Distinguishing wheezing phenotypes from infancy to adolescence: a pooled analysis of five birth cohorts
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Published version
Author(s)
Type
Journal Article
Abstract
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. 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.
Date Issued
2019-07-01
Date Acceptance
2019-03-19
Citation
Annals of the American Thoracic Society, 2019, 16 (7), pp.868-876
ISSN
2329-6933
Publisher
American Thoracic Society
Start Page
868
End Page
876
Journal / Book Title
Annals of the American Thoracic Society
Volume
16
Issue
7
Copyright Statement
© 2019 by the American Thoracic Society. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). For commercial usage and reprints, please contact Diane Gern (dgern@thoracic.org)
Sponsor
Medical Research Council (MRC)
Wellcome Trust
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30888842
Grant Number
MR/K002449/2
108818/Z/15/Z and 108818/Z/15/
Subjects
Science & Technology
Life Sciences & Biomedicine
Respiratory System
wheezing phenotypes
childhood
adolescence
latent class
1ST 6 YEARS
LOW LUNG-FUNCTION
ASTHMA
CHILDREN
CHILDHOOD
ASSOCIATIONS
LIFE
PARENTS
adolescence
childhood
latent class
wheezing phenotypes
STELAR investigators, breathing Together investigators
Respiratory System
1103 Clinical Sciences
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-03-19