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

Pavlidis, Stelios; Takahashi, Kentaro; Kwong, Francois Ng Kee; 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; Chung, Kian Fan

Abstract

Copyright ©ERS 2019. 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.

Citation

Pavlidis, S., Takahashi, K., Kwong, F. N. K., Xie, J., Hoda, U., Sun, K., …Chung, K. F. (2019). “T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin. European Respiratory Journal, 53(1), Article 1800938. https://doi.org/10.1183/13993003.00938-2018

• Journal Article Type: Article
• Acceptance Date: Oct 26, 2018
• Online Publication Date: Jan 3, 2019
• Publication Date: Jan 1, 2019
• Deposit Date: May 12, 2020
• 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
• DOI: https://doi.org/10.1183/13993003.00938-2018
• Keywords: Pulmonary and Respiratory Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/1856732
• 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