{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:09Z","timestamp":1792789089770,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Laboratory of Experimental Therapeutics, Faculty of Medicine, University of S\u00e3o Paulo","id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2018\/02537-5"],"award-info":[{"award-number":["2018\/02537-5"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2018\/02537-5"],"award-info":[{"award-number":["2018\/02537-5"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Asthma and chronic obstructive pulmonary disease (COPD) are distinct chronic airway diseases with different pathophysiological mechanisms, but they may coexist and share clinical, functional, inflammatory, and structural features. The historical terminology used to describe this coexistence has shifted away from the notion of a single overlap syndrome toward a traits-based framework, emphasizing coexisting clinical, functional, inflammatory, and structural features rather than a uniform disease entity. Within this context, neutrophil extracellular traps (NETs) are emerging as a potential mechanistic link between allergic airway inflammation, cigarette smoke injury, neutrophilic activation, mucus obstruction, and tissue remodeling. Animal models combining allergen exposure with cigarette smoke, lipopolysaccharide, infection, or elastase provide useful platforms to dissect specific components of the asthma-COPD interface. This review examines NET biology with a primary focus on animal models that reproduce overlapping asthma and COPD features, emphasizing how epithelial injury, oxidative stress, protease activity, neutrophilic inflammation, and inflammatory cytokine networks converge to promote NET formation. NETs, composed of extracellular deoxyribonucleic acid (DNA), citrullinated histone H3, myeloperoxidase, neutrophil elastase, and granular proteins, may amplify mucus viscosity, epithelial damage, innate immune activation, airway remodeling, emphysema-like injury, and persistent airflow limitation. Strategies to target this axis include deoxyribonuclease I (DNase I), peptidylarginine deiminase 4 (PAD4) inhibition, neutrophil elastase and myeloperoxidase blockade, antioxidant approaches, C-X-C motif chemokine receptor 2 (CXCR2) modulation, and interleukin-17 (IL-17) inhibition. These interventions act at distinct stages of neutrophil recruitment, NET formation, NET persistence, or NET-mediated tissue injury. A rigorous interpretation of these models requires precise terminology, multiparametric NET detection, and integration of lung mechanics, histology, inflammatory profiling, and structural outcomes. Targeting NETs may help shift preclinical research from broad overlap labels toward mechanism-driven therapeutic strategies for coexisting asthma and COPD features.<\/jats:p>","DOI":"10.3390\/cells15191769","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:12:42Z","timestamp":1790669562000},"page":"1769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil Extracellular Traps at the Asthma + COPD Interface: Mechanisms, Experimental Models, and Therapeutic Targeting"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7593-2481","authenticated-orcid":false,"given":"Leandro do Nascimento","family":"Camargo","sequence":"first","affiliation":[{"name":"Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"},{"name":"Servi\u00e7o de Reabilita\u00e7\u00e3o, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo 01308-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6234-1458","authenticated-orcid":false,"given":"Renato Fraga","family":"Righetti","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"},{"name":"Servi\u00e7o de Reabilita\u00e7\u00e3o, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo 01308-050, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5662-7895","authenticated-orcid":false,"given":"Iolanda de F\u00e1tima Lopes Calvo","family":"Tib\u00e9rio","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina FMUSP, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref_1","unstructured":"Global Initiative for Chronic Obstructive Lung Disease (GOLD) (2026). 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