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Maison, N. ; Omony, J. ; Illi, S. ; Thiele, D.* ; Skevaki, C.* ; Dittrich, A.M.* ; Bahmer, T.* ; Rabe, K.F.* ; Weckmann, M.* ; Happle, C.* ; Schaub, B.* ; Meier, M.* ; Foth, S.* ; Rietschel, E.* ; Renz, H.* ; Hansen, G.* ; Kopp, M.V.* ; von Mutius, E. ; Grychtol, R.*

T-high asthma phenotypes across life span.

Eur. Respir. J., DOI: 10.1183/13993003.02288-2021 (2022)
Open Access Green as soon as Postprint is submitted to ZB.
RATIONALE: In adults, personalised asthma treatment targets patients with 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 multicenter 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 LPS or anti-CD3/CD28. MEASUREMENTS AND MAIN RESULTS: Based on blood eosinophil counts and allergen-specific serum IgE antibodies (sIgE), 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 younger age.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0903-1936
e-ISSN 1399-3003
Publisher European Respiratory Society
Publishing Place Sheffield
Reviewing status Peer reviewed
Institute(s) Institute of Asthma and Allergy Prevention (IAP)
Grants Bundesministerium für Bildung und Forschung
Deutsches Zentrum für Lungenforschung
Wilsing Stiftung