{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:10:29Z","timestamp":1789582229149,"version":"build-2803163510"},"reference-count":38,"publisher":"European Respiratory Society (ERS)","issue":"4","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.ersjournals.com\/user-licence"}],"funder":[{"name":"Shipowner Per Henriksen, R. and Wife Foundation"},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2022,2,14]]},"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Severe eosinophilic asthma is characterised by frequent exacerbations and a relative insensitivity to steroids. Experimentally, smoking may induce eosinophilic airway inflammation, but the impact in patients with severe asthma is not clear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the association between smoking exposure in patients with severe asthma, and eosinophilic inflammation and activation, as well as airway autoimmunity and steroid responsiveness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with severe asthma according to European Respiratory Society\/American Thoracic Society criteria were assessed with sputum samples, analysed by cell differential count, and for the presence of free eosinophil granules (FEGs), autoantibodies against eosinophil peroxidase (EPX) and macrophage receptor with collagenous structure (MARCO). A subgroup of patients with eosinophilic airway inflammation was re-assessed after a 2-week course of prednisolone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>132 severe asthmatics were included in the study. 39 (29.5%) patients had \u226510\u2005pack-years of smoking history: 36 (27.3%) were former smokers and three (2.3%) current smokers; and 93 (70.5%) had &lt;10\u2005pack-years exposure. Eosinophilic airway inflammation was more prevalent among patients with \u226510\u2005pack-years (66.7%), compared to patients with &lt;10\u2005pack-years (38.7%, p=0.03), as was the level of FEGs (p=0.001) and both anti-EPX and anti-MARCO (p&lt;0.05 and p&lt;0.0001, respectively). Omitting current smokers did not affect these associations. Furthermore, prednisolone reduced, but did not normalise, sputum eosinophils in patients with a \u226510\u2005pack-year smoking history.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with severe asthma, a former smoking history is associated with eosinophilic airway inflammation and activation and relative insensitivity to steroids, as well as airway autoimmunity.<\/jats:p><\/jats:sec>","DOI":"10.1183\/13993003.02446-2021","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T16:55:53Z","timestamp":1646240153000},"page":"2102446","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Impact of former smoking exposure on airway eosinophilic activation and autoimmunity in patients with severe asthma"],"prefix":"10.1183","volume":"60","author":[{"given":"Ditte K.","family":"Klein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Silberbrandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurits","family":"Fr\u00f8ssing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7995-2965","authenticated-orcid":false,"given":"Morten","family":"Hvidtfeldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"von B\u00fclow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parameswaran","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-7211","authenticated-orcid":false,"given":"Manali","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste","family":"Porsbjerg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"2024102102535084000_60.4.2102446.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2011.03929.x"},{"key":"2024102102535084000_60.4.2102446.2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201107-1317PP"},{"key":"2024102102535084000_60.4.2102446.3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/cea.13966","article-title":"Airway gene expression identifies subtypes of type 2 inflammation in severe asthma","volume":"52","author":"Fr\u00f8ssing","year":"2022","journal-title":"Clin Exp Allergy"},{"key":"2024102102535084000_60.4.2102446.4","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1002\/eji.201444557","article-title":"Innate lymphoid cells in asthma: will they take your breath away?","volume":"46","author":"Kim","year":"2016","journal-title":"Eur J Immunol"},{"key":"2024102102535084000_60.4.2102446.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.02.008"},{"key":"2024102102535084000_60.4.2102446.6","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3049"},{"key":"2024102102535084000_60.4.2102446.7","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(91)90214-9"},{"key":"2024102102535084000_60.4.2102446.8","doi-asserted-by":"crossref","first-page":"428","DOI":"10.4168\/aair.2018.10.5.428","article-title":"Autoimmune responses in severe asthma","volume":"10","author":"Mukherjee","year":"2018","journal-title":"Allergy Asthma Immunol Res"},{"key":"2024102102535084000_60.4.2102446.9","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.jaci.2017.06.033","article-title":"Sputum autoantibodies in patients with severe eosinophilic asthma","volume":"141","author":"Mukherjee","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"2024102102535084000_60.4.2102446.10","doi-asserted-by":"crossref","first-page":"S216","DOI":"10.1016\/j.jaci.2006.12.216","article-title":"Does cigarette smoke modify eosinophil properties? 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