A Principal Component Analysis-Based Endophenotype Definition for Change in Lung Function and Inhaled Corticosteroid Treatment Response in Childhood Asthma

Asthma is a clinically and biologically heterogeneous syndrome with variable symptom patterns, severity, and treatment responses. Understanding this heterogeneity is important to develop personalized management strategies. In this study, we applied the principal component analysis to systematically assess baseline clinical features in three independent pediatric asthma cohorts. Our goal was to define clinically meaningful and reproducible endophenotypes. The analysis revealed distinct endophenotypes with consistent clinical profiles between cohorts and were distinguished by different patterns of loss of lung function and risk of exacerbation. We further observed that the derived endophenotypes enhanced the ability to predict individual responses to inhaled corticosteroid therapy (ICS). This endophenotype framework provides a practical and scalable approach to stratifying pediatric asthma using baseline clinical features and facilitates targeted treatment strategies guided by endophenotype classification.