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This review proposes a novel \u201cpulmonary hypertensive phenotype\u201d hypothesis, suggesting that the permanent reduction of the pulmonary vascular bed after anatomical resection acts as the primary upstream driver of systemic vulnerability. While the ventilatory capacity may partially recover through enlargement of the airspace and compensatory remodeling, restoration of the pulmonary vascular bed is often incomplete. This deficit leads to a sustained right ventricular afterload and chronic endothelial stress. We integrated clinical and experimental evidence to suggest that this cardiopulmonary strain triggers systemic catabolic signaling, potentially mediated by factors such as GDF-15, which accelerates skeletal muscle proteolysis and attrition. This metabolic \u201cphase-shift\u201d can push patients beyond a critical threshold of vulnerability, increasing the risk of sarcopenia and non-cancer death. This could be particularly evident after extensive resections, such as pneumonectomy and lobectomy, compared with sublobar-sparing approaches. Ultimately, surgical invasiveness should be re-evaluated not only by lung volume loss but also by the preservation of the pulmonary vascular bed necessary to maintain systemic homeostasis. This framework provides a biologically plausible pathway linking the extent of resection to long-term systemic resilience and should be regarded as a conceptual integrative model that requires clinical validation.<\/jats:p>","DOI":"10.1007\/s00595-026-03336-7","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:55:09Z","timestamp":1780574109000},"page":"2111-2117","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The lung-muscle metabolic axis: a proposed mechanism for post-resection systemic frailty"],"prefix":"10.1007","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6865-0104","authenticated-orcid":false,"given":"Ichiro","family":"Yoshino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Saji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidemi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"3336_CR1","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1001\/jama.1933.02740430017005","volume":"101","author":"EA Graham","year":"1933","unstructured":"Graham EA, Singer J. 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