Associations of wheezing phenotypes with late asthma outcomes in the Avon Longitudinal Study of Parents and Children: A population-based birth cohort

Background: Variable patterns of childhood wheezing might indicate differences in the cause and prognosis of respiratory illnesses. Better understanding of these patterns could facilitate identification of modifiable factors related to development of asthma. Objectives: We characterized childhood wheezing phenotypes from infancy to adolescence and their associations with asthma outcomes. Methods: Latent class analysis was used to derive phenotypes based on patterns of wheezing recorded at up to 14 time points from birth to 16 years among 12,303 participants from the Avon Longitudinal Study of Parents and Children. Measures of lung function (FEV1, forced vital capacity [FVC], and forced expiratory flow between 25% and75%[FEF25-75]) and fraction of exhaled nitric oxide (FENO) were made at 14 to 15 years of age. Results: Six wheezing phenotypes were identified: never/infrequent, preschool-onset remitting, midchildhood-onset remitting, school age-onset persisting, late childhood-onset persisting, and continuous wheeze. The 3 persistent phenotypes were associated with bronchodilator reversibility of 12% or greater (BDR) from baseline (odds ratio [OR] range, 2.14-3.34), a FENO value of 35 ppb or greater (OR range, 3.82-6.24), and lung function decrements (mean range of differences: -0.22 to -0.27 SD units (SDU) for FEV1/FVC ratio and -0.21 to -0.33 SDU for FEF25-75) compared with never/infrequent wheeze. Midchildhood-onset (41/2 years) remitting wheeze was associated with BDR(OR, 1.77; 95% CI, 1.11-2.82), a FENO value of 35 ppb or greater (OR, 1.72; 95% CI, 1.14-2.59), FEV1/FVC ratio decrements (OR, -0.22 SDU; 95% CI, -0.36 to -0.08 SDU), and FEF25-75 decrements (OR, -0.16 SDU; 95% CI, -0.30 to -0.01 SDU). Preschool-onset (18 months) remitting wheeze was only associated with FEV1/FVC ratio decrements (OR, -0.15 SDU; 95% CI, -0.25 to -0.05 SDU) and FEF25-75 decrements (OR, -0.14 SDU; 95% CI, -0.24 to -0.04 SDU). The persisting phenotypes showed evidence of sex stratification during adolescence. Conclusions: Early childhood-onset wheezing that persists into adolescence represents the clearest target group for interventions to maximize lung function outcomes.