Nasal epithelial gene expression identifies relevant asthma endotypes in the ATLANTIS study.

Asthma is an inflammatory airways disease encompassing multiple phenotypes and endotypes. Several studies suggested gene expression in nasal epithelium to serve as a proxy for bronchial epithelium, being a non-invasive approach to investigate lung diseases. We hypothesised that molecular differences in upper airway epithelium reflect asthma-associated differences in the lower airways and are associated with clinical expression of asthma. We analysed nasal epithelial gene expression data from 369 patients with asthma and 58 non-asthmatic controls from the Assessment of Small Airways Involvement in Asthma study. Unsupervised hierarchical clustering was performed on asthma-associated genes. Asthma-associated gene signatures were replicated in independent cohorts with nasal and bronchial brushes data by comparing Gene Set Variation Analysis scores between asthma patients and non-asthmatic controls. We identified 67 higher expressed and 59 lower expressed genes in nasal epithelium from asthma patients compared with controls (false discovery rate<0.05), including Our results show that the nasal epithelial gene expression profile reflects asthma-related processes in the lower airways. We suggest that nasal epithelium may be a useful non-invasive tool to identify asthma endotypes and may advance personalised management of the disease.

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Competing interests: The ATLANTIS study is supported by Chiesi. MK has received grants or contracts or consulting fees or payment or honoraria or support for meetings from National Institutes of Health, American Lung Association, Synairgen, Janssen, Astra-Zeneca, Sanofi, Chiesi, GSK, Kinaset, Genentech, European Respiratory Society, has patents planned, issued or pending from CoFounder and Chief Medical Officer, RaeSedo, has participated on advisory boards for ALung DSMB and has received stock or stock options from Equity ownership in RaeSedo, and other financial or non-financial interests from Section Editor, UptoDate. MCN has received grants or contracts or support for meetings from Chan Zuckerberg Initiative, European commission, Lung Foundation Netherlands, Stichting Astma Bestrijding, Belgian Respiratory Society and has a leadership role in Lung Bionetwork of the Human Cell Atlas. IHH has received grants or contracts from Boehringer Ingelheim, Roche, Rousselot. BB has received payment or honoraria from AZ, GSK, Guidotti,Chiesi, Menarini. KFR has received payment or honoraria from Astra Zeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, Novartis, Sanofi & Regeneron, GlaxoSmithKline, Berlin Chemie, Roche Pharma, has participated in advisory boards for AstraZeneca, Boehringer Ingelheim, Sanofi & Regeneron, and has a leadership role in German Center for Lung Research (DZL), German Chest Society (DGP), American Thoracic Society (ATS). AP has received grants or contracts or consulting fees from Chiesi, AstraZeneca, GSK, Sanofi, Agenzia Italiana del farmaco (AIFA), Novartis,Avillion, ELPEN Pharmaceuticals, has received payment or honoraria from Chiesi, AstraZeneca, GSK, Menarini, Novartis, Zambon, Mundipharma, Sanofi, Edmond Pharma, IQVIA, Avillion, ELPEN Pharmaceuticals, has participated on Advisory Board for Chiesi, AstraZeneca, GSK, MSD, Novartis, Sanofi, IQVIA, Avillion, ELPEN Pharmaceuticals. CB has received grants or contracts or consulting fees from GSK, AZ, Sanofi, Regeneron, Roche, Genentech, BI, Chiesi, Novartis, Mologic, Areteia. DS has received consulting fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, EpiEndo, Genentech, GlaxoSmithKline, Glenmark, Gossamer Bio, Kinaset Therapeutics, Menarini, Novartis, Orion, Pulmatrix, Sanofi, Synairgen, Teva, Theravance Biopharma, Verona Pharma. TvdM has received payment or honoraria or support for attending meetings from GSK, Chiesi. SS has received consulting fees or payment or honoraria from Chiesi, Astra Zeneca, GSK, Areteia therapeutics, CSL Behring, AZ, Medscape. SC has received grants or contracts or consulting fees from NIH, American Lung Association, Sanofi, Regeneron, GlaxoSmithKline, AstraZeneca, Glenmark Pharmaceuticals, Amgen, Axon Advisors, and has received payment or honoraria from Sanofi/Regeneron, MJH Holdings: Physicians’ Education Resource, UpToDate, Wolters Kluwer Health, GlaxoSmithKline, has received support for attending meeting from AstraZeneca, GlaxoSmithKline, Sanofi/Regeneron, has participated on advisory boards for anofi/Regeneron, AstraZeneca, GlaxoSmithKline, and has leadership or fiduciary role in American Thoracic Society. MvdB has received grants or contracts from GlaxxoSmithKline, Astra Zeneca, Novartis, Genentech, Roche.