Clinical, cellular and molecular features of T2-high asthma

Asthma is the most frequent chronic inflammatory airway disease with a prevalence reaching 5-10%. Historically, two principal forms of asthma have been described : allergic and non-allergic asthma. In the first section of this thesis, we showed that, while sharing many demographic, lung function and inflammatory features, atopic and non-atopic asthmatic patients showed clear differences with respect to the age of onset, smoking history and FENO levels. In the second part, we focused on eosinophilic asthma, a clinical inflammatory phenotype wherein a significant number of airway or blood eosinophils are present. We demonstrated that the more severe airway eosinophilic inflammation in IgE-low non-atopic eosinophilic asthmatics despite similar treatment with ICS and a higher burden of OCS pointed to a certain corticosteroid resistance in this asthma phenotype. The third part covers mechanistic insights describing how treating severe eosinophilic asthma with biologic therapies alter the molecular milieu in the blood compartment. Our objective was to unravel their longitudinal effects on proteomic and transcriptomic signatures. The last segment addresses the heterogeneity in clinical responses to biologics and reinforces the importance to examine sputum eosinophils in severe asthmatic patients as it was associated with the intensity of response to anti-IL-5(R) biologics.