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.
Abstract
T2-high was found in 45% of nonsmoking and 33% of smoking/ex-smoking severe asthma and 28% of mild–moderate asthma. This can be predicted from raised levels of nitric oxide in exhaled breath, blood and sputum eosinophil counts, but not from serum periostin. http://ow.ly/Zsq630myR9t
Footnotes
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Conflict of interest: S. Pavlidis has nothing to disclose.
Conflict of interest: K. Takahashi reports personal fees from Asahi General Hospital, during the conduct of the study.
Conflict of interest: F. Ng Kee Kwong has nothing to disclose.
Conflict of interest: J. Xie has nothing to disclose.
Conflict of interest: U. Hoda has nothing to disclose.
Conflict of interest: K. Sun has nothing to disclose.
Conflict of interest: V. Elyasigomari has nothing to disclose.
Conflict of interest: P. Agapow has nothing to disclose.
Conflict of interest: M. Loza is employed by Janssen R&D and owns stock in parent company Johnson & Johnson, outside the submitted work.
Conflict of interest: F. Baribaud reports being an employee of Janssen R&D and being a share holder of Johnson & Johnson.
Conflict of interest: P. Chanez has provided consultancy services for Boehringer Ingelheim, Johnson & Johnson, GlaxoSmithKline, Merck Sharp & Dohme, AstraZeneca, Novartis, Teva, Chiesi, Sanofi and SNCF; served on advisory boards for Almirall, Boehringer Ingelheim, Johnson & Johnson, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi and Sanofi; received lecture fees from Boehringer Ingelheim, Centocor, GlaxoSmithKline, AstraZeneca, Novartis, Teva, Chiesi, Boston Scientific and ALK; and received industry-sponsored grants from Roche, Boston Scientific, Boehringer Ingelheim, Centocor, GlaxoSmithKline, AstraZeneca, ALK, Novartis, Teva, ABscience and Chiesi.
Conflict of interest: S.J. Fowler reports grants from IMI, during the conduct of the study; personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim and Novartis, outside the submitted work.
Conflict of interest: D.E. Shaw reports personal fees for advisory board work from GSK, AZ, Teva and Boehringer Ingelheim, outside the submitted work.
Conflict of interest: L.J. Fleming reports personal fees for advisory board work from Novartis, Vectura and Boehringer Ingelheim, grants from Asthma UK and BLF, and personal fees for speaking engagements from Novartis, outside the submitted work.
Conflict of interest: P.H. Howarth reports grants from IMI, during the conduct of the study; part-time employment by GSK as Global Medical Expert, outside the submitted work.
Conflict of interest: A.R. Sousa has nothing to disclose.
Conflict of interest: J. Corfield has nothing to disclose.
Conflict of interest: C. Auffray reports grants (U-BIOPRED Consortium IMI number 115010) from Innovative Medicine Initiative, during the conduct of the study.
Conflict of interest: B. De Meulder reports grants (U-BIOPRED Consortium IMI number 115010) from Innovative Medicine Initiative, during the conduct of the study.
Conflict of interest: R. Knowles is an employee of Knowles Consulting Ltd, outside the submitted work; and is a former employee (to 2011) and current shareholder in GlaxoSmithKline Ltd, and drug discovery consultant for Knowles Consulting Ltd, Peptinnovate Ltd and Imperial College London.
Conflict of interest: P.J. Sterk reports grants from Innovative Medicines Initiative (IMI), during the conduct of the study.
Conflict of interest: Y. Guo has nothing to disclose.
Conflict of interest: I.M. Adcock reports personal fees for advisory board work from GSK, A-Z, Novartis, Boehringer Ingelheim and Vectura, grants from Pfizer, GSK, MRC, EU, BI and IMI, and personal fees for speaking from AZ and BI, outside the submitted work.
Conflict of interest: R. Djukanovic reports personal fees for lectures at company sponsored symposia and consulting on advisory boards from TEVA, grants and personal fees for lectures at company sponsored symposia and consulting on advisory boards from Novartis, and personal fees for consultancy from and hold shares in Synairgen, outside the submitted work.
Conflict of interest: K.F. Chung reports grants and personal fees for advisory board work from GlaxoSmithKline, personal fees for advisory board work and speaking from AstraZeneca and Novartis, grants and personal fees for advisory board work and speaking from Merck, and personal fees for advisory board work from Boehringer Ingelheim, TEVA and Menlo Therapeutics, outside the submitted work.
Support statement: This study was funded by Innovative Medicine Initiative, grant agreement 115010. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received May 18, 2018.
- Accepted October 26, 2018.
- Copyright ©ERS 2019