Multidimensional assessment of asthma identifies clinically relevant phenotype overlap: a cross-sectional study

Abstract Background Asthma is a heterogenous disease with multiple phenotypes; however, the relevance of phenotype overlap remains largely unexplored. Objective To examine the relationship between phenotype overlap and clinical and inflammatory profiles of asthma. Methods In this cross-sectional study, adult participants with stable asthma (n=522) underwent multidimensional assessments. The 10 most common phenotypes of asthma were defined and then classified into those commonly associated with Type (T) 2 or non-T2 inflammation. Furthermore, phenotype overlap scores (POS), representing the cumulative concomitant phenotypes, were used to analyze its association with clinical and inflammatory asthmatic profiles. Results Among the 522 participants, 73.4% (n=383) had phenotype overlap, and mixed T2 and non-T2 inflammation coexisted in 47.5% (n=248). T2 POS was positively associated with eosinophils, IgE, and FeNO, and negatively with AQLQ, sputum neutrophils, IL-17A, IL-8, and TNF-α. Non-T2 POS was positively associated with ACQ, neutrophils and sputum IL-8, and negatively with AQLQ, FEV1, blood eosinophils, IgE, and FeNO (all P Conclusions Phenotype overlap is extremely common in asthmatic patients and significantly associated with clinical and inflammatory profiles. Patients with phenotypes associated with mixed T2 and non-T2 inflammation might be unresponsive to medications owing to increased non-T2 inflammation. Multidimensional asthma assessment identifies clinically relevant phenotype overlap.