T2-high asthma phenotypes across lifespan

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.

Automated summary

This study aimed to define T2-high asthma in children using easily accessible biomarkers and compare phenotypes across different age groups. Results showed that T2-high asthma can be identified in all ages, including very young children, and is associated with childhood onset. Excessive production of specific IgE antibodies to allergens was observed in both children and adults with T2-high asthma. Early treatment with biologicals may benefit these patients.