Sex-Specific Asthma Phenotypes, Inflammatory Patterns, and Asthma Control in a Cluster Analysis

Background: Asthma is a heterogeneous disease with complex mechanisms and involves many risk factors and in vivo cellular molecules. It is notable that sex differences may have a potential effect on asthma phenotype. Objective: To identify sex-specific phenotypes and health outcomes of asthma. Methods: We conducted the Taiwanese Adult Asthma Cohorts study to enroll female (n = 421) and male (n = 299) adult patients with stable asthma. Eight variables were selected by a factor analysis. We further performed a 2-step sensitivity cluster analysis to classify asthma clusters. The risks of asthma-related outcomes among the clusters were assessed using simple logistic regressions. Results: Three different clusters were identified in males and females. In the female clusters, atopy/eosinophil-predominant (cluster 2), and obesity/neutrophil-predominant pattern (cluster 3) had more than a 2-fold risk of asthma exacerbations (odds ratio, 2.51; 95% CI, 1.12-5.59 and odds ratio, 2.22; 95% CI, 1.01-4.93). In the male clusters, current smoker/neutrophilic atopic cluster (cluster 5) and ex-smoker/eosinophil-predominant or mixed inflammatory pattern (cluster 6) also had a higher risk of asthma exacerbations. Conclusions: This study identified heterogeneous characteristics between sexes. In females, the analysis showed atopy with eosinophil-predominant and obese with neutrophil-predominant inflammation. Two distinct asthma phenotypes were found in current and ex-smokers in males. Understanding asthma phenotypes and explaining the potentially biological pathways have become important.