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1. Real-world use of inhaled corticosteroid/formoterol as needed in adults with mild asthma: the PRIME study

Author: Guy Brusselle, Francesco Blasi, Christian Gessner, Piotr Kuna, Peter Wark, Glauco Cappellini, Emilie Oosterom, Marielle Van Der Deijl, Enrica Bucchioni, and Eva Topole
Subjects: Medicine
Abstract: Introduction Inhaled corticosteroid/formoterol fumarate (ICS/FF) as needed is recommended by the Global Initiative for Asthma (GINA) as sole therapy in adults with mild asthma, with low-dose maintenance ICS plus short-acting β2-agonist (SABA) as an alternative. SABA alone is no longer recommended. Given these changes in recommendations, the observational PRIME study aimed to describe real-world treatment patterns in mild asthma in Europe. Methods Adults with asthma receiving low-dose maintenance ICS, or as needed ICS/FF or SABA were followed for 6 months. Data collected included Asthma Control Test (ACT), Asthma Control Questionnaire 5-item (ACQ-5), forced expiratory volume in 1 s (FEV1) and asthma exacerbations. Results The study was conducted in 883 patients in Germany, Italy, Poland and Spain; 833 (94.3%) completed follow-up. At enrolment, 32.2% received maintenance ICS, 56.3% ICS/FF as needed and 11.6% SABA as needed; 57.4%, 61.2% and 54.9%, respectively, had well-controlled asthma (ACQ-5/ACT definition). After 6 months, changes in mean FEV1 were small in the maintenance ICS and ICS/FF as needed groups, whereas there was a decline in FEV1 in the SABA as needed group. ACQ-5 total score improved from baseline in all three groups; 0.4%, 0.4% and 2.0% patients, respectively, had a severe exacerbation during the study. Conclusions More patients received ICS/FF as needed than SABA as needed, suggesting that physicians are aware of the latest treatment recommendations. This real-world study provides additional support to the use of ICS/FF as needed as preferred treatment for patients with mild asthma, whereas SABA as needed was associated with a fall in lung function and more severe exacerbations.
Published: 2024
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2. Characteristics of severe asthma patients on biologics: a real-life European registry study

Author: Stefania Principe, Levi B. Richards, Simone Hashimoto, Johannes Anthon Kroes, Job J.M.H. Van Bragt, Susanne J. Vijverberg, Jacob K. Sont, Nicola Scichilone, Kristina Bieksiene, Anneke Ten Brinke, Zsuzsanna Csoma, Barbro Dahlén, Bilun Gemicioglu, Ineta Grisle, Piotr Kuna, Zorica Lazic, Florin Mihaltan, Sanja Popović-Grle, Sabina Škrgat, Alessandro Marcon, Marco Caminati, Ratko Djukanovic, Celeste Porsbjerg, and Anke-Hilse Maitland Van Der Zee
Subjects: Medicine
Abstract: Background The use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs. Materials and methods We performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs (four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies. Results Patients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: ≥10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score ≤1.5 and low-dose inhaled corticosteroids. Conclusion A large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma.
Published: 2023
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3. Heterogeneity in the use of biologics for severe asthma in Europe: a SHARP ERS study

Author: Anne-Noelle Frix, Liam G. Heaney, Barbro Dahlén, Florin Mihaltan, Svetlana Sergejeva, Sanja Popović-Grle, Vratislav Sedlak, Lauri Lehtimäki, Arnaud Bourdin, Stephanie Korn, Eleftherios Zervas, Zsuzsanna Csoma, Dora Lúðvíksdóttir, Marcus Butler, Giorgio Walter Canonica, Ineta Grisle, Kristina Bieksiene, Anneke Ten Brinke, Piotr Kuna, Claudia Chaves Loureiro, Natalia M. Nenasheva, Zorica Lazic, Sabina Škrgat, David Ramos-Barbon, Joerg Leuppi, Bilun Gemicioglu, Apostolos Bossios, Celeste M. Porsbjerg, Elisabeth H. Bel, Ratko Djukanovic, and Renaud Louis
Subjects: Medicine
Abstract: Introduction Treatment with biologics for severe asthma is informed by international and national guidelines and defined by national regulating bodies, but how these drugs are used in real-life is unknown. Materials and methods The European Respiratory Society (ERS) SHARP Clinical Research Collaboration conducted a three-step survey collecting information on asthma biologics use in Europe. Five geographically distant countries defined the survey questions, focusing on seven end-points: biologics availability and financial issues, prescription and administration modalities, inclusion criteria, continuation criteria, switching biologics, combining biologics and evaluation of corticosteroid toxicity. The survey was then sent to SHARP National Leads of 28 European countries. Finally, selected questions were submitted to a broad group of 263 asthma experts identified by national societies. Results Availability of biologics varied between countries, with 17 out of 28 countries having all five existing biologics. Authorised prescribers (pulmonologists and other specialists) also differed. In-hospital administration was the preferred deliverance modality. While exacerbation rate was used as an inclusion criterion in all countries, forced expiratory volume in 1 s was used in 46%. Blood eosinophils were an inclusion criterion in all countries for interleukin-5 (IL-5)-targeted and IL-4/IL-13-targeted biologics, with varying thresholds. There were no formally established criteria for continuing biologics. Reduction in exacerbations represented the most important benchmark, followed by improvement in asthma control and quality of life. Only 73% (191 out of 263) of surveyed clinicians assessed their patients for corticosteroid-induced toxicity. Conclusion Our study reveals important heterogeneity in the use of asthma biologics across Europe. To what extent this impacts on clinical outcomes relevant to patients and healthcare services needs further investigation.
Published: 2022
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4. The prevalence of asthma work relatedness: Preliminary data

Author: Wojciech Dudek, Izabela Kupryś-Lipińska, Tomasz Wittczak, Dominika Świerczyńska-Machura, Maciej Kupczyk, Jolanta Walusiak-Skorupa, Piotr Kuna, and Cezary Pałczyński
Subjects: asthma, occupational diseases, epidemiology, Medicine
Abstract: Objectives: About 5–10% of asthmatics do not respond well to standard treatment plan. Occupational exposure may be one of the factors that can be linked with treatment failure. The aim of the study was to assess the prevalence of work-related asthma (WRA) among adult asthmatics under follow up in an outpatient allergy clinic and to create a useful tool for detecting individuals with possible WRA. Material and Methods: Preliminary 5-question questionnaire designed to recognize WRA was presented to 300 asthmatics. All patients with positive preliminary verification along with 50 subjects from control group were asked to fill up a detailed questionnaire. The WRA was diagnosed by positive match for asthma symptoms in combination with workplace exposure indicated in the detailed WRA questionnaire followed by confirmation of each WRA case by detailed exposure analysis. Results: Work-related asthma was recognized in 63 subjects (21% of study group). The preliminary questionnaire has 76.9% sensitivity and 94% specificity in recognition of WRA. Occupational exposure to irritants is a risk factor of WRA recognition (relative risk (RR) = 2.09 (1.44:3.03)). Working in exposure-free environment is a factor against WRA recognition (RR = 0.38 (0.24:0.61)). Among subjects with work-related asthma, the uncontrolled course of the disease is significantly more frequent (p = 0.012). Subjects with WRA more often report sickness absenteeism due to asthma than those without WRA (9.6% vs. 3.2%, respectively), but the observed differences did not reach the statistical significance. Conclusions: Short 5-question questionnaire seems to be a promising tool to detect individuals with possible work-related asthma in the outpatient setting for further evaluation and additional attention.
Published: 2015
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5. Knowledge of medical law amongst doctors of internal diseases

Author: Justyna Zajdel, Radosław Zajdel, and Piotr Kuna
Subjects: medical law, informed consent, legal awareness, patients’ rights, Medicine
Abstract: Objectives: In Poland, 95% of medical personnel had not received legal education before they completed their studies. Having been given these facts, we have started questioning legal awareness of people providing medical services. Aim of the study: The study aimed at evaluating the knowledge of allergists and pulmonologists. Material and Methods: The group consisting of 328 allergists and/or pulmonologist completed the questionnaire. Results: The participants possess the best knowledge in providing information to patients about their health status (CV1). Sixty nine % of responders replied correctly, and the difference was significant (p < 0.001) in comparison with next aspect referring to the principles of providing medical services following guidelines created by think-tanks and also possibilities to take autonomous decisions by physicians (CV2). The correct answers in relation to CV2 were given by 57% of responders. The third compared aspect was physicians' awareness of patients' right to giving a consent or refusal before undertaking the medical procedure CV3. Only 55% of physicians gave correct answers and the difference was significant compared to CV1 (p < 0.001) as well as CV2 (p < 0.05). Younger doctors showed to have better knowledge than their older colleagues (p < 0.05). Working in urban workplaces proved to be more associated with better knowledge than in rural ones (p < 0.05). Discussion: Insufficient knowledge results in a low quality of provided services and puts the doctors at risk of being liable. The rates indicate that doctors are not aware of the fact that only legal regulations are binding, while standards not published by the Minister of Health are not legally valid. Half of the respondents have the wrong belief that the opinions expressed by experts make the doctor feel exempt from liability. Probably there are specialities, like occupational medicine which are specially linked with awareness of valid legal rules.
Published: 2013
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6. Brak związku polimorfizmu –590 C/T genu IL-4 oraz –1082 A/G genu IL-10 z rozwojem atopowego zapalenia skóry

Author: Anna Sysa-Jędrzejowska, Piotr Kuna, Iwona Stelmach, Karolina Przybyłowska, Aleksandra Lesiak, Marcin Zakrzewski, and Joanna Narbutt
Subjects: atopowe zapalenie skóry, polimorfizm –590 C/T genu IL-4, polimorfizm –1082 A/G genu IL-10, patogeneza, Medicine, Dermatology, RL1-803
Abstract: Wprowadzenie: Atopowe zapalenie skóry (AZS) jest przewlekłą,zapalną dermatozą, często współistniejącą z innymi chorobami atopowymi,takimi jak astma, alergiczny nieżyt nosa bądź spojówek. Wśródwielu czynników etiopatogenetycznych podłoże genetyczne, obejmującepolimorfizmy i mutacje w genach kodujących białka zaangażowanew prawidłową budowę bariery naskórkowej oraz odpowiedź immunologiczną,jest przedmiotem wielu prac badawczych. W patogenezieAZS szczególną rolę przypisuje się cytokinom Th2-zależnym, w tyminterleukinom 4 i 10 (IL-4 i IL-10). Cel pracy: Ocena polimorfizmów regionu promotorowego –590 C/Tgenu IL-4 oraz 1082 A/G genu IL-10 u pacjentów z AZS zamieszkującychteren województwa łódzkiego. Materiał i metodyka: Grupę badawczą stanowiło 163 chorych na AZS,u których rozpoznanie choroby ustalono na podstawie kryteriów Hanifinai Rajki, natomiast grupę kontrolną 204 zdrowych wolontariuszy.Nasilenie procesu chorobowego u wszystkich chorych oceniono przyużyciu skali Rajki i Langelanda. Analizę wariantów polimorficznychw regionie promotorowym genów IL-4 i IL-10 przeprowadzono metodąRFLP-PCR z wykorzystaniem enzymów restrykcyjnych do wykrywaniazmian w sekwencji DNA. Wyniki: Nie wykazano istotnych statystycznie różnic w rozkładziegenotypów polimorfizmów –590 C/T dla IL-4 oraz –1082 A/G genuIL-10 między grupą pacjentów a grupą kontrolną (p > 0,05 dla wszystkichporównań). W badanych polimorfizmach genów kodujących IL-4i IL-10 rozkład genotypów nie różnił się statystycznie istotnie w grupiepacjentów mających łagodny przebieg AZS od chorych z AZS o umiarkowanymi ciężkim przebiegu. Nie stwierdzono (p > 0,05) równieżzwiązku między badanymi polimorfizmami genów IL-4 i IL-10 a wczesnymzachorowaniem na astmę. Wnioski: Brak pozytywnej korelacji między obecnością polimorfizmówgenów IL-4 oraz IL-10 a rozwojem AZS w badanej grupie chorychmoże świadczyć o odmienności genetycznej badanej populacji,a także o dużej różnorodności czynników genetycznych zaangażowanychw patogenezę tego schorzenia, zależnie od pochodzenia chorych.
Published: 2010

7. Management of anaphylaxis due to COVID-19 vaccines in the elderly

Author: Paulo Augusto Moreira Camargos, Radolslaw Gawlik, Mirko Petrovic, Gunter J. Sturm, Kristof Nekam, Sergio Bonini, Zhanat Ispayeva, Marilyn Urrutia Pereira, Jean Bousquet, Antti Lauerma, Menachem Rottem, Arzu Yorgancioglu, Hubert Blain, Antonio Cherubini, Mário Morais-Almeida, Nathalie Salles, Charlotte G. Mortz, Sylwia Smolinska, Davor Plavec, A. Bedbrook, Torsten Zuberbier, Helga Kraxner, M. Beatrice Bilò, Sinthia Bosnic-Anticevich, Gaëtan Gavazzi, Finbarr C. Martin, Alvaro A. Cruz, K. S. Bennoor, Isabella Annesi-Maesano, Mohamed H. Shamji, Karin Hoffmann-Sommergruber, Marina Atanaskovic-Markovic, Carsten Bindslev-Jensen, Lan Tt Le, Isabel Skypala, Ana Todo-Bom, Vincenzo Patella, Lorenzo Cecchi, Charlotte Suppli Ulrik, Oscar Palomares, Joaquin Sastre, Hans Jürgen Hoffmann, Knut Brockow, Eva Untersmayr, Martin Hrubisko, Bernadette Eberlein, Aziz Sheikh, Milan Sova, Osman M. Yusuf, Violeta Kvedariene, G. Walter Canonica, Dana Wallace, Ioana Agache, Milena Sokolowska, Jos M. G. A. Schols, Susan Waserman, Stéphanie Miot, Carla Irani, Regina E Roller-Winsberger, Michael Levin, Yves Rolland, Emma Montella, Bilun Gemicioglu, Bolesław Samoliński, Stefano Del Giacco, Madda lenaIllario, Yehia El-Gamal, Olga Lourenço, Jean-Christoph Roger J-P Caubet, Luisa Brussino, Marysia Recto, De Yun Wang, Igor Kaidashev, Renaud Louis, Antonino Romano, Mario E. Zernotti, Jacques Reynes, Pedro Carreiro-Martins, Alexandra F. Santos, Marek Niedoszytko, M. Gotua, Musa Khaitov, Thomas B. Casale, Andrea Matucci, Bernardo Sousa-Pinto, Rafael Stelmach, Dejan Dokic, Joana Vitte, Motohiro Ebisawa, Maria Teresa Ventura, Joaquim Mullol, Tomas Chivato, Petr Panzner, Oliver Pfaar, Sanna Toppila-Salmi, Ioanna Tsiligianni, Wytske Fokkens, Alessandra Vultaggio, H. Neffen, Juan Carlos Ivancevich, Ya-dong Gao, Anna Sediva, Maja Hofmann, Ana Maria Carriazo, João Fonseca, Marek Jutel, A. Benetos, Nhân Pham-Thi, Mona Al-Ahmad, Arunas Valiulis, Mihaela Zidarn, Elizabeth Angier, Yoshitaka Okamoto, Montserrat Fernandez-Rivas, Cezmi A. Akdis, Philip W. Rouadi, Olivier Guérin, John Farrell, Mikaela Odemyr, George Christoff, Vera Mahler, Claus Bachert, Edward F. Knol, Wienczyslawa Czarlewski, Robyn E O'Hehir, Victoria Cardona, Ludger Klimek, Tari Haahtela, Vincent Le Moing, Branislava Milenkovic, Carmen Rondon, Kaja Julge, Jolanta Walusiak-Skorupa, Nikolaos G. Papadopoulos, Aslı Gelincik, Markus Ollert, Piotr Kuna, Leyla Namazova-Baranova, Margitta Worm, Annick Barbaud, Elena Camelia Berghea, Todor A. Popov, Derek K. Chu, María José Torres, Faradiba Sarquis Serpa, Nicola Scichilone, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Gianni Passalacqua, Humboldt-Universität zu Berlin, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Humboldt University Of Berlin, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Transylvania University, Wrocław Medical University, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Cagliari, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Università Politecnica delle Marche [Ancona] (UNIVPM), Medical Consulting Czarlewski, Universiti Putra Malaysia, University of Southampton, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Belgrade [Belgrade], Ghent University Hospital, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Dhaka Shishu Hospital [Bangladesh], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Odense University Hospital (OUH), Italian National Research Council, National Research Council [Italy] (CNR), The University of Sydney, Technische Universität München = Technical University of Munich (TUM), Università degli studi di Torino = University of Turin (UNITO), Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), IRCCS Research Hospital, Milan, Vall d'Hebron University Hospital [Barcelona], Centro Hospitalar de Lisboa Central E.P.E, University of South Florida [Tampa] (USF), Geneva University Hospital (HUG), Azienda Usl Toscana centro [Firenze], Софийски университет = Sofia University, McMaster University [Hamilton, Ontario], State University of Bahia, Institute of Public Health of Republic of North Macedonia [Skopje], Ain Shams University (ASU), Sagamihara National Hospital [Kanagawa, Japan], Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Amsterdam UMC - Amsterdam University Medical Center, Universidade do Porto = University of Porto, Wuhan University [China], CHU Grenoble, Silesian University of Medicine, Istanbul Faculty of Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Centre Hospitalier Universitaire de Nice (CHU Nice), Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Medizinische Universität Wien = Medical University of Vienna, Aarhus University [Aarhus], Oncology Institute of St Elisabeth, University of Naples Federico II = Università degli studi di Napoli Federico II, St Joseph University, Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Kazakh National Medical University, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Tartu University Institute of Clinical Medicine, Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Federal Medicobiological Agency [Moscow, Russian Federation], University Medical Center [Utrecht], Semmelweis University [Budapest], Medical University of Łódź (MUL), Vilnius University [Vilnius], University of Medicine and Pharmacy (VIETNAM), University of Cape Town, CHU Sart Tilman, Université de Liège, University of Beira Interior [Portugal] (UBI), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), uBibliorum, Ear, Nose and Throat, AII - Inflammatory diseases, CHU Montpellier, Wroclaw Medical University [Wrocław, Pologne], University of Bari Aldo Moro (UNIBA), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sagamihara National Hospital, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Toulouse [Toulouse], RS: CAPHRI - R1 - Ageing and Long-Term Care, Health Services Research, Bousquet J., Agache I., Blain H., Jutel M., Ventura M.T., Worm M., Del Giacco S., Benetos A., Bilo B.M., Czarlewski W., Abdul Latiff A.H., Al-Ahmad M., Angier E., Annesi-Maesano I., Atanaskovic-Markovic M., Bachert C., Barbaud A., Bedbrook A., Bennoor K.S., Berghea E.C., Bindslev-Jensen C., Bonini S., Bosnic-Anticevich S., Brockow K., Brussino L., Camargos P., Canonica G.W., Cardona V., Carreiro-Martins P., Carriazo A., Casale T., Caubet J.-C., Cecchi L., Cherubini A., Christoff G., Chu D.K., Cruz A.A., Dokic D., El-Gamal Y., Ebisawa M., Eberlein B., Farrell J., Fernandez-Rivas M., Fokkens W.J., Fonseca J.A., Gao Y., Gavazzi G., Gawlik R., Gelincik A., Gemicioglu B., Gotua M., Guerin O., Haahtela T., Hoffmann-Sommergruber K., Hoffmann H.J., Hofmann M., Hrubisko M., Illario M., Irani C., Ispayeva Z., Ivancevich J.C., Julge K., Kaidashev I., Khaitov M., Knol E., Kraxner H., Kuna P., Kvedariene V., Lauerma A., Le L.T.T., Le Moing V., Levin M., Louis R., Lourenco O., Mahler V., Martin F.C., Matucci A., Milenkovic B., Miot S., Montella E., Morais-Almeida M., Mortz C.G., Mullol J., Namazova-Baranova L., Neffen H., Nekam K., Niedoszytko M., Odemyr M., O'Hehir R.E., Okamoto Y., Ollert M., Palomares O., Papadopoulos N.G., Panzner P., Passalacqua G., Patella V., Petrovic M., Pfaar O., Pham-Thi N., Plavec D., Popov T.A., Recto M.T., Regateiro F.S., Reynes J., Roller-Winsberger R.E., Rolland Y., Romano A., Rondon C., Rottem M., Rouadi P.W., Salles N., Samolinski B., Santos A.F., S Sarquis F., Sastre J., M. G. A. Schols J., Scichilone N., Sediva A., Shamji M.H., Sheikh A., Skypala I., Smolinska S., Sokolowska M., Sousa-Pinto B., Sova M., Stelmach R., Sturm G., Suppli Ulrik C., Todo-Bom A.M., Toppila-Salmi S., Tsiligianni I., Torres M., Untersmayr E., Urrutia Pereira M., Valiulis A., Vitte J., Vultaggio A., Wallace D., Walusiak-Skorupa J., Wang D.-Y., Waserman S., Yorgancioglu A., Yusuf O.M., Zernotti M., Zidarn M., Chivato T., Akdis C.A., Zuberbier T., Klimek L., HUS Inflammation Center, University of Helsinki, and Department of Dermatology, Allergology and Venereology
Subjects: Male, Allergy, Pediatrics, Eaaci Position Paper, COVID-19 vaccines, older (adults, GUIDELINES, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Immunology and Allergy, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Geriatrics, MESH: Aged, RISK, Vaccines, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, people), EPINEPHRINE, Epinephrine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, COVID -19 vaccines, Anaphylaxis, medicine.drug, older (adults/people), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), MESH: Covid-19, MESH: Epinephrine, Immunology, adrenaline, anaphylaxis, Aged, COVID-19 Vaccines, Humans, SARS-CoV-2, COVID-19, Settore MED/10 - Malattie Dell'Apparato Respiratorio, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes mellitus, Anaphylaxis/etiology, MESH: SARS-CoV-2, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, COVID‐19 vaccines, Older - Adults/people, Asthma, MESH: Humans, business.industry, adrenaline, anaphylaxis, COVID-19 vaccines, older (adults/people), medicine.disease, Obesity, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: Anaphylaxis, Older, 3121 General medicine, internal medicine and other clinical medicine, business, MESH: Covid-19 vaccines, 030215 immunology
Abstract: Submitted by (omml@ubi.pt) on 2021-07-05T10:47:24Z No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2021-07-05T10:49:11Z (GMT) No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Rejected by Pessoa (pfep@ubi.pt), reason: Rever os nomes dos autores. Depois da correção é só voltar a submeter. on 2021-07-05T10:54:19Z (GMT) Submitted by (omml@ubi.pt) on 2021-07-05T11:52:24Z No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2021-07-05T13:34:51Z (GMT) No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2021-07-05T13:35:49Z (GMT) No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Made available in DSpace on 2021-07-05T13:35:49Z (GMT). No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Previous issue date: 2021-04-02 info:eu-repo/semantics/publishedVersion
Published: 2021
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8. House dust mite sensitization and frequent antibiotic courses may suppress remission of rhinosinusitis and asthma symptoms in young children

Author: Łukasz Błażowski, Piotr Kuna, Błażej Rychlik, Dominik Strapagiel, Paweł Majak, Katarzyna Molińska, Joanna Jerzyńska, Jakub Lach, Joanna Majak, and Marta Latek
Subjects: medicine.medical_specialty, medicine.drug_class, Chronic rhinosinusitis, Dermatophagoides pteronyssinus, Immunology, Antibiotics, medicine, Animals, Humans, Immunology and Allergy, Antigens, Dermatophagoides, Child, Sensitization, Asthma, House dust mite, Mites, biology, business.industry, Pyroglyphidae, Dust, Asthma symptoms, Allergens, biology.organism_classification, medicine.disease, Dermatology, Anti-Bacterial Agents, medicine.anatomical_structure, Child, Preschool, business
Published: 2021
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9. Relationship between CCR5+FoxP3+ Treg cells and forced expiratory volume in 1 s, peak expiratory flow in patients with severe asthma

Author: Łukasz Kraszula, Piotr Kuna, Makandjou-Ola Eusebio, and M. Pietruczuk
Subjects: Spirometry, Severe asthma, chemical and pharmacologic phenomena, Dermatology, Treg cell, Flow cytometry, immune system diseases, medicine, Immunology and Allergy, In patient, Internal medicine, Asthma, medicine.diagnostic_test, business.industry, FOXP3, hemic and immune systems, Airway obstruction, asthma, medicine.disease, tregs, ccr5, RC31-1245, respiratory tract diseases, RL1-803, Immunology, business
Abstract: Introduction Severe asthma is a special clinical problem. CD4+CD25highCD127lowFoxp3+ Tregs play a role in maintaining appropriate immunological response. It is a known fact that Treg cells with CCR5 expression represent strong suppressive activity. It has been shown that a low number or altered function of FoxP3+ Tregs is associated with the inflammatory process and airway obstruction in asthma. Aim To evaluate whether CCR5 Tregs expression and surface density on FoxP3+ Treg cells depend on the severity of asthma. Material and methods The study included 50 patients with asthma (25 with severe and 25 with mild-to-moderate asthma). The control group comprised 25 healthy volunteers. The phenotype of CD4+CD25highCD127lowFoxp3+CCR5+ cells was evaluated by multicolour flow cytometry. The degree of airflow obstruction was assessed by spirometry as forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF). Results The absolute count of FoxP3+ Treg cells in patients with severe asthma was significantly decreased in comparison with the control group. MFI (median fluorescence intensity) of CCR5 expression on FoxP3+ Treg cells was significantly decreased in severe asthma compared to the mild-to-moderate asthma and control groups. CCR5 expression on FoxP3+ Treg cells as MFI positively correlated with lung function parameters FEV1% and PEF% in patients with severe asthma. Conclusions High CCR5 Tregs expression as MFI is associated with improved in lung function parameters: FEV1% and PEF% in patients with severe asthma. The measurement of CCR5 expression on the surface of peripheral blood FoxP3+ Treg cells as MFI could be an additional tool to estimate the severity of asthma.
Published: 2021

10. COVID-19 pandemic

Author: W. J. Fokkens, Jürgen Schwarze, Cezmi A. Akdis, J Mullol, W. Czarlewski, Claudia Traidl-Hoffmann, Claus Bachert, D. Larenas-Linnemann, Tomas Chivato, M. Gotua, Mateo Bonini, Ludger Klimek, Vincenzo Patella, A. A. Cruz, Stephanie Dramburg, Kari C. Nadeau, H W Fritsch, K. Ohta, Thomas Eiwegger, Robert M. Naclerio, Antti Lauerma, A. Yorgancioglu, Aslı Gelincik, Piotr Kuna, Oliver Pfaar, Carmen Riggioni, Violeta Kvedariene, Markus Ollert, Sinthia Bosnic-Anticevich, V. Cardona, S. Del Giacco, Sanna Toppila-Salmi, Helen A. Brough, Heimo Breiteneder, Valérie Hox, B. Samolinski, Zuzana Diamant, G.W. Canonica, Lihong Zhang, María José Torres, Y. Okamoto, Liam O'Mahony, Radosław Gawlik, Jolanta Walusiak-Skorupa, Sharon Chinthrajah, Winfried Rief, T. Haatela, M. Morais-Almeida, Ioana Agache, Manfred Schedlowski, I Skypala, R. Brehler, D. Y. Wang, João Fonseca, I. J. Ansotegui, Robyn E O'Hehir, Oscar Palomares, Charlotte G. Mortz, J. C. Ivancevich, C. Suppli Ulrik, M. T. Ventura, P M Matricardi, S Untersmayr, Gabrielle L. Onorato, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Vanitha Sampath, Arũnas Valiulis, Marek Jutel, Luisa Brussino, Pedro Carreiro-Martins, Jean Bousquet, Nikolaos G. Papadopoulos, A. Bedbrook, Torsten Zuberbier, Karin Hoffmann-Sommergruber, Edward F. Knol, Ear, Nose and Throat, AII - Inflammatory diseases, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service d'oto-rhino-laryngologie, Philipps Universität Marburg = Philipps University of Marburg, Allergologie, Stimm und Sprachstörungen [Wiesbaden, Germany], Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], University of Wrocław [Poland] (UWr), ALL-MED, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Medizinische Universität Wien = Medical University of Vienna, Stanford University, Skane University Hospital [Malmo], Lund University [Lund], Charles University [Prague] (CU), University Medical Center Groningen [Groningen] (UMCG), Univ Toronto, Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Mol Med, Toronto, ON M5G 0A4, Canada, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Amsterdam UMC - Amsterdam University Medical Center, Alfred Health, Victoria University [Melbourne], University College Cork (UCC), Sean N. Parker Center for Allergy and Asthma Research [Stanford], Stanford Medicine, Stanford University-Stanford University, University Clinics of Essen, University of Essen, Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Helmholtz Zentrum München = German Research Center for Environmental Health, University Hospital Augsburg, National University of Singapore (NUS), Beijing Tongren Hospital, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Evelina London Children's Hospital, King‘s College London, CEU-San Pablo University and HM-Hospitals School of Medicine, University of Cagliari, Medical University of Silesia (SUM), Istanbul University, Cliniques Universitaires Saint-Luc [Bruxelles], University Medical Center [Utrecht], Helsinki University Central Hospital, University of Helsinki, Odense University Hospital (OUH), Luxembourg Institute of Health (LIH), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Hospital Sant Joan de Déu [Barcelona], Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain], University of Edinburgh, NHS Foundation Trust [London], The Royal Marsden, Nofer Institute of Occupational Medicine (NIOM), Hospital Quirónsalud Bizkaia [Bilbao], Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], Woolcock Institute of Medical Research [Sydney], The University of Sydney, University of Turin, Mauriziano Umberto I Hospital, Humanitas University [Milan] (Hunimed), Vall d'Hebron University Hospital [Barcelona], Hospital de Dona Estefania, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Federal University of Bahia School of Medicine, Global Alliance Against Chronic Respiratory Diseases (GARD-WHO), Medical Consulting Czarlewski, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, MEDIDA, Lda, David Tvildiani Medical University (DTMU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Barlicki University Hospital, Vilnius University [Vilnius], Hospital Medica Sur [Mexico City, Mexico], Pantai Hospital [Kuala Lumpur], Hospital CUF Descobertas, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIBER de Epidemiología y Salud Pública (CIBERESP), Johns Hopkins University School of Medicine [Baltimore], Fukujuji Hospital, Tokyo National Hospital, Chiba Rosai Hospital, Chiba University Hospital, Royal Manchester Children's Hospital, University of Manchester [Manchester], General Children's Hospital of Athens P & A Kyriakou, 'Santa Maria della Speranza' Hospital, Centro Hospitalar e Universitário [Coimbra], Coimbra Institute for Clinical and Biomedical Research [Coimbra, Portugal] (iCBR - Faculty of Medicine), University of Coimbra [Portugal] (UC), Medical University of Warsaw - Poland, Hvidovre Hospital, University of Copenhagen = Københavns Universitet (UCPH), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Manisa Celal Bayar University, Transilvania University of Brasov, Salvy-Córdoba, Nathalie, Department of Dermatology, Allergology and Venereology, and HUS Inflammation Center
Subjects: 0301 basic medicine, viruses, Eaaci Position Paper, Medizin, Cochrane Library, GUIDELINES, FOOD ALLERGY, allergen immunotherapy, allergy clinic, anaphylaxis, asthma, clinical trials, COVID-19, Position Paper, psychological impact, SARS-CoV-2, Allergists, Health Personnel, Humans, Hypersensitivity, Information Technology, Patient Care Team, Triage, SARS‐CoV‐2, DESENSITIZATION, 0302 clinical medicine, MESH: Patient Care Team, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HDE ALER, Pandemic, Health care, Immunology and Allergy, ATOPIC-DERMATITIS, MESH: COVID-19, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, allergen immunotherapy (AIT), virus diseases, DRUG HYPERSENSITIVITY REACTIONS, 3. Good health, INFECTIONS, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Triage, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Allergen immunotherapy, medicine.medical_specialty, MESH: Information Technology, MESH: Hypersensitivity, Immunology, education, MEDLINE, DIAGNOSIS, psychological COVID, 03 medical and health sciences, MESH: Allergists, COVID‐19, medicine, MESH: SARS-CoV-2, ddc:610, RHINOSINUSITIS, MESH: Humans, business.industry, Clinical trial, Coronavirus, EXACERBATIONS, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, 3121 General medicine, internal medicine and other clinical medicine, Position paper, MESH: Health Personnel, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: BackgroundThe Coronavirus disease 2019 (COVID‐19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.MethodThe scientific information on COVID‐19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet.ResultsBased on diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.ConclusionsThis international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID‐19 pandemic.
Published: 2021
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11. A Phase 2a, Double-Blind, Placebo-controlled Randomized Trial of Inhaled TLR9 Agonist AZD1419 in Asthma

Author: Vibeke Backer, Mahdi Hashemi, Sofia Necander, Malin Aurell, Piotr Kuna, Ziad Taib, David J. Keeling, Robert L. Coffman, Robert Palmér, Fanyi Jiang, Sara Asimus, Stephen Delaney, Ioannis Psallidas, Katerina Pardali, Katarina Korsback, Joachim Almquist, Per Gustafson, Tariq Sethi, and Sam Jackson
Subjects: Pulmonary and Respiratory Medicine, Agonist, business.industry, medicine.drug_class, TLR9, chemical and pharmacologic phenomena, Pharmacology, Critical Care and Intensive Care Medicine, medicine.disease, Placebo, Type 2 immune response, law.invention, Double blind, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Randomized controlled trial, immune system diseases, law, Medicine, 030212 general & internal medicine, business, Receptor, Asthma
Abstract: Rationale: To examine the potential of TLR9 (Toll-like receptor 9) activation to modulate the type 2 immune response in asthma.Objectives: To evaluate efficacy and safety of AZD1419, an inhaled TLR...
Published: 2021
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12. Recommendations of the Polish Society of Allergology on the qualification of person with allergies and anaphylaxis to vaccination against COVID-19

Author: Ewa Czarnobilska, Cezary Pałczyński, Marita Nittner-Marszalska, Maciej Kupczyk, Marek Niedoszytko, Ewa Cichocka-Jarosz, Bolesław Samoliński, Justyna Zajdel-Całkowska, Radosław Śpiewak, Marek Jutel, Barbara Rogala, Marek Kulus, Piotr Kuna, and Jerzy Kruszewski
Subjects: szczepienia przeciw COVID-19, 2019-20 coronavirus outbreak, Allergy, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.disease, Vaccination, Family medicine, anafilaksja, General Earth and Planetary Sciences, Medicine, business, Anaphylaxis, General Environmental Science, Asthma
Abstract: Przedstawiono rekomendacje Polskiego Towarzystwa Alergologicznego dotyczące kwalifikacji osób z alergią i anafilaksją do szczepienia przeciw COVID-19, zarówno dla lekarzy kwalifikujących do szczepień przeciw COVID-19 niebędących alergologami, jak i dla alergologów konsultujących pacjentów z wywiadem przebytej anafilaksji lub ciężkiego (niekontrolowanego) przebiegu chorób alergicznych i astmy szczepionych przeciw COVID-19. Recommendations of the Polish Society of Allergology regarding the qualification of person with allergies and anaphylaxis for vaccination against COVID-19 were presented, both for doctors qualifying for vaccination against COVID-19 who are not allergologists and for allergologists consulting patients with a history of anaphylaxis or severe (uncontrolled) allergic diseases and asthma vaccinated against COVID-19.
Published: 2021
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13. Comparison of Dry-Powder Inhaler and Pressurized Metered-Dose Inhaler Formulations of Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium in Patients with COPD: The TRI-D Randomized Controlled Trial

Author: Piotr Kuna, George Georges, Kai-Michael Beeh, Massimo Corradi, Alessandro Guasconi, and Isabelle Viaud
Subjects: International Journal of Chronic Obstructive Pulmonary Disease, chronic obstructive pulmonary disease, law.invention, Pulmonary Disease, Chronic Obstructive, Double-Blind Method, Fumarates, Randomized controlled trial, law, Formoterol Fumarate, Administration, Inhalation, medicine, Humans, In patient, Metered Dose Inhalers, muscarinic antagonists, Original Research, COPD, Cross-Over Studies, business.industry, respiratory function tests, Inhaler, Beclomethasone, Area under the curve, General Medicine, respiratory system, medicine.disease, Glycopyrrolate, Metered-dose inhaler, Dry-powder inhaler, Bronchodilator Agents, Treatment Outcome, Anesthesia, Powders, adrenergic beta-2 receptor agonists, business, steroids
Abstract: Kai-Michael Beeh,1 Piotr Kuna,2 Massimo Corradi,3 Isabelle Viaud,4 Alessandro Guasconi,4 George Georges4 1Insaf Respiratory Research Institute, Wiesbaden, Germany; 2Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, ÅódÅº, Poland; 3Department of Medicine and Surgery, University of Parma, Parma, Italy; 4Global Clinical Development, Chiesi Farmaceutici SpA, Parma, ItalyCorrespondence: Kai-Michael BeehInsaf Respiratory Research Institute, Wiesbaden, GermanyTel +49 611 9854347Email k.beeh@insaf-wi.deBackground: Three 52-week studies in COPD have assessed the efficacy and safety of single-inhaler extrafine formulation triple therapy combining beclomethasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) delivered via pressurized metered-dose inhaler (pMDI). BDP/FF/G is now being developed for delivery via multi-dose dry-powder inhaler (DPI; NEXThaler). This study aimed to demonstrate non-inferiority of BDP/FF/G DPI vs pMDI for lung function.Methods: Multicenter, randomized, double-blind, double-dummy, active-controlled, three-way cross-over study in patients with COPD and post-bronchodilator forced expiratory volume in 1 second (FEV1) 30– 80% predicted. Patients received BDP/FF/G 100/6/10μg via DPI and pMDI, and BDP/FF 100/6μg via pMDI, all two inhalations twice daily for four weeks, with treatments separated by two-week washout. The two co-primary objectives were to demonstrate non-inferiority between the two BDP/FF/G formulations for FEV1 area under the curve between 0 and 12 hours post-dose (AUC0-12h) normalized by time and trough FEV1 at 24 hours, both on Day 28. EudraCT 2017– 004405-41.Results: Of 449 patients screened, 366 were randomized, with 342 (93.4%) completing all three treatment periods. The primary objectives were met, with changes from baseline in FEV1 AUC0– 12h and trough FEV1 on Day 28 similar for the two BDP/FF/G formulations, and the confidence intervals for the difference lying entirely within the pre-specified non-inferiority criterion (– 50mL): – 20 (– 35, – 6) mL and 3 (– 15, 20) mL for AUC0– 12h and trough FEV1, respectively. BDP/FF/G pMDI and DPI were statistically superior to BDP/FF for these endpoints (p< 0.001). A similar proportion of patients experienced adverse events with each treatment (15.5%, 18.7% and 15.4% with BDP/FF/G DPI and pMDI, and BDP/FF, respectively); the majority were mild or moderate, with few related to treatment.Conclusion: Extrafine BDP/FF/G DPI and pMDI demonstrated similar efficacy and safety in patients with COPD, supporting the DPI formulation as a valid alternative.Keywords: adrenergic beta-2 receptor agonists, muscarinic antagonists, steroids, respiratory function tests, chronic obstructive pulmonary disease
Published: 2021
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14. Upper‐airway dysbiosis related to frequent sweets consumption increases the risk of asthma in children with chronic rhinosinusitis

Author: Marta Sobalska-Kwapis, Katarzyna Molińska, Piotr Kuna, Marcin Wachulec, Cezary Pałczyński, Dorota Czech, Monika Baranowska, Dominik Strapagiel, Andrzej Błauż, Klaudyna Królikowska, Aleksandra Budniok, Jakub Lach, Błażej Rychlik, Marta Latek, Paweł Majak, Martyna Gruchała, and Joanna Majak
Subjects: medicine.medical_specialty, Immunology, Mucous membrane of nose, Atopy, 03 medical and health sciences, Nasal Polyps, 0302 clinical medicine, Immune system, Quality of life, Internal medicine, otorhinolaryngologic diseases, Humans, Immunology and Allergy, Medicine, Microbiome, Sinusitis, Child, Rhinitis, Asthma, business.industry, respiratory system, medicine.disease, respiratory tract diseases, 030228 respiratory system, Child, Preschool, Chronic Disease, Pediatrics, Perinatology and Child Health, Quality of Life, Dysbiosis, Airway, business, 030215 immunology
Abstract: Background Innate immunity response to local dysbiosis seems to be one of the most important immunological backgrounds of chronic rhinosinusitis (CRS) and concomitant asthma. We aimed to assess clinical determinants of upper-airway dysbiosis and its effect on nasal inflammatory profile and asthma risk in young children with CRS. Methods We recruited one hundred thirty-three children, aged 4-8 years with doctor-diagnosed CRS with or without asthma. The following procedures were performed in all participants: face-to-face standardized Sinus and Nasal Quality of Life questionnaire, skin prick test, taste perception testing, nasopharynx swab, and sampling of the nasal mucosa. Upper-airway dysbiosis was defined separately by asthma specific microbiome composition and reduced biodiversity. Multivariate methods were used to define the risk factors of asthma and upper-airway dysbiosis and their specific inflammatory profile of nasal mucosa. Results The asthma-specific upper-airway microbiome composition reflected by the decreased ratio of Patescibacteria/Actinobacteria independently of atopy increased the risk of asthma (OR:8.32; 95%CI:2.93-23.6). This asthma-specific microbiome composition was associated with ≥7/week sweets consumption (OR:2.64; 95%C:1.11-6.28), reduced biodiversity (OR:3.83; 95%CI:1.65-8.87), the presence of Staphylococcus strains in the nasopharynx (OR:4.25; 95%CI:1.12-16.1), and lower expression of beta-defensin 2, IL-5, IL-13 in the nasal mucosa. The reduced biodiversity was associated with frequent antibiotic use and with a higher nasal expression of IL-17 and T1R3 (sweet taste receptor). In asthmatic children reduced sweet taste perception was observed. Conclusions Specific upper-airway dysbiosis related to frequent sweets consumption, frequent antibiotics courses, and altered nasal immune function increases the risk of asthma in young children with CRS.
Published: 2020
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15. The -463G/A and -129G/A Myeloperoxidase-Encoding Gene Polymorphism in Chronic Obstructive Pulmonary Disease

Author: Łukasz Mokros, Andrzej Witusik, Tadeusz Pietras, Piotr Kuna, and Janusz Szemraj
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Locus (genetics), Gastroenterology, Pathogenesis, Pulmonary Disease, Chronic Obstructive, Gene Frequency, genotype, gene expression, polymorphic sites, Risk Factors, Internal medicine, Gene expression, Genotype, medicine, Humans, Genetic Predisposition to Disease, Gene, Peroxidase, COPD, Polymorphism, Genetic, Pulmonary Surfactant-Associated Protein A, biology, business.industry, Middle Aged, medicine.disease, Case-Control Studies, Myeloperoxidase, biology.protein, Female, Gene polymorphism, business
Abstract: Introduction: Neutrophils are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Myeloperoxidase is an important bactericidal granulocytic enzyme. It is of interest to question whether or not the polymorphic variants of the myeloperoxidase-encoding gene are associated with the risk of developing COPD. Material and methods: The study determined the risk of COPD development in 186 COPD patients and 220 healthy subjects in the context of two selected polymorphic sites of the promoter region of the myeloperoxidase-encoding gene. Results: It has been demonstrated that the AA genotype of locus -463 in the myeloperoxidase-encoding gene increases the risk of developing COPD (OR: 2.87; CI: 1.651–4.997). This genotype also correlates with a higher gene expression in patients (0.56 ± 0.12 vs. 0.31 ± 0.18 in patients with AG genotype and 0.29 ± 0.17, p < 0.01 in those with GG genotype). In healthy indivi-duals, the AA genotype was also characterized by increased expression of the myeloperoxidase-encoding gene (0.41 ± 0.16 vs. 0.29 ± 0.15 for AG genotype, p < 0.01 and 0.25 ± 0.16 for GG genotype p < 0.01). Patients with the AA genotype had a significantly higher gene expression than healthy subjects with this genotype. Conclusions: The polymorphic site −129 of the myeloperoxidase-encoding gene was unrelated to the development of COPD. The gene expression did not differ for the individual genotypes. Our studies indicate that the polymorphism of the myeloperoxidase-encoding gene may be related to chronic obstructive pulmonary disease.
Published: 2020
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16. Artificial neural network identifies nonsteroidal anti‐inflammatory drugs exacerbated respiratory disease (N‐ERD) cohort

Author: Lucyna Mastalerz, Piotr Kuna, Adrianna Kot, Bogdan Jakiela, Natalia Celejewska-Wójcik, Katarzyna Ewa Tyrak, Marek Sanak, Adam Ćmiel, Anna Urbańska, Izabela Kupryś-Lipińska, Krzysztof Oleś, Ewa Konduracka, Radosław Kacorzyk, Gabriela Trąd, Kinga Pajdzik, and Ewa Zabiegło
Subjects: 0301 basic medicine, Drug, medicine.medical_specialty, medicine.drug_class, media_common.quotation_subject, Immunology, Asthma and Lower Airway Disease, Anti-inflammatory, support vector machines, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Immunology and Allergy, Medicine, Humans, Asthma, media_common, Aspirin, Receiver operating characteristic, business.industry, nonsteroidal antiinflammatory drug (NSAID)–exacerbated respiratory disease (N-ERD), Respiratory disease, Anti-Inflammatory Agents, Non-Steroidal, aspirin‐tolerant asthma, nonsteroidal anti‐inflammatory drug (NSAID)–exacerbated respiratory disease (N‐ERD), aspirin-tolerant asthma, medicine.disease, Respiration Disorders, 030104 developmental biology, 030228 respiratory system, induced sputum, Pharmaceutical Preparations, Cohort, Sputum, Original Article, Neural Networks, Computer, medicine.symptom, ORIGINAL ARTICLES, business, artificial neural network, medicine.drug
Abstract: Background To date, there has been no reliable in vitro test to either diagnose or differentiate nonsteroidal anti‐inflammatory drug (NSAID)–exacerbated respiratory disease (N‐ERD). The aim of the present study was to develop and validate an artificial neural network (ANN) for the prediction of N‐ERD in patients with asthma. Methods This study used a prospective database of patients with N‐ERD (n = 121) and aspirin‐tolerant (n = 82) who underwent aspirin challenge from May 2014 to May 2018. Eighteen parameters, including clinical characteristics, inflammatory phenotypes based on sputum cells, as well as eicosanoid levels in induced sputum supernatant (ISS) and urine were extracted for the ANN. Results The validation sensitivity of ANN was 94.12% (80.32%‐99.28%), specificity was 73.08% (52.21%‐88.43%), and accuracy was 85.00% (77.43%‐92.90%) for the prediction of N‐ERD. The area under the receiver operating curve was 0.83 (0.71‐0.90). Conclusions The designed ANN model seems to have powerful prediction capabilities to provide diagnosis of N‐ERD. Although it cannot replace the gold‐standard aspirin challenge test, the implementation of the ANN might provide an added value for identification of patients with N‐ERD. External validation in a large cohort is needed to confirm our results., Artificial neural network based on a set of clinical and biochemical parameters is able to stratify N‐ERD patients among asthmatic population. The sensitivity of the present artificial neural network is 94.12% and specificity is 73.08% for the prediction of N‐ERD. Artificial neural network could become a screening tool and allow to quickly identify patients with a high suspicion of N‐ERD
Published: 2020

17. Severe uncontrolled allergic eosinophilic asthma – looking for the best therapeutic option

Author: Izabela Kupryś-Lipińska and Piotr Kuna
Subjects: medicine.medical_specialty, business.industry, General Earth and Planetary Sciences, Medicine, Eosinophilic asthma, Allergic asthma, business, Dermatology, General Environmental Science
Published: 2020
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18. New insights into the regulation of TGF-β/Smad and MPK signaling pathway gene expressions by nasal allergen and methacholine challenge test in asthma

Author: Marcelina Koćwin, Grzegorz Kardas, Karol Maksymilian Górski, Mateusz Marynowski, Piotr Kuna, Michał Panek, and Michał Seweryn Karbownik
Subjects: Pulmonary and Respiratory Medicine, Allergen, Immunology, medicine, Tgf β smad, Immunology and Allergy, Biology, medicine.disease_cause, medicine.disease, Signaling Pathway Gene, Methacholine challenge, Asthma
Abstract: Asthma is a heterogeneous chronic inflammatory disease of the bronchi, the course of which is significantly influenced by extrinsic factors (specific and non-specific).The aim of this study was to evaluate the effect of these factors represented by nasal allergen challenge (specific factors) and methacholine challenge test (non-specific) on changes in mRNA expression of genes encoding the TGF-β (TGF-β1 and TGF-β3)‒Smad (mitogen-activated protein kinase 1/3 [MPK1/3], Smad1/3/6/7) signaling pathway in asthmatic patients.Seventy-five subjects were included in the study, of whom 27 were applied an intranasal allergen provocation and 48 a methacholine provocation. There were 9 men and 18 women in the intranasal provocation group, and 17 men and 31 women in the methacholine test group. We found that both examined the types of challenges contributed to changes in the relative expression of genes of the TGF-β (TGF-β1 and TGF-β3)‒Smad (MPK1/3, Smad1/3/6/7) signaling pathway in asthmatic patients. A decrease was noted for MAPK1, MAPK3, Smad3, Smad6, and Smad7 genes and an increase of up to 2.5 times for TGF-β1 gene.Our experiment allows us to conclude that the change in the mRNA expression of the TGF-β1-MPK1/3 and Smad3/6/7 genes occurs after an intranasal allergen and bronchial methacholine challenge.
Published: 2022

19. 'Health outcomes in COPD smokers using heated tobacco products: a 3‑year follow‑up: comment'

Author: Karolina Semczuk-Kaczmarek, Piotr Kuna, and Filip M. Szymański
Subjects: medicine.medical_specialty, COPD, business.industry, Family medicine, Emergency Medicine, Internal Medicine, medicine, MEDLINE, business, medicine.disease, Health outcomes
Published: 2021
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20. High levels of anxiety during the COVID-19 pandemic as a risk factor of clinical worsening in patients with severe asthma

Author: Piotr Lacwik, Dorota Szydłowska, Maciej Kupczyk, Piotr Kuna, and Cezary Pałczyński
Subjects: Adult, Male, severe asthma, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe asthma, MEDLINE, Anxiety, Severity of Illness Index, Risk Factors, Internal medicine, Pandemic, Humans, Immunology and Allergy, Medicine, In patient, Anti-Asthmatic Agents, Risk factor, Pandemics, Aged, Biological Products, SARS-CoV-2, business.industry, COVID-19, Clinical Communications, STAI, Middle Aged, Asthma, Mental Health, Female, medicine.symptom, business
Published: 2021
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21. Improving the risk-to-benefit ratio of inhaled corticosteroids through delivery and dose: current progress and future directions

Author: Grzegorz Kardas, Piotr Kuna, Michał Panek, Piotr Damiański, and Maciej Kupczyk
Subjects: Drug deposition, medicine.medical_specialty, Combination therapy, business.industry, Mometasone furoate, Inhaled corticosteroids, General Medicine, Ciclesonide, Fluticasone propionate, Asthma, Unmet needs, chemistry.chemical_compound, chemistry, Adrenal Cortex Hormones, Administration, Inhalation, Medicine, Humans, Pharmacology (medical), Drug Therapy, Combination, Anti-Asthmatic Agents, business, Intensive care medicine, Adverse effect, Mometasone Furoate, medicine.drug
Abstract: Introduction Inhaled corticosteroids (ICS) are known to increase the risk of systemic and local adverse effects, especially with high doses and long term use. Hence, considerable resources are invested to improve pharmacokinetic/pharmacodynamic (PK/PD) properties of ICS, effective delivery systems and novel combination therapies to enhance the risk-to-benefit ratio of ICS. Areas covered There is an unmet need for new solutions to achieve optimal clinical outcomes with minimal dose of ICS. This paper gives an overview of novel treatment strategies regarding the safety of ICS therapy on the basis of the 3 most recent molecules introduced to our everyday clinical practice - ciclesonide, mometasone furoate, and fluticasone furoate. Advances in aerosol devices and new areas of inhalation therapy are also discussed. Expert opinion Current progress in improving the risk-to-benefit ratio of ICS through dose and delivery probably established pathways for further developments. This applies both to the improvement of the PK/PD properties of ICS molecules but also includes technical aspects that lead to simplified applicability of the device with simultaneous optimal drug deposition in the lungs. Indubitably, the future of medicine lies not only in the development of new molecules but also in technology and digital revolution.
Published: 2021

22. Mental health indices may fully mediate the relationship between morningness-eveningness and disease control among adult asthma patients

Author: Tadeusz Pietras, Dorota Szydłowska, Piotr Kuna, Konrad S. Jankowski, Łukasz Mokros, and Andrzej Witusik
Subjects: Pulmonary and Respiratory Medicine, Adult, Mediation (statistics), business.industry, Chronotype, Disease, medicine.disease, Mental health, Asthma, Circadian Rhythm, Cross-Sectional Studies, Medically Unexplained Symptoms, Mental Health, Sleep Initiation and Maintenance Disorders, Pediatrics, Perinatology and Child Health, medicine, Immunology and Allergy, Anxiety, Humans, medicine.symptom, General Health Questionnaire, business, Depression (differential diagnoses), Clinical psychology
Abstract: Objective: The aim of this study was to assess the association between morningness–eveningness and disease control with consideration of mental state as a mediator and the control of confounding factors among adult asthma patients. Methods: This is a cross-sectional study, which included a nonrandom sample of N = 66 patients from an outpatient unit with a confirmed asthma diagnosis, who gave an informed consent and completed a set of questionnaires: a survey comprising questions about sociodemographic and clinical characteristics, the Asthma Control Test (ACT), the Composite Scale of Morningness (CSM), and the General Health Questionnaire (GHQ-28). Mediation models were created separately for each GHQ-28 dimension (somatic symptoms, anxiety/insomnia, social dysfunction and depressive symptoms), for a total score and for four GHQ-28 dimensions together, considered as mediators. Results: Low morning affect was related to poor disease symptom control among patients with asthma. The effect was fully mediated by non-psychotic mental health indices. Evening-time preference was associated with a rise in asthma control, and mediated by somatic symptoms and anxiety/insomnia, when controlled for morning affect. Conclusions: The current study underlines the significance of assessment of both individual morningness–eveningness preference and mental health in the management of asthma symptoms.
Published: 2021

23. 3TR

Author: Heribert Staudinger, Judith Axmann, Maarten van den Berge, Sven-Erik Dahlén, Liam G Heaney, Franca Rusconi, Rekha Chaudhuri, Anke H. Maitland-van der Zee, Valeria Ramiconi, Guy Brusselle, Maciej Kupczyk, Piotr Kuna, Rosa Faner, Marc P. van der Schee, Claus Vogelmeier, Giorgio Walter Canonica, Kian Fan Chung, Arnaud Bourdin, Ratko Djukanovic, Sejla Saglani, Celeste Porsbjerg, Graham W. Clarke, Graham Roberts, Courtney Coleman, Jadwiga A. Wedzicha, Charles Pilette, Martijn C. Nawijn, Alvar Agusti, Christopher E. Brightling, Bispebjerg University Hospital, University of Amsterdam [Amsterdam] (UvA), Ghent University Hospital, IRCCS Humanitas [Rozzano, Italy], Humanitas University [Milan] (Hunimed), University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Philipps University of Marburg, German Center for Lung Research, University of Groningen [Groningen], Children's Hospital A. Meyer-University of Florence, Université Catholique de Louvain = Catholic University of Louvain (UCL), European Federation of Allergy and Airways Diseases Patients' Associations (EFA), The European Lung Foundation (ELF), University of Glasgow, Imperial College London, Royal Brompton Hospital, Queen's University [Belfast] (QUB), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Southampton, University Hospital Southampton NHS Foundation Trust, The David Hide Asthma and Allergy Research Centre, St Mary's Hospital-University Hospital Southampton NHS Foundation Trust, NIHR Southampton Biomedical Research Centre, Medical University of Łódź (MUL), Roche Pharma Research and Early Development [Basel] (pRED), F. Hoffmann-La Roche [Basel], Sanofi Genzyme, AstraZeneca, Gothenburg, Sweden, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University of Leicester, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Centre de l'allergie, UCL - (SLuc) Service de pneumologie, Philipps Universität Marburg = Philipps University of Marburg, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), MORNET, Dominique, and Groningen Research Institute for Asthma and COPD (GRIAC)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], education, Disease, Pulmonary Disease, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Pan european, medicine, Immune Diseases, Humans, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Asthma, COPD, Asthma/drug therapy, business.industry, 030503 health policy & services, biochemical phenomena, metabolism, and nutrition, medicine.disease, Pulmonary Disease, Chronic Obstructive/drug therapy, humanities, 3. Good health, respiratory tract diseases, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, 030228 respiratory system, Chronic Obstructive/drug therapy, bacteria, 0305 other medical science, business
Abstract: The 3TR (Taxonomy, Treatments, Targets and Remission) consortium is the largest IMI (Innovative Medicine Initiative) project ever started in the field of immune diseases (https://3tr-imi.eu/). 3TR is unique in bringing several medical specialties, encompassing respiratory medicine, rheumatology, neurology and gastroenterology, together, to study disease mechanisms across seven disease entities: asthma, COPD, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, ulcerative colitis and Crohn's disease. [...]
Published: 2021
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24. COEXISTENCE OF PULMONARY FIBROSIS AND PROLIFERATION OF PULMONARY NEUROENDOCRINE CELLS FORMING TUMORLET

Author: Patrycja Węglarz, Piotr Kuna, Igor Rakoczy, Iga Panek, Maciej Liczek, Marcin Braun, and Michał Panek
Subjects: High-resolution computed tomography, Pathology, medicine.medical_specialty, Lung Neoplasms, Pulmonary Fibrosis, Lung biopsy, Neuroendocrine Cells, Pulmonary fibrosis, medicine, Humans, Neuroendocrine cell, Aged, Cell Proliferation, Hyperplasia, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, medicine.anatomical_structure, Dyspnea, Immunohistochemistry, Female, Differential diagnosis, business, Respiratory tract
Abstract: Tumorlet is a disease rarely diagnosed in clinical practice. It is characterized by pulmonary neuroendocrine cell (PNEC) proliferation which invades the bronchiolar basement membrane and forms nodules with a diameter smaller than 5 mm. Case report: 72-year-old female patient was suffered for many years from progressive dyspnea and coughing with evidence of pulmonary fibrosis on high resolution computed tomography (HRCT). As a result of a lung biopsy, based on immunohistochemical tests, a 2 mm cluster of neuroendocrine cells (NEC) was found and it was diagnosed as tumorlet. Due to a long-term, insidious progress of the disease, as well as sex and age of the patient, the case emphasizes that differential diagnosis should include tumorlet as well as diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) as a more extensive manifestation of neuroendocrine cell proliferation in the respiratory tract.
Published: 2021

25. ARIA-Versorgungspfade für die Allergenimmuntherapie 2019

Author: Igor Kaidashev, Victoria Cardona, Mohamed Shamji, George Du Toit, Hae-Sim Park, Holger Schünemann, Elisio Costa, Graham Roberts, Maria Teresa VENTURA, Sanna Toppila-Salmi, João Fonseca, Jean Bousquet, Arzu Yorgancıoglu, Juan Carlos Ivancevich, Stefania La Grutta, Peter Hellings, Torsten Zuberbier, Susanne Halken, Violeta Kvedarienė, Enrica Menditto, Piotr Kuna, Valentina Orlando, Derek Chu, Motohiro Ebisawa, and Olga Lourenço
Subjects: Allergen immunotherapy, medicine.medical_specialty, business.industry, Cost effectiveness, medicine.medical_treatment, Immunotherapy, medicine.disease, medicine.disease_cause, 3. Good health, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Allergen, Pharmacotherapy, 030228 respiratory system, medicine, Immunology and Allergy, ALLERGEN EXPOSURE, business, Intensive care medicine, mHealth, Asthma
Abstract: Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence- based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as on the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow up of patients.
Published: 2019
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26. Produkty tytoniowe oparte na podgrzewaniu tytoniu (heat-not-burn) a zdrowie pacjentów — opinia grupy ekspertów

Author: Krzysztof Filipiak, Anna E. Płatek, Filip M. Szymański, Robert Kowalik, Joann Gotlib, and Piotr Kuna
Subjects: Cigarette smoking, business.industry, Addiction, media_common.quotation_subject, Environmental health, Medicine, General Medicine, business, media_common
Abstract: Smoking, especially of cigarettes, is one of the best-recognised and most widely studied risk factors for cardiovascular disease and death. Despite the availability of many methods of counteracting tobacco addiction, their effective- ness is still insufficient. An alternative to smoking cigarettes could be tobacco products based on heating tobacco (‘heat-not-burn’), the use of which may be associated with a lower cardiovascular risk. this article presents a summary of the current state of knowledge and the recommendations of Polish experts regarding the safety of these products.
Published: 2019
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27. Endoplasmic reticulum aminopeptidase 1 polymorphism Ile276Met is associated with atopic dermatitis and affects the generation of an <scp>HLA</scp> ‐C associated antigenic epitope in vitro

Author: Piotr Kuna, K. Zwolińska, Wanda Niepiekło-Miniewska, Rafał Płoski, Efstratios Stratikos, Karolina Wilczyńska, Anastasia Mpakali, Piotr Kuśnierczyk, Andrzej Wiśniewski, Jacek C Szepietowski, Izabela Nowak, Aleksandra Lesiak, Joanna Narbutt, Łukasz Matusiak, and Joanna Ponińska
Subjects: Adult, Male, 0301 basic medicine, Adolescent, Single-nucleotide polymorphism, HLA-C Antigens, Dermatology, Human leukocyte antigen, In Vitro Techniques, Endoplasmic Reticulum, Aminopeptidases, Polymorphism, Single Nucleotide, Epitope, Dermatitis, Atopic, Minor Histocompatibility Antigens, Epitopes, Young Adult, 03 medical and health sciences, HLA-C, Methionine, 0302 clinical medicine, Genotype, Humans, Medicine, Isoleucine, Allele, Child, Gene, Genetics, business.industry, Middle Aged, Allotype, 030104 developmental biology, Infectious Diseases, Case-Control Studies, Child, Preschool, Female, business, Biomarkers, 030215 immunology
Abstract: Background Atopic dermatitis (AD) is a common inflammatory skin disease of complex aetiology, with interactions between susceptibility genes and environmental factors. We have previously described a protective effect of the KIR2DS1 gene encoding the natural killer cell receptor, whose ligands are HLA-C molecules. Here, we found an association of HLA-C*05:01 allele with AD. KIR-HLA-C interactions are affected by peptides presented by HLA-C. The generation of these peptides is strongly influenced by endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2). Expression and activity of ERAP molecules depend on the polymorphisms of their genes. Objective Possible associations of several single nucleotide polymorphisms (SNPs) in the ERAP1 and ERAP2 genes with susceptibility to AD. Methods Peripheral blood DNA isolation from 318 patients and 549 controls. PCR-SSO or PCR-SSP for HLA-C typing; TaqMan Genotyping Assay for ERAP typing. Results Only one SNP in the ERAP1 gene, rs26618T>C, causing the amino acid change Ile276Met, had an association with AD. To gain insight on the functional role of this SNP, we produced recombinant variants differing only at position 276 (Ile or Met) and tested their aminopeptidase activity against a N-terminally extended precursor LIVDRPVTLV of the HLA-C*05:01 epitope IVDRPVTLV. Both ERAP1 variants were able to efficiently generate the epitope, although the 276Ile allotype was able to do this about 50% faster. Furthermore, both variants were quite inefficient in further degradation of the mature epitope. Finally, we found that the effect of 276Met on susceptibility to AD was seen only in KIR2DS1-negative individuals, not protected by this KIR. Conclusion Associations of HLA-C*05:01 allele and rs26618T>C (Ile276Met) ERAP1 polymorphism with AD, and a significant difference between these two ERAP1 variants in their ability to generate an epitope for the HLA-C*05:01 molecule was found.
Published: 2019
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28. Bronchial asthma control degree and the temperament structure according to the Eysenck model

Author: Andrzej Witusik, Tadeusz Pietras, Piotr Kuna, Izabela Kuprys-Lipinska, and Łukasz Mokros
Subjects: disease control, media_common.quotation_subject, Disease, Dermatology, immune system diseases, Psychoticism, Asthma control, medicine, Immunology and Allergy, Personality, neuroticism, Internal medicine, media_common, Asthma, Original Paper, business.industry, medicine.disease, Neuroticism, RC31-1245, respiratory tract diseases, Poor control, personality, RL1-803, psychoticism, Temperament, business, logistic models, Clinical psychology
Abstract: Introduction Asthma is a disease of a psychosomatic nature. The control of asthma is still poor in approximately 5% of patients, despite introduction of modern inhalant drugs and psychotherapeutic interventions. Aim To evaluate whether the degree of bronchial asthma control is related to the characteristics of temperament according to Eysenck’s concept. Material and methods The study was conducted on a group of 111 bronchial asthma patients and 44 healthy subjects. In all of them, the Eysenck temperament questionnaire was administered and the level of asthma control was determined. Results Increase in the scale of neuroticism was associated with an 1.83-fold increase in the likelihood of poor asthma control. Increase in the result on the psychoticism scale and lie scale of about one point was associated with a slightly smaller increased risk of poor asthma control (respectively: 1.49-fold and 1.61-fold). Conclusions The structure of temperament of a person with poor control of bronchial asthma can be characterized. Patients with poor asthma control have a higher level of neuroticism, psychoticism and propensity to lie, compared with the healthy population and subjects with good or partial bronchial asthma control.
Published: 2019

29. Sublingual allergen immunotherapy with a liquid birch pollen product in patients with seasonal allergic rhinoconjunctivitis with or without asthma

Author: Pieter-Jan de Kam, Piotr Kuna, Ludger Klimek, Petr Panzner, Maroesja J. van Nimwegen, Dirk Jan E. Opstelten, Mária Džupinová, Claus Bachert, Oliver Pfaar, Donghui Yu, and Johan D. Boot
Subjects: Male, 0301 basic medicine, Allergy, combined symptom and medication score, IMPACT, efficacy, CHILDHOOD, RECOMMENDATIONS, 0302 clinical medicine, Medicine and Health Sciences, Clinical endpoint, pivotal phase III trial, Immunology and Allergy, Medicine, Betula, Conjunctivitis, Allergic, Middle Aged, Treatment Outcome, Pollen, Female, CLINICAL-TRIALS, safety, Adult, medicine.medical_specialty, Allergen immunotherapy, Adolescent, Immunology, ORGANIZATION, sublingual immunotherapy, MECHANISMS, Young Adult, 03 medical and health sciences, Double-Blind Method, Multicenter trial, Humans, Adverse effect, Aged, Asthma, Sublingual Immunotherapy, Birch pollen allergy, Intention-to-treat analysis, INTERNATIONAL CONSENSUS, business.industry, allergic rhinoconjunctivitis, RHINITIS, Rhinitis, Allergic, Seasonal, STANDARDIZATION, Allergens, Antigens, Plant, medicine.disease, Dermatology, Clinical trial, 030104 developmental biology, quality of life, 030228 respiratory system, allergen immunotherapy, business
Abstract: Background: Sublingual allergen immunotherapy (SLIT) has been demonstrated to be both clinically efficacious and safe. However, in line with the current regulatory guidance from the European Medicines Agency, allergen immunotherapy (AIT) products must demonstrate their efficacy and safety in pivotal phase III trials for registration. Objective: We sought to investigate the efficacy and safety of sublingual high-dose liquid birch pollen extract (40,000 allergy units native [AUN]/mL) in adults with birch pollen allergy. Methods: A randomized, double-blind, placebo-controlled, parallel-group multicenter trial was conducted in 406 adult patients with moderate-to-severe birch pollen-induced allergic rhinoconjunctivitis with or without mild-to-moderate controlled asthma. Treatment was started 3 to 6 months before the birch pollen season and continued during the season in 40 clinical study centers in 5 European countries. For primary end point assessment, the recommended combined symptom and medication score of the European Academy of Allergy and Clinical Immunology was used. Secondary end points included quality-of-life assessments, immunologic parameters, and safety. Results: Primary efficacy results demonstrated a significant (P < .0001) and clinically relevant (32%) reduction in the combined symptom and medication score compared with placebo after 3 to 6 months of SLIT. Significantly better rhinoconjunctivitis quality-of-life scores (P < .0001) and the patient's own overall assessment of his or her health status, including the visual analog scale score (Euro Quality of Life Visual Analogue Scale; P = .0025), were also demonstrated. In total, a good safety profile of SLIT was observed. Conclusion: This study confirmed both the clinical efficacy and safety of a sublingual liquid birch pollen extract in adults with birch pollen allergy in a pivotal phase III trial (EudraCT: 2013-005550-30; ClinicalTrials. gov: NCT02231307).
Published: 2019
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30. 2019 ARIA – Care pathways for allergic rhinitis – Poland

Author: Agnieszka Lipiec, Marek Niedoszytko, Barbara Piekarska, Peter Hellings, Dana Wallace, Filip Raciborski, Wienczyslawa Czarlewski, Piotr Kuna, Edyta Krzych-Fałta, Maciej Kupczyk, Holger J. Schünemann, Jean Bousquet, Marek L. Kowalski, Oliver Pfaar, Bolesław Samoliński, Anna Bedbrook, Marek Jutel, Ewa Jassem, and Claus Bachert
Subjects: recommendation, medicine.medical_specialty, Allergy, IMPACT, CHILDREN, COST-EFFECTIVENESS, Medicine and Health Sciences, medicine, QUALITY, integrated care, General Environmental Science, Asthma, EAACI AIT GUIDELINES, Science & Technology, allergic rhinitis, business.industry, FLUTICASONE FUROATE, asthma, medicine.disease, Integrated care, URBAN-POPULATION, SUBLINGUAL IMMUNOTHERAPY, Family medicine, General Earth and Planetary Sciences, AZELASTINE NASAL SPRAY, business, Life Sciences & Biomedicine
Abstract: Integrated health care plays a pivotal role in allergic diseases. It identifies key actions (based on guidelines) in the management of allergy patients that are transferred to the local level and implemented in clinical practice. It is particularly important for allergic rhinitis to develop a new generation of guidelines for pharmacotherapy and allergen immunotherapy. Allergen-specific immunotherapy is a parallel therapy that has a preventive (or prophylactic) character and not a method indicated for those who do not respond to pharmacotherapy.
Published: 2019
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31. Next-generation care pathways for allergic rhinitis and asthma multimorbidity: a model for multimorbid non-communicable diseases -Meeting Report (Part 1)

Author: Elaine Colgan, Mario Sánchez-Borges, Jim Phillips, Ignacio J. Ansotegui, Bolesław Samoliński, Olga Lourenço, Giorgio Walter Canonica, F. Portejoie, Isabella Annesi-Maesano, Gabrielle L. Onorato, Victoria Cardona, João O. Malva, Eugene Cash, Christine Rolland, Hilary Pinnock, Samantha Walker, Yoshitaka Okamoto, Ana Maria Carriazo, Lorenzo Cecchi, Nikos G. Papadopoulos, Jean Bousquet, L. T. T. Le, João Fonseca, Oliver Pfaar, Luis Caraballo, Elísio Costa, Maritta Perala, Pablo Quinones-Delgado, Torsten Zuberbier, Holger J. Schünemann, Tomohisa Iinuma, Enrica Menditto, Maddalena Illario, Nils E. Billo, Arunas Valiulis, Sinthia Bosnic-Anticevich, Josep M. Antó, Nick A. Guldemond, Maria Teresa Ventura, Claus Bachert, Wytske Fokkens, Lars Münter, Mohamed H. Shamji, Ioana Agache, Ulysse Rodts, Daniel Laune, Sanna Toppila-Salmi, Joaquim Mullol, Ioanna Tsiligianni, Motohiro Ebisawa, Isabelle Bosse, Samuel Benveniste, Arzu Yorgancioglu, Alkis Togias, M. Bewick, Nhân Pham-Thi, Stephen R. Durham, Moises A. Calderon, Marina Erhola, Violeta Kvedariene, Omar S. Usmani, Alvaro A. Cruz, Anna Bedbrook, Abigail Phillips, Desiree Larenas-Linneman, Guy Brusselle, Gert Marien, Dana Wallace, David Somekh, Sian Williams, Wienczyslawa Czarlewski, Ludger Klimek, Piotr Kuna, Jean-Luc Fauquert, Rianne van der Kleij, Derek K. Chu, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris], Transilvania University of Brasov, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital Quiròn Bizkaia Erandio, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Ghent University Hospital, Centre de Recherche en Informatique (CRI), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], iQ4U consultants Ltd, University of Joensuu, The University of Sydney, Imperial College London, Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Institute for Immunological Research (University of Cartagena), Vall d'Hebron University Hospital [Barcelona], Servicio Andaluz de Salud, Nova Southeastern University (NSU), Azienda Sanitaria di Prato, McMaster University [Hamilton, Ontario], DEPARTMENT OF HEALTH ( Social Services and Public Safety), Universidade do Porto, Universidade Federal da Bahia (UFBA), UCB Pharma, Colombes, Sagamihara National Hospital, National Institute for Health and Welfare [Helsinki], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Faculdade de Medicina da Universidade do Porto (FMUP), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Chiba University Hospital, 'Federico II' University of Naples Medical School, Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], Medical University of Łódź (MUL), Vilnius University [Vilnius], Hospital Medica Sur [Mexico City, Mexico], KYomed INNOV, Ho Chi Minh City University of Technology (HCMUT), Faculty of Health Sciences and CICS-UB (Health Sciences Research Centre), University of Coimbra [Portugal] (UC), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Department of Public Health [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), University of Manchester [Manchester], University of Athens Medical School [Athens], University of Oulu, Philipps University of Marburg, Cardiff University, University of Edinburgh, Regional Government for Equality, Medical University of Warsaw - Poland, Centro Medico-Docente La Trinidad, Department of Clinical Epidemiology and Biostatistics and Medicine, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), University of Helsinki, University of Crete [Heraklion] (UOC), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, King's College Hospital (KCH), Leiden University Medical Center (LUMC), University of Bari Aldo Moro (UNIBA), Manisa Celal Bayar University, Humboldt-Universität zu Berlin, Association Asthme et Allergie, Health Services Management & Organisation (HSMO), University Hospital Montpellier, Montpellier, France, MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, France, INSERM U 1168, VIMA, Ageing and Chronic Diseases Epidemiological and Public Health Approaches, Villejuif, France, Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny le Bretonneux, France, EUFOREA, Brussels, Belgium, Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany, Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin, Germany, Allergy Department, Pasteur Institute, Paris, France, Faculty of Medicine, Transylvania University, Brasov, Romania, Epidemiology of Allergic and Respiratory Diseases, Department Institute Pierre Louis of Epidemiology and Public Health, INSERM, Sorbonne Universités, Medical School Saint Antoine, Paris, France, Department of Allergy and Immunology, Hospital Quirónsalud Bizkaia, Erandio, Spain, ISGlobAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, Universitat Pompeu Fabra (UPF), Barcelona, Spain, CIBER Epidemiolog a y Salud Pública (CIBERESP), Barcelona, Spain, Upper Airways Research Laboratory, ENT Dept., Ghent University Hospital, Ghent, Belgium, National Center of Expertise in Cognitive Stimulation (CEN STIMCO), Broca Hospital, Paris, France, Mines ParisTech CRI - PSL Research University, Fontainebleau, France, iQ4U Consultants Ltd., London, United Kingdom, Joensuu, Finland, Woolcock Institute of Medical Research, University of Sydney, Woolcock Emphysema Centre, Sydney Local Health District, Glebe, NSW, Australia, La Rochelle, France, Dept. of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium, Imperial College London, National Heart and Lung Institute, London, United Kingdom, Personalized Medicine Clinic Asthma and Allergy, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy, Institute for Immunological Research, University of Cartagena, Campus de Zaragocilla, Edificio Biblioteca Primer piso, Cartagena, Colombia, Foundation for the Development of Medical and Biological Sciences (Fundemeb), Cartagena, Colombia, Allergy Section, Department of Internal Medicine, Hospital Vall d’Hebron and ARADyAL Research Network, Barcelona, Spain, Regional Ministry of Health of Andalusia, Seville, Spain, College of Psychology, Nova Southeastern University, School-related Psychological Assessments and Clinical Interventions Clinic, Ft Lauderdale, FL, United States, SOS Allergology and Clinical Immunology, USL Toscana Centro, Prato, Italy, Department of Health Research Methods, Evidence, and Impact, Division of Immunology and Allergy, Department of Medicine, McMaster University, Hamilton, ON, Canada, Department of Health, Social Services and Public Safety, Belfast, United Kingdom, UCIBIO, REQUIMTE, Faculty of Pharmacy, Competence Center on Active and Healthy Ageing of University of Porto (AgeUPNetWork), University of Porto, Porto, Portugal, ProAR-Nucleo de Excelencia em Asma, Federal University of Bahia, Brasil and WHO GARD Executive Committee, Bahia, Brazil, Medical Consulting Czarlewski, Levallois, France, Allergy and Clinical Immunology Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan, National Institute for Health and Welfare, Helsinki, Finland, CHU Clermont-Ferrand, Unité d’Allergologie de l’Enfant, Pôle Pédiatrique, Hôpital Estaing, Clermont-Ferrand, France, Department of Otorhinolaryngology, Amsterdam University Medical Centres, AMC, Amsterdam, Netherlands, CINTESIS, Center for Research in Health Technology and Information Systems, Faculdade de Medicina, Universidade do Porto, Medida, Lda, Porto, Portugal, Institute of Health Policy and Management iBMG, Erasmus University, Rotterdam, Netherlands, Dept. of Otorhinolaryngology, Chiba University Hospital, Chiba, Japan, Division for Health Innovation, Campania Region and Federico II University Hospital Naples (R and D and DISMET), Naples, Italy, Center for Rhinology and Allergology, Wiesbaden, Germany, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland, Institute of Biomedical Sciences, Department of Pathology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Institute of Clinical Medicine, Clinic of Chest Diseases and Allergology, Faculty of Medicine, Vilnius, Lithuania, Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico, KYomed INNOV, Montpellier, France, University of Medicine and Pharmacy, Hochiminh City, Viet Nam, Faculty of Health Sciences, CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Ageing@Coimbra EIP-AHA Reference Site, Coimbra, Portugal, CIRFF, Center of Pharmacoeconomics, University of Naples Federico II, Naples, Italy, Rhinology Unit and Smell Clinic, ENT Department, Hospital Cl nic, Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Danish Committee for Health Education, Copenhagen East, Denmark, Division of Infection, Immunity and Respiratory Medicine, Royal Manchester Children’s Hospital, University of Manchester, Manchester, United Kingdom, Allergy Department, 2nd Pediatric Clinic, Athens General Children’s Hospital 'P and A Kyriakou', University of Athens, Athens, Greece, University of Oulu, Faculty of Medicine, Oulun Yliopisto, Finland, Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Phillipps-Universität Marburg, Germany, Department of Health and Social Services, Welsh Government, Cardiff, United Kingdom, Centre For Empowering Patients and Communities, Dublin, Ireland, Asthma UK Centre for Applied Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom, Agency for Social Services and Dependency, Regional Government for Equality, Social Policies and Conciliation of Andalucia, Seville, Spain, Association Asthme et Allergie, Paris, France, KanopyMed, Paris, France, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland, Allergy and Clinical Immunology Department, Centro Medico-Docente La Trinidad, Caracas, Venezuela, Immunomodulation and Tolerance Group, Imperial College London, London, United Kingdom, Allergy and Clinical Immunology, Imperial College London, London, United Kingdom, European Health Futures Forum (EHFF), Dromahair, Ireland, Division of Allergy, Immunology, and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States, Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland, Health Planning Unit, Department of Social Medicine, Faculty of Medicine, University of Crete, Crete, Greece, International Primary Care Respiratory Group IPCRG, Aberdeen, United Kingdom, National Heart and Lung Institute (NHLI), Imperial College London, Royal Brompton Hospital, Airways Disease Section, London, United Kingdom, Asthma UK, London, United Kingdom, Nova Southeastern University, Fort Lauderdale, FL, United States, Vilnius University, Faculty of Medicine, Institute of Clinical Medicine, Institute of Health Sciences, Vilnius, Lithuania, Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands, University of Bari Medical School, Unit of Geriatric Immunoallergology, Bari, Italy, Department of Pulmonary Diseases, Celal Bayar University, Faculty of Medicine, Manisa, Turkey, Universitätsmedizin Berlin, Humboldt-Uniersität zu Berlin, Berlin, Germany, Berlin Institute of Health, Comprehensive Allergy-Centre, Department of Dermatology and Allergy, Berlin, Germany, uBibliorum, Ear, Nose and Throat, AII - Inflammatory diseases, Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hospital Quirónsalud Bizkaia [Bilbao], Mines Paris - PSL (École nationale supérieure des mines de Paris), Universidade do Porto = University of Porto, Sagamihara National Hospital [Kanagawa, Japan], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Philipps Universität Marburg = Philipps University of Marburg, Centro Médico Docente La Trinidad, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Humboldt University Of Berlin, Salvy-Córdoba, Nathalie, Universiteit Leiden, Bousquet, J., Pham-Thi, N., Bedbrook, A., Agache, I., Annesi-Maesano, I., Ansotegui, I., Anto, J. M., Bachert, C., Benveniste, S., Bewick, M., Billo, N., Bosnic-Anticevich, S., Bosse, I., Brusselle, G., Calderon, M. A., Canonica, G. W., Caraballo, L., Cardona, V., Carriazo, A. M., Cash, E., Cecchi, L., Chu, D. K., Colgan, E., Costa, E., Cruz, A. A., Czarlewski, W., Durham, S., Ebisawa, M., Erhola, M., Fauquert, J. -L., Fokkens, W. J., Fonseca, J. A., Guldemond, N., Iinuma, T., Illario, M., Klimek, L., Kuna, P., Kvedariene, V., Larenas-Linneman, D., Laune, D., Le, L. T. T., Lourenco, O., Malva, J. O., Marien, G., Menditto, E., Mullol, J., Munter, L., Okamoto, Y., Onorato, G. L., Papadopoulos, N. G., Perala, M., Pfaar, O., Phillips, A., Phillips, J., Pinnock, H., Portejoie, F., Quinones-Delgado, P., Rolland, C., Rodts, U., Samolinski, B., Sanchez-Borges, M., Schunemann, H. J., Shamji, M., Somekh, D., Togias, A., Toppila-Salmi, S., Tsiligianni, I., Usmani, O., Walker, S., Wallace, D., Valiulis, A., Van Der Kleij, R., Ventura, M. T., Williams, S., Yorgancioglu, A., and Zuberbier, T.
Subjects: Pulmonary and Respiratory Medicine, Allergy, medicine.medical_specialty, Allergic and chronic respiratory diseases, [SDV.IMM] Life Sciences [q-bio]/Immunology, Allergic rhinitis - Asthma - Multimorbidity, Health care system, Health literacy, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Health care, medicine, Patient participation, mHealth, Asthma, Rhinitis, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Newsletter of GARD Section, business.industry, Environmental exposure, medicine.disease, 3. Good health, Integrated care, [SDV.EE] Life Sciences [q-bio]/Ecology, environment, 030228 respiratory system, 13. Climate action, Family medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system for integrated care with organizational health literacy. MASK (Mobile Airways Sentinel NetworK) (1), a new development of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health) (2), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life integrated care pathways (ICPs) (3)-centred around the patient with rhinitis and using mHealth monitoring of environmental exposure (4).An expert meeting took place at the Pasteur Institute in Paris, December 3, 2018. The aim was to discuss next-generation care pathways: (I) Patient participation, health literacy and self-care through technology-assisted “patient activation”; (II) Implementation of care pathways by pharmacists and (III) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) assessed by mobile technology.The EU (5) and global political agendas are of great importance in supporting health care transformation. MASK has been recognized by DG Santé as a Good Practice (6) in the field of digitally-enabled, integrated, person-centred care.The one-day meeting objectives were clear (Figure 1). The meeting was followed by a workshop. The present paper reports the background of the two-day meeting.
Published: 2019
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32. The usefulness of flow cytometry method in pleocytosis estimation in cerebrospinal fluid cells differentiation – preliminary results

Author: Magdalena Szyszka vel Syska, Mirosława Pietruczuk, Agnieszka Kobiela-Mednis, Makandjou-Ola Eusebio, Kinga Bartczak, Łukasz Kraszula, and Piotr Kuna
Subjects: Pathology, medicine.medical_specialty, Cerebrospinal fluid, medicine.diagnostic_test, Chemistry, medicine, Pleocytosis, Flow cytometry
Abstract: Evaluation of CSF pleocytosis is routinely determined by microscopic examination. To shorten TAT automated methods are used. The aim of this study was to compare the automatic and microscopic methods in the evaluation of pleocytosis and the differentiation of white blood cells in CSF. Cerebrospinal fluid samples were collected from 89 patients. The examination was performed microscopically using the Fuchs-Rosenthal chamber and flow cytometry. There were no significant differences in group A (Pleocytosis
Published: 2018
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33. Reductions in Inflammatory Biomarkers in Patients with Oral Corticosteroid-Dependent Asthma Treated with Tezepelumab

Author: Tobias Welte, Kinga Sałapa, Michael E. Wechsler, P. Kaur, Gun Almqvist, Tor Skärby, Gene L. Colice, A. Menzies Gow, Janet M. Griffiths, Christopher E. Brightling, Åsa Hellqvist, Stephanie Korn, and Piotr Kuna
Subjects: medicine.medical_specialty, business.industry, medicine.drug_class, Internal medicine, Medicine, Corticosteroid, In patient, business, medicine.disease, Inflammatory biomarkers, Gastroenterology, Asthma
Published: 2021
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34. Personalized medicine for allergy treatment: Allergen immunotherapy still a unique and unmatched model

Author: Paolo Maria Matricardi, Ludger Klimek, Thomas B. Casale, Oliver Pfaar, Miguel Tortajada-Girbés, Ignacio J. Ansotegui, Cristoforo Incorvaia, Pascal Demoly, Marek Jutel, Petra Zieglmayer, Maximiliano Gómez, Philippe Devillier, Philippe Gevaert, Jean Bousquet, Petr Panzner, Giorgio Walter Canonica, Mona Al-Ahmad, Ralph Mösges, Stefania Arasi, Alain Didier, Piotr Kuna, Carmen Vidal, Peter Schmid-Grendelmeier, Carla Irani, Oxana Kurbacheva, Moises A. Calderon, Frédéric de Blay, Ulrich Wahn, Enrico Heffler, Alessandro Fiocchi, Adam T. Fox, Hae-Sim Park, Ruby Pawankar, Davide Caimmi, Claus Bachert, Natalija Novak, Margitta Worm, Nikolaos G. Papadopoulos, Silvia Scurati, Andrzej Bozek, Mário Morais-Almeida, Giovanni Passalacqua, Catherine Bos, Yoshitaka Okamoto, Natalia Ilina, Efstrathios Karagiannis, Robin O'Hehir, J. Christian Virchow, Adnan Custovic, ASST Pini-CTO, Kuwait University, Al-Rashed Allergy Center [Kuwait City], Hospital Quirónsalud Bizkaia [Bilbao], Bambino Gesù Children’s Hospital [Rome, Italy], Ghent University Hospital, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Stallergenes Greer (France, Antony), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Silesian Medical University, Katowice, Poland, Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University of South Florida [Tampa] (USF), University of Manchester [Manchester], University Hospital of South Manchester, CHU Strasbourg, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Montpellier (UM), Hôpital Foch [Suresnes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Guy's and St Thomas' Hospital [London], Hospital San Bernardo, Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Humanitas University [Milan] (Hunimed), Federal Institute of Immunology of Russia [Moscou], Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Wrocław Medical University, Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Barlicki University Hospital, Medical University of Łódź (MUL), Monash University [Melbourne], Federal Medical-Biological Agency of Russia, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Hospital CUF Descobertas, University of Cologne, University Hospital Bonn, Chiba University Hospital, Charles University [Prague] (CU), Royal Manchester Children's Hospital, General Children's Hospital of Athens P & A Kyriakou, Ajou University School of Medicine, Ospedale Policlinico San Martino [Genoa], Università degli studi di Genova = University of Genoa (UniGe), Nippon Medical School [Tokyo, Japan], Philipps Universität Marburg = Philipps University of Marburg, University hospital of Zurich [Zurich], Dr Peset University Hospital, Universitat de València (UV), Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne] (CHUS), University of Rostock, Herrada, Anthony, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Toulouse [Toulouse], Wroclaw Medical University [Wrocław, Pologne], University of Genoa (UNIGE), and Philipps Universität Marburg
Subjects: Allergen immunotherapy, Endotype, MESH: Allergens, MESH: Hypersensitivity, Immunology, Disease, Bioinformatics, MESH: Precision Medicine, 03 medical and health sciences, 0302 clinical medicine, molecular diagnosis, Hypersensitivity, Immunology and Allergy, Medicine, Humans, Precision Medicine, MESH: Desensitization, Immunologic, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, MESH: Humans, business.industry, Mechanism (biology), MESH: Genomics, Genomics, personalized medicine, Allergens, treatable traits, Molecular diagnostics, Omics, 3. Good health, Biomarker (cell), omics, allergen immunotherapy, 030228 respiratory system, Desensitization, Immunologic, Personalized medicine, business, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, 030215 immunology
Abstract: International audience; The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.
Published: 2021
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35. Contribution of Antigen-Processing Machinery Genetic Polymorphisms to Atopic Dermatitis

Author: Łukasz Matusiak, Andrzej Wiśniewski, Wanda Niepiekło-Miniewska, Piotr Kuśnierczyk, Joanna Narbutt, Aleksandra Lesiak, Piotr Kuna, and Izabela Kuprys-Lipinska
Subjects: 0301 basic medicine, LMP7, Single-nucleotide polymorphism, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, SNP, genetics, LMP2, Allele, lcsh:Science, Gene, Ecology, Evolution, Behavior and Systematics, TAP2, biology, atopic dermatitis, business.industry, Paleontology, Atopic dermatitis, Odds ratio, medicine.disease, TAP1, 030104 developmental biology, Space and Planetary Science, 030220 oncology & carcinogenesis, Immunology, biology.protein, lcsh:Q, business
Abstract: Atopic dermatitis (AD) is a chronic and recurrent inflammatory dermatosis. We recently described an association of the C allele of the single nucleotide polymorphism (SNP) rs26618 in the ERAP1 gene and a synergism of ERAP1 and ERAP2 effects on AD risk. Here, we examined whether polymorphisms of other antigen-presenting machinery genes encoding immunoproteasome components LMP2 and LMP7 and peptide transporter components TAP1 and TAP2 may also affect susceptibility to AD or its outcome. We found that the LMP7 rs2071543*T allele decreased disease risk by about 1.5-fold (odds ratio 0.66, 95% confidence interval 0.44–0.99). On the other hand, the LMP2 rs1351383*C allele reduced the mean age at diagnosis from 23 to 15 years (p &lt, 0.001). Similarly, the TAP1 rs1135216*C allele decreased the mean age at diagnosis from almost 20 to 14 years (p = 0.033). The results are discussed in light of other reports on the role of these polymorphisms in human disease.
Published: 2021

36. Heterogeneity of the pharmacologic treatment of allergic rhinitis in Europe based on MIDAS and OTCims platforms

Author: Torsten Zuberbier, Julia Saueressig, Joaquim Mullol, Glenis Scadding, João Fonseca, G. Walter Canonica, Eric Van Ganse, Claus Bachert, Bolesław Samoliński, Olga Lourenço, Oliver Pfaar, Philippe Devillier, Ann-Kathrin Stroh, Wienczyslawa Czarlewski, Jean Bousquet, Ludger Klimek, Elísio Costa, Piotr Kuna, Detlef Schroder-Bernhardi, Victoria Cardona, Sophie Scheire, Nhan Pham Thi, Institut Català de la Salut, [Bousquet J] Charité Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. Department of Dermatology and Allergy, Comprehensive Allergy Center, Berlin Institute of Health, Berlin, Germany. University Hospital Montpellier, Montpellier, France. MACVIA-France, Montpellier, France. [Schröder-Bernhardi D] IQVIA Consumer Health, Frankfurt, Germany. [Bachert C] Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium. International Airway Research Center, First Affiliated Hospital Guangzou, Sun Yat-sen University, Guangzou, China. Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden. Department of ENT Diseases, Karolinska University Hospital, Stockholm, Sweden. [Canonica GW] Personalized Medicine Asthma, & Allergy Clinic-Humanitas University & Research Hospital, IRCCS-Milano, Milano, Italy. [Cardona V] Servei d’Al·lergologia, Servei de Medicina Interna, Vall d'Hebron Hospital Universitari, Barcelona, Spain. ARADyAL Research Network, Barcelona, Spain. [Costa EM] UCIBIO, REQUINTE, Faculty of Pharmacy and Competence Center on Active and Healthy Ageing of University of Porto (Porto4Ageing), Porto, Portugal, Vall d'Hebron Barcelona Hospital Campus, uBibliorum, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), IQVIA, Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], IRCCS Istituto Nazionale dei Tumori [Milano], Vall d'Hebron University Hospital [Barcelona], Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Universidade do Porto = University of Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Hôpital Foch [Suresnes], Universidade do Porto = University of Porto, University Medical Center [Mainz], Medical University of Łódź (MUL), University of Beira Interior [Portugal] (UBI), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Philipps Universität Marburg = Philipps University of Marburg, Institut de Recherche Biomédicale des Armées (IRBA), Medical University of Warsaw - Poland, University College of London [London] (UCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Retiveau, Nolwenn
Subjects: 0301 basic medicine, Allergy, IMPACT, Database analysis, Medications, costs, MESH: Allergy and Immunology, Medication, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Allergic rhinitis, 0302 clinical medicine, medications, MESH: Anti-Allergic Agents, Anti-Allergic Agents, Medicine and Health Sciences, Medicine, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Practice Patterns, Physicians', health care economics and organizations, International market, Medication use, Units, enfermedades respiratorias::enfermedades nasales::rinitis::rinitis alérgica [ENFERMEDADES], Medicaments - Prescripció - Europa, Europe, MESH: Rhinitis, Allergic, [SDV.IMM]Life Sciences [q-bio]/Immunology, preparados farmacéuticos::medicamentos por prescripción [COMPUESTOS QUÍMICOS Y DROGAS], localizaciones geográficas::Europa (continente) [DENOMINACIONES GEOGRÁFICAS], MIDAS, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Rinitis - Tractament - Europa, Healthcare system, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Respiratory Tract Diseases::Nose Diseases::Rhinitis::Rhinitis, Allergic [DISEASES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Geographic Locations::Europe [GEOGRAPHICALS], Eu countries, PERSON-CENTERED CARE, Pharmacological treatment, 03 medical and health sciences, units, Environmental health, Allergy and Immunology, MANAGEMENT, Humans, Pharmaceutical Preparations::Prescription Drugs [CHEMICALS AND DRUGS], MESH: Humans, allergic rhinitis, OTC Medicines, business.industry, PATHWAYS, Al·lèrgia - Tractament - Europa, AIR-POLLUTION, medicine.disease, Rhinitis, Allergic, Costs, 030104 developmental biology, 030228 respiratory system, Analytics, Family medicine, MESH: Practice Patterns, Physicians', ASTHMA, MESH: Europe, business
Abstract: Rinitis al·lèrgica; Costos; Medicaments Rinitis alérgica; Costos; Medicamentos Allergic rhinitis; Costs; Medications Background The practice of allergology varies widely between countries, and the costs and sales for the treatment of rhinitis differ depending on practices and health systems. To understand these differences and their implications, the rhinitis market was studied in some of the EU countries. Methods We conducted a pharmaco-epidemiological database analysis to assess the medications that were being prescribed for allergic rhinitis in the years 2016, 2017 and 2018. We used the IQVIA platforms for prescribed medicines (MIDAS®—Meaningful Integration of Data, Analytics and Services) and for OTC medicines (OTC International Market Tracking—OTCims). We selected the five most important markets in the EU (France, Germany, Italy, Poland and Spain). Results Intranasal decongestants were excluded from the analyses because they are rarely prescribed for allergic rhinitis. For both Standard Units (SU) and costs, France is leading the other countries. In terms of SU, the four other countries are similar. For costs, Poland is lower than the three others. However, medication use differs largely. For 2018, in SU, intranasal corticosteroid is the first treatment in Poland (70.0%), France (51.3%), Spain (51.1%) and Germany (50.3%), whereas the Italian market is dominated by systemic antihistamines (41.4%) followed by intranasal corticosteroids (30.1%). Results of other years were similar. Discussion There are major differences between countries in terms of rhinoconjunctivitis medication usage.
Published: 2021
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37. Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA

Author: Jere Reijula, De Yun Wang, Ralph Mösges, Tomohisa Iinuma, Jean Luc Fauquert, Nelson Rosario, Yehia El-Gamal, René Maximiliano Gómez, Tari Haahtela, Vincenzo Patella, Lorenzo Cecchi, Petr Panzner, Yoshitaka Okamoto, Oliver Pfaar, Luis Caraballo, Paulo Augusto Moreira Camargos, Filip Raciborski, Florin Mihaltan, Ken Ohta, Brian J. Lipworth, Kimi Okubo, Juan Carlos Ivancevich, Fulvio Braido, Ioana Agache, Frederico S. Regateiro, Neven Miculinic, Tuula Vasankari, R. Emuzyte, Arunas Valiulis, Yousser Mohammad, Torsten Zuberbier, Osman M. Yusuf, Ewa Jassem, Cezmi A. Akdis, Jean Bousquet, Alessandro Fiocchi, Jan Hagemann, Claus Bachert, Davor Plavec, K. S. Bennoor, Marek Jutel, Désirée Larenas-Linnemann, Stephen Montefort, Stefano Del Giacco, Przemyslaw Kardas, Erkka Valovirta, Mark S. Dykewicz, Antonio Valero, Wienczyslawa Czarlewski, Thomas B. Casale, Gabrielle L. Onorato, Omer Kalayci, Ludger Klimek, Joaquin Sastre, João Fonseca, Siân Williams, Karl Christian Bergmann, Marek Niedoszytko, Bilun Gemicioglu, Mario E. Zernotti, Musa Khaitov, H. Neffen, Robert M. Naclerio, Joaquim Mullol, Ana Pereira, Piotr Kuna, Michael Makris, Maria Teresa Ventura, Ioanna Tsiligianni, Dirceu Solé, Arzu Yorgancioglu, Charlotte Suppli-Ulrik, M. Gotua, Emmanuel P. Prokopakis, Dana Wallace, Jorge Maspero, Wytske Fokkens, Eckard Hamelmann, Antonino Romano, Dejan Dokic, Todor A. Popov, Violeta Kvedariene, Derek K. Chu, Anna Bedbrook, Dermot Ryan, Motohiro Ebisawa, Tomas Chivato, Giovanni Passalacqua, Menachem Rottem, Mário Morais-Almeida, Victoria Cardona, Bolesław Samoliński, Cristiana Stellato, Nikolaos G. Papadopoulos, Milan Sova, Jaime Correia-de-Sousa, Sietze Reitsma, Cemal Cingi, Francesca Puggioni, Robyn E O'Hehir, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, HUS Internal Medicine and Rehabilitation, Department of Public Health, Clinicum, Keuhkosairauksien yksikkö, Helsinki University Hospital Area, University of Helsinki, University Medical Center of the Johannes Gutenberg-University Mainz, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Wrocław [Poland] (UWr), Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Transilvania University of Brasov, Humboldt University Of Berlin, Medical Consulting Czarlewski, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), MASK-air, Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], National Institute of Diseases of the Chest and Hospital (NIDCH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Ospedale Policlinico San Martino [Genoa], Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), University of Cartagena, Foundation for the Development of Medical and Biological Sciences (FUNDEMEB), Vall d'Hebron University Hospital [Barcelona], Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], University of South Florida [Tampa] (USF), Azienda Usl Toscana centro [Firenze], CEU-San Pablo University and HM-Hospitals School of Medicine, McMaster University [Hamilton, Ontario], Eskisehir Osmangazi University, Universidade do Minho = University of Minho [Braga], Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], The International Primary Care Respiratory Group (IPCRG), Università degli Studi di Cagliari = University of Cagliari (UniCa), Sts. Cyril and Methodius University, Saint Louis University School of Medicine [St Louis], Sagamihara National Hospital [Kanagawa, Japan], Ain Shams University (ASU), Vilnius University [Vilnius], Service de Pédiatrie Générale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Bambino Gesù Children’s Hospital [Rome, Italy], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto = University of Porto, CUF Porto Hospital, Cerrahpasa Faculty of Medicine, Istanbul University, ALAS Medical Institute, Center for Allergy and Immunology Research [Tbilisi], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Universität Bielefeld = Bielefeld University, Chiba University Hospital, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Medical University of Gdańsk, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Medical University of Łódź (MUL), Federal Medicobiological Agency [Moscow, Russian Federation], Hospital Medica Sur [Mexico City, Mexico], Ninewells Hospital and Medical School [Dundee], University General Hospital ' Attikon ' [Athens, Greece], Argentine Association of Allergy and Immunology, Marius Nasta Institute of Pneumology, Tishreen University, Université de Damas = Damascus University, University of Malta [Malta], Hospital CUF Descobertas, Clinical Research International Ltd [Hamburg, Germany] (CRI), Johns Hopkins University School of Medicine [Baltimore], Nemours/Alfred I. du Pont Hospital for Children, Monash University [Melbourne], Tokyo National Hospital, Nippon Medical School [Tokyo, Japon], Medicine Charles University and General Faculty Hospital in Prague, Royal Manchester Children's Hospital, University of Manchester [Manchester], Università degli studi di Genova = University of Genoa (UniGe), 'Santa Maria della Speranza' Hospital, Philipps Universität Marburg = Philipps University of Marburg, J.J. Strossmayer University of Osijek, Children’s Hospital Srebrnjak [Zagreb, Croatia], St. Ivan Rilski University Hospital, University of Crete [Heraklion] (UOC), IRCCS Humanitas [Rozzano, Italy], Medical University of Warsaw - Poland, Centro Hospitalar e Universitário [Coimbra], Amsterdam UMC - Amsterdam University Medical Center, Istituto di Ricovero e Cura a Carattere Scientifico [Troina, Italy] (IRCCS), Oasi Maria Santissima Srl [Troina, Italy], Clinica G.B. Morgagni (Fondazione Mediterranea), Pontifical Catholic University of Paraná (PUCPR), Pontifícia Universidade Católica do Paraná (PUCPR), Ha’Emek Medical Center [Afula, Israel], Pediatric Endocrine Institute [Afula, Israel], Usher Institute of Population Health Sciences and Informatics [Edinburgh, U.K.], University of Edinburgh, Federal University of Sao Paulo (Unifesp), University Hospital Olomouc [Czech Republic], University of Salerno (UNISA), Copenhagen University Hospital, Universitat de Barcelona (UB), European Academy of Paediatrics (EAP/UEMS-SP), University of Turku, Suomen Terveystalo Allergy Clinic, Finnish Lung Health Association, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Nova Southeastern University (NSU), Yong Loo Lin School of Medicine [Singapore], Department of Biology, Faculty of Sciences & Liberal Arts, Celal Bayar University, Manisa Celal Bayar University, The Allergy & Asthma Institute, Pakistan (IPCRG), Universidad Nacional de Villa María, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Allergiezentrum Wiesbaden, Salvy-Córdoba, Nathalie, Ear, Nose and Throat, and AII - Inflammatory diseases
Subjects: 0301 basic medicine, Allergy, MESH: Asthma, Common Cold, allergic rhinitis, common cold, cough, COVID-19, smell, Consensus, Humans, SARS-CoV-2, Asthma, Rhinitis, Allergic, Disease, Care, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, MESH: COVID-19, Rhinitis, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Common cold, 3. Good health, MESH: Rhinitis, Allergic, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Original Article, medicine.symptom, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Immunology, Signs and symptoms, Asymptomatic, 03 medical and health sciences, Allergic, COVID‐19, Internal medicine, medicine, MESH: SARS-CoV-2, MESH: Consensus, MESH: Humans, business.industry, Rhinitis, Sinusitis, and Upper Airway Disease, CARE, medicine.disease, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ORIGINAL ARTICLES, Airway, business, MESH: Common Cold
Abstract: Background Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. Methods A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. Results Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). Conclusions This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.
Published: 2021
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38. Expression of cPLA2γ mRNA and protein differs the response of PBMC from severe and non-severe asthmatics to bacterial lipopolysaccharide and house dust mite allergen

Author: Izabela Kupryś-Lipińska, Piotr Kuna, Ewa Pniewska-Dawidczyk, Gabriela Turek, Dorota Kacprzak, Joanna Wieczfinska, Rafał Pawliczak, and Paulina Kleniewska
Subjects: 0301 basic medicine, Adult, Lipopolysaccharides, Male, cPLA2, Lipopolysaccharide, Immunology, Histone Deacetylase 2, Inflammation, Histone Deacetylase 1, macromolecular substances, medicine.disease_cause, Peripheral blood mononuclear cell, Severity of Illness Index, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Phospholipase A2, Allergen, HDAC, Immunology and Allergy, Medicine, Humans, Original Research Article, Antigens, Dermatophagoides, RNA, Messenger, Pharmacology, Histone Acetyltransferases, House dust mite, biology, business.industry, Histone deacetylase 2, Group IV Phospholipases A2, asthma, Allergens, Middle Aged, biology.organism_classification, 030104 developmental biology, 030228 respiratory system, chemistry, Spirometry, HAT, biology.protein, Leukocytes, Mononuclear, Female, medicine.symptom, business, E1A-Associated p300 Protein
Abstract: Chronic inflammation in asthmatics is initiated/exacerbated by many environmental factors, such as bacterial lipopolysaccharide and allergens. Phospholipase A2 and histone acetyltransferase/deacetylases are enzymes involved in inflammatory process, particularly in lipid inflammatory mediators production and control of transcription of many inflammatory genes, respectively. The aim of the study was to identify differences in the inflammatory process in patients with severe and non-severe asthma, taking as a criterion expression of two groups of enzymes: phospholipases A2 and histone acetyltransferases/deacetylases. Thirty-two patients with severe, non-severe atopic to house dust mite asthmatics and 14 healthy volunteers were recruited. Peripheral blood mononuclear cells were stimulated with Dermatophagoides pteronyssinus allergen (nDer p1) and bacterial lipopolysaccharide (LPS). The expression of phospholipases A2 and histone acetyltransferases and deacetylases were assessed using TaqMan Low Density Array Cards. The protein expression was analyzed with immunoblot. Increased expression of phospholipase A2 Group IVC ( PLA2G4C) and cytosolic phospholipase A2 gamma (cPLA2γ) protein was observed in peripheral blood mononuclear cells (PBMC) from severe asthmatics in response to LPS and nDer p1, compared to non-severe asthmatics. nDer p1-stimulated PBMC from severe asthmatics exhibit induced expression of HDAC1 and similar trend was observed in protein concentration. Decreased expression of EP300 occurred in PBMC of severe asthmatics. PBMC from non-severe asthmatics showed decreased expression of HDAC2 and PLA2G15 after LPS treatment. In conclusion, in response to LPS and dust mite allergen, PBMC from severe and non-severe asthmatics modulate expression of selected phospholipase A2, histone acetyltransferases and deacetylases, while increased expression of cPLA2γ characterizes PBMC response from severe asthmatics.
Published: 2021

39. Potential Interplay between Nrf2, TRPA1, and TRPV1 in Nutrients for the Control of COVID-19

Author: Désirée Larenas-Linnemann, Jacques Reynes, Josep M. Antó, Juan Carlos Ivancevich, Nieves Pizarro Lozano, Vincent Le Moing, Torsten Zuberbier, Adrian R. Martineau, Susana C. Fonseca, Wienczyslawa Czarlewski, Frederico S. Regateiro, Ludger Klimek, Sanna Toppila-Salmi, Hak Jong Choi, Erik Melén, Arunas Valiulis, Piotr Kuna, Helga Kraxner, Cezmi A. Akdis, G. Walter Canonica, Yoshitaka Okamoto, Marek Jutel, Nikolaos G. Papadopoulos, Joaquim Mullol, Bilun Gemicioglu, Philip W. Rouadi, Hubert Blain, Guido Iaccarino, Bolesław Samoliński, Alessandro Fiocchi, Rafael de la Torre, Oliver Pfaar, Jean Bousquet, Aziz Sheikh, Yves Rolland, Tari Haahtela, João Fonseca, Hyun Ju Kim, Alvaro A. Cruz, Anna Bedbrook, Jean-Paul Cristol, Ioana Agache, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Bousquet, J., Czarlewski, W., Zuberbier, T., Mullol, J., Blain, H., Cristol, J. -P., De La Torre, R., Pizarro Lozano, N., Le Moing, V., Bedbrook, A., Agache, I., Akdis, C. A., Canonica, G. W., Cruz, A. A., Fiocchi, A., Fonseca, J. A., Fonseca, S., Gemicioglu, B., Haahtela, T., Iaccarino, G., Ivancevich, J. C., Jutel, M., Klimek, L., Kraxner, H., Kuna, P., Larenas-Linnemann, D. E., Martineau, A., Melen, E., Okamoto, Y., Papadopoulos, N. G., Pfaar, O., Regateiro, F. S., Reynes, J., Rolland, Y., Rouadi, P. W., Samolinski, B., Sheikh, A., Toppila-Salmi, S., Valiulis, A., Choi, H. -J., Kim, H. J., Anto, J. M., and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Taste, medicine.medical_treatment, Oxytocin, Severity of Illness Index, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Antioxidants, Transient receptor potential channel, 0302 clinical medicine, COVID-19 Testing, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, 030223 otorhinolaryngology, TRPA1 Cation Channel, Clinical Immunology − Letter to the Editor, Desensitization (medicine), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, musculoskeletal, neural, and ocular physiology, food and beverages, General Medicine, 3. Good health, Up-Regulation, Cough challenge, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Vomiting, medicine.symptom, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, psychological phenomena and processes, Diet therapy, NF-E2-Related Factor 2, Immunology, Pungent food, TRPV1, Down-Regulation, TRPV Cation Channels, Inflammation, Brassica, TRAP-1, Nrf2, 03 medical and health sciences, Severity of illness, medicine, Clinical Immunology − Review Article, Humans, business.industry, SARS-CoV-2, Broccoli, COVID-19, Nutrients, Pungent foods, Oxidative Stress, 030228 respiratory system, nervous system, Desensitization, Immunologic, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers
Abstract: International audience; In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment sensory or vagal nerve discharges to evoke pain and several symptoms of COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden and severe loss of smell and taste. TRPA1 can be activated by reactive oxygen species and may therefore be up-regulated in COVID-19. TRPA1 and TRPV1 channels can be activated by pungent compounds including many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading to channel desensitization. Interactions between Nrf2-associated nutrients and TRPA1/TRPV1 may be partly responsible for the severity of some of the COVID-19 symptoms. The regulation by Nrf2 of TRPA1/TRPV1 is still unclear, but suggested from very limited clinical evidence. In COVID-19, it is proposed that rapid desensitization of TRAP1/TRPV1 by some ingredients in foods could reduce symptom severity and provide new therapeutic strategies.
Published: 2021
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40. Expression of Transcript Variants of PTGS1 and PTGS2 Genes among Patients with Chronic Rhinosinusitis with Nasal Polyps

Author: Wioletta Pietruszewska, Piotr Kuna, Adam J. Białas, Maciej Borowiec, Izabela Kupryś-Lipińska, Marta Podwysocka, and Wojciech Fendler
Subjects: Gene isoform, medicine.medical_specialty, Chronic rhinosinusitis, NSAIDs, prostaglandin-endoperoxide synthase 2 gene, PTGS2 gene, Clinical Biochemistry, transcript variant, PTGS1, Disease, macromolecular substances, chronic rhinosinusitis with nasal polyps, Gastroenterology, Article, 03 medical and health sciences, PTGS1 gene, 0302 clinical medicine, Internal medicine, Medicine, non-steroidal anti-inflammatory drugs, Nasal polyps, 030223 otorhinolaryngology, Gene, Aspirin, lcsh:R5-920, Direct sequencing, business.industry, CRSwNP, prostaglandin-endoperoxide synthase 1 gene, medicine.disease, 030228 respiratory system, cyclooxygenase-2, cyclooxygenase-1, business, lcsh:Medicine (General), medicine.drug
Abstract: To date, there has been no reliable test to identify unfavorable course of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), especially in aspirin intolerant patients. The research aimed to analyze the expression of transcript variants of PTGS1 and PTGS2 genes in the pathobiology of the disease. The study was performed on 409 adult patients: 206 CRSwNP patients including 44 (21.36%) aspirin intolerant patients and 203 healthy volunteers in the control group. Transcript variants of the PTGS1 and PTGS2 genes named as follows: COX1.1 for NM_000962, COX1.2 for NM_080591, COX1.3 for NM_001271165.1, COX1.4 for NM_001271368.1, COX1.5 for NM_001271166.1, COX2.1 for NM_000963.3, COX2.2 for AY_151286 and COX2.3 for BQ_722004 were confirmed using direct sequencing and quantified using targeted qPCR. The coexistence of all examined transcript variants in the study and the control group and significant differences between both were found. In aspirin sensitive patients, the levels of COX1.2, COX1.3, COX1.4 and COX1.5 isoforms were higher compared to aspirin-tolerant patients. The severity of symptoms was bigger in patients with higher expressions of variants: COX1.1 (R with dCt = &minus, 0.134, p = 0.0490), COX1.3 (R = &minus, 0.1429, p = 0.0400) and COX1.5 (Rs = &minus, 0.1499, p = 0.032). The expression of COX1.1 (Rs = &minus, 0.098, p = 0.049) and COX1.5 (Rs = &minus, 0.141, p = 0.043) isoforms increased with polyposis advancement in endoscopy. With the CT extent of sinuses opacification, COX1.1 isoform also significantly increased (Rs = &minus, 0.163, p = 0.020). The isoforms COX1.3, COX1.4, COX1.5 and COX2.1 may promote milder CRSwNP course. On the contrary, the variants COX1.1, COX1.2 and COX2.2 may be involved in a more aggressive disease.
Published: 2021

41. Efficacy of broccoli and glucoraphanin in COVID-19: From hypothesis to proof-of-concept with three experimental clinical cases

Author: Josep M. Antó, Nieves Pizarro Lozano, Tari Haahtela, Hubert Blain, Piotr Kuna, Rafael de la Torre, Arunas Valiulis, Torsten Zuberbier, Jean-Paul Cristol, Erik Melén, Jacques Reynes, Jean Bousquet, Alvaro A. Cruz, Wienczyslawa Czarlewski, Anna Bedbrook, Vincent Le Moing, Bolesław Samoliński, Ludger Klimek, Joaquim Mullol, Guido Iaccarino, Alessandro Fiocchi, Humboldt-Universität zu Berlin, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Euromov (EuroMov), Université de Montpellier (UM), AIR (AIR), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Universitat Pompeu Fabra [Barcelona] (UPF), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Advanced Biomedical Sciences, University of Naples Federico II, Vilnius Gediminas Technical University, CIBER de Epidemiología y Salud Pública (CIBERESP), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Department of Dermatology, Allergology and Venereology, HUS Inflammation Center, Bousquet, J., Le Moing, V., Blain, H., Czarlewski, W., Zuberbier, T., de la Torre, R., Pizarro Lozano, N., Reynes, J., Bedbrook, A., Cristol, J. -P., Cruz, A. A., Fiocchi, A., Haahtela, T., Iaccarino, G., Klimek, L., Kuna, P., Melen, E., Mullol, J., Samolinski, B., Valiulis, A., Anto, J. M., Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), CHU Montpellier, Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hospital del Mar Medical Research Institute [Barcelona, Spain] (IMIM), Federal University of Bahia, University of Helsinki, Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, University of Lódź, Karolinska Institutet [Stockholm], Universitat de Barcelona (UB), and Medical University of Warsaw - Poland
Subjects: MECHANISM, TRPV1, Transient receptor potential vanillin 1, SARS, Severe acute respiratory syndrome, VAS, Visual analogue scale, [SDV]Life Sciences [q-bio], Angiotensin II receptor type 1, COVID-19, Coronavirus 19 disease, TRPA1 Channel, AT1R, TRP, ACTIVATION, chemistry.chemical_compound, TRPA1, Transient receptor potential ankyrin 1, 0302 clinical medicine, Visual analogue scale, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Severe acute respiratory syndrome coronavirus 2, Medicine, Immunology and Allergy, 030223 otorhinolaryngology, Body mass index, Glucoraphanin, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SULFORAPHANE, Fast onset, 3. Good health, Cough challenge, Severe acute respiratory syndrome, NAPQI, Coronavirus 19 disease, Transient receptor potential vanillin 1, Angiotensin converting enzyme, TRP, Transient receptor potential, Broccoli seed capsules, AT1R, Angiotensin II receptor type 1, lcsh:Immunologic diseases. Allergy, CHEMOPREVENTION, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), SARS-Cov-2, Transient receptor potential ankyrin 1, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Broccoli, Broccoli seed capsules, BMI, Body mass index, Nrf2, Nuclear factor (erythroid-derived 2)-like 2, TRPA1, Article, Nrf2, BMI, 03 medical and health sciences, Internal medicine, COVID-19, broccoli, cough challenge, TRPV1, STRATEGY, RICH, ACE, SARS, INDUCED CARDIOMYOPATHY, COUGH, Nuclear factor (erythroid-derived 2)-like 2, business.industry, Broccoli, RHINITIS, medicine.disease, ACE, Angiotensin converting enzyme, Clinical trial, 030228 respiratory system, chemistry, Transient receptor potential, 3121 General medicine, internal medicine and other clinical medicine, N-acetyl-p-benzoquinone imine, VAS, business, Cytokine storm, lcsh:RC581-607, NAPQI, N-acetyl-p-benzoquinone imine, SARS-Cov-2, Severe acute respiratory syndrome coronavirus 2, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; COVID-19 is described in a clinical case involving a patient who proposed the hypothesis that Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-interacting nutrients may help to prevent severe COVID-19 symptoms. Capsules of broccoli seeds containing glucoraphanin were being taken before the onset of SARS-CoV-2 infection and were continued daily for over a month after the first COVID-19 symptoms. They were found to reduce many of the symptoms rapidly and for a duration of 6-12 h by repeated dosing. When the patient was stable but still suffering from cough and nasal obstruction when not taking the broccoli capsules, a double-blind induced cough challenge confirmed the speed of onset of the capsules (less than 10 min). A second clinical case with lower broccoli doses carried out during the cytokine storm confirmed the clinical benefits already observed. A third clinical case showed similar effects at the onset of symptoms. In the first clinical trial, we used a dose of under 600 μmol per day of glucoraphanin. However, such a high dose may induce pharmacologic effects that require careful examination before the performance of any study. It is likely that the fast onset of action is mediated through the TRPA1 channel. These experimental clinical cases represent a proof-of-concept confirming the hypothesis that Nrf2-interacting nutrients are effective in COVID-19. However, this cannot be used in practice before the availability of further safety data, and confirmation is necessary through proper trials on efficacy and safety.
Published: 2021
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42. Home self-monitoring in patients with asthma using a mobile spirometry system

Author: Paweł Nastałek, Krzysztof Buczyłko, Piotr Dąbrowiecki, Anna Hofman, Piotr Kuna, Maciej Kupczyk, Mateusz Łukaszyk, Łukasz Kołtowski, Mateusz Soliński, and Anna Bodzenta-Łukaszyk
Subjects: Pulmonary and Respiratory Medicine, Spirometry, Adult, Male, medicine.medical_specialty, spirometry, digital health, Monitoring, Ambulatory, law.invention, 03 medical and health sciences, 0302 clinical medicine, prevention, law, Immunology and Allergy, Medicine, Humans, home monitoring, In patient, 030212 general & internal medicine, Prospective Studies, Asthma, AioCare, Asthma exacerbations, medicine.diagnostic_test, business.industry, Self-Management, Middle Aged, medicine.disease, Digital health, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Emergency medicine, Self-monitoring, Female, business, Spirometer
Abstract: Self-management is an appealing strategy for prevention of asthma exacerbations. This study aimed to evaluate the feasibility and safety of a portable spirometer for unsupervised home spirometry measurements among patients with asthma.A multi-center, prospective, single-arm, open study recruited 86 patients with controlled or partly controlled asthma (41 women, 38.6 ± 10.4 y/o and 45 men, 36.2 ± 12.1 y/o). After a training session, patients performed daily spirometry at home with the AioCareOf 78 patients with complete data, 67 (86%) achieved the primary endpoint. Seventy-five (96%) participants used the device correctly once or more, and 10 (13%) patients succeeded every single day over the three-week follow-up. The rate of acceptable spirometry examinations differed between the sites (Self-monitoring of asthma with a connected mobile spirometer is feasible, safe and satisfactory for patients with asthma. It remains to be established whether unsupervised home spirometry measurements may improve early diagnosis and outcomes of self-management in cases of exacerbation or loss of asthma control.Highlights BoxThis study aimed to evaluate the ability of patients with asthma to perform high-quality daily spirometry examinations at home with using the AioCare
Published: 2021

43. Biomarkers for predicting response to aspirin therapy in aspirin-exacerbated respiratory disease

Author: Adam Ćmiel, Bogdan Jakiela, Katarzyna Ewa Tyrak, Piotr Kuna, Marek Sanak, Izabela Kupryś-Lipińska, Gabriela Trąd, Lucyna Mastalerz, Radosław Kacorzyk, and Kinga Pajdzik
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Immunology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Desensitization (telecommunications), Internal medicine, Humans, Immunology and Allergy, Medicine, Clinical significance, Aspirin, biology, business.industry, Respiratory disease, Middle Aged, medicine.disease, 030104 developmental biology, Cytokine, 030228 respiratory system, Eicosanoid, Desensitization, Immunologic, biology.protein, Sputum, Asthma, Aspirin-Induced, Female, Antibody, medicine.symptom, business, Biomarkers, medicine.drug
Abstract: Background Aspirin desensitization followed by daily aspirin use is an effective treatment for aspirin-exacerbated respiratory disease (AERD). Objective To assess clinical features as well as genetic, immune, cytological, and biochemical biomarkers that might predict a positive response to high-dose aspirin therapy in AERD. Methods We enrolled 34 AERD patients with severe asthma who underwent aspirin desensitization followed by 52-week aspirin treatment (650 mg/d). At baseline and at 52 weeks, clinical assessment was performed; phenotypes based on induced sputum cells were identified; eicosanoid, cytokine, and chemokine levels in induced sputum supernatant were determined; and induced sputum expression of 94 genes was assessed. Responders to high-dose aspirin were defined as patients with improvement in 5-item Asthma Control Questionnaire score, 22-item Sino-Nasal Outcome Test (SNOT-22) score, and forced expiratory volume in 1 second at 52 weeks. Results There were 28 responders (82%). Positive baseline predictors of response included female sex (P=0.002), higher SNOT-22 score (P=0.03), higher blood eosinophil count (P=0.01), lower neutrophil percentage in induced sputum (P=0.003), higher expression of the hydroxyprostaglandin dehydrogenase gene, HPGD (P=0.004), and lower expression of the proteoglycan 2 gene, PRG2 (P=0.01). The best prediction model included Asthma Control Test and SNOT-22 scores, blood eosinophils, and total serum immunoglobulin E. Responders showed a marked decrease in sputum eosinophils but no changes in eicosanoid levels. Conclusions and clinical relevance Female sex, high blood eosinophil count, low sputum neutrophil percentage, severe nasal symptoms, high HPGD expression, and low PRG2 expression may predict a positive response to long-term high-dose aspirin therapy in patients with AERD.
Published: 2021

44. A severity grading system of food-induced acute allergic reactions to avoid the delay of epinephrine administration

Author: Paweł Majak, Lukasz Blazowski, Joanna Jerzyńska, Ryszard Kurzawa, and Piotr Kuna
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Allergy, Adolescent, Epinephrine, Immunology, Severity of Illness Index, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Severity of illness, medicine, Immunology and Allergy, Humans, Clinical significance, 030212 general & internal medicine, Grading (education), Child, Anaphylaxis, business.industry, Incidence (epidemiology), Infant, Newborn, Infant, Allergens, medicine.disease, Inter-rater reliability, 030228 respiratory system, Child, Preschool, Female, business, Food Hypersensitivity, medicine.drug
Abstract: Background Substantial discrepancies among anaphylaxis severity scores may delay epinephrine administration. Objective The study aims to develop a transparent severity grading system of food-induced acute allergic reactions with a decision model for epinephrine use. Methods The natural course of 315 acute food-induced allergic reactions in children hospitalized at the Allergology department between May 2016 and July 2019 owing to follow-up treatment and allergy diagnostics was evaluated. The severity of episodes was classified according to the 5 most accepted grading systems. The interrater reliability of classification between anaphylaxis severity scores was assessed. All symptoms were grouped into a heat map according to their real-life incidence and clinical relevance. Based on the heat map analysis, a severity grading system of food-induced acute allergic reactions in children with the epinephrine administration decision model was created. Results Data from 259 food-induced anaphylaxis episodes in 157 children were included in the analysis. Comparing the grading systems, we observed a 24.7% to 70.2% disagreement between severity scores. The heat map illustrated a strong association between 29 symptoms and their categorization. A new severity grading system was developed and a 2-stage decision model was proposed: “epinephrine yes” (any rapidly progressing symptoms, even mild ones or from 1 organ system; any symptoms from more than 1 organ system; or every grade of anaphylaxis), and “epinephrine available and prepared to use” (nonprogressing mild systemic allergic reaction from 1 system area only; no anaphylaxis). Conclusion A new severity grading system of food-induced acute allergic reactions in children could serve as a clinical tool for health care professionals to avoid epinephrine administration delay.
Published: 2020

45. Treatment of allergic rhinitis during and outside the pollen season using mobile technology. a MASK study

Author: Sietze Reitsma, Josep M. Antó, Dermot Ryan, C. Stellato, W. Czarlewski, S. Shamai, G. De Vries, Elísio Costa, E. Melen, Esben Eller, Tari Haahtela, Carsten Bindslev-Jensen, Dana Wallace, Ricardo Pio Monti, P. V. Tomazic, A. Yorgancioglu, Oliver Pfaar, Michel Thibaudon, B. Samolinski, Asiyah Sheikh, Daniel Laune, J. C. Ivancevich, M. Morais-Almeida, Niels H. Chavannes, Ralph Mösges, Lorenzo Cecchi, Susan Waserman, Regina Roller-Wirnsberger, V. Cardona, Piotr Kuna, P. Devillier, M. van Eerd, Mikhail Sofiev, Rute Almeida, I. Kull, Isabelle Bosse, J Mullol, A Valero, Ioana Agache, João Fonseca, Violeta Kvedariene, J. F. Fontaine, A. Bedbrook, Sylvie Arnavielhe, Fotis Psarros, Jean Bousquet, Peter Schmid-Grendelmeier, A. A. Cruz, Ludger Klimek, Ruta Dubakiene, Nhân Pham-Thi, Judith Garcia-Aymerich, Benoit Pugin, G. De Feo, Thomas B. Casale, Ruth Murray, Nikolaos G. Papadopoulos, Annabelle Bédard, I. J. Ansotegui, Claus Bachert, Magnus Wickman, Michael Makris, J. Correia da Sousa, Emmanuel P. Prokopakis, Ana Todo-Bom, Enrica Menditto, Xavier Basagaña, W. J. Fokkens, Peter Hellings, Gabrielle L. Onorato, Sinthia Bosnic-Anticevich, D. Larenas-Linnemann, François Spertini, A. Valiulis, R. Emuzyte, M. T. Ventura, Sanna Toppila-Salmi, I. Annesi-Maesano, Maddalena Illario, Erkka Valovirta, Bedard, A., Basagana, X., Anto, J. M., Garcia-Aymerich, J., Devillier, P., Arnavielhe, S., Bedbrook, A., Onorato, G. L., Czarlewski, W., Murray, R., Almeida, R., Fonseca, J. A., Correia da Sousa, J., Costa, E., Morais-Almeida, M., Todo-Bom, A., Cecchi, L., De Feo, G., Illario, M., Menditto, E., Monti, R., Stellato, C., Ventura, M. T., Annesi-Maesano, I., Bosse, I., Fontaine, J. F., Pham-Thi, N., Thibaudon, M., Schmid-Grendelmeier, P., Spertini, F., Chavannes, N. H., Fokkens, W. J., Reitsma, S., Dubakiene, R., Emuzyte, R., Kvedariene, V., Valiulis, A., Kuna, P., Samolinski, B., Klimek, L., Mosges, R., Pfaar, O., Shamai, S., Roller-Wirnsberger, R. E., Tomazic, P. V., Ryan, D., Sheikh, A., Haahtela, T., Toppila-Salmi, S., Valovirta, E., Cardona, V., Mullol, J., Valero, A., Makris, M., Papadopoulos, N. G., Prokopakis, E. P., Psarros, F., Bachert, C., Hellings, P. W., Pugin, B., Bindslev-Jensen, C., Eller, E., Kull, I., Melen, E., Wickman, M., De Vries, G., van Eerd, M., Agache, I., Ansotegui, I. J., Bosnic-Anticevich, S., Cruz, A. A., Casale, T., Ivancevich, J. C., Larenas-Linnemann, D. E., Sofiev, M., Wallace, D., Waserman, S., Yorgancioglu, A., Laune, D., Bousquet, J., Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique (LOBIP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), KYomed INNOV [Montpellier], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département Centre de Soins d'enseignement et de recherche dentaires [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Allergist [La Rochelle], Allergist [Reims], Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, 92123 Brétignysur- Orge cedex, France (IRBA), Institut de Recherche Biomédicale des Armées, Département Neurosciences et Contraintes Opérationnelles, Unité de Neurophysiologie du Stress, Réseau National de Surveillance Aérobiologique (RNSA), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Allergy, IMPACT, Respiratory Medicine and Allergy, Review, Allergic rhinitis, 0302 clinical medicine, Anti-histamines, Corticosteroids, ICT, MASK, Mobile health, Treatment, Allergic symptoms, Medicine and Health Sciences, Immunology and Allergy, Medicine, Corticosteroid, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Lungmedicin och allergi, 0303 health sciences, Anti-histamine, IMPAIRMENT, 3. Good health, Life Sciences & Biomedicine, medicine.drug, Pulmonary and Respiratory Medicine, Immunology, AZELASTINE/FLUTICASONE, Mometasone furoate, PERSON-CENTERED CARE, Fluticasone propionate, 03 medical and health sciences, INTERMITTENT, Allergic rhiniti, 030304 developmental biology, Asthma, Science & Technology, Pollen season, business.industry, GUIDANCE, AIR-POLLUTION, medicine.disease, SEVERITY, 030228 respiratory system, ASTHMA, Observational study, business, Demography
Abstract: Background The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. Methods The Allergy Diary–MASK-air–mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. Results 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines. Conclusions This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year.
Published: 2020
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46. Cluster analysis of 505 real-life food-induced anaphylaxis in children reveals two stable clinical phenotypes

Author: Paweł Majak, Ryszard Kurzawa, Joanna Jerzyńska, Piotr Kuna, and Lukasz Blazowski
Subjects: business.industry, Food induced anaphylaxis, Immunology, Disease cluster, medicine.disease, Phenotype, Immunology and Allergy, Medicine, Cluster Analysis, Humans, business, Child, Anaphylaxis, Food Hypersensitivity
Published: 2020

47. Benralizumab for the Prevention of COPD Exacerbations

Author: Criner, G. J., Celli, B. R., Brightling, C. E., Agusti, A., Papi, A., Singh, D., Sin, D. D., Vogelmeier, C. F., Sciurba, F. C., Bafadhel, M., Backer, V., Kato, M., Ramirez-Venegas, A., Wei, Y. -F., Bjermer, L., Shih, V. H., Jison, M., O'Quinn, S., Makulova, N., Newbold, P., Goldman, M., Martin, U. J., GALATHEA Study Investigators, TERRANOVA Study Investigators, Otto, Burghuber, Bernhard, Forstner, Gerhard, Köberl, Bernd, Lamprecht, Judith, Löffler-Ragg, Horst, Olschewski, Michael, Studnicka, Francois, Beaucage, Guy, Chouinard, Anthony, Dechant, Anthony, Dowell, Jacques, Hebert, Sohail, Khattak, Kieran, Killian, William, Killorn, Andy, Lam, Francois, Maltais, Darcy, Marciniuk, Lyle, Melenka, Bonavuth, Pek, Jeremy, Road, Donald, Sin, Alain, Vaugeois, Brandie, Walker, Tomas, Dvorak, Stanislav, Holub, Otakar, Hokynar, Vitezslav, Kolek, Daniela, Kopecka, Jan, Krepelka, Jaroslav, Mares, Josef, Veverka, Vladimir, Zindr, Sabine, Ballenberger, Rolf, Dichmann, Christian, Geßner, Margret, Jandl, Claus, Keller, Joachim, Kirschner, Marc, Kornmann, Petra, Mikloweit, Ingomar, Naudts, Axel, Overlack, Isabelle, Schenkenberger, Volker, Schlegel, Lutz Von Versen, Claus Franz Vogelmeier, Stefan, Zielen, István, Albert, Beatrix, Bálint, Mária Csilla Hangonyi, Teréz, Kecskés, Anikó, Kurucz, Balázs, Medgyasszay, Lajos, Molnár, János, Mucsi, Márta, Papp, Magdolna, Póczi, Éva, Radeczky, Zsolt Pápai Székely, Csilla, Szabó, Gyöngyi, Szabó, Melinda, Szabó, Alfredo Antonio Chetta, Giuseppe Di Maria, Giulio, Donazzan, Federica, Meloni, Elisabetta, Pace, Pierluigi, Paggiaro, Alberto, Papi, Ricciardolo, Fabio Luigi Massimo, Antonio, Spanevello, Fumiaki, Aoki, Ryosuke, Eda, Takeo, Endo, Yasushi, Fukushima, Kenichi, Gemba, Naoki, Hagimoto, Hiromasa, Harada, Yasuko, Harada, Norihiko, Hata, Osamu, Hataji, Nobuo, Hatakeyama, Takahiko, Horiguchi, Gen, Ideura, Motoyasu, Iikura, Azusa, Ikegami, Shirou, Imokawa, Yoshikazu, Inoue, Takeshi, Isobe, Ryoji, Ito, Susumu, Iwata, Tadashi, Kamei, Motokazu, Kato, Hideki, Katsura, Yuji, Kawarada, Norio, Kihara, Masaharu, Kinoshita, Takashi, Kinoshita, Tomoo, Kishaba, Hideo, Kita, Arihiro, Kiyosue, Shigeru, Komatsu, Kazuki, Konishi, Sekiya, Koyama, Makoto, Kudo, Kazuhiko, Machida, Hironi, Makita, Hiroto, Matsuse, Naoki, Miyazawa, Hiroyuki, Nakamura, Yuji, Nakatani, Kazuyuki, Nishimura, Takashi, Nishimura, Junichi, Ogawa, Hiroyuki, Ohbayashi, Tetsuro, Ohdaira, Tsukasa, Ohnishi, Kazuhiko, Oki, Masahiko, Saito, Kenji, Sakamoto, Osamu, Sakamoto, Hisakuni, Sekino, Noriharu, Shijubo, Masaharu, Shinkai, Hideo, Soto, Yoshitaka, Sugawara, Noriaki, Suko, Hisaho, Takahashi, Masamitsu, Takahashi, Tsuneyuki, Takahashi, Hiroshi, Tanaka, Hiroyuki, Taniguchi, Tadayuki, Terada, Takao, Tochigi, Kazuyo, Tohyama, Hirokazu, Tokuyasu, Keisuke, Tomii, Tomomasa, Tsuboi, Mitsuyoshi, Utsugi, Katsumaru, Yamamoto, Michiko, Yamamoto, Shuichi, Yano, Makoto, Yoshida, Frank, Custers, Richard, Dekhuijzen, Remco, Djamin, Jan Willem Van Dan Berg, Lowie, Vanfleteren, Pascal, Wielders, Bogusława, Cimoszko, Anna, Doboszyńska, Andrzej, Dyczek, Andrzej, Fal, Krystyna, Folcik, Łukasz, Goliński, Marek, Jutel, Andrzej, Kolczyński, Piotr, Kuna, Ewa, Łączyńska, Wojciech, Machowiak, Maciej, Marczak, Joanna, Markiewicz, Janusz, Milanowski, Grzegorz, Mincewicz, Maria, 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Patel, Allan, Reid, Dinesh, Saralaya, Tariq, Sethi, Sukh Dave Singh, Anthony, G de Soyza, Tom, Wilkinson, Alice, Turner, Helen, Ward, Chandar, Abboy, Ivan, Ackerman, Idalia, Acosta, Arun, Adlakha, Bassil, Aish, Mohamed, Ali, Charles, Andrews, Robby, Ayoub, Anil, Badhwar, Dennis, Bassetti, Sherif El Bayadi, Richard, Beasley, Shashi, Bellam, Jonathan, Bernstein, Maria, Blahey, Scott, Bloom, Eugene, Bleecker, Wesley, Bray, Johnathan, Brewer, Robert, Buynak, William, Calhoun, Edward, Campbell, Anthony, Captain, Birjis, Chinoy, Kenneth, Chinsky, Geoffrey, Chupp, Arsenio, Columbie, Clinton, Corder, Gerard, Criner, Humberto, Cruz, Edward, Cullen, Kevin, Deboer, Michael, Denenberg, Mark, Dransfield, Leonard, Dunn, Miles, Elmore, David, Erb, Faisal, Fakih, Gary, Ferguson, Charles, Fogarty, Mark, Freed, Stephen, Fritz, David, Fuentes, Shariar, Cohen-Gadol, Robert, Garver, John, Given, Luis Ramos Gonez, Raul Ebran Gonzalez, Robert, Gordon, Gregory, Gottschlich, Donald, Graham, David, Grant, Gary, 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Ricci, Gary, Richmond, Eugene, Ryan, Fadi, Saba, Boris, Sagalovich, C Andrew Schroeder, Timothy, Scialla, Frank, Sciurba, Amit, Shah, Nirav, Shah, Zeeshan, Shaikh, Akhtar, Siddiqui, Barry, Sigal, Thomas, Siler, Howard, Silverboard, William, Sims, Clyde, Southwell, Selwyn, Spangenthal, Peruvemba, Sriram, James, Stocks, Tony, Su, John, Suen, Robert, Sussman, Horia, Tatu, Antonio, Terrelonge, Alan, Thomas, Mario, Torres, Rodolfo, Trejo, Miguel, Trevino, Banks, Turner, Manuel, Villareal, Janine, Vintch, Neal, Warshoff, Jan, Westerman, Philip, Wexler, Thomas, Yunger, Amir, Zeki, Mariano Fernandez Acquier, Norma, Aramayo, German, Arce, Juan, Belloni, Víctor, Cambursano, Carlos De La Vega, Fernando Rodriguez Chariarse, Pedro, Elias, Marcelo, Fernández, Ana, Lopez, Andrea, Medina, María, Otaola, Maria Salazan Saez, Maria De Salvo, Fernando, Scherbovsky, Ana, Stok, Jorge, Taborda, Alberto, Tolcachier, Fernando, Verra, Carlos, Victorio, Rita Gisela Delgado Vizcarra, Philip, Bardin, Peter, Bremner, Martin, Phillips, John, Upham, Peter, Wark, Antoine, Bolly, Alain, Delobbe, Peter, Driesen, Eduard, Janssens, Wim, Janssens, Olivier, Michel, Bernard, Vandooren, Martti, Antila, Jussara, Fiterman, Carlos, Fritscher, Jorge, Hetzel, Jose, Jardim, Waldo De Mattos, Rafael, Martins, Maria Eunice De Oliveira, Andreia, Pez, Maria, Sales, Rafael, Stelmach, Priscila, Wolff, Svetla, Andreeva, Reneta, Antonova, Ana, Dancheva, Yuliya, Ivanova, Slavcho, Ivanov, Hristo, Metev, Iveta, Naydenova, Tatyana, Petkova, Galina, Petrova, Kostadinka, Sotirova, Mariyana, Stoyanova, Rumen, Tiholov, Iliyana, Valkanova, Oleg, Yakov, Rosa, Feijoo, Juana, Pavie, Patricia, Schönffeldt, Absalon, Silva, Victor, Martinez, David, Espinosa, Alejandro, Londono, Dora, Molina, Gonzalo, Prada, Andrés, Rico, Gregorio Sanchez Vallejo, Alvaro, Urbina, Ana, Vanegas, Maria, Villegas, Josip, Aralica, Gordana, Stjepanovic, Vibeke, Backer, Uffe, Bødtger, Christian, Meyer, Læge Sven Nielsen, Anders Loekke Ottesen, Ingrid, Titlestad, Nathalie, Bautin, Arnaud, Bourdin, Pascal, Chanez, Francis, Couturaud, Antoine, Cuvelier, Gilles, Devouassoux, Pierre-Olivier, Girodet, Jean-François, Muir, Jean-Louis, Pépin, Alain, Proust, Azzedine, Yaici, Yochai, Adir, Gershon, Fink, Zvi, Fridlender, Gabriel, Izbicki, Mordechai, Kramer, Yehuda, Schwartz, Juan Moreno Hoyos Abril, Ricardo Campos Cerda, Efraín Montaño Gonzalez, Ricardo Ramirez Terrones, Rodolfo Posadas Valay, Alejandra, Ramirez-Venegas, Paul, Dawkins, Syed, Hussain, Benedict, Brockway, John, Richmond, Colin, Helm, Catherina, Chang, Jørn, Ahlqvist, Terje, Tollåli, Tadeusz, Tomala, Socorro, Castro, William, Chavez, Octavio, Cubas, Rolando, Estrella, Efrain, Felix, Ronal, Gamarra, Alfredo, Guerreros, Alberto, Matsuno, Danilo, Salazar, Miguel, Tsukayama, Albert Albay Jr, Teresita, Aquino, Tito, Atienza, Joven Roque Gonong, Ronnie, Samoro, Joel, Santiaguel, Beata, Asankowicz-Bargiel, Ewa, Pisarczyk-Bogacka, Renata, Bijata-Bronisz, Marta, Chełmińska, Małgorzata, Dobryniewska, Anna, Olech-Cudzik, Tomasz, Fijołek, Krzysztof, Filipek, Agata, Kot, Bożena, Kucińska, Krzysztof, Lis, Elżbieta, Rybicka-Liszewska, Marzenna, Tarnowska-Matusiak, Robert, Mróz, Piotr, Napora, Wojciech, Naumnik, Artur, Niemiec, Władysław, Pierzchała, Grzegorz, Przybylski, Katarzyna, Styka, Danuta, Wrońska, Branislava, Milenkovic, Dobrivoje, Novkovic, Matijaz, Flezar, Niksa, Segota, Snezana Ulcar Kostic, Albert, Klobucar, Leif, Bjermer, Dan, Curiac, Christer, Janson, Pekka, Koskinen, Lundback, Bo, Åke, Olsson, Shih-Lung, Cheng, Ming-Lin, Ho, Jeng-Yuan, Hsu, Wu-Huei, Hsu, Ping-Hung, Kuo, Chin-Chou, Wang, Yu-Feng, Wei, Kuang-Yao, Yang, Watchara, Boonsawat, Somchai, Chantarothorn, Warangkana, Keeratichananont, Kittipong, Maneechotesuwan, Kanok, Pipatvech, Piamlarp, Sangsayunh, Sibel, Arinc, Sermin, Borekci, Arzu Kaner Erturk, Filiz, Kosar, Hakan, Gunen, Ismail, Hanta, Pinar Akin Kabalak, Tunc Alp Demir, Sibel, Nayci, Serir Aktogu Ozkan, Abdullah, Sayiner, Esra, Uzaslan, Viktor, Blazhko, Volodymyr, Gavrysyuk, Olena, Golub, Liudmyla, Iashyna, Tetiana, Ilashchuk, Volodymyr, Koshlia, Olena, Krakhmalova, Vitali, Kryvenko, Lesia, Kuryk, Olena, Levchenko, Yuriy, Mostovoy, Mykola, Ostrovskyy, Tetyana, Pertseva, Olena, Piura, Nadiya, Rudnytska, Ganna, Stupnytska, Nataliia, Velychko, Oleh, Yakovenko, Lilia Rodriguez Ables, Roger, Abrahams, Jose, Alvarez, Fernando, Arencibia, Chander, Arora, Samir, Arora, Francis, Averill, Kwabena, Ayesu, Stephen, Basheda, Steven, Bauer, Jose, Bautista, Matthew, Beacom, Hernando, Bernal, Subodh, Bhuchar, J'Cinda, Bitters, John, Burk, Elizabeth, Burkett, James, Cain, Robert, Call, Christopher, Chappel, Bartolome, Celli, Tom, Christensen, Jeremy, Cole, Jerome, Daniel, Nguyen, Dang, Enrique, Davis, Samuel, Deleon, Robert, Deluca, Ernesto, Diaz, Anthony, Dimarco, Calvin, Dixon, Ankur, Doshi, Hugh, Durrence, Alain, Eid, John, Elsen, Herbon, Fleming, May, Flores, Scott, Franczek, Gregory, Funk, Stuart, Garay, Bernard, Garcia, Joseph, Graif, 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Mercedes, Samson, Jay, Sandberg, Jose, Santiago, William, Sargeant, Alan, Schecter, Jeffrey, Scott, Ilia, Segal, Sudhir, Sehgal, Frederic, Seifer, Sudhir, Sekhsaria, Richard, Sellman, Paul, Shapero, Jeffrey, Shea, Lawrence, Sher, John, Sibille, Jawed, Siddiqui, Toniya, Singh, Deren, Sinkowitz, Denise, Smyth, Daniel, Soteres, Daniel, Sousa, Ralph, Steele, Thomas, Stern, Jose, Suarez, Sever, Surdulescu, Ricardo, Tan, Tonny, Tanus, Raymond, Tidman, Aurelio, Torres-Consuegra, Barry, Troyan, John, Updegrove, Sanjay, Vadgama, Armando, Pineda-Velez, Eduardo, Viera, Andrew, Wachtel, Ralph, Wade, Jimin, Wang, Dave, Webster, Paul, Weinberg, Terry, Wells, Jeffrey, White, Bram, Wieskopf, Hugh, Windom, Patrick, Wright, David, Wyatt, Bassam, Yousef, Zahid, Zafar, Chau, Ngo, Huong, Le, Lan, Nguyen, Thanh, Nguyen, Nhung, Nguyen, SALAS, Danielle, Temple University [Philadelphia], Pennsylvania Commonwealth System of Higher Education (PCSHE), Harvard Medical School [Boston] (HMS), University of Leicester, University of Barcelona, Università degli Studi di Ferrara = University of Ferrara (UniFE), University of Manchester [Manchester], St. Paul’s Hospital - University of British Columbia [Vancouver, BC, Canada] (SPH-UBC), Philipps Universität Marburg = Philipps University of Marburg, University of Pittsburgh School of Medicine, University of Oxford, Bispebjerg University Hospital [Copenhagen, Denmark] (BUH), Kishiwada City Hospital [Osaka, Japan] (KCH), Instituto Nacional de Enfermedades Respiratorias [México, Mexico], I-Shou University [Kaohsiung, Taiwan] (ISU), Lund University [Lund], AstraZeneca [Gaithersburg, MD, USA] (AZ), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and Otto Burghuber, Bernhard Forstner, Gerhard Köberl, Bernd Lamprecht, Judith Löffler-Ragg, Horst Olschewski, Michael Studnicka, Francois Beaucage, Guy Chouinard, Anthony Dechant, Anthony Dowell, Jacques Hebert, Sohail Khattak, Kieran Killian, William Killorn, Andy Lam, Francois Maltais, Darcy Marciniuk, Lyle Melenka, Bonavuth Pek, Jeremy Road, Donald Sin, Alain Vaugeois, Brandie Walker, Tomas Dvorak, Stanislav Holub, Otakar Hokynar, Vitezslav Kolek, Daniela Kopecka, Jan Krepelka, Jaroslav Mares, Josef Veverka, Vladimir Zindr, Sabine Ballenberger, Rolf Dichmann, Christian Geßner, Margret Jandl, Claus Keller, Joachim Kirschner, Marc Kornmann, Petra Mikloweit, Ingomar Naudts, Axel Overlack, Isabelle Schenkenberger, Volker Schlegel, Lutz Von Versen, Claus Franz Vogelmeier, Stefan Zielen, István Albert, Beatrix Bálint, Mária Csilla Hangonyi, Teréz Kecskés, Anikó Kurucz, Balázs Medgyasszay, Lajos Molnár, János Mucsi, Márta Papp, Magdolna Póczi, Éva Radeczky, Zsolt Pápai Székely, Csilla Szabó, Gyöngyi Szabó, Melinda Szabó, Alfredo Antonio Chetta, Giuseppe Di Maria, Giulio Donazzan, Federica Meloni, Elisabetta Pace, Pierluigi Paggiaro, Alberto Papi, Fabio Luigi, Massimo Ricciardolo, Antonio Spanevello, Fumiaki Aoki, Ryosuke Eda, Takeo Endo, Yasushi Fukushima, Kenichi Gemba, Naoki Hagimoto, Hiromasa Harada, Yasuko Harada, Norihiko Hata, Osamu Hataji, Nobuo Hatakeyama, Takahiko Horiguchi, Gen Ideura, Motoyasu Iikura, Azusa Ikegami, Shirou Imokawa, Yoshikazu Inoue, Takeshi Isobe, Ryoji Ito, Susumu Iwata, Tadashi Kamei, Motokazu Kato, Hideki Katsura, Yuji Kawarada, Norio Kihara, Masaharu Kinoshita, Takashi Kinoshita, Tomoo Kishaba, Hideo Kita, Arihiro Kiyosue, Shigeru Komatsu, Kazuki Konishi, Sekiya Koyama, Makoto Kudo, Kazuhiko Machida, Hironi Makita, Hiroto Matsuse, Naoki Miyazawa, Hiroyuki Nakamura, Yuji Nakatani, Kazuyuki Nishimura, Takashi Nishimura, Junichi Ogawa, Hiroyuki Ohbayashi, Tetsuro Ohdaira, Tsukasa Ohnishi, Kazuhiko Oki, Masahiko Saito, Kenji Sakamoto, Osamu Sakamoto, Hisakuni Sekino, Noriharu Shijubo, Masaharu Shinkai, Hideo Soto, Yoshitaka Sugawara, Noriaki Suko, Hisaho Takahashi, Masamitsu Takahashi, Tsuneyuki Takahashi, Hiroshi Tanaka, Hiroyuki Taniguchi, Tadayuki Terada, Takao Tochigi, Kazuyo Tohyama, Hirokazu Tokuyasu, Keisuke Tomii, Tomomasa Tsuboi, Mitsuyoshi Utsugi, Katsumaru Yamamoto, Michiko Yamamoto, Shuichi Yano, Makoto Yoshida, Frank Custers, Richard Dekhuijzen, Remco Djamin, Jan Willem Van Dan Berg, Lowie Vanfleteren, Pascal Wielders, Bogusława Cimoszko, Anna Doboszyńska, Andrzej Dyczek, Andrzej Fal, Krystyna Folcik, Łukasz Goliński, Marek Jutel, Andrzej Kolczyński, Piotr Kuna, Ewa Łączyńska, Wojciech Machowiak, Maciej Marczak, Joanna Markiewicz, Janusz Milanowski, Grzegorz Mincewicz, Maria Nittner-Marszalska, Wojciech Papiewski, Małgorzata Pawlukiewicz, Witold Pomiećko, Barbara Rewerska, Cezary Rybacki, Wojciech Skucha, Ewa Trębas-Pietraś, Ewa Uhryn, Małgorzata Żurowska-Gębala, Laurentia Andrei, Traian Mihaescu, Stefan Mihaicuta, Eniko Vera Pall, Ioan Petrui, Angelica Savu, Claudia Toma, Ana Trailescu, Vladimir Abrosimov, Nataliya Astafyeva, Evgenyi Bazdyrev, Nadezhda Berdnikova, Laura Bolieva, Ekaterina Bukreeva, Valery Chistyakov, Anna Galustyan, Halida Gantseva, Svetlana Goncharova, Sergey Grigoriev, Galina Ignatova, Inna Ilyashevich, Nadezhda Izmozherova, Magomed Kamalov, Yaroslava Khovaeva, Natalia Kuzubova, Lyudmila Kvitkova, Liudmila Lenskaya, Igor Leshchenko, Olga Magnitskaya, Boris Molotilov, Artem Molotkov, Svetlana Myasoedova, Sergey Nedogoda, Vladimir Nosov, Marina Osipenko, Andrey Peskov, Veronika Popova, Oksana Ratushnay, Irina Ryzhova, Olga Shangina, Natalia Shaporova, Evgeny Shmelev, Lybov Shpagina, Alexander Shutkin, Yuri Shvarts, Mikhail Smirnov, Irina Stitsenko, Maksim Vasilev, Arkadiy Vertkin, Elena Vishneva, Alexander Vizel, Anna Zateyschikova, Mohamed Abdool-Gaffar, Ismail Abdullah, Axel Bruning, Nyda Fourie, Michael Greenblatt, Mohammed Tayob, K Venter, An Soo Jang, Kwan Ho Lee, Sang Haak Lee, Sook Young Lee, Suk Joong Yong, Kwang Ha Yoo, Soo Taek Uh, Ramón Agüero Balbín, David Ramos Barbón, Álvar Agustí García-Navarro, José Luis Velasco Garrido, Sergi Pascual Guardia, Eduard Monso Molas, Luis De Teresa Parreño, Borja García-Cosio Piqueras, German Peces-Barba Romero, Myriam Calle Rubio, Fernando Sánchez-Toril López, Alicia Marín Tapia, Heidi Martin Braschler, Martin Brutsche, Michael Grob, Jörg Leuppi, Daiana Stolz, Alexander Turk, Nawar Bakerley, Mona Bafadhel, Christopher Brightling, Rekha Chaudhuri, Gourab Choudhury, Graham Devereux, Imran Hussain, Kai Lee, William MacNee, Ravindran Mahadeva, Matthew Masoli, Monica Nordstrom, Manish Patel, Allan Reid, Dinesh Saralaya, Tariq Sethi, Sukh Dave Singh, Anthony G de Soyza, Tom Wilkinson, Alice Turner, Helen Ward, Chandar Abboy, Ivan Ackerman, Idalia Acosta, Arun Adlakha, Bassil Aish, Mohamed Ali, Charles Andrews, Robby Ayoub, Anil Badhwar, Dennis Bassetti, Sherif El Bayadi, Richard Beasley, Shashi Bellam, Jonathan Bernstein, Maria Blahey, Scott Bloom, Eugene Bleecker, Wesley Bray, Johnathan Brewer, Robert Buynak, William Calhoun, Edward Campbell, Anthony Captain, Birjis Chinoy, Kenneth Chinsky, Geoffrey Chupp, Arsenio Columbie, Clinton Corder, Gerard Criner, Humberto Cruz, Edward Cullen, Kevin Deboer, Michael Denenberg, Mark Dransfield, Leonard Dunn, Miles Elmore, David Erb, Faisal Fakih, Gary Ferguson, Charles Fogarty, Mark Freed, Stephen Fritz, David Fuentes, Shariar Cohen-Gadol, Robert Garver, John Given, Luis Ramos Gonez, Raul Ebran Gonzalez, Robert Gordon, Gregory Gottschlich, Donald Graham, David Grant, Gary Greenwald, James Greenwald, Kenneth Haft, Gregory Hammond, Nadia Hansel, Jeffrey Harris, Humberto Hernandez, Marvin Heuer, Albrecht Heyder, David Hill, Willis Holloway, Octavian Ioachimescu, Richard Jackson, Ajay Jain, Nan Jiang, Thomas Kaelin, Adolfo Kaplan, Mitchell Kaye, Akram Khan, Yekaterina Khronusova, Ryan Klein, Joel Kline, Firas Koura, Ritsu Kuno, Ware Kuschner, Jean Claude Labissiere, David Laman Jr, John Lee, Mitchell Lee, Lawrence Levinson, Njira Lugogo, M Mador, Nathaniel Marchetti, Rafael Martinez, Richard Martinez, Peter Mattar, David Maybee, Dennis McGraw, Michael McGuire, Curtis Mello, Aaron Milstone, John Mitchell, Wendy Moore, Timothy Moriarty, Cheta Nand, Brooke Nevins, Ikeadi Ndukwu, Rachel Nisbet, David Nyanjom, Maria Nualart, Thomas O'Brien, Mikhail Palatnik, Gnyandev Patel, Amit Patel, Guido Perez, Christopher Perry, Michael Pfeffer, Krishna Pudi, Marina Raikhel, Murali Ramaswamy, Joe Ramsdell, Donato Ricci, Gary Richmond, Eugene Ryan, Fadi Saba, Boris Sagalovich, C Andrew Schroeder, Timothy Scialla, Frank Sciurba, Amit Shah, Nirav Shah, Zeeshan Shaikh, Akhtar Siddiqui, Barry Sigal, Thomas Siler, Howard Silverboard, William Sims, Clyde Southwell, Selwyn Spangenthal, Peruvemba Sriram, James Stocks, Tony Su, John Suen, Robert Sussman, Horia Tatu, Antonio Terrelonge, Alan Thomas, Mario Torres, Rodolfo Trejo, Miguel Trevino, Banks Turner, Manuel Villareal, Janine Vintch, Neal Warshoff, Jan Westerman, Philip Wexler, Thomas Yunger, Amir Zeki, Mariano Fernandez Acquier, Norma Aramayo, German Arce, Juan Belloni, Víctor Cambursano, Carlos De La Vega, Fernando Rodriguez Chariarse, Pedro Elias, Marcelo Fernández, Ana Lopez, Andrea Medina, María Otaola, Maria Salazan Saez, Maria De Salvo, Fernando Scherbovsky, Ana Stok, Jorge Taborda, Alberto Tolcachier, Fernando Verra, Carlos Victorio, Rita Gisela Delgado Vizcarra, Philip Bardin, Peter Bremner, Martin Phillips, John Upham, Peter Wark, Antoine Bolly, Alain Delobbe, Peter Driesen, Eduard Janssens, Wim Janssens, Olivier Michel, Bernard Vandooren, Martti Antila, Jussara Fiterman, Carlos Fritscher, Jorge Hetzel, Jose Jardim, Waldo De Mattos, Rafael Martins, Maria Eunice De Oliveira, Andreia Pez, Maria Sales, Rafael Stelmach, Priscila Wolff, Svetla Andreeva, Reneta Antonova, Ana Dancheva, Yuliya Ivanova, Slavcho Ivanov, Hristo Metev, Iveta Naydenova, Tatyana Petkova, Galina Petrova, Kostadinka Sotirova, Mariyana Stoyanova, Rumen Tiholov, Iliyana Valkanova, Oleg Yakov, Rosa Feijoo, Juana Pavie, Patricia Schönffeldt, Absalon Silva, Victor Martinez, David Espinosa, Alejandro Londono, Dora Molina, Gonzalo Prada, Andrés Rico, Gregorio Sanchez Vallejo, Alvaro Urbina, Ana Vanegas, Maria Villegas, Josip Aralica, Gordana Stjepanovic, Vibeke Backer, Uffe Bødtger, Christian Meyer, Læge Sven Nielsen, Anders Loekke Ottesen, Ingrid Titlestad, Nathalie Bautin, Arnaud Bourdin, Pascal Chanez, Francis Couturaud, Antoine Cuvelier, Gilles Devouassoux, Pierre-Olivier Girodet, Jean-François Muir, Jean-Louis Pépin, Alain Proust, Azzedine Yaici, Yochai Adir, Gershon Fink, Zvi Fridlender, Gabriel Izbicki, Mordechai Kramer, Yehuda Schwartz, Juan Moreno Hoyos Abril, Ricardo Campos Cerda, Efraín Montaño Gonzalez, Ricardo Ramirez Terrones, Rodolfo Posadas Valay, Alejandra Ramirez-Venegas, Paul Dawkins, Syed Hussain, Benedict Brockway, John Richmond, Colin Helm, Catherina Chang, Jørn Ahlqvist, Terje Tollåli, Tadeusz Tomala, Socorro Castro, William Chavez, Octavio Cubas, Rolando Estrella, Efrain Felix, Ronal Gamarra, Alfredo Guerreros, Alberto Matsuno, Danilo Salazar, Miguel Tsukayama, Albert Albay Jr, Teresita Aquino, Tito Atienza, Joven Roque Gonong, Ronnie Samoro, Joel Santiaguel, Beata Asankowicz-Bargiel, Ewa Pisarczyk-Bogacka, Renata Bijata-Bronisz, Marta Chełmińska, Małgorzata Dobryniewska, Anna Olech-Cudzik, Tomasz Fijołek, Krzysztof Filipek, Agata Kot, Bożena Kucińska, Krzysztof Lis, Elżbieta Rybicka-Liszewska, Marzenna Tarnowska-Matusiak, Robert Mróz, Piotr Napora, Wojciech Naumnik, Artur Niemiec, Władysław Pierzchała, Grzegorz Przybylski, Katarzyna Styka, Danuta Wrońska, Branislava Milenkovic, Dobrivoje Novkovic, Matijaz Flezar, Niksa Segota, Snezana Ulcar Kostic, Albert Klobucar, Leif Bjermer, Dan Curiac, Christer Janson, Pekka Koskinen, Bo Lundback, Åke Olsson, Shih-Lung Cheng, Ming-Lin Ho, Jeng-Yuan Hsu, Wu-Huei Hsu, Ping-Hung Kuo, Chin-Chou Wang, Yu-Feng Wei, Kuang-Yao Yang, Watchara Boonsawat, Somchai Chantarothorn, Warangkana Keeratichananont, Kittipong Maneechotesuwan, Kanok Pipatvech, Piamlarp Sangsayunh, Sibel Arinc, Sermin Borekci, Arzu Kaner Erturk, Filiz Kosar, Hakan Gunen, Ismail Hanta, Pinar Akin Kabalak, Tunc Alp Demir, Sibel Nayci, Serir Aktogu Ozkan, Abdullah Sayiner, Esra Uzaslan, Viktor Blazhko, Volodymyr Gavrysyuk, Olena Golub, Liudmyla Iashyna, Tetiana Ilashchuk, Volodymyr Koshlia, Olena Krakhmalova, Vitali Kryvenko, Lesia Kuryk, Olena Levchenko, Yuriy Mostovoy, Mykola Ostrovskyy, Tetyana Pertseva, Olena Piura, Nadiya Rudnytska, Ganna Stupnytska, Nataliia Velychko, Oleh Yakovenko, Lilia Rodriguez Ables, Roger Abrahams, Bassil Aish, Jose Alvarez, Fernando Arencibia, Chander Arora, Samir Arora, Francis Averill, Kwabena Ayesu, Stephen Basheda, Steven Bauer, Jose Bautista, Matthew Beacom, Richard Beasley, Hernando Bernal, Subodh Bhuchar, J'Cinda Bitters, John Burk, Elizabeth Burkett, James Cain, Robert Call, Christopher Chappel, Bartolome Celli, Tom Christensen, Jeremy Cole, Jerome Daniel, Nguyen Dang, Enrique Davis, Samuel Deleon, Robert DeLuca, Ernesto Diaz, Anthony DiMarco, Calvin Dixon, Ankur Doshi, Hugh Durrence, Alain Eid, John Elsen, Herbon Fleming, May Flores, Charles Fogarty, Scott Franczek, Stephen Fritz, Gregory Funk, Stuart Garay, Bernard Garcia, Luis Ramos Gonez, Gregory Gottschlich, Joseph Graif, Carl Griffin, Yamirka Duardo Guerra, David Headley, Mitzie Hewitt, Susan Hole, Robert Holladay, Ira Horowitz, Yu-Luen Hsu, Jonathan Ilowite, Stephen Jones, Ravindra Kashyap, Edward Kerwin, Ahtaram Khan, Nicole Kimzey, James Krainson, Flory Kreutter, Kannappan Krishnaswamy, Shahrukh Kureishy, Albert Lai, Alex Lechin, Daria Lee, Marcus Lee, Williams Leeds, Joseph Lillo, Edward Lisberg, Lawrence Madoff, Narendra Maheskwari, Mujibur Majumder, Sashi Makam, Douglas Mapel, Matthew Mardiney, Jennifer Martin, David Maybee, Isaac Melamed, Elvin Mendez, Stuart Millstone, Joseph Montes, Lee Morrow, Frank Murphy, Dany Obeid, France Occy, Godson Oguchi, Juan Ortiz, Francisco Padron, Ward Paine, James Pearle, Enrique Pelayo, Vandely Perez, David Pham, Carlos Piniella, Kevin Pritchett, Padmashri Rastogi, Stephen Ryan, Syed Rehman, Jackson Rhudy, Eustace Riley, James Riser, Clifford Risk, Emory Robinette, Christopher Roney, Gary Ruoff, David Russian, Mercedes Samson, Jay Sandberg, Jose Santiago, William Sargeant, Alan Schecter, Frank Sciurba, Jeffrey Scott, Ilia Segal, Sudhir Sehgal, Frederic Seifer, Sudhir Sekhsaria, Richard Sellman, Paul Shapero, Jeffrey Shea, Lawrence Sher, John Sibille, Jawed Siddiqui, William Sims, Toniya Singh, Deren Sinkowitz, Denise Smyth, Daniel Soteres, Daniel Sousa, Ralph Steele, Thomas Stern, Jose Suarez, Sever Surdulescu, Ricardo Tan, Tonny Tanus, Raymond Tidman, Aurelio Torres-Consuegra, Barry Troyan, John Updegrove, Sanjay Vadgama, Armando Pineda-Velez, Eduardo Viera, Andrew Wachtel, Ralph Wade, Jimin Wang, Dave Webster, Paul Weinberg, Terry Wells, Jeffrey White, Bram Wieskopf, Hugh Windom, Patrick Wright, David Wyatt, Bassam Yousef, Zahid Zafar, Chau Ngo, Huong Le, Lan Nguyen, Thanh Nguyen, Nhung Nguyen
Subjects: Male, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Anti-asthmatic Agent, law.invention, Pulmonary Disease, Chronic Obstructive, Leukocyte Count, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Monoclonal, Receptors, Medicine, Anti-Asthmatic Agents, 030212 general & internal medicine, Humanized, COPD Exacerbations, benralizumab, clinical trials, COPD, Subcutaneous, General Medicine, Middle Aged, anti–IL-5Rα, Benralizumab, Pulmonary Disease, Chronic Obstructive/drug therapy, [SDV] Life Sciences [q-bio], Female, Antibodies, Monoclonal, Humanized/administration & dosage, Chronic Obstructive, Benralizumab COPD exacerbations, Injections, Subcutaneous, Socio-culturale, Aged, Antibodies, Monoclonal, Humanized, Double-Blind Method, Eosinophils, Humans, Patient Acuity, Receptors, Interleukin-5, Antibodies, chronic obstructive pulmonary disease, Injections, Pulmonary Disease, 03 medical and health sciences, Phase III, Anti-Asthmatic Agents/administration & dosage, In patient, business.industry, Eosinophils/metabolism, medicine.disease, Clinical trial, Receptors, Interleukin-5/antagonists & inhibitors, chemistry, Multicenter study, randomized controlled trial, Immunology, Interleukin-5, business
Abstract: BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).
Published: 2019
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48. Primary non-adherence to inhaled medications measured with e-prescription data from Poland

Author: Przemyslaw Kardas, Grzegorz Kardas, Michał Panek, Piotr Kuna, and Izabela Kuprys-Lipinska
Subjects: Pulmonary and Respiratory Medicine, e-prescription, medicine.medical_specialty, Allergy, Treatment adherence, Immunology, Prescription data, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Immunology and Allergy, Medicine, 030212 general & internal medicine, Inhalators, COPD adherence, Asthma, COPD, business.industry, Research, Significant difference, RC581-607, medicine.disease, Non adherence, 030228 respiratory system, Dry powder, Primary non-adherence, Immunologic diseases. Allergy, Inhaled medications, business, Asthma adherence
Abstract: Background Treatment adherence greatly influences the clinical outcomes in various fields of medicine, including management of asthma and COPD. With the recent implementation of a nationwide e-Health solutions in Poland, new and unique opportunities for studying primary non-adherence in asthma and COPD emerged. The aim was to study primary non-adherence to inhaled medications available in Poland indicated in asthma and/or COPD and analyse the impact of patients’ demographics and inhalers’ characteristics (dry powder inhalers (DPIs) vs metered dose inhalers (MDIs) and presence of a dosage counter) on primary non-adherence. Methods A retrospective analysis of all e-prescriptions issued in Poland in 2018 (n = 119,880) from the national e-prescription pilot framework. Results Primary non-adherence for inhalable medications reached 15.3%. It significantly differed among age groups—the lowest (10.8%) was in 75 + years-old patients, highest (18%) in 65–74 years-old patients. No gender differences in primary non-adherence were found. The highest non-adherence was observed for ICS + LABA combinations (18.86%). A significant difference was found between MDI and DPI inhalers and between inhalers with/without a dosage counter. Conclusions Out of e-prescriptions for inhaled medications issued in 2018 in Poland, 15.3% were not redeemed. The degree of primary non-adherence was influenced by age, but not gender. Significant differences between MDIs and DPIs and between inhalers with/without a dosage counter were observed.
Published: 2020
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49. Comparison of a dry powder inhaler (DPI) to a pressurized metered-dose inhaler (pMDI) formulation of extra fine beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) in patients with COPD: The TRI-D study

Author: Isabelle Viaud, George Georges, Kai Michael Beeh, Alessandro Guasconi, Piotr Kuna, and Massimo Corradi
Subjects: COPD, medicine.medical_specialty, business.industry, Urology, Treatment options, respiratory system, medicine.disease, Metered-dose inhaler, Dry-powder inhaler, Medicine, Formoterol Fumarate, Glycopyrronium bromide, In patient, business, Lung function, medicine.drug
Abstract: Introduction: A DPI formulation (NEXThaler®) of the extra fine BDP/FF/GB triple therapy has been developed as an alternative to pMDI to meet patients’ preference and to provide treatment options. Aims and Objectives: To demonstrate the non-inferiority of the DPI versus pMDI formulations of extra fine BDP/FF/GB on lung function. Methods: TRI-D was a, randomized, double-blind, double-dummy, active controlled, 3-way cross-over trial comparing 4 weeks of treatment with BDP/FF/GB 100/6/12.5 µg DPI and pMDI and BDP/FF 100/6 µg pMDI each delivered as 2 inhalations bid, separated by 2-week wash-outs in patients with stable, moderate-to-severe COPD. The co-primary efficacy endpoints were the change from baseline in FEV1 AUC0-12h normalised by time and in trough FEV1 at 24 hours on Day 28. Treatment-emergent adverse events (TEAEs) were collected. Results: 366 patients were randomized. Non-inferiority of BDP/FF/GB DPI vs pMDI was demonstrated for both co‑primary endpoints, with the lower limits of confidence interval of the adjusted mean differences falling above the non-inferiority threshold of -50 mL (-35 mL and -15 mL). Both DPI and pMDI triple therapies significantly improved FEV1 AUC0‑12h vs BDP/FF pMDI by 85 and 105 mL, respectively (p Conclusion: DPI and pMDI formulations of extra fine BDP/FF/GB demonstrated similar efficacy and safety in patients with COPD supporting the new DPI formulation as a valid option for both patient and physician.
Published: 2020
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50. Synergy of endoplasmic reticulum aminopeptidase 1 and 2 (ERAP1 and ERAP2) polymorphisms in atopic dermatitis: Effects on disease prevalence

Author: Łukasz Matusiak, Andrzej Wiśniewski, Izabela Nowak, Karolina Piekarska, Wanda Niepiekło-Miniewska, Piotr Kuśnierczyk, Joanna Narbutt, Aleksandra Lesiak, Piotr Kuna, and Izabela Kuprys-Lipinska
Subjects: 0301 basic medicine, Adult, Male, Adolescent, Immunology, Single-nucleotide polymorphism, Human leukocyte antigen, Biology, Aminopeptidases, Polymorphism, Single Nucleotide, Severity of Illness Index, Dermatitis, Atopic, Minor Histocompatibility Antigens, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, Genotype, medicine, Odds Ratio, Prevalence, Immunology and Allergy, Humans, Genetic Predisposition to Disease, Child, chemistry.chemical_classification, Endoplasmic reticulum, Histocompatibility Antigens Class I, General Medicine, Atopic dermatitis, Odds ratio, Middle Aged, medicine.disease, Molecular biology, Amino acid, 030104 developmental biology, Enzyme, chemistry, Case-Control Studies, Child, Preschool, Female, 030215 immunology
Abstract: Endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 trim peptides to a length of 8–10 amino acids optimal for binding by HLA class I molecules. Although these two enzymes may work separately, but they may also form a heterodimer of enhanced trimming efficiency. We have earlier described a role for ERAP1 single nucleotide polymorphism rs26618 and HLA-C*05:01 as risk factors for atopic dermatitis (AD). Here, we examined whether ERAP2 single nucleotide polymorphism rs2248374, determining the presence or absence of the functional form of enzyme, would influence the rs26618 effect. Out of nine rs2248374 – rs26618 genotypic combinations, only one, rs2248374*A/A – rs26618*C/C, was associated with a risk of AD. Interestingly, the odds ratio increased from 1.10 (CI95%: 0.72; 1.69; p = 0.657) for ERAP2 rs2248374*A/A and 1.88 (CI95%: 1.07; 3.28; p = 0.025) for ERAP1 rs26618*C/C to 3.36 (CI95%: 1.41; 8.01; p = 0.004) for their combination, therefore revealing a synergistic effect.
Published: 2020

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