{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:36:20Z","timestamp":1788543380791,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0800649"],"award-info":[{"award-number":["G0800649"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0900453"],"award-info":[{"award-number":["G0900453"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>IL\u201013 is considered an archetypal T2 cytokine central to the clinical disease expression of asthma. The IL\u201013 response genes, which are upregulated in central airway bronchial epithelial of asthma patients, can be normalized by high\u2010dose inhaled steroid therapy in severe asthma. However, this is not the case within the peripheral airways. We have sought to further understand IL\u201013 in the peripheral airways in severe asthma through bronchoalveolar analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bronchoalveolar lavage samples were collected from 203 asthmatic and healthy volunteers, including 78 with severe asthma. Inflammatory mediators were measured using a multiple cytokine immunoassay platform. This analysis was replicated in a further 59 volunteers, in whom 16S rRNA analysis of BAL samples was undertaken by terminal restriction fragment length polymorphism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Severe asthma patients with high BAL IL\u201013, despite treatment with high\u2010dose inhaled corticosteroids, had more severe lung function and significantly higher BAL neutrophil percentages, but not BAL eosinophils than those with normal BAL\u201013 concentrations. This finding was replicated in the second cohort, which further associated BAL IL\u201013 and neutrophilia with a greater abundance of potentially pathogenic bacteria in the peripheral airways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings demonstrate a steroid unresponsive source of IL\u201013 that is associated with BAL neutrophilia and bacterial dysbiosis in severe asthma. Our findings highlight the biological complexity of severe asthma and the importance of a greater understanding of the innate and adaptive immune responses in the peripheral airways in this disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.14732","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T23:24:46Z","timestamp":1610321086000},"page":"2070-2078","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Peripheral airways type 2 inflammation, neutrophilia and microbial dysbiosis in severe asthma"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5960-1159","authenticated-orcid":false,"given":"Adnan","family":"Azim","sequence":"first","affiliation":[{"name":"Faculty of Medicine Academic Unit of Clinical and Experimental Sciences University of Southampton Southampton UK"},{"name":"NIHR Respiratory Biomedical Research Unit University Hospital 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