{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:54:04Z","timestamp":1787806444489,"version":"build-2784847793"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000362","name":"Asthma and Lung UK","doi-asserted-by":"publisher","award":["WADR22\\100015"],"award-info":[{"award-number":["WADR22\\100015"]}],"id":[{"id":"10.13039\/501100000362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]},{"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"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease\u2010related genes and disease\u2010related alterations in ICS responsiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Randomized open\u2010label bronchoscopy study of high\u2010dose ICS therapy in 30 healthy adult volunteers randomized 2:1 to (i) fluticasone propionate 500 mcg bd daily or (ii) no treatment, for 4\u2009weeks. Laboratory staff were blinded to allocation. Biopsies and brushings were analysed by immunohistochemistry, bulk RNA sequencing, DNA methylation array and metagenomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ICS induced small between\u2010group differences in blood and lamina propria eosinophil numbers, but not in other immunopathological features, blood neutrophils, FeNO, FEV\n                      <jats:sub>1<\/jats:sub>\n                      , microbiome or DNA methylation. ICS treatment upregulated 72 genes in brushings and 53 genes in biopsies, and downregulated 82 genes in brushings and 416 genes in biopsies. The most downregulated genes in both tissues were canonical markers of type\u20102 inflammation (FCER1A, CPA3, IL33, CLEC10A, SERPINB10 and CCR5), T cell\u2010mediated adaptive immunity (TARP, TRBC1, TRBC2, PTPN22, TRAC, CD2, CD8A, HLA\u2010DQB2, CD96, PTPN7), B\u2010cell immunity (CD20, immunoglobulin heavy and light chains) and innate immunity, including CD48, Hobit, RANTES, Langerin and GFI1. An IL\u201017\u2010dependent gene signature was not upregulated by ICS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In healthy airways, 4\u2010week ICS exposure reduces gene expression related to both innate and adaptive immunity, and reduces markers of type\u20102 inflammation. This implies that homeostasis in health involves tonic type\u20102 signalling in the airway mucosa, which is exquisitely sensitive to ICS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.16146","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T03:50:04Z","timestamp":1714449004000},"page":"1831-1843","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The effects of inhaled corticosteroids on healthy airways"],"prefix":"10.1111","volume":"79","author":[{"given":"Emanuele","family":"Marchi","sequence":"first","affiliation":[{"name":"NIHR Oxford Respiratory BRC and Respiratory Medicine Unit, Experimental Medicine, Nuffield Department of Medicine John Radcliffe Hospital  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0699-2373","authenticated-orcid":false,"given":"Timothy S. 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Leong Centre for Healthy Aging, Department of Medical Genetics University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences University of Leicester, Leicester Respiratory NIHR BRC, Glenfield Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan S.","family":"Mar","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Arron","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Choy","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  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