"T2-high" in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin
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Supporting information
Accepted version
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild-moderate asthma into a T2-high phenotype. We examined whether currently-available clinical biomarkers can predict AEC-defined T2-high phenotype within U-BIOPRED cohort. METHODS: The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from IL-13-exposed AECs. RESULTS: 37% of asthmatics (45% non-smoking severe asthma, n=49, 33% of smoking or ex-smoking severe asthma, n=18 and 28% mild-moderate asthma, n=36) were T2-high using AEC gene expression. They were more symptomatic with higher levels of nitric oxide in exhaled breath (FeNO) and of blood and sputum eosinophils but not of serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature. FeNO (≥30 ppb) and blood eosinophils (≥300/µL) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression. CONCLUSION: T2-high severe asthma can be predicted to some extent from raised levels of FeNO, blood and sputum eosinophil counts, but serum IgE or serum periostin were poor predictors. Better bedside biomarkers are needed to detect T2-high.
Date Issued
2019-01-01
Date Acceptance
2018-10-26
Citation
European Respiratory Journal, 2019, 53 (1)
ISSN
0903-1936
Publisher
European Respiratory Society
Journal / Book Title
European Respiratory Journal
Volume
53
Issue
1
Copyright Statement
© 2019 ERS. This is an author-submitted, peer-reviewed version of a manuscript that has been accepted for publication in the European Respiratory Journal, prior to copy-editing, formatting and typesetting. This version of the manuscript may not be duplicated or reproduced without prior permission from the copyright owner, the European Respiratory Society. The publisher is not responsible or liable for any errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final, copy-edited, published article, which is the version of record, is available without a subscription 18 months after the date of issue publication.
Sponsor
Commission of the European Communities
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30578390
PII: 13993003.00938-2018
Grant Number
115010
Subjects
on behalf of the U-BIOPRED Study Group
11 Medical And Health Sciences
Respiratory System
Publication Status
Published
Coverage Spatial
England
Article Number
1800938
Date Publish Online
2019-01-03