@article{Custovic:2018:10.1164/rccm.201708-1762OC,
author = {Custovic, A and Belgrave, D and Lin, L and Bakhsoliani, E and Telcian, AG and Solari, R and Murray, CS and Walton, RP and Curtin, J and Edwards, MR and Simpson, A and Rattray, M and Johnston, SL},
doi = {10.1164/rccm.201708-1762OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {1265--1274},
title = {Cytokine responses to rhinovirus and development of asthma, allergic sensitization and respiratory infections during childhood},
url = {http://dx.doi.org/10.1164/rccm.201708-1762OC},
volume = {197},
year = {2018}
}

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TY  - JOUR
AB  - 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-
AU  - Custovic,A
AU  - Belgrave,D
AU  - Lin,L
AU  - Bakhsoliani,E
AU  - Telcian,AG
AU  - Solari,R
AU  - Murray,CS
AU  - Walton,RP
AU  - Curtin,J
AU  - Edwards,MR
AU  - Simpson,A
AU  - Rattray,M
AU  - Johnston,SL
DO  - 10.1164/rccm.201708-1762OC
EP  - 1274
PY  - 2018///
SN  - 1073-449X
SP  - 1265
TI  - Cytokine responses to rhinovirus and development of asthma, allergic sensitization and respiratory infections during childhood
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.201708-1762OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29466680
UR  - https://www.atsjournals.org/doi/10.1164/rccm.201708-1762OC
UR  - http://hdl.handle.net/10044/1/57394
VL  - 197
ER  - 

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