{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:58:23Z","timestamp":1791381503511,"version":"4.3.3"},"reference-count":55,"publisher":"BioExcel","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["DIC"],"abstract":"<jats:p>The management of chronic obstructive lung diseases, particularly severe asthma, chronic obstructive pulmonary disease (COPD) and non-cystic fibrosis bronchiectasis, is complicated by frequent overlap syndromes such as asthma\u2013bronchiectasis overlap and bronchiectasis\u2013 COPD overlap syndrome. These overlapping phenotypes are characterized by severe symptoms, frequent exacerbations, accelerated lung function decline and increased mortality, driven by a common, destructive endotype: persistent, neutrophil-dominant airway inflammation. This inflammation is fuelled by the overactivity of neutrophil serine proteases, notably neutrophil elastase, which drives the self-perpetuating \u2018vicious vortex\u2019 of structural damage and infection. Traditional therapies, including inhaled corticosteroids and type 2 (T2) inflammation-targeted biologics, are often ineffective against this non-T2, neutrophilic inflammation. Brensocatib, a first-in-class, oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), offers a novel, targeted strategy. By inhibiting DPP1 \u2014 the master activator of neutrophil serine proteases in the bone marrow \u2014 brensocatib effectively \u2018disarms\u2019 neutrophils before they reach the lungs. The phase III ASPEN trial in non-cystic fibrosis bronchiectasis demonstrated its disease-modifying potential, showing a significant reduction in the annualized rate of exacerbations and, critically, a statistically significant slowing of the decline in forced expiratory volume in 1 second in the 25 mg arm (a benefit not observed with the 10 mg dose). Subgroup analysis confirmed consistent efficacy in the high-risk bronchiectasis\u2013COPD overlap syndrome population. These findings validate DPP1 inhibition as a first potential disease-modifying therapy. This strategy is poised to fundamentally shift clinical focus from symptom control to the preservation of lung function for patients with severe, neutrophilic-driven neutrophilic overlap syndromes.\n\nDownload the Plain Language Summary of this article: https:\/\/www.drugsincontext.com\/plain-language-summaries\/plain-language-summary-the-convergent-pathway-of-obstructive-lung-disease-the-disease-modifying-potential-of-dipeptidyl-peptidase-1-inhibition-in- copd-asthma-and-bronchiectasis-overlap<\/jats:p>","DOI":"10.7573\/dic.2025-11-3","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T13:41:16Z","timestamp":1769694076000},"page":"1","source":"Crossref","is-referenced-by-count":1,"title":["The convergent pathway of obstructive lung disease: the disease-modifying potential of dipeptidyl peptidase 1 inhibition in COPD, asthma and bronchiectasis overlap"],"prefix":"10.7573","author":[{"given":"Francesco","family":"Menzella","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00vj45j81","id-type":"ROR","asserted-by":"publisher"}],"name":"AULSS 2 Marca Trevigiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Cottini","sequence":"additional","affiliation":[{"name":"Allergy and Pneumology Outpatient Clinic, Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Fondazione Poliambulanza, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Chan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03h2bxq36","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Dundee"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10047","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"1.\tSobala R, De Soyza A. 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