{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:56:11Z","timestamp":1793318171590,"version":"4.5.0"},"reference-count":89,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":905,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Regeneron Pharmaceuticals Inc."},{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004339","name":"Regeneron Pharmaceuticals Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous, progressive inflammatory airway disease associated with a significant impact on patients\u2019 lives, including morbidity and mortality, and significant healthcare costs. Current pharmacologic strategies, including first- and second-line therapies such as long-acting \u03b22-agonists, long-acting muscarinic antagonists, inhaled corticosteroids, phosphodiesterase-4 inhibitors, and macrolides, provide relief to patients with COPD. However, many patients remain symptomatic, with persistent symptoms and\/or acute exacerbations and progressive lung function loss. Although neutrophilic inflammation is the most common type of inflammation in COPD, 20\u201340% of patients with COPD exhibit type 2 inflammation, with roles for CD4+ (cluster of differentiation 4) T-helper cell type 1 cells, type 2 innate lymphoid cells, eosinophils, and alternatively activated macrophages. On the basis of the current limitations of available therapies, a significant unmet need exists in COPD management, including the need for targeted therapies to address the underlying pathophysiology leading to disease progression, such as type 2 inflammation, as well as biomarkers to help select the patients who would most benefit from the new therapies. Significant progress is being made, with evolving understanding of the pathobiology of COPD leading to novel therapeutic targets including epithelial alarmins. In this review, we describe the current therapeutic landscape in COPD, discuss unmet treatment needs, review the current knowledge of type 2 inflammation and epithelial alarmins in COPD, explore potential biomarkers of type 2 inflammation in COPD, and finally provide a rationale for incorporating therapies targeting type 2 inflammation and epithelial alarmins in COPD.<\/jats:p>\n                  <jats:p>Video Abstract available online at www.atsjournals.org.<\/jats:p>","DOI":"10.1164\/rccm.202303-0455ci","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T17:58:39Z","timestamp":1687456719000},"page":"395-405","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":134,"title":["Targeting Type 2 Inflammation and Epithelial Alarmins in Chronic Obstructive Pulmonary Disease: A Biologics Outlook"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7020-1401","authenticated-orcid":false,"given":"Klaus F.","family":"Rabe","sequence":"first","affiliation":[{"name":"LungenClinic Grosshansdorf, Grosshansdorf, Germany"},{"name":"Christian Albrechts University of Kiel, Kiel, Germany"},{"name":"Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Rennard","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando J.","family":"Martinez","sequence":"additional","affiliation":[{"name":"NewYork-Presbyterian Hospital\/Weill Cornell Medical Center, New York, New 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9993-2478","authenticated-orcid":false,"given":"Mona","family":"Bafadhel","sequence":"additional","affiliation":[{"name":"School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jigna","family":"Heble","sequence":"additional","affiliation":[{"name":"Sanofi, Bridgewater, New Jersey; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Radwan","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc., Tarrytown, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Soler","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc., Tarrytown, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juby A.","family":"Jacob 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