Comparison of phenotypes of childhood wheeze and cough in 2 independent cohorts.
BACKGROUND
Among children with wheeze and recurrent cough there is great variation in clinical presentation and time course of the disease. We previously distinguished 5 phenotypes of wheeze and cough in early childhood by applying latent class analysis to longitudinal data from a population-based cohort (original cohort).


OBJECTIVE
To validate previously identified phenotypes of childhood cough and wheeze in an independent cohort.


METHODS
We included 903 children reporting wheeze or recurrent cough from an independent population-based cohort (validation cohort). As in the original cohort, we used latent class analysis to identify phenotypes on the basis of symptoms of wheeze and cough at 2 time points (preschool and school age) and objective measurements of atopy, lung function, and airway responsiveness (school age). Prognostic outcomes (wheeze, bronchodilator use, cough apart from colds) 5 years later were compared across phenotypes.


RESULTS
When using a 5-phenotype model, the analysis distinguished 3 phenotypes of wheeze and 2 of cough as in the original cohort. Two phenotypes were closely similar in both cohorts: Atopic persistent wheeze (persistent multiple trigger wheeze and chronic cough, atopy and reduced lung function, poor prognosis) and transient viral wheeze (early-onset transient wheeze with viral triggers, favorable prognosis). The other phenotypes differed more between cohorts. These differences might be explained by differences in age at measurements.


CONCLUSIONS
Applying the same method to 2 different cohorts, we consistently identified 2 phenotypes of wheeze (atopic persistent wheeze, transient viral wheeze), suggesting that these represent distinct disease processes. Differences found in other phenotypes suggest that the age when features are assessed is critical and should be considered carefully when defining phenotypes.
Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. Electronic address: bspycher@ispm.unibe.ch.
Ben D
BD
Spycher
Michael
M
Silverman
Anina M
AM
Pescatore
Caroline S
CS
Beardsmore
Claudia E
CE
Kuehni
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003371:Cough / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D063868:Patient Outcome Assessment; D010641:Phenotype; D011379:Prognosis; D012135:Respiratory Sounds / Q000175:diagnosis*; D011795:Surveys and Questionnaires
ALSPAC; Avon Longitudinal Study of Parents and Children; BHR; BIC; BLRT; Bayesian Information Criterion; Bootstrap likelihood ratio test; Bronchial hyper-responsiveness; LCA; Latent class analysis; Wheeze; allergy; asthma; bronchial responsiveness; children; cluster analysis; cohort study; cough; latent class analysis; phenotypes