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1. Mechanismen bei AIT: Erkenntnisse 2021

Author: P. Satitsuksanoa, A. Angelina, O. Palomares, and M. Akdis
Subjects: Immunology and Allergy
Published: 2022

2. Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN)

Author: F. Braido, N. Scichilone, F. Lavorini, O. S. Usmani, L. Dubuske, L. P. Boulet, R. Mosges, C. Nunes, M. Sanchez-Borges, I. J. Ansotegui, M. Ebisawa, F. Levi-Schaffer, L. J. Rosenwasser, J. Bousquet, T. Zuberbier, G. Walter Canonica, A. Cruz, A. Yanez, A. Yorgancioglu, D. Deleanu, G. Rodrigo, J. Berstein, K. Ohta, P. Vichyanond, R. Pawankar, S. N. Gonzalez-Diaz, S. Nakajima, T. Slavyanskaya, A. Fink-Wagner, C. Baez Loyola, D. Ryan, G. Passalacqua, J. Celedon, J. C. Ivancevich, K. Dobashi, M. Zernotti, M. Akdis, S. Benjaponpitak, S. Bonini, W. Burks, L. Caraballo, Z. Awad El-Sayed, S. Fineman, P. Greenberger, E. Hossny, J. A. Ortega-Martell, H. Saito, M. Tang, L. Zhang, for Interasma Executive Board, ARIA, and GA2LEN
Subjects: Asthma, Chronic Obstructive Pulmonary Disease, Chronic Obstructive Pulmonary Disease Patient, Allergic Rhinitis, Small Airway, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter
Published: 2016
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3. Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma

Author: Kirstin Jansen, Tatiana Kebadze, Oliver F. Wirz, David Mirer, Kari C. Nadeau, Willem van de Veen, James E. Gern, Pattraporn Satitsuksanoa, Patrick Mallia, Nikolaos G. Papadopoulos, Cezmi A. Akdis, M. Akdis, Simon D. Message, Ge Tan, Nicholas Glanville, Sebastian L. Johnston, Barbara Stanic, and Milena Sokolowska
Subjects: Picornaviridae Infections, Rhinovirus, business.industry, viruses, Immunology, medicine.disease_cause, Antiviral Agents, Asthma, Virus, In vitro, respiratory tract diseases, Proinflammatory cytokine, stomatognathic system, Downregulation and upregulation, In vivo, Humoral immunity, Gene expression, medicine, Cytokines, Humans, Immunology and Allergy, Interferons, business
Abstract: Background Rhinoviruses are the predominant cause of respiratory viral infections and are strongly associated with asthma exacerbations. While humoral immunity plays an important role during virus infections, cellular aspects of this response are less well understood. Here, we investigated the antiviral response of circulating B cells upon experimental rhinovirus infection in healthy individuals and asthma patients. Methods We purified B cells from experimentally infected healthy individuals and patients with asthma and subjected them to total RNA-sequencing. Rhinovirus-derived RNA was measured in isolated B cells using a highly sensitive PCR. B cells were stimulated with rhinovirus in vitro to further study gene expression, expression of antiviral proteins and B-cell differentiation in response rhinovirus stimulation. Protein expression of pro-inflammatory cytokines in response to rhinovirus was assessed using a proximity extension assay. Results B cells isolated from experimentally infected subjects exhibited an antiviral gene profile linked to IFN-alpha, carried viral RNA in vivo and were transiently infected by rhinovirus in vitro. B cells rapidly differentiated into plasmablasts upon rhinovirus stimulation. While B cells lacked expression of interferons in response to rhinovirus exposure, co-stimulation with rhinovirus and IFN-alpha upregulated pro-inflammatory cytokine expression suggesting a potential new function of B cells during virus infections. Asthma patients showed extensive upregulation and dysregulation of antiviral gene expression. Conclusion These findings add to the understanding of systemic effects of rhinovirus infections on B-cell responses in the periphery, show potential dysregulation in patients with asthma and might also have implications during infection with other respiratory viruses.
Published: 2021

4. SEVERE CHRONIC ALLERGIC (AND RELATED) DISEASES: A UNIFORM APPROACH — A MEDALL-GA2LEN-ARIA POSITION PAPER IN COLLABORATION WITH THE WHO COLLABORATING CENTER FOR ASTHMA AND RHINITIS (ENGLISH & RUSSIAN VARIANTS)

Author: J. Bousquet, J.M. Anto, P. Demoly, H.J. Schunemann, A. Togias, and M. Akdis
Subjects: Pediatrics, RJ1-570, Therapeutics. Pharmacology, RM1-950
Abstract: Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria, atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as co-morbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.Key words: IgE, allergy, severity, control, risk, asthma, rhinitis, rhinosinusitis, urticaria, atopic dermatitis.
Published: 2011

5. Mechanical Blood Pumps for Cardiac Assistance

Author: M. Akdis and H. Reul
Subjects: Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5
Abstract: Cardiac assist devices are classified into the traditional engineering categories of displacement and rotary pumps. Clinical use and indications of the various pump categories are outlined and a detailed description of currently available systems is given. The first part deals with extracorporeal as well as implantable ventricular assist devices (VAD) of the displacement type and is followed by a section on current developments in the field of total artificial hearts (TAH). The second part covers the rotary pump category from cardiopulmonary bypass applications to implantable systems, including specific design aspects of radial, diagonal, and axial pumps.
Published: 2005
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6. Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA2LEN consensus

Author: Hagemann, J. Onorato, G.L. Jutel, M. Akdis, C.A. Agache, I. Zuberbier, T. Czarlewski, W. Mullol, J. Bedbrook, A. Bachert, C. Bennoor, K.S. Bergmann, K.-C. Braido, F. Camargos, P. Caraballo, L. Cardona, V. Casale, T. Cecchi, L. Chivato, T. Chu, D.K. Cingi, C. Correia-de-Sousa, J. del Giacco, S. Dokic, D. Dykewicz, M. Ebisawa, M. El-Gamal, Y. Emuzyte, R. Fauquert, J.-L. Fiocchi, A. Fokkens, W.J. Fonseca, J.A. Gemicioglu, B. Gomez, R.-M. Gotua, M. Haahtela, T. Hamelmann, E. Iinuma, T. Ivancevich, J.C. Jassem, E. Kalayci, O. Kardas, P. Khaitov, M. Kuna, P. Kvedariene, V. Larenas-Linnemann, D.E. Lipworth, B. Makris, M. Maspero, J.F. Miculinic, N. Mihaltan, F. Mohammad, Y. Montefort, S. Morais-Almeida, M. Mösges, R. Naclerio, R. Neffen, H. Niedoszytko, M. O’Hehir, R.E. Ohta, K. Okamoto, Y. Okubo, K. Panzner, P. Papadopoulos, N.G. Passalacqua, G. Patella, V. Pereira, A. Pfaar, O. Plavec, D. Popov, T.A. Prokopakis, E.P. Puggioni, F. Raciborski, F. Reijula, J. Regateiro, F.S. Reitsma, S. Romano, A. Rosario, N. Rottem, M. Ryan, D. Samolinski, B. Sastre, J. Solé, D. Sova, M. Stellato, C. Suppli-Ulrik, C. Tsiligianni, I. Valero, A. Valiulis, A. Valovirta, E. Vasankari, T. Ventura, M.T. Wallace, D. Wang, D.Y. Williams, S. Yorgancioglu, A. Yusuf, O.M. Zernotti, M. Bousquet, J. Klimek, L.
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
Published: 2021

7. COVID-19 pandemic: Practical considerations on the organization of an allergy clinic—An EAACI/ARIA Position Paper

Author: Pfaar, O. Klimek, L. Jutel, M. Akdis, C.A. Bousquet, J. Breiteneder, H. Chinthrajah, S. Diamant, Z. Eiwegger, T. Fokkens, W.J. Fritsch, H.-W. Nadeau, K.C. O’Hehir, R.E. O’Mahony, L. Rief, W. Sampath, V. Schedlowski, M. Torres, M.J. Traidl-Hoffmann, C. Wang, D.Y. Zhang, L. Bonini, M. Brehler, R. Brough, H.A. Chivato, T. Del Giacco, S.R. Dramburg, S. Gawlik, R. Gelincik, A. Hoffmann-Sommergruber, K. Hox, V. Knol, E.F. Lauerma, A. Matricardi, P.M. Mortz, C.G. Ollert, M. Palomares, O. Riggioni, C. Schwarze, J. Skypala, I. Untersmayr, E. Walusiak-Skorupa, J. Ansotegui, I.J. Bachert, C. Bedbrook, A. Bosnic-Anticevich, S. Brussino, L. Canonica, G.W. Cardona, V. Carreiro-Martins, P. Cruz, A.A. Czarlewski, W. Fonseca, J.A. Gotua, M. Haahtela, T. Ivancevich, J.C. Kuna, P. Kvedariene, V. Larenas-Linnemann, D.E. Abdul Latiff, A.H. Mäkelä, M. Morais-Almeida, M. Mullol, J. Naclerio, R. Ohta, K. Okamoto, Y. Onorato, G.L. Papadopoulos, N.G. Patella, V. Regateiro, F.S. Samoliński, B. Suppli Ulrik, C. Toppila-Salmi, S. Valiulis, A. Ventura, M.-T. Yorgancioglu, A. Zuberbier, T. Agache, I.
Subjects: education
Abstract: Background: The coronavirus disease 2019 (COVID-19) has evolved into a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Allergists and other healthcare providers (HCPs) in the field of allergies and associated airway diseases are on 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. Method: The scientific information on COVID-19 was analysed by a literature search in MEDLINE, PubMed, the National and International Guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library, and the internet. Results: Based on the 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, and 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)” initiative 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. Conclusions: This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients while ensuring the necessary safety measures in the current COVID-19 pandemic. © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Published: 2021

8. EUFOREA Rhinology Research Forum 2017: report of the brainstorming sessions on endotype-driven treatment, patient empowerment and digital future in airways care

Author: I. Koren, K. Talavera-Perez, J.A. Castillo, Valerie J. Lund, N.S. Seyed-Tabib, J.A.M. Claes, Ruth Murray, M. Koennecke, B Lange, C. Bachert, K. Sleurs, G. De Carlo, Guy Joos, I. Kortekaas-Krohn, A. Van Hoolst, M. Akdis, S.K. Chung, R. Boscke, C. Akdis, Ph. Rombaux, B. Verhaeghe, Maria Doulaptsi, S. Vaitkus, D. O'Sullivan, T. Zuberbier, Sven Seys, Benoit Pugin, V. Boeva, P. Gevaert, Brecht Steelant, J. Staikuniene, K. Golebski, C. Rondon, S. Gallo, Michel Djandji, A.-J. Tasman, J. Lee, J. Feijen, I. Kloeck, G.W. Canonica, J Mullol, C. Taube, W.J. Fokkens, A. Jagerschmidt, T.A. Popov, Sanna Toppila-Salmi, T. Tran-Le, S Vlaminck, Jean Bousquet, K. van Gool, G.Y. Ban, K. Biswas, Claire Hopkins, J. Vaitkus, Anette Drøhse Kjeldsen, Simon B. Gane, Olga Krysko, Leen Cools, Kato Speleman, R. Verbrugge, Martin Wagenmann, Thomas Hummel, O. Kokorina, E. De Corso, P W Hellings, D. Morghenti, Katleen Martens, Emmanuel P. Prokopakis, Carl Philpott, I. Izquierdo, Leda Mannent, S. Halewyck, N. Launders, L. Van Gerven, Basile Nicolas Landis, P.J. Rowe, G. Lekakis, Ear, nose & throat, and Ear, Nose and Throat
Subjects: Rhinology, medicine.medical_specialty, Medical education, Endotype, business.industry, Patient Empowerment, ehealth, precision medicine, education, General Medicine, Precision medicine, patient empowerment, rhinitis, Otorhinolaryngology, RF1-547, Brainstorming, medicine, eHealth, endotype, business, rhinosinusitis, health care economics and organizations
Abstract: The second European Rhinology Reserach Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held on 9-10th November 2017, combined with a specific symposium on air pollution and mobile Health technology (mHealth) with the GARD (Global Alliance against Chronic Respiratory Diseases) initiative of WHO (World Health Organization). Physicians from different specialities, researchers, as well as patients and industry representatives from more than 40 countries took part in the Forum. Relevant topics were debated with the aim of allowing the implementation of precision medicine (PM) in daily respiratory care. All debates started with positioning the current state of the art: identification of current gaps in practice, the current consensus and the need for implementation of novel approaches such as endotype-driven treatment, patient empowerment and eHealth tools. This report provides a summry of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2017, highlighting the research needs in PM, with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key drivers for improving current clinical practice.
Published: 2018

9. Development and Characterization of Antisense Oligonucleotides Against Human Rhinovirus for Efficient Prevention of Asthma Exacerbation

Author: Nan Zhang, Styliani Taka, B. Alashkar Alhamwe, Chrysanthi Skevaki, Spyridon Megremis, Stephan Becker, Sebastian D. Unger, Nikolaos G. Papadopoulos, M. Akdis, Michael R. Edwards, Daniel P. Potaczek, Markus Eickmann, Anne Sadewasser, Feng Lan, Markus Helfer, Sven Michel, Cezmi A. Akdis, Claus Bachert, Holger Garn, Harald Renz, Christoph Hudemann, Nesibe Akdag, Fahd Alhamdan, and Sebastian L. Johnston
Subjects: Asthma exacerbations, business.industry, Antisense oligonucleotides, Immunology, Medicine, Rhinovirus, business, medicine.disease_cause
Published: 2019

10. Paving the way of systems biology and precision medicine in allergic diseases: the Me <scp>DALL</scp> success story

Author: Erik Melén, Rudolph Valenta, Fanny Rancière, C. Tischer, I. Skrindo, Hamida Hammad, V. Anastasova, Leda Chatzi, C. Hohman, Magnus Wickman, M P Fantini, M. Torrent, Pascal Demoly, S. Palkonen, Esben Eller, Carsten Bindslev-Jensen, N. Anderson, A. Bedbrook, Torsten Zuberbier, Rachel Nadif, Francesco Forastiere, K. Wenger, Sybille Koletzko, I. Annesi-Maesano, Jonathan M. Coquet, Yvan Saeys, Joachim Heinrich, Steffen Lau, Marit Westman, Bénédicte Jacquemin, L. von Hertzen, M. Standl, Marta Benet, Martijn J. Schuijs, Mirela Curin, Dirkje S. Postma, Valérie Siroux, Bart N. Lambrecht, E. Minina, Christian Lupinek, Vegard Hovland, Irina Lehmann, Jordi Sunyer, Dieter Maier, Stephane Ballereau, Anna Asarnoj, Jean Bousquet, Isabelle Momas, A. Rial-Sebbag, Gerard H. Koppelman, Cezmi A. Akdis, Isabelle Pin, A. von Berg, Henriette A. Smit, Manolis Kogevinas, Beatrix Gerhard, Claus Bachert, Emilie Burte, S. Guerra, Sandra Wieser, Bert Brunekreef, Johann Pellet, Ulrike Gehring, Renata Kiss, Petter Mowinckel, Cheng-Jian Xu, Anne Cambon-Thomsen, Jordi Mestres, Theresa Keller, Martijn C. Nawijn, Ferran Ballester, N. Ballardini, Tari Haahtela, Mariona Pinart, Charles Auffray, J. Garcia-Aymerich, J. Just, R. Albang, Marek L. Kowalski, Marjan Kerkhof, Inger Kull, Mika J. Mäkelä, G. De Carlo, J. De Vocht, Kai-Håkon Carlsen, Sam Oddie, A. Arno, Rosemary R. C. McEachan, X. Basagana, Thomas Keil, Daniela Porta, M. Akdis, Anna Bergström, Nathanaël Lemonnier, Raphaëlle Varraso, John Wright, Josep M. Antó, K. C. Lødrup Carlsen, and D. Smagghe
Subjects: 0301 basic medicine, Allergy, education.field_of_study, business.industry, Systems biology, Immunology, Population, Atopic dermatitis, Omics, medicine.disease, Precision medicine, 3. Good health, Review article, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030228 respiratory system, Immunology and Allergy, Medicine, media_common.cataloged_instance, European union, business, education, media_common
Abstract: MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.
Published: 2016

11. Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology

Author: Karin C. Lødrup Carlsen, L. Cecchi, F. Portejoie, T. Vontetsianos, Olivier Vandenplas, M. van Hague, D. Mora Bogado, M. Illario, Dana Wallace, L. Namazova-Baranova, E. Asayag, I. Ribeirinho, E. Costa, Shona Pedersen, Inger Kull, Davor Plavec, M. Morais-Almeida, Mickael Bewick, N.H. Chavannes, I. J. Ansotegui, G. De Carlo, K. S. Bennoor, Faradiba Sarquis Serpa, S. Arnavielle, F. Corti, Moises A. Calderon, Martín Bedolla-Barajas, Mette Sørensen, Isabella Annesi-Maesano, Elaine Colgan, Przemyslaw Kardas, M. van Eerd, Jorge Maspero, Valérie Siroux, Isabelle Momas, Ralph Mösges, Yves Dauvilliers, T. Keil, T. Bieber, Marit Westman, Rachel Nadif, O. Pfaar, A.C. Carvalho Coehlo, R. M. Cortés-Grimaldo, I. Skrindo, Piotr Kuna, Nicola Scichilone, Antonella Muraro, Kimihiro Okubo, Paulo Augusto Moreira Camargos, C. Cartier, Oliver Pfaar, K. Ohta, Barbara P. Yawn, Igor Kaidashev, Michel Thibaudon, X. Basagana, I. Kaidashev, Bilun Gemicioglu, S. Genova, Hae-Sim Park, J.J. Matta Campos, Simon Walker, Ulf Darsow, Fulvio Braido, J. Salimäki, T. Zuberbier, Raphaël Chiron, Mohammad Reza Masjedi, G.D. Marshall, Branislava Milenkovic, W. J. Fokkens, Eric D. Bateman, Robert M. Naclerio, Steve Montefort, M. de Fátima Emerson, T. Werfel, Cemal Cingi, A. Szylling, Martin Wagenmann, I. Baiardini, L. T. T. Le, N. Khaltaev, Ki-Suck Jung, Agnieszka Lipiec, Panayiotis K. Yiallouros, A Valero, R. Gerth van Wijk, L. Hernández, Marek L. Kowalski, C. Zubrinich, Sinthia Bosnic-Anticevich, Miguel A. Sierra, Erik Melén, T. Haahtela, Rute Almeida, Violeta Kvedariene, R. Pawankar, T.A. Popov, Flore Amat, Sanna Toppila-Salmi, M. Gotua, A. Sheikh, A. Bedbrook, Torsten Zuberbier, B. De Martino, Gérard Dray, Francesca Avolio, E. Mandajieva, B. Samolinski, Petr Panzner, P. Kuna, Philippe-Jean Bousquet, T. D. Nyembue, Luo Zhang, Leyla Namazova-Baranova, Ana Maria Carriazo, João Fonseca, E. Van Ganse, Roland Buhl, M. Bochenska Marciniak, Cristiana Stellato, J. da Silva, J. E. Gereda, Han-Jung Park, M.C. Costa-Dominguez, W. Carr, Dirceu Solé, S. Forti, Nanshan Zhong, Jordi Sunyer, Alain Didier, Y. Z. Chen, Thomas B. Casale, Jim Phillips, Isabelle Bosse, Manuel Teixeira Veríssimo, D. Y. Wang, U. Trama, Cristina Bárbara, David Somekh, T. Camuzat, R. N. Naclerio, Enrico Novellino, Leszek Klimek, M. Rodriguez Gonzalez, Holger J. Schünemann, Mario Barbagallo, D. Larenas-Linnemann, Mario Sánchez-Borges, Massimo Triggiani, Y. Okamoto, E. Mathieu-Dupas, N. Di Carluccio, S. Toppila-Salmi, Omer Kalayci, Rudolf Valenta, J. Coll, F. de Blay, Wienczyslawa Czarlewski, W. Pohl, Piotr Wroczyński, Kian Fan Chung, Nikolaos G. Papadopoulos, Pascal Demoly, Hubert Blain, M. Crescenzo, O. Kalayci, Leocadio Rodríguez-Mañas, G. Moda, L. Cox, Z. Gutter, A. Mair, Andrew Bush, Maria-Dolores Mogica-Martinez, Giorgio Walter Canonica, Antonio Valero, Daniel Laune, A. Zurkuhlen, Paul C. Potter, D. Wallace, Gabrielle L. Onorato, Mihaela Zidarn, E.P. Prokopakis, Anne Lise Courbis, Sergio Bonini, Ruta Dubakiene, A. Papi, Y. El-Gamal, Jacques Mercier, Wytske Fokkens, Rodolphe Bourret, S. Palkonen, A. Yorgancioglu, G. Vezzani, J. A. Rizzo, D. Plavec, D. Caillot, G. De Feo, E. Menditto, Caterina Bucca, A. C. Pozzi, Hironori Sagara, I. Grisle, I. Pin, Christopher E. Brightling, Ludger Klimek, F.F. Morato-Castro, Désirée Larenas-Linnemann, Alessandro Vatrella, A. A. Cruz, Guy Joos, E.D. Bateman, Erendira Rodriguez-Zagal, H. Douagui, T. To, Edgardo Jares, C. Bindslev-Jensen, G. Levato, J. O. B. Hourihane, R. Rajabian-Soderlund, C. Odzhakova, J. Bousquet, M. T. Ventura, Arzu Yorgancioglu, Osman M. Yusuf, H. J. Zar, Giovanni Rolla, Sebastian L. Johnston, M.S. Dykewicz, Esben Eller, A. Gamkrelidze, Filip Raciborski, Renzo Angles, Rafael Stelmach, M. Nogues, David Price, Mário Morais-Almeida, Tari Haahtela, Teresa To, D. Conforti, Stephen R. Durham, S. Gonzalez Diaz, V. Cardona, Werner Aberer, B. Milenkovic, Luigi Napoli, K. C. Bergmann, P W Hellings, M. Lessa, P. Panzner, Alfonso M. Cepeda Sarabia, M. Guidacci, A.L. Matos, Todor A. Popov, C. Suppli Ulrik, Diana Deleanu, N. de Paula Motta Rubini, Carsten Bindslev-Jensen, I. Majer, Ioana Agache, B. A. Barreto, R. Picard, Erkka Valovirta, A. Fink-Wagner, L. Colas, João O. Malva, Thomas Keil, M. T. Burguete Cabañas, Bolesław Samoliński, M.H. Garcia-Cruz, L.P. Boulet, K. Nekam, Edyta Krzych-Fałta, P. Devillier, J. Ferreira de Mello, Jussi Karjalainen, I. Bogus-Buczynska, Susan Waserman, Marcus Maurer, Tomas Chivato, Elena Bacci, M. Przemecka, Olga Lourenço, José Miguel Fuentes-Pérez, M. Zidarn, Talant Sooronbaev, J.M. Anto, W. Czarlewski, R. Murray, Luís Nogueira-Silva, G. Passalacqua, E. Chkhartishvili, Oscar Mayora, Victoria Cardona, M. Sondermann, Piotr Lacwik, S. Ouedraogo, I. Baroni, Artur Z. Białoszewski, G Scadding, J. Strozek, R. Emuzyte, Neven Miculinic, Ruby Pawankar, Ken Ohta, I. Agache, J.L. Gálvez-Romero, Nikos G. Papadopoulos, E. O. Meltzer, I. Annesi-Maesano, E. De Manuel Keenoy, Jorge A. Luna-Pech, Ana Margarida Pereira, Paul Potter, M. Ortega Cisneros, J. Li, K. F. Rabe, M. Rottem, Mikael Benson, Ali Fuat Kalyoncu, Dermot Ryan, Dieter Maier, C.Y. García-Cobas, S. Bialek, G. Du Toit, S. Shamai, S. Mavale-Manuel, Rojin Rajabian-Soderlund, Maddalena Illario, Philippe Devillier, F. Rodenas, Emmanuel P. Prokopakis, De Yun Wang, Niels H. Chavannes, E.H.D. Bel, Bianca Beghe, Sietze Reitsma, John Wright, O. Lourenço, L.T.T. Le, Josep M. Antó, T. Casale, Paul K. Keith, K. C. Lødrup Carlsen, P. Demoly, Mikael Kuitunen, Marc Humbert, A. M. Cepeda Sarabia, Ignacio J. Ansotegui, M.C. Rizzo, Davide Caimmi, Milan Sova, Nick A. Guldemond, P. Yakovliev, Judah A. Denburg, Jaime Correia de Sousa, Elisabete Melo-Gomes, Aziz Sheikh, I. Bosse, M. M. Ciaravolo, S. Di Capua Ercolano, Alpana Mair, P. Lieberman, Isabella Pali-Schöll, Leif Bjermer, G. De Vries, M. Roman Rodriguez, Johanna Salimäki, Carmen Panaitescu, F. Mihaltan, Giulia De Feo, F. E. R. Simons, A. Blua, B. Mahboub, D. Ryan, M. Bewick, Anabela Mota-Pinto, J.A. Fonseca, Neil Wilson, Marek Jutel, Dennis M. Williams, M. Akdis, Menachem Rottem, Marcello Persico, J. C. Ivancevich, Nelson Rosario, A. Farsi, Alvaro A. Cruz, Liguo Zhang, Anna Bedbrook, L. Bertorello, Magnus Wickman, Marilyn Urrutia-Pereira, O. Spranger, René Maximiliano Gómez, C. Bachert, Renaud Louis, Musa Khaitov, C. Stellato, Constantinos Pitsios, Roland Buonaiuto, A. Romano, Sîan A Williams, R. Puy, Daniela Rivero-Yeverino, Y. Mohammad, J. Farrell, Jan Brozek, Ricardo Pio Monti, E. Paulino, J. Correia de Sousa, Miguel Alejandro Medina-Ávalos, Jocelyne Just, Peter Valentin Tomazic, Jean-François Ferrero, Antoine Magnan, S. Waserman, J Rosado-Pinto, Maciek Kupczyk, C.S. Bosnic-Anticevich, T. Dedeu, Tommi Vasankari, R. Mösges, Robin O'Hehir, Ema Paulino, Peter Hellings, A. Neou, M. Wickman, D. Lauri, Jean Bousquet, A. Ciceran, Jacques Bouchard, Yehia El-Gamal, M.G. Dominguez-Silva, M.R. Alberti, Jean-Louis Pépin, Kimi Okubo, Juan Carlos Ivancevich, Patrik Eklund, Benoit Pugin, C. Dario, Mussa Khaitov, Luisa Brussino, A.G. Chuchalin, Elísio Costa, Susanna Palkonen, Lars Münter, Pedro Carreiro-Martins, R.E. Pulido Ross, Ettore Novellino, Kai-Håkon Carlsen, María Antonieta Guzmán, G.W. Canonica, Gabriel Onorato, Giuseppe De Carlo, R.E. Roller-Wirnsberger, Brian J. Lipworth, M. A. Guzman, J.N. Tebyriçá, Adnan Custovic, Yoshitaka Okamoto, Rimantas Stukas, P. Manning, J. Sastre-Dominguez, Caroline L.S. George, Robyn E O'Hehir, K. Maciej, Bassam Mahboub, J. F. Fontaine, Arũnas Valiulis, Xavier Rodó, D. Vicheva, G. Canfora, Vitalis Briedis, S. Rodrigues Valle, Mark S. Dykewicz, Joanne Rimmer, G. Castellano, B. Pigearias, A. L. Boner, Yunuen Rocío Huerta-Villalobos, Christine Rolland, H. Neffen, H. Arshad, Javier Gómez-Vera, P. Moura Santo, Frederic Viart, F. Blasi, J. Garcia-Aymerich, Lorenzo Cecchi, V. Niedeberger, Giorgio Ciprandi, F. Caballero-Fonseca, Jean-François Fontaine, J Mullol, Maurizio Romano, M. Viegi, Mario E. Zernotti, Arunas Valiulis, Anna Asarnoj, Antonio Nieto, J. Lavrut, D. Dokic, V. Kvedariene, Ewa Jassem, Cezmi A. Akdis, Ruth Murray, Claus Bachert, Peter Schmid-Grendelmeier, Emilie Burte, Joaquim Mullol, Guido Iaccarino, J. Kleine-Tebbe, P. V. Tomazic, E. Eller, Alessandro Fiocchi, H.J. Schunemann, M. Sorlini, C. Robalo-Cordeiro, Ana-Maria Todo-Bom, J. Brozek, Marco Nalin, Matteo Bonini, J. C. Sisul, S.E. Dahlen, F. 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Emuzyte R., Farrell J., Farsi A., Ferreira de Mello J., Ferrero J., Fink-Wagner A., Fiocchi A., Forti S., Fuentes-Perez J.M., Galvez-Romero J.L., Gamkrelidze A., Garcia-Aymerich J., Garcia-Cobas C.Y., Garcia-Cruz M.H., Gemicioglu B., Genova S., George C., Gereda J.E., Gerth van Wijk R., Gomez R.M., Gomez-Vera J., Gonzalez Diaz S., Gotua M., Grisle I., Guidacci M., Guldemond N.A., Gutter Z., Hajjam J., Hernandez L., Hourihane J.O., Huerta-Villalobos Y.R., Humbert M., Iaccarino G., Jares E.J., Jassem E., Johnston S.L., Joos G., Jung K.S., Jutel M., Kalyoncu A.F., Karjalainen J., Kardas P., Keith P.K., Khaltaev N., Kleine-Tebbe J., Kuitunen M., Kull I., Kupczyk M., Krzych-Falta E., Lacwik P., Lauri D., Lavrut J., Lessa M., Levato G., Li J., Lieberman P., Lipiec A., Lipworth B., Lodrup Carlsen K.C., Louis R., Luna-Pech J.A., Maciej K., Magnan A., Maier D., Majer I., Malva J., Mandajieva E., Manning P., De Manuel Keenoy E., Marshall G.D., Masjedi M.R., Maspero J.F., Mathieu-Dupas E., Matta Campos J.J., Matos A.L., Maurer M., Mavale-Manuel S., Mayora O., Medina-Avalos M.A., Melen E., Melo-Gomes E., Meltzer E.O., Mercier J., Miculinic N., Mihaltan F., Moda G., Mogica-Martinez M.D., Mohammad Y., Momas I., Montefort S., Monti R., Mora Bogado D., Morato-Castro F.F., Mota-Pinto A., Moura Santo P., Munter L., Muraro A., Nadif R., Nalin M., Napoli L., Neffen H., Niedeberger V., Nekam K., Neou A., Nieto A., Nogueira-Silva L., Nogues M., Nyembue T.D., Odzhakova C., Ortega Cisneros M., Ouedraogo S., Pali-Scholl I., Papi A., Passalacqua G., Pedersen S., Pepin J.L., Pereira A.M., Persico M., Phillips J., Picard R., Pigearias B., Pin I., Pitsios C., Pohl W., Portejoie F., Pozzi A.C., Price D., Puy R., Pugin B., Pulido Ross R.E., Przemecka M., Rabe K.F., Raciborski F., Reitsma S., Ribeirinho I., Rimmer J., Rivero-Yeverino D., Rizzo J.A., Rizzo M.C., Robalo-Cordeiro C., Rodenas F., Rodo X., Rodriguez Gonzalez M., Rodriguez-Manas L., Rolland C., Rodrigues Valle S., Roman Rodriguez M., 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M., Bachert, Clau, Bateman, Eric D., Bedbrook, Anna, Bennoor, Kazi, Bewick, Mickael, Bindslev-Jensen, Carsten, Bosnic-Anticevich, Sinthia, Bosse, Isabelle, Brozek, Jan, Brussino, Luisa, Canonica, Giorgio W., Cardona, Victoria, Casale, Thoma, Cepeda Sarabia, Alfonso M., Chavannes, Niels H., Cecchi, Lorenzo, Correia de Sousa, Jaime, Costa, Elisio, Cruz, Alvaro A., Czarlewski, Wienczyslawa, De Carlo, Giuseppe, De Feo, Giulia, Demoly, Pascal, Devillier, Philippe, Dykewicz, Mark S., El-Gamal, Yehia, Eller, Esben E., Fonseca, Joao A., Fontaine, Jean-Françoi, Fokkens, Wytske J., Guzmán, Maria-Antonieta, Haahtela, Tari, Illario, Maddalena, Ivancevich, Juan-Carlo, Just, Jocelyne, Kaidashev, Igor, Khaitov, Musa, Kalayci, Omer, Keil, Thoma, Klimek, Ludger, Kowalski, Marek L., Kuna, Piotr, Kvedariene, Violeta, Larenas-Linnemann, Desiree, Laune, Daniel, Le, Lan T. T., Carlsen, Karin Lodrup, Lourenço, Olga, Mahboub, Bassam, Mair, Alpana, Menditto, Enrica, Milenkovic, Branislava, Morais-Almeida, Mario, Mösges, Ralph, Mullol, Joaquim, Murray, Ruth, Naclerio, Robert, Namazova-Baranova, Leyla, Novellino, Ettore, O'Hehir, Robyn E., Ohta, Ken, Okamoto, Yoshitaka, Okubo, Kimi, Onorato, Gabrielle L., Palkonen, Susanna, Panzner, Petr, Papadopoulos, Nikos G., Park, Hae-Sim, Paulino, Ema, Pawankar, Ruby, Pfaar, Oliver, Plavec, Davor, Popov, Ted A., Potter, Paul, Prokopakis, Emmanuel P., Rottem, Menachem, Ryan, Dermot, Salimäki, Johanna, Samolinski, Boleslaw, Sanchez-Borges, Mario, Schunemann, Holger J., Sheikh, Aziz, Sisul, Juan-Carlo, Rajabian-Söderlund, Rojin, Sooronbaev, Talant, Stellato, Cristiana, To, Teresa, Todo-Bom, Ana-Maria, Tomazic, Peter-Valentin, Toppila-Salmi, Sanna, Valero, Antonio, Valiulis, Aruna, Valovirta, Erkka, Ventura, Maria-Teresa, Wagenmann, Martin, Wang, De Yun, Wallace, Dana, Waserman, Susan, Wickman, Magnu, Yorgancioglu, Arzu, Zhang, Luo, Zhong, Nanshan, Zidarn, Mihaela, Zuberbier, Torsten, Bousquet, J., Hellings, P. W., Aberer, W., Agache, I., Akdis, C. A., Akdis, M., Alberti, M. R., Almeida, R., Amat, F., Angles, R., Annesi-Maesano, I., Ansotegui, I. J., Anto, J. M., Arnavielle, S., Asayag, E., Asarnoj, A., Arshad, H., Avolio, F., Bacci, E., Bachert, C., Baiardini, I., Barbara, C., Barbagallo, M., Baroni, I., Barreto, B. A., Basagana, X., Bateman, E. D., Bedolla-Barajas, M., Bedbrook, A., Bewick, M., Beghé, B., Bel, E. H., Bergmann, K. C., Bennoor, K. S., Benson, M., Bertorello, L., Białoszewski, A. Z., Bieber, T., Bialek, S., Bindslev-Jensen, C., Bjermer, L., Blain, H., Blasi, F., Blua, A., Bochenska Marciniak, M., Bogus-Buczynska, I., Boner, A. L., Bonini, M., Bonini, S., Bosnic-Anticevich, C. S., Bosse, I., Bouchard, J., Boulet, L. P., Bourret, R., Bousquet, P. J., Braido, F., Briedis, V., Brightling, C. E., Brozek, J., Bucca, C., Buhl, R., Buonaiuto, R., Panaitescu, C., Burguete Cabañas, M. T., Burte, E., Bush, A., Caballero-Fonseca, F., Caillot, D., Caimmi, D., Calderon, M. A., Camargos, P. A. M., Camuzat, T., Canfora, G., Canonica, G. W., Cardona, V., Carlsen, K. H., Carreiro-Martins, P., Carriazo, A. M., Carr, W., Cartier, C., Casale, T., Castellano, G., Cecchi, L., Cepeda Sarabia, A. M., Chavannes, N. H., Chen, Y., Chiron, R., Chivato, T., Chkhartishvili, E., Chuchalin, A. G., Chung, K. F., Ciaravolo, M. M., Ciceran, A., Cingi, C., Ciprandi, G., Carvalho Coehlo, A. C., Colas, L., Colgan, E., Coll, J., Conforti, D., Correia de Sousa, J., Cortés-Grimaldo, R. M., Corti, F., Costa, E., Costa-Dominguez, M. C., Courbis, A. L., Cox, L., Crescenzo, M., Cruz, A. A., Custovic, A., Czarlewski, W., Dahlen, S. E., Dario, C., da Silva, J., Dauvilliers, Y., Darsow, U., De Blay, F., De Carlo, G., Dedeu, T., de Fátima Emerson, M., De Feo, G., De Vries, G., De Martino, B., de Paula Motta Rubini, N., Deleanu, D., Demoly, P., Denburg, J. A., Devillier, P., Di Capua Ercolano, S., Di Carluccio, N., Didier, A., Dokic, D., Dominguez-Silva, M. G., Douagui, H., Dray, G., Dubakiene, R., Durham, S. R., Du Toit, G., Dykewicz, M. S., El-Gamal, Y., Eklund, P., Eller, E., Emuzyte, R., Farrell, J., Farsi, A., Ferreira de Mello, J., Ferrero, J., Fink-Wagner, A., Fiocchi, A., Fokkens, W. J., Fonseca, J. A., Fontaine, J. F., Forti, S., Fuentes-Perez, J. M., Gálvez-Romero, J. L., Gamkrelidze, A., Garcia-Aymerich, J., García-Cobas, C. Y., Garcia-Cruz, M. H., Gemicioğlu, B., Genova, S., George, C., Gereda, J. E., Gerth van Wijk, R., Gomez, R. M., Gómez-Vera, J., González Diaz, S., Gotua, M., Grisle, I., Guidacci, M., Guldemond, N. A., Gutter, Z., Guzmán, M. A., Haahtela, T., Hajjam, J., Hernández, L., Hourihane, J. O. 'B., Huerta-Villalobos, Y. R., Humbert, M., Iaccarino, G., Illario, M., Ivancevich, J. C., Jares, E. J., Jassem, E., Johnston, S. L., Joos, G., Jung, K. S., Jutel, M., Kaidashev, I., Kalayci, O., Kalyoncu, A. F., Karjalainen, J., Kardas, P., Keil, T., Keith, P. K., Khaitov, M., Khaltaev, N., Kleine-Tebbe, J., Klimek, L., Kowalski, M. L., Kuitunen, M., Kull, I., Kuna, P., Kupczyk, M., Kvedariene, V., Krzych-Fałta, E., Lacwik, P., Larenas-Linnemann, D., Laune, D., Lauri, D., Lavrut, J., Le, L. T. T., Lessa, M., Levato, G., Li, J., Lieberman, P., Lipiec, A., Lipworth, B., Lodrup Carlsen, K. C., Louis, R., Lourenço, O., Luna-Pech, J. A., Maciej, K., Magnan, A., Mahboub, B., Maier, D., Mair, A., Majer, I., Malva, J., Mandajieva, E., Manning, P., De Manuel Keenoy, E., Marshall, G. D., Masjedi, M. R., Maspero, J. F., Mathieu-Dupas, E., Matta Campos, J. J., Matos, A. L., Maurer, M., Mavale-Manuel, S., Mayora, O., Medina-Avalos, M. A., Melén, E., Melo-Gomes, E., Meltzer, E. O., Menditto, E., Mercier, J., Miculinic, N., Mihaltan, F., Milenkovic, B., Moda, G., Mogica-Martinez, M. D., Mohammad, Y., Momas, I., Montefort, S., Monti, R., Mora Bogado, D., Morais-Almeida, M., Morato-Castro, F. F., Mösges, R., Mota-Pinto, A., Moura Santo, P., Mullol, J., Münter, L., Muraro, A., Murray, R., Naclerio, R., Nadif, R., Nalin, M., Napoli, L., Namazova-Baranova, L., Neffen, H., Niedeberger, V., Nekam, K., Neou, A., Nieto, A., Nogueira-Silva, L., Nogues, M., Novellino, E., Nyembue, T. D., O'Hehir, R. E., Odzhakova, C., Ohta, K., Okamoto, Y., Okubo, K., Onorato, G. L., Ortega Cisneros, M., Ouedraogo, S., Pali-Schöll, I., Palkonen, S., Panzner, P., Papadopoulos, N. G., Park, H. S., Papi, A., Passalacqua, G., Paulino, E., Pawankar, R., Pedersen, S., Pépin, J. L., Pereira, A. M., Persico, M., Pfaar, O., Phillips, J., Picard, R., Pigearias, B., Pin, I., Pitsios, C., Plavec, D., Pohl, W., Popov, T. A., Portejoie, F., Potter, P., Pozzi, A. C., Price, D., Prokopakis, E. P., Puy, R., Pugin, B., Pulido Ross, R. E., Przemecka, M., Rabe, K. F., Raciborski, F., Rajabian-Soderlund, R., Reitsma, S., Ribeirinho, I., Rimmer, J., Rivero-Yeverino, D., Rizzo, J. A., Rizzo, M. C., Robalo-Cordeiro, C., Rodenas, F., Rodo, X., Rodriguez Gonzalez, M., Rodriguez-Mañas, L., Rolland, C., Rodrigues Valle, S., Roman Rodriguez, M., Romano, A., Rodriguez-Zagal, E., Rolla, G., Roller-Wirnsberger, R. E., Romano, M., Rosado-Pinto, J., Rosario, N., Rottem, M., Ryan, D., Sagara, H., Salimäki, J., Samolinski, B., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G. K., Schunemann, H. J., Scichilone, N., Schmid-Grendelmeier, P., Serpa, F. S., Shamai, S., Sheikh, A., Sierra, M., Simons, F. E. R., Siroux, V., Sisul, J. C., Skrindo, I., Solé, D., Somekh, D., Sondermann, M., Sooronbaev, T., Sova, M., Sorensen, M., Sorlini, M., Spranger, O., Stellato, C., Stelmach, R., Stukas, R., Sunyer, J., Strozek, J., Szylling, A., Tebyriçá, J. N., Thibaudon, M., To, T., Todo-Bom, A., Tomazic, P. V., Toppila-Salmi, S., Trama, U., Triggiani, M., Suppli Ulrik, C., Urrutia-Pereira, M., Valenta, R., Valero, A., Valiulis, A., Valovirta, E., van Eerd, M., van Ganse, E., van Hague, M., Vandenplas, O., Ventura, M. T., Vezzani, G., Vasankari, T., Vatrella, A., Verissimo, M. T., Viart, F., Viegi, M., Vicheva, D., Vontetsianos, T., Wagenmann, M., Walker, S., Wallace, D., Wang, D. Y., Waserman, S., Werfel, T., Westman, M., Wickman, M., Williams, D. M., Williams, S., Wilson, N., Wright, J., Wroczynski, P., Yakovliev, P., Yawn, B. P., Yiallouros, P. K., Yorgancioglu, A., Yusuf, O. M., Zar, H. J., Zhang, L., Zhong, N., Zernotti, M. E., Zidarn, M., Zuberbier, T., Zubrinich, C., Zurkuhlen, A., CHU Montpellier, 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), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratory of clinical immunology, Department of Allergy and Clinical Immunology, Transylvania University of Brasov, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Department of Allergy and Immunology, Hospital Quirónsalud Bizkaia [Bilbao], Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hacettepe University = Hacettepe Üniversitesi, Mechanobiology Institute [Singapore] (MBI), National University of Singapore (NUS), Department of Clinical Epidemiology and Biostatistics and Medicine, McMaster University [Hamilton, Ontario], Department of Dermatology [Graz, Austria], Medical University Graz, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Department Engineering Quimica (ICEMS), Ghent University Hospital, Istituto Nazionale di Fisica Nucleare, sezione di Bari (INFN, sezione di Bari), Istituto Nazionale di Fisica Nucleare (INFN), IMIM-Hospital del Mar, Generalitat de Catalunya, University of Cape Town, Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton-School of Medicine, Centre de gérontologie, Department of Pathophysiology and Transplantation, Università degli Studi di Milano = University of Milan (UNIMI), Istituto di Geoscienze e Georisorse, Pavia, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II = Università degli studi di Napoli Federico II, Woolcock Institute of Medical Research [Sydney], The University of Sydney, Université Laval [Québec] (ULaval), Departments of Clinical Epidemiology and Biostatistics and Medicine [Ontario], Service greffe de moelle osseuse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Royal Brompton Hospital, Région Languedoc-Roussillon-Midi-Pyrénées, Vall d'Hebron University Hospital [Barcelona], University of South Florida [Tampa] (USF), Università degli Studi di Firenze = University of Florence (UniFI), University of Michigan, Department of Atmospheric, Centres de Ressources et de Compétences de la Mucoviscidose [Montpellier] (CRCM [Montpellier]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Service des Maladies Respiratoires, Russian State Medical University, Universidade do Porto, Instituto de Biologia Molecular e Celular (IBMC), UCB Pharma, Colombes, Hôpital Gui de Chauliac [CHU Montpellier], CHU Strasbourg, European Federation of Allergy (EFA), Airways Diseases Patients' Associations, Università degli Studi di Salerno = University of Salerno (UNISA), Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique (LOBIP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Linköping University (LIU), Department of Dermatology and Allergy Centre, Odense University Hospital, Vilnius University [Vilnius], Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto = University of Porto, Institut d'Electronique du Solide et des Systèmes (InESS), Centre National de la Recherche Scientifique (CNRS), Son Pisa Primary Care Centre, IB-Salut Balearic Health Service, Center for Allergy and Immunology Research [Tbilisi], Department of Dermatology, Helsinki University Hospital-Skin and Allergy Hospital, Swedish Meteorological and Hydrological Institute (SMHI), CORYSS-TESS, Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Institute of Social Medicine, Epidemiology and Health Economics-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Biologie des organismes marins et écosystèmes (BOME), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), NRC Institute of immunology FMBA, Moscow Russian federation, Allergy and Asthma Center Westend, German Society for Otorhinolaryngology HNS, Rheinische Friedrich-Wilhelms-Universität Bonn, The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Medical University of Łódź (MUL), Hospital Medica Sur, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Applied Physical Chemistry Laboratory (APCLab), Institute of Geophysics and Planetary Physics [Los Angeles] (IGPP), University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Équipe de Recherche en Textes, Informatique, Multilinguisme (ERTIM), Institut National des Langues et Civilisations Orientales (Inalco), Institute of Oceanology [China], University of Beira Interior [Portugal] (UBI), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Pulmonary and allergy unit, American University of Sharjah-Rashid Hospital-Dubai Health Authority (DHA), Astrophysique Interprétation Modélisation (AIM (UMR7158 / UMR_E_9005 / UM_112)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Sysdiag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (SysDiag ), BIO-RAD-Centre National de la Recherche Scientifique (CNRS), 'Federico II' University of Naples Medical School, 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), Pneumology Department, Marius Nasta Institute of Pneumology, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw - Poland-Faculté de Pharmacie de Paris, Allergy and Clinical Immunology Department, Hospital CUF Descobertas, Universität zu Köln = University of Cologne, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Section of Otolaryngology-Head & Neck Surgery (OHNS), University of Chicago, Department of Pharmacy Naples, Université de Naples, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital-Monash University Building, AMREP, Dept. of Electronic Engineering, Chubu University, Department of Otorhinolaryngology, Chiba University Hospital, Department of Allergology and Clinical Immunology, Charles University [Prague] (CU)-Medical Faculty in Pilsen, Department of Earth and Planetary Sciences [Cambridge, USA] (EPS), Harvard University, Allergy and Respiratory Diseases, Università degli studi di Genova = University of Genoa (UniGe), Department of Pediatrics, Nippon Medical School, Centre Hospitalier Universitaire [Grenoble] (CHU), Department of Otorhinolaryngology, Head and Neck Surgery [Mannheim, Germany], University Hospital Mannheim, Laboratoire de physique et chimie des nano-objets (LPCNO), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, Children’s Hospital Srebrnjak [Zagreb, Croatia], Department of Physics [UMIST Manchester], University of Manchester Institute of Science and Technology (UMIST), Laboratori Nazionali del Sud (LNS), Getafe University Hospital, Madrid, Karl-Franzens-Universität Graz, Ecologie comportementale (EC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Rennes (UR)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Allergy Asthma and Immunology [Haifa, Israel], Ha'Emek Medical Center, Afula-Rappaport Faculty of Medicine, University of Edinburgh, Medical University of Warsaw - Poland, Department of Allergy and Clinical Immunology [Caracas, Venezuela], Centro Médico Docente La Trinidad, Department of Computer Science [Haifa], University of Haifa [Haifa], Allergy and Respiratory Research Group, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), National Centre of Cardiology and Internal Medicine, Ministry of Health Kyrgyz Republic, Réseau National de Surveillance Aérobiologique (RNSA), Berkeley Seismological Laboratory, Division of Clinical Immunology and Allergy, University of Naples Federico II = Università degli studi di Napoli Federico II, CIRCE, Ctr Res Energy Resources & Consumpt, Zaragoza 50018, Spain, Vilnius University Clinic of Children's Diseases, Suomen Terveystalo Allergy Clinic, Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre d'EPistémologie et d'ERgologie Comparatives (CEPERC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institute for Climate and Atmospheric Science [Leeds] (ICAS), School of Earth and Environment [Leeds] (SEE), University of Leeds-University of Leeds, Nova Southeastern University (NSU), Department of Otolaryngology, National University of Singapore (NUS)-Yong Loo Lin School of Medicine, Sachs' Children's Hospital, IAES, Department of Pulmonology, Manisa Celal Bayar University, Center for Evolutionary and Theoretical Immunology [Albuquerque, New Mexico] (CETI), The University of New Mexico [Albuquerque], National Key State Laboratory for ThermoStructural Composites (TSCM), Northwestern Polytechnical University [Xi'an] (NPU), Respiratory and Allergic Diseases, University Clinic of Respiratory and Allergic Diseases Golnik, University Hospital of Cologne [Cologne], Supported by the European Innovation Partnership on Active and Healthy Ageing and POLLAR (EIT Health, European Union)., European Project: 643803,H2020,H2020-HCO-2014,PROEIPAHA(2015), UCL - (MGD) Service de pneumologie, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, 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), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidemiology of Allergic and Respiratory Diseases Department [Paris] (EPAR), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital Quiròn Bizkaia Erandio, Université Pierre et Marie Curie - Paris 6 (UPMC), University of Milan, University of Naples Federico II-CNR, Rome, Italy and Department of Medicine, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Università degli Studi di Salerno (UNISA), Institut de Physique du Globe de Paris (IPGP), Centre National de la Recherche Scientifique (CNRS)-Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Institut national des sciences de l'Univers (INSU - CNRS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]-Epidemiology and Health Economics, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Muséum national d'Histoire naturelle (MNHN), University of California-University of California, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospital CUF-Descobertas, Universität zu Köln, Medical Faculty in Pilsen-Charles University in Prague - the First Faculty of Medicine, Harvard University [Cambridge], University of Genoa (UNIGE), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Graz, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université Claude Bernard Lyon 1 (UCBL), Centro Medico-Docente La Trinidad, Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Università degli studi di Napoli Federico II, Center for Evolutionary and theoretical Immunology, Biology, National Institute for Health Research, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II, Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Karl-Franzens-Universität [Graz, Autriche], Department of Dermatology, Allergology and Venereology, Clinicum, University of Helsinki, Children's Hospital, Faculty of Law, HUS Children and Adolescents, HUS Inflammation Center, University Hospitals Leuven [Leuven], Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, University of Zürich [Zürich] (UZH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of South Florida (USF), Università degli Studi di Firenze = University of Florence [Firenze], Laboratoire Magmas et Volcans (LMV), Observatoire de Physique du Globe de Clermont-Ferrand (OPGC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Universidade do Porto [Porto], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin -Epidemiology and Health Economics, Université Pierre et Marie Curie - Paris 6 (UPMC)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Sondra, CentraleSupélec, Université Paris-Saclay (COmUE) (SONDRA), ONERA-CentraleSupélec-Université Paris Saclay (COmUE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), RNSA, Centre d'EPistémologie et d'ERgologie Comparatives - UMR 7304 (CEPERC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Ear, Nose and Throat, AII - Inflammatory diseases, Pulmonology, Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nîmes (CHRU 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), National Institute for Nuclear Physics (INFN), Université Laval, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Università degli Studi di Firenze [Firenze], University of Salerno (UNISA), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Observatoire de Physique du Globe de Clermont-Ferrand (OPGC), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Sondra, CentraleSupélec, Université Paris-Saclay (SONDRA), ONERA-CentraleSupélec-Université Paris-Saclay, Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), École normale supérieure - Paris (ENS Paris)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Rennes 1 (UR1), Universidade do Minho, İÜC, Cerrahpaşa Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, uBibliorum, and Internal Medicine
Subjects: Allergy, Medicina Básica [Ciências Médicas], asthma -- guideline, Allergic asthma, DECISION-MAKING, Allergic Rhinitis and Its Impact on Asthma, GUIDELINES, Medical and Health Sciences, Medical Records, 0302 clinical medicine, Health care, Immunology and Allergy, 030212 general & internal medicine, asthma, Change management, rhinitis, Immunology, MASK-RHINITIS, ComputingMilieux_MISCELLANEOUS, Rinitis, mobilne aplikacije, upravljanje sprememb, Medical record, GLOBAL STRATEGY, WORK PRODUCTIVITY, Telemedicine, mobile applications, 3. Good health, Asma alérgica, rhiniti, 1107 Immunology, Ciências Médicas::Medicina Básica, klinične poti, allergic -- guideline, Life Sciences & Biomedicine, Human, PATIENT PARTICIPATION, Allergic Rhinitis, medicine.medical_specialty, animal structures, multimorbidity, EUROPEAN INNOVATION PARTNERSHIP, Change Management, [object Object], Settore MED/10 - Malattie Dell'Apparato Respiratorio, Asthma/diagnosis, CHRONIC DISEASES, MACVIA-ARIA, 03 medical and health sciences, medicine, multimorbidnost, QUALITY, Humans, critical pathways, astma -- smernica, Patient participation, Asma, udc:616.2, Asthma, Science & Technology, ARIA, business.industry, Multimorbidity, Rhinitis, Allergic, Settore MED/09 - MEDICINA INTERNA, change management, Mobile Airways Sentinel Network (MASK) Study Group, Guideline, ta3121, medicine.disease, Rinite alérgica, Rhinitis, Allergic/diagnosis, Integrated care, alergijski rinitis -- smernica, Allergic Rhinitis and Its Impact on Asthma, asthma, Change management, rhinitis, Immunology and Allergy, Immunology, 030228 respiratory system, Family medicine, 3121 General medicine, internal medicine and other clinical medicine, Medical Record, Clinical Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Impact on Asthma
Abstract: Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional., EAACI -European Academy of Allergy and Clinical Immunology(undefined), info:eu-repo/semantics/acceptedVersion
Published: 2018

12. WITHDRAWN: Scaling up strategies of the Chronic Respiratory Disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3 – Area 5)

Author: M. Nogues, David Price, Tari Haahtela, Bianca Beghe, John Wright, Josep M. Antó, J. O'b. Hourihane, K. C. Lødrup Carlsen, Justin Michel, June Roberts, Robert M. Naclerio, M. Roman Rodriguez, Amiran Gamkrelidze, P. Manning, Panayiotis K. Yiallouros, John Farrell, Gérard Dray, A. Ben Kheder, Branislava Milenkovic, W. J. Fokkens, Susanne Lau, Ronald Dahl, J. E. Gereda, Pma Calverley, O. Jonquet, D. Poethig, Erkka Valovirta, Z. Gutter, Grégory Ninot, Yehia El-Gamal, M. van Hage, Claus Vogelmeier, S. Mara, P. Matignon, Talant Sooronbaev, Ratko Djukanovic, Carel Thijs, Davide Caimmi, Ralph Mösges, G. Moda Y. Mohammad, Friedrich Horak, Joachim Heinrich, Y. Z. Chen, Leonardo M. Fabbri, Y. Magard, B. Pigearias, F. Rodenas, A.G. Chuchalin, NM Siafakas, Rodolphe Bourret, A. L. Boner, A. Fink Wagner, T. Similowski, Diana Deleanu, I. Skrindo, Ulf Darsow, Bilun Gemicioglu, Stephen R. Durham, S.I. Rennard, Mohammad Reza Masjedi, Arunas Valiulis, S. Gonzalez Diaz, Brian J. Lipworth, Philip Lieberman, Christine Rolland, H. Neffen, Pierluigi Paggiaro, Henriette A. Smit, Bart N. Lambrecht, P. Devillier, Bodo Niggemann, D. Dokic, Dennis M. Williams, M. Akdis, R. Pengelly, Bassam Mahboub, Oliver Pfaar, Cezmi A. Akdis, L. Namazova-Baranova, Lanny J. Rosenwasser, Hans F. Merk, B. P. Yawn, Alpana Mair, Thomas B. Casale, Claus Bachert, Cristina Bárbara, Martin Wagenmann, Francesco Forastiere, T. Dedeu, Shona Pedersen, Giorgio Walter Canonica, Antonio Valero, Werner Aberer, Andrew Briggs, Alberto Papi, Peter Burney, Paulo Augusto Moreira Camargos, D. J. Costa, Magnus Wickman, Hans-Ulrich Schulz, T. Strandberg, T. Camuzat, Michael E. Hyland, Mario Sánchez-Borges, L. T. T. Le, N. Khaltaev, Lawrence Grouse, O. Spranger, F. de Blay, H. Douagui, Ki-Suck Jung, R. Picard, S. Repka-Ramirez, Philippe-Jean Bousquet, A. Yorgancioglu, U. Wahn, J. Garcia-Aymerich, Kaja Julge, D. Plavec, A. Bedbrook, Torsten Zuberbier, A. Romano, Sîan A Williams, Monica Fletcher, Mark S. Dykewicz, A. Montilla-Santana, B. Samolinski, Joël Ankri, Albert Alonso, Filip Raciborski, Antonella Muraro, Kian Fan Chung, L. Rodriguez Manas, Rafael Stelmach, G. Passalacqua, José Roberto Jardim, K. Ohta, Renaud Louis, Rudolph Valenta, M. Gotua, Massimo Triggiani, E. Melo-Gomes, Y. Okamoto, William MacNee, Ludger Klimek, Holger J. Schünemann, Dirkje S. Postma, Hasan Arshad, Gailen D. Marshall, M. Adachi, Nikolaos G. Papadopoulos, Mikael Benson, Kai-Håkon Carlsen, E. Chkhartishvili, Gerard H. Koppelman, R. Emuzyte, Chunxue Bai, Ruby Pawankar, Ana Todo-Bom, Claude Jeandel, Ilaria Baiardini, Osman M. Yusuf, Josep Roca, Giovanni Viegi, Pascal Demoly, Daniel Laune, S. E. Dahlen, Giorgio Ciprandi, M. Rottem, E. O. Meltzer, Sebastian L. Johnston, Mika J. Mäkelä, Edgardo Jares, Kimi Okubo, Paul K. Keith, Fulvio Braido, M. R. Kaitov, Alessandro Fiocchi, F. Caballero-Fonseca, Jørgen Vestbo, Carsten Bindslev-Jensen, Jing Li, Guy Joos, M. A. Guzman, S. Palkonen, K. Nekam, G. Vezzani, A. M. Cepeda Sarabia, Anh Tuan Dinh-Xuan, Adnan Custovic, C. Robalo-Cordeiro, Christine Jenkins, Niels H. Chavannes, E.H.D. Bel, A. Hendry, Neven Miculinic, T. Bieber, João O. Malva, Thomas Keil, Matteo Bonini, Klaus F. Rabe, F. Radier Pontal, F. Mihaltan, D. Y. Wang, J. C. Sisul, Benoit Wallaert, Teresa To, Robyn E O'Hehir, Jan Brozek, Ian D. Pavord, Luo Zhang, Nelson Rosario, Simon Walker, P H Howarth, J. Correia de Sousa, I. Majer, L.-P. Boulet, Marcus Maurer, J Mullol, S. Ouedraogo, Andrew Menzies-Gow, T. Vontetsianos, Mario E. Zernotti, Paul Potter, Mathieu Molimard, M. Morgan, Aziz Sheikh, Pakit Vichyanond, Isabella Pali-Schöll, Leif Bjermer, Peter Schmid-Grendelmeier, F. E. R. Simons, Antoine Magnan, T. D. Nyembue, J. Just, W. Carr, Leda Chatzi, I. Pin, E. Melen, Dirceu Solé, J. Garces, I. Grisle, Christopher E. Brightling, Peter Frith, E. Serrano, Inger Kull, F. Portejoie, M. Morais-Almeida, I. J. Ansotegui, G. De Carlo, K. S. Bennoor, S. Nafti, B. Hellquist-Dahl, Ali Fuat Kalyoncu, Dermot Ryan, J. Mercier, Marc Humbert, S. Bosnic-Anticevitch, Abay Baigenzhin, Olivier Vandenplas, Sakari Reitamo, M. Bewick, R. Chiron, Eric D. Bateman, Nanshan Zhong, Jordi Sunyer, Hubert Blain, O. Kalayci, Andrew Bush, D. Henderson, Désirée Larenas-Linnemann, K. C. Bergmann, J. C. Ivancevich, Bruno Vellas, Alvaro A. Cruz, A. Didier, M. Gaga, I. Annesi-Maesano, Maddalena Illario, P. Panzner, G. Crooks, Judah A. Denburg, Moises A. Calderon, Francesco Blasi, W. Pohl, Sergio Bonini, Ruta Dubakiene, Alvar Agusti, Violeta Kvedariene, G. K. Scadding, E. De Manuel Keenoy, E. Valia, S. Mavale-Manuel, Sylvie Arnavielhe, Piotr Kuna, Yves Sibille, Marek L. Kowalski, A. Zaidi, Todor A. Popov, V. Kolek, J Rosado-Pinto, Tommi Vasankari, Liam G Heaney, B. Koffi N'Goran, D. Heve, A. Neou, Isabelle Momas, Jean Bousquet, Igor Kaidashev, Hae-Sim Park, P W Hellings, Michael D. Shields, P. J. Sterk, Ana Maria Carriazo, João Fonseca, E. Van Ganse, Roland Buhl, L. Cox, Mihaela Zidarn, I. Cirule, and H. J. Zar
Subjects: Gerontology, medicine.medical_specialty, business.industry, Respiratory disease, Alternative medicine, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, General partnership, Action plan, medicine, General Earth and Planetary Sciences, 030212 general & internal medicine, Healthy ageing, business, General Environmental Science
Published: 2017

13. Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: An EAACI Position Paper

Author: Adam Chaker, Carsten B. Schmidt-Weber, Jörg Kleine-Tebbe, Moises A. Calderon, Stephen J. Till, Pascal Demoly, M. Akdis, Mohamed H. Shamji, Lars Jacobsen, Oliver Pfaar, Stephen R. Durham, Jasper H. Kappen, Erika Jensen-Jarolim, Rudolf Valenta, Edward F. Knol, Lars K. Poulsen, and Barbara Bohle
Subjects: 0301 basic medicine, Allergen immunotherapy, Allergy, Immunology, Provocation test, Immunoglobulin E, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, Humans, Asthma, Conjunctivitis, Allergic, biology, Allergen Immunotherapy, Basophil Activation, Biomarkers, Ige-fab, Igg4, business.industry, Allergens, medicine.disease, Prognosis, Rhinitis, Allergic, Lymphocyte Subsets, Basophils, Clinical trial, Basophil activation, 030104 developmental biology, Treatment Outcome, 030228 respiratory system, Desensitization, Immunologic, Immunoglobulin G, biology.protein, Biomarker (medicine), Cytokines, business
Abstract: Background Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers. Method The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?). Results All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed. Conclusions It is recommended to explore the use of allergen-specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE-FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed.
Published: 2017

14. MOESM1 of Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)

Author: J. Bousquet, J. Farrell, G. Crooks, P. Hellings, E. Bel, M. Bewick, N. Chavannes, J. Sousa, A. Cruz, T. Haahtela, G. Joos, N. Khaltaev, J. Malva, A. Muraro, M. Nogues, S. Palkonen, S. Pedersen, C. Robalo-Cordeiro, B. Samolinski, T. Strandberg, A. Valiulis, A. Yorgancioglu, T. Zuberbier, A. Bedbrook, W. Aberer, M. Adachi, A. Agusti, C. Akdis, M. Akdis, J. Ankri, A. Alonso, I. Annesi-Maesano, I. Ansotegui, J. Anto, S. Arnavielhe, H. Arshad, C. Bai, I. Baiardini, C. Bachert, A. Baigenzhin, C. Barbara, E. Bateman, B. Beghé, A. Kheder, K. Bennoor, M. Benson, K. Bergmann, T. Bieber, C. Bindslev-Jensen, L. Bjermer, H. Blain, F. Blasi, A. Boner, M. Bonini, S. Bonini, S. Bosnic-Anticevitch, L. Boulet, R. Bourret, P. Bousquet, F. Braido, A. Briggs, C. Brightling, J. Brozek, R. Buhl, P. Burney, A. Bush, F. Caballero-Fonseca, D. Caimmi, M. Calderon, P. Calverley, P. Camargos, G. Canonica, T. Camuzat, K. Carlsen, W. Carr, A. Carriazo, T. Casale, A. Cepeda Sarabia, L. Chatzi, Y. Chen, R. Chiron, E. Chkhartishvili, A. Chuchalin, K. Chung, G. Ciprandi, I. Cirule, L. Cox, D. Costa, A. Custovic, R. Dahl, S. Dahlen, U. Darsow, G. Carlo, F. Blay, T. Dedeu, D. Deleanu, E. Manuel Keenoy, P. Demoly, J. Denburg, P. Devillier, A. Didier, A. Dinh-Xuan, R. Djukanovic, D. Dokic, H. Douagui, G. Dray, R. Dubakiene, S. Durham, M. Dykewicz, Y. El-Gamal, R. Emuzyte, L. Fabbri, M. Fletcher, A. Fiocchi, A. Fink Wagner, J. Fonseca, W. Fokkens, F. Forastiere, P. Frith, M. Gaga, A. Gamkrelidze, J. Garces, J. Garcia-Aymerich, B. Gemicioğlu, J. Gereda, S. González Diaz, M. Gotua, I. Grisle, L. Grouse, Z. Gutter, M. Guzmán, L. Heaney, B. Hellquist-Dahl, D. Henderson, A. Hendry, J. Heinrich, D. Heve, F. Horak, J. Hourihane, P. Howarth, M. Humbert, M. Hyland, M. Illario, J. Ivancevich, J. Jardim, E. Jares, C. Jeandel, C. Jenkins, S. Johnston, O. Jonquet, K. Julge, K. Jung, J. Just, I. Kaidashev, M. Kaitov, O. Kalayci, A. Kalyoncu, T. Keil, P. Keith, L. Klimek, B. Koffi N’Goran, V. Kolek, G. Koppelman, M. Kowalski, I. Kull, P. Kuna, V. Kvedariene, B. Lambrecht, S. Lau, D. Larenas-Linnemann, D. Laune, L. Le, P. Lieberman, B. Lipworth, J. Li, K. Lodrup Carlsen, R. Louis, W. MacNee, Y. Magard, A. Magnan, B. Mahboub, A. Mair, I. Majer, M. Makela, P. Manning, S. Mara, G. Marshall, M. Masjedi, P. Matignon, M. Maurer, S. Mavale-Manuel, E. Melén, E. Melo-Gomes, E. Meltzer, A. Menzies-Gow, H. Merk, J. Michel, N. Miculinic, F. Mihaltan, B. Milenkovic, G. Mohammad, M. Molimard, I. Momas, A. Montilla-Santana, M. Morais-Almeida, M. Morgan, R. Mösges, J. Mullol, S. Nafti, L. Namazova-Baranova, R. Naclerio, A. Neou, H. Neffen, K. Nekam, B. Niggemann, G. Ninot, T. Nyembue, R. O’Hehir, K. Ohta, Y. Okamoto, K. Okubo, S. Ouedraogo, P. Paggiaro, I. Pali-Schöll, P. Panzner, N. Papadopoulos, A. Papi, H. Park, G. Passalacqua, I. Pavord, R. Pawankar, R. Pengelly, O. Pfaar, R. Picard, B. Pigearias, I. Pin, D. Plavec, D. Poethig, W. Pohl, T. Popov, F. Portejoie, P. Potter, D. Postma, D. Price, K. Rabe, F. Raciborski, F. Radier Pontal, S. Repka-Ramirez, S. Reitamo, S. Rennard, F. Rodenas, J. Roberts, J. Roca, L. Rodriguez Mañas, C. Rolland, M. Roman Rodriguez, A. Romano, J. Rosado-Pinto, N. Rosario, L. Rosenwasser, M. Rottem, D. Ryan, M. Sanchez-Borges, G. Scadding, H. Schunemann, E. Serrano, P. Schmid-Grendelmeier, H. Schulz, A. Sheikh, M. Shields, N. Siafakas, Y. Sibille, T. Similowski, F. Simons, J. Sisul, I. Skrindo, H. Smit, D. Solé, T. Sooronbaev, O. Spranger, R. Stelmach, P. Sterk, J. Sunyer, C. Thijs, T. To, A. Todo-Bom, M. Triggiani, R. Valenta, A. Valero, E. Valia, E. Valovirta, E. Ganse, M. Hage, O. Vandenplas, T. Vasankari, B. Vellas, J. Vestbo, G. Vezzani, P. Vichyanond, G. Viegi, C. Vogelmeier, T. Vontetsianos, M. Wagenmann, B. Wallaert, S. Walker, D. Wang, U. Wahn, M. Wickman, D. Williams, S. Williams, J. Wright, B. Yawn, P. Yiallouros, O. Yusuf, A. Zaidi, H. Zar, M. Zernotti, L. Zhang, N. Zhong, M. Zidarn, and J. Mercier
Abstract: Additional file 1. IPCRG scaling up activities.
Published: 2016
Full Text: View/download PDF

15. The effect of CD14 C159T polymorphism on in vitro IgE synthesis and cytokine production by PBMC from children with asthma

Author: C, Sackesen, E, Birben, O U, Soyer, U M, Sahiner, T S, Yavuz, E, Civelek, E, Karabulut, M, Akdis, C A, Akdis, O, Kalayci, University of Zurich, and Sackesen, C
Subjects: Lipopolysaccharides, Male, 2403 Immunology, Polymorphism, Genetic, Adolescent, Genotype, Lipopolysaccharide Receptors, 610 Medicine & health, Immunoglobulin E, Asthma, Th2 Cells, 10183 Swiss Institute of Allergy and Asthma Research, Leukocytes, Mononuclear, 2723 Immunology and Allergy, Cytokines, Humans, Female, Genetic Predisposition to Disease, Child
Abstract: BACKGROUND Even though the genotype at the promoter region of the CD14 molecule is known to affect the atopic phenotypes the cellular and molecular basis of this association is largely unknown. OBJECTIVE To investigate the effect of lipopolysaccharide (LPS) on IgE production and cytokine profile by peripheral blood mononuclear cells (PBMC) obtained from asthmatic children with the TT and the CC genotypes at position 159 of the CD14 gene. METHODS Peripheral blood mononuclear cells from asthmatic children with alternative genotypes at CD14 C159T locus were stimulated with 2 and 200 ng/ml LPS in vitro. The IgE IgG and IgM response was determined by ELISA and Ig ? germline IgG and IgM transcription by real time PCR. A cluster of cytokines was measured by cytometric bead array. RESULTS Asthmatic children with the TT genotype but not those with the CC genotype responded with increased IgE synthesis and germline transcription to LPS stimulation. There were no genotype related differences in IgG and IgM. TT but not the CC genotype was associated with significantly increased interleukin (IL) 4/IL 12 and IL 4/interferon gamma (IFN ?) ratios in the culture supernatant. There were no genotype related differences in IL 1ß IL 7 IL 10 IL 13 IL 17A granulocyte colony stimulating factor granulocyte macrophage colony stimulating factor monocyte chemotactic protein and tumor necrosis factor alpha. CONCLUSION Peripheral blood mononuclear cells from asthmatic children with the TT genotype at position 159 of the CD14 gene make more IgE than those with the CC genotype following LPS stimulation because of increased germline transcription and have an augmented Th2 cytokine profile.
Published: 2011

16. Immune regulation by CD4+CD25+T cells and interleukin-10 in birch pollen-allergic patients and non-allergic controls

Author: C. Trollmo, M. Akdis, Cezmi A. Akdis, R. Grönneberg, Guro Gafvelin, Sarah Thunberg, M. van Hage, and V. Malmstrom
Subjects: Adult, Male, Allergy, medicine.medical_treatment, Immunology, Biology, T-Lymphocytes, Regulatory, Th2 Cells, Immune system, Antigen, Hypersensitivity, Immune Tolerance, medicine, Homeostasis, Humans, Immunology and Allergy, IL-2 receptor, Betula, Cells, Cultured, T lymphocyte, Allergens, Middle Aged, Th1 Cells, medicine.disease, Coculture Techniques, Interleukin-10, Interleukin 10, Cytokine, Cell culture, Cytokines, Pollen, Female
Abstract: Background CD4 + CD25 + regulatory T (Treg) cells and the cytokines IL-10 or TGF-β play key roles in the maintenance ofT cell homeostasis and tolerance to infectious and non-infectious antigens such as allergens. Objective To investigate the regulation of immune responses to birch pollen allergen compared with influenza antigen by Treg cells obtained from birch pollen-allergic patients and non-allergic controls. Methods Peripheral blood was collected from 10 birch pollen-allergic patients and 10 non-allergic healthy controls. CD4 + CD25 + and CD4 + CD25 - cells isolated by magnetic-activated cell sorting were co-cultured and stimulated with birch pollen extract or influenza vaccine in the absence or presence of anti-IL-10 or soluble TGF-βRII. Results CD4 + CD25 + cells from non-allergic controls were able to suppress influenza antigen and birch pollen stimulated effector cell proliferation, whereas CD4 + CD25 + cells from allergic patients suppressed influenza antigen-, but not birch pollen-stimulated proliferation. The production of Th1 cytokines, but not Th2 cytokines, was suppressed by CD4 + CD25 + cells from both allergic patients and controls, upon stimulation with birch pollen extract. Neutralization of IL-10 led to significantly increased production of IFN-γ in cultures with CD4 + CD25 - T effector cells. In addition, six-fold higher concentrations of TNF-α were detected after neutralization of IL-10 in both CD4 + CD25 - and CD4 + CD25 + cell cultures from allergic patients and controls. Conclusion We demonstrate that the allergen-specific suppressive function of CD4 + CD25 + cells from allergic patients is impaired compared with non-allergic controls. Moreover, neutralization of IL- 10 enhances the production of TNF-α, suggesting counter-acting properties of IL- 10 and TNF-α, where IL-10 promotes tolerance and suppression by Treg cells and TNF-α promotes inflammatory responses.
Published: 2007

17. Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling?: The MeDALL hypothesis

Author: Cezmi A. Akdis, Monique Mommers, Claus Bachert, Emilie Burte, Hamida Hammad, Marta Benet, Moises A. Calderon, Erik Melén, A. Bedbrook, Torsten Zuberbier, Leda Chatzi, U. Gehrig, Rachel Nadif, Johann Pellet, Dieter Maier, J. Just, Mariona Pinart, Jean Bousquet, Niklas Andersson, Stephane Ballereau, C. Tischer, L. von Hertzen, Angela Neubauer, M. Akdis, Esben Eller, Valérie Siroux, Judith Garcia-Aymerich, Kai-Håkon Carlsen, Anna Bergström, Sam Oddie, Carsten Bindslev-Jensen, Joachim Heinrich, Christian Lupinek, Anna Asarnoj, Natalia Ballardini, Thomas Keil, Jordi Sunyer, Stefano Guerra, Nathanaël Lemonnier, Charles Auffray, Henriette A. Smit, Manolis Kogevinas, C. Hohman, M. van Hage, John Wright, Josep M. Antó, Magnus Wickman, K. C. Lødrup Carlsen, Tari Haahtela, Daniela Porta, Anne Cambon-Thomsen, M P Fantini, Marjan Kerkhof, Isabelle Momas, Susanne Lau, Pascal Demoly, S. Palkonen, I. Skrindo, Syed Hasan Arshad, Y. Saes, I. Annesi-Maesano, M. Torrent, Francesco Forastiere, Rudolf Valenta, Martijn C. Nawijn, G. De Carlo, Gerard H. Koppelman, Carel Thijs, Bart N. Lambrecht, Bert Brunekreef, Inger Kull, Dirkje S. Postma, Marek L. Kowalski, Isabelle Pin, 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), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Helsinki, Ghent University Hospital, European Institute for Systems Biology and Medicine (EISBM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Crete [Heraklion] (UOC), IMIM-Hospital del Mar, Generalitat de Catalunya, Karolinska Institutet [Stockholm], Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, European Synchrotron Radiation Facility (ESRF), University Hospital of Cologne [Cologne], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service d'Allergologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The Institute of Environmental Medicine [Stockholm] (IMM), CHU Grenoble, Epidemiologie, RS: CAPHRI School for Public Health and Primary Care, RS: CAPHRI - R5 - Optimising Patient Care, LS IRAS EEPI ME (Milieu epidemiologie), Dep IRAS, Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA2, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), J Bousquet, JM Anto, M Wickman, T Keil, R Valenta, T Haahtela, K Lodrup Carlsen, M van Hage, C Akdi, C Bachert, M Akdi, C Auffray, I Annesi-Maesano, C Bindslev-Jensen, A Cambon-Thomsen, KH Carlsen, L Chatzi, F Forastiere, J Garcia-Aymerich, U Gehrig, S Guerra, J Heinrich, GH Koppelman, ML Kowalski, B Lambrecht, C Lupinek, D Maier, E Melén, I Moma, S Palkonen, M Pinart, D Postma, V Siroux, HA Smit, J Sunyer, J Wright, T Zuberbier, SH Arshad, R Nadif, C Thij, N Anderson, A Arsanoj, N Balardini, S Ballereau, A Bedbrook, M Benet, A Bergstrom, B Brunekreef, E Burte, M Calderon, G De Carlo, P Demoly, E Eller, MP Fantini, H Hammad, C Hohman, J Just, M Kerkhof, M Kogevina, I Kull, S Lau, N Lemonnier, M Mommer, M Nawijn, A Neubauer, S Oddie, J Pellet, I Pin, D Porta, Y Sae, I Skrindo, CG Tischer, M Torrent, L von Hertzen, and Groningen Research Institute for Asthma and COPD (GRIAC)
Subjects: Allergy, Ige, Asthma, Atopic Dermatitis, Polysensitization, Rhinitis, [SDV]Life Sciences [q-bio], Genome-wide association study, Review, Comorbidity, Immunoglobulin E, 0302 clinical medicine, Antibody Specificity, Pregnancy, Hypersensitivity/epidemiology, Immunology and Allergy, HEALTH-SURVEY-I, Family history, GENERAL-POPULATION SAMPLE, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, biology, atopic dermatitis, ACTIVE EOSINOPHILIC ESOPHAGITIS, Atopic dermatitis, EPITHELIAL BARRIER FUNCTION, 3. Good health, ALLERGY, Phenotype, Prenatal Exposure Delayed Effects, Antibody Specificity/immunology, Immunoglobulin E/immunology, Female, IgE, Signal Transduction, Immunology, SOYBEAN EPIDEMIC ASTHMA, Allergens/immunology, 03 medical and health sciences, rhinitis, Journal Article, Hypersensitivity, medicine, Humans, Multimorbidity, Genetic Predisposition to Disease, Epigenetics, GENOME-WIDE ASSOCIATION, SERUM IMMUNOGLOBULIN-E, 030304 developmental biology, SKIN PRICK TEST, business.industry, Allergens, asthma, medicine.disease, ORAL FOOD CHALLENGES, 030228 respiratory system, polysensitization, biology.protein, Immunization, business, SEVERE ATOPIC-DERMATITIS
Abstract: Allergic diseases (asthma, rhinitis and atopic dermatitis) are complex. They are associated with allergen-specific IgE and non-allergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono or polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal Type 2 signalling. Asthma, rhinitis and atopic dermatitis are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This paper proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes in order to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis, and (iii) propose novel strategies of treatment and prevention.
Published: 2015

18. MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): The new generation guideline implementation

Author: Bousquet, J. Schunemann, H.J. Fonseca, J. Samolinski, B. Bachert, C. Canonica, G.W. Casale, T. Cruz, A.A. Demoly, P. Hellings, P. Valiulis, A. Wickman, M. Zuberbier, T. Bosnic-Anticevitch, S. Bedbrook, A. Bergmann, K.C. Caimmi, D. Dahl, R. Fokkens, W.J. Grisle, I. Lodrup Carlsen, K. Mullol, J. Muraro, A. Palkonen, S. Papadopoulos, N. Passalacqua, G. Ryan, D. Valovirta, E. Yorgancioglu, A. Aberer, W. Agache, I. Adachi, M. Akdis, C.A. Akdis, M. Annesi-Maesano, I. Ansotegui, I.J. Anto, J.M. Arnavielhe, S. Arshad, H. Baiardini, I. Baigenzhin, A.K. Barbara, C. Bateman, E.D. Beghé, B. Bel, E.H. Ben Kheder, A. Bennoor, K.S. Benson, M. Bewick, M. Bieber, T. Bindslev-Jensen, C. Bjermer, L. Blain, H. Boner, A.L. Boulet, L.P. Bonini, M. Bonini, S. Bosse, I. Bourret, R. Bousquet, P.J. Braido, F. Briggs, A.H. Brightling, C.E. Brozek, J. Buhl, R. Burney, P.G. Bush, A. Caballero-Fonseca, F. Calderon, M.A. Camargos, P.A.M. Camuzat, T. Carlsen, K.H. Carr, W. Cepeda Sarabia, A.M. Chavannes, N.H. Chatzi, L. Chen, Y.Z. Chiron, R. Chkhartishvili, E. Chuchalin, A.G. Ciprandi, G. Cirule, I. Correia De Sousa, J. Cox, L. Crooks, G. Costa, D.J. Custovic, A. Dahlen, S.E. Darsow, U. De Carlo, G. De Blay, F. Dedeu, T. Deleanu, D. Denburg, J.A. Devillier, P. Didier, A. Dinh-Xuan, A.T. Dokic, D. Douagui, H. Dray, G. Dubakiene, R. Durham, S.R. Dykewicz, M.S. El-Gamal, Y. Emuzyte, R. Fink Wagner, A. Fletcher, M. Fiocchi, A. Forastiere, F. Gamkrelidze, A. Gemicioʇlu, B. Gereda, J.E. González Diaz, S. Gotua, M. Grouse, L. Guzmán, M.A. Haahtela, T. Hellquist-Dahl, B. Heinrich, J. Horak, F. Hourihane, J.O.B. Howarth, P. Humbert, M. Hyland, M.E. Ivancevich, J.C. Jares, E.J. Johnston, S.L. Joos, G. Jonquet, O. Jung, K.S. Just, J. Kaidashev, I.P. Kalayci, O. Kalyoncu, A.F. Keil, T. Keith, P.K. Khaltaev, N. Klimek, L. Koffi N'Goran, B. Kolek, V. Koppelman, G.H. Kowalski, M.L. Kull, I. Kuna, P. Kvedariene, V. Lambrecht, B. Lau, S. Larenas-Linnemann, D. Laune, D. Le, L.T.T. Lieberman, P. Lipworth, B. Li, J. Louis, R. Magard, Y. Magnan, A. Mahboub, B. Majer, I. Makela, M.J. Manning, P. De Manuel Keenoy, E. Marshall, G.D. Masjedi, M.R. Maurer, M. Mavale-Manuel, S. Melén, E. Melo-Gomes, E. Meltzer, E.O. Merk, H. Miculinic, N. Mihaltan, F. Milenkovic, B. Mohammad, Y. Molimard, M. Momas, I. Montilla-Santana, A. Morais-Almeida, M. Mösges, R. Namazova-Baranova, L. Naclerio, R. Neou, A. Neffen, H. Nekam, K. Niggemann, B. Nyembue, T.D. O'Hehir, R.E. Ohta, K. Okamoto, Y. Okubo, K. Ouedraogo, S. Paggiaro, P. Pali-Schöll, I. Palmer, S. Panzner, P. Papi, A. Park, H.S. Pavord, I. Pawankar, R. Pfaar, O. Picard, R. Pigearias, B. Pin, I. Plavec, D. Pohl, W. Popov, T.A. Portejoie, F. Postma, D. Potter, P. Price, D. Rabe, K.F. Raciborski, F. Radier Pontal, F. Repka-Ramirez, S. Robalo-Cordeiro, C. Rolland, C. Rosado-Pinto, J. Reitamo, S. Rodenas, F. Roman Rodriguez, M. Romano, A. Rosario, N. Rosenwasser, L. Rottem, M. Sanchez-Borges, M. Scadding, G.K. Serrano, E. Schmid-Grendelmeier, P. Sheikh, A. Simons, F.E.R. Sisul, J.C. Skrindo, I. Smit, H.A. Solé, D. Sooronbaev, T. Spranger, O. Stelmach, R. Strandberg, T. Sunyer, J. Thijs, C. Todo-Bom, A. Triggiani, M. Valenta, R. Valero, A.L. Van Hage, M. Vandenplas, O. Vezzani, G. Vichyanond, P. Viegi, G. Wagenmann, M. Walker, S. Wang, D.Y. Wahn, U. Williams, D.M. Wright, J. Yawn, B.P. Yiallouros, P.K. Yusuf, O.M. Zar, H.J. Zernotti, M.E. Zhang, L. Zhong, N. Zidarn, M. Mercier, J.
Abstract: Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards. © 2015 John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Published: 2015

19. Immunological mechanisms of sublingual immunotherapy

Author: Isil Barlan, Nerin N. Bahceciler, M. Akdis, and Cezmi A. Akdis
Subjects: Allergy, medicine.medical_treatment, Immunology, Administration, Sublingual, medicine.disease_cause, T-Lymphocytes, Regulatory, Immune tolerance, Immune system, Humans, Immunology and Allergy, Medicine, Immunity, Mucosal, Rhinitis, B-Lymphocytes, biology, business.industry, Dendritic Cells, Immunotherapy, Dendritic cell, Allergens, medicine.disease, Slit, Asthma, Desensitization, Immunologic, Allergic response, biology.protein, Antibody, business
Abstract: Administration of allergen-specific immunotherapy by the oral route, sublingual immunotherapy (SLIT), has been shown to be effective, with an improved safety profile compared with subcutaneous administration. However, the precise mechanisms underlying the induction of immune tolerance by SLIT remain unclear. Contact of the allergen with the antigen-presenting cells in oral mucosa is likely to be critical. Mucosal Langerhans cells can capture the allergen and transport it to local lymph nodes, which may favour the induction of T lymphocytes that suppress the allergic response. In addition, the production of blocking IgG4 antibodies and the involvement of mucosal B cells appear to play a role. There is a growing evidence to support the role of regulatory T cells in controlling the development of asthma and allergic disease. Nevertheless, there remains a lack of firm evidence that SLIT induces regulatory T cells, although preliminary in vitro data suggest that SLIT may increase interleukin-10, which has a clear role in suppressing the allergic immune response. Further studies are required to determine the involvement of regulatory T cells, the role of different dendritic cell subsets, mucosal B cells as well as the potential use of adjuvants during SLIT.
Published: 2006

20. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report

Author: Philippe Eigenmann, Cezmi A. Akdis, Carsten Bindslev-Jensen, Qutayba Hamid, Alexander Kapp, Annika Scheynius, T. Bieber, Thomas Werfel, M. Akdis, Ulrich Wahn, Torsten Zuberbier, Lanny J. Rosenwasser, Thomas A.E. Platts-Mills, Thomas A. Luger, K Turjanmaa, S Weidinger, Jonathan M. Spergel, Antonella Muraro, F. E. R. Simons, Natalija Novak, J Lipozencic, Donald Y.M. Leung, and Mark Boguniewicz
Subjects: Adult, Male, Allergy, Dermatitis, Atopic/diagnosis/etiology/prevention & control/therapy, Clinical immunology, T-Lymphocytes, Immunoglobulin E/blood, Immunology, MEDLINE, Atopic dermatitis, adults, childhood, diagnosis, treatment, consensus, Dermatitis, Atopic, Diagnosis, Differential, Atopy, Cytokines/biosynthesis, Dermatitis, Atopic/diagnosis/immunology/therapy, T-Lymphocytes/physiology, Patient Education as Topic, Risk Factors, Dendritic Cells/physiology, medicine, Skin/metabolism, Humans, Immunology and Allergy, Child, atopic dermatitis, prevention, diagnostic and therapeutic mangement, Societies, Medical, Skin, Asthma, ddc:618, business.industry, Dendritic Cells, Guideline, Immunoglobulin E, medicine.disease, United States, Clinical Practice, Europe, Chemokines/biosynthesis, Child, Preschool, Cytokines, Female, Chemokines, business
Abstract: There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.
Published: 2006

21. Mechanisms of allergen specific immunotherapy - T-cell tolerance and more

Author: Cezmi A. Akdis, Kurt Blaser, Marek Jutel, and M. Akdis
Subjects: T cell, medicine.medical_treatment, Immunology, Administration, Sublingual, Immunoglobulins, T-Lymphocytes, Regulatory, Immune tolerance, Interleukin 21, Immune system, T-Lymphocyte Subsets, Hypersensitivity, Immune Tolerance, medicine, Humans, Immunology and Allergy, Cytotoxic T cell, Receptors, Histamine H2, IL-2 receptor, Inflammation, business.industry, Peripheral tolerance, Immunotherapy, Allergens, medicine.anatomical_structure, Desensitization, Immunologic, business
Abstract: Specific immune suppression and induction of tolerance are essential processes in the regulation and circumvention of immune defence. The balance between allergen-specific T-regulatory (Treg) cells and T helper 2 cells appears to be decisive in the development of allergic and healthy immune response against allergens. Treg cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals. In contrast, there is a high frequency of allergen-specific T helper 2 cells in allergic individuals. A decrease in interleukin (IL)-4, IL-5 and IL-13 production by allergen-specific CD4+ T cells due to the induction of peripheral T cell tolerance is the most essential step in allergen-specific immunotherapy (SIT). Suppressed proliferative and cytokine responses against the major allergens are induced by multiple suppressor factors, such as cytokines like IL-10 and transforming growth factor (TGF)-beta and cell surface molecules like cytotoxic T lymphocyte antigen-4, programmed death-1 and histamine receptor 2. There is considerable rationale for targeting T cells to increase efficacy of SIT. Such novel approaches include the use of modified allergens produced using recombinant DNA technology and adjuvants or additional drugs, which may increase the generation of allergen-specific peripheral tolerance. By the application of the recent knowledge in Treg cells and related mechanisms of peripheral tolerance, more rational and safer approaches are awaiting for the future of prevention and cure of allergic diseases.
Published: 2006

22. Different natural killer (NK) receptor expression and immunoglobulin E (IgE) regulation by NK1 and NK2 cells

Author: Sema Bilgic, Esin Aktas, Cezmi A. Akdis, Kurt Blaser, M. Akdis, Christine S. Falk, Günnur Deniz, and Rainer Disch
Subjects: Adult, Immunology, Apoptosis, Immunoglobulin E, CD49b, Dermatitis, Atopic, Interferon-gamma, Interleukin 21, Receptors, KIR, allergy, IgE, IgG4, KIR receptors, natural killer cells, Clinical Studies, Humans, Immunology and Allergy, Receptors, Immunologic, Cells, Cultured, CD40, Lymphokine-activated killer cell, biology, Chemistry, Janus kinase 3, Natural killer T cell, Interleukin-12, Coculture Techniques, Killer Cells, Natural, Leukocytes, Mononuclear, biology.protein, Interleukin 12, Cytokines, Interleukin-4
Abstract: Summary Many studies concerning the role of T cells and cytokines in allergy have been performed, but little is known about the role of natural killer (NK) cells. Accordingly, the expression of co-stimulatory, inhibitory and apoptosis receptors, cytokine profiles and their effect on immunoglobulin isotypes were investigated in polyallergic atopic dermatitis (AD) patients with hyper immunoglobulin E (IgE) and healthy individuals. AD patients showed significantly decreased peripheral blood NK cells compared to healthy individuals. Freshly isolated NK cells of polyallergic patients spontaneously released higher amounts of interleukin (IL)-4, IL-5, IL-13 and interferon (IFN)-γ compared to healthy individuals. NK cells were differentiated to NK1 cells by IL-12 and neutralizing anti-IL-4 monoclonal antibodies (mAb), and to NK2 cells by IL-4 and neutralizing anti-IL-12 mAb. Following IL-12 stimulation, NK cells produced increased levels of IFN-γ and decreased IL-4. In contrast, stimulation of NK cells with IL-4 inhibited IFN-γ, but increased IL-13, production. The effect of NK cell subsets on IgE regulation was examined in co-cultures of in vitro differentiated NK cells with peripheral blood mononuclear cells (PBMC) or B cells. NK1 cells significantly inhibited IL-4- and soluble CD40-ligand-stimulated IgE production; however, NK2 cells did not have any effect. The inhibitory effect of NK1 cells on IgE production was blocked by neutralization of IFN-γ. Except for CD40, NK cell subsets showed different expression of killer-inhibitory receptors and co-stimulatory molecules between the polyallergic and healthy subjects. These results indicate that human NK cells show differences in numbers, surface receptor and cytokine phenotypes and functional properties in AD.
Published: 2005

23. 20. Fortbildungskongress Davos — Vorträge

Author: C. Wiesend, Kurt Blaser, B Liebl, Martine Grosber, W. Mansfeld, Wolfgang Schober, J. Wohlrab, J. Ring, W.-H. Boehncke, Jeroen Buters, R. Engst, Thomas Zilker, E Vocks, V. Meineke, P. Prochazka, A. Konstantinow, R. Hein, V. Junghans, Cezmi A. Akdis, M. Akdis, A. Steinmann, C. Lemmen, E. Wanka, Helen Kalies, E.-B. Bröcker, Johan Verhagen, Claudia Traidl-Hoffmann, F. Kreuziger, Susanne Bornschein, Maja Mockenhaupt, G. Haeberli, Ulrich Müller, Heidrun Behrendt, Dennis Nowak, R. von Kries, R. Philipona, Michael Meurer, Knut Brockow, and P. Höppe
Subjects: medicine.medical_specialty, Otorhinolaryngology, business.industry, medicine, Immunology and Allergy, business, Dermatology
Published: 2004

24. Genes of tolerance

Author: Kurt Blaser, M. Akdis, and Cezmi A. Akdis
Subjects: biology, T-Lymphocytes, medicine.medical_treatment, Immunology, Peripheral tolerance, Dendritic Cells, Immunotherapy, Immunoglobulin E, T-Lymphocytes, Regulatory, Allergic inflammation, Immune tolerance, Immunoglobulin Isotypes, Immune system, Immune Tolerance, medicine, biology.protein, Animals, Humans, Receptors, Histamine, Immunology and Allergy, Cytokine secretion, Antibody
Abstract: Activation-induced cell death, anergy and/or immune response modulation by T-regulatory cells (T(Reg)) are essential mechanisms of peripheral T-cell tolerance. There is growing evidence that anergy, tolerance and active suppression are not entirely distinct, but rather, represent linked mechanisms possibly involving the same cells and multiple suppressor mechanisms. Skewing of allergen-specific effector T cells to T(Reg) cells appears as a crucial event in the control of healthy immune response to allergens and successful allergen-specific immunotherapy. The T(Reg) cell response is characterized by abolished allergen-induced specific T-cell proliferation and suppressed T helper 1 (Th1)- and Th2-type cytokine secretion. In addition, mediators of allergic inflammation that trigger cAMP-associated G-protein coupled receptors, such as histamine receptor 2 may contribute to peripheral tolerance mechanisms. The increased levels of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) that are produced by T(Reg) cells potently suppress immunoglobulin E (IgE) production, while simultaneously increasing production of noninflammatory isotypes IgG4 and IgA, respectively. In addition, T(Reg) cells directly or indirectly suppress effector cells of allergic inflammation such as mast cells, basophils and eosinophils. In conclusion, peripheral tolerance to allergens is controlled by multiple active suppression mechanisms. It is associated with regulation of antibody isotypes and effector cells to the direction of a healthy immune response and opens a window for novel therapies of allergic diseases.
Published: 2004

25. Immunological differences between intrinsic and extrinsic types of atopic dermatitis

Author: M. Akdis and Cezmi A. Akdis
Subjects: biology, business.industry, Immunology, Atopic dermatitis, medicine.disease, Immunoglobulin E, Apoptosis, biology.protein, Lymphocyte activation, Immunology and Allergy, Medicine, business, Skin pathology
Published: 2003

26. Poster-Abstracts

Author: M. Akdis, A. Trautmann, S. Klunker, I. Daigle, U. C. Kücüksezer, W. Deglmann, R. Disch, K. Blaser, C. A. Akdis, K. Forschner, T. Zuberbier, M. Worm, J. Gutermuth, J. Huss-Marp, B. Eberlein-König, K. Breuer, S. Mair, U. Darsow, A. Ansel, U. Krämer, E. Mayer, K. Gertis, J. Ring, H. Behrendt, U. Jappe, M. Farrar, E. Ingham, K. Holland, F. Karamloo, P. Schmid-Grendelmeier, F. Kussebi, C. Manhart, L. Soldatova, Z. Hously-Markovic, M. D. Spangfort, S. Kunzmann, C. B. Schmidt-Weber, V. Mahler, C. Gutgesell, Th. Fuchs, D. Kraft, R. Valenta, D. Münch, S. Borelli, R. Fukrop, I. Reese, U.-Ch. Hipler, S. Weissenbacher, R. Engst, J. Rakoski, M. Ollert, R. Wilkening, S. Soost, R. Klinger, and T. Wuske
Subjects: Immunology and Allergy
Published: 2002

27. Immunology

Author: Tim Elliott, Marc Bonneville, Ada Kruisbeek, Paul R Walker, David Essayan, Nicolas Glaichenhaus, Anna Vyakarnam, Jean-Laurent Casanova, N Liu, Hugh Auchincloss, Gerry Waneck, Christian LeGuern, M Akdis, and W.C Greene
Subjects: Immunology, Immunology and Allergy
Published: 2002

28. [Untitled]

Author: Cezmi A. Akdis, Axel Trautmann, M. Akdis, and Kurt Blaser
Subjects: Pharmacology, Cancer Research, integumentary system, business.industry, Inflammatory skin disease, Biochemistry (medical), Clinical Biochemistry, Pharmaceutical Science, Cell Biology, Atopic dermatitis, Immune dysregulation, medicine.disease, medicine.disease_cause, body regions, Pathogenesis, Apoptosis, Immunology, medicine, Eczematous dermatitis, Effector functions, business, Homing (hematopoietic)
Abstract: Atopic dermatitis is a chronic inflammatory skin disease with a complex immune dysregulation and interplay of genetic, environmental and psychological factors. Activation and skin-selective homing of peripherial-blood T cells, and effector functions in the skin, represent sequential events in the pathogenesis. Dysregulated apoptosis in skin-homing T cells, eosinophils and keratinocytes contributes to the elicitation and persistence of atopic derrmatitis.
Published: 2000

29. Skin Homing (Cutaneous Lymphocyte-Associated Antigen-Positive) CD8+ T Cells Respond to Superantigen and Contribute to Eosinophilia and IgE Production in Atopic Dermatitis

Author: M, Akdis, H U, Simon, L, Weigl, O, Kreyden, K, Blaser, and C A, Akdis
Subjects: Adult, Antigens, Differentiation, T-Lymphocyte, CD4-Positive T-Lymphocytes, Male, Staphylococcus aureus, Cell Survival, Immunology, Receptors, Lymphocyte Homing, Apoptosis, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Dermatitis, Atopic, Enterotoxins, Th2 Cells, Antigens, Neoplasm, T-Lymphocyte Subsets, Eosinophilia, Humans, Immunology and Allergy, Skin, Interleukin-13, Membrane Glycoproteins, Superantigens, Immunoglobulin E, Leukocytes, Mononuclear, Cytokines, Leukocyte Common Antigens, Female, Interleukin-5, Immunologic Memory
Abstract: In allergic inflammations of the skin, activation of CD4+ T cells was demonstrated to play an important role; however, a minor role for CD8+ T cells is implied. In the present study, we compared cutaneous lymphocyte-associated Ag (CLA)-expressing CD4+ and CD8+ subsets, which were isolated from peripheral blood and lesional skin biopsies in atopic dermatitis (AD) patients. We demonstrated that CD8+CLA+ T cells proliferate in response to superantigen and are as potent as CD4+CLA+ T cells in IgE induction and support of eosinophil survival. In atopic skin inflammation, the existence of high numbers of CD4+ and CD8+ T cells was demonstrated by immunohistochemistry and by culturing T cells from skin biopsies. In peripheral blood, both CD4+ and CD8+ subsets of CLA+CD45RO+ T cells were in an activated state in AD. The in vivo-activated CLA+ T cells of both subsets spontaneously released an IL-5- and IL-13-dominated Th2 type cytokine pattern. This was confirmed by intracytoplasmic cytokine staining immediately after isolation of the cells from peripheral blood. In consequence, both CD4+ and CD8+, CLA+ memory/effector T cells induced IgE production by B cells mainly by IL-13, and enhanced eosinophil survival in vitro by delaying eosinophil apoptosis, mainly by IL-5. These results indicate that in addition to the CD4+ subset, the CD8+CLA+ memory/effector T cells are capable of responding to superantigenic stimulation and play an important role in the pathogenesis of AD.
Published: 1999

30. Differential regulation of human T cell cytokine patterns and IgE and IgG4 responses by conformational antigen variants

Author: Cezmi A. Akdis, D. Wymann, Thorsten Blesken, M. Akdis, and Kurt Blaser
Subjects: biology, medicine.medical_treatment, T cell, Immunology, Antigen presentation, Immunoglobulin E, Molecular biology, Peripheral blood mononuclear cell, Isotype, Cytokine, medicine.anatomical_structure, Antigen, biology.protein, medicine, Immunology and Allergy, Antibody
Abstract: Bee venom phospholipase A2 (PLA) represents the major allergen and antigen in allergic and non-allergic individuals sensitized to bee sting. We have studied specific activation of peripheral T cells by different structural and conformational variants of PLA and secretion of cytokines regulating IgE and IgG4 antibody (Ab) formation. PLA molecules expressing the correctly folded tertiary structure, which show high affinity to membrane phospholipids and were recognized by Ab from bee sting allergic patients, induced high IL-4, IL-5 and IL-13 production in peripheral blood mononuclear cell cultures. In contrast, non-refolded recombinant PLA (rPLA) and reduced and alkylated native PLA (nPLA) induced more IFN-gamma and IL-2 and higher proliferative responses. Differences in proliferation and cytokine patterns among correctly folded and non-refolded PLA resulted from conformation-dependent involvement of different antigen-presenting cell (APC) types. Antigen (Ag)-presenting B cells recognized PLA only in its natural conformation, stimulated Th2 type cytokines and induced IgE Ab. Non-refolded PLA was recognized, processed and presented exclusively by monocytes and induced a Th1 dominant cytokine profile leading to IgG4 production by B cells. The possibility that production of particular cytokine patterns and Ig isotype was influenced by the enzymatic activity of PLA was excluded by using enzymatically inactive H34Q point-mutated, refolded rPLA. These findings demonstrate the decisive role of specific Ag recognition by different APC, depending on structural features, membrane phospholipid binding property and the existence of conformational B cell epitopes, in the differential regulation of memory IgE and IgG4 Ab. Furthermore, they show that a change from IgE-mediated allergy to normal immunity against a major allergen can be induced by rPLA variants that are not recognized by specific Ab and B cells but still carry the T cell epitopes. These features may enable new applications for safer immunotherapy.
Published: 1998

31. Skin-homing, CLA+ memory T cells are activated in atopic dermatitis and regulate IgE by an IL-13-dominated cytokine pattern: IgG4 counter-regulation by CLA- memory T cells

Author: M Akdis, C A Akdis, L Weigl, R Disch, and K Blaser
Subjects: Immunology, Immunology and Allergy
Abstract: Cutaneous lymphocyte-associated Ag (CLA) is a skin-homing receptor displayed by memory/effector T cells recognizing skin-related allergens. Here we demonstrate that peripheral blood CLA+ CD45RO+ T cells in patients with atopic dermatitis (AD) are in vivo activated. They spontaneously proliferate and release an IL-13-dominated Th2 cytokine profile and are capable of inducing IgE in autologous B cells without further activation. The spontaneous cytokine release occurred within the first hour of culture and was not inhibited by cycloheximide or by other immunosuppressive drugs, indicating that cytokine transcription and translation had been completed in vivo. In contrast, the CLA- CD45RO+ T cells from the same patients and from nonatopic controls represented a resting memory T cell subset, secreted borderline quantities of cytokines, and induced IgG4. Polyclonal activation by the anti-CD2/anti-CD3/anti-CD28 mAb mixture generated distinct cytokine patterns in the two memory/effector T cell subsets. CLA+ T cells secreted Th2 cytokines with high IL-13 levels, and the CLA- subset mainly produced IFN-gamma. There was no difference in in vitro activated cytokine pattern between AD patients and nonatopic subjects. These results indicate that the CLA+ memory/effector T cells of AD patients are activated in vivo and play a pivotal role in allergic inflammation by production of IL-13 and induction of IgE Abs. In contrast, the CLA- resting memory T cell population may exert immunoprotective properties toward allergen by high IFN-gamma secretion and induction of IgG4.
Published: 1997

32. Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: A Mechanisms of the Development of Allergy (MeDALL) seminar

Author: Cisca Wijmenga, Valérie Siroux, Renato T. Stein, Isabella Annesi-Maesano, John Wright, Josep M. Antó, Torsten Zuberbier, Cynthia Hohmann, Jordi Sunyer, Marjan Kerkhof, James P. Kiley, Martijn C. Nawijn, Weiniu Gan, Robert A. Smith, Antoon J. M. van Oosterhout, Patricia Noel, Bénédicte Jacquemin, Sabina Illi, Rudolf Valenta, Pascal Demoly, S. Palkonen, Ferran Ballester, Willem van de Veen, Görkem Yaman, Karin C. Lødrup Carlsen, Dieter Maier, Jonathan M. Coquet, Dirkje S. Postma, Kai-Håkon Carlsen, Jean Bousquet, Sam Oddie, Christian Lupinek, Henriette A. Smit, Manolis Kogevinas, Jocelyne Just, Magnus Wickman, Mariona Pinart, Sergio Valverde, Raphaëlle Varraso, M. Herr, Stefano Guerra, Chantal Guihenneuc-Jouyaux, Anne Cambon-Thomsen, Isabelle Pin, Judith Garcia-Aymerich, Cezmi A. Akdis, Claus Bachert, Isabelle Momas, Francine Kauffmann, Elena Gimeno-Santos, Marta Benet, Bart N. Lambrecht, Leena von Hertzen, Marek L. Kowalski, Xavier Basagaña, M. Akdis, Charles Auffray, Gerard H. Koppelman, Thomas Keil, Susanne Lau, Daniela Porta, Peter J. Sterk, Barbara Stanic, Leda Chatzi, Tari Haahtela, Fernando D. Martinez, Joachim Heinrich, Antonello Punturieri, Fanny Rancière, Faculteit Medische Wetenschappen/UMCG, Groningen Research Institute of Pharmacy, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Amsterdam institute for Infection and Immunity, and Pulmonology
Subjects: Allergy, WORLD-HEALTH-ORGANIZATION, Bioinformatics, Epigenesis, Genetic, 0302 clinical medicine, Risk Factors, Immunology and Allergy, Medicine, Young adult, Child, Epigenesis, media_common, Mechanisms of the Development of Allergy, 0303 health sciences, education.field_of_study, phenotypes, Seventh Framework Program, IgE, asthma, RUSSIAN KARELIA, Phenotype, 3. Good health, LUNG-FUNCTION, Child, Preschool, BRONCHIAL HYPERRESPONSIVENESS, BIRTH-COHORT, Adolescent, ASTHMA RESEARCH-PROGRAM, Systems biology, Immunology, Population, OBSTRUCTIVE PULMONARY-DISEASE, Young Adult, 03 medical and health sciences, DIAGNOSTIC GATEKEEPERS, Hypersensitivity, Animals, Humans, media_common.cataloged_instance, European union, education, 030304 developmental biology, CLUSTER-ANALYSIS, business.industry, Mechanism (biology), Research, Immunoglobulin E, medicine.disease, 030228 respiratory system, business, T-REGULATORY-CELLS
Abstract: Mechanisms of the Development of Allergy (MeDALL), a Seventh Framework Program European Union project, aims to generate novel knowledge on the mechanisms of initiation of allergy. Precise phenotypes of IgE-mediated allergic diseases will be defined in MeDALL. As part of MeDALL, a scientific seminar was held on January 24, 2011, to review current knowledge on the IgE-related phenotypes and to explore how a multidisciplinary effort could result in a new integrative translational approach. This article provides a summary of the meeting. It develops challenges in IgE-related phenotypes and new clinical and epidemiologic approaches to the investigation of allergic phenotypes, including cluster analysis, scale-free models, candidate biomarkers, and IgE microarrays; the particular case of severe asthma was reviewed. Then novel approaches to the IgE-associated phenotypes are reviewed from the individual mechanisms to the systems, including epigenetics, human in vitro immunology, systems biology, and animal models. The last chapter deals with the understanding of the population-based IgE-associated phenotypes in children and adolescents, including age effect in terms of maturation, observed effects of early-life exposures and shift of focus from early life to pregnancy, gene-environment interactions, cohort effects, and time trends in patients with allergic diseases. This review helps to define phenotypes of allergic diseases in MeDALL. (J Allergy Clin Immunol 2012;129:943-54.)
Published: 2012

33. Mechanisms of immunotherapy to wasp and bee venom

Author: C, Ozdemir, U C, Kucuksezer, M, Akdis, and C A, Akdis
Subjects: Bee Venoms, Epitopes, Hypersensitivity, Animals, Humans, Wasp Venoms, Immunotherapy, Allergens, Antibodies, Neutralizing, T-Lymphocytes, Regulatory, Histamine
Abstract: Hymenoptera venoms are important allergens that can elicit both local and systemic allergic reactions, including life-threatening anaphylaxis. Venom immunotherapy (VIT) remains the most effective treatment, reducing the risk of systemic reactions in individuals with Hymenoptera venom allergy. VIT can restore normal immunity against venom allergens and provide patients with a lifetime of tolerance to venoms. During VIT, peripheral tolerance is induced by the generation of allergen-specific regulatory T (Treg) cells, which suppress proliferative and cytokine responses against the venom allergens. Treg cells are characterized by IL-10 secretion that directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. Treg cells also have influence on B cells, suppressing IgE production and inducing the production of blocking type IgG4 antibodies against venom allergens. An accumulating body of evidence suggests that Treg cells may affect allergen sensitization and methods for enhancing this cell population may eventually improve the efficacy of VIT. In this article, immune mechanisms enrolled in bee and wasp VIT are reviewed.
Published: 2011

34. Regulatory effects of histamine and histamine receptor expression in human allergic immune responses

Author: C, Akdis, M, Jutel, and M, Akdis
Subjects: Hypersensitivity, Immediate, Inflammation, Immunity, Cellular, Organ Specificity, Antibody Formation, Histamine H1 Antagonists, Intracellular Signaling Peptides and Proteins, Humans, Receptors, Histamine, Cell Communication, Granulocytes, Histamine, Signal Transduction
Abstract: Histamine influences several immune/inflammatory and effector functions in addition to its dominant role in type I hypersensitivity reactions. Histamine can selectively recruit the major effector cells into tissue sites and affect their maturation, activation, polarization, and other functions leading to chronic inflammation. Histamine also regulates monocytes, dendritic cells, T cells and B cells, as well as related antibody isotype responses. The diverse effects of histamine on immune regulation appear to be due to differential expression and regulation of four types of histamine receptors and their distinct intracellular signals. In addition, differences in affinities of these receptors for histamine are highly decisive for the biological effects of histamine and drugs that target histamine receptors.
Published: 2008

35. Highlights in cellular and molecular mechanisms of allergic diseases. XXVth Congress of the European Academy of Allergology and Clinical Immunology in Vienna

Author: T, Basinski, C, Ozdemir, C, Sackesen, P-Y, Mantel, I, Barlan, M, Akdis, M, Jutel, and C A, Akdis
Subjects: Europe, Allergy and Immunology, Hypersensitivity, Animals, Humans, Congresses as Topic
Abstract: This year, the annual congress of the European Academy of Allergology and Clinical Immunology was held on 10-14 June in Vienna. More than 6,000 delegates, practicing bench or bedside work or both, gathered from over 50 countries throughout the world. Health professionals, basic scientists and fellows in training could choose between a variety of activities in plenary, main, educational and workshop sessions, highlights of the past year, pros and cons, and oral abstract and poster sessions, and met with experts. A total of 1,713 abstracts, 31 symposia, and 54 workshops were presented, ranging from basic science to clinical trials and modern treatment of allergic diseases. Here, we summarize the highlights of cellular and molecular mechanisms of allergic disease.
Published: 2006

36. Role of T Cells in Atopic Eczema

Author: Johan Verhagen, M. Akdis, Cezmi A. Akdis, and K. Blaser
Subjects: business.industry, Immunology, medicine, medicine.disease, business, Allergic contact dermatitis, Allergic inflammation
Published: 2006

37. Immunological differences between intrinsic and extrinsic types of atopic dermatitis

Author: C A, Akdis and M, Akdis
Subjects: Keratinocytes, Langerhans Cells, T-Lymphocytes, Cytokines, Humans, Apoptosis, Dendritic Cells, Lymphocyte Count, Immunoglobulin E, Lymphocyte Activation, Dermatitis, Atopic, Skin
Published: 2003

38. Skin homing T cells

Author: M, Akdis, S, Klunker, K, Blaser, and C A, Akdis
Subjects: Antigens, Differentiation, T-Lymphocyte, Keratinocytes, Chemotaxis, Leukocyte, Membrane Glycoproteins, Antigens, Neoplasm, Interleukins, T-Lymphocytes, Animals, Humans, Dermatitis, Atopic, Skin
Published: 2003

39. T Cells and Effector Mechanisms in Atopic Dermatitis

Author: M. Akdis, Sven Klunker, K. Blaser, Cezmi A. Akdis, and Axel Trautmann
Subjects: integumentary system, biology, Effector, medicine.medical_treatment, Immunoglobulin E, Immune system, Cytokine, Lymphatic system, Antigen, Immunology, biology.protein, medicine, Superantigen, Homing (hematopoietic)
Abstract: T cells constitute a large population of cellular infiltrate in atopic dermatitis (AD) and a dysregulated, cytokine mediated immune response appears to be an important pathogenetic factor.The great majority of T cells homing to skin express CD45RO+ memory/effector phenotype and the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen (CLA). Aeroallergens, food antigens, autoantigens and bacterial superantigens activate T cells in AD. Continuous Stimulation of T cells in lymphatic organs and skin plays an important role in AD with induction of hyper IgE and eosinophilia. Activated T cells induce keratinocyte apoptosis as a key pathogenetic event in the formation of eczema. To mediate these effector functions after skin homing, activated T cells show continuous survival in the skin. Activât ion-induced cell death of T cells (AICD) is prevented by cytokines and extracellular matrix components in the eczematous skin.
Published: 2002

40. Cytokine network and dysregulated apoptosis in atopic dermatitis

Author: Cezmi A. Akdis, Kurt Blaser, Sven Klunker, Axel Trautmann, and M. Akdis
Subjects: Antigens, Differentiation, T-Lymphocyte, Keratinocytes, Fas Ligand Protein, T cell, T-Lymphocytes, Receptors, Lymphocyte Homing, Apoptosis, Immunoglobulin E, Ligands, Lymphocyte Activation, Dermatitis, Atopic, Interferon-gamma, Antigen, Antigens, Neoplasm, Cell Movement, medicine, Cytotoxic T cell, Humans, IL-2 receptor, fas Receptor, General Dentistry, Skin, Membrane Glycoproteins, integumentary system, biology, Interleukins, General Medicine, T lymphocyte, Extracellular Matrix, Eosinophils, medicine.anatomical_structure, Immunology, Antigens, Surface, biology.protein, Cytokines, CD8, Homing (hematopoietic)
Abstract: Activation and skin-selective homing of peripheral blood memory/effector T cells and effector functions in the skin represent sequential immunological events in the pathogenesis of atopic dermatitis (AD). T cells infiltrating the skin utilize the cutaneous lymphocyte-associated antigen (CLA) and other receptors to recognize and cross the vascular endothelium. In the peripheral blood of AD patients, both CD4+ and CD8 subsets of CLA+CD45RO+ T cells are in an activated state with high CD25, HLA-DR, and CD40-ligand expression. They express upregulated Fas and Fas-ligand and undergo activation-induced apoptosis. After homing to skin these T cells form dermal infiltrates which play a key role in the pathogenesis of the disease. Skin-infiltrating T cells in AD are protected from activation-induced cell death, although they express both Fas and Fas-ligand. They are protected from apoptosis by cytokines such as IL-2, IL-4, and IL-15 and extracellular matrix components such as fibronectin and transferrin. CLA+, skin-homing T cells may play a role in peripheral blood eosinophilia and hyper IgE production by high IL-5 and IL-13 expression, respectively. These T cells secrete IFN-gamma in the skin, which upregulates Fas on keratinocytes and renders them susceptible to apoptosis. Keratinocyte apoptosis is induced by Fas-ligand, either soluble or expressed on the surface of T cells, leading to eczema formation. Here we discuss the mechanisms of skin-selective T cell homing and activation, and emphasize the concept of dysregulated apoptosis of T cells, eosinophils, and keratinocytes as essential pathogenetic episodes in AD and other eczematous disorders.
Published: 2001

41. Role of dysregulated apoptosis in atopic dermatitis

Author: A, Trautmann, M, Akdis, K, Blaser, and C A, Akdis
Subjects: T-Lymphocytes, Animals, Humans, Apoptosis, Lymphocyte Activation, Dermatitis, Atopic
Abstract: Atopic dermatitis is a chronic inflammatory skin disease with a complex immune dysregulation and interplay of genetic, environmental and psychological factors. Activation and skin-selective homing of peripherial-blood T cells, and effector functions in the skin, represent sequential events in the pathogenesis. Dysregulated apoptosis in skin-homing T cells, eosinophils and keratinocytes contributes to the elicitation and persistence of atopic derrmatitis.
Published: 2001

42. Role of T cells and cytokines in the intrinsic form of atopic dermatitis

Author: C A, Akdis, M, Akdis, D, Simon, B, Dibbert, M, Weber, S, Gratzl, O, Kreyden, R, Disch, B, Wüthrich, K, Blaser, and H U, Simon
Subjects: Adult, Male, Lymphokines, Enzyme-Linked Immunosorbent Assay, Immunoglobulin E, Middle Aged, Dermatitis, Atopic, Leukocyte Count, T-Lymphocyte Subsets, Humans, Female, Lymphocyte Count, Aged, Skin
Published: 1999

43. Differential regulation of human T cell cytokine patterns and IgE and IgG4 responses by conformational antigen variants

Author: C A, Akdis, T, Blesken, D, Wymann, M, Akdis, and K, Blaser
Subjects: Adult, B-Lymphocytes, Membrane Glycoproteins, Protein Conformation, CD40 Ligand, Antigen-Presenting Cells, Immunoglobulin E, Th1 Cells, Lymphocyte Activation, Monocytes, Phospholipases A, Bee Venoms, Phospholipases A2, Th2 Cells, T-Lymphocyte Subsets, Immunoglobulin G, Hypersensitivity, Cytokines, Humans
Abstract: Bee venom phospholipase A2 (PLA) represents the major allergen and antigen in allergic and non-allergic individuals sensitized to bee sting. We have studied specific activation of peripheral T cells by different structural and conformational variants of PLA and secretion of cytokines regulating IgE and IgG4 antibody (Ab) formation. PLA molecules expressing the correctly folded tertiary structure, which show high affinity to membrane phospholipids and were recognized by Ab from bee sting allergic patients, induced high IL-4, IL-5 and IL-13 production in peripheral blood mononuclear cell cultures. In contrast, non-refolded recombinant PLA (rPLA) and reduced and alkylated native PLA (nPLA) induced more IFN-gamma and IL-2 and higher proliferative responses. Differences in proliferation and cytokine patterns among correctly folded and non-refolded PLA resulted from conformation-dependent involvement of different antigen-presenting cell (APC) types. Antigen (Ag)-presenting B cells recognized PLA only in its natural conformation, stimulated Th2 type cytokines and induced IgE Ab. Non-refolded PLA was recognized, processed and presented exclusively by monocytes and induced a Th1 dominant cytokine profile leading to IgG4 production by B cells. The possibility that production of particular cytokine patterns and Ig isotype was influenced by the enzymatic activity of PLA was excluded by using enzymatically inactive H34Q point-mutated, refolded rPLA. These findings demonstrate the decisive role of specific Ag recognition by different APC, depending on structural features, membrane phospholipid binding property and the existence of conformational B cell epitopes, in the differential regulation of memory IgE and IgG4 Ab. Furthermore, they show that a change from IgE-mediated allergy to normal immunity against a major allergen can be induced by rPLA variants that are not recognized by specific Ab and B cells but still carry the T cell epitopes. These features may enable new applications for safer immunotherapy.
Published: 1998

44. Defective TCR stimulation in anergized type 2 T helper cells correlates with abrogated p56(lck) and ZAP-70 tyrosine kinase activities

Author: A, Faith, C A, Akdis, M, Akdis, H U, Simon, and K, Blaser
Subjects: Enzyme Activation, Antigen Presentation, Th2 Cells, ZAP-70 Protein-Tyrosine Kinase, src-Family Kinases, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Receptors, Antigen, T-Cell, Humans, Protein-Tyrosine Kinases, Lymphocyte Activation, Clone Cells, Signal Transduction
Abstract: Development of IgE-mediated allergic conditions is dependent on the secretion of a Th2 cytokine pattern, including IL-4, IL-5, and IL-13. The induction of anergy would be one mechanism to abrogate cytokine secretion by Th2 cells, which may be pivotal to the allergic response. We demonstrate here that incubation of cloned human CD4+ phospholipase A2 (PLA)-specific Th2 cells with antigenic peptide, in the absence of professional APC, results in a state of nonresponsiveness. The anergic T cells failed to proliferate or secrete IL-4 in response to optimal stimulation with PLA and autologous, professional APC. Secretion of IL-5 and IL-13, however, was only partially inhibited. The anergic state of the Th2 cells was not associated with CD3 or CD28 down-regulation. However, anergy did appear to be closely related to alterations in signaling pathways, mediated through the TCR, of the cells. In contrast to untreated Th2 cells, anergized Th2 cells failed to respond to anti-CD3 mAb with either increased tyrosine kinase activity or increased levels of tyrosine phosphorylation of p56(lck) or ZAP70. A strong and sustained intracellular calcium flux, observed in untreated Th2 cells in response to anti-CD3 mAb, was absent in anergic Th2 cells. Furthermore, the induction of anergy seems to represent an active process, associated with increased levels of basal tyrosine kinase activity, cytokine production, and CD25 up-regulation in anergic Th2 cells. Together, our results indicate that anergy in Th2 cells is associated with defective transmembrane signaling through the TCR.
Published: 1997

45. Erratum

Author: Patrick G. Holt, Stephen J. Galli, Carsten B. Schmidt-Weber, Georg Schäppi, Ulf Darsow, Ernst Rietschel, S. Hildemann, J. Ring, U. Mueller, H. zur Hausen, Ruby Pawankar, M. Akdis, S. T. Holgate, T. Bieber, Kurt Blaser, E. M. De Villiers, Jean Bousquet, Thomas A.E. Platts-Mills, Gianni Marone, Claudia Traidl-Hoffmann, Caroline Roduit, Judah A. Denburg, E. von Mutius, Bruce S. Bochner, C. Czerkinsky, Günther Menz, A. Jung, Roger Lauener, Ulrich Wahn, Cezmi A. Akdis, Martin Mempel, Thilo Jakob, John Bienenstock, Liam O'Mahony, Tari Haahtela, M. Kemeny, H. Koren, R. Lockey, Heidrun Behrendt, B. Menné, Adnan Custovic, Markus Ollert, Donald Y.M. Leung, Jeffrey M. Drazen, Reto Crameri, A. Fire, Harald Renz, O. de Beaumont, and W. Ammann
Subjects: 0303 health sciences, Pediatrics, medicine.medical_specialty, Allergy, Clinical immunology, business.industry, Immunology, Declaration, Global problem, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Family medicine, medicine, Immunology and Allergy, business, 030304 developmental biology
Published: 2012

46. Suppression of Toll-like Receptors 3-, 7- and 9-induced B cell Activation and Antibody Production by Repetitive Oligonucleotides from Mammalian Telomere

Author: Ihsan Gursel, M. Akdis, S.S. Alkan, Cezmi A. Akdis, Judith Zumkehr, Cansin Sackesen, and Kurt Blaser
Subjects: Antibody production, Oligonucleotide, Immunology, Immunology and Allergy, Biology, Receptor, Molecular biology, B-cell activation, Telomere
Published: 2006

47. Low thresholds for activation and apoptosis of Th1 cells as a mechanism of Th2 predominance in atopic diseases

Author: Kurt Blaser, Tunc Akkoc, P. de Konig, M. Akdis, Cezmi A. Akdis, Judith Zumkehr, and Isil Barlan
Subjects: Apoptosis, Mechanism (biology), Chemistry, Immunology, Immunology and Allergy
Published: 2005

48. T helper (Th) 2 predominance in atopy is due to preferential Th1 memory/effector cell apoptosis

Author: Kurt Blaser, Sven Klunker, W. Deglmann, Umut Can Kucuksezer, Rainer Disch, Isabelle Daigle, M. Akdis, Cezmi A. Akdis, and Axel Trautmann
Subjects: Atopy, Apoptosis, Immunology, medicine, Immunology and Allergy, Biology, medicine.disease, Effector cell
Published: 2003

49. 479 Differential histamine H1 and H2 receptor expression determines up-regulation of Th1 and down-regulation of Th2 responses following histamine stimulation

Author: M. Akdis, Cezmi A. Akdis, Józef Małolepszy, Marek Jutel, Sven Klunker, Zak-Nejmark T, and Kurt Blaser
Subjects: Histamine receptor, chemistry.chemical_compound, Histamine H2 receptor, Downregulation and upregulation, Th2 response, Chemistry, Immunology, Immunology and Allergy, Histamine H4 receptor, Histamine H1 receptor, Histamine H3 receptor, Pharmacology, Histamine
Published: 2000

50. 508 Life span of skin homing T cells in atopic dermatitis: Survival in skin, activation induced apoptosis in peripheral blood

Author: Kurt Blaser, M. Akdis, Axel Trautmann, and C.A Akids
Subjects: medicine.medical_specialty, Life span, business.industry, Immunology, Atopic dermatitis, medicine.disease, Dermatology, Peripheral blood, Skin homing, Apoptosis, medicine, Immunology and Allergy, business
Published: 2000

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