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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.* ; ALLIANCE Study Group (Marzi, C. ; Zissler, U.M. ; Schmidt-Weber, C.B.)

T-high asthma phenotypes across life span.

Eur. Respir. J. 60:2102288 (2022)

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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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