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

Ceyda Oksel, Raquel Granell, Sadia Haider, Sara Fontanella, Angela Simpson, Steve Turner, Graham Devereux, Syed Hasan Arshad, Clare S. Murray, Graham Roberts, John W. Holloway, Paul Cullinan, John Henderson*, Adnan Custovic

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)
7 Downloads (Pure)


Rationale: Pooling data from multiple cohorts and extending the time frame across childhood should minimize study-specific effects, enabling better characterization of childhood wheezing. Objectives: 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 7,719 participants from five birth cohorts with complete report of wheeze at five time periods. We tested the associations 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 preschool remitting (23.9%), early onset midchildhood remitting (9%), persistent (7.9%), and late-onset wheeze (7.1%). Compared with the never/infrequent wheeze, all phenotypes had higher odds of asthma and lower forced expiratory volume in 1 second and forced expiratory volume in 1 second/forced vital capacity in adolescence. The association with asthma was strongest for persistent wheeze (adjusted odds ratio, 56.54; 95% confidence interval, 43.75-73.06). We observed considerable withinclass heterogeneity at the 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, whereas many children assigned to early onset preschool remitting class reported wheezing at later time points. Conclusions: All wheeze phenotypes had significantly diminished lung function in school-age children, 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.

Original languageEnglish
Pages (from-to)868-876
Number of pages9
JournalAnnals of the American Thoracic Society
Issue number7
Publication statusPublished - 1 Jul 2019

Bibliographical note

The authors thank all the families who took part in this study; the midwives for their help in recruiting them; and the MAAS, IOW, Ashford, SEATON, and ALSPAC teams, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses.


  • Adolescence
  • Childhood
  • Latent class
  • Wheezing phenotypes
  • childhood
  • latent class
  • wheezing phenotypes
  • adolescence
  • 1ST 6 YEARS
  • LIFE


Dive into the research topics of 'Distinguishing wheezing phenotypes from infancy to adolescence: A pooled analysis of five birth cohorts'. Together they form a unique fingerprint.

Cite this