Phenotypes of Recurrent Wheezing in Preschool Children: Identification by Latent Class Analysis and Utility in Prediction of Future Exacerbation

Abstract

To identify predictors of future exacerbations and response to inhaled corticosteroid (ICS) treatment in preschool children with recurrent wheezing.This was a study of 1708 well-characterized and medication-adherent children aged 12 to 71 months with recurrent wheezing enrolled in multicenter trials sponsored by the National Heart, Lung, and Blood Institute’s AsthmaNet and Childhood Asthma Research and Education Network.Latent class analysis, a statistical method used to identify group membership, was applied using 10 demographic, sensitization, and exposure variables within the merged data set to identify classes of recurrent wheeze and determine optimal classification. Within each class, annual exacerbation rate and response to daily ICS therapy were defined.Four groups with different patterns of environmental sensitization, exposures, and exacerbations were identified, with highest rates of both exacerbations and ICS response in groups 2 and 4. Annual exacerbation rates (mean ± SEM per year) were 0.65 ± 0.06 for class 1 (“minimal sensitization”), 0.93 ± 0.10 for class 2 (“sensitization with indoor pet exposure”), 0.60 ± 0.07 for class 3 (“sensitization with tobacco smoke exposure”), and 0.81 ± 0.10 for class 4 (“multiple sensitization and eczema”) (P < .001). Notably, current symptoms and historical exacerbations did not differ between groups.Type 2 inflammatory features were a marker for more-frequent exacerbations in children with recurrent preschool wheezing. Researchers in this study identified 4 distinct groups of recurrent wheeze among preschool children, which differed with regard to allergen sensitization and/or exposure as well as annual exacerbation rate and response to ICS therapy. Daily ICS treatment reduced exacerbations rates in groups 2 and 4, but not other groups, in a high-adherence research setting. However, exacerbations still occurred in children with minimal sensitization, likely caused by triggers independent of type 2 inflammation.Preschoolers with recurrent wheeze represent a mixed group. Investigators in this study suggest that those sensitized to allergens in their environment with either indoor pet exposure or eczema are more likely to experience more-frequent exacerbations but also respond better to asthma controller therapy. As we consider early persistent and transient wheezing phenotypes of preschool children, this study adds to a growing literature to help identify our youngest patients with asthma and optimize management to maximize value.