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“T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin

Pavlidis, Stelios; Takahashi, Kentaro; Ng Kee Kwong, Francois; Xie, Jiaxing; Hoda, Uruj; Sun, Kai; Elyasigomari, Vahid; Agapow, Paul; Loza, Matthew; Baribaud, Fred; Chanez, Pascal; Fowler, Steve J.; Shaw, Dominic E.; Fleming, Louise J.; Howarth, Peter H.; Sousa, Ana R.; Corfield, Julie; Auffray, Charles; De Meulder, Bertrand; Knowles, Richard; Sterk, Peter J.; Guo, Yike; Adcock, Ian M.; Djukanovic, Ratko; Fan Chung, Kian

Authors

Stelios Pavlidis

Kentaro Takahashi

Francois Ng Kee Kwong

Jiaxing Xie

Uruj Hoda

Kai Sun

Vahid Elyasigomari

Paul Agapow

Matthew Loza

Fred Baribaud

Pascal Chanez

Steve J. Fowler

Louise J. Fleming

Peter H. Howarth

Ana R. Sousa

Julie Corfield

Charles Auffray

Bertrand De Meulder

Richard Knowles

Peter J. Sterk

Yike Guo

Ian M. Adcock

Ratko Djukanovic

Kian Fan Chung



Abstract

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 the U-BIOPRED cohort.

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 interleukin (IL)-13-exposed AECs.

37% of asthmatics (45% nonsmoking 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 exhaled nitric oxide fraction (FeNO) and blood and sputum eosinophils, but not serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature. FeNO (≥30 ppb) and blood eosinophils (≥300 cells·µL−1) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression.

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.

Journal Article Type Article
Publication Date Jan 3, 2019
Journal European Respiratory Journal
Print ISSN 0903-1936
Electronic ISSN 1399-3003
Publisher European Respiratory Society
Peer Reviewed Peer Reviewed
Volume 53
Issue 1
Article Number 1800938
APA6 Citation Pavlidis, S., Takahashi, K., Ng Kee Kwong, F., Xie, J., Hoda, U., Sun, K., …Fan Chung, K. (2019). “T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin. European Respiratory Journal, 53(1), https://doi.org/10.1183/13993003.00938-2018
DOI https://doi.org/10.1183/13993003.00938-2018
Keywords Pulmonary and Respiratory Medicine
Publisher URL https://erj.ersjournals.com/content/53/1/1800938
Additional Information Stelios Pavlidis, Kentaro Takahashi, Francois Ng Kee Kwong, Jiaxing Xie, Uruj Hoda, Kai Sun, Vahid Elyasigomari, Paul Agapow, Matthew Loza, Fred Baribaud, Pascal Chanez, Steve J. Fowler, Dominic E. Shaw, Louise J. Fleming, Peter H. Howarth, Ana R. Sousa, Julie Corfield, Charles Auffray, Bertrand De Meulder, Richard Knowles, Peter J. Sterk, Yike Guo, Ian M. Adcock, Ratko Djukanovic, Kian Fan Chung, “T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin, European Respiratory Journal, Jan 2019, 53 (1) 1800938; DOI: 10.1183/13993003.00938-2018
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