T2-high asthma phenotypes across lifespan.

Autor:	Maison N; Institute for Asthma and Allergy Prevention (IAP), Helmholtz Zentrum Munich, German Research Center for Environmental Health (GmbH), Munich, Germany.; Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany.; Comprehensive Pneumology Center - Munich (CPC-M), Member of German Center for Lung Research (DZL), Munich, Germany., Omony J; Institute for Asthma and Allergy Prevention (IAP), Helmholtz Zentrum Munich, German Research Center for Environmental Health (GmbH), Munich, Germany.; Comprehensive Pneumology Center - Munich (CPC-M), Member of German Center for Lung Research (DZL), Munich, Germany., Illi S; Institute for Asthma and Allergy Prevention (IAP), Helmholtz Zentrum Munich, German Research Center for Environmental Health (GmbH), Munich, Germany.; Comprehensive Pneumology Center - Munich (CPC-M), Member of German Center for Lung Research (DZL), Munich, Germany., Thiele D; Institute of Medical Biometry and Statistics (IMBS), University Medical Center Schleswig-Holstein, Luebeck, Germany.; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Luebeck, Germany., Skevaki C; Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps-University Marburg, Marburg, Germany.; Universities of Giessen and Marburg Lung Center (UGMLC), Philipps University Marburg, German Center for Lung Research (DZL), Marburg, Germany., Dittrich AM; Dept of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany., Bahmer T; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Luebeck, Germany.; University Hospital Schleswig-Holstein, Campus Kiel, Internal Medicine Department I, Pneumology, Kiel, Germany.; LungenClinic Grosshansdorf GmbH, Grosshansdorf, Germany., Rabe KF; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Luebeck, Germany.; LungenClinic Grosshansdorf GmbH, Grosshansdorf, Germany., Weckmann M; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Luebeck, Germany.; Division of Pediatric Pneumology and Allergology, University Medical Center Schleswig-Holstein, Luebeck, Germany., Happle C; Dept of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany., Schaub B; Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany.; Comprehensive Pneumology Center - Munich (CPC-M), Member of German Center for Lung Research (DZL), Munich, Germany., Meyer M; Faculty of Medicine, University Children's Hospital, University of Cologne, Cologne, Germany., Foth S; Universities of Giessen and Marburg Lung Center (UGMLC), Philipps University Marburg, German Center for Lung Research (DZL), Marburg, Germany.; University Children's Hospital Marburg, University of Marburg, Marburg, Germany., Rietschel E; Faculty of Medicine, University Children's Hospital, University of Cologne, Cologne, Germany., Renz H; Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps-University Marburg, Marburg, Germany.; Universities of Giessen and Marburg Lung Center (UGMLC), Philipps University Marburg, German Center for Lung Research (DZL), Marburg, Germany.; Dept of Clinical Immunology and Allergology, Sechenov University, Moscow, Russia., Hansen G; Dept of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany., Kopp MV; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Luebeck, Germany.; Division of Pediatric Pneumology and Allergology, University Medical Center Schleswig-Holstein, Luebeck, Germany.; Dept of Pediatric Respiratory Medicine, Inselspital, University Children's Hospital of Bern, University of Bern, Bern, Switzerland., von Mutius E; Institute for Asthma and Allergy Prevention (IAP), Helmholtz Zentrum Munich, German Research Center for Environmental Health (GmbH), Munich, Germany erika.von.mutius@med.lmu.de.; Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany.; Comprehensive Pneumology Center - Munich (CPC-M), Member of German Center for Lung Research (DZL), Munich, Germany., Grychtol R; Dept of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany., Fuchs O, Roesler B, Welchering N, Kohistani-Greif N, Kurz J, Landgraf-Rauf K, Laubhahn K, Liebl C, Ege M, Hose A, Zeitlmann E, Berbig M, Marzi C, Schauberger C, Zissler U, Schmidt-Weber C, Ricklefs I, Diekmann G, Liboschik L, Voigt G, Sultansei L, Nissen G, König IR, Kirsten AM, Pedersen F, Watz H, Waschki B, Herzmann C, Abdo M, Biller H, Gaede KI, Bovermann X, Steinmetz A, Husstedt BL, Nitsche C, Veith V, Szewczyk M, Brinkmann F, Malik A, Schwerk N, Dopfer C, Price M, Jirmo AC, Habener A, DeLuca DS, Gaedcke S, Liu B, Calveron MR, Weber S, Schildberg T, van Koningsbruggen-Rietschel S, Alcazar M
Jazyk:	angličtina
Zdroj:	The European respiratory journal [Eur Respir J] 2022 Sep 29; Vol. 60 (3). Date of Electronic Publication: 2022 Sep 29 (Print Publication: 2022).
DOI:	10.1183/13993003.02288-2021
Abstrakt:	Rationale: In adults, personalised asthma treatment targets patients with type 2 (T2)-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children. Objectives: To define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages. Methods: In the multicentre clinical All Age Asthma Cohort (ALLIANCE), 1125 participants (n=776 asthmatics, n=349 controls) were recruited and followed for 2 years (1 year in adults). Extensive clinical characterisation (questionnaires, blood differential count, allergy testing, lung function and sputum induction (in adults)) was performed at baseline and follow-ups. Interleukin (IL)-4, IL-5 and IL-13 were measured after stimulation of whole blood with lipopolysaccharide (LPS) or anti-CD3/CD28. Measurements and Main Results: Based on blood eosinophil counts and allergen-specific serum IgE antibodies, patients were categorised into four mutually exclusive phenotypes: "atopy-only", "eosinophils-only", "T2-high" (eosinophilia + atopy) and "T2-low" (neither eosinophilia nor atopy). The T2-high phenotype was found across all ages, even in very young children in whom it persisted to a large degree even after 2 years of follow-up. T2-high asthma in adults was associated with childhood onset, suggesting early origins of this asthma phenotype. In both children and adults, the T2-high phenotype was characterised by excessive production of specific IgE to allergens (p<0.0001) and, from school age onwards, by increased production of IL-5 after anti-CD3/CD28 stimulation of whole blood. Conclusions: Using easily accessible biomarkers, patients with T2-high asthma can be identified across all ages delineating a distinct phenotype. These patients may benefit from therapy with biologicals even at a younger age. Competing Interests: Conflict of interest: N. Maison, J. Omony, S. Illi, D. Thiele, A.M. Dittrich, C. Happle, M. Meyer, S. Foth and R. Grychtol have nothing to disclose. C. Skevaki reports grants and personal fees from Hycor Biomedical, Bencard Allergie, Thermo Fisher Scientific as well as grants from Mead Johnson Nutrition (MJN), Universities Giessen and Marburg Lung Centre, the German Centre for Lung Research (DZL), University Hospital Giessen and Marburg, Deutsche Forschungsgemeinschaft (DFG). T. Bahmer reports grants from the Federal Ministry for Education and Research (BMBF) for the German Center for Lung Research (DZL) and personal fees from AstraZeneca, GlaxoSmithKline, Novartis, Roche and Chiesi. M. Weckmann reports grants from Federal Ministry for Education and Research (BMBF), University of Luebeck and German Academic Exchange Service. B. Schaub reports grants from DFG, BMBF, the EU as well from GlaxoSmithKline, Sanofi and Novartis. H. Renz reports grants from German Center for Lung Disease (DZL) and Universities Giessen Marburg Lung Center. M.V. Kopp reports grants and personal fees from Allergopharma GmbH and Vertex GmbH; additional, personal fees from Sanofi GmbH, Infectopharm GmbH and Leti GmbH. E. Rietschel reports personal lecture payments for Nutricia Milupa GmbH and Novartis Pharma, and honoraria for participation in advisory boards for MICE-Mylan, Novartis Pharma GmbH and Boehringer Ingelheim GmbH. K.F. Rabe recieved personal payments or honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, Novartis, Sanofi & Regeneron, GlaxoSmithKline, Berlin Chemie and Roche; K.F. Rabe also discloses participation on data safety monitoring boards/advisory boards for AstraZeneca and Sanofi Regeneron, and leadership or fiduciary role in the German Center for Lung Research (DZL), German Chest Society (DGP) and American Thoracic Society (ATS). G. Hansen reports grants from German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG) as well as personal fees from Sanofi GmbH, MedUpdate, and Abbvie. E. von Mutius reports grants from the German Center for Lung Research (DZL) as well as royalties/licenses held by Elsevier GmbH, Gerog Thieme Verlag, Springer Verlag GmbH, Elsevier Ltd; furthermore, consultation fees were received from the Chinese University of Hong Kong, European Commission, HiPP GmbH and AstraZeneca; E. von Mutius also received payments and/or support for meetings/travel from the Massachusetts Medical Society, Springer-Verlag GmbH, Elsevier Ltd, Böhringer Ingelheim International GmbH, European Respiratory Society (ERS), University Utrecht, Salzburg, Colorado and Imperial College London, Springer Medizin Verlag GmbH, Japanese Society of Pediatric Allergy and Clinical Immunology, Klinkum Rechts der Isar, Paul-Martini-Stiftung; further support for meetings/travel was granted by Verein zur Förderung der Pneumologie am Krankenhaus Groshansdorf, Pneumologie Development Mondial Congress & Events GmbH, American Academy of Allergy, Asthma & Immunology, Margaux Orange, Volkswagen Stiftung, Österreichische Gesellschaft für Allergologie & Immunologie, OM Pharma SA, Hanson Wade Ltd, iKOMM GmbH, DSI Dansk Bornestma Center, American Thoracic Society, HiPP GmbH; E. von Mutius has patent EP2361632, EP1411977, EP1637147 and EP 1964570 (licensed to Protectimmun), furthermore patent LU101064 is pending; E. von Mutius participates in the following data monitoring or advisory boards: EXPANSE, BEAMS External Scientific Advisory Board, Journal of Allergy and Clinical Immunology: in Practice, Children's Respiratory and Environmental Workgroup (CREW), International Scientific & Societal Advisory Board of Utrecht Life Sciences, External Review Panel of the Faculty of Veterinary Science (University of Utrecht), Gottfried Wilhelm Leibniz Programme, Asthma UK for Applied Research, Advisory Board of The Lancet Respiratory Medicine, CHILD (Canadian Healthy Infant Longitudinal Development Study). (Copyright ©The authors 2022.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu