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

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cam.issuedOnline2018-10-15
dc.contributor.authorTang, Howard Hf
dc.contributor.authorTeo, Shu Mei
dc.contributor.authorBelgrave, Danielle Cm
dc.contributor.authorEvans, Michael D
dc.contributor.authorJackson, Daniel J
dc.contributor.authorBrozynska, Marta
dc.contributor.authorKusel, Merci Mh
dc.contributor.authorJohnston, Sebastian L
dc.contributor.authorGern, James E
dc.contributor.authorLemanske, Robert F
dc.contributor.authorSimpson, Angela
dc.contributor.authorCustovic, Adnan
dc.contributor.authorSly, Peter D
dc.contributor.authorHolt, Patrick G
dc.contributor.authorHolt, Kathryn E
dc.contributor.authorInouye, Michael
dc.contributor.orcidTang, Howard Hf [0000-0001-6422-0270]
dc.contributor.orcidEvans, Michael D [0000-0001-7449-3993]
dc.contributor.orcidCustovic, Adnan [0000-0001-5218-7071]
dc.contributor.orcidInouye, Michael [0000-0001-9413-6520]
dc.date.accessioned2018-12-08T00:31:58Z
dc.date.available2018-12-08T00:31:58Z
dc.date.issued2018-10-15
dc.description.abstractEvents 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.
dc.format.mediumElectronic
dc.identifier.doi10.17863/CAM.33877
dc.identifier.eissn2050-084X
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286567
dc.languageeng
dc.language.isoeng
dc.publishereLife Sciences Publications, Ltd
dc.publisher.urlhttp://dx.doi.org/10.7554/elife.35856
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectallergy
dc.subjectbioinformatics
dc.subjectcomputational biology
dc.subjecthuman
dc.subjectimmune development
dc.subjectrespiratory disease
dc.subjectsystems biology
dc.subjectAsthma
dc.subjectAustralia
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectFemale
dc.subjectHumans
dc.subjectHypersensitivity
dc.subjectImmune System
dc.subjectInfant
dc.subjectMale
dc.subjectRespiratory System
dc.subjectRisk Factors
dc.titleTrajectories of childhood immune development and respiratory health relevant to asthma and allergy.
dc.typeArticle
dcterms.dateAccepted2018-10-05
prism.publicationDate2018
prism.publicationNameElife
prism.volume7
pubs.funder-project-idMedical Research Council (MR/L003120/1)
pubs.funder-project-idBritish Heart Foundation (None)
rioxxterms.licenseref.startdate2018-10-15
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.7554/eLife.35856

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