. Based on diagnostic findings, comorbidities, drug tolerance and overall prognosis the most appropriate treatment strategy is implemented. Our case report demonstrates that with adequate diagnostic approach the patient with severe PH can live a quality life without hospitalisations and reach a great age. Figure 2: NT-proBNP values at examination References: 1. Escardio.org. 2020. ESC Guidelines On Pulmonary Hypertension (Diagnosis And Treatment Of ). [online] Available at: [Accessed 22 July 2020]. 2. Galič, N., McLaughlin, V., Rubin, L. and Simonneau, G., 2019. An Overview Of The 6Th World Symposium On Pulmonary Hypertension. [online] NCBI. Available at: [Accessed 22 July 2020]. 3. Frost, A., Badesch, D., Gibbs, J., Gopalan, D., Khanna, D., Manes, A., Oudiz, R., Satoh, T., Torres, F. and Torbicki, A., 2019. Diagnosis Of Pulmonary Hypertension. [online] NCBI. Available at: [Accessed 22 July 2020]. 4. Fedullo, P., 2019. Clinical Manifestations And Diagnosis Of Chronic Thromboembolic Pulmonary Hypertension. [online] Uptodate.com. Available at: [Accessed 22 July 2020]. Polona Mlakar1,3, Ana Žaže Bertoncel1, Barbara Salobir1,3, Janez Toplišek2, Irene Lang4 1Department of Pulmonary Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Department of Cardiology, University Medical Center Ljubljana, Ljubljana, Slovenia 3Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 4Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria polona.mlakar@live.com Background: Pulmonary thrombendarterectomy is the primary treatment for patients with chronic thrombembolic pulmonary hypertension. However, if the lesions are too distal to be surgically removed, they can be effectively treated with the balloon pulmonary angioplasty in addition to specific drugs for pulmonary arterial hypertension (1). Case presentation: We present a 60-year old male with severe, inoperable chronic thromboembolic pulmonary hypertension, who was successfully treated with combination of specific pharmacological therapy (riociguat, macitentan and iloprost) and balloon pulmonary angioplasty (BPA). This patient presented for the first time in April 2014 with progressive dyspnea, unexplained syncope and a month later with acute pulmonary embolism. Lung ventilation/perfusion scan, CT-A of pulmonary arteries, echocardiography, and right heart catheterization (RHC) in January 2015 confirmed severe, distal chronic thromboembolic pulmonary hypertension (mPAP 48 mmHg, PVR 10.7 WU, PAWP 6 mmHg). We started treatment with riociguat, but pulmonary artery pressures remained severely elevated and RV function continued to worsen. In 2017 we added subcutaneous treprostinil, which was discontinued due to adverse effects. Further disease progression was shown by echocardiography and RHC (PAWP 9 mmHg, mPAP 59 mmHg, PVR 8.2 wu, CI 2.0), repetitive syncopes and worsened 6MWT result. In 2018 patient started with inhalations of iloprost and in January 2019 a treatment with macitentan was added with no significant improvement. In January 2019, the first BPA was performed in AKH Vienna. Until now 10 BPA procedures were performed in total. After only two BPAs syncopes ceased and patient's physical performance improved with every additional BPA. After last BPA invasive measurements showed near normalization of pressures and pulmonary vascular resistance and cardiac index significantly increased (PAWP 8 mmHg, mPAP 29 mmHg, PVR 3.28 wu, CI 3.28, sVO2 72.8). Quality of life has since than practically normalized. Conclusion: This case report demonstrates drastic improvement of hemodynamic parameters, physical capacity and quality of life in a patient with severe, inoperable chronic thromboembolic pulmonary hypertension. It proves that combination of medical therapy and several repeated BPAs is very effective method of treatment also in patients with severe disease. Polona Mlakar1,4, Barbara Salobir1,4, Janez Toplišek2,4, Matjaž Baraga3, Samo Vesel5, Irene Lang6 1Department of Pulmonary Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Department of Cardiology, University Medical Center Ljubljana, Ljubljana, Slovenia 3Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia 4Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 5Pediatric Cardiology Outpatient Clinic, General Hospital Celje, Celje, Slovenia 6Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria polona.mlakar@live.com Background: Peripheral pulmonary artery stenosis (PAS) is a rare disease entity, which can be misdiagnosed as idiopathic pulmonary hypertension or chronic thromboembolic pulmonary hypertension. It is most often seen in children and young adults. Physicians should have PAS in mind in differential diagnosis of all patients with pulmonary arterial hypertension, especially young patients with unexplained dyspnea on exertion - to make the correct diagnosis as early as possible. CT-A of pulmonary arteries and also invasive diagnostic measures (pulmonary angiography) should always be performed for correct diagnosis. The current treatment options for PAS include balloon pulmonary angioplasty (BPA), with a possibility of stenting, which is a novelty, and lung transplantation1. Case presentation: A nine year old boy started noticing progressive dyspnea on exertion and diminishing levels of physical fitness. At the age of sixteen, first echocardiogram was performed. It showed signs of mild pulmonary hypertension, no left heart disease and no congenital heart disease. Right heart catheterisation showed no pulmonary hypertension(PH) at rest, but stress echocardiography showed severe PH upon exertion. At the age of 19, he was admitted to our department due to hemoptysis occurred during acute respiratory tract infection. CT-A of the chest showed acute pulmonary embolisms with two pulmonary infarctions. He was treated with antibiotics, but no anticoagulant treatment. Echocardiography showed signs of severe pulmonary hypertension and reduced systolic function of the right ventricle. Prof. Lang from AKH Vienna organized a consultation with Prof. Matsubara from Japan, and we agreed to perform BPA with stent placement at AKH Vienna. Since June 2019 six procedures were performed with 10 drug eluting stents implanted. Dual antiplatelet treatment and riociguat were introduced after the first BPA. The results of the treatment are encouraging: mPAP and PVR dropped to almost normal, desaturation during his six minutes walking test reduced and hemoptysis ceased. The ambition of this modern type of treatment is to postpone lung transplantation as much as possible, but at the same time reduce symptoms and preserve the function of the right heart. Conclusions: We presented novel treatmet of pulmonary artery stenoses with repetitive balloon pulmonary angioplasties and stenting with encouraging results, which improved the prognosis, quality of life, and postponed the need for possible lung transplantation. References: 1. Kim CW, et al. Treatment of peripheral pulmonary artery stenosis. [published online ahead of print, 2020 Feb 12]. Cardiol Rev. 2020;10.1097/CRD.0000000000000300. doi:10.1097/ CRD.0000000000000300) Veronika Podlogar1, Karmen Krejan1, Robert Marcun2 1Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 2University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia veronika.podlogar7@gmail.com Introduction: Pulmonary hypertension is defined by mean pulmonary arterial pressure at rest of 25 mmHg or higher, assessed by right heart catheterization. Clinical presentation is non-specific and may include dyspnoea on exertion, fatigue, chest pain and headaches. Time from symptom onset to definitive diagnosis has not been shortened in the last twenty years, but new specific treatment available calls for changes in the diagnostic procedures and screening. Case report: A 16-year-old adolescent has been experiencing shortness of breath, poorer physical performance compared to his peers and fatigue for several years; his problems have priorly been diagnosed as exercise-induced asthma although there were no significant changes with inhalers. He has a congenital enamel disorder as well as his brother and father. At the age of seven he was diagnosed with mild aortic isthmus stenosis and arterial hypertension, for which he was receiving amlodipine and enalapril, but he discontinued the therapy. In June 2016, more extensive diagnostics were performed at our clinic. Examinations of lung functions were within normal values; methacholine testing was negative. Transthoracic echocardiography showed a structurally and functionally normal heart. Ultrasound-assessed systolic pressure in the right ventricle was slightly elevated (40 mmHg + CVP) at rest, while stress echocardiography showed a severe increase in systolic pressure to 110 mmHg + CVP. Cardiac catheterization was performed and pressures in the right ventricle (30/4 mmHg) and pulmonary artery with normal saturation (30/6-17 mmHg) were measured. Pulmonary angiography revealed several peripheral pulmonary stenoses, slightly more pronounced on the left side. No known genetic disease was detected by diagnostic genetic testing. Conclusion: Pulmonary arterial hypertension in children and adults often presents similarly as other more common diseases of the lungs and cardiovascular system therefore special attention should be paid to patients with higher risk for pulmonary hypertension. Genetic testing is recommended in all patients with idiopathic pulmonary hypertension, as it can reveal the cause of the disease. Further research is needed to detect yet unrecognized genetic syndromes, among which we could find a common cause of idiopathic pulmonary hypertension, mild narrowing of the aortic isthmus, arterial hypertension detected in childhood and congenital enamel disorder. Anže Žgank, Polona Mlakar, David Lestan, Luka Petric, Matevž Harlander, Barbara Salobir Department of Pulmonary Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia anze.zgank@kclj.si Introduction: Pulmonary hypertension (PH) is a disease characterized by blood pressure higher than 25 millimeters of mercury (mmHg) in the pulmonary artery measured by right-sided cardiac catheterization (RHC) at rest. The disease itself is multifactorial and associated with a poor prognosis. The course of the disease is influenced by several factors that have not yet been definitively determined. Up to date research has shown that one such a factor might be uric acid (UA). Higher serum values of UA are associated with a more severe course of the disease and higher mortality in patients with pulmonary hypertension (1). The purpose of this analysis of our clinical work is to determine whether there is a relationship between UA, mean pulmonary artery pressure (mPAP) and N-terminal pro-brain natriuretic peptide (NTproBNP) - a reliable diagnostic marker of cardiac decompensation. Methods: At our PH Center at the University Clinical Center Ljubljana we performed 49 right heart catheterizations in 2019. Two patients with extremely high NT-proBNP due to advanced chronic renal failure were excluded from analysis. We included in further analysis 28 patients (average age 63.5 years, min 39 max 80 years, 63,6% women) with confirmed PH who also had a measurement of UA besides NT-proBNP in close temporal proximity to the hemodynamic evaluation. The statistical analysis was performed with the IBM SPSS program (version 20). Since values were not distributed normally and due to low number of patients non-parametric methods were used and values were expressed as medians with interquartile ranges. Results: According to PH classification 8 patients(28.6%) had PH from group I, 8 patients (28.6%) had PH due to left heart diseases, 11 (39.3%) had chronic thromboembolic disease and one patient had PH due to multifactorial reasons (3.6%); mPAP was 44 (34 49) mmHg, NT-proBNP 1345 (397 – 2331) ng/l and UA 411 (313 - 541) µmol/L. We found higher levels of mPAP (45; 42-52 vs. 40; 30-40, p=0,065) and NT-proBNP (1867; 12452529 vs. 564; 126-2032, p=0,029) in patients with increased (>430 µmol/L) vs. normal levels of UA. Correlation of UA with mPAP was almost significant (r=0.33, p=0.081) and non-significant with NT-proBNP. Conclusion: Analysis showed expected positive correlation between UA and mPAP, furthermore both mPAP and NT-proBNP were higher in patients with high UA. Results (although some not statistically strong due to low number of patients and group heterogeneity) are in line with previous studies, which showed that uric acid is a marker of disease severity. In advanced PH UA might be increased directly due to hypoxemia (2) or as a result of several other factors such as use of diuretics, increased oxidative stress and metabolic syndrome, which are associated with advanced PH. On the other hand, UA might also play a role in the pathogenesis of pulmonary hypertension through impact on endothelial dysfunction (3). Thus, the relationship between PH and high levels of uric acid, confirmed also with our short preliminary analysis, might go in both directions. However, question about the role of UA in pathogenesis of PH remains unsolved. Further studies are needed to provide the answer on this intriguing topic. D. Buklioska Ilievska, I. Trajkovska, A. Doneva City General Hospital ,,8-th September“, Skopje, Macedonia dbuklioska@yahoo.com Introduction: Many studies have shown that COPD is a moderate and independent factor for PE. Patients with COPD are at a high risk for PE because of systemic inflammation, limited mobility and co-existing comorbidities: cardiovascular disease, anemia, polycythemia, malnutrition, muscle disorder, osteoporosis, metabolic syndrome, diabetes, gastroesophageal reflux, anxiety, depression, hormonal imbalance, infections, lung cancer, thrombosis. Methods: Prospective, observational study of 50 hospitalized patients with COPD, diagnosed according to GOLD criteria (stages I-IV), 40-75 years (mean age 65.4±12.3 divided in subgroups (PE-diagnosed/non-PE and with known/undetermined exacerbation etiology). Investigations: clinical risk assessment, laboratory, spirometry, gas-analysis, electrocardiogram, D-dimer (DD), chest X-ray, chest ultrasound. Doppler-ultrasonography of deep-veins of lower-extremities. Patients with high DD and deep vein thrombosis (DVT) or high DD and abnormal chest ultrasound underwent computed-tomography pulmonary-angiography. Results: PE was diagnosed in 13(26%) of 50 hospitalized COPD patients. Frequencies of PE in PE-diagnosed group according to GOLD-stages I-IV, were 0(0.0%), 1(7.7%), 4(30.8%), 8(61.5%) respectively with positive correlation between airflow limitation and PE. Patients with pleuritic chest-pain, chest ultrasound abnormality, DVT and high DD were more likely to develop PE. DD was significantly higher among patients with PE than those without (2.14±1.4µg/ml vs. 1.5±0.4µg/ml, P<0.0001). There was positive correlation between the presence of PE and elevated DD>2.0µg/ml (P<0.05). There was no statistically significant difference between patients with PE and without, according to age, gender and comorbidities (P>0.05). Immobility and obesity were significantly higher among PE patients, P<0.05 and P<0,0001 respectively. Conclusion: Clinical manifestations of PE like pleuritic chest pain, dyspnoea are nonspecific, and easily could be underestimated in COPD patients, which leads to disease worsening, delay of anticoagulant therapy and higher mortality rate. D. Dimitrievska, M. Zdraveska, D. Todevski, M. Tushevska Mitkovska, N. Chamurovski PHI University Clinic of Pulmology and Allergy, Skopje, Macedonia deskadimitrievska@gmail.com Asthma is one of the most common chronic diseases all over the world, resulting from a state of persistent sub-acute inflammation of the airways. The main attribute of asthma is inflammation, which leads to airway remodeling, bronchial hyper-reactivity and reversible or partly reversible airway obstruction. Asthma is a chronic inflammatory disorder of the airways in which many cells and inflammatory mediators play a role. (GINA). Many cells and mediators take part in creating the asthmatic inflammatory reaction, but eosinophils play a central role. All of the inflammatory cells and mediators can be detected in the airflow tissue. Some of them can be detected in the asthmatics peripheral blood too. This study includes 30 patients of the Pulmology and Allergy Clinic, Skopje, with confirmed bronchial asthma, treated with ICS. In all of the patients we followed Eo count, ECP and IL-5 in peripheral blood at the beginning of the study, after 2 and 6 months treatment. Following the parameters during treatment with ICS we registered changes in all of the tested parameters. Our conclusion is that the ICS objectively suppress the inflammatory reaction in asthma and the biologic markers (IL-5, Eo and ECP), which we have followed, can measure the accomplished effect. They could be used in every day practice, not only as diagnostic parameters but also as valid therapeutic guides in the treatment of asthma. Y. Feshchenko, L. Iashyna, M. Polianska, V. Ignatiena, S. Moskalenko, S. Opimakh, I. Zvol, N. Vlasova, L. Halai, I. Chumak SO “National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine”, Kyiv, Ukraine iashyna@ukr.net Aim of the investigation: to evaluate the effectiveness of basic therapy with ultrafine glucocorticosteroids, tiotropium bromide (Respimat) in standard therapeutic doses and 10% acetylcysteine (via nebulizer) in asthma patients with neutrophilic type of inflammation. Materials and methods: 30 patients with neutrophilic type of inflammation (blood neutrophils = 4000/µl) were randomized 1:1 to receive fixed combination budesonide/ formoterol 320/9 mcg BID (I, control group: male 5, female 10, mean age (53,6 ± 3,8) years, post BD FEV1 (51,5 ± 4,7) %, FEV1/FVC (67,2 ± 3,5) or (II, main group: male 9, female 6, mean age (53,6 ± 3,8) years, post BD FEV1 (51,5 ± 4,7) %, FEV1/FVC (67,2 ± 3,5) ultrafine beclomethasone 250 mcg, formoterol 12 mcg BID, tiotropium (Respimat) 5 mcg 2 inhalations QD during 3 monthes, additionaly - solution of acetylcysteine 10% 3 ml via nebulaiser during 10 days. Result: After 3 months of treatment in II group the effectiveness of treatment was 93.3%: statistically significant increased the total score of ACT - from (14.3 ± 1.3) to (20.3 ± 0.8) points (p <0.05), total score of ACQ decreased from (2.3 ± 0.2) to (1.1 ± 0.1) points (p <0.05). Clinically significantly decreased symptom score in SGRQ - from (71.4 ± 5.6) to (51.3 ± 5.0) points, p <0.05. Improvement of clinical symptoms accompanied with increase in MEF50 from (28.9 ± 4.5)% to (41.6 ± 4.2)%, MEF25 from (19.1 ± 2.9)% to (27.6 ± 2.6)% which indicated an improvement in bronchial patency at the level of small bronchi. Studied course of treatment improved the physical tolerability - 6MWT increased from (266.3 ± 16.2) to (312.0 ± 14.4) m, with decrease in shortness of breath (Borg scale) before the test from (2.5 ± 0.3) to (1 , 5 ± 0,1) points and after the test - from (4,1 ± 0,3) to (3,1 ± 0,3) points. Complex therapy was well tolerated by patients and was not accompanied by the development of side effects. In patients of the control group, statistically significant dynamics of the studied indicators were not detected. Conclusions: In asthma patients with neutrophilic inflammation use in basic therapy ultrafine inhaled glucocorticosteroids + tiotropium bromide (Respimat) in a standard therapeutic dose, formoterol 12 µg BID and inhalations of 10% of QD led to a positive dynamics of clinical symptoms improved the tolerance to physical load, improved quality of life, resulting in 93.3% effectiveness of treatment. Matevž Harlander1,2, David Lestan1, Matjaž Turel1 1Department of Pulmonary Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia matevz.harlander@gmail.com Introduction: This study aimed to determine the association between peripheral blood cell counts and exacerbations of COPD. Methods: This observational prospective study comprised 97 patients (44 females) with COPD. Their clinical characteristics and a history of exacerbations in the last 12 months were noted. Upon inclusion, all patients had to be in a stable state, at least 4 weeks after the last COPD exacerbation and not receiving systemic corticosteroids. Peripheral blood cell counts were determined upon the first visit. Patients were followed up for 12 months, and the number of moderate and severe exacerbations during this period was recorded. Results: Patients who had at least one moderate or severe exacerbation during the observational period had lower BMI (24.5 [4.0] vs. 26.4 [4.8], p = 0.046), lower age (65 [9] vs. 68 [7] years, p = 0.037), worse lung function (FEV1: 45 [17] vs. 63 [21] %, p < 0.001 and FVC: 75 [16] vs. 86 [20] %, p = 0.005) and more frequent history of at least one exacerbation in previous 12 months (50.0 vs. 26.2 %, p = 0.027), while there was no difference in sex, smoking history or CAT. Peripheral blood cell counts showed higher relative and absolute eosinophil counts in patients with at least one exacerbation as compared to patients without exacerbations (3.01 [2.60] vs. 1.91 [1.27] %, p = 0.006 and 225 (190) vs. 154 (99) cells/µL, p = 0.017) but there were no significant differences in other parameters. Multivariate analysis using Cox regression model identified lung function (FEV1) as the only independent predictor of future exacerbations (HR [95% CI]: 0.976 [0.956 - 0.996], p = 0.019). Conclusion: In our cohort of patients with COPD, higher relative and absolute eosinophil counts were seen in patients with at least one observed moderate or severe exacerbation. However, the multivariate analysis confirmed only lung function as an independent predictor of exacerbations. L. Iashyna, Y. Feshchenko, M. Polianska, V. Ignatiena, S. Moskalenko, S. Opimakh, I. Zvol, N. Vlasova, L. Halai L, I. Chumak SO “National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine”, Kyiv, Ukraine iashyna@ukr.net The aim of the investigation: to evaluate the effectiveness of ultrafine glucocorticosteroide in the basic therapy of patients with bronchial asthma (BA) with neutrophilic type of inflammation. Materials and methods: 30 persistent asthma patients with a predominantly neutrophilic phenotype of inflammation (blood neutrophil count > 4000/µl) and small bronchi and fixed obstruction were divided into 2 groups: I (main group, n=15) - received ultrafine beclomethasone (solution) at a dose of 250 µg and formoterol at a dose of 12 µg 2 BID; II (control group, n=15) continued their previous baseline therapy with fixed combination 320 mcg budesonide and 9 mcg formoterol BID. All patients received salbutamol PRN. The duration of the study course - 3 months. The work was performed at the expense of the state budget. Results: The use of ultrafine ICS in basic therapy of asthma patients with neutrophilic inflammation and small bronchi and fixed obstruction allowed to achieve clinical and functional efficacy in 80% of patients: significant reduction in bronchoobstruction at the level of small bronchi - increase in MEF25 from (19.1 ± 2.9)% to (31.9 ± 5.2)%, p <0.05; stabilization of clinical symptoms and increased exercise tolerance - increase of ACT by 3.2 points (from (14.3 ± 1.3) to (17.1 ± 0.3) points), p <0.05, and the number of meters passed by test with a 6-minute walk (6MWT) from (266.3 ± 16.2) m to (283.3 ± 18.8) m, p <0.05. In the control group the studied indicators did not change significantly. Conclusion: The use of ultrafine glucocorticosteroids in the basic therapy of patients with asthma with neutrophilic inflammation with the presence of small bronchial obstruction, fixed bronchoobstruction allowed to achieve clinical and functional efficacy in 80% of patients. Treatment was well tolerated by patients and was not accompanied by the development of side effects. The method is easy to use and easily accessible to the practitioner. Maruša Kopac1, Sabina Škrgat1,2,3, Peter Korošec1, Urška Bidovec Stojkovic1, Izidor Kern1, Romana Vantur1 1University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 2University Medical Centre Ljubljana, Ljubljana, Slovenia 3The Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia kopac.marusa@gmail.com Background: Severe eosinophilic asthma (SEA) is characterized by an increased sputum and/or blood eosinophils, frequent exacerbations and consequent prescribing of an oral corticosteroid (OCS). Anti-IL-5 is therapy of choice for SEA phenotype. Response to anti-IL-5 biologics is not equal in every patient. Some patients are »responders« and reach complete asthma control, on the other hand are »non-responders« who show no improvement or even have clinical worsening. The underlying mechanisms of these different responses are not yet understood. Aims:To evaluate differences in non-responders and responders to anti–IL-5 treatment. Methods: We included 17 adult patients with SEA in the Severe Asthma Registry (12 responders and 5 nonresponders). Parameters were assesed at baseline and after 4 months of treatment with mepolizumab 100 mg subcutaneously (in one case benralizumab 30 mg subcutaneously) at University Hospital of Respiratory and Allergic Diseases in Golnik, Slovenia. The following parameters were evaluated: pulmonary function (FEV1), Asthma Control Test (ACT), OCS dose reduction and number of exacerbations, eosinophil count and IL-5 concentration in induced sputum and eosinophil count in peripheral blood. Statistical analysis was performed by GraphPad Prism 8.0.1. Results: In responders, anti–IL-5 therapy led to significant increase in FEV1 (in mililiters p = 0,002) and ACT score (p = 0,001) and decrease in the exacerbations rate (p = 0,001) and OCS dose (p = 0,0002). Reduction of blood eosinophil count was observed at follow-up in both groups (non-responders p = 0,018; responders p = 0,0004) without significantly differing magnitude. A significant drop in sputum eosinophilia in the responders group at follow-up (p = 0,05) was demonstrated. Comparing to responders, non-responders had 6 times more sputum eosinophils at follow-up. No differences were showed in IL-5 concentrations at follow-up between the groups in serum (p = 0,366) or induced sputum (p = 0,809). Conclusions: Opposed to non-responders, anti–IL-5 therapy in responders significantly improves lung function, number of exacerbations, OCS burden and subjective condition. Sputum eosinophil count has proved to be a significant cellular biomarker of response to anti–IL-5 therapy and better in defining the response to as blood eosinophil count. IL-5 concentration as an alternative biomarker was not demonstrated in neither serum nor induced sputum. S. Momchilovikj, T. Jakjovska, I. Arnaudova-Danevska CF Department, Institute for respiratory diseases in children, Skopje, Republic of North Macedonia drsonjab@gmail.com Introduction: 28 years old female with CF(Cystic Fibrosis), genotype F508del/1811+1G->C. Stabile condition till two years ago when she started with intermittent temperature , weight loss, dry deep cough, haemoptysis and in the last 4 months pain behind right eye and headache. Temperature as a symptom has multifactorial cause. Finding the cause of the temperature is important for maintaining good lung function and better FEV1 (forced expiratory volume in the first second) in CF patients. Methods: We performed many investigations: laboratory (Total IgE=58.0 IU/ml, Specific IgE for Aspergillus fumigatus=0.04 IU/ml), immunological-antinuclear antibodies for all muscular and tissues diseases - negative, Viral markers (Hepatitis/ HIV – negative), microbiological (sputum isolation Staphylococcus aureus -chronic infection and Staphylococcus aureus meticilin resistant-intermittent infection, sputum for Mycobacterium tuberculosis and non typical mycobacterium - negative) and diagnostic imaging (Chest X-Ray, CT chest - bronchiectasis, inflammation zone - tree in bud, solitary cystic bronchiectasis filled with mucus in upper right part of the lungs, Fiber nasal endoscopy with mild hyperemia of the nasal mucosa with poor adhesive secretion, CT head was normal, skin prick test for Aspergillus fumigatus negative), bronchoscopy and in the bronchoalveolar lavage, Aspergillus fumigatus was isolated, which had not been found in any analysis before, Magnetic resonance on head - drainage obstruction of the sphenoidal sinus, filled with dense contents suspected for Aspergillum. Results: According to the results of the investigations she was threated with Itraconasol for 3 months and the patient became afebrile after. During the patient's treatment, the headache became more intense, so we have consulted a team of ear nose throat (ENT) specialist, ophthalmologist and a neurosurgeon. They concluded that the best option is transnasal access and biopsy of the sphenoidal sinus for completing the diagnosis, but it cannot be done because of the high risk of postoperative complications due to the main disease. Conclusion: Prolonged fever as a symptom should never be overlooked. On the contrary, it is an alarm for an infection in the body and needs to be thoroughly investigated. D. Buklioska Ilievska, I. Trajkovska, A. Buklioska General Hospital “8th September”, Skopje, Macedonia Medical Faculty “Ss. Cyril and Methodius”, Skopje, Macedonia dbuklioska@yahoo.com Background: MetS represents a cluster of risk factors (abdominal obesity, atherogenic dyslipidemia, hypertension and insulin resistance) that predispose affected patients to systemic inflammation, cardiovascular disease and physical inactivity. COPD is a major health problem worldwide, the fourth leading cause of death with prevalence in increase. There is a limited data about the prevalence of MetS in COPD. The aim of the study is to determine the frequency of coexisting MetS in COPD. Methods: Case control study of 120 patients with COPD (82 men and 38 women, aged 40-75 years, mean age 64.2±10.4), diagnosed according to Global Initiative for Chronic Obstructive Lung Disease, 30 healthy non-COPD subjects, randomly selected as controls. Anthropometric measurements, fasting blood sugar (FBS), lipid profile, high-sensitivity C-reactive protein (hsCRP), spirometry, CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires, were assessed. COPD subjects were stratified based on combined assessment test (ABCD criteria) and spirometry (stages I - IV). Results: The presence of MetS was diagnosed in 50(41.67%) of COPD patients vs. 5(16.67%) of controls (p=0.01). The frequencies of the MetS in patients with COPD, GOLD stages I, II, III, and IV, were 50(41,67%), 66(55%), 60(50%), 42(35%) respectively. Frequency of MetS according to combined assessment test (A, B, C, D) was 42(35%), 54(45%), 25(30%), 36(30%) respectively. The presence of MetS was associated with significantly worse cough, sleep and mood (p<0.01) and higher total CAT score (p=0.031). Average BMI was 29.18. There was a correlation between the presence of MetS and hs-CRP (p=0.02) and no correlation with the pulmonary function. FBS was higher in COPD than controls (8.5±1.2mmol/L vs 5.4±1.1mmol/L) with statistical significance (p<0.0001), but HDL was lower in COPD than controls (42.1±5.4mg/dl vs 53±3.6mg/dl) with statistical significance (p<0.0001). Waist circumference and blood pressure were higher in COPD than controls 93.8s±2.4m vs. 92.3±3.1sm, p=0.004, and mean systolic BP 135±10mmHg vs. 113.5±8.1mmHg, p < 0.0001. Conclusion: The high prevalence of MetS in patients with COPD show the urgent need to develop comprehensive strategies for prevention, screening and start of treatment in early stage. Correction of the MetS may have a significant role in prevention of complications related with the COPD. Olesea Nicu, Ecaterina Stasii State University of Medicine and Pharmacy “Nicolae Testemitanu”, Chisinau, Republic of Moldova nicu.olesea8@gmail.com Background: The psychological factors are becoming increasingly relevant in children with asthma. Many patients report anxiety and depression, which are psychological conditions that have a negative impact on the therapeutic adherence and in order to maintain control of asthma. Objective of the study: Capitalizing on the importance of mental health and assessing the impact of psycho-emotional state on the evolution of bronchial asthma in children. Material and Methods: The descriptive study included 60 children, 10-18 years old, with asthma. All patients completed the specially developed survey, which included clinical data, disease history and life history; Asthma Control Test (ACT), Perceived Stress Scale (SSP) and Questionnaire DASS 21 (which assesses three dimensions: depression, anxiety and stress). Results: According to ACT, uncontrolled asthma was detected in 8 children (13%), partially controlled in 41 children (68.3%), uncontrolled in 11 children (18.3%). According to SSP, 21 children (35%) had moderate stress levels, all with uncontrolled and partially controlled asthma; level of intense stress, had 4 children (6%), all with uncontrolled asthma. According to DASS 21, moderate level of anxiety had 23 children (38%), moderate level of depression - 18 children (30%), moderate level of stress 7 children (11.6%); all with uncontrolled and partially controlled asthma, but also with a moderate level of stress perception. From the group with controlled asthma, moderate level of anxiety was in 8 children (13.3%). Severe levels were not reported. Conclusion: Psycho-emotional profile play a significant role on the asthma control level. Understanding the importance of the mental health can lead to elaboration of the interventions in this field that well increase the level of asthma control, and decrease anxiety and stress level. Snežana Cvetkovic1 , Ljudmila Nagorni–Obradovic1,2, Tatjana Vujic1, Dajana Trifunovic1, Aleksandra Todorovic1, Ana Samardžic1 1Clinic for Pulmonary Diseases, Clinical Center Serbia, Belgrade, Serbia 2School of Medicine, University of Belgrade, Belgrade, Serbia cvetkovicsnezana70@gmail.com Introduction: Dissemination of tuberculous bacilli from the primary hearth can occur in persons with poor immune defenses, in poor socio-economic and hygienic conditions, in social shelters… Case report: Patient male 23 years old, migrant from Pakistan, accommodated at Obrenovac Reception and Transit Center with cough problems with difficulty coughing, shortness of breath, shortness of breath and abdominal pain. Initially examined at the Emergency Center, native radiography done and abdominal ultrasound-finding neat. Chest radiography revealed a spotty inhomogeneous shading in the upper pulmonary fields and the tips of the lungs. Positive inflammatory syndrome, serological analyzes (HIV, HbsAg, HCV) negative. Direct microscopy sputum M negative. Done bronchological examination, endoscopic findings neat, signs of mild inflammation .PCR fiberaspirata-detected Mycobacterium tuberculosis complex. MGIT fibeaspirata-observed acid-alcohol resistant bacilli severe abdominal pain occurs, with several hydroaeric levels observed on native abdominal radiography. Abdominal ultrasound shows distended intestinal curves up to 3.5 cm filled with content of slow peristalsis. Due to ileus emergency surgery performed, pathohistological finding: Inflamacio chr granulomatosa. Continued treatment with antituberculostatics. The patient recovered successfully, K sputum negative. Conclusion: Tuberculosis is a curable disease. The key to success in treatment is early diagnosis and timely treatment. Maria Gotovska, Simona Slacek, Risto Krechev, Štefan Horvat General Hospital Murska Sobota, Murska Sobota, Slovenia gotovskam@yahoo.com Introduction:Tuberculous pericarditis is a serious form of extrapulmonary tuberculosis. The diagnosis can be difficult to establish and is often delayed or missed, resulting in late complications such as constrictive pericarditis and increased mortality. Case Report: A 53 year old man, with hyperlipidemia present with a 10 days history of shortness of breath, chest pain, palpitation was admitted to hospital. The patient was in good condition, with a temperature of 37,8°C, his blood pressure was 170/100 mmHg, pulse 170 beats/min and oxygen saturation 94%. The findings of chest radiogram showed normal lungs and enlarged heart. The heart rhythm was irregular. The patient’s hemoglobin level was 137g/l, WBC count was 6,5x109/l, CRP was 10 mg/l. The findings of blood chemistry tests, tumor markers, troponin, pBNP were normal. An ECHO cardiogram revealed a small pericardial effusion without right ventricular collapse. CT chest scan showed a small pericardial effusion, 13mm calcified lymph node in aortopulmonary window, some subpleural nodules < 5 mm, without pleural effusion. Multiplex PCR respiratory panel test and microbiological tests of intestinal infections were negative. Serology tests of hepatitis, HIV, Chlamydia, Legionella, Mycoplasma, Borrelia, EBV (IgM), CMV(IgG,IgM) were also negative. Immunoserology tests (ANA, ENA, abti DNA) were negative too. The result of the QuantiFERON-TB test was positive. The pericardial fluid had a WBC count of 0,9x109/l (97% lymphocytes and 3% neutrophils), proteins 51g/l, glucose 0,4 mmol/l. Pericardial fluid and 3 sputum specimens were AFB negative. 2 sputum cultures were contaminated and 1 was negative (repeated sputum cultures are in progress). Culture of pericardial fluid became positive on the 23rd day. Treatment: Isoniazid, rifampicin, ethambutol and pyrazinamide. The patient is under control by a cardiologist and pulmonologist. Conclusion: The clinical manifestations of tuberculous pericarditis can be nonspecific. The diagnosis is established by detection of tubercle bacilli in smear or culture of pericardial fluid or by detection of tubercle bacilli or caseating granulomata on histological examination of the pericardium. Options for management of advanced disease are limited. Ljudmila Nagorni-Obradovic1,2, Tatjana Vujic2, Snežana Cvetkovic2, Ana Samardžic2 1School of Medicine, University of Belgrade, Belgrade, Serbia 2Clinic for Pulmonary Diseases, Clinical Center Serbia, Belgrade, Serbia ljudmila.nagorni.kcs@gmail.com In this report we described case a 64-year-old non-smoking patient who had cough and exhaustion for 8 years. Because of these symptoms she was examined as outpatient and bronchoscopy was done, three times in the following period, but investigation did not explain the cause of the disease. The symptoms persisted in varying degrees of intensity, and she was taking symptomatic therapy without doctors controlees. After 8 years existence of symptoms CT thorax showed an excavated change to the right, and the Quantiferon TB GOLD test was positive. Tuberculostatics were started but after one month were discontinued as toxic hepatitis occurred. Then first time hospital examination performed with detail analyzes. The existence of malignant, systemic disease and pulmonary tuberculosis was excluded. But this time fiberaspirate is documented the existence of respiratory infection caused by non-tuberculous mycobacteriosis (NTM). Identification of mycobacterial culture was done by hybridization reaction (Geno Type Mycobacterium CM-Hain analysis): Mycobacterium abscessus. Published studies worldwide indicate that the number of people suffering from diseases caused by NTM is on the rise. The greater isolation of pathogens today is also due to the availability of molecular techniques for their identification. The disease can affect the lungs, eye, CNS, skin and soft issues. Therapy is complicated by the causative agent's resistance to antimicrobials. They are urgently needed quick and inexpensive methods of identification also preventive measures of the spread of infection. It is also necessary to identify more active treatments and perform clinical trials to assess standard effective regimens. Slacek Kovšca Simona1, Maria Gotovska1, Risto Krechev1, Nadja Triller2 1Pulmonary Department, General Hospital Murska Sobota, Murska Sobota, Slovenia 2Health Center Murska Sobota, Murska Sobota, Slovenia simona.slacek@gmail.com Introduction: Tuberculous pleural effusion (TPE) is one of the most common sites of extrapulmonary tuberculosis. Diagnosis is challenging. The gold standard for diagnosis of TPE remains the detection of Mycobacterium tuberculosis in pleural fluid, or pleural biopsy specimens, either by microscopy and/or culture, or the histological demonstration of caseating granulomas in the pleura along with acid fast bacilli (AFB). The following case illustrates the clinical presentation and diagnostic approach to TPE in a case of a young man who was sent to hospital for a large pleural effusion and suspected empyema. Case report: A 32-year- old man without chronic illness presented to clinic with a 10 days history of fever up to 38.9° C, right- sided pleuritic chest pain and cough with productive green sputum. An antibiotic amoxicillin was prescribed ten days before hospital admission. After antibiotic therapy he became subfebrile and the chest pain was gone. He additionally complained of loss of appetite and general weakness. He smoked last 7 years and drink alcohol occasionally. He had no known past exposures to tuberculosis. He had not traveled in the past few years. He works as a painter his entire life. At hospital admission the patient was subfebrile (37.6° C), with normal blood pressure and normal heart rate. The saturation was 94% while breathing room air. Physical examination revealed dullness to percussion and decreased breath sounds throughout his right hemithorax. Basic laboratory tests were normal with the exception of elevated level of CRP (130 mg/l). A chest radiograph revealed a large right sided pleural effusion with a gentle small infiltrate in the apex of the right upper lobe. A CT of the chest revealed parenhymal disease – 2 cm large nodular, partialiy calcined irregular infiltrate in the apex of right upper lobe, right sided pleural effusion with septations, thickened pleura and reactive lymph nodes in the mediastinum. Thoracentesis removed 1750 ml of straw coloured fluid that had 1000 white blood cells/ µl (91% lymphocytes, 1% mesothelial cells, 2% neutrophils and 6% monohistiocytes). The glucose was 3 mmol/l, total potein 52 g/l, LDH 12,44 µkat/l, pH 7.31. Serum total protein was 76 g/l and serum LDH was 2,01 µkat/l. Expectorated sputum revealed 3 negative stains for AFB and cultures were also negative for AFB after six weeks of incubation. Sputum and pleural fluid Gram stain and culture were negative. Two weeks after thoracentesis 3 colonies of Mycobacterium tuberculosis grew in the culture of the pleural fluid, so no further investigations were necessary. Conclusions: 48-96% of TPE is negative by sputum acid-fast bacilli (AFB) stain and culture. Thoracentesis is the next step to distinguish among malignant, tuberculous, parapneumonic pleural effusion and empyema. Thoracentesis in TPE shows an exudative, lymphocytic pleural effusion in more than 90% of cases, but pleural fluid AFB cultures are positive in less than 20-30% of cases. More invasive diagnostic measures (closed percutaneous needle biopsy or thoracoscopy) are usually required to confirm TPE. Manca Lavtižar, Janez Toni, Petra Svetina University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia manca.lavtizar@klinika-golnik.si Introduction: Treatment of NTM- MD is long-term and relapse may occure. The new BTS guidelines for management of NTM - PD define the regimens and duration of treatment more accurately and take into account the resistance of non-tuberculous mycobacteria and the difficulty of the clinical presentation. Nebulised amikacin may be considered in many cases. Methods: We occluded patients with NTM-PD, who were treated with nebulised amikacin for the past two years. Results: 9 people (8 women, 1 man) were treated with nebulised amikacin. The mean age was 62.8 years. Most of them had pre-existing lung disease, the bronchiectasis are being the most commonly reported (77.8%). Most frequently, M.avium was isolated (66.7%), besides this M.abscessus, M. intracellulare, M.kansasii and M.chimaera. 8 patients were treated with rifampicin, ethambutol, clarithromycin and 1 patient with tigecycline and clarithromycin. In addition, all patients received nebulised amikacin, two started with the intravenous amikacin and then continued with the nebulised amikacin, and in one patient switched from the nebulised to the intravenous amikacin. 8 patients (88.9%) reported side effects, 7 patients (77.8%) experienced hoarseness and 1 patient experienced worsening asthma. In 2 patients, nebulised amikacin was previously discontinued due to side effects. 8 patients had a negative outcome of culturing at the end of amikacin treatment, and 1 patient is still positive. Discussion: According to BTS guidelines, treatment with nebulised amikacin for severe M. avium complex -pulmonary disease (MAC-PD), including M.avium, M.intracellulare and M. chimaera, and for M.abscessus-PD, is recommended. Systemic side effects (ototoxicity) with inhaled amikacin are rare, but respiratory side effects (hoarseness, cough, bronchospasm) are common, as confirmed by our results. The outcome of the cultivation after treatment was negative in 8 patients and for 1 patient we have no negative results so far as he has only been treated for one month. Conclusion: Treatment of NTM-PD is considered very successful, since all patients are negative after completion with nebulised amikacin. However, follow-up because of possibility of relapse is recommended. Eva Sodja1, Simon Koren2, Nataša Toplak2, Manca Žolnir-Dovc1 1University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia 2Omega d.o.o., Ljubljana, Slovenia eva.sodja@klinika-golnik.si Background: Slovenia and North Macedonia are low-incidence countries with tuberculosis (TB) incidence rates of 5.3 and 13.0 in 2018, respectively. In both countries, the percentage of drug resistant TB is very low with sporadic cases of MDR-TB. However, global burden of drug-resistant TB continues to increase stimulating the detection of gene variants related with TB drug resistance. Next-generation sequencing (NGS) can provide comprehensive analysis of gene variants linked to drug resistance in Mycobacterium tuberculosis. The aim of our study was to examine the feasibility of a full-length gene analysis for the drug resistance related genes (inhA, katG, rpoB) using Ion Torrent technology and to compare the NGS results with those obtained from conventional phenotypic drug susceptibility testing (DST) in TB isolates. Methods: Between 1996 and 2017, we retrospectively selected 56 TB strains from our National mycobacterial culture collection. Of those, 33 TB isolates from Slovenian patients were isolated from various clinical samples and subjected to phenotypic DST in Laboratory for Mycobacteria (University Clinic Golnik, Slovenia). The remaining 23 TB isolates were isolated from Macedonian patients and sent to our laboratory for assistance in phenotypic DST. TB strains included were either mono-, poly- or multidrug resistant. For control purposes, we also randomly selected five TB strains susceptible to first-line anti-TB drugs. To identify gene variants related with drug resistance in genomic DNA extracted from TB isolates, AmpliSeq libraries were generated using the AmpliSeq™ Kit for Chef DL8 and the Ion AmpliSeq TB Research Panel. The sequencing data were analysed manually, comparing the determined variants with published data and data available in the Tuberculosis Drug Resistance Database. Results: High concordance between genetic (Ion Torrent technology) and standard phenotypic DST testing for isoniazid and rifampicin was observed, with percent of agreement of 77% and 93.4%, sensitivities of 68.2% and 100%, and specificities of 100% and 88.2%, respectively. In TB strains with phenotypic isoniazid resistance (44) the majority of mutations were detected in katG codon 315 (20/44; 45,5%), while in TB strains with rifampicin resistance (41) the most prevalent mutation detected was rpoB Ser450Leu (17/41; 41,5%). Conclusion: In conclusion, the genotypic DST using Ion Torrent semiconductor NGS successfully predicted drug resistance with significant shortening of time needed to obtain the resistance profiles from several weeks to just a few days. Urška Skamen, Eva Sodja, Manca Žolnir-Dovc Laboratory for Mycobacteria, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia urska.skamen@klinika-golnik.si Background: Without treatment, 5-10 % of people with latent tuberculosis (TB) infection develop active TB at some time in their lives. Patients with compromised immune system, like those with HIV and those receiving anti-TNFa therapy, are especially at risk of developing active TB. It is important to diagnose and treat both active and latent TB with the main goal being the prevention of new outbreaks. The aim of our study is retrospective analysis of QuantiFERON TB (QFT) results in 12-years period in our country. Method: From 2005 we have been identifying latent TB infection with the IFN-. test called QFT TB. It uses collection tubes with specific TB antigens and test controls coated on their inner surface. The QFT method was upgraded over time. At first only two, from 2008 three and from 2015 four blood collection tubes were used. The blood for the test must be collected and transported (at room temperature) to the laboratory in less than 16 hours. After the blood is received, it is incubated for 16-24 h on 37 °C. The following day the amount of released IFN-. is measured by ELISA method. Results: Between 2008 and 2019 the Laboratory for Mycobacteria of University Clinic Golnik received 29293 blood samples for latent TB testing. The share of positive QFT results has decreased from 21,0 % in 2008 to 10,7 % in 2019. The number of indeterminate QFT test results has decreased from 11,3 % to 5,9 % in the first year and has since then stayed in the 2,4 % to 6,7 % range. The proportion of rejected blood samples has remained constant with an average of 1,2 %. Conclusions: Monitoring of QFT test results in the last decade shows that the share of positive latent TB infections is slowly decreasing. This is a consequence of the decrease in the incidence of active TB which has fallen by 46,2 % in the years between 2008 and 2019. In the next few years we may see an increase in the number of active and consequently latent TB cases due to immigration from countries with higher incidence of TB as well as asset re-allocation to battle covid-19 pandemic. Irena Grmek Košnik1, Urška Dermota1, Petra Svetina2, Manca Žolnir-Dovc2 1National Laboratory of Health, Environment and Food, Kranj, Slovenia 2University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia irena.grmek.kosnik@nlzoh.si Background: Skin and soft tissue infections caused by nontuberculous mycobacteria (NTM), especially the rapid growing mycobacteria (RGM), apper to be increasing in incidence. Mycobacterium fortuitum complex have been isolated from soil and various water-related sources, rarely cause infections. These opportunistic pathogens most commonly cause localized skin and soft tissue infections, especially common after breast surgery. Case presentations: In the department of surgery post-operative wound infection of four previously healthy women were detected. In three breast implants were inserted and abdominal operation was performed in the fourth patient. All four patients were operated by the same team in the same operating theatre. The clinical picture was characterized by only localized inflammation of the wounds and the lack of systemic signs of inflammation. Epidemiological investigations: Unfiltered water was sampled from hand-wash tap water in the operating room area, the tap water, the staff shower. Results: M. senegalense, which belongs to M. fortuitum complex was isolated from four patients and from the nozzle of the washbasin in the staff bathroom. Conclusion: This report describes the second laboratory-confirmed cases of M. fortuitum complex breast infections related to the hospital water supply. In most reported cases of RGM infection, the source of contamination is difficult to identify. M. fortuitum complex is resistant to chlorination and is capable of biofilm formation. Colonization of the hospital water supply with pathogens that are relatively resistant to common disinfection protocols is a concern, and eradication of NTMs is difficult. Domen Kulovec, Naneta Legan Kokol, Sara Maraž Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia domen.kulovec@outlook.com Covid-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and can present a wide range of symptoms, ranging from mild to severe respiratory symptoms and even death. 4-12% of all covid-19 patients develop a severe form of the disease, thus it is vital to find new treatments. A literature review was performed and it identified studies indexed in the bibliographic database MEDLINE, published up to the 13th September of 2020. Data from 17 articles was employed. Out of all the treatments, convalescent plasma therapy (CPT) and dexamethasone are possibly the best additional therapies for critically ill patients. CTP is a form of passive immunisation using the blood of recovered patients. Almost all the patients treated with CTP experienced a decrease in symptom severity, including resolution of ARDS, absorption of lung lesions and normalisation of body temperature. CTP may shorten the duration of disease and reduce mortality of critically ill patients. So far, there have been no reports of adverse drug reactions. Risks regarding CTP are mostly associated with transfusion of blood-borne diseases and reactions to serum components. This risk of transfusion-related acute lung injury and antibody-dependent enhancement should be taken into consideration when deciding whether to use CTP, however unlikely these complications are. Dexamethasone is a synthetic corticosteroid, that has been shown to possess anti-inflammatory and immunosuppressive properties. Administration of dexamethasone has been shown to shorten the duration of hospitalisation, when compared to the control group. Additionally, it reduced the mortality of patients receiving invasive mechanical ventilation by 12,1 % and of patients receiving oxygen support without invasive mechanical ventilation by 2,9%. Dexamethasone did not prove to be useful for treating patients without oxygen therapy. Patients reported no serious adverse drug reactions. SARS-CoV-2 pandemic poses new challenges for the treatment of the critically ill, due to the severity of the disease it causes and the sheer number of patients. New approaches will hopefully decrease the fatality of covid-19 and help sustain the operating state of healthcare systems. Uporaba gojenih alogenskih mezenhimskih maticnih/ stromalnih celic (MSC) za zdravljenje Akutnega respiratornega distresnega sindroma (ARDS) ter brazgotinjenja pljuc zaradi virusa SARS-Cov 2 Lenart Girandon, Ema Randl, Gregor Cuzak, Ariana Barlic, Matija Veber, Miomir Kneževic Educell podjetje za celicno biologijo d.o.o., Trzin, Slovenia lenart.girandon@educell.si MSC v zadnjem casu dobivajo vse vec pozornosti zaradi njihove mocne sposobnosti uravnavanja imunskega sistema in protivnetnega delovanja, kar je bilo dokazano na razlicnih medicinskih indikacijah. Imunomodulacija, ki jo povzrocijo MSC, ni odvisna od poglavitnega histokompatibilnega kompleksa (MHC), ni odvisna od specificnega antigena in vkljucuje vse imunske celice. Kar dodatno govori v prid zdravljenju z MSC sta dejstvi, da se MSC iz krvi primarno prefiltrirajo skozi pljuca (cca v 48h so vsi MSC v pljucih) ter dejstvo, da MSC uravnavajo vnetje preko širokega spektra citokinov in rastnih faktorjev (kar ni zanemarljivo predvsem zaradi tega, ker tudi virus vnetje stimulira preko široke palete citokinov). Poleg imunomodulacije mezenhimske maticne/stromalne celice tudi zmanjšujejo nastanek fibroze, kar je prav tako velika težava pri hudih oblikah covida-19, tudi pri prebolevnikih. Spodbudni rezultati o zdravljenju hudih oblik covida-19 z MSC so prišli kmalu po zacetku epidemije iz Kitajske. V preliminarni klinicni študiji intravenske aplikacije alogenskih MSC (1x106 MSC/kg pacientove teže) je bilo vkljucenih 7 pacientov (45 – 75 let). Pljucna funkcija in bolezenski simptomi so se mocno izboljšali v 2 dneh po administraciji MSC. Vecina MSC se akumulirajo v pljucih, kar izboljša pljucno mikrookolje, ustavlja pretiran imunski odziv, šcitijo epitelne celice pljucnih mešickov spodbujajo popravilo tkiv, zmanjšujejo pljucno fibrozo in izboljšujejo pljucno funkcijo. Infuzija MSC je pri pacientih sistemsko mocno zmanjšalo vnetje. Koncentracije pro-inflamatornih citokinov v serumu so se mocno zmanjšale. Za zdravljenje covida-19 se testira mnogo pristopov, MSC pa kažejo veliko uporabnost za zdravljenje covida-19. V septembru 2020 je bilo na platformi ClinicalTrials.gov registriranih 42 klinicnih študij, ki raziskujejo potencial MSC za zdravljenje covida-19. Poleg tega tudi vecja podjetja, aktivna na podrocju celicnih terapij, objavljajo zacetke študij in pozitivne rezultate (Athersys Inc., Mesoblast Ltd., Pluristem Therapeutics Inc., itd.) Maja Badovinac, David Lestan, Matevž Harlander, Matjaž Turel, Marjeta Tercelj Department of Pulmonary Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia maja.badovinac@kclj.si Background: Tracheobronchial foreign body (FB) aspiration in adults is an uncommon but potentially life-threatening event. It usually presents as choking, followed by cough and dyspnoea. However, these findings are inconsistent and may mimic chronic lung diseases, atelectasis or pneumonia. Bronchoscopy remains the gold standard for diagnosis and management of FB aspiration. We present our experience of dealing with various types of FB aspiration in airways of adult patients with focus on bronchoscopic techniques and potential complications of FB extraction and late consequences on the tracheobronchial tree. Methods: Analysis of patients between 2000 and 2020 admitted to our department for FB removal from airways was performed. Patients underwent local or general anaesthesia. Flexible bronchoscopy with forceps, snares, basket or flexible cryoprobe was used. Results: 39 patients were admitted with an average age 59.8 year. Nine patients had a clinical picture of acute FB aspiration, while others had signs and symptoms such as atelectasis, pneumonia, chronic cough. One third of patients had general anesthesia while the rest had local anaesthesia with flexible bronchoscope. Discovered FBs were hazelnuts, grape seed, speaking apparatus, bone, tumour, teeth, cherry pawn, stone, peanut, garlic, stent fibres, petiole, corn, coagulated aspirated blood, mucus aspiration and pills. Two had lobar atelectasis after intubation. Two had massive hemoptysis with acute respiratory insufficiency. Massive blood coagula were successfully removed with cryoprobe. Mortality rate due to FB aspiration and intervention itself was zero. Conclusion: FB aspiration still accounts for about 1 in 400 bronchoscopic procedures. This makes it difficult for an individual to develop adequate experiences for successful FB extraction. An experienced team including bronchoscopist, bronchoscopy assistants, nurse, and anesthesiologist are required for successful extraction of airway FB. The vast majority of FBs can be extracted safely with flexible bronchoscopy and the use of forceps, baskets and cryoprobe. M. Dišic, M. Smodiš Community health center, Murska Sobota, Slovenia mitja.disic@zd-ms.si Background: It is well documented that pulmonary rehabilitation program (PRP) including physical activity improves physical abilities and fitness to all patients. Exercise training of patients with severe chronic obstructive pulmonary disease (COPD) should be individualized with regard to their limitations. The benefits of such rehabilitation are greater control, prolonged monitoring and better outcome of treatment. Methods: Two patients with a similar stage of the disease, but very different in terms of body composition and abilities were included into individualized PRP with respiratory physiotherapy and exercise program for improving strength, flexibility and cardiovascular endurance (compiled by the master of kinesiology). Patient 1: 66 old man with COPD D on long-term oxygen therapy (LTOT) was normally nourished. The patient's limitation were breathlessness and poor cardiovascular endurance. Patient 2: 65 old man with COPD D on LTOT, with a first degree obesity. The patient's limitation was severe COPD disease and obesity, which consequently limits activities of daily living and health enhancing physical activity. Once per week strength exercises were repeated under supervision and perform an endurance (cardiovascular) training. Physical fitness and cardiovascular endurance were tested at the beginning of rehabilitation and after two months: Grip strength test, 30 s sit to stand test and 30 s biceps curl test. Results: Case 1 Case 2 T1 Grip strength (dynamometer) 24 kg 35 kg Sit to stand test 30s 6 8 (stopped at 24s) Biceps curl 30 s 5 14 T2 (two months later) Grip strength test (dynamometer) 27 kg 36 kg Sit to stand test 30s 5 9 Biceps curl 30 s 7 16 Conclusion: Pulmonary rehabilitation program in patients with severe COPD on longterm oxygen therapy has to be individualized, under careful control and continuous monitoring. Matevž Harlander1,2, David Lestan1, Matjaž Turel1, Mojca Drnovšek Globokar3, Suada Filekovic Ribaric3, Michael Gradišek3, Boris Greif4, Tomaž Štupnik4 1Department of Pulmonary Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia 2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 3Department of Anaesthesiology and Surgical Intensive Therapy, University Medical Centre Ljubljana, Ljubljana, Slovenia 4Department of Thoracic Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia matevz.harlander@gmail.com Introduction: Lung transplantation is a highly complex method of treatment for selected patients with terminal lung disease. With the increase of the number of eligible candidates and the standardization of the method, it was possible to set up a transplantation centre in University Medical Centre (UMC) Ljubljana in 2018. We report our initial experience. Methods: Analysis of internal registry of patients with lung transplantation was done. Patient’s characteristics were compared to the previous group that was referred to AKH Vienna for lung transplantation. Results: From 15.9.2018 to 15.3.2020 there were 13 lung transplantations (4 females) done in UMC Ljubljana. Indications were COPD (n = 6 [46.2 %]), cystic fibrosis (n = 3 [23.1 %]), idiopathic pulmonary fibrosis (n = 2 [15.4 %]), bronchiectasis (n = 1 [7.7 %]) and lymphangioleiomyomatosis (n = 1 [7.7 %]). Compared to previous cohort referred for transplantation to AKH Vienna (71 patients, 35 females), there was a tendency towards higher proportion of patients with COPD (p = 0.080) and the patients were older (median [Q1 - Q3], 58 [33 - 60] vs. 42 [23 - 58] years, p = 0.052). Only one patient died during the first 90 days post-transplantation, yielding 92.3 % 90-days survival, which is similar to survival of the cohort referred to AKH Vienna (94.4 % 90-days survival). Conclusions: Initial results show comparable early lung transplantation success rate as noted in a previous cohort of patients referred to AKH. Ljiljana Ledina, Mirko Lekic Hospital Topolšica, Topolšica, Slovenia ljiljanaledina@yahoo.com Treatment with positive pressure (CPAP) is the most effective way to treat sleep apnoea. It successfully eliminates breathing pauses, hypoxia and night unrest. It diminishes cardiovascular risk and proneness to work-related and traffic injuries. Even so, it was noted that a quarter of patients do not use their PAP treatment regularly, long enough or at all. Aim: to determine why there is a low compliance to CPAP treatment. We contacted all patients who did not use at all or properly their CPAP and considered the reasons for abandoning therapy. We analyzed 208 patients (195 male, 37 female) independently of AHI/ODI, 65 abandoned treatment, 52 male, 13 female. According to daytime sleepiness and naps during work or driving, they were divided in: a. Symptomatic, 18 abandoned (16 men 2 women) b. Asymptomatic, 47 abandoned, (36 men, 11 women) 1. immediate abandonment, did not even agree to CPAP, (6a+15b) These feared suffocation, had claustrophobia, uncomfortable mask, convicted there was an easier way (internet), wish to be operated on, and poor understanding from the patient or surroundings. 2. early abandonment after the first control, 2 to 3 months of treatment, (4a+10b). They were convinced there was an easier way (internet) dry and swollen nose mucosa, conjunctivitis, ill-fitting masks. 3. late abandonment a year or more after beginning therapy, (5a+14b) Aesthetic reasons, believing there was an easier way (internet), dry, swollen nose mucosa, conjunctivitis, ill-fitting masks, desire for surgery 4. irregular usage of more than 70% of the night, less than 4 hours of continuous use during the night,(2a+9b).The reasons were work in shifts or outdoors, uncomfortable mask, belief that all night PAP is useless. Conclusion: the reasons for rejecting and abandonment of CPAP treatment are bad mask choice, claustrophobia, belief that there is no problem, aesthetics, partner’s bad co-operation, work in shifts or outdoors, bad internet information or desire for surgery. The percentage of women abandoning treatment in every category is higher than for men. Abandonment of CPAP treatment during sleep is connected to a subjective feeling of drowsiness during daytime. Suggestion: 2 masks to be issued at the same time, as by patients’ choice. Alternate use would increase compliance. Suvad Dedic, Dženan Halilovic, Edin Jusufovic Klinika za plucne bolesti UKC Tuzla, Tuzla, Bosnia and Herzegovina dedicsuvad@gmail.com Introduction: Air pollution is the largest health risk in the world. Today, 92% of the world's population inhales polluted air. More than 7 million people (WHO) die annually from the effects of polluted air in the world. Air pollution is primarily responsible for increasing the prevalence of respiratory and cardiovascular diseases. Of particular importance are gases: Ozone, Carbon monoxide, Nitrogen dioxide, Sulfur dioxide and particulate matter PM 2.5, PM 10. Studies by the European Health Risk Agency and WHO are consistent and confirm that air pollution has a significant negative impact on health and development asthma. Research objective: To evaluate the impact of harmful gases and dust particles on the increase of acute exacerbations of asthma. Material and Methods: The following parameters of the measurement stations of the Ministry of Physical Planning and Environment were used: PM 2,5, SO2, NO2, CO2 and O3. All hospitalized patientes with asthma exacerbations during one year. Results: An increased percentage of acute asthma exacerbations and hospitalizations were observed in months when concentrations of particulate matter and gas were increased beyond the allowable values. Conclusion: The concentration of pollutant pollutants and exposure lengths have a significant effect on asthma exacerbations and an increased percentage of hospitalizations. David Ravnik, Sandra Martinuc Faculty of Health Sciences, University of Primorska, Izola, Slovenia david.ravnik@fvz.upr.si Introduction: Respiration is a natural process, a function controlled by the central nervous system. Breathing movements influence not only the basic metabolic processes, but also our posture or the mobility of the spine itself. Correct breathing is also a prerequisite for the physiological stabilization of the spine and vice versa. Depending on our lifestyle, we begin to influence and restrict these breathing movements through our inappropriate motor habits. As our posture deteriorates, we also change our breathing. Methods: By reviewing the literature, we aim to highlight both directional causality and the relationship between the biomechanics of breathing and the biomechanics of posture, and to emphasize the techniques of their evaluation. Results: Poor posture affects the breathing, which is limited, shallow and natural can cause many other problems with breathing, such as chest stiffness and chest inspiration, congestion of each area of the spine (from neck to sacrum, most thoracic transition), Problems in the abdominal cavity, insufficient involvement of muscles and muscle imbalance, disorders of fixation of the upper and lower chest, improper use or a high diaphragm, impaired functioning of internal organs and glands, etc ... Discussion and conclusion: Respiration is usually analyzed in terms of respiratory measurements and vital functions, and too little attention is paid to postural function. Both respiratory and motor diagnostics and therapy must include both components - the influence of breathing on posture and the influence of posture on breathing. The latter can be achieved by combining respiratory therapy, manual therapy and kinesiotherapy. Z ZDRAVILOM FASENRA DO NICLE NIC POSLABŠANJ pri 74 % bolnikov v 2. letu zdravljenja v 56-tedenski raziskavi varnosti ob podaljšanem zdravljenjuą* OGK NIC pri 52 % ustreznih bolnikov v primerjavi z 19 % bolnikov ob placebu˛** EOZINOFILCEV NIC v krvi (mediana) po 1. dnevuł *BORA: Bolniki iz predhodnih raziskav (SIROCCO in CALIMA), ki so med 56-tedenskim ocenjevalnim obdobjem še naprej prejemali zdravilo na vsakih 8 tednov. Ob izhodišcu so imeli bolniki število eozinofilcev v krvi = 300 celic/µl **ZONDA: Bolniki z izhodišcnim odmerkom OGK = 12,5 mg so opustili uporabo teh zdravil (p = 0,002). Ob izhodišcu so imeli bolniki število eozinofilcev v krvi = 150 celic/µl SKRAJŠAN POVZETEK GLAVNIH ZNACILNOSTI ZDRAVILA Za to zdravilo se izvaja dodatno spremljanje varnosti. Tako bodo hitreje na voljo nove informacije o njegovi varnosti. Zdravstvene delavce naprošamo, da porocajo o katerem koli domnevnem neželenem ucinku zdravila. Fasenra 30 mg raztopina za injiciranje v napolnjeni injekcijski brizgi Fasenra 30 mg raztopina za injiciranje v napolnjenem injekcijskem peresniku SESTAVA: Ena napolnjena injekcijska brizga vsebuje 30 mg benralizumaba v 1 ml. En napolnjen injekcijski peresnik vsebuje 30 mg benralizumaba v 1 ml. Benralizumab je humanizirano monoklonsko protitelo, pridobljeno v celicah jajcnika kitajskega hrcka s tehnologijo rekombinantne DNA. INDIKACIJE: Zdravilo Fasenra je indicirano kot dodatno vzdrževalno zdravljenje za odrasle bolnike s hudo eozinofilno astmo, ki ni ustrezno urejena kljub velikim odmerkom inhalacijskih kortikosteroidov in dolgodelujocih agonistov ß. ODMERJANJE IN NACIN UPORABE: Zdravljenje z zdravilom Fasenra mora uvesti zdravnik, ki ima izkušnje z diagnosticiranjem in zdravljenjem hude astme. Samoinjiciranje pride v poštev le pri bolnikih, ki že imajo izkušnje z zdravljenjem z zdravilom Fasenra. Priporoceni odmerek je 30 mg v subkutani injekciji na 4 tedne prve 3 odmerke, pozneje pa na 8 tednov. Starejšim bolnikom, bolnikom z okvaro ledvic ali jeter odmerka ni treba prilagoditi. Varnost in ucinkovitost zdravila Fasenra pri otrocih, starih od 6 do 18 let, nista bili dokazani. Zdravilo Fasenra se uporablja kot subkutana injekcija. Zdravilo je treba injicirati v stegno ali trebuh. Ce da injekcijo zdravnik ali skrbnik, lahko uporabi tudi nadlaket. KONTRAINDIKACIJE: Preobcutljivost za zdravilno ucinkovino ali katerokoli pomožno snov. POSEBNA OPOZORILA IN PREVIDNOSTNI UKREPI: Zdravila Fasenra se ne sme uporabljati za zdravljenje akutnih poslabšanj astme. Ce je primerno zmanjšanje odmerkov kortikosteroida, mora biti zmanjšanje postopno in mora potekati pod nadzorom zdravnika. Preobcutljivostne reakcije: po uporabi benralizumaba so se pojavile akutne sistemske reakcije, vkljucno z anafilakticnimi reakcijami in preobcutljivostnimi reakcijami (npr. urtikarija, papularna urtikarija, izpušcaj). Te reakcije se lahko pojavijo v nekaj urah po uporabi, a v nekaterih primerih se pojavijo v nekaj dneh. Anamneza anafilaksije, nepovezane z benralizumabom, je lahko dejavnik tveganja za anafilaksijo po uporabi zdravila Fasenra. V skladu s klinicno prakso je treba bolnike po uporabi zdravila Fasenra ustrezen cas spremljati. V primeru preobcutljivostne reakcije je treba zdravilo Fasenra trajno prenehati uporabljati in uvesti ustrezno zdravljenje. Parazitske okužbe (okužbe s helminti): Eozinofilci so lahko vpleteni v imunski odziv na nekatere okužbe s helminti. Bolniki, ki so imeli znano okužbo s helminti, niso bili vkljuceni v klinicna preskušanja. Bolnike z obstojecimi okužbami s helminti je treba zdraviti pred uvedbo zdravljenja z zdravilom Fasenra. Ce se bolnik okuži med zdravljenjem z zdravilom Fasenra in se ne odzove na zdravljenje z antihelmintiki, je treba zdravljenje z zdravilom Fasenra prekiniti, dokler okužba ne mine. MEDSEBOJNO DELOVANJE Z DRUGIMI ZDRAVILI: Randomizirana, dvojno slepa študija vzporednih skupin, ki je zajela 103 bolnike s hudo astmo, stare od 12 do 21 let, ni pokazala, da bi zdravljenje z benralizumabom neugodno vplivalo na odzive humoralnih protiteles, ki jih povzroci cepljenje proti sezonskim virusom influence. Vpliva benralizumaba na farmakokinetiko socasno uporabljenih zdravil ni pricakovati. Encimi citokroma P450, mehanizmi iztocne crpalke in mehanizmi vezave na beljakovine niso vkljuceni v ocistek benralizumaba. O izraženosti IL-5Ra na jetrnih celicah ni dokazov. Izguba eozinofilcev ne povzroci kronicnih sistemskih sprememb vnetnih citokinov. NEŽELENI UCINKI: Najpogosteje opisana neželena ucinka med zdravljenjem sta glavobol (8 %) in faringitis (3 %). Porocali so o anafilakticnih reakcijah. V klinicnih študijah je benralizumab v obdobju od 48 do 56 tednov prejemalo skupno 2514 bolnikov, od katerih jih je 1663 imelo hudo, neurejeno eozinofilno astmo. Pogosti neželeni ucinki: faringitis (opredeljen z naslednjimi združenimi prednostnimi izrazi: faringitis, bakterijski faringitis, virusni faringitis in streptokokni faringitis), preobcutljivostne reakcije (opredeljene z naslednjimi združenimi prednostnimi izrazi: urtikarija, papularna urtikarija in izpušcaj), glavobol, zvišana telesna temperatura in reakcija na mestu injiciranja. Anafilakticne reakcije so porocane z neznano pogostnostjo. V podaljšanem preskušanju bolnikov z astmo o dolgorocni varnosti zdravila Fasenra je bil porocan profil neželenih ucinkov podoben kot v predhodnih preskušanjih. POSEBNA NAVODILA ZA SHRANJEVANJE: Shranjujte v hladilniku (2 °C do 8 °C). Zdravilo Fasenra je lahko shranjeno na sobni temperaturi do 25 °C najvec 14 dni. Ko zdravilo Fasenra vzamete iz hladilnika, ga je treba uporabiti v 14 dneh ali ga zavreci. Napolnjeno injekcijsko brizgo/napolnjen injekcijski peresnik (Fasenra Pen) shranjujte v originalni ovojnini za zagotovitev zašcite pred svetlobo. Ne zamrzujte. Ne pretresajte. Ne izpostavljajte vrocini. VRSTA IN VSEBINA OVOJNINE: Napolnjena injekcijska brizga: En mililiter raztopine v napolnjeni injekcijski brizgi za enkratno uporabo iz stekla tipa I, z namešceno 1/2-colsko iglo debeline 29 G iz nerjavnega jekla, s togim šcitnikom igle in s Fluorotecom prekritim cepom bata v pasivni varnostni napravi. Pakiranje vsebuje 1 napolnjeno injekcijsko brizgo za enkratno uporabo. Napolnjen injekcijski peresnik (Fasenra Pen): En mililiter raztopine v sterilnem napolnjenem injekcijskem peresniku za enkratno uporabo iz stekla tipa I, z namešceno 1/2-colsko iglo debeline 29 G iz nerjavnega jekla, s togim šcitnikom igle in s Fluorotecom prekritim cepom bata v napolnjenem injekcijskem peresniku. Pakiranje vsebuje 1 napolnjen injekcijski peresnik za enkratno uporabo (Fasenra Pen). NACIN IZDAJANJA ZDRAVILA: Rp/Spec - Predpisovanje in izdaja zdravila je le na recept zdravnika specialista ustreznega podrocja medicine ali od njega pooblašcenega zdravnika. DATUM REVIZIJE BESEDILA: junij 2019 (SI-0682). IMETNIK DOVOLJENJA ZA PROMET: AstraZeneca AB, S-151 85, Sodertalje, Švedska. Pred predpisovanjem, prosimo, preberite celoten povzetek glavnih znacilnosti zdravila. Dodatne informacije so na voljo pri družbi AstraZeneca UK Limited, Podružnica v Sloveniji, Verovškova 55, Ljubljana. REFERENCE: 1. Busse WW, et al. Lancet Respir Med. 2019;7(1):46-59. doi: 10.1016/S2213-2600(18)30406-5.9. 2. Nair P, et al. N Engl J Med. 2017; 376:2448-58. doi:10.1056/NEJMoa1703501. 3. Laviolette M, et al. J Allergy Clin Immunol. 2013;132:1086-1096. doi:10.1016/j.jaci.2013.05.020. Dodatne informacije so na voljo pri družbi AstraZeneca UK Limited, Podružnica v Sloveniji, Verovškova 55, 1000 Ljubljana, t. 01/51 35 600 Samo za strokovno javnost. Informacija pripravljena: junij 2020 SI – 0961 PRELOMNICA V ZDRAVLJENJU Mediana OS 38,6 m V PRIMERJAVI Z 31,8 m Zdravilo Tagrisso v primerjavi z gefitinibom/erlotinibom Skrajšan povzetek glavnih značilnosti zdravila Za to zdravilo se izvaja dodatno spremljanje varnosti. Tako bodo hitreje na voljo nove informacije o njegovi varnosti. Zdravstvene delavce naprošamo, da poročajo o katerem koli domnevnem ne.elenem učinku zdravila. TAGRISSO 40 mg filmsko oblo.ene tablete / TAGRISSO 80 mg filmsko oblo.ene tablete SESTAVA: Ena filmsko oblo.ena tableta vsebuje 40 ali 80 mg osimertiniba. INDIKACIJE: Zdravilo Tagrisso je kot monoterapija indicirano za prvo linijo zdravljenja odraslih bolnikov z lokalno napredovalim ali metastatskim nedrobnoceličnim rakom pljuč, katerega receptor za epidermalni rastni faktor ima aktivirajoče mutacije in za zdravljenje odraslih bolnikov z lokalno napredovalim ali metastatskim NSCLC, pozitivnim za mutacijo T790M EGFR. ODMERJANJE IN NAČIN UPORABE: Zdravljenje z zdravilom Tagrisso mora uvesti zdravnik, ki ima izkušnje z zdravili za zdravljenje raka. Pri odločanju o uporabi zdravila Tagrisso je treba določiti stanje mutacije EGFR v vzorcih tumorja ali plazme z uporabo validirane testne metode. Priporočeni odmerek je 80 mg osimertiniba enkrat na dan do napredovanja bolezni ali nesprejemljivih toksičnih učinkov. Zdravilo Tagrisso je mogoče vzeti s hrano ali brez nje, vsak dan ob istem času. Glede na varnost in prenašanje pri posameznem bolniku je lahko potrebna prekinitev odmerjanja in/ali zmanjšanje odmerka. V primeru potrebe po zmanjšanju odmerka je treba odmerek zmanjšati na 40 mg enkrat na dan. Bolnikom, ki po zmanjšanju odmerka zdravila ne prenesejo, je treba osimertinib ukiniti in razmisliti o drugačni terapiji. Bolnikom z blago ali zmerno okvaro jeter odmerka ni treba prilagoditi, vendar je treba zdravilo Tagrisso pri teh bolnikih uporabljati previdno. Na podlagi kliničnih študij in populacijske farmakokinetične analize prilagajanje odmerka ni potrebno pri bolnikih z blago ali z zmerno okvaro jeter. Varnost in učinkovitost zdravila nista ugotovljeni pri bolnikih s hudo okvaro jeter. Na podlagi kliničnih študij in populacijske farmakokinetične analize bolnikom z blago, zmerno ali hudo okvaro ledvic odmerka ni treba prilagoditi. Varnost in učinkovitost tega zdravila nista ugotovljeni pri bolnikih s končno odpovedjo ledvic (očistek kreatinina manj kot 15 ml/min, izračunan po Cockroft-Gaultovi enačbi) in pri bolnikih na dializi. Pri zdravljenju bolnikov s hudo okvaro ledvic in končno odpovedjo ledvic je potrebna previdnost. KONTRAINDIKACIJE: Preobčutljivost za zdravilno učinkovino ali katerokoli pomo.no snov. Šentjan.evke se ne sme uporabljati skupaj z zdravilom Tagrisso. OPOZORILA IN PREVIDNOSTNI UKREPI: Pri odločanju o uporabi zdravila Tagrisso za zdravljenje lokalno napredovalega ali metastatskega NSCLC je pomembno določiti stanje mutacije T790M EGFR. Opraviti je treba validirano preiskavo tumorske DNK, dobljene iz vzorca tkiva, ali tumorske DNK v obtoku (ctDNA – circulating tumor DNA), dobljene iz vzorca plazme. Določitev prisotne mutacije T790M v vzorcu tkiva ali plazme pomeni, da je bolnik primeren za zdravljenje z zdravilom Tagrisso. O intersticijski bolezni pljuč (IBP) ali ne.elenih učinkih, podobnih IBP (npr. o pnevmonitisu), so poročali pri 3,9 % od 1142 bolnikov, ki so v študijah FLAURA in AURA prejemali zdravilo Tagrisso; opa.ali so hude, .ivljenjsko ogro.ajoče in včasih smrtne primere intersticijske bolezni pljuč (IBP) ali ne.elenih učinkov, podobnih IBP (npr. pnevmonitisa). Večina primerov se je po prenehanju zdravljenja izboljšala ali je izginila. Bolniki z anamnezo IBP, z zdravili izzvane IBP, radiacijskega pnevmonitisa, ki je zahteval zdravljenje s steroidi, ali kakršnimi koli znaki klinično aktivne IBP niso bili vključeni v klinične študije. Vse bolnike z akutnim nastankom in/ali nepojasnjenim poslabšanjem pljučnih simptomov je treba skrbno pregledati, da bi izključili IBP. V času preiskovanja teh simptomov je treba zdravljenje s tem zdravilom prekiniti. Če je diagnosticirana IBP, je treba ukiniti zdravljenje z zdravilom Tagrisso in uvesti ustrezno zdravljenje, kot je potrebno. Ponovna uvedba zdravila TAGRISSO pride v poštev le po skrbnem pretehtanju koristi in tveganj pri posameznem bolniku. Stevens-Johnsonov sindrom: V povezavi z zdravljenjem z zdravilom TAGRISSO so poročali o redkih primerih Stevens Johnsonovega sindroma (SJS). Pred uvedbo zdravljenja je treba bolnike seznaniti z znaki in simptomi SJS. Če se pojavijo znaki ali simptomi, ki nakazujejo SJS, je treba zdravljenje z zdravilom TAGRISSO nemudoma prekiniti ali končati. Podaljšanje intervala QTc: Bolnikom, zdravljenim z zdravilom Tagrisso, se pojavi podaljšanje intervala QTc. Takšno podaljšanje lahko poveča tveganje za ventrikularne tahiaritmije (npr. torsade de pointes) ali nenadno smrt. Uporabi osimertiniba se je treba pri bolnikih s prirojenim sindromom dolgega intervala QT izogniti, če je le mogoče. O rednih kontrolah elektrokardiograma (EKG) in elektrolitov je treba razmisliti pri bolnikih s kongestivnim srčnim popuščanjem, elektrolitskimi motnjami in prejemnikih zdravil, za katera je znano, da podaljšajo interval QTc. Prekinite uporabo pri bolnikih, ki se jim interval QTc podaljša preko 500 msec na vsaj 2 ločenih posnetkih EKG, in ga ne uporabljajte, dokler ni interval QTc manj kot 481 msec oziroma do njegove vrnitve na izhodiščno vrednost, če je izhodiščni interval QTc 481 msec ali več. Potem začnite zdravilo Tagrisso znova uporabljati v manjšem odmerku. Trajno ukinite zdravljenje z osimertinibom, če se bolniku pojavi podaljšanje intervala QTc v kombinaciji s čimer koli od naslednjega: torsade de pointes, polimorfna ventrikularna tahikardija, znaki/simptomi resne motnje srčnega ritma. Spremembe v krčljivosti srca: Pri bolnikih s srčnimi dejavniki tveganja in bolnikih s stanji, ki prizadenejo LVEF, je treba razmisliti o nadziranju delovanja srca, vključno z ocenjevanjem LVEF izhodiščno in med zdravljenjem. Pri bolnikih, ki se jim med zdravljenjem pojavijo pomembni srčni znaki ali simptomi, je treba razmisliti o nadziranju delovanja srca, vključno z ocenjevanjem LVEF. Keratitis: O keratitisu so poročali pri 0,7 % bolnikov, zdravljenih z zdravilom Tagrisso v študijah FLAURA in AURA. Bolnike z znaki in simptomi, ki nakazujejo keratitis (na primer vnetje očesa, solzenje, občutljivost na svetlobo, zamegljen vid, bolečine v očesu in/ali pordelost očesa), je treba nemudoma napotiti k specialistu oftalmologu. Starost in telesna masa: Pri bolnikih starih nad 65 let ali bolnikih z telesno maso pod 50 kg je lahko prisotno povečano tveganje za pojav ne.elenih učinkov 3. ali višje stopnje. Pri teh bolnikih je priporočeno skrbno spremljanje. MEDSEBOJNO DELOVANJE Z DRUGIMI ZDRAVILI: Močni induktorji CYP3A lahko zmanjšajo izpostavljenost osimertinibu. Osimertinib lahko poveča izpostavljenost substratom BCRP in P-glikoproteina (P-gp). Študije in vitro so pokazale, da poteka presnova I. faze osimertiniba prete.no s CYP3A4 in CYP3A5. Podatki iz klinične farmakokinetične študije so pokazali, da ni verjetno, da bi zaviralci CYP3A4 vplivali na izpostavljenost osimertinibu. Dodatnih katalizacijskih encimov niso odkrili. Podatki klinične farmakokinetične študije o sočasno uporabi z rifampicinom ka.ejo, da se je sočasni uporabi močnih induktorjev CYP3A (npr. fenitoina, rifampicina, karbamazepina) in zdravila Tagrisso priporočljivo izogniti. Izpostavljenost osimertinibu lahko zmanjšajo tudi zmerni induktorji CYP3A4 (npr. bosentan, efavirenz, etravirin, modafinil), zato jih je treba uporabljati previdno oziroma se jim je treba izogniti, če je mogoče. Kliničnih podatkov, ki bi omogočali priporočilo za prilagoditev odmerka zdravila Tagrisso, ni na voljo. Sočasna uporaba šentjan.evke je kontraindicirana. Glede na podatke klinične farmakokinetične študije je pri sočasni uporabi zdravila Tagrisso in rosuvastatina ter ostalih zdravil, katerih odstranjevanje je odvisno od BCRP in imajo ozek terapevtski indeks, treba bolnike skrbno spremljati glede znakov spremenjenega prenašanja zaradi večje izpostavljenosti sočasnemu zdravilu med prejemanjem zdravila Tagrisso. Tveganja za manjšo izpostavljenost hormonskim kontraceptivom ni mogoče izključiti. Bolnike, ki sočasno jemljejo zdravila, katerih odstranjevanje je odvisno od P-gp in imajo ozek terapevtski indeks (npr. digoksin, dabigatran, in aliskiren), je treba skrbno spremljati glede znakov spremenjenega prenašanja zaradi večje izpostavljenosti sočasnemu zdravilu v času prejemanja zdravila Tagrisso. NE.ELENI UČINKI: Podatki iz dveh randomiziranih študijah lll. faze (FLAURA – prva linija in AURA3 – le druga linija) in iz dveh študij z eno samo skupino (AURAex in AURA2 – druga linija ali več) in eni študiji l. faze (AURA1 – prva linija ali več) povzemajo izpostavljenost zdravilu Tagrisso pri 1142 bolnikih z nedrobnoceličnim rakom pljuč in pozitivno mutacijo EGFR. Večina ne.elenih učinkov je bila glede na resnost 1. ali 2. stopnje. Najpogostejša ne.elena učinka zdravila sta bila driska (49 %) in izpuščaj (47 %). V obeh študijah skupaj je bilo ne.elenih učinkov 3. stopnje 9,7 % in 4. stopnje 0,9 %. Med bolniki, ki so prejemali zdravilo Tagrisso 80 mg enkrat na dan, so zaradi ne.elenih učinkov odmerek zmanjšali 2,1 % bolnikom. Ukinitev uporabe zdravila zaradi ne.elenih učinkov je bilo 4,3 %. Zelo pogosti ne.eleni učinki: driska, stomatitis, izpuščaj, suha ko.a, paronihija, srbenje ter zmanjšano število trombocitov, levkocitov, limfocitov in nevtrofilcev. Pogosti ne.eleni učniki: intersticijska bolezen pljuč.VRSTA IN VSEBINA OVOJNINE: Al/Al perforirani pretisni omoti za enkratni odmerek. Škatle z 28 x 1 tableto (4 pretisni omoti). NAČIN IZDAJANJA ZDRAVILA: samo na recept DATUM REVIZIJE BESEDILA: julij 2020 (SI-0991) IMETNIK DOVOLJENJA ZA PROMET: AstraZeneca AB, S-151 85, Sodertalje, Švedska Pred predpisovanjem, prosimo, preberite celoten povzetek glavnih značilnosti zdravila. 1. Ramalingam SS. Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced Dodatne informacije so na voljo pri dru.bi AstraZeneca UK Limited, Podru.nica v Sloveniji, Verovškova 55, Ljubljana. NSCLC (FLAURA): Final overall survival analysis [oral presentation]. Predstavljeno na: European Society of Medical Oncology; September 27-October 1, 2019; Barcelona, Spain. Abstract LBA5. SI-1003 SYMBICORT® OLAJŠEVALEC PO POTREBI OB VZDRŽEVALNEMZDRAVLJENJU SPREMINJAŽIVLJENJA1 SYMBICORT® ZDAJ OLAJŠEVALEC PRVE IZBIRE za bo nike z zmerno do težko astmo, izkoriš€a njihovo naravno vedenje, da iš€ejo o ajšanje, in tako zmanjša števi o pos abšanj.2 SKRAJŠAN POVZETEK GLAVNIH ZNA/ILNOSTI ZDRAVILA Symbicort Turbuhaler 80 µg/4,5 µg na odmerek, prašek za inhaliranje / Symbicort Turbuhaler 160 µg/4,5.µg na odmerek, prašek za inhaliranje / Symbicort Turbuhaler 320 µg/9.µg na odmerek, prašek za inhaliranje SESTAVA: Vsak inhalator Symbicort Turbuhaler 80 µg/4,5 µg na odmerek vsebuje 120 odmerkov, pri …emer vsak oddani odmerek (tisti, ki pride iz ustnika) vsebuje u…inkovini budezonid (80 µg na vdih) in formoterolijev fumarat dihidrat (4,5/µg na vdih). Vsak inhalator Symbicort Turbuhaler 160 µg/4,5 µg na odmerek vsebuje 120 odmerkov, pri …emer vsak oddani odmerek vsebuje u…inkovini budezonid (160 µg na vdih) in formoterolijev fumarat dihidrat (4,5 µg na vdih). Vsak inhalator Symbicort Turbuhaler 320 µg/ /µg na odmerek vsebuje 60 odmerkov, pri …emer vsak oddani odmerek vsebuje u…inkovini budezonid (320 µg na vdih) in formoterolijev fumarat dihidrat ( µg na vdih). INDIKACIJE: ASTMA: Zdravilo Symbicort Turbuhaler je indicirano za redno zdravljenje astme, kadar je primerna uporaba kombinacije (vdihanega kortikosteroida in dolgodelujo…ega agonista adrenergi…nih receptorjev ° 2). Zdravilo Symbicort Turbuhaler 80 µg/4,5 µg je indicirano pri odraslih, mladostnikih in otrocih, starih 6 let ali ve…. Zdravili Symbicort Turbuhaler 160 µg/4,5 µg in Symbicort Turbuhaler 320 µg/ µg sta indicirani pri odraslih in mladostnikih, starih 12 let in starejših. Opomba: Zdravilo Symbicort Turbuhaler 80 µg/4,5 µg ni primerno za bolnike s hudo astmo. KOPB: Zdravili Symbicort Turbuhaler 160 µg/4,5 µg in Symbicort Turbuhaler 320 µg/ µg sta indicirani pri odraslih, starih 18 let ali ve…, za simptomatsko zdravljenje bolnikov s KOPB s forsiranim ekspiracijskim volumnom v 1 sekundi (FEV1) < 70 % predvidenega normalnega (post-bronhodilatatorno) in anamnezo poslabšanj kljub rednemu bronhodilatatornemu zdravljenju. ODMERJANJE: Bolnika je treba opozoriti, da mora natan…no prebrati navodila za uporabo. ASTMA: Zdravilo Symbicort Turbuhaler ni namenjeno za za…etno zdravljenje astme. Odmerek je treba titrirati o najmanjšega odmerka, ki še u…inkovito nadzoruje simptome bolezni. źe najmanjši priporo…eni odmerek dolgoro…no obvladuje simptome, lahko naslednji korak obsega poskus zdravljenja z IGK samim. Z zdravilom Symbicort Turbuhaler sta možna dva na…ina zdravljenja astme: A. Vzdrže alno zdra ljenje z zdra ilom Symbicort Turbuhaler: Bolnik za redno vzdrževalno zdravljenje uporablja zdravilo Symbicort Turbuhaler, kot olajševalec pa lo…eno uporablja hitrodelujo… bronhodilatator. Bolnikom je treba naro…iti, naj imajo vedno na razpolago lo…en hitrodelujo… bronhodilatator za rešilno uporabo. Priporoeni odmerki: Odrasli (stari 18 let ali ve): Symbicort Turbuhaler 80 µg/4,5 µg in Symbicort Turbuhaler 160 µg/4,5 µg 1-2 vdiha dvakrat na dan, nekateri bolniki lahko potrebujejo do najve… 4 vdihe dvakrat na dan. Symbicort Turbuhaler 320 µg/ µg 1 vdih dvakrat na dan, nekateri bolniki lahko potrebujejo do najve… dva vdiha dvakrat na dan. Mladostniki (1 do 17 let): Symbicort Turbuhaler 80 µg/4,5 µg in Symbicort Turbuhaler 160 µg/4,5 µg 1-2 vdiha dvakrat na dan. Symbicort Turbuhaler 320 µg/ µg 1 vdih dvakrat na dan. Otroci (stari 6 -1 let): 2 vdiha dvakrat na dan (samo Symbicort Turbuhaler 80 µg/4,5 µg). Ko je v obi…ajni praksi dosežen nadzor simptomov z uporabo inhalatorja dvakrat na dan, lahko titracija do najmanjšega u…inkovitega odmerka vklju…uje zdravilo Symbicort Turbuhaler enkrat na dan. Otroci, mlajši od 6 let: Ker je na voljo le malo podatkov, zdravilo Symbicort Turbuhaler ni priporo…ljivo za otroke, mlajše od 6 let. B. Vzdrže alno in olajše alno zdra ljenje z zdra ilom Symbicort (samo z zdra ili Symbicort Turbuhaler 80 µg/4,5 µg i Symbicort Turbuhaler 160 µg/4,5 ): Bolniki uporabljajo dnevni vzdrževalni odmerek zdravila Symbicort, dodatno pa ga uporabijo po potrebi, …e se pojavijo simptomi.Bolnikom je treba naro…iti, naj imajo zdravilo Symbicort kot olajševalec vedno pri sebi. źe bolnik uporablja zdravilo Symbicort Turbuhaler kot olajševalec za prepre…evanje bronhokonstrikcije, izzvane z alergeni ali telesno obremenitvijo, se morata zdravnik in bolnik pogovoriti o takšni uporabi; priporo…ilo za uporabo mora upoštevati pogostnost bolnikove potrebe po zdravilu. V primeru pogoste potrebe po bronhodilataciji brez hkratne potrebe po ve…jem odmerku inhalacijskih kortikosteroidov je treba uporabiti nek drug olajševalec. Priporoeni odmerki: Odrasli in mladostniki (stari 1 let in starejši): Priporo…eni vzdrževalni odmerek sta 2 vdiha na dan, bodisi kot 1 vdih zjutraj in 1 vdih zve…er bodisi kot 2 vdiha zjutraj ali zve…er. Za nekatere bolnike, ki prejemajo Symbicort Turbuhaler 160 µg/4,5 µg je lahko primeren vzdrževalni odmerek 2 vdiha dvakrat na dan.źe se pojavijo simptomi, mora bolnik narediti še 1 dodaten vdih. źe so simptomi po nekaj minutah še prisotni, mora uporabiti 1 dodatno inhalacijo. Naenkrat ne sme uporabiti ve… kot 6 inhalacij. Celotni dnevni odmerek ve…ji od 8 vdihov v normalnih okoliš…inah ni potreben, a za krajše obdobje se lahko uporablja celotni dnevni odmerek do 12 vdihov. Bolniki, ki jemljejo ve… kot 8 vdihov na dan, se morajo vsekakor posvetovati z zdravnikom. Zdravnik mora ponovno oceniti njihovo stanje in pretehtati njihovo vzdrževalno zdravljenje. Otroci do 1 . leta: Vzdrževalno in olajševalno zdravljenje z zdravilom Symbicort Turbuhaler za otroke ni priporo…ljivo. KOPB: Priporoeni odmerki za odrasle: Symbicort Turbuhaler 160/ µg/4,5/ µg 2 vdiha dvakrat na dan in Symbicort Turbuhaler 320 µg/ /µg 1 vdih dvakrat na dan. KONTRAINDIKACIJE: Preob…utljivost za budezonid, formoterol ali inhalirano laktozo. POSEBNA OPOZORILA IN PREVIDNOSTNI UKREPI: V primeru prenehanja zdravljenja se z uporabo zdravila ne sme prekiniti nenadoma, ampak je treba odmerek zmanjševati postopoma. O popolni opustitvi inhalacijskih kortikosteroidov se ne sme razmišljati, razen …e je potrebna za…asno za potrditev diagnoze astme. źe bolnik ugotovi, da je zdravljenje neu…inkovito ali …e preseže najve…ji priporo…eni odmerek zdravila Symbicort Turbuhaler, mora poiskati zdravniško pomo…. Bolnike je treba opozoriti, naj uporabljajo vzdrževalne odmerke zdravila Symbicort Turbuhaler, kot jih je predpisal zdravnik, tudi …e nimajo simptomov. Ko so simptomi astme pod nadzorom, pride v poštev postopno zmanjševanje odmerka zdravila Symbicort Turbuhaler. Med zmanjševanjem odmerka je potrebno bolnike redno spremljati. Uporabljati je treba najmanjši u…inkoviti odmerek. Bolnikom zdravila Symbicort Turbuhaler ne smemo uvesti med poslabšanjem astme ali kadar se jim simptomi astme bistveno ali akutno poslabšajo. źe se bolniku pojavi paradoksalni bronhospazem, je treba uporabo zdravila Symbicort Turbuhaler takoj prekiniti; bolnika je treba pregledati in uvesti drugo zdravljenje, …e je treba. Možne u…inke na mineralno gostoto kosti je treba še zlasti upoštevati pri bolnikih, ki dolga obdobja dobivajo velike odmerke in imajo so…asne dejavnike tveganja za osteoporozo. źe obstaja razlog za sum o motenem delovanju nadledvi…nih žlez zaradi predhodnega sistemskega zdravljenja s steroidi, je pri prehodu na zdravilo Symbicort Turbuhaler potrebna previdnost. Tudi dolgotrajno zdravljenje z velikimi odmerki IGK, zlasti v odmerkih, ve…jih od priporo…enih, lahko klini…no pomembno zavre delovanje nadledvi…nih žlez. Zato pride med obdobji stresa, npr. v primeru hudih okužb ali elektivne operacije, v poštev dodatna zaš…ita s sistemskimi kortikosteroidi. Da bi …im bolj zmanjšali tveganje orofaringealne kandidoze, je treba bolniku naro…iti, da si mora po inhaliranju vzdrževalnega odmerka usta sprati z vodo. źe se pojavi orofaringealna kandidoza, si mora bolnik usta sprati tudi po vsaki inhalaciji po potrebi. Zdravilo Symbicort Turbuhaler predpisujte previdno pri bolnikih s tirotoksikozo, feokromocitomom, sladkorno boleznijo, nezdravljeno hipokaliemijo, hipertro˙…no obstruktivno kardiomiopatijo, idiopatsko subvalvularno aortno stenozo, hudo hipertenzijo, anevrizmo ali drugimi hudimi sr…no-žilnimi boleznimi. Previdnost je potrebna pri zdravljenju bolnikov s podaljšanim intervalom QTc. Tudi formoterol sam lahko povzro…i podaljšanje interval QTc. Pri sistemski in topi…ni uporabi kortikosteroidov lahko poro…ajo o motnjah vida. Pediatri…na populacija: priporo…ljivo je redno spremljanje telesne višine otrok, ki dolgotrajno dobivajo IGK. Za preostala opozorila in previdnostne ukrepe glejte celoten povzetek. INTERAKCIJE: Z mo…nimi zaviralci CYP3A4 (ketokonazol, klaritromicin, nefazodon, zaviralci proteaz HIV…) je verjetno izrazito pove…anje koncentracije budezonida v plazmi, zato se je so…asni uporabi treba izogniti. Zdravila Symbicort Turbuhaler se zato ne sme dajati skupaj z inhibitorji adrenergi…nih receptorjev beta (vklju…no s kapljicami za oko), …e za to ne obstajajo tehtni razlogi. So…asno zdravljenje s kinidinom, dizopiramidom, prokainamidom, fenotiazini, antihistaminiki (terfenadin) in tricikli…nimi antidepresivi lahko podaljša interval QTc in pove…a tveganje ventrikularnih aritmij. Poleg tega lahko L-dopa, L-tiroksin, oksitocin in alkohol poslabšajo toleranco srca za simpatikomimetike ° 2. So…asno zdravljenje z zaviralci monoaminooksidaze, vklju…no z zdravili, ki imajo podobne lastnosti kot furazolidon in prokarbazin, lahko sproži hipertenzivne reakcije. Bolniki, ki so…asno dobijo anestezijo s halogeniranimi ogljikovodiki, imajo ve…je tveganje za pojav aritmij. So…asna uporaba drugih beta-adrenergi…nih ali antiholinergi…nih zdravil ima lahko aditiven bronhodilatatoren u…inek. Pri bolnikih, ki prejemajo glikozide digitalisa, lahko hipokaliemija pove…a nagnjenost k aritmijam. Hipokaliemija je lahko posledica zdravljenja z ° 2 agonisti in se lahko okrepi ob so…asnem zdravljenju z derivati ksantina, kortikosteroidi in diuretiki. Medsebojnega delovanja budezonida in formoterola z drugimi zdravili za zdravljenje astme niso opazili. Študije medsebojnega delovanja so izvedli le pri odraslih. NOSE/NOST IN DOJENJE: Med nose…nostjo je treba zdravilo Symbicort Turbuhaler uporabiti le, …e koristi odtehtajo morebitna tveganja. Uporabljati je treba najmanjši u…inkoviti odmerek budezonida, potreben za vzdrževanje ustreznega obvladanja astme. Uporaba zdravila Symbicort Turbuhaler pri doje…i ženski pride v poštev le, …e je pri…akovana korist za mater ve…ja od morebitnega tveganja za otroka. GLAVNI NEŽELENI U/INKI: Pogosti: okužbe orofarinksa s kandido, plju…nica (pri bolnikih s KOPB), glavobol, tremor, palpitacije, blago draženje žrela, kašelj, hripavost. Ob…asni: agresija, psihomotori…na hiperaktivnost, anksioznost, motnje spanja, omotica, zamegljen vid, tahikardija, miši…ni kr…i, navzea, podplutbe. Redki: zgodnje in zapoznele preob…utljivostne reakcije, npr. eksantem, urtikarija, srbenje, dermatitis, angioedem in ana˙lakti…na reakcija, hipokaliemija, bronhospazem, motnje sr…nega ritma, npr. atrijska ˙brilacija, supraventrikularna tahikardija, ekstrasistole. REŽIM IZDAJE ZDRAVILA: Zdravilo se izdaja le na recept. IMETNIK DOVOLJENJA ZA PROMET: AstraZeneca AB, Kvarnbergagatan, SE-151 85 Södertälje, Švedska ZADNJA REVIZIJA BESEDILA: julij 201 (SI-0721) Pred predpiso anjem, prosimo, preberite celoten po zetek gla nih zna‚ilnosti zdra ila. Dodatne informacije so na voljo pri družbi AstraZeneca UK Limited, Podružnica v Sloveniji, Verovškova 55, Ljubljana. REFERENCE: 1. Povzetek glevnih zna…ilnosti zdravila Symbicort Turbohaler 160 µg/4,5 µgna odmerek prašek za inhaliranje, julij 201 2. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2020. Dostopano na http://www.ginasthma.org/, maj 2020 Samo za strokovno javnost. Datum priprave: maj 2020. SI - 0 20. 6:00 7:00 8:10 Kava spotoma Kako vaša izbira IGK/LABA doloc.a 24-urni svet? Stalna 24-urna uc.inkovitost z eno samo inhalacijo na dan*1 *Pomembno povec.anje od izhodišc.a do 12. tedna v povprec.nem zaporednem (0-24 ur) uteženem FEV1 s kombinacijo flutikazonfuroat/vilanterol (FF/VI v nadaljevanju) 100/25 µg enkrat dnevno v primerjavi s FF (p < 0.001, primarni cilj); ni bilo pomembne razlike med FF/VI 100 ali 200/25 µg enkrat dnevno (le opisna primerjava).1 Prospektivna, aktivno kontrolirana, randomizirana, dvojno slepa, stratificirana, multicentric.na raziskava vzporednih skupin, faze III, izpeljana v vec. državah, ki je primerjala uc.inkovitost FF/Vl 100 ali 200/25 µg, enkrat dnevno, v Ellipta vdihovalniku (n = 346 za vsako skupino) s FF 100 µg enkrat dnevno (n = 347) pri bolnikih z zmerno do hudo perzistentno astmo, starosti = 12 let (n = 1.039, randomizacija 1:1:1), v trajanju 12 tednov. Primarni cilj raziskave je bila sprememba od izhodišc.a do 12. tedna v povprec.nem zaporednem (0-24 ur) uteženem FEV1 s FF/VI 100/25 µg enkrat dnevno v primerjavi s FF 100 µg enkrat dnevno.1 IGK, inhalacijski glukokortikoid; LABA, dolgodelujoc.i agonist receptorjev beta2; FEV1, forsirani ekspiracijski volumen v 1. sekundi 1. Bernstein DI et al. J Asthma 2015;52(10):1073–83. 2. Relvar Ellipta povzetek glavnih znac.ilnosti zdravila, datum rev. 12/18. Terapevtske indikacije2: Astma. Zdravilo Relvar Ellipta je indicirano za redno zdravljenje astme pri odraslih in mladostnikih, starih 12 let ali vec., za katere je primerna uporaba kombiniranega zdravila (dolgodelujoc.ega agonista adrenergic.nih receptorjev beta2 in inhalacijskega kortikosteroida): bolniki, ki bolezni nimajo ustrezno urejene ob uporabi inhalacijskih kortikosteroidov in inhalacijskih kratkodelujoc.ih agonistov adrenergic.nih receptorjev beta2 ‘’po potrebi’’; bolniki, ki imajo bolezen ustrezno urejeno ob uporabi inhalacijskih kortikosteroidov in dolgodelujoc.ih agonistov adrenergic.nih receptorjev beta2. KOPB (kronic.na obstruktivna pljuc.na bolezen). Zdravilo Relvar Ellipta je indicirano za simptomatsko zdravljenje odraslih s KOPB, ki imajo FEV1 < 70 % predvidenega normalnega (po bronhodilatatorju), z anamnezo poslabšanj kljub rednemu zdravljenju z bronhodilatatorjem. Relvar Ellipta 92 mikrogramov/22 mikrogramov prašek za inhaliranje, odmerjeni Relvar Ellipta 184 mikrogramov/22 mikrogramov prašek za inhaliranje, odmerjeni Sestava: Ena inhalacija zagotavlja oddani odmerek (odmerek, ki pride iz ustnika inhalatorja) 92 µg oziroma 184 µg flutikazonfuroata in 22 µg vilanterola (v obliki trifenatata). To ustreza odmerjenemu odmerku 100 µg oziroma 200 µg flutikazonfuroata, kar ustreza 25 µg vilanterola (v obliki trifenatata). Pomožne snovi: laktoza monohidrat. Terapevtske indikacije: Astma: Zdravilo Relvar Ellipta je indicirano za redno zdravljenje astme pri odraslih in mladostnikih, starih 12 let ali vec, za katere je primerna uporaba kombiniranega zdravila (dolgodelujocega agonista adrenergicnih receptorjev beta2 in inhalacijskega kortikosteroida): bolniki, ki bolezni nimajo ustrezno urejene ob uporabi IKS in inhalacijskih kratkodelujocih agonistov adrenergicnih receptorjev beta2 ‚‘po potrebi‘‘ in bolniki, ki imajo bolezen ustrezno urejeno ob uporabi IKS in dolgodelujocih agonistov adrenergicnih receptorjev beta2. KOPB: Zdravilo Relvar Ellipta je indicirano za simptomatsko zdravljenje odraslih s KOPB, ki imajo FEV1 < 70 % predvidenega normalnega (po bronhodilatatorju), z anamnezo poslabšanj kljub rednemu zdravljenju z bronhodilatatorjem. Odmerjanje in nacin uporabe: Bolniki z astmo morajo dobiti tisto jakost zdravila Relvar Ellipta, ki vsebuje odmerek flutikazonfuroata (FF), ustrezen izrazitosti njihove bolezni. Zdravniki, ki predpisujejo to zdravilo, morajo vedeti, da je pri bolnikih z astmo odmerek 100 µg flutikazonfuroata (FF) enkrat na dan približno enakovreden odmerku 250 µg flutikazonpropionata (FP) dvakrat na dan, odmerek 200 µg FF enkrat na dan pa je približno enakovreden odmerku 500 µg FP dvakrat na dan. ASTMA Odrasli in mladostniki, stari 12 let ali vec: Za odrasle in mladostnike v starosti 12 let ali vec, ki potrebujejo nizek do srednji odmerek IKS v kombinaciji z dolgodelujocim agonistom adrenergicnih receptorjev beta2, pride v poštev zacetni odmerek ene inhalacije zdravila Relvar Ellipta 92/22 µg enkrat dnevno. Ce bolniki z zdravilom Relvar Ellipta 92/22 µg bolezni nimajo ustrezno urejene, pride v poštev zvišanje odmerka na 184/22 µg; to lahko prinese dodatno izboljšanje urejenosti astme. Zdravnik mora bolnike redno kontrolirati, da ostane jakost uporabljane kombinacije flutikazonfuroat/vilanterol optimalna in se spremeni le po nasvetu zdravnika. Odmerek je treba titrirati do najnižjega odmerka, ki ucinkovito obvladuje simptome. Za odrasle bolnike in mladostnike, stare 12 let ali vec, ki potrebujejo višji odmerek IKS v kombinaciji z dolgodelujocim agonistom adrenergicnih receptorjev beta2, pride v poštev zdravilo Relvar Ellipta 184/22 µg. Bolnikom se pljucna funkcija po navadi izboljša v 15 minutah po inhaliranju zdravila Relvar Ellipta. Vendar je treba bolnikom povedati, da je za vzdrževanje nadzora nad simptomi astme potrebna redna vsakodnevna uporaba in da morajo zdravilo uporabljati tudi, ko nimajo simptomov. Ce se simptomi pojavijo v obdobju med odmerki, mora bolnik za takojšnje olajšanje uporabiti inhalirani kratkodelujoci agonist adrenergicnih receptorjev beta2. Otroci, mlajši od 12 let: Varnost in ucinkovitost zdravila Relvar Ellipta pri otrocih, mlajših od 12 let, za indikacijo astme še nista ugotovljeni. KOPB Odrasli, stari 18 let ali vec: Ena inhalacija zdravila Relvar Ellipta 92/22 µg enkrat na dan. Zdravilo Relvar Ellipta 184/22 µg ni indicirano pri bolnikih s KOPB. Ta odmerek v primerjavi z odmerkom 92/22 µg nima dodatnih koristi, obstaja pa lahko vecje tveganje za pljucnico in sistemske neželene ucinke, povezane s kortikosteroidi.Bolnikom se pljucna funkcija po navadi izboljša v 16 do 17 minutah po inhaliranju zdravila Relvar Ellipta. Zdravilo Relvar Ellipta ni primerno za uporabo v pediatricni populaciji za indikacijo KOPB. Starejši ljudje (> 65 let), bolniki z okvaro ledvic: Prilagoditev odmerka v tej populaciji ni potrebna. Bolniki z okvaro jeter: Uporaba pri bolnikih z okvaro jeter zahteva previdnost. Bolniki z okvaro jeter imajo lahko vecje tveganje za sistemske neželene ucinke kortikosteroidov. Za bolnike z zmerno ali hudo okvaro jeter je najvišji odmerek 92/22 µg Za inhalacijsko uporabo. Zdravilo je treba uporabljati vsak dan ob istem casu. Dokoncna odlocitev o uporabi zvecer ali zjutraj mora biti prepušcena presoji zdravnika. Ce je zdravilo shranjeno v hladilniku, je treba inhalator vsaj eno uro pred uporabo pustiti zunaj, da se ogreje na sobno temperaturo. Bolnike je treba pouciti o tem, kako pravilno vzamejo zdravilo. Kontraindikacije: Preobcutljivost na ucinkovini ali katero koli pomožno snov. Posebna opozorila in previdnostni ukrepi: Flutikazonfuroat/vilanterol se ne sme uporabljati za zdravljenje simptomov akutne astme ali akutnega poslabšanja KOPB; za to je potreben kratkodelujoc bronhodilatator. Ce bolnikova uporaba kratkodelujocih bronhodilatatorjev za olajšanje narašca, to kaže na slabšanje urejenosti bolezni in bolnikovo stanje je treba znova oceniti. Bolniki zdravljenja astme ali KOPB s flutikazonfuroatom/vilanterolom ne smejo koncati brez zdravniškega nadzora, ker se lahko simptomi po prenehanju ponovijo.Med zdravljenjem s flutikazonfuroatom/ vilanterolom se lahko pojavijo z astmo povezani neželeni ucinki in poslabšanja. Bolnikom je treba narociti, naj v primeru, da simptomi astme po uvedbi zdravila Relvar Ellipta niso obvladani ali se poslabšajo, zdravljenje nadaljujejo, a naj se hkrati posvetujejo z zdravnikom. Pojavi se lahko paradoksni bronhospazem s takojšnjim pojacanjem piskajocega dihanja po uporabi zdravila. Takšno stanje je treba nemudoma zdraviti s hitrodelujocim inhalacijskim bronhodilatatorjem. Uporabo zdravila Relvar Ellipta je treba takoj prekiniti, bolnika pregledati in uvesti drugo zdravljenje, ce je potrebno. Med uporabo simpatikomimeticnih zdravil, vkljucno z zdravilom Relvar Ellipta, se lahko pojavijo kardiovaskularni ucinki, npr. motnje srcnega ritma, kakršne so supraventrikularna tahikardija in ekstrasistole. Bolniki s hudo kardiovaskularno boleznijo ali motnjami srcnega ritma, hipertiroidizmom, nekorigirano hipokaliemijo ali pri bolnikih, ki so nagnjeni k nizkim vrednostim kalija v serumu, flutikazonfuroat /vilanterol uporabljati previdno. Pri bolnikih z zmerno do hudo okvaro jeter je treba uporabiti odmerek 92/22 µg in bolnike je treba kontrolirati glede sistemskih neželenih ucinkov, povezanih s kortikosteroidi. Med uporabo vseh IKS se lahko pojavijo sistemski ucinki, zlasti med dolgotrajno uporabo velikih odmerkov. Ti ucinki so veliko manj verjetni kot med uporabo peroralnih kortikosteroidov. Med možnimi sistemskimi ucinki so Cushingov sindrom, Cushingoidne znacilnosti, supresija nadledvicnih žlez, zmanjšanje mineralne gostote kosti, upocasnitev rasti pri otrocih in mladostnikih, katarakta in glavkom ter, redkeje, razlicni psihološki ali vedenjski ucinki, med njimi psihomotoricna hiperaktivnost, motnje spanja, anksioznost, depresija ali agresivnost (zlasti pri otrocih). Flutikazonfuroat/vilanterol je treba uporabljati previdno pri bolnikih s pljucno tuberkulozo in bolnikih s kronicnimi ali nezdravljenimi okužbami. Pri sistemski in topicni uporabi kortikosteroidov lahko porocajo o motnjah vida. Ce se pri bolniku pojavijo simptomi, kot so zamegljen vid ali druge motnje vida, ga je potrebno upoštevati za napotitev k oftalmologu zaradi ovrednotenja možnih vzrokov, ki lahko vkljucujejo katarakto, glavkom ali redke bolezni, kot je centralna serozna horioretinopatija, o katerih so porocali po sistemski in topicni uporabi kortikosteroidov. Opisani so primeri zvišane koncentracije glukoze v krvi pri sladkornih bolnikih; to morate upoštevati, ce zdravilo predpišete bolnikom z anamnezo sladkorne bolezni. Pri bolnikih s KOPB, ki so prejemali IKS, so opažali vecjo pojavnost pljucnice, tudi pljucnice, ki je zahtevala sprejem v bolnišnico. Obstajajo doloceni dokazi, da se tveganje za pljucnico povecuje s povecevanjem odmerka steroida, vendar to ni bilo dokoncno dokazano v vseh študijah. Ni dokoncnih klinicnih dokazov, da se stopnja tveganja za pljucnico znotraj skupine IKS zdravil razlikuje. Zdravniki morajo biti pri bolnikih s KOPB pozorni na morebiten pojav pljucnice, kajti klinicne znacilnosti takšne okužbe se prekrivajo s simptomi poslabšanj KOPB. Med dejavniki tveganja za pljucnico pri bolnikih s KOPB so trenutno kajenje, višja starost, nizek indeks telesne mase (ITM) in huda KOPB. Z višjim odmerkom je bila incidenca pljucnice pri bolnikih z astmo pogosta. Incidenca pljucnice je bila številsko vecja pri bolnikih z astmo, ki so jemali flutikazonfuroat/vilanterol 184/22 µg, kot pri tistih, ki so jemali flutikazonfuroat / vilanterol 92/22 µg ali placebo. Bolniki z redko dedno intoleranco za galaktozo, laponsko obliko zmanjšane aktivnosti laktaze ali malabsorpcijo glukoze/galaktoze ne smejo jemati tega zdravila. Medsebojno delovanje z drugimi zdravili in druge oblike interakcij: Klinicno pomembna medsebojna delovanja z zdravili zaradi flutikazonfuroata/vilanterola v klinicnih odmerkih niso verjetna, ker je koncentracija v plazmi po inhaliranju nizka. Antagonisti adrenergicnih receptorjev beta2 lahko oslabijo ali antagonizirajo ucinek agonistov adrenergicnih receptorjev beta2. Socasni uporabi z antagonisti adrenergicnih receptorjev beta2 (tako neselektivnih kot selektivnih) se je treba izogibati, razen ce ostajajo nujni razlogi za njihovo uporabo. Flutikazonfuroat in vilanterol se oba hitro ocistita z obsežno presnovo prvega prehoda z jetrnim encimom CYP3A4. Previdnost je potrebna med socasno uporabo z mocnimi zaviralci CYP3A4 (npr. ketokonazol, ritonavir, zdravila, ki vsebujejo kobicistat), ker obstaja možnost vecje sistemske izpostavljenosti flutikazonfuroatu in vilanterolu. Socasni uporabi se je treba izogniti, razen ce korist odtehta povecano tveganje za pojav sistemskih neželenih ucinkov kortikosteroidov; v tem primeru je treba bolnike nadzorovati glede sistemskih neželenih ucinkov kortikosteroidov. Flutikazonfuroat in vilanterol sta oba substrata P-gp. Socasna uporaba drugih simpatikomimeticnih zdravil (samih ali kot sestavin kombiniranega zdravljenja) lahko stopnjuje neželene ucinke flutikazonfuroata/vilanterola. Zdravila Relvar Ellipta se ne sme uporabljati skupaj z drugimi dolgodelujocimi agonisti adrenergicnih receptorjev beta2 ali z zdravili, ki vsebujejo dolgodelujoce agoniste adrenergicnih receptorjev beta2. Nosecnost: Uporaba flutikazonfuroata /vilanterola pri nosecnicah pride v poštev le, ce je pricakovana korist za mater vecja od možnega tveganja za plod. Dojenje: Odlociti se je treba bodisi za prenehanje dojenja bodisi za prenehanje zdravljenja s flutikazonfuroat/vilanterolom, upoštevaje koristi dojenja za otroka in korist zdravljenja za žensko. Plodnost: Podatkov o plodnosti pri cloveku ni. Študije na živalih niso pokazale, da bi flutikazonfuroat/vilanterol vplival na plodnost. Vpliv na sposobnost vožnje in upravljanja s stroji: Flutikazonfuroat in vilanterol nimata vpliva ali imata zanemarljiv vpliv na sposobnost vožnje in upravljanja strojev. Neželeni ucinki: Zelo pogosti: glavobol, nazofaringitis. Pogosti: pljucnica, okužba zgornjih dihal, bronhitis, gripa, kandidoza ust in žrela, orofaringealne bolecine, sinuzitis, vnetje žrela, rinitis, kašelj, disfonija, bolecine v trebuhu, artralgija, bolecine v hrbtu, zlomi, mišicni krci, pireksija. Obcasni: hiperglikemija, zamegljen vid, ekstrasistole. Ostali neželeni ucinki so navedeni v Povzetku glavnih znacilnosti zdravila. Vrsta in vsebina ovojnine: Škatla, ki vsebuje 1 inhalator s 30 odmerki. Uporabite v 6 tednih od odprtja vrecke. Imetnik dovoljenja za promet: GlaxoSmithKline (Ireland) Limited, Irska Nacin in režim izdaje: Predpisovanje in izdaja zdravila je le na recept. Datum zadnje revizije besedila: 12/2018 Dodatne informacije so na voljo pri: BERLIN-CHEMIE / A. Menarini Distribution Ljubljana d.o.o., Dolenjska cesta 242c, 1000 Ljubljana, telefon 01 300 2160, faks 01 300 2169; e-mail: slovenia@berlin-chemie.com GSK zašc.itene znamke so last ali licenca skupine družb GSK. Datum priprave informacije junij 2019. Te informacije o zdravilu na recept so namenjene izkljuc.no strokovni javnosti. Pred predpisovanjem, ©2019 skupina družb GSK ali njihovi jemalci licenc. prosimo, preberite celoten povzetek glavnih znac.ilnosti imetnika dovoljenja za promet z zdravilom. Berlin-Chemie/A. Menarini Distribution Zdravilo Relvar je bilo razvito v sodelovanju z . Ljubljana d.o.o. ne priporoc.a uporabe tega zdravila drugac.e kot je navedeno v povzetku glavnih znac.ilnosti zdravila. bronhodilatatorja1 krat dnevno1 koraka za inhalacijo1 2 22 SI-BRI-04-2019_ad one sided, datum priprave: oktober 2019, datum veljavnosti: oktober 2021 Brimica® Genuair® je indicirana za vzdrževalno bronhodilatacijsko zdravljenje za lajšanje simptomov pri odraslih bolnikih s kronicno obstruktivno pljucno boleznijo (KOPB).1 Literatura: 1 Brimica® Genuair® Povzetek glavnih znacilnosti zdravila, 08/2019 Samo za strokovno javnost. Za to zdravilo se izvaja dodatno spremljanje varnosti. Tako bodo hitreje na voljo nove informacije o njegovi varnosti. Zdravstvene delavce naprošamo, da porocajo o katerem koli domnevnem neželenem ucinku zdravila. Glejte poglavje 4.8, kako porocati o neželenih ucinkih. Brimica Genuair 340 mikrogramov/12 mikrogramov, prašek za inhaliranje Sestava: En dostavljen odmerek (odmerek, ki pride iz ustnika) vsebuje 396 mikrogramov aklidinijevega bromida (kar ustreza 340 mikrogramom aklidinija) in 11,8 mikrogramov formoterolijevega fumarat dihidrata. To ustreza izmerjenemu odmerku 400 mikrogramov aklidinijevega bromida (kar ustreza 343 mikrogramov aklidinija) in izmerjenemu odmerku 12 mikrogramov formoterolijevega fumarat dihidrata. En dostavljen odmerek vsebuje približno 11 mg laktoze (v obliki monohidrata). Terapevtske indikacije: Zdravilo Brimica Genuair je indicirano za vzdrževalno bronhodilatacijsko zdravljenje za lajšanje simptomov pri odraslih bolnikih s kronicno obstruktivno pljucno boleznijo (KOPB). Odmerjanje in nacin uporabe: Priporocen odmerek je en vdih dvakrat na dan. Za starejše bolnike, za bolnike z okvaro ledvic ali jeter ni potrebno prilagajanje odmerka. Pediatricna populacija: Ni primerno za uporabo pri otrocih in mladostnikih za indikacijo KOPB. Za inhaliranje. Bolnike je treba pouciti o tem, kako pravilno vzamejo zdravilo, ker lahko inhalator Genuair deluje drugace od inhalatorjev, ki so jih bolniki že prej uporabljali. Pomembno je bolnike pouciti, da natancno preberejo navodila za uporabo v Navodilu za uporabo. Pred prvo uporabo je treba zapecateno vrecko pretrgati in jo tako odpreti ter iz nje vzeti inhalator. Vrecko in sušilno sredstvo je treba zavreci. Kontraindikacije: Preobcutljivost na ucinkovini ali katero koli pomožno snov. Posebna opozorila in previdnostni ukrepi: Astma: Zdravilo ni namenjeno uporabi pri astmi; klinicne študije z zdravilom Brimica Genuair pri astmi niso bile izvedene. Paradoksni bronhospazem: V klinicnih študijah z zdravilom Brimica Genuair v priporocenem odmerku niso opazili paradoksnega bronhospazma. Paradoksni bronhospazem pa so opazili pri drugih vrstah inhalacijskih terapij. Ce pride do tega, je treba zdravljenje z zdravilom prekiniti in razmisliti o drugacnem zdravljenju. Zdravilo ni indicirano za zdravljenje akutnih epizod bronhospazma. Kardiovaskularni ucinki: Zdravilo morate pri bolnikih, ki so imeli v zadnjih 6 mesecih miokardialni infarkt, nestabilno angino pektoris, na novo diagnosticirano aritmijo v zadnjih 3 mesecih, interval QTc (metoda po Bazettu) nad 470 ms ali so bili v zadnjih 12 mesecih hospitalizirani zaradi odpovedi srca funkcijskega razreda III in IV po razvrstitvi NYHA, uporabljati previdno. Agonisti ß2-adrenergicnih receptorjev lahko pri nekaterih bolnikih zvišajo srcni utrip in krvni tlak, povzrocijo spremembe v elektrokardiogramu (EKG). Agoniste ß2-adrenergicnih receptorjev z dolgotrajnim delovanjem je treba uporabljati previdno pri bolnikih z anamnezo podaljšanja intervala QTc ali znanim podaljšanjem tega intervala in pri bolnikih, ki se zdravijo z zdravili, ki vplivajo na interval QTc. Sistemski ucinki: Zdravilo je treba pri bolnikih s hudimi srcnožilnimi boleznimi, konvulzivnimi motnjami, tirotoksikozo in feokromocitomom uporabljati previdno. Pri visokih odmerkih agonistov ß2-adrenergicnih receptorjev se lahko pojavijo presnovni ucinki hiperglikemije in hipokaliemije. Antiholinergicni ucinek: Suha usta, ucinek, ki opažajo pri zdravljenju z antiholinergiki, so lahko dolgorocno povezana z zobnim kariesom. Zaradi njegovega antiholinergicnega delovanja je treba zdravilo Brimica Genuair uporabljati previdno pri bolnikih s simptomaticno hiperplazijo prostate, zastajanjem urina ali glavkomom zaprtega zakotja. Vsebnost laktoze: bolniki z redko dedno intoleranco na galaktozo, odsotnostjo encima laktaze ali malabsorpcijo glukoze/galaktoze, ne smejo jemati tega zdravila. Medsebojno delovanje z drugimi zdravili in druge oblike interakcij: Socasno dajanje zdravila Brimica Genuair z drugimi zdravili, ki vsebujejo antiholinergike in/ali dolgo delujoce agoniste ß2-adrenergicnih receptorjev, ni bilo raziskano, zato ni priporoceno. Hipokaliemicno zdravljenje: Socasno hipokaliemicno zdravljenje z metilksantinskimi derivati, steroidi ali diuretiki, ki ne ohranjajo kalija, lahko stopnjuje možni hipokaliemicni ucinek agonistov ß2-adrenergicnih receptorjev, zato je pri socasni uporabi potrebna previdnost. Zaviralci ß-adrenergicnih receptorjev: Zdravila, ki vsebujejo zaviralce ß-adrenergicnih receptorjev, lahko oslabijo ali antagonizirajo ucinek agonistov ß2-adrenergicnih receptorjev. Druga zdravila: Zdravilo Brimica Genuair je treba pri bolnikih, ki prejemajo zdravila, ki dokazano podaljšujejo interval QTc, kot so zaviralci MAO, triciklicnimi antidepresivi, antihistaminiki ali makrolidi, uporabljati previdno zaradi njihove možne okrepitve delovanja formoterola. Nosecnost: Podatkov o uporabi zdravila Brimica Genuair pri nosecnicah ni. Zdravilo Brimica Genuair se lahko uporablja med nosecnostjo samo, ce se pricakuje, da koristi odtehtajo morebitna tveganja. Dojenje: Ni znano, ali se aklidinij (in/ali njegovi presnovki) ali formoterol izloca v materino mleko. Študije na podganah so pokazale izlocanje majhne kolicine aklidinija (in/ali presnovkov) in formoterola v materino mleko, zato je treba o nadaljevanju zdravljenja z zdravilom Brimica Genuair pri dojecih materah razmišljati samo, ce se pricakuje, da koristi za mater odtehtajo morebitna tveganja za novorojenca. Plodnost: Ni verjetno, da bi dajanje priporocenih odmerkov Brimica vplivalo na plodnost pri ljudeh. Vpliv na sposobnost vožnje in upravljanja s stroji: Zdravilo Brimica Genuair nima vpliva ali ima zanemarljiv vpliv na sposobnost vožnje in upravljanja s stroji. Pojav zamegljenega vida ali omotice lahko vpliva na sposobnost vožnje ali upravljanja s stroji. Neželeni ucinki: Pogosti: nazofaringitis, okužba secil, sinusitis, zobni absces, nespecnost, tesnoba, glavobol, omotica, tresavica, kašelj, diareja, navzea, suha usta, mialgija, mišicni krci, zvišana vrednost kreatin fosfokinaze v krvi. Ostali neželeni ucinki so navedeni v Povzetku glavnih znacilnosti zdravila. Vrsta in vsebina ovojnine: Škatla, ki vsebuje 1 inhalator s 60 odmerki. Uporabite v 60 dneh od odprtja vrecke. Imetnik dovoljenja za promet: AstraZeneca AB, SE-151 85 Södertälje, Švedska Nacin in režim izdaje: Predpisovanje in izdaja zdravila je le na recept. Datum zadnje revizije besedila: 08/2019 Dodatne informacije so na voljo pri: BERLIN-CHEMIE / A. Menarini Distribution Ljubljana d.o.o., Dolenjska cesta 242c, 1000 Ljubljana, telefon 01 300 2160, faks 01 300 2169; e-mail: slovenia@berlin-chemie.com Cas je kljucnega pomena pri diagnozi IPF-a*1-3 Pljucni bolnik in koronavirus Na kaj posebej paziti? Bolnniki s pljucnnimiboleznimi sooditevbbolj tveganno skupiinoza resnejše zaplete, zato še bolj dosledno uupošttevvajte vse naasvete NNIJZ. Samoizolacijain dobrahigienarokssta zato za vasizrednno pomembni. Izogibajte se vsem nenujnim stikom z drugimi ljudmi. Dobro razmislite tudi o nujnosti stikov z bližnjimi, predvsem najmlajšimi, saj majhni otroci še niso sposobni upoštevanja zašcitnih ukrepov in so lahko prenašalci virusa. Poskrbite za raznovrstno prehrano z dovolj sadja in zelenjave. Za obisk trgovine ali lekarne prosite svoje bližnje, ki so mlajši in zdravi. Naredite spisek stvari, ki vam zadostujejo vsaj za nekaj dni. Sprehod v naravi je zelo priporocljiv. (Seveda pa upoštevajte trenutne nasvete vlade in NIJZ.) Izogibajte se le mocno obljudenih poti. Ohranite razdaljo nekaj metrov do vseh, ki jih srecate. Poskrbite, da ohranite telesno kondicijo! Tudi doma se lahko dobro razgibate. Nekaj predlogov: Uporabite sobno kolo. Med sedenjem nekajkrat vstanite in sedite nazaj. Izvajajate dihalne in raztezne vaje. Za ohranjanje mišicne mase rok, dvigujte uteži, ki jih lahko zamenjate s polnimi plocevinkami ali plastenkami. Redno jemljite inhalacijska zdravila. V primeru poslabšanja simptomov, ravnajte v skladu z navodili vašega zdravnika (povecajte odmerke inhalacijskih zdravil). Za nasvet poklicite po telefonu ali pošljite elektronsko pošto. Pred obiskom zdravnika ga poklicite po telefonu. Ne ostanite brez stikov. Po telefonu poklicite prijatelje in bližnje. Ce vam je domaca tehnologija in racunalnik, se povežite preko Skype, Viber, Whatsup, Facebooka,.. In..ostanite pozitivni! Kljub resni situaciji je vedno cas za smeh in hvaležnost Ostanite zdravi! Viri: www.nijz.si; www.copdfoundation.org; https://www.blf.org.uk/support-for-you/coronavirus/people-living-with-lung-condition; www.ginaasthma.org; www.goldcopd.orgDostop do vseh virov: marec 2020 Boehringer Ingelheim RCV, MPR-SL-100036 Podružnica Ljubljana, Datum priprave informacije: marec 2020 Šlandrova 4b, 1231 Ljubljana - Crnuce Informacijsko gradivo za javnost BISTVENI PODATKI IZ POVZETKA GLAVNIH ZNACILNOSTI ZDRAVILA Kakovostna in kolicinska sestava: En dostavljen odmerek (odmerek, ki zapusti ustnik) vsebuje 87 mikrogramov beklometazondipropionata, 5 mikrogramov formoterolijevega fumarata dihidrata in 9 mikrogramov glikopironija (v obliki 11 mikrogramov glikopironijevega bromida). Indikacije: Vzdrževalno zdravljenje pri odraslih bolnikih z zmerno do hudo obliko kronicne obstruktivne pljucne bolezni (KOPB), ki ni ustrezno zdravljena s kombinacijo inhalacijskega kortikosteroida in dolgodelujocega agonista adrenergicnih receptorjev beta2 ali s kombinacijo dolgodelujocega agonista adrenergicnih receptorjev beta2 in dolgodelujocega antagonista muskarinskih receptorjev. Odmerjanje: Priporoceni odmerek sta dve inhalaciji zdravila dvakrat na dan. Najvecji odmerek sta dve inhalaciji dvakrat na dan. Pri starejših bolnikih odmerka ni treba prilagajati. Zdravilo se lahko uporablja v priporocenem odmerku pri bolnikih z blago do zmerno okvaro ledvic. Uporaba zdravila pri bolnikih s hudo okvaro ledvic ali s koncno ledvicno odpovedjo, ki zahteva dializno zdravljenje, zlasti v povezavi s pomembnim zmanjšanjem telesne mase, je možna le, ce so pricakovane koristi vecje od možnih tveganj. Relevantnih podatkov o uporabi zdravila pri bolnikih s hudo okvaro jeter ni, zato je treba zdravilo pri teh bolnikih uporabljati previdno. Zdravilo ni namenjeno za uporabo pri pediatricni populaciji. Nacin uporabe: Za inhaliranje. Za zagotovitev pravilne uporabe zdravila mora zdravnik ali drug zdravstveni delavec bolniku pokazati, kako se inhalator pravilno uporablja, nato pa redno preverjati ustreznost bolnikove tehnike inhaliranja. Bolniku je treba svetovati, da natancno prebere Navodilo za uporabo in sledi napotkom v navodilu. Kontraindikacije: Preobcutljivost na beklometazondipropionat, formoterolijev fumarat dihidrat, glikopironij ali katero koli pomožno snov. Posebna opozorila in previdnostni ukrepi: Zdravilo ni indicirano za zdravljenje akutnih epizod bronhospazmov ali za zdravljenje akutnega poslabšanja KOPB (tj. kot rešilno zdravljenje). Po jemanju zdravila so porocali o takojšnjih preobcutljivostnih reakcijah. Ce se pojavijo znaki, ki kažejo na alergijsko reakcijo, zlasti angioedem, urtikarijo ali kožni izpušcaj, je treba uporabo zdravila takoj prekiniti in uvesti drugo zdravljenje. Lahko se pojavi paradoksni bronhospazem. Zdravilo je treba uporabljati previdno pri bolnikih s srcnimi aritmijami, zlasti z atrioventrikularnim blokom tretje stopnje in tahiaritmijami, idiopatsko subvalvularno aortno stenozo, hipertroficno obstruktivno kardiomiopatijo, hudo boleznijo srca, okluzivnimi boleznimi žilja, arterijsko hipertenzijo in anevrizmo. Previdnost je potrebna tudi pri zdravljenju bolnikov z znanim podaljšanjem intervala QTc ali sumom nanj. Ce je nacrtovana anestezija s halogeniranimi anestetiki, je treba zagotoviti, da se zdravilo ne uporabi vsaj 12 ur pred zacetkom anestezije, saj obstaja tveganje srcnih aritmij. Previdnost je potrebna tudi pri bolnikih s tirotoksikozo, sladkorno boleznijo, feokromocitomom in nezdravljeno hipokaliemijo. Pri bolnikih s KOPB, ki so prejemali inhalacijske kortikosteroide, so opažali vecjo pojavnost pljucnice, tudi pljucnice, ki je zahtevala sprejem v bolnišnico. Pri vseh inhalacijskih kortikosteroidih se lahko pojavijo sistemski ucinki, zlasti ob visokih odmerkih, ki se jih jemlje dolgo casa. Dnevni odmerek zdravila Trimbow ustreza srednjemu odmerku inhalacijskega kortikosteroida. Ti ucinki so bistveno manj verjetni med uporabo inhaliranih kortikosteroidov kot med uporabo peroralnih kortikosteroidov. Zdravilo je treba uporabljati previdno pri bolnikih z aktivno ali mirujoco pljucno tuberkulozo ter glivicno in virusno okužbo dihal. Zdravljenje z agonistom adrenergicnih receptorjev beta2 lahko povzroci potencialno resno hipokaliemijo. Posebna pozornost se svetuje pri hudi obliki KOPB, ker lahko hipoksija stopnjuje ta ucinek. Hipokaliemijo lahko okrepi tudi socasno zdravljenje z drugimi zdravili, ki lahko inducirajo hipokaliemijo, kot so derivati ksantina, steroidi in diuretiki. Inhaliranje formoterola lahko povzroci povišanje ravni glukoze v krvi. Glikopironij je treba pri bolnikih z glavkomom z zaprtim zakotjem, prostaticno hiperplazijo ali zastajanjem urina uporabljati previdno, bolnike pa obvestiti o znakih in simptomih akutnega glavkoma z zaprtim zakotjem in jim narociti, naj prenehajo uporabljati zdravilo in se takoj posvetujejo z zdravnikom, ce se pojavijo ti znaki ali simptomi. Zaradi antiholinergicnega ucinka glikopironija se ne priporoca dolgotrajnega socasnega dajanja zdravila Trimbow z drugimi zdravili, ki vsebujejo antiholinergike. Pri bolnikih s hudo okvaro ledvic in pri bolnikih s hudo okvaro jeter, se lahko zdravilo uporablja le, ce so pricakovane koristi vecje od možnih tveganj. Z namenom zmanjšanja orofaringealnih okužb s kandido je treba bolnikom svetovati, da si usta izperejo z vodo ali jo grgrajo, a naj je ne pogoltnejo, ali da si po inhaliranju predpisanega odmerka umijejo zobe. Pri sistemski in topicni uporabi kortikosteroidov lahko porocajo o motnjah vida. Ce se pri bolniku pojavijo simptomi, kot so zamegljen vid ali druge motnje vida, ga je potrebno upoštevati za napotitev k oftalmologu zaradi ovrednotenja možnih vzrokov, ki lahko vkljucujejo katarakto, glavkom ali redke bolezni, kot je centralna serozna horioretinopatija. Interakcije: Cimetidin, zaviralci CYP3A (npr. ritonavir, kobicistat), nekardioselektivni zaviralci beta adrenergicnih receptorjev (vkljucno s kapljicami za oko), druga beta-adrenergicna zdravila, kinidin, dizopiramid, prokainamid, antihistaminiki, zaviralci MAO, triciklicni antidepresivi, fenotiazini, L-dopa, L-tiroksin, oksitocin, alkohol, zdravila, ki imajo podobne lastnosti kot furazolidon in prokarbazin, anestetiki iz skupine halogeniranih ogljikovodikov, derivati ksantina, steroidi, diuretiki, digitalisovi glikozidi, disulfiram in metronidazol. Ne priporoca se dolgotrajnega socasnega dajanja zdravila Trimbow z drugimi zdravili, ki vsebujejo antiholinergike. Neželeni ucinki:Pogosti: pljucnica (pri bolnikih s KOPB), faringitis, oralna kandidiaza, okužba secil, nazofaringitis, glavobol, disfonija. Obcasni: gripa, oralna glivicna okužba, orofaringealna kandidiaza, ezofagealna kandidiaza, sinusitis, rinitis, gastroenteritis, vulvovaginalna kandidiaza, granulocitopenija, alergijski dermatitis, hipokaliemija, hiperglikemija, nemir, tremor, omotica, disgevzija, hipoestezija, otosalpingitis, atrijska fibrilacija, podaljšanje intervala QT na elektrokardiogramu, tahikardija, tahiaritmija, palpitacije, hiperemija, vrocinski oblivi, hipertenzija, kašelj, produktivni kašelj, draženje žrela, epistaksa, driska, suha usta, disfagija, navzea, dispepsija, skelec obcutek na ustnicah, zobni karies, (aftozni) stomatitis, izpušcaj, urtikarija, pruritus, hiperhidroza, mišicni spazem, mialgija, bolecine v okoncinah, mišicno - skeletna bolecina v prsnem košu, utrujenost, zvecanje ravni C-reaktivnega proteina, povecano število trombocitov, zvecanje vrednosti prostih mašcobnih kislin, zvecanje ravni insulina v krvi, zvecanje vrednosti ketonskih teles v krvi, zmanjšanje ravni kortizola. Nacin in režim izdaje: Predpisovanje in izdaja zdravila je le na recept. Imetnik dovoljenja za promet: Chiesi Farmaceutici S.p.A., Via Palermo 26/A, 43122 Parma, Italija. Datum zadnje revizije besedila: 23.01.2019. Pred predpisovanjem se seznanite s celotnim povzetkom glavnih znacilnosti zdravila. Datum priprave informacije: december 2020 . Podrobnejše informacije so na voljo pri predstavniku imetnika dovoljenja za promet z zdravilom v Sloveniji: CHIESI SLOVENIJA, d.o.o., Šmartinska cesta 53, Ljubljana SAMO ZA STROKOVNO JAVNOST TR 8/20 1Trimbow SmPC 1 viala – 1 koncentracija Podjezicna Imunoterapija Priporoceno odmerjanje •1 viala vsebuje 24 ml •Zadostuje za približno 3 mesece •V petih dneh do vzdrževalnega odmerka •Enostavna uporaba •Prilagodljiv odmerek kapljic SI 03/20 1 viala – 1 koncentracija Podjezicna Imunoterapija Skrajšan povzetek glavnih znacilnosti zdravila SUBLIVAC® in SUBLIVAC® FIX Sestava: podjezicne kapljice vsebujejo na ml 10.000 au, AUN ali PUN alergenskega ekstrakta, pripravljenega v skladu z zdravnikovim navodilom. Pomožne snovi: glicerol, aminokaprojska kislina, dinatrijev fosfat hidrat, natrijev dihidrogen, fosfat dihidrat, olje iz poprove mete, precišcena voda. Terapevtske indikacije: zdravljenje alergijskih reakcij takojšnje preobcutljivosti(IgE posredovanih), kot so alergijski rinitis, alergijski konjunktivitis in alergijska bronhialna astma, induciranih z alergeni. Odmerjanje in uporaba: prvi dan zacetnega zdravljenja se zacne z eno kapljico. Ta odmerek se povecuje vsak dan za eno kapljico, dokler se ne doseže najvišjega dnevnega odmerka petih kapljic. Zdravljenje se nadaljuje s petimi kapljicami. Kapljice se aplicira pod jezik vsaj 1 minuto (optimalno 2-3 minute) pred požiranjem. Za odmerjanje in aplikacijo kapljic se lahko uporablja žlica. Priporocamo, da se po uporabi kapalka ocisti, na primer z mokro krpo. Zdravljenje je potrebno nadaljevati od 3 do 5 let. Kontraindikacije: nekontrolirana bronhialna astma s FEV1 pod 70%, hude avtoimunske bolezni, imunska pomanjkljivost in imunosupresija, neoplasticne bolezni s prisotnimi simptomi, uvedba zdravljenja med nosecnostjo, hudo vnetje ustne sluznice, preobcutljivost na katerokoli pomožno snov. Neželeni ucinki: lokalne reakcije v ustih in žrelu, otekanje ustnic ali jezika. Pojav specificnih alergijskih simptomov kot so blage sistemske reakcije (srbenje oci, kihanje, kašljanje, atopicni ekcem). V redkih primerih se lahko pojavijo intenzivne sistemske reakcije npr. kratka sapa, generalizirana urtikarija ali Quinckejev edem. Po zaužitju se lahko pojavi driska in bolecine v trebuhu. Ti simptomi se obicajno pojavijo v 30 minutah po zaužitju zdravila, lahko se pojavijo tudi po nekaj urah. V posameznih primerih so porocali o anafilakticnem šoku. Nacin in režim izdajanja: SUBLIVAC® in SUBLIVAC® FIX sta na voljo na recept, neposredno predpisan pacientu. Za vse dodatne informacije se lahko obrnete na zastopnika zdravila: Iris, Mednarodna trgovina d.o.o., Cesta v Gorice 8, 1000 Ljubljana. Imetnik dovoljenja za promet: HAL Allergy BV, P.O. Box 1204, 2302 BE Leiden, The Netherlands. Datum zadnje revizije besedila: 02/2020. Zastopa in prodaja:. Iris, Mednarodna trgovina d.o.o. Cesta v Gorice 8, 1000 Ljubljana Tel: 01/200-66-46 narocilo@iris.si HAL Allergy B.V. | J.H. Oortweg 15 - 17 |2333 CH Leiden | The Netherlands Tel.: +31 (0)88 1959 000 | Fax: +31 (0)88 1959 001 | info@hal-allergy.com | www.hal-allergy.com VSAK BOLNIK JE EDINSTVEN. TAKA MORA BITI TUDI RESITEV ZANJ. SKRAJŠAN POVZETEK GLAVNIH ZNACILNOSTI ZDRAVILA IME ZDRAVILA: Staloral 10 IR/ml + 100 IR/ml ali 10 IC/ml + 100 IC/ml podjezicno pršilo, raztopina; Staloral 10 IR/ml + 300 IR/ml podjezicno pršilo, raztopina; Staloral 100 IR/ml ali 100 IC/ml podjezicno pršilo, raztopina; Staloral 300 IR/ml podjezicno pršilo, raztopina. KAKOVOSTNA IN KOLICINSKA SESTAVA: ena viala vsebuje 10 ml raztopine z 10, 100 ali 300 IR/ml (standardizirani alergenski ekstrakti) ali 10 ali 100 IC/ ml (nestandardizirani alergenski ekstrakti) enega ali mešanice vec alergenskih ekstraktov. KLINICNI PODATKI Terapevtske indikacije: Alergije tipa I (klasifikacija po Gellu in Coombsu) zajemajo predvsem rinitis, konjunktivitis, rinokonjunktivitis ali astmo (blago do zmerno) in so lahko sezonske ali celoletne. Cilj specificne imunoterapije je prepreciti klinicne posledice stika senzbilizirane osebe z alergenom, ce so etiološki dejavniki jasno ugotovljeni. Odmerjanje in nacin uporabe: Specificno imunoterapijo je treba uvesti takoj, ko je postavljena diagnoza. Prej ko se zacne zdravljenje, vecja bo ucinkovitost zdravila. Pri otrocih lahko zacnete z zdravljenjem pri starosti od 3 do 4 let, najbolje pa je zaceti okoli 5. leta starosti. Pri otrocih ali mlajših odraslih uvedete to zdravljenje kot terapijo prve izbire takoj, ko bo to glede na jakost simptomov potrebno. Pri sezonskih alergijah je priporocljivo zaceti zdravljenje pred sezono cvetenja. Odmerek pred zacetkom sezone cvetenja najprej povecate na najvecji odmerek, ki ga bolnik še dobro prenaša. Bolnik nadaljuje z jemanjem najvecjega odmerka, ki ga še dobro prenaša, do konca sezone cvetenja. Odmerjanje zdravila ni odvisno od starosti, ampak mora biti prilagojeno jakosti odzivanja posameznega bolnika. Terapija zajema 2 fazi: zacetna faza zdravljenja s postopnim povecevanjem odmerka in vzdrževalna faza zdravljenja s stalnimi odmerki. Pred jemanjem zdravila je treba preveriti oz. zagotoviti, da uporabljeni ekstrakt res ustreza predpisanemu ekstraktu in preveriti tudi rok uporabnosti. 1. Zacetno zdravljenje: povecevanje odmerka Zdravilo se jemlje dnevno, v narašcajocih odmerkih, dokler ni dosežen vzdrževalni odmerek. 2. Vzdrževalno zdravljenje: stalni odmerek Ko bolnik enkrat doseže najvecji odmerek, naj ga jemlje bodisi vsak dan ali trikrat na teden. Priporoceno odmerjanje je najmanj 8 pritiskov 3-krat na teden ali 4 pritiski na dan z uporabo koncentracije 300 IR/ml. V klinicnih raziskavah so bolniki dobro prenašali odmerjanje v kolicinah, ki so ustrezale 10 pritiskom na dan v koncentraciji 300 IR/ml. Dolžina zdravljenja Splošno pravilo je, da je treba specificno imunoterapijo izvajati od 3 do 5 let. Pri sezonskih alergijah lahko traja zdravljenje tudi vec sezon. Nacin uporabe Zdravilo se jemlje zjutraj na tešce. Odmerek ekstrakta si da bolnik tako, da pritisne na odmerno crpalko (1 pritisk odmeri 0,1 ml), ki jo usmeri naravnost pod jezik in ekstrakt zadrži pod jezikom še 2 minuti, nato ga pogoltne. Uporabo zdravila pri otrocih morajo nadzirati odrasli. KONTRAINDIKACIJE: Preobcutljivost za katerokoli pomožno snov (glejte seznam pomožnih snovi), težja imunska pomanjkljivost, maligne bolezni, nestabilna astma, avtoimunske bolezni, trajno zdravljenje z zaviralci receptorjev beta. POSEBNA OPOZORILA IN PREVIDNOSTNI UKREPI: Po potrebi pred terapijo nadzirajte simptome s primernim zdravljenjem. Bolniki, ki jim predpišete podjezicno uporabo alergenov, morajo imeti na voljo tudi standardno simptomatsko zdravljenje (kortikosteroidi, agonisti beta-2 receptorjev, antagonisti histaminskih receptorjev H1). Zdravilo ni primerno za zdravljenje otrok, ki so mlajši od 3 let. To zdravilo vsebuje 1 mmol natrija na ml (ali 1 mmol natrija na maksimalni dnevni odmerek 10 pritiskov alergenskega ekstrakta s koncentracijo 10 IR/ml). To je treba upoštevati pri bolnikih, ki so na dieti z nadzorovanim vnosom natrija. MEDSEBOJNO DELOVANJE Z DRUGIMI ZDRAVILI IN DRUGE OBLIKE INTERAKCIJ: Ni porocil o medsebojnem delovanju tega zdravila z drugimi zdravili. PLODNOST, NOSECNOST IN DOJENJE: Bolnice, ki zanosijo v teku ciklusa specificne imunoterapije v vzdrževalnem odmerku (t.j. stalnem odmerku), lahko zdravljenje nadaljujejo. Ce pa bolnica zanosi v fazi zacetnega zdravljenja (postopno povecevanje odmerka), je bolje, da s terapijo preneha. SPOSOBNOST VOŽNJE IN UPRAVLJANJA S STROJI: Zdravilo Staloral nima vpliva ali ima zanemarljiv vpliv na sposobnost vožnje in upravljanja s stroji. NEŽELENI UCINKI: Desenzitizacija je alergensko zdravljenje, ki lahko sproži neželene alergijske ucinke, ki so lahko lokalni in/ali sistemski. Ni nujno, da bolnik prejeti odmerek dobro prenaša. To se lahko skozi cas spreminja v funkciji specificne reaktivnosti posameznika in okolja. V primeru pojava neželenih ucinkov je treba nacin odmerjanja znova oceniti. Pogosti neželeni ucinki: oralni pruritus, edem, orofaringealno neugodje, navzea, bolecina v trebuhu, bruhanje, diareja. Obcasni neželeni ucinki: konjunktivitis, rinitis, astma, urtikarija. Neznana pogostnost: angioedem, anafilakticni šok, laringealni edem, kašelj, orofaringealni edem. Vecino casa so pogosti neželeni ucinki blagi do zmerni in ni potrebno spreminjati režima odmerjanja. Sistemski ucinki, kot so rinitis, konjunktivitis, urtikarija ali astma, so obcasni in je lahko potrebno simptomatsko zdravljenje z antagonisti histaminskih receptorjev H1, beta-2 mimetiki ali morda peroralnimi kortikosteroidi. V vsakem primeru mora zdravnik, ki predpiše zdravilo, ponovno oceniti shemo odmerjanja ali koristi nadaljnje specificne imunoterapije. V vsakem primeru mora bolnik obvestiti zdravnika o pojavu neželenega ucinka med prejemanjem specificne imunoterapije. Pri zmernih sindromskih reakcijah (urtikarija, rinitis, astma) je lahko potrebno simptomatsko zdravljenje z antagonisti histaminskih receptorjev H1, beta-2 mimetiki ali morda celo peroralnimi kortikosteroidi. IMETNIK DOVOLJENJA ZA PROMET: STALLERGENES, 6 rue Alexis de Tocqueville, 92160 ANTONY, Francija. DATUM ZADNJE REVIZIJE BESEDILA:29.8.2018 REŽIM IZDAJE: Rp/Spec LISTA: V* SAMO ZA STROKOVNO JAVNOST! Celoten Povzetek glavnih znacilnosti zdravila dobite pri naših strokovnih sodelavcih ali na sedežu družbe! V Sloveniji zastopa: Ewopharma d.o.o., Cesta 24. junija 23, 1231 Lj - Crnuce. Privacy notice: Za vec informacij o tem, kako podjetje Ewopharma obdeluje osebne podatke, obišcite spletno stran https://www.ewopharma.si/politika-zasebnosti/ Neželene ucinke je potrebno porocati. Obrazce in informacije najdete na: https://www.jazmp.si/humana-zdravila/farmakovigilanca/porocanje-onezelenih-ucinkih-zdravil/. Datum priprave: 12/2020; SI.20.STALORAL.05 Ewopharma d.o.o. Cesta 24. junija 23 I 1231 Ljubljana-Crnuce T: +386 (0) 590 848 40 I E: info@ewopharma.si Life beyond allergy Edith Zeltner-Nikšic • Product manager • Mob.: +385 98 401 402 Zdravilo Opsumit je kot samostojno zdravilo ali v kombinaciji indicirano za dolgotrajno zdravljenje pljucne arterijske hipertenzije (PAH) pri odraslih bolnikih s funkcionalnim razredom (FR) II do III po SZO. Ucinkovitost je bila ugotovljena v populaciji s PAH, vkljucno z idiopaticno in dedno PAH, PAH, povezano z boleznimi vezivnega tkiva, in PAH, povezano z zdravljeno preprosto prirojeno boleznijo srca1. Referenca: 1. SmPC Opsumit 10 mg filmsko obložene tablete. Datum zadnje revizije besedila: 17. april 2020 Pred predpisovanjem zdravila Opsumit natancno preberite celoten Povzetek glavnih znacilnosti zdravila, ki je na voljo na sedežu podjetja Medis, d.o.o. ali na spletni strani Evropske agencije za zdravila http://www.ema.europa.eu. Imetnik dovoljenja za promet z zdravilom: Janssen-Cilag International NV; Turnhoutseweg 30; B-2340 Beerse Belgija. SAMO ZA STROKOVNO JAVNOST SI-OPS-1120-001 Skrajšan povzetek glavnih znacilnosti zdravila Opsumit / macitentan Ime zdravila: Opsumit 10 mg filmsko obložene tablete. Sestava zdravila: Ena filmsko obložena tableta vsebuje 10 mg macitentana. Pomožne snovi z znanim ucinkom: Ena filmsko obložena tableta vsebuje približno 37 mg laktoze (v obliki monohidrata) in približno 0,06 mg sojinega lecitina (E322). Terapevtske indikacije: Zdravilo Opsumit je kot samostojno zdravilo ali v kombinaciji indicirano za dolgotrajno zdravljenje pljucne arterijske hipertenzije (PAH) pri odraslih bolnikih s funkcionalnim razredom (FR) II do III po SZO. Ucinkovitost je bila ugotovljena v populaciji s PAH, vkljucno z idiopaticno in dedno PAH, PAH, povezano z boleznimi vezivnega tkiva, in PAH, povezano z zdravljeno preprosto prirojeno boleznijo srca. Odmerjanje in nacin uporabe: Zdravljenje mora uvesti in nadzirati zdravnik z izkušnjami v zdravljenju PAH. Odmerjanje: Priporoceni odmerek je 10 mg enkrat na dan. Starejši: Prilagajanje odmerka pri bolnikih, starih vec kot 65 let, ni potrebno. Klinicnih izkušenj pri bolnikih, starejših od 75 let, je malo. Zato je treba zdravilo Opsumit v tej populaciji uporabljati previdno. Jetrna okvara: Na podlagi farmakokineticnih (FK) podatkov odmerka pri bolnikih z blago, zmerno ali hudo jetrno okvaro ni treba prilagajati. Vendar pa klinicnih izkušenj z uporabo macitentana pri bolnikih s PAH z zmerno ali hudo jetrno okvaro ni. Zdravila Opsumit se ne sme uvesti pri bolnikih s hudo jetrno okvaro ali s klinicno pomembno zvišanimi jetrnimi aminotransferazami (vec kot trikratna zgornja normalna meja (> 3 × ULN (Upper Limit of Normal)). Ledvicna okvara: Na podlagi FK podatkov prilagoditev odmerka pri bolnikih z ledvicno okvaro ni potrebna. Klinicnih izkušenj z uporabo macitentana pri bolnikih s PAH s hudo ledvicno okvaro ni. Uporaba zdravila Opsumit se ne priporoca pri bolnikih, ki se zdravijo z dializo. Pediatricna populacija: Varnost in ucinkovitost macitentana pri otrocih in mladostnikih, starih manj kot 18 let še nista bili dokazani. Nacin uporabe:Filmsko obloženih tablet ni mogoce prelomiti in jih je treba cele pogoltniti z vodo. Jemati jih je možno s hrano ali brez nje. Zdravilo Opsumit je treba jemati vsak dan ob istem casu. Ce bolnik izpusti odmerek zdravila Opsumit, je treba bolniku povedati, da ga vzame cim prej, nato pa z naslednjim odmerkom nadaljuje ob nacrtovanem casu. Bolniku je treba povedati, da naj ne vzame dveh odmerkov hkrati, ce je kateri odmerek izpustil. Kontraindikacije: preobcutljivost na ucinkovino, sojo ali katero koli pomožno snov; nosecnost; ženske v rodni dobi, ki ne uporabljajo ucinkovite kontracepcije; dojenje; bolniki s hudo jetrno okvaro; izhodišcne vrednosti jetrnih aminotransferaz (aspartat aminotransferaze (AST) in/ali alanin aminotransferaz (ALT) > 3 × ULN). Posebna opozorila in previdnostni ukrepi: Razmerja med koristmi in tveganje macitentana pri bolnikih s funkcionalnim razredom pljucne arterijske hipertenzije I po SZO niso ugotavljali. Delovanje jeter: S PAH in z antagonisti receptorjev endotelina (ERA, endothelin receptor antagonists) je povezano zvišanje jetrnih aminotransferaz (AST, ALT). Zdravila Opsumit se ne sme uvesti pri bolnikih s hudo jetrno okvaro ali zvišanimi aminotransferazami (> 3-kratna ULN) in se ne priporoca pri bolnikih z zmerno jetrno okvaro. Pred uvedbo zdravila Opsumit je treba pridobiti rezultate preiskav jetrnih encimov. Bolnike je treba spremljati za pojav znakov poškodbe jeter, priporoca pa se tudi mesecno spremljanje vrednosti ALT in AST. Ce se pojavijo trdovratna, nepojasnjena, klinicno pomembna zvišanja aminotransferaz, ali ce zvišanja spremlja zvišanje bilirubina > 2 × ULN ali klinicni simptomi poškodbe jeter (npr. zlatenica), je treba zdravljenje z zdravilom Opsumit prekiniti. O ponovni uvedbi zdravila Opsumit lahko razmislimo, ko se ravni jetrnih encimov pri bolnikih, ki niso imeli klinicnih simptomov poškodbe jeter, vrnejo v normalni razpon. Priporoca se pridobitev nasveta hepatologa. Koncentracije hemoglobina: Zdravljenje z antagonisti receptorja endotelina, vkljucno z macitentanom, je povezano z zmanjšanjem koncentracij hemoglobina. V s placebom kontroliranih študijah z macitentanom povezano zmanjšanje koncentracij hemoglobina ni bilo progresivno in se je po prvih 4-12 tednih zdravljenja stabiliziralo, nato pa je ostalo med kronicnim zdravljenjem stabilno. Z macitentanom in drugimi ERA so porocali o primerih anemije, zaradi katere je bilo potrebno zdravljenje s transfuzijo krvnih celic. Uvedba zdravila Opsumit se ne priporoca pri bolnikih s hudo anemijo. Priporocljivo je, da pred uvedbo zdravljenja izmerite koncentracije hemoglobina, nato pa preiskave med zdravljenjem ponavljate, kot je klinicno indicirano. Pljucna vensko-okluzivna bolezen: Pri uporabi vazodilatatorjev (v glavnem prostaciklinov) pri bolnikih s pljucno vensko-okluzivno boleznijo so porocali o primerih pljucnega edema. Posledicno je treba pomisliti na možnost pljucne vensko-okluzivne bolezni, ce se pojavijo znaki pljucnega edema pri bolnikih s PAH, ki dobivajo macitentan. Uporaba pri ženskah v rodni dobi: Zdravljenje z zdravilom Opsumit se sme pri ženskah v rodni dobi uvesti samo, ce je bila odsotnost nosecnosti potrjena, ce je bilo ženski ustrezno svetovano glede uporabe kontracepcije in ce uporablja ucinkovito kontracepcijo. Ženske še 1 mesec po prekinitvi uporabe zdravila Opsumit ne smejo zanositi. V casu zdravljenja z zdravilom Opsumit se priporocajo mesecni testi nosecnosti za zgodnje prepoznavanje morebitne nosecnosti. Socasna uporaba z mocnimi induktorji CYP3A4: V prisotnosti mocnih induktorjev CYP3A4 se lahko ucinkovitost macitentana zmanjša. Kombinaciji macitentana z mocnimi induktorji CYP3A4 (npr. rifampicin, šentjanževka, karbamazepin in fenitoin) se je treba izogniti. Socasna uporaba z mocnimi zaviralci CYP3A4: Previdnost je potrebna, ko se macitentan daje socasno z mocnimi zaviralci CYP3A4 (npr. itrakonazol, ketokonazol, vorikonazol, klaritromicin, telitromicin, nefazodon, ritonavir in sakvinavir). Ledvicna okvara: Bolniki z ledvicno okvaro so morda med zdravljenjem z macitentanom bolj izpostavljeni tveganju hipotenzije in anemije. Zato se priporoca spremljanje krvnega tlaka in hemoglobina. Klinicnih izkušenj z uporabo macitentana pri bolnikih s PAH in hudo ledvicno okvaro ni. Pri tej populaciji se priporoca previdnost. Z uporabo zdravila Opsumit pri bolnikih na dializi ni izkušenj, zato se macitentan v tej populaciji ne priporoca. Starejši: Izkušenj z macitentanom je pri bolnikih, starih vec kot 75 let, malo, zato je treba zdravilo Opsumit pri tej populaciji uporabljati previdno. Pomožne snovi: Zdravilo Opsumit vsebuje laktozo. Bolniki z redko dedno intoleranco za galaktozo, popolnim pomanjkanjem laktaze ali malabsorpcijo glukoze/galaktoze ne smejo jemati tega zdravila. Tablete zdravila Opsumit vsebujejo sojin lecitin. Bolniki, preobcutljivi na sojo, zdravila Opsumit ne smejo uporabljati. Interakcije: Študije in vitro: V presnovi macitentana in nastajanju njegovih presnovkov sodelujejo encimi citokroma P450, CYP3A4, CYP2C8, CYP2C9 in CYP2C19. Macitentan in njegovi aktivni presnovki nimajo klinicno pomembnega zaviralnega ali indukcijskega ucinka na encime citokroma P450. Macitentan in njegov aktivni presnovek v klinicno pomembnih koncentracijah nista zaviralca jetrnih ali ledvicnih privzemnih prenašalcev, vkljucno z organskimi anionskimi prenašalskimi polipeptidi (OATP1B1 in OATP1B3). Macitentan in njegov aktivni presnovek nista pomembna substrata za OATP1B1 in OATP1B3, vendar vstopata v jetra s pasivno difuzijo. Macitentan in njegov aktivni presnovek v klinicno pomembnih koncentracijah nista zaviralca jetrne ali ledvicne iztocne crpalke, vkljucno s proteinom odpornosti na vec zdravil (P-gp, MDR-1), prenašalci vec zdravil in prenašalci toksinske ekstruzije (MATE1 in MATE2-K). Macitentan ni substrat za P-gp/MDR-1. Macitentan in njegov aktivni presnovek v klinicno koncentracijah ne delujejo medsebojno z beljakovinami, ki sodelujejo pri jetrnem prenosu žolcne soli, tj. z eksportno crpalko žolcne soli (BSEP, bile salt export pump) in polipeptidom, ki je soprenašalec od natrija odvisnega tavroholata (NTCP, sodium-dependent taurocholate co-transporting polypeptide). Študije in vivo: Mocni induktorji CYP3A4: Socasno zdravljenje z rifampicinom 600 mg na dan, mocnim induktorjem CYP3A4, je zmanjšalo izpostavljenost macitentanu v stanju dinamicnega ravnovesja za 79 %, vendar pa ni vplivalo na izpostavljenost aktivnemu presnovku. Upoštevati je treba zmanjšano ucinkovitost macitentana v prisotnosti mocnih induktorjev CYP3A4, kot je rifampicin. Zato se je treba socasni uporabi macitentana z mocnimi induktorji CYP3A4 izogniti. Ketokonazol: V prisotnosti ketokonazola 400 mg enkrat na dan, mocnim zaviralcem CYP3A4, se je izpostavljenost macitentanu zvišala za približno 2-krat. Predvideno zvišanje je bilo približno 3-kratno v prisotnosti ketokonazola 200 mg dvakrat na dan z uporabo fiziološkega modela farmakokineticnega modeliranja (PBPK). Upoštevati je treba negotovosti tega modeliranja. Izpostavljenost aktivnemu presnovku macitentana se je zmanjšala za 26 %. Previdnost je potrebna pri socasni uporabi macitentana z mocnimi zaviralci CYP3A4. Varfarin: Dajanje macitentana v vec odmerkih po 10 mg enkrat na dan ni vplivalo na izpostavljenost S-varfarinu (substrat CYP2C9) ali R-varfarinu (substrat CYP3A4) po enem odmerku 25 mg varfarina. Macitentan ni vplival na farmakodinamicni ucinek varfarina na mednarodno normalizirano razmerje (INR, International Normalized Ratio). Varfarin ni vplival na farmakokinetiko macitentana in njegovega aktivnega presnovka. Sildenafil: V stanju dinamicnega ravnovesja se je izpostavljenost sildenafilu 20 mg trikrat na dan zvecala za 15 % med socasno uporabo macitentana 10 mg enkrat na dan. Sildenafil, ki je substrat CYP3A4, ni vplival na farmakokinetiko macitentana, medtem ko se je izpostavljenost aktivnemu presnovku macitentana zmanjšala za 15 %. Te spremembe niso klinicno pomembne. Ucinkovitost in varnost macitentana v kombinaciji s sildenafilom pri bolnikih s PAH so dokazali v s placebom kontroliranem preskušanju. Ciklosporin A: Socasno zdravljenje s ciklosporinom A 100 mg dvakrat na dan, kombiniranim zaviralcem CYP3A4 in OATP, v stanju dinamicnega ravnovesja ni spremenila izpostavljenosti macitentanu in njegovemu aktivnemu presnovku v klinicno pomembnem obsegu. Hormonski kontraceptivi: Macitentan 10 mg enkrat na dan ni vplival na farmakokinetiko peroralnega kontraceptiva (noretisteron 1 mg in etinilestradiol 35 µg). Zdravila, ki so substrati proteina odpornosti na raka dojke (BCRP-Breast cancer resistance protein): Macitentan v odmerku 10 mg enkrat na dan ni vplival na farmakokinetiko substrata BCRP (1 mg rociguata; 10 mg rosuvastatina). Plodnost, nosecnost in dojenje: Nosecnost: Podatkov o uporabi macitentana pri nosecnicah ni. Študije na živalih so pokazale vpliv na sposobnost razmnoževanja. Možno tveganje za ljudi še ni znano. Zdravilo Opsumit je kontraindicirano med nosecnostjo in pri ženskah v rodni dobi, ki ne uporabljajo ucinkovite kontracepcije. Uporaba pri ženskah v rodni dobi/kontracepcija pri moških in ženskah: Zdravljenje z zdravilom Opsumit se sme pri ženskah v rodni dobi uvesti samo, ce je bila odsotnost nosecnosti potrjena, ce je bilo ženski ustrezno svetovano glede uporabe kontracepcije in ce uporablja ucinkovito kontracepcijo. Ženske še 1 mesec po prekinitvi uporabe zdravila Opsumit ne smejo zanositi. V casu zdravljenja z zdravilom Opsumit se priporocajo mesecni testi nosecnosti za zgodnje prepoznavanje morebitne nosecnosti. Dojenje: Ni znano, ali se macitentan izloca v materino mleko. Pri podganah se macitentan in njegovi presnovki med dojenjem izlocajo v mleko. Tveganja za dojenega otroka ne moremo izkljuciti. Zdravilo Opsumit je kontraindicirano med dojenjem. Plodnost pri moških: Po zdravljenju z macitentanom so pri samcih živali opazili razvoj testikularne tubularne atrofije. Pomen tega izsledka za ljudi ni znan, vendar poslabšanja spermatogeneze ni mogoce izkljuciti. Povzetek neželenih ucinkov: Zelo pogosti: nazofaringitis, bronhitis, anemija, zmanjšana raven hemoglobina, glavobol, edem, zastajanje tekocine. Pogosti: faringitis, gripa, okužba secil, levkopenija, trombocitopenija, zvišane ravni aminotransferaze, hipotenzija, kongestija nosu. Nacin in režim predpisovanja in izdaje zdravila: Predpisovanje in izdaja zdravila je le na recept, zdravilo pa se uporablja samo v bolnišnicah. Izjemoma se lahko uporablja pri nadaljevanju zdravljenja na domu ob odpustu iz bolnišnice in nadaljnjem zdravljenju. Imetnik dovoljenja za promet: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgija. Pred predpisovanjem, prosimo, preberite povzetek glavnih znacilnosti zdravila. Datum revizije besedila: 04/2020 SI-OPS-1120-001 Preuredi življenje, preoblikuj prihodnost (treprostinil) raztopina za infundiranje BODI REMODULIN® Pred predpisovanjem zdravila Remodulin natacno preberite celoten Povzetek glavnih znacilnosti zdravila, ki je na voljo na sedežu podjetja Medis d.o.o. ali na spletni strani www.cbz.si.Imetnik dovoljenja za promet z zdravilom: Ferrer Internacional S.A., Gran Via Carlos III, 94, 08028 - Barcelona, Španija. SAMO ZA STROKOVNO JAVNOST SI-REM-1120-001 Skrajšan povzetek glavnih znacilnosti zdravila REMODULIN / treprostinil Ime zdravila in sestava: REMODULIN 1 mg/ml raztopina za infundiranje. En mililiter vsebuje 1 mg treprostinila v obliki natrijevega treprostinilata. Ena 20 ml viala z raztopino vsebuje 20 mg treprostinila v obliki natrijevega treprostinilata (natrijeva sol nastane in situ med proizvodnjo koncnega zdravila). REMODULIN 2,5 mg/ml raztopina za infundiranje. En mililiter vsebuje 2,5 mg treprostinila v obliki natrijevega treprostinilata. Ena 20 ml viala z raztopino vsebuje 50 mg treprostinila v obliki natrijevega treprostinilata (natrijeva sol nastane in situ med proizvodnjo koncnega zdravila). REMODULIN 5 mg/ml raztopina za infundiranje. En mililiter vsebuje 5 mg treprostinila v obliki natrijevega treprostinilata. Ena 20 ml viala z raztopino vsebuje 100 mg treprostinila v obliki natrijevega treprostinilata (natrijeva sol nastane in situ med proizvodnjo koncnega zdravila). REMODULIN 10 mg/ml raztopina za infundiranje. En mililiter vsebuje 10 mg treprostinila v obliki natrijevega treprostinilata. Ena 20 ml viala z raztopino vsebuje 200 mg treprostinila v obliki natrijevega treprostinilata (natrijeva sol nastane in situ med proizvodnjo koncnega zdravila). Terapevtske indikacije: Zdravljenje idiopatske ali dedne pljucne arterijske hi-pertenzije (PAH) za izboljšanje tolerance za telesno aktivnost in simptomov pri bolnikih, razvršcenih v 3. razred po razvrstitvi New York Heart Association (NYHA). Odmerjanje in nacin uporabe: Zdravilo Remodulin se daje v obliki neprekinjene subkutane ali intravenske infuzije. Zaradi tveganj, povezanih s kronicno vstavljenimi centralnimi venskimi katetri, vkljucno z resnimi okužbami krvi, je subkutano infundiranje (nerazredceno) prednostni nacin dajanja, neprekinjeno intravensko infundiranje pa je pridržano za bolnike, ki so stabilizirani s subkutanim infundiranjem treprostinila vendar subkutane poti vec ne prenašajo in pri katerih se to tveganje smatra za sprejemljivo. Zdravljenje lahko zacnejo in nadzorujejo le zdravniki, izkušeni v zdravljenju pljucne hipertenzije. Odmerjanje: Odrasli: Zacetek zdravljenja pri bolnikih, ki predhodno še niso prejemali prostaciklinov: Zdravljenje je treba zaceti pod skrbnim zdravniškim nadzorom v enoti, kjer je mogoce zagotoviti intenzivno nego. Priporocena zacetna hitrost infundiranja je 1,25 ng/kg/min. Ce bolniki zacetni odmerek slabo prenašajo, je treba hitrost infundiranja zmanjšati na 0,625 ng/kg/min. Prilagoditve odmerka: V prvih štirih tednih zdravljenja je treba hitrost infundiranja povecevati pod zdravniškim nadzorom postopno po 1,25 ng/kg/min tedensko, nato pa po 2,5 ng/kg/min tedensko. Da bi dosegli vzdrževalni odmerek, pri katerem se simptomi izboljšajo in ki ga bolniki prenašajo, je treba odmerek prilagoditi individualno in pod zdravniškim nadzorom. Med 12-tedenskim preskušanjem je bila ucinkovitost ohranjena samo, ce je bil odmerek v povprecju povecan 3-krat do 4-krat mesecno. Namen stalne prilagoditve odmerka je dolociti odmerek, pri katerem se izboljšajo simptomi PAH in hkrati minimalizirajo prekomerni farmakološki ucinki zdravila Remodulin. Neželeni ucinki, kot so vrocinski oblivi, glavobol, hipotenzija, slabost, bruhanje in driska, so v splošnem odvisni od uporabljenega odmerka treprostinila. V nadaljevanju zdravljenja lahko izginejo, ce pa vztrajajo ali jih bolniki ne morejo vec prenašati, je treba hitrost infuzije zmanjšati, da se zmanjša njihova intenziteta. V fazi spremljanja klinicnih preskušanj so bili povprecni odmerki, doseženi po 12 mesecih, 24 mesecih in 48 mesecih, 26 ng/kg/min, 36 ng/kg/min in 42 ng/kg/min. Pri bolnikih s cezmerno telesno maso (= 30 % nad idealno telesno maso) je zacetni odmerek in povecanje odmerkov potrebno dolociti glede na idealno teles-no maso. Nenadna ukinitev ali nenadno znatno zmanjšanje odmerka zdravila Remodulin lahko povzroci povratni ucinek pljucne arterijske hipertenzije. Zato se priporoca izogibanje prekinitvi zdravljenja z zdravilom Remodulin in ponovno uvedbo zdravila takoj po nenadnem nenamernem zmanjšanju odmerka ali prekinitvi. Usposobljeno zdravniško osebje doloci optimalno strategijo za ponovno uvedbo infundiranja zdravila Remodulin za vsak posamezni primer posebej. V vecini primerov se lahko infundiranje zdravila Remodulin po nekajurni prekinitvi uvede z enako stopnjo odmerka; pri prekinitvah, ki trajajo dalj casa, pa je treba odmerek zdravila Remodulin ponovno titrirati. Starejši: Na splošno je treba odmerek pri starejših izbrati previdno, ob upoštevanju zmanjšanega delovanja jeter, ledvic in srca, socasnih bolezni ali drugih zdravil, ki jih bolnik jemlje. Otroci in mladostniki: Podatki za bolnike pod 18. letom starosti so omejeni. Na osnovi klinicnih preskušanj, ki so na voljo, ni mogoce oceniti ali ucinkovitost in varnost priporocene sheme odmerjanja za odrasle lahko ekstrapoliramo na otroke in mladostnike. Skupine bolnikov z vecjim tveganjem: Bolniki z jetrno okvaro: Pri bolnikih z okvaro jeter je potrebna previdnost zaradi tveganja za povecano sistemsko izpostavljenost, ki lahko zmanjša toleranco in poveca od odmerka odvisne neželene ucinke. Zacetni odmerek zdravila Remodulin je treba zmanjšati na 0,625 ng/kg/min, nato pa ga previdno postopoma povecevati. Bolniki z ledvicno okvaro: Ker se treprostinil in njegovi presnovki izlocajo vecinoma z urinom, je treba bolnike z ledvicno okvaro zdraviti previdno, da bi preprecili škodljive posledice zaradi morebitnega povecanja sistemske izpostavljenosti. Nacin prehoda na intravensko zdravljenje z epoprostenolom: Kadar je potreben prehod na intravensko dajanje epoprostenola, je treba prehodno fazo opraviti pod strogim zdravniškim nadzorom. Pri tem se lahko uporabi naslednja priporocena shema prehoda. Infuzije treprostinila je treba najprej pocasi zmanjšati na 2,5 ng/kg/min. Po najmanj eni uri novega doseženega odmerka treprostinila se lahko zacne zdravljenje z najvecjim odmerkom epoprostenola, 2 ng/kg/min. Odmerek treprostinila je treba nato zmanjševati v zaporednih presledkih po najmanj dve uri in socasno, po vzdrževanju zacetnega odmerka najmanj eno uro, vecati odmerek epoprostenola. Za nacin uporabe glejte celoten Povzetek glavnih znacilnosti zdravi-la za posamezno jakost. Kontraindikacije: Znana preobcutljivost za treprostinil ali katerokoli pomožno snov; pljucna arterijska hipertenzija, povezana z vensko okluzivno boleznijo; kongestivna srcna odpoved zaradi hude okvare delovanja levega prekata; hudo okvarjeno delovanje jeter (Child-Pughov razred C).; aktiven cir na želodcu, intrakranialna krvavitev, poškodba ali drugo stanje s krvavitvijo; prirojene ali pridobljene okvare zaklopk s klinicno pomembno disfunkcijo srcne mišice, ki ni povezana s pljucno hipertenzijo; huda koronarna srcna bolezen ali nestabilna angina pektoris; miokardni infarkt v preteklih šestih mesecih; dekompenzirana srcna odpoved, ki ni pod skrbnim zdravniškim nadzorom; hude aritmije; cerebrovaskularni dogodki (na primer tranzitorna ishemicna ataka, kap) v preteklih treh mesecih. Posebna opozorila in previdnostni ukrepi: Pri odlocitvi o zacetku zdravljenja z zdravilom Remodulin morate upoštevati veliko verjetnost, da bo neprekinjeno infundiranje trajalo dalj casa. Zato je treba pretehtati bolnikovo pripravljenost in odgovornost za sprejetje vstavljenega katetra in naprave za infundiranje. Treprostinil je mocan pljucni in sistemski vazodilatator. Pri osebah, pri katerih je sistemski arterijski tlak nizek, lahko zdravljenje s treprostinilom poveca tveganje za sistemsko hipotenzijo. Zdravljenje ni priporoceno pri bolnikih s sistolicnim arterijskim tlakom, nižjim od 85 mmHg. Priporocljivo je, da se ob spremembi odmerka spremlja sistemski krvni tlak in srcni utrip, infundiranje pa je treba prekineti, ce se razvijejo simptomi hipotenzije oziroma, ce sistolicni krvni tlak pade pod 85 mmHg. Nenadna odtegnitev ali hitro znatno zmanjšanje odmerka zdravila Remodulin lahko povzroci ponovni pojav pljucne arterijske hipertenzije. Ce bolnik med zdravljenjem z zdravilom Remodulin dobi pljucni edem, je treba upoštevati možnost, da je s tem povezana pljucna venska okluzivna bolezen. Zdravljenje morate prekiniti. Pri bolnikih s cezmerno telesno maso (ITM vecji od 30 kg/m2) je ocistek treprostinila pocasnejši. Korist subkutanega zdravljenja z zdravilom Remodulin pri bolnikih s hujšo pljucno arterijsko hipertenzijo (4. razred po razvrstitvi NYHA) ni bila ugotovljena. Razmerja ucinkovitosti in varnosti zdravila Remodulin pri pljucni arterijski hipertenziji, povezani z levo--desnim srcnim spojem, portalno hipertenzijo ali okužbo z virusom HIV, niso raziskovali. Bolnikom z jetrno in ledvicno okvaro je treba zdravilo odmerjati previdno. Ker se treprostinil in njegovi presnovki izlocajo vecinoma z urinom, je treba bolnike z okvarjenim delovanjem ledvic zdraviti previdno, da bi preprecili škodljive posledice zaradi morebitnega povecanja sistemske izpostavljenosti. Bodite previdni v primerih, pri katerih lahko treprostinil z zaviranjem agregacije trombocitov poveca nevarnost krvavitve. Socasna uporaba zaviralca encima citokroma P450 (CYP) 2C8 (npr. gemfibrozila) lahko poveca izpostavljenost (tako Cmax kot tudi AUC) treprostinilu. Povecana izpostavljenost pa povecuje verjetnost neželenih ucinkov, povezanih z uporabo treprostinila. Zato je treba razmisliti o zmanjšanju odmerka treprostinila. Socasna uporaba spodbujevalca encima CYP2C8 (npr. rifampicina) lahko zmanjša izpostavljenost treprostinilu. Manjša izpostavljenost pa verjetno zmanjša klinicno ucinkovitost. Zato je treba razmisliti o povecanju odmerka treprostinila. Neželeni ucinki, pripisani intravenskemu sistemu dovajanja zdravila: Pri bolnikih, ki so prejemali zdravilo Remodulin v obliki intravenske infuzije, so porocali o okužbah krvi in sepsi, povezanih s centralnim venskim katetrom. Ta tveganja se pripisujejo sistemu dovajanja zdravila. Retrospektivna ocena sedmih centrov v Združenih državah Amerike, kjer so za zdravljenje PAH zdravilo Remodulin uporabljali intravensko, je pokazala stopnjo incidence za okužbe krvi, povezane s katetrom, 1,10 dogodka na 1.000 katetrskih dni. Zdravniki morajo poznati niz možnih po Gramu negativnih in po Gramu pozitivnih organizmov, s katerimi se lahko bolnik pri centralnem venskem katetrom dolgorocno okuži, zato je neprekinjeno subkutano infundiranje nerazredcenega zdravila Remodulin prednostni nacin dajanja. Klinicna ekipa, odgovorna za zdravljenje, mora zagotoviti, da je bolnik povsem usposobljen in zmožen za uporabo izbrane infundirne naprave. Interakcije: Upoštevati je treba interakcije z diuretiki, antihipertenzivi ali drugimi vazodilatatorji, zaviralci agregacije trombocitov, vkljucno z nesteroidnimi protivnetnimi in protirevmaticnimi zdravili in antikoagulanti, furosemidom, spodbujevalci/zaviralci encima citokroma P450 (CYP) 2C8, bosentanom, sildenafilom. Plodnost, nosecnost in dojenje: Ženskam v rodni dobi se med zdravljenjem z zdravilom Remodulin priporoca uporaba kontracepcije. Uporaba zdravila Remodulin med nosecnostjo je dovoljena samo, ce potencialna korist za nosecnico upravicuje potencialno tveganje za zarodek. Ženskam, ki jemljejo Remodulin, je treba svetovati, da prenehajo z dojenjem. Povzetek neželenih ucinkov: Za popoln seznam neželenih ucinkov glejte celoten Povzetek glavnih znacilnosti zdravila, te informacije vkljucujejo zelo pogoste in pogoste neželene ucinke. Zelo pogosti ( = 1/10): glavobol, vazodilatacija, zardevanje, driska, siljenje na bruhanje, izpušcaj, bolecine v celjustih, bolecine na mestu infundiranja, reakcija na mestu infundiranja, krvavitev ali hematom. Pogosti (= 1/100 do < 1/10): omotica, hipotenzija, krvavitve, bruhanje, pruritus, mialgija, artralgija, bolecina v okoncini, edem. Nacin in režim predpisovanja in izdaje zdravila: Predpisovanje in izdaja zdravila je le na recept, zdravilo pa se uporablja samo v bolnišnicah. Izjemoma se lahko uporablja pri nadaljevanju zdravljenja na domu ob odpustu iz bolnišnice in nadaljnjem zdravljenju. Imetnik dovoljenja za promet: FERRER INTERNACIONAL, S.A., Gran Vía Carlos III, 94, 08028 – Barcelona, Španija. Pred predpisovanjem, prosimo, preberite povzetek glavnih znacilnosti zdravila. Datum revizije besedila: 10/2018. SI-REM-1120-001 80 mikrogramov in 160 mikrogramov. Drobni delci zdravila Alvesco dosežejo do velikih in malih dihalnih poti2 Odlicna ucinkovitost pri nadzoru vnetja in zmanjšanju simptomov astme1, 3-4 Visoka pljucna depozicija in distribucija1, 3-4 Majhna sistemska izpostavljenost1, 3-4 SKRAJŠAN POVZETEK GLAVNIH ZNACILNOSTI ZDRAVILA ALVESCO / CIKLEZONID Titriranje odmerka (korak naprej in korak nazaj) brez ogrožanja varnosti1, 5-6 Majhna pojavnost neželenih ucinkov1 Ucinkovitost pri odmerjanju enkrat na dan1, 3 Hiter zacetek delovanja (znotraj 2,5 ur)7 Ime zdravila in sestava: Alvesco 80 mikrogramov/odmerek inhalacijska raztopina pod tlakom. En vpih (odmerek iz ustnika) vsebuje 80 mikrogramov ciklezonida. Alvesco 160 mikrogramov/odmerek inhalacijska raztopina pod tlakom. En vpih (odmerek iz ustnika) vsebuje 160 mikrogramov ciklezonida. Terapevtske indikacije:Zdravljenje za nadzor kronicne astme pri odraslih in mladostnikih (starejših od 12 let). Odmerjanje in nacin uporabe: Zdravilo se uporablja samo za inhaliranje. Odmerjanje: Priporoceni odmerki za odrasle in mladostnike: 160 mikrogramov enkrat na dan, kar pri vecini bolnikov vodi do obvladovanja astme. Pri nekaterih bolnikih s hudo obliko astme se lahko ob jemanju manjšega odmerka ali prenehanju peroralnega jemanja kortikosteroidov uporabijo vecji odmerki do 640 mikrogramov na dan (odmerjen dvakrat na dan po 320 mikrogramov). Bolnikom je treba dati inhalacijski odmerek ciklezonida glede na resnost njihove bolezni. Simptomi se zacnejo izboljševati v roku 24 ur po zdravljenju z zdravilom Alvesco. Ko je nadzor astme dosežen, je treba odmerek zdravila Alvesco individualno prilagoditi in titrirati do najmanjšega odmerka, potrebnega za vzdrževanje ustreznega nadzora astme. Zmanjšanje odmerka na 80 mikrogramov enkrat na dan je za nekatere bolnike lahko ucinkovit vzdrževalni odmerek. Alvesco inhalacijska raztopina pod tlakom naj bi se uporabljala zvecer, ceprav je dokazano, da je tudi jutranje odmerjanje Alvesco inhalacijske raztopine pod tlakom ucinkovito. Koncna odlocitev o jutranjem ali vecernem odmerjanju je prepušcena zdravniku. Bolniki s hudo astmo so izpostavljeni tveganju akutnih napadov, zato je potrebno redno ocenjevati nadzor astme, vkljucno s preiskavami pljucne funkcije. Pogostejša uporaba bronhodilatatorjev s kratkotrajnim delovanjem za lajšanje simptomov astme kaže na poslabšanje nadzora astme. Ce bolnik ugotovi, da se je ucinkovitost lajšanja simptomov z bronhodilatatorjem s kratkotrajnim delovanjem zmanjšala, ali da potrebuje vec inhalacij kot obicajno, mora poiskati zdravniško pomoc. V takem primeru je potrebno znova oceniti stanje bolnika in presoditi o potrebi po intenzivnejšem protivnetnem zdravljenju (npr. višji odmerki Alvesco inhalacijske raztopine pod tlakom za kratko obdobje ali zdravljenje s peroralnimi kortikosteroidi). Huda poslabšanja astme je treba zdraviti na obicajen nacin. Da bi se zadovoljile posebne potrebe bolnika, kot so težave pri sprožitvi inhalatorja in hkratnem vdihu, se Alvesco inhalacijska raztopina pod tlakom lahko uporablja z nastavkom AeroChamber Plus. Starejši bolniki in bolniki z okvaro ledvic ali jeter: Pri starejših bolnikih in bolnikih z okvaro jeter ali ledvic odmerka ni treba prilagajati. Pediatricna populacija: Zaenkrat ni na voljo dovolj podatkov o zdravljenju s ciklezonidom pri otrocih do 12 let starosti. Nacin uporabe: Bolnika je treba pouciti o pravilni uporabi inhalatorja. Kontraindikacije:Preobcutljivost na ciklezonid ali katerokoli pomožno snov. Posebna opozorila in previdnostni ukrepi: Kot velja za vse inhalacijske kortikosteroide, je pot-rebno uporabljati Alvesco inhalacijsko raztopino pod tlakom previdno pri bolnikih z aktivno ali mirujoco pljucno tuberkulozo, glivicnimi, virusnimi ali bakterijskimi okužbami in to le, ce so ti bolniki ustrezno zdravljeni. Kot velja za vse inhalacijske kortikosteroide, Alvesco inhalacijska raztopina pod tlakom ni indicirana za zdravljenje astmaticnega statusa ali drugih akutnih epizod astme, ki zahtevajo intenzivne ukrepe. Alvesco inhalacijska raztopina pod tlakom ni namenjena lajšanju akutnih simptomov astme, pri katerih je potrebna uporaba inhalacijskega bronhodilatatorja s kratkotrajnim delovanjem. Bolnikom je treba svetovati, naj imajo tak olajševalec na razpolago. Pojavijo se lahko sistemski ucinki inhalacijskih kortikosteroidov, še posebno pri velikih odmerkih, predpisanih za daljše obdobje. Ti ucinki so manj verjetni kot pri uporabi peroralnih kortikosteroidov. Možni sistemski ucinki so supresija delovanja nadledvicne žleze, upocasnjena rast pri otrocih in mladostnikih, zmanjšanje mineralne gostote kosti, siva mrena in glavkom, redkeje pa spekter psiholoških ali vedenjskih ucinkov, vkljucno s psihomotoricno hiperaktivnostjo, motnjami spanja, tesnobo, depresijo ali agresijo (zlasti pri otrocih). Pri otrocih in mladostnikih, ki se dolgotrajno zdravijo z inhalacijskimi kortikosteroidi, je priporocljivo redno nadziranje telesne višine. Pri bolnikih s hudo okvaro jeter se pricakuje vecja izpostavljenost, zato je takšne bolnike treba nadzirati glede možnega pojava sistemskih ucinkov. Zaradi ugodnega ucinka inhalacijskega ciklezonida bi se morala potreba po peroralnih steroidih zmanjšati. Bolniki, ki preidejo s peroralnih steroidov na inhalacijski ciklezonid, so še dolgo casa po prehodu izpostavljeni tveganju okvare nadledvicne žleze. Možnost pojava posameznih simptomov lahko traja še nekaj casa. Za podrobne informacije glejte celoten povzetek glavnih znacilnosti zdravila. Interakcije: Socasnemu dajanju mocnih zaviralcev CYP3A4 (npr. ketokonazol, itrakonazol in ritonavir ali nelfinavir) se je torej treba izogibati, razen ce pricakovana korist odtehta pove-cano tveganje za sistemske neželene ucinke kortikosteroidov. Nosecnost in dojenje: Kot druge glukokortikoide se tudi ciklezonid med nosecnostjo lahko uporablja le, ce je morebitna korist za mater vecja od morebitnega tveganja za plod. Uporabiti je treba najnižji ucinkoviti odmerek ciklezonida, potreben za vzdrževanje ustreznega nadzora astme. Neželeni ucinki: Obcasni: navzea, bruhanje, neprijeten okus v ustih, reakcije na mestu uporabe, suha sluznica na mestu uporabe, glivicne infekcije v ustih, glavobol, hripavost, kašelj po inhaliranju, paradoksni bronhospazem, ekcem in izpušcaj. Redki: palpitacije, bolecine v trebuhu, dispepsija, angioedem, preobcutljivost, hipertenzija. Neznana pogostnost: psihomotoricna hiperaktivnost, motnje spanja, tesnoba, depresija, agresija, vedenjske spremembe (pretežno pri otrocih). Nacin in režim predpisovanja in izdaje zdravila: Predpisovanje in izdaja zdravila je le na recept.Imetnik dovoljenja za promet: Covis Pharma Europe B.V., Gustav Mahlerplein 2, 1082MA Amsterdam, Nizozemska. Pred predpisovanjem, prosimo, preberite povzetek glavnih znacilnostizdravila. Datum revizije besedila: 08/2020. Seznam referenc: 1. ALVESCO SMPC 2. NEWMAN, S. ET AL. RESPIRATORY MEDICINE (2006) 100, 375–384. 3. DERENDORF , H. ET AL. EUR RESPIR J 2006; 28: 1042–1050 4. MUKKER, J. ET AL. JOURNAL OF PHARMACEUTICAL SCIENCES 105 (2016) 2509-2514. 5. CHIU, K-C. ET AL. PRIMARY CARE RESPIRATORY MEDICINE (2014) 24, ARTICLE NUMBER: 14010. 6. KNOX, A. CURRENT MEDICAL RESEARCH AND OPINION VOL. 23, NO. 10, 2007, 2387–2394. 7. ERIN, E. ET AL. CHEST 2008;134;740-745. Alvesco is a Covis registered trademark.© Copyright 2019 Covis Pharma. All rights reserved. SI-ALV-0920-002, september 2020 SAMO ZA STROKOVNO JAVNOST glave in vratu1 References: 1. Keytruda EU SmPC SKRAJŠAN POVZETEK GLAVNIH ZNACILNOSTI ZDRAVILA Pred predpisovanjem, prosimo, preberite celoten Povzetek glavnih znacilnosti zdra vila! Ime zdravila: KEYTRUDA 25 mg/ml koncentrat za raztopino za infundiranje vsebuje pem brolizumab. Terapevtske indikacije: Zdravilo KEYTRUDA je kot samostojno zdravljenje indicirano za zdravljenje: napredovalega (neoperabilnega ali metastatskega) melanoma pri odraslih; za adjuvantno zdravljenje odraslih z melanomom v stadiju III, ki se je razširil na bezgavke, po popolni kirurški odstranitvi; metastatskega nedrobnocelicnega pljucnega raka (NSCLC) v prvi liniji zdravljenja pri odraslih, ki imajo tumorje z = 50 % izraženostjo PD-L1 (TPS) in brez pozitivnih tumorskih mutacij EGFR ali ALK; lokalno napredovalega ali metastatskega NSCLC pri odraslih, ki imajo tumorje z = 1 % izraženostjo PD-L1 (TPS) in so bili predhod no zdravljeni z vsaj eno shemo kemoterapije, bolniki s pozitivnimi tumorskimi mutacijami EGFR ali ALK so pred prejemom zdravila KEYTRUDA morali prejeti tudi tarcno zdravljenje; odraslih bolnikov s ponovljenim ali neodzivnim klasicnim Hodgkinovim limfomom (cHL), pri katerih avtologna presaditev maticnih celic (ASCT) in zdravljenje z brentuksimabom vedotinom (BV) nista bila uspešna, in odraslih bolnikov, ki za presaditev niso primerni, zdravljenje z BV pa pri njih ni bilo uspešno; lokalno napredovalega ali metastatskega uro telijskega raka pri odraslih, predhodno zdravljenih s kemoterapijo, ki je vkljucevala platino; lokalno napredovalega ali metastatskega urotelijskega raka pri odraslih, ki niso primerni za zdravljenje s kemoterapijo, ki vsebuje cisplatin in imajo tumorje z izraženostjo PD-L1 = 10, ocenjeno s kombinirano pozitivno oceno (CPS); ponovljenega ali metastatskega plošcatocelicnega raka glave in vratu (HNSCC) pri odraslih, ki imajo tumorje z = 50 % izraženostjo PD-L1 (TPS), in pri katerih je bolezen napredovala med zdravljenjem ali po zdravljenju s kemoterapijo, ki je vkljucevala platino. Zdravilo KEYTRUDA je kot samostojno zdravljenje ali v kombinaciji s kemoterapijo s platino in 5-fluorouracilom (5-FU) indicirano za prvo linijo zdravljenja metastatskega ali neoperabilnega ponovljenega plošcatocelicnega raka glave in vratu pri odraslih, ki imajo tumorje z izraženostjo PD-L1 s CPS = 1. Zdravilo KEYTRUDA je v kombinaciji s pemetreksedom in kemoterapijo na osnovi platine indicirano za prvo linijo zdravljenja metastatskega neplošcatocelicnega NSCLC pri odraslih, pri katerih tumorji nimajo pozitivnih mutacij EGFR ali ALK; v kombinaciji s karboplatinom in bodisi pak litakselom bodisi nab-paklitakselom je indicirano za prvo linijo zdravljenja metastatskega plošcatocelicnega NSCLC pri odraslih; v kombinaciji z aksitinibom je indicirano za prvo linijo zdravljenja napredovalega raka ledvicnih celic (RCC) pri odraslih. Odmerjanje in nacin uporabe: Testiranje PD-L1 pri bolnikih z NSCLC, urotelijskim rakom ali HNSCC: Za samostojno zdravljenje z zdravilom KEYTRUDA je priporocljivo opraviti testiranje izraženosti PD-L1 tumorja z validirano preiskavo, da izberemo bolnike z NSCLC ali predhodno nezdravljenim urotelijskim rakom. Bolnike s HNSCC je treba za samostojno zdravljenje z zdravilom KEYTRUDA ali v kombinaciji s kemoterapijo s platino in 5-fluorouracilom (5-FU) izbrati na podlagi izraženosti PD-L1, potrjene z validirano preiskavo. Odmerjanje: Priporoceni odmerek zdravila KEYTRUDA za samostojno zdravljenje je bodisi 200 mg na 3 tedne ali 400 mg na 6 tednov, apliciran z intravensko infuzijo v 30 minutah. Priporoceni odmerek za kombinirano zdravljenje je 200 mg na 3 tedne, apliciran z intravensko infuzijo v 30 minutah. Za uporabo v kombinaciji glejte povzetke glavnih znacilnosti socasno uporabljenih zdravil. Ce se uporablja kot del kombiniranega zdravljenja skupaj z intraven sko kemoterapijo, je treba zdravilo KEYTRUDA aplicirati prvo. Bolnike je treba zdraviti do napredovanja bolezni ali nesprejemljivih toksicnih ucinkov. Pri adjuvantnem zdravljenju melanoma je treba zdravilo uporabljati do ponovitve bolezni, pojava nesprejemljivih to ksicnih ucinkov oziroma mora zdravljenje trajati do enega leta. Ce je aksitinib uporabljen v kombinaciji s pembrolizumabom, se lahko razmisli o povecanju odmerka aksitiniba nad zacetnih 5 mg v presledkih šest tednov ali vec. Pri bolnikih starih = 65 let, bolnikih z blago do zmerno okvaro ledvic, bolnikih z blago okvaro jeter prilagoditev odmerka ni potrebna. Odložitev odmerka ali ukinitev zdravljenja: Zmanjšanje odmerka zdravila KEYTRUDA ni priporocljivo. Za obvladovanje neželenih ucinkov je treba uporabo zdravila KEYTRUDAzadržati ali ukiniti, prosimo, glejte celoten Povzetek glavnih znacilnosti zdravila. Kontrain dikacije: Preobcutljivost na ucinkovino ali katero koli pomožno snov. Povzetek posebnih opozoril, previdnostnih ukrepov, interakcij in neželenih ucinkov: Imunsko pogojeni neželeni ucinki (pnevmonitis, kolitis, hepatitis, nefritis, endokrinopatije, neželeni ucinki na kožo in drugi): Pri bolnikih, ki so prejemali pembrolizumab, so se pojavili imunsko pogojeni neželeni ucinki, vkljucno s hudimi in smrtnimi primeri. Vecina imunsko pogojenih neželenih ucinkov, ki so se pojavili med zdravljenjem s pembrolizumabom, je bila reverzibilnih in so jih obvladali s prekinitvami uporabe pembrolizumaba, uporabo kortikosteroidov in/ali pod porno oskrbo. Pojavijo se lahko tudi po zadnjem odmerku pembrolizumaba in hkrati prizadanejo vec organskih sistemov. V primeru suma na imunsko pogojene neželene ucinke je treba poskrbeti za ustrezno oceno za potrditev etiologije oziroma izkljucitev drugih vzrokov. Glede na izrazitost neželenega ucinka je treba zadržati uporabo pembrolizumaba in uporabiti kortikosteroide za natancna navodila, prosimo, glejte Povzetek glavnih znacilnosti zdravila Keytruda. Zdravljenje s pembrolizumabom lahko poveca tveganje za zavrnitev pri prejemnikih presadkov cvrstih organov. Pri bolnikih, ki so prejemali pembrolizumab, so porocali o hudih z infuzijo povezanih reakcijah, vkljucno s preobcutljivostjo in anafilaksijo. Pembrolizumab se iz obtoka odstrani s katabolizmom, zato presnovnih medsebojnih delovanj zdravil ni pricakovati. Uporabi sistemskih kortikosteroidov ali imunosupresivov pred uvedbo pembrolizumaba se je treba izogibati, ker lahko vplivajo na farmakodinamicno aktivnost in ucinkovitost pembrolizumaba. Vendar pa je kortikosteroide ali druge imunosupresive mogoce uporabiti za zdravljenje imunsko pogojenih neželenih ucinkov. Kortikosteroide je mogoce uporabiti tudi kot premedikacijo, ce je pembrolizumab uporabljen v kombinaciji s kemoterapijo, kot antiemeticno profilakso in/ali za ublažitev neželenih ucinkov, povezanih s kemoterapijo. Ženske v rodni dobi morajo med zdravljenjem s pembrolizumabom in vsaj še 4 mesece po zadnjem odmerku pembrolizumaba uporabljati ucinkovito kontracepcijo, med nosecnostjo in dojenjem se ga ne sme uporabljati.Varnost pembrolizumaba pri samostojnem zdravljenju so v klinicnih študijah ocenili pri 5.884 bolnikih z napredovalim melanomom, kirurško odstranjenim melanomom v stadiju III (adjuvantno zdravljenje), NSCLC, cHL, urotelijskim rakom ali HNSCC s štirimi odmerki (2 mg/kg na 3 tedne, 200 mg na 3 tedne in 10 mg/kg na 2 ali 3 tedne). V tej populaciji bolnikov je mediani cas opazovanja znašal 7,3 mesece (v razponu od 1 dneva do 31 mesecev), najpogostejši neželeni ucinki zdravljenja s pembrolizumabom so bili utrujenost (32 %), navzea (20 %) in diareja (20 %). Vecina porocanih neželenih ucinkov pri samostojnem zdravljenju je bila po izrazitosti 1. ali 2. stopnje. Najresnejši neželeni ucinki so bili imunsko pogojeni neželeni ucinki in hude z infuzijo povezane reakcije. Varnost pembrolizumaba pri kombiniranem zdravljenju s kemoterapijo so ocenili pri 1.067 bolnikih NSCLC ali HNSCC, ki so v klinicnih študijah prejemali pembrolizumab v odmerkih 200 mg, 2 mg/kg ali 10 mg/kg na vsake 3 tedne. V tej populaciji bolnikov so bili najpogostejši neželeni ucinki naslednji: anemija (50 %), navzea (50 %), utrujenost (37 %), zaprtost (35%), diareja (30 %), nevtropenija (30 %), zmanjšanje apetita (28 %) in bruhanje (25 %). Pri kombiniranem zdravljenju s pembrolizumabom je pri bolnikih z NSCLC pojavnost neželenih ucinkov 3. do 5. stopnje znašala 67 %, pri zdravljenju samo s kemoterapijo pa 66 %, pri kombiniranem zdravljenju s pembrolizumabom pri bolnikih s HNSCC 85 % in pri zdravljenju s kemoterapijo v kombinaciji s cetuksimabom 84 %. Varnost pembrolizumaba v kombinaciji z aksitinibom so ocenili v klinicni študiji pri 429 bolnikih z napredovalim rakom ledvicnih celic, ki so prejemali 200 mg pembrolizumaba na 3 tedne in 5 mg aksitiniba dvakrat na dan. V tej populaciji bolnikov so bili najpogostejši neželeni ucinki diareja (54 %), hipertenzija (45 %), utrujenost (38 %), hipotiroidizem (35 %), zmanjšan apetit (30 %), sindrom palmarno-plantarne eritrodisestezije (28 %), navzea (28 %), zvišanje vrednosti ALT (27 %), zvišanje vrednosti AST (26 %), disfonija (25 %), kašelj (21 %) in zaprtost (21 %). Pojavnost neželenih ucinkov 3. do 5. stopnje je bila med kombiniranim zdravljenjem s pembrolizumabom 76 % in pri zdravljenju s sunitinibom samim 71 %. Za celoten seznam neželenih ucinkov, prosimo, glejte celoten Povzetek glavnih znacilnosti zdravilaNacin in režim izdaje zdravila: H Predpisovanje in izdaja zdravila je le na recept, zdra vilo se uporablja samo v bolnišnicah. Imetnik dovoljenja za promet z zdravilom: Merck Sharp & Dohme B.V. , Waarderweg 39, 2031 BN Haarlem, Nizozemska. Merck Sharp & Dohme inovativna zdravila d.o.o., Šmartinska cesta 140, 1000 Ljubljana, tel: +386 1/ 520 42 01, fax: +386 1/ 520 43 50Pripravljeno v Sloveniji, September 2020; SI-KEY-00145 EXP: 09/2022 Samo za strokovno javnost.H - Predpisovanje in izdaja zdravila je le na recept, zdravilo pa se uporablja samo v bolnišnicah. Pred predpisovanjem, prosimo, preberite celoten Povzetek glavnih znacilnosti zdravila Keytruda, ki je na voljo pri naših strokovnih sodelavcih ali na lokalnem sedežu družbe. P. zer Luxembourg SARL, GRAND DUCHY OF LUXEMBOURG, 51, Avenue J.F. Kennedy, L – 1855, LOR-07-20 P. zer, podružnica Ljubljana, Letališka cesta 29a, 1000 Ljubljana “SAMO ZA STROKOVNO JAVNOST” SAMO ZA ZDRAVSTVENE DELAVCE. Sanofi-aventis d.o.o., Letališka cesta 29A, 1000 Ljubljana, Slovenija MAT-SI-2000235-1.0-12/2020 Zdravilo Alunbrig se uporablja kot monoterapija za zdravljenje odraslih bolnikov z napredovalim nedrobnocelicnim pljucnim rakom (NSCLC – non small cell lung cancer), pozitivnim na anaplasticno limfomsko kinazo (ALK), ki še niso bili zdravljeni z inhibitorjem ALK. 1 SKRAJŠANI POVZE EK G AVNIH ZNACILNOS ZDRAVILA .• a o zd vo e v a dodano pemane vano ako bodo h ee na voo nove noma e o negovvano dav vene deave napoamoda pooao o kaeem ko domnevnem neeenem u nku zdavaPed pedp ovanem pebe e ceoen poveek g vnh zn no i zdava (mPC me zdava: AUNBRG 30 mg f mko oboene tabee; AUNBRG 90 mg f mko oboene tabee; AUNBRG 180 mg f mko oboene tabee Kakovo na n ko nka e avaAUNBRG 0 mg mko oboene abeeEna mko oboena abea vebue 0 mg bganbaAUNBRG 90 mg mko oboene abete n mko oboena abea vebue 0 mg bganba AUNBRG 0 mg mko oboene abee na mko oboena abea vebue 0 mg bg nband a e davo Aunbg e upoaba komonoeap a zdavene oda h bonkov napedovam nedobnoe nm punm akom NSCLC non ma eung ane pozvnm na anapa no momko knao AKke no bzdaven nhboem AKZdavo Aunbg e upoaba komonoeap a zdavene odah bonkov napedovam NSCLC poz vnm na AK o b pedhodno zdaven zdavom k onbOdmeanenan upoabePpooen aenodmeek e 90 mg en ana dan pvh dnnao p 0 mg enkana dan e e emane zdava Aunbg pekne a 4 dn a de dugegaaoga ko o neeen ucnk e ebadavene nadaeva odmekom 90 mg enka na dana obdobe 7 dn pedene odmeek poveca na pedhodnooe an odmeek. Ce odmeek n b au a ee po u u poavo buhane e dodanga odme nem au n poebno naedn odmee au ob p dhodno na ovanemau P agodve odme Huda o a e ppoo man naen odmee 60 mg en a n dan v pvh dnehenao 0 mg enana danHuda ovaa edv ppoo v manan aenodmeek 60 mg enkana dan v pvh dnehenao 90 mg enana dan ae odmea n eba pagaa Konandae Peobu vo na unkovno a ateo kopomono novPoebna opozoa n pevdnonueppupoabbganbaNeeenunkna pua Pbonh ahko pde do hudh venko nevnh n mnh neeenh unkov na puhvkuno nanomko enake kopPBpnevmon uVena neeenh unkov na pua e ba opaena v pvh dneh zdavenaNeeenunkna pua opne 2 o bodpavenpeknvo zdvena a pemembo odmekaVa ao n atek ntevamanko dnmed adnm odmekom onba n pvm odmekom zdava Aunbg a ba neodvno poveana poveano opno eh neeenh unkov na puaNekatebon o ad pnevmon a boekanee med zdavenem zdavom AunbgBonke e a v pvem ednu zdavena eba bno pema aadnovh apo banh mpomov dhanpdpneakae dBonkepkaeh o e poav naki pnevmon a s poabanmi smpomi boeni dha, je teba nemudoma pegeda. Ce sume na pnevmon , je teba odmeane zd va Aunbg zaano pe n , bon a pa oeni gede moebnh dugh v okov smpomov nppuna emboanapedovane umoanekc a punaOdmeek e eba u eno pemen Hpeena eba e edno nadoova vn akBadadaRedno e eba pema nup n kvn aMone vda Boniome ebaveova na pooao o kakrnih ko mpomih moen vda Zvišane kreanooknaeCPK Boniome ebaveova na pooao o kakrniho nepoasnenih boenah v mišiah obu vo al šibko miši Zvanje enmovebune navke eba jeedno nadoova konenajo amazenpaze Hepaook no poavoe jevana jenh enmovapataamnoanseaza aannamnoanseazan biubin Glede naeno aboao ko odk h nepavno e eba zdavene aano pen n u eno pemen odmeekMedebono deovane zdav ogba e e eba oanupoabzd va Aunbg monm av YPA e e oanupoab monh avaev YPA nmogoe ogn e eba odmeezdava Aunbg mana 80 mg na 90 mg 90 mg na 60 mgPo peknvupoabe monega avaa CYPA e eba zdavene zdavom Aunbg nadaeva odmekomkgaebon penašapedaekomupoabemonegaavaaCYPA ogba ee ebaoanupoab davaAunbg monmnmenmnduko CYPAPodnost Ženkamvodndobe ebaveova na med zdavenem in vaj 4 meee po zadnem odmeku upoabao u nkovo nehomonko kon aep o. Mo m s pa ne mi v rodni dobi je teba sveov , naj upoabo u nkovo kon aep o med zd venem in vaj 3 meee po dnem odmeu zdava Aunbgaoza davo Aunbg vebue aozo monohdaBonk edko dedno noeano a ga ozoodono o enm aae amaabopo gukozegaakoze ne meo ema ega zdava Medebono deovane dugmzdav n duge obke neakc Unkovne ahko vao konena o bganba v pamZava YPA bganb e ub aCYPA4 Soana upoaba vek nh odmekov akonaoake moan avae YPAe poveaa konenao bganba v vSoanupoabmonh av ev YPA zdavom Aunbgvkuno neaempovunmzdav npndnavemnenvem onavemavnvem maodnm anboknp ka omnome omnom oeandomnom anmo np eoonazoom vo onazoom mbeadomn neazodonomeeebazogba menava CYPAnp d aemn vepam ahko poveao AUbganba a pbno 0%Pkombna menmava YPA pagaane odmea npoebnoGenvka a ok genvke ahko pav ako va konenae bganba v pamn e e eba ogbaZava CYP2C8bganb e ub aYP Soana upoaba vek nh odmekov gembozake mo n vae YP e manaa konenao bganba v kvP o nem odmeanu monh avaev CYP2C8 pagaane odmea npoebnoava Pgp n BCRPP oanupoab ava Pgp n BCRP p agaane odmeka zdava Aunbg npoebnoUnkovne hko nao konena o bganba v pam ndu o CYP o na upoaba ve anh odmekov ampn e manaa konenao bganba v v eba e e ogba oanupoabmonh nduoev YPA zdavom Aunbgvuno ampnomkabamazepnomenonom abunomenobabaom n enanevkoZmenndu o CYPA hko manao AUC bganb a pb no 50% ogba e e eba oanupoab menh ndu oev CYPA zdavom Aunbgv uno vendane omeeno na eaven modan boenaneav n n na nUnkovnekaem ahko bg nb pemenkonena o v pamSub a YPAbganb e ndu o YPA4 mana ahko konena e v pamp oano upoabenh zd vhk e v gavnem penavao CYPAZo e eba p oanupoabzdava Aunbg ub aCYPA ozm eapev m ndeom npaenanomenanom ndnom koponom omuomaomuom ogba kee ahko mana nhovunkovo Zdavo Aunbg ahko ndu a udduge enme n anpoe npCYP2CPgppeko enakh mehnmov o odgovon a ndukco YPA npakva a pegnankega X eepoa npon ub a Soana upoaba bganba ub aPgp npdgo ndabgaankohnpavaanBRP npmeoeka ouv nuaaanogan m aonkm penaaem O poena ek uo vezdavn oknov Mae n 2K MA E K ahko pove a njihovo kon ent a o v pa m Bon e e eba k bno p emjat ko e d av o Aunb g o a no upo ab eno ub at eh an po e ev o kim e apev kim ndek om np dgoksin dabgat an me o ek at Podno noeno n doene Ženke v odndobKonaep a a moke n enke Žen am v odndobe eba veova nane ano o n va4 meee po adnem odmeku upo bo unkovo nehomonko konaep o n mo m named zdavenem ne apodo ooaMokm pane amv odndobe eba veov n upoabo unkovo konaep o med zdavenem n va meee po dnem odme u zdav AunbgNoeno V pmeu emana zdav Aunbg med noeno oahko o povoovao podae e zdavo Aunbg upoba med noeno o a e bona anomed emanem tega zdavae eba bono enan poenano nevano o podDoene Ni znano, ai se zdavo Aunbg ioa v maeno mekoPodno : Na voo ni nobenh podakov o vpvu zdava Aunbg na podno . Neeeni un : Napogo ei neeeni uni (= 5% , o ka e h so po o ai p i bon h, ki so se zd av zdavom Aunbg pppooenem emu odmeanao vana A hpegkemahpenunem anemavana CPKnavzeapoveana paamanano evo moovpoveana A daeapoveana am uueno kae gavobo poveana a nao aa hpooaemavan vedno AP pu buhne dpne hpeenamananoe o bh vnhe magan p en nvopa Napogoe n neeen unk =2%), o aeh o pooapbonhzdavenh zdavom Aunbg pppooenem emu odmeanaaen punhpoveanh napedovanem neop meo bpnevmon puna n dpneaZa podoben poneeenh unkov davla Alunbgn medebono deovane dugmdav gleeeoen poveekglavnh znano davla Oaeem kodomnevnem neeenem unkudavla moae pooa naavno ageno Repube Soveneadavlan mednke ppomokeSeoa amkovganoNaonanenea amkovgano oveneva ua 2 000 ubanae+6 08 000 500ak+6 02000 50epoahamakovgana@amp pena anwww amp Poebna navod a hanevane a h nevane zdava no poebna poebna navodamen dovoena pome zdavom akeda Phama A DybendaAe 0260 aa upDan aDaum adne ev e beeda 0. ap. 2020. Daum ppave inoma e: apl 2020. Rem izdae zdava: Rp pe. Dodane inoma e so na voo p: Tkeda GmbH, Poduna Sovena, Beweova ce a 30, Lubana, te: 059 082 40 . Pov ek ga h zn n i zda a A UN RG, wwweuop m u, D um r e b d a: 0. s p. 20 0 Takeda GmbH, Podružnica Slovenija Bleiweisova cesta 30, 1000 Ljubljana, Slovenija SAMO ZA STROKOVNO JAVNOST tel.: + 386 (0) 59082480 C APROM/SI/BRI/0005 Datum priprave: oktober 2020 www.takeda.com Intuitivno oblikovan za nedvoumno uporabo. Nagrajeno oblikovanje1 Nared za uporabo zgolj z dvigom pokrovcka SKRAJŠAN POVZETEK GLAVNIH ZNACILNOSTI ZDRAVILA Spiolto® Respimat® 2,5 mikrograma/2,5 mikrograma raztopina za inhaliranje Kakovostna in kolicinska sestava: prejeti odmerek vsebuje 2,5 mikrograma tiotropija (v obliki bromida monohidrata) in 2,5 mikrograma olodaterola (v obliki klorida) na vpih. Prejeti odmerek je kolicina, ki jo bolnik prejme po prehodu zdravila skozi ustnik. Pomožna snov z znanim ucinkom: to zdravilo vsebuje 0,0011 mg benzalkonijevega klorida ob vsaki sprožitvi (vpihu). Za celoten seznam pomožnih snovi glejte poglavje 6.1. Terapevtske indikacije: zdravilo Spiolto Respimat je indicirano za vzdrževalno bronhodilatacijsko zdravljenje, ki zmanjša simptome pri odraslih bolnikih s kronicno obstruktivno pljucno boleznijo (KOPB). Odmerjanje in nacin uporabe: zdravilo je namenjeno samo za inhaliranje. Vložek je možno vstaviti samo v inhalator Respimat in ga z njim uporabljati. Dva vpiha z inhalatorjem Respimat predstavljata en odmerek zdravila. Priporoceni odmerek je 5 mikrogramov tiotropija in 5 mikrogramov olodaterola, vnesenih z dvema vpihoma z inhalatorjem Respimat enkrat na dan, vsak dan ob istem casu. Bolnik priporocenega odmerka ne sme preseci. Okvara jeter: o uporabi olodaterola pri bolnikih s hudo okvaro jeter ni podatkov. Okvara ledvic: pri bolnikih s hudo okvaro ledvic je malo izkušenj z uporabo olodaterola. Pediatricna populacija: zdravilo Spiolto Respimat ni namenjeno za uporabo pri pediatricni populaciji (mlajši od 18 let). Kontraindikacije: preobcutljivost na ucinkovini ali katero koli pomožno snov. Preobcutljivost za atropin ali njegove derivate, npr. ipratropij ali oksitropij, v anamnezi. Posebna opozorila in previdnostni ukrepi: astma (zdravila Spiolto Respimat ne smejo uporabljati bolniki z astmo), ni primeren za akutne epizode, paradoksni bronhospazem (lahko povzroci paradoksni bronhospazem), previdno ga je treba uporabljati pri glavkomu z ozkim zakotjem, hiperplaziji prostate in zapori vratu secnega mehurja, ocesni simptomi (bolnike je treba opozoriti, naj pazijo, da razpršeno zdravilo ne bi zašlo v oci), zobni karies (zaradi suhih ust, se lahko v daljšem obdobju razvije zobni karies), okvara ledvic (pri bolnikih z zmerno do hudo okvaro ledvic smemo uporabljati zdravilo Spiolto Respimat samo, ce je pricakovana korist zdravljenja vecja od možnega tveganja. Pri bolnikih s hudo okvaro ledvic ni na voljo izkušenj z dolgotrajno uporabo). Ucinki na srce in ožilje; pri bolnikih, ki so v preteklem letu utrpeli srcni infarkt, bolnikih z nestabilno ali življenjsko nevarno srcno aritmijo, bolnikih, ki so se v preteklem letu zdravili v bolnišnici zaradi srcnega popušcanja ali so imeli diagnozo paroksizmalne tahikardije je treba zdravilo uporabljati previdno. Olodaterol ima lahko pri nekaterih bolnikih klinicno pomembne ucinke na srce in ožilje, ki se kažejo kot pospešen pulz, zvišan krvni tlak in/ali simptomi. Zdravilo lahko povzroci tudi spremembe na EKG, npr. splošcenost vala T in depresijo segmenta ST. Previdnost je potrebna pri bolnikih s srcnožilnimi boleznimi, zlasti z ishemicno boleznijo srca, hudo srcno dekompenzacijo, srcnimi aritmijami, hipertroficno obstrukcijsko kardiomiopatijo, hipertenzijo in anevrizmo, konvulzivnimi motnjami ali tirotoksikozo, znanim ali domnevnim podaljšanjem intervala QT in bolnikih, ki so neobicajno odzivni na simpatikomimeticne amine). Lahko povzroci hipokaliemijo, hiperglikemijo (lahko zviša raven glukoze v plazmi). Previdnost je potrebna pri anesteziji (potrebna je previdnost pri nacrtovanih operacijah s halogeniranimi ogljikovodikovimi anestetiki). Zdravila Spiolto Respimat ne smemo uporabljati hkrati z zdravili, ki vsebujejo dolgodelujoce agoniste adrenergicnih receptorjev beta2. Zdravila Spiolto Respimat bolniki ne smejo uporabiti pogosteje kot enkrat na dan. Po uporabi zdravila Spiolto Respimat se lahko pojavijo takojšnje preobcutljivostne reakcije. Benzalkonijev klorid lahko povzroci sopenje ali težave z dihanjem. Pri bolnikih z astmo je tveganje za tovrstne neželene ucinke povecano. Medsebojno delovanje z drugimi zdravili in druge oblike interakcij: antiholinergicna zdravila, druge adrenergicne ucinkovine, derivati ksantina, steroidi ali diuretiki; agonisti adrenergicnih receptorjev beta, zaviralci MAO in triciklicni antidepresivi, zdravila, ki podaljšajo QTc; .ukonazol in ketokonazol. Iz previdnostnih razlogov se je med nosecnostjo bolje izogibati uporabi zdravila Spiolto Resimat. Tako kot drugi agonisti adrenergicnih receptorjev beta2 lahko tudi olodaterol zaradi sprošcajocega ucinka na gladke maternicne mišice zavre porod. Med dojenjem je uporaba kontraindicirana. Pri vožnji avtomobila in upravljanju s stroji je potrebna previdnost. Ce se pojavita omotica ali zamegljen vid, naj se bolniki izogibajo dejavnostim, ki so lahko nevarne, npr. vožnji in upravljanju s stroji. Neželeni ucinki: pogosti: suha usta. Obcasni: omotica, nespecnost, glavobol, atrijska .brilacija, palpitacije, tahikardija, hipertenzija, kašelj, disfonija in zaprtje. Redki: nazofaringitis, zamegljen vid, supraventrikularna tahikardija, epistaksa, laringitis, faringitis, gingivitis, navzea, orofaringealna kandidoza, angioedem, urtikarija, preobcutljivost, pruritus, bolecina v hrbtu, artralgija, retencija urina, okužba secil in dizurija. Neznana pogostnost: dehidracija, glavkom, povišan ocesni tlak, bronhospazem, sinusitis, crevesna zapora, paraliticni ileus, zobni karies, disfagija, gastroezofagealna re.uksna bolezen, glositis, stomatitis, ana.lakticna reakcija, izpušcaj, suha koža, kožne okužbe in razjede ter oteklost sklepov. Nacin in režim izdaje: Rp. Imetnik dovoljenja za promet: Boehringer Ingelheim International GmbH, Binger Strasse 173, D-55216 Ingelheim am Rhein, Nemcija. Za podrobnejše informacije glejte Povzetek glavnih znacilnosti zdravila z dne 20.03.2020. Literatura: 1. Dhand R s sod. Int J COPD 2019. DOI 10.2147.COPD.S190639 2. SPIOLTO® RESPIMAT® Povzetek glavnih znacilnosti zdravila. Marec 2020. 3. Buhl R s sod. ERJ. 2015;45:969-79. 4. Singh D s sod. Respir Med. 2015; 109(10):1312-9. V kolikor imate medicinsko vprašanje v povezavi z zdravilom podjetja Boehringer Ingelheim, Podružnica Ljubljana, Vas prosimo, da poklicete na telefonsko številko 01/5864-000 ali pošljete vaše vprašanje na elektronski naslov: medinfo@boehringer-ingelheim.com. Samo za strokovno javnost. Boehringer Ingelheim RCV, Datum priprave informacije: oktober 2020 Podrućnica Ljubljana, ©landrova 4b, Ljubljana PC-SL-100326