{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T14:21:51Z","timestamp":1782224511345,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1175134"],"award-info":[{"award-number":["1175134"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001775","name":"University of Technology Sydney","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001775","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Smoking disturbs the bronchial\u2010mucus\u2010barrier. This study assesses the cellular composition and gene expression shifts of the bronchial\u2010mucus\u2010barrier with smoking to understand the mechanism of mucosal damage by cigarette smoke exposure. We explore whether single\u2010cell\u2010RNA\u2010sequencing (scRNA\u2010seq) based cellular deconvolution (CD) can predict cell\u2010type composition in RNA\u2010seq data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RNA\u2010seq data of bronchial biopsies from three cohorts were analysed using CD. The cohorts included 56 participants with chronic obstructive pulmonary disease [COPD] (38 smokers; 18 ex\u2010smokers), 77 participants without COPD (40 never\u2010smokers; 37 smokers) and 16 participants who stopped smoking for 1\u2009year (11 COPD and 5 non\u2010COPD\u2010smokers). Differential gene expression was used to investigate gene expression shifts. The CD\u2010derived goblet cell ratios were validated by correlating with staining\u2010derived goblet cell ratios from the COPD cohort. Statistics were done in the R software (false discovery rate <jats:italic>p<\/jats:italic>\u2010value\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both CD methods indicate a shift in bronchial\u2010mucus\u2010barrier cell composition towards goblet cells in COPD and non\u2010COPD\u2010smokers compared to ex\u2010 and never\u2010smokers. It shows that the effect was reversible within a year of smoking cessation. A reduction of ciliated and basal cells was observed with current smoking, which resolved following smoking cessation. The expression of mucin and sodium channel (ENaC) genes, but not chloride channel genes, were altered in COPD and current smokers compared to never smokers or ex\u2010smokers. The goblet cell\u2010derived staining scores correlate with CD\u2010derived goblet cell ratios.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Smoking alters bronchial\u2010mucus\u2010barrier cell composition, transcriptome and increases mucus production. This effect is partly reversible within a year of smoking cessation. CD methodology can predict goblet\u2010cell percentages from RNA\u2010seq.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.14401","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T02:31:41Z","timestamp":1669170701000},"page":"132-142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Smoking induces shifts in cellular composition and transcriptome within the bronchial mucus barrier"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5631-7264","authenticated-orcid":false,"given":"Senani N. H.","family":"Rathnayake","sequence":"first","affiliation":[{"name":"University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences  Sydney New South Wales Australia"},{"name":"The University of Sydney, Respiratory Cellular and Molecular Biology (RCMB), Woolcock Institute of Medical Research  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Ditz","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5374-0609","authenticated-orcid":false,"given":"Jos","family":"van Nijnatten","sequence":"additional","affiliation":[{"name":"University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences  Sydney New South Wales Australia"},{"name":"University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD  Groningen the Netherlands"},{"name":"Department of Pathology &amp; Medical Biology University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayyaba","family":"Sadaf","sequence":"additional","affiliation":[{"name":"University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences  Sydney New South Wales Australia"},{"name":"Centre for Inflammation Centenary Institute, and the University of Technology Sydney, Faculty of Science  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4741-3035","authenticated-orcid":false,"given":"Philip M.","family":"Hansbro","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Centenary Institute, and the University of Technology Sydney, Faculty of Science  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corry A.","family":"Brandsma","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD  Groningen the Netherlands"},{"name":"Department of Pathology &amp; Medical Biology University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4146-6363","authenticated-orcid":false,"given":"Wim","family":"Timens","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD  Groningen the Netherlands"},{"name":"Department of Pathology &amp; Medical Biology University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie","family":"van Schadewijk","sequence":"additional","affiliation":[{"name":"Department of Pulmonology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0238-5982","authenticated-orcid":false,"given":"Peter S.","family":"Hiemstra","sequence":"additional","affiliation":[{"name":"Department of Pulmonology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick H. T.","family":"ten Hacken","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7122-9262","authenticated-orcid":false,"given":"Brian","family":"Oliver","sequence":"additional","affiliation":[{"name":"The University of Sydney, Respiratory Cellular and Molecular Biology (RCMB), Woolcock Institute of Medical Research  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7705-7927","authenticated-orcid":false,"given":"Huib A. 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