Trajectories of childhood immune development and respiratory health relevant to asthma and allergy

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Title: Trajectories of childhood immune development and respiratory health relevant to asthma and allergy
Author(s): Tang, HHF
Teo, SM
Belgrave, DCM
Evans, MD
Jackson, DJ
Brozynska, M
Kusel, MMH
Johnston, SL
Gern, JE
Lemanske, RF
Simpson, A
Custovic, A
Sly, PD
Holt, PG
Holt, KE
Inouye, M
Item 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.
Publication Date: 15-Oct-2018
Date of Acceptance: 5-Oct-2018
URI: http://hdl.handle.net/10044/1/65299
DOI: https://dx.doi.org/10.7554/eLife.35856.001
ISSN: 2050-084X
Publisher: eLife Sciences Publications Ltd
Journal / Book Title: eLife
Volume: 7
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MR/M015181/1
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.
Keywords: 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
allergy
bioinformatics
computational biology
human
immune development
respiratory disease
systems biology
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
Appears in Collections:National Heart and Lung Institute
Department of Medicine
Faculty of Medicine



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