{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:56:38Z","timestamp":1785761798684,"version":"3.56.0"},"reference-count":68,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Muscles"],"abstract":"<jats:p>Skeletal muscle dysfunction and exercise intolerance are major extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), yet their severity is not fully predicted by pulmonary impairment. This narrative review examines extracellular vesicles (EVs) as candidate mediators of lung\u2013muscle communication within a broader network of inflammatory, metabolic, vascular, nutritional, and inactivity-related mechanisms. The evidence is asymmetrical. COPD provides direct human skeletal muscle evidence for quadriceps microRNA dysregulation, impaired protein synthesis and mitochondrial function, oxidative stress, and abnormalities of the regenerative microvascular niche; however, none of these observations demonstrates delivery of pathogenic cargo from the lung by EVs. In IPF, EV-mediated epithelial\u2013mesenchymal signalling, fibroblast activation, and profibrotic remodelling are well supported within the lung, whereas skeletal muscle effects remain indirect. Accordingly, the lung\u2013muscle EV axis should be viewed as a biologically plausible, evidence-weighted hypothesis rather than an established causal pathway. Progress will require experiments that identify the cellular source of EVs, trace their vascular transit and skeletal muscle uptake, and demonstrate functional cargo transfer using EV-depletion, rescue, and integrated muscle readouts. Conventional size and morphology measurements do not reliably distinguish muscle- from lung-derived EVs; source discrimination currently depends more on molecular cargo and cell-associated markers. Hypoxia and transient or sustained oxygen desaturation may modify EV release and cargo through HIF- and redox-sensitive signalling, but disease-specific evidence connecting these changes to lung-to-muscle transfer in COPD or IPF remains limited.<\/jats:p>","DOI":"10.3390\/muscles5030055","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:50:21Z","timestamp":1785757821000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Skeletal Muscle Dysfunction and Exercise Intolerance in COPD and Idiopathic Pulmonary Fibrosis: Extracellular Vesicles as Candidate Mediators of a Lung\u2013Muscle Axis"],"prefix":"10.3390","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7416-7765","authenticated-orcid":false,"given":"Georgios I.","family":"Barkas","sequence":"first","affiliation":[{"name":"Laboratory of Human Pathophysiology, Department of Nursing, School of Health Sciences, University of Thessaly, 41500 Larissa, Greece"},{"name":"Department of Respiratory Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1058-9125","authenticated-orcid":false,"given":"Zoe","family":"Daniil","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5219-6971","authenticated-orcid":false,"given":"Ourania S.","family":"Kotsiou","sequence":"additional","affiliation":[{"name":"Laboratory of Human Pathophysiology, Department of Nursing, School of Health Sciences, University of Thessaly, 41500 Larissa, Greece"},{"name":"Department of Respiratory Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/jcsm.12062","article-title":"Cachexia in chronic obstructive pulmonary disease: New insights and therapeutic perspective","volume":"7","author":"Sanders","year":"2016","journal-title":"J. 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