{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:28Z","timestamp":1787029288564,"version":"build-2736575974"},"reference-count":92,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T00:00:00Z","timestamp":1755993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objetives: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Nutritional disorders, particularly cachexia, significantly impact morbidity and mortality in IPF but remain under-investigated. This study aimed to characterize cachexia phenotypes in IPF through morphofunctional assessment (MFA) and to evaluate their prognostic relevance, including the role of mitochondrial biomarkers. Methods: In this prospective bicenter study, 85 IPF patients underwent MFA including bioelectrical impedance vector analysis (BIVA), nutritional ultrasound (NU), and T12-level computed tomography (T12-CT) for body composition. Functional and strength assessments included timed up and go test (TUG) and handgrip strength (HGS), respectively. Cachexia was defined by Evans\u2019 criteria, Martin\u2019s CT-based criteria, and our IPF-specific proposed definition. Serum GDF-15 and PGC-1\u03b1 levels were also measured. Results: Cachexia prevalence varied by definition: 24.71% (Evans), 29.5% (Martin) and 42.4% (IPF Cachexia Syndrome). Cachectic patients showed significantly lower muscle mass, function, and quality (measured by reduced muscle attenuation at T12-CT), along with higher GDF-15 and lower PGC-1\u03b1 levels. The presence of IPF Cachexia syndrome (HR 2.56; 95% CI, 1.08\u20136.07; p = 0.033), GDF-15 &gt; 4412.0 pg\/mL (HR 3.21; 95% CI, 1.04\u20139.90; p = 0.042) and impaired TUG (&gt;8 s) (HR 3.77; 95% CI, 1.63\u20138.71; 0.002) were all independently associated with increased 24-month mortality. Conclusions: Cachexia is prevalent in IPF and showed strong concordance between the three diagnostic criteria. The IPF Cachexia syndrome, based on comprehensive morphofunctional phenotyping, demonstrated superior discriminatory capacity. The addition of mitochondrial biomarkers may improve early detection and support personalized interventions to improve patient outcomes.<\/jats:p>","DOI":"10.3390\/nu17172739","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:09:32Z","timestamp":1756080572000},"page":"2739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cachexia Phenotyping Through Morphofunctional Assessment and Mitocondrial Biomarkers (GDF-15 and PGC-1\u03b1) in Idiopathic Pulmonary Fibrosis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0569-6842","authenticated-orcid":false,"given":"Alicia","family":"Sanmart\u00edn-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Nutrition, Son Espases University Hospital, 07120 Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7469-5488","authenticated-orcid":false,"given":"Roc\u00edo","family":"Fern\u00e1ndez-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Malaga, Spain"},{"name":"Department of Medicine and Dermatology, M\u00e1laga University, 29016 Malaga, Spain"},{"name":"Department of Endocrinology and Nutrition, Quironsalud M\u00e1laga Hospital, Av. Imperio Argentina, 29004 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefina","family":"Olivares-Alcolea","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Son Espases University Hospital, 07120 Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Cabrera-C\u00e9sar","sequence":"additional","affiliation":[{"name":"Department of Neumology, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Esp\u00edldora-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Neumology, Regional University Hospital, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Vegas-Aguilar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda del Mar","family":"Amaya-Campos","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3896-7992","authenticated-orcid":false,"given":"V\u00edctor Jos\u00e9","family":"Sim\u00f3n-Frapolli","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Malaga, Spain"},{"name":"Department of Medicine and Dermatology, M\u00e1laga University, 29016 Malaga, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Carlos III Health Institute (ISCIII), University of M\u00e1laga, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Villaplana-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Son Espases University Hospital, 07120 Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8664-8697","authenticated-orcid":false,"given":"Isabel","family":"Cornejo-Pareja","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Heart Area, Victoria Virgen University Hospital, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"S\u00e1nchez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6482-192X","authenticated-orcid":false,"given":"Mora","family":"Murri","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Heart Area, Victoria Virgen University Hospital, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8473-4279","authenticated-orcid":false,"given":"Patricia","family":"Guirado-Pel\u00e1ez","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3667-4678","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Vidal-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Garrido-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Malaga, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Carlos III Health Institute (ISCIII), University of M\u00e1laga, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Tinahones","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Malaga, Spain"},{"name":"Department of Medicine and Dermatology, M\u00e1laga University, 29016 Malaga, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Carlos III Health Institute (ISCIII), University of M\u00e1laga, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Velasco-Garrido","sequence":"additional","affiliation":[{"name":"Department of Neumology, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8570-184X","authenticated-orcid":false,"given":"Jose Manuel","family":"Garc\u00eda-Almeida","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Malaga, Spain"},{"name":"Department of Medicine and Dermatology, M\u00e1laga University, 29016 Malaga, Spain"},{"name":"Department of Endocrinology and Nutrition, Quironsalud M\u00e1laga Hospital, Av. Imperio Argentina, 29004 Malaga, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Carlos III Health Institute (ISCIII), University of M\u00e1laga, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1056\/NEJMra1705751","article-title":"Idiopathic Pulmonary Fibrosis","volume":"378","author":"Lederer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1164\/rccm.2009-040GL","article-title":"An Official ATS\/ERS\/JRS\/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management","volume":"183","author":"Raghu","year":"2011","journal-title":"Am. J. Respir. Crit. 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