T2-high asthma across all ages – comparative analysis in children and adults from the ALLIANCE cohort

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Background Personalized monoclonal antibody-based therapies for asthma target cytokines involved in type 2 inflammation. However, definitions of type 2 high asthma (T2H) vary and ha ve been mainly developed in adults studies. We defined T2 high asthma with easily accessible biomarkers and compared 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 characterization including 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. Results Based on blood eosinophil counts using age-adjusted thresholds and allergen-specific serum IgE antibodies (specific immunoglobulin E (sIgE) ≥ 0.7 kU/L against ≥ 1/ 36 allergens), patients were categorized into four exclusive phenotypes: ‘Atopy-only’, ‘Eosinophils-only’, ‘T2-high’ (eosinophilia + atopy) and ‘T2-low’ (neither eosinophilia nor atopy). The T2-high phenotype was present across all ages with the highest prevalence in children > 6 years (40.2%) compared to adults (24.6%) and preschoolers (16.9%) .In very young children it persisted to a large degree even after two years of follow-up. In adults, T2-high was associated with childhood onset suggesting early origins of this asthma phenotype. In both children and adults, the T2-high phenotype was characterized by increased production of specific IgE to allergens, elevated FeNO, and, from school age onwards, by increased production of IL-5 after anti-CD3/CD28 stimulation of whole blood. Conclusion T2 high asthma defined by easily assessable biomarkers identifies a distinct phenotype with childhood-onset asthma, increased sIgE and IL-5. Patients with T2H asthma may benefit from therapy with biologicals at younger age. Publication History Article published online: 21 September 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

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