Causes of variability in latent phenotypes of childhood wheeze

Background: Latent class analysis (LCA) has been used extensively to identify (latent) phenotypes of childhood wheezing. However, the number and trajectory of discovered phenotypes differed substantially between studies.Objective: To investigate sources of variability affecting the classification of phenotypes, identify key time points for data collection to understand wheeze heterogeneity, and ascertain the association of childhood wheeze phenotypes with asthma and lung function in adulthood. Methods: We used LCA to derive wheeze phenotypes among 3167 participants in the ALSPAC cohort who had complete information on current wheeze recorded at 14 time points from birth to age 16½ years. We examined the effects of sample size, data collection age and intervals on the results, and identified time points. We examined the associations of derived phenotypes with asthma and lung function at age 23-24 years.Results: A relatively large sample size (>2000) underestimated the number of phenotypes under some conditions (e.g. number of time points <11). Increasing the number of data points resulted in an increase in the optimal number of phenotypes, but an identical number of randomly selected follow-up points led to different solutions. A variable selection algorithm identified 8 informative time points (months 18, 42, 57, 81, 91, 140, 157 and 166). The proportion of asthmatics at age 23-24 years differed between phenotypes, while lung function51 was lower among persistent wheezers.Conclusions: Sample size, frequency, and timing of data collection have a major influence on the number and type of wheeze phenotypes identified by LCA in longitudinal data.