Longitudinal phenotypes of respiratory health in a high-risk urban birth cohort

Rationale: Characterization of patterns of wheezing and allergic sensitization in early life may allow for identification of specific environmental exposures impacting asthma development. Objectives: To define respiratory phenotypes in inner-city children and their associations with early-life environmental exposures. Methods: Data were collected prospectively from 442 children in the URECA (Urban Environment and Childhood Asthma) birth cohort through age 7 years, reflecting symptoms (wheezing), aeroallergen sensitization, pulmonary function, and body mass index. Latent class mixed models identified trajectories of wheezing, allergic sensitization, and pulmonary function. Cluster analysis defined nonoverlapping groups (termed phenotypes). Potential associations between phenotypes and early-life environmental exposures were examined. Measurements and Main Results: Five phenotypes were identified and mainly differentiated by patterns of wheezing and allergic sensitization (low wheeze/low atopy; low wheeze/high atopy; transient wheeze/low atopy; high wheeze/low atopy; high wheeze/high atopy). Asthma was most often present in the high-wheeze phenotypes, with greatest respiratory morbidity among children with frequent wheezing and allergic sensitization. These phenotypes differentially related to early-life exposures, including maternal stress and depression, antenatal environmental tobacco smoke, house dust microbiome, and allergen content (all P, 0.05). Prenatal smoke exposure, maternal stress, and depression were highest in the high-wheeze/low-atopy phenotype. The high-wheeze/high-atopy phenotype was associated with low household microbial richness and diversity. Early-life aeroallergen exposure was low in high-wheeze phenotypes. Conclusions: Patterns of wheezing, allergic sensitization, and lung function identified five respiratory phenotypes among inner-city children. Early-life environmental exposure to stress, depression, tobacco smoke, and indoor allergens and microbes differentially associate with specific phenotypes.