{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:35:34Z","timestamp":1786628134735,"version":"build-2736575974"},"reference-count":102,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Chronic obstructive pulmonary disease (COPD) disproportionately affects older adults. While targeted biologic therapies have shown efficacy in type 2 eosinophilic endotypes, elderly patients remain underrepresented in pivotal clinical trials. This narrative review examines the pathophysiological rationale, efficacy data, and unique geriatric challenges of biologic therapies in older adults. Methods: A literature search was conducted in PubMed and Scopus for phase II and III randomized controlled trials (RCTs) and observational studies evaluating biologic agents (anti-IL-5, anti-IL-4\/IL-13, and anti-alarmins) in COPD, focusing on populations aged \u2265 65 years, comorbidities, and frailty. Discussion: Phase III data for dupilumab and mepolizumab indicate significant reductions in annualized exacerbations in patients with blood eosinophils \u2265 300 cells\/\u03bcL. However, the mean age in the landmark trials (65 years) is a decade lower than the real-world average. Age-related immune remodeling\u2014specifically immunosenescence and inflammaging\u2014coexists with disease-specific pathways, potentially altering therapeutic responses. Furthermore, clinical trials systematically exclude older individuals with severe multimorbidity, physical frailty, cognitive impairment, and malnutrition. Conclusions: Biologics provide a precise, mechanism-based approach, yet evidence in the oldest-old remains limited. Future management should utilize the treatable traits framework, shifting selection criteria from chronological age to biological age metrics, including frailty status and functional reserve.<\/jats:p>","DOI":"10.3390\/jcm15166277","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T12:47:11Z","timestamp":1786625231000},"page":"6277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biologics in Older Adults with Chronic Obstructive Pulmonary Disease: A Narrative Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-2708","authenticated-orcid":false,"given":"Simone","family":"Scarlata","sequence":"first","affiliation":[{"name":"Unit of Respiratory Pathophysiology, Department of Internal Medicine and Geriatrics, Campus Bio Medico University and Teaching Hospital, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7779-7931","authenticated-orcid":false,"given":"Alessio","family":"Marinelli","sequence":"additional","affiliation":[{"name":"Institute of Respiratory Disease, Department of Traslational Biomedicine and Applied Neuroscience, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8608-9223","authenticated-orcid":false,"given":"Panaiotis","family":"Finamore","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Pathophysiology, Department of Internal Medicine and Geriatrics, Campus Bio Medico University and Teaching Hospital, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9920-780X","authenticated-orcid":false,"given":"Vitaliano Nicola","family":"Quaranta","sequence":"additional","affiliation":[{"name":"Institute of Respiratory Disease, Department of Traslational Biomedicine and Applied Neuroscience, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2770-6750","authenticated-orcid":false,"given":"Giulia","family":"Amoroso","sequence":"additional","affiliation":[{"name":"Institute of Respiratory Disease, Department of Traslational Biomedicine and Applied Neuroscience, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8508-7728","authenticated-orcid":false,"given":"Alessandra","family":"Tomasello","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, PROMISE Department, \u201cPaolo Giaccone\u201d University Hospital, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8306-3012","authenticated-orcid":false,"given":"Claudio","family":"Sorino","sequence":"additional","affiliation":[{"name":"Department of Pulmonology and Cardiorespiratory Rehabilitation, Sant\u2019Antonio Hospital, 22063 Cantu, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7931-4704","authenticated-orcid":false,"given":"Giovanna Elisiana","family":"Carpagnano","sequence":"additional","affiliation":[{"name":"Institute of Respiratory Disease, Department of Traslational Biomedicine and Applied Neuroscience, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6400-6573","authenticated-orcid":false,"given":"Nicola","family":"Scichilone","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, PROMISE Department, \u201cPaolo Giaccone\u201d University Hospital, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1563-6864","authenticated-orcid":false,"given":"Silvano","family":"Dragonieri","sequence":"additional","affiliation":[{"name":"Institute of Respiratory Disease, Department of Traslational Biomedicine and Applied Neuroscience, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","first-page":"101","article-title":"The global burden of COPD: Epidemiology and effect of tobacco control measures and treatments","volume":"13","author":"Celli","year":"2025","journal-title":"Lancet Respir. 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