{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:03:22Z","timestamp":1791864202473,"version":"4.3.4"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["211050\/Z\/18\/z"],"award-info":[{"award-number":["211050\/Z\/18\/z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Severe asthma is a heterogeneous disease. The mechanisms driving airway pathology when type 2 (T2) cytokine activity is suppressed remain poorly understood. This study aimed to provide insight by identifying the airway molecular pathways of T2 biomarker\u2010high and \u2010low severe asthma. We analysed clinical and transcriptomic data from bronchial biopsies and brushes in the UK Refractory Asthma Stratification Programme multi\u2010centre severe asthma cohort (18 corticosteroid\u2010resistant T2 biomarker\u2010high [T2\u2010high], 23 T2 biomarker\u2010intermediate [T2\u2010intermediate], 11 T2 biomarker\u2010low [T2\u2010low]) plus 20 healthy controls pre\u2010 and post\u2010treatment with high\u2010dose inhaled corticosteroids (ICS). Many genes dysregulated in asthma vs. health were concordantly dysregulated in healthy subjects receiving ICS. Severe asthma as a whole, independent of confounding by ICS, was characterised by upregulation of mucins,\n                    <jats:italic>CEACAM5<\/jats:italic>\n                    , typical T2\u2010genes (\n                    <jats:italic>POSTN<\/jats:italic>\n                    ,\n                    <jats:italic>CLCA1, CCL26<\/jats:italic>\n                    ), epithelial mast cell genes, and\n                    <jats:italic>CPA4<\/jats:italic>\n                    . T2\u2010high severe asthma demonstrated upregulated T2\u2010dependent genes, epithelial barrier and keratin genes, adaptive immune responses, and impaired ciliary function. T2\u2010low asthma showed upregulated Th1\u2010 and IL\u201017\u2010associated genes (\n                    <jats:italic>IDO1<\/jats:italic>\n                    ,\n                    <jats:italic>CXCL10<\/jats:italic>\n                    ,\n                    <jats:italic>GBP1<\/jats:italic>\n                    ,\n                    <jats:italic>LAG3<\/jats:italic>\n                    ), interferon\u2010\u03b3 signalling, neuroimmune pathways, airway smooth muscle\u2010related genes, and neutrophil enrichment. T2\u2010intermediate asthma exhibited a mixed molecular profile sharing features of T2\u2010high and T2\u2010low endotypes, with selective expression of the pathogen defence and antiviral response genes. The results were validated using bronchoscopy data from the U\u2010BIOPRED Consortium. This study defines airway molecular endotypes of severe asthma associated with T2 biomarker high and low phenotypes, independent of corticosteroid effects. These findings offer insights for severe asthma management and the development of targeted biologic therapies.\n                  <\/jats:p>","DOI":"10.1111\/all.70441","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:02:49Z","timestamp":1784534569000},"page":"3300-3317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Airway Transcriptome in Type 2 Cytokine Biomarker\u2010High and \u2010Low Severe Asthma"],"prefix":"10.1111","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0176-0274","authenticated-orcid":false,"given":"Jiashu","family":"Shen","sequence":"first","affiliation":[{"name":"NIHR Oxford Respiratory BRC, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rekha","family":"Chaudhuri","sequence":"additional","affiliation":[{"name":"Gartnavel General Hospital, Glasgow, and Institute of Infection&amp; 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