%0 Journal Article %A Stelios Pavlidis %A Kentaro Takahashi %A Francois Ng Kee Kwong %A Jiaxing Xie %A Uruj Hoda %A Kai Sun %A Vahid Elyasigomari %A Paul Agapow %A Matthew Loza %A Fred Baribaud %A Pascal Chanez %A Steve J Fowler %A Dominic E. Shaw %A Louise J. Fleming %A Peter H. Howarth %A Ana R Sousa %A Julie Corfield %A Charles Auffray %A Bertrand De Meulder %A Richard Knowles %A Peter J. Sterk %A Yike Guo %A Ian M. Adcock %A Ratko Djukanovic %A Kian Fan Chung %A , %T “T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin %D 2018 %R 10.1183/13993003.00938-2018 %J European Respiratory Journal %P 1800938 %X 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Pavlidis has nothing to disclose.Conflict of interest: Dr. Takahashi reports personal fees from Asahi General Hospital, during the conduct of the study.Conflict of interest: Dr. Xie has nothing to disclose.Conflict of interest: Dr. Hoda has nothing to disclose.Conflict of interest: Dr. Sun has nothing to disclose.Conflict of interest: Dr. Elyasigomari has nothing to disclose.Conflict of interest: Dr. Agapow has nothing to disclose.Conflict of interest: Dr. reports other from Janssen R&D, 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: PC had: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?Received industry-sponsored grants from Roche, Boston Scientific, Boehringer Ingelheim, Centocor, GlaxoSmithKline, AstraZeneca, ALK, Novartis, Teva, ABscience and ChiesiConflict of interest: Dr. Fowler reports grants from IMI, during the conduct of the study; personal fees from GlaxoSmithKline, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Novartis, outside the submitted work.Conflict of interest: Dr. Shaw reports personal fees from GSK, AZ, Teva, Boehringer Ingelheim, outside the submitted work.Conflict of interest: Dr. Fleming reports personal fees from Novartis, Vectura and Boeringher Ingelheim , grants from Asthma UK and BLF , personal fees from Novartis, outside the submitted work.Conflict of interest: Dr. Howarth reports grants from IMI, during the conduct of the study; personal fees from GSK, outside the submitted work.Conflict of interest: Dr. Sousa has nothing to disclose.Conflict of interest: Miss Corfield has nothing to disclose.Conflict of interest: Dr. Auffray reports grants from Innovative Medicine Initiative, during the conduct of the study.Conflict of interest: Dr. De Meulder reports grants from Innovative Medicine Initiative, during the conduct of the study.Conflict of interest: Dr. Knowles reports other from Knowles Consulting Ltd, outside the submitted work; and Former employee (to 2011) and current shareholder in GlaxoSmithKline Ltd.Conflict of interest: Dr. Sterk reports grants from Innovative Medicines Initiative (IMI), during the conduct of the study.Conflict of interest: Dr. Guo has nothing to disclose.Conflict of interest: Dr. Adcock reports personal fees from GSK, A-Z, Novartis, Boeringher Ingelheim and Vectura, grants from Pfizer, GSK, MRC, EU, BI and IMI, personal fees from AZ and BI, outside the submitted work.Conflict of interest: Dr. Djukanovic reports personal fees from TEVA, grants and personal fees from Novartis, and personal fees and other support from Synairgen outside the submitted work.Conflict of interest: Dr. Chung reports grants and personal fees from GlaxoSmithKline, personal fees from Astra-Zeneca, personal fees from Novartis, grants and personal fees from Merck, personal fees from Boehringer Ingelheim, personal fees from TEVA, personal fees from Menlo Therapeutics, outside the submitted work.Conflict of interest: Dr. Ng Kee Kwong has nothing to disclose. %U https://erj.ersjournals.com/content/erj/early/2018/11/01/13993003.00938-2018.full.pdf