Events in early life contribute to subsequent risk of asthma; however, the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma. Similarly, not all atopic individuals develop wheeze, and vice versa. The reasons for these differences are unclear. Using unsupervised model-based cluster analysis, we identified latent clusters within a prospective birth cohort with deep immunological and respiratory phenotyping. We characterised each cluster in terms of immunological profile and disease risk, and replicated our results in external cohorts from the UK and USA. We discovered three distinct trajectories, one of which is a high-risk 'atopic' cluster with increased propensity for allergic diseases throughout childhood. Atopy contributes varyingly to later wheeze depending on cluster membership. Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis and provide a foundation for improving management and prevention of childhood asthma.
- Michael Inouye
- Howard HF Tang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: Ethics approval and consent requirements for each cohort were met as follows: The CAS study was approved by the ethics committees of the King Edward Memorial and Princess Margaret Hospitals in Western Australia; fully informed parental consent was obtained for all subjects. The COAST study was approved by the Human Subjects Committee of the University of Wisconsin. The MAAS study was approved by a Manchester Local Research Ethics Committee (ERP/94/032; SOU/00/258; 03/SM/400; Study registration ISRCTN72673620); fully informed parental consent was obtained for all subjects across all cohorts.
- M Dawn Teare, University of Sheffield, United Kingdom
© 2018, Tang et al.
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