Trajectories of childhood immune development and respiratory health relevant to asthma and allergy
File(s)
Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2018-10-15
Date Acceptance
2018-10-05
Citation
eLife, 2018, 7
ISSN
2050-084X
Publisher
eLife Sciences Publications Ltd
Journal / Book Title
eLife
Volume
7
Copyright Statement
© Tang et al. This
article is distributed under the
terms of the Creative Commons
Attribution License, which
permits unrestricted use and
redistribution provided that the
original author and source are
credited.
article is distributed under the
terms of the Creative Commons
Attribution License, which
permits unrestricted use and
redistribution provided that the
original author and source are
credited.
Sponsor
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000449454800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MR/M015181/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
2 BIRTH COHORTS
1ST 6 YEARS
ATOPY PHENOTYPES
VIRAL-INFECTIONS
CLUSTER-ANALYSIS
YOUNG-CHILDREN
PEANUT ALLERGY
FOLLOW-UP
SENSITIZATION
RISK
Publication Status
Published
Article Number
ARTN e35856