School-age lung function was significantly lower in individuals with all types of early life wheeze, according to a study published in Annals of the American Thoracic Society. This finding suggests that transient wheeze may not be associated with a benign prognosis.

This multicohort study included 7719 participants from 5 different birth cohorts, all of whom had complete wheeze reports. The association between derived phenotypes and late outcomes/lung function for asthma was examined, with further investigation into phenotype assignment uncertainty. Logistic regression models with adjustments for potential confounders were used to examine the correlation between derived phenotypes and asthma/use of asthma medication and lung function.

The participants in this study were categorized into 5 phenotypes: 52.1% with never or infrequent wheeze, 23.9% with early onset preschool remitting wheeze, 9% with early onset midchildhood remitting wheeze, 7.9% with persistent wheeze, and 7.1% with late-onset wheeze. In comparison with those in the never/infrequent group, lower forced expiratory volume in 1 second (FEV1) and FEV1/forced volume capacity were more common in all other phenotypes during adolescence. Persistent wheeze showed the strongest correlation (relative risk ratio, 56.54; 95% CI, 43.75-73.06; P <.0001). Allergic sensitization between the ages of 4 and 7.5 years was also greatest in the persistent wheeze group (relative risk ratio, 5.12; 95% CI, 4.04-6.47; P <.0001).

There was strong heterogeneity within individual classes, and 12% (n=913) of participants had membership probability of <0.60 for any phenotype. This probability was lowest in individuals with late-onset wheeze (51% with probabilities <0.80) and greatest in those with persistent or never/infrequent wheeze (probability >0.80). The late-onset group showed especially heterogeneous individual wheezing patterns. There was high reporting of later wheeze in the early onset preschool remitting wheeze group.

One limitation to this study was intercohort variation in areas such as data collection tools, question phrasing and types, time and intervals of data collection, and criteria for recruitment.

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The study researchers concluded that “early life episodic wheeze may not have a benign prognosis for a proportion of transient wheezers. Up to 12% of children have low membership probability of any wheezing phenotype, and the mere presence or absence of a wheeze may be insufficient to derive homogenous phenotypes for probing causality. It is likely that more holistic indicators of wheeze (including frequency and severity) are needed to describe individual trajectories and derive more homogenous phenotypes to facilitate better understand the natural history and causality of childhood wheezing illness.”

Disclosures: This study received funding from the Wellcome Trust Strategic Award.


Oksel C, Granell R, Haider S, et al; on behalf of STELAR and Breathing Together Investigators. Distinguishing wheezing phenotypes from infancy to adolescence: A pooled analysis of five birth cohorts [published online March 19, 2019]. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.201811-837OC