Nutrients, Vol. 17, Pages 2739: Cachexia Phenotyping Through Morphofunctional Assessment and Mitocondrial Biomarkers (GDF-15 and PGC-1α) in Idiopathic Pulmonary Fibrosis

Nutrients, Vol. 17, Pages 2739: Cachexia Phenotyping Through Morphofunctional Assessment and Mitocondrial Biomarkers (GDF-15 and PGC-1α) in Idiopathic Pulmonary Fibrosis

Nutrients doi: 10.3390/nu17172739

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

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.

​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. Read More

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