Journal Article

Cachexia Phenotyping Through Morphofunctional Assessment and Mitocondrial Biomarkers (GDF-15 and PGC-1α) in Idiopathic Pulmonary Fibrosis

Murri, Mora, Amaya-Campos, María del Mar, Olivares-Alcolea, Josefina, Vidal-Suárez, Álvaro, Vegas-Aguilar, Isabel, Espíldora-Hernández, Francisco, Sánchez-García, Ana, Tinahones, Francisco J., Villaplana-García, María, Sanmartín-Sánchez, Alicia, Cornejo-Pareja, Isabel, García-Almeida, Jose Manuel, Garrido-Sánchez, Lourdes, Cabrera-César, Eva, Simón-Frapolli, Víctor José, Velasco-Garrido, Jose Luis, Fernández-Jiménez, Rocío, Guirado-Peláez, Patricia

2025

Overview

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’ criteria, Martin’s CT-based criteria, and our IPF-specific proposed definition. Serum GDF-15 and PGC-1α 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-1α levels. The presence of IPF Cachexia syndrome (HR 2.56; 95% CI, 1.08–6.07; p = 0.033), GDF-15 > 4412.0 pg/mL (HR 3.21; 95% CI, 1.04–9.90; p = 0.042) and impaired TUG (>8 s) (HR 3.77; 95% CI, 1.63–8.71; 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.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Aged / Analysis / Biological markers / Biomarkers / Biomarkers - blood / Body Composition / Body fat / Cachexia / Cachexia - blood / Cachexia - diagnosis / Cachexia - etiology / Cachexia - physiopathology / Chronic illnesses / Chronic obstructive pulmonary disease / CT imaging / Cytokines / Development and progression / Female / Growth Differentiation Factor 15 - blood / Hand Strength / Health aspects / Humans / Idiopathic Pulmonary Fibrosis - blood / Idiopathic Pulmonary Fibrosis - complications / Idiopathic Pulmonary Fibrosis - physiopathology / Inflammation / Lung diseases / Male / Medical prognosis / Medical research / Medicine, Experimental / Metabolism / Middle Aged / Mitochondria - metabolism / Mortality / Muscle strength / Musculoskeletal system / Patients / Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - blood / Phenotype / Physiological aspects / Prognosis / Prospective Studies / Pulmonary fibrosis / Sarcopenia / Spain / Tumor necrosis factor-TNF / Ultrasonic imaging / Womens health