Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early-life risk factors and late asthma outcomes

Abstract

Introduction: Exacerbation-prone asthma subtype has been reported in studies using data-driven methodologies. However, patterns of severe exacerbations have not been studied. Objective: To investigate longitudinal trajectories of severe wheeze exacerbations from infancy to school age. Methods: We applied longitudinal k-means clustering to derive exacerbation trajectories among 887 participants from a population-based birth cohort with severe wheeze exacerbations confirmed in healthcare records. We examined early-life risk factors of the derived trajectories, and their asthma-related outcomes and lung function in adolescence. Results: 498/887 children (56%) had physician-confirmed wheeze by age 8 years, of whom 160 had at least one severe exacerbation. A two-cluster model provided the optimal solution for severe exacerbation trajectories among these 160 children: “Infrequent exacerbations (IE)” (n = 150, 93.7%) and “Early-onset frequent exacerbations (FE)” (n = 10, 6.3%). Shorter duration of breastfeeding was the strongest early-life risk factor for FE (weeks, median [IQR]: FE, 0 [0-1.75] vs. IE, 6 [0-20], P