Distinguishing wheezing phenotypes from infancy to adolescence: a pooled analysis of five birth cohorts

Rationale: Pooling data from multiple cohorts and extending the time−frame across childhood should minimize study−specific effects, enabling better characterization of the childhood wheezing. 
Objective: To analyze wheezing patterns from early childhood to adolescence using combined data from five birth cohorts.
Methods: We used latent class analysis to derive wheeze phenotypes among 7719 participants from five birth cohorts with complete report of wheeze at five time−periods. We tested the association of derived phenotypes with late asthma outcomes and lung function, and investigated the uncertainty in phenotype assignment.
Main Results: We identified five phenotypes: Never/Infrequent wheeze (52.1%), Early−onset pre−school remitting (23.9%), Early−onset mid−childhood remitting (9%), Persistent (7.9%) and Late−onset wheeze (7.1%). Compared to the Never/infrequent wheeze, all phenotypes had higher odds of asthma and lower FEV1 and FEV1/FVC in adolescence. The association with asthma was strongest for Persistent wheeze (adjusted odds ratio 56.54, 95%CI 43.75−73.06). We observed considerable within−class heterogeneity at individual level, with 913 (12%) children having low membership probability (<0.60) of any phenotype. Class membership certainty was highest in Persistent and Never/infrequent, and lowest in Late−onset wheeze (with 51% of participants having membership probabilities<0.80). Individual wheezing patterns were particularly heterogeneous in Late−onset wheeze, while many children assigned to Early−onset pre−school remitting class reported wheezing at later time points.
Conclusions: All wheeze phenotypes had significantly diminished lung function in school-age, suggesting that the notion that early-life episodic wheeze has a benign prognosis may not be true for a proportion of transient wheezers. We observed considerable within−phenotype heterogeneity in individual wheezing patterns.