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Cytokine responses to rhinovirus and development of asthma, allergic sensitization and respiratory infections during childhood

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Title: Cytokine responses to rhinovirus and development of asthma, allergic sensitization and respiratory infections during childhood
Authors: Custovic, A
Belgrave, D
Lin, L
Bakhsoliani, E
Telcian, AG
Solari, R
Murray, CS
Walton, RP
Curtin, J
Edwards, MR
Simpson, A
Rattray, M
Johnston, SL
Item Type: Journal Article
Abstract: BACKGROUND: Immunophenotypes of anti-viral responses, and their relationship with asthma, allergy and lower respiratory tract infections (LRTIs) are poorly understood. We characterized multiple cytokine responses of peripheral-blood mononuclear cells to rhinovirus stimulation, and their relationship with clinical outcomes. METHODS: In a population-based birth cohort, we measured 28 cytokines post-stimulation with rhinovirus-16 in 307 children aged 11 years. We used machine learning to identify patterns of cytokine responses, and related these patterns to clinical outcomes using longitudinal models. We also ascertained phytohaemagglutinin-induced TH2-cytokine responses [PHA-TH2]. RESULTS: We identified six clusters of children based on their rhinovirus-16 responses, which were differentiated by the expression of four cytokine/chemokine groups: interferon-related-(IFN); pro-inflammatory-(Inflam); TH2-chemokine-(TH2-chem); regulatory-(Reg). Clusters differed in their clinical characteristics. Children with IFNmodInflamhighestTH2-chemhighestReghighestrhinovirus-16-induced pattern had PHA-TH2lowresponse, and a very low asthma risk (OR:0.08 [95%CI 0.01-0.81], P=0.03). Two clusters had high risk of asthma and allergic sensitization, but with different trajectories from infancy to adolescence. The IFNlowestInflamhighTH2-chemlowRegmodcluster exhibited PHA-TH2lowestresponse, and was associated with early-onset asthma and sensitization, and the highest risk of asthma exacerbations (1.37 [1.07-1.76], P=0.014) and LRTI hospitalizations (2.40 [1.26-4.58], P=0.008) throughout childhood. In contrast, cluster with IFNhighestInflammodTH2-chemmodReghighrhinovirus-16-cytokine pattern was characterized by PHA-TH2highestresponse, and a low prevalence of asthma/sensitization in infancy which increased sharply to become the highest among all clusters by adolescence (but with low risk of asthma exacerbations). CONCLUSIONS: Early-onset troublesome asthma with early-life sensitization, later-onset milder allergic asthma, and disease protection are each associated with different patterns of rhinovirus-induced immune responses.
Issue Date: 15-May-2018
Date of Acceptance: 20-Feb-2018
URI: http://hdl.handle.net/10044/1/57394
DOI: https://dx.doi.org/10.1164/rccm.201708-1762OC
ISSN: 1073-449X
Publisher: American Thoracic Society
Start Page: 1265
End Page: 1274
Journal / Book Title: American Journal of Respiratory and Critical Care Medicine
Volume: 197
Issue: 10
Copyright Statement: © 2018 American Thoracic Society
Sponsor/Funder: Asthma UK
Asthma UK
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Funder's Grant Number: CH11SJ
CH11SJ
G1000758
G1000758
MR/L012693/1
NF-SI-0514-10092
Keywords: asthma
cytokines
machine learning
rhinovirus
Asthma, rhinovirus, cytokines, machine learning
11 Medical And Health Sciences
Respiratory System
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-02-21
Appears in Collections:National Heart and Lung Institute
Department of Medicine
Faculty of Medicine



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