Abstract:
: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.
journal_name
Elifejournal_title
eLifeauthors
Tang HH,Teo SM,Belgrave DC,Evans MD,Jackson DJ,Brozynska M,Kusel MM,Johnston SL,Gern JE,Lemanske RF,Simpson A,Custovic A,Sly PD,Holt PG,Holt KE,Inouye Mdoi
10.7554/eLife.35856subject
Has Abstractpub_date
2018-10-15 00:00:00issn
2050-084Xpii
35856journal_volume
7pub_type
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