Alterations in circulating mitochondrial signals at hospital admission for COPD exacerbation

Autores de IDIVAL

• 

  Carlos Antonio Amado Diago

  Autor

• Paula Martín Audera

  Autor

• Juan Agüero Calvo

  Autor

• Diego Jose Ferrer Pargada

  Autor

• Maria De Begoña Josa Laorden

  Autor

• Daymara Bouclé Tirador

  Autor

• Ana Berja Miguel

  Autor

• 

  Bernardo Alio Lavín Gómez

  Autor

• 

  Armando Raul Guerra Ruiz

  Autor

• Cristina Ghadban Garrido

  Autor

• 

  Pedro Muñoz Cacho

  Autor

Autores ajenos al IDIVAL

• Garcia-Unzueta, M

Unidades

• INVESTIGACIÓN CARDIOVASCULAR

  

  Investigador Responsable

  José María De La Torre Hernández

• PSIQUIATRÍA Y SALUD MENTAL

  

  Investigador Responsable

  Javier Vázquez Bourgon

• SALUD COMUNITARIA

  

  Investigador Responsable

  Pedro Muñoz Cacho

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) exacerbation (ECOPD) alters the natural course of the disease. To date, only C-reactive protein has been used as a biomarker in ECOPD, but it has important limitations. The mitochondria release peptides (Humanin (HN), FGF-21, GDF-15, MOTS-c and Romo1) under certain metabolic conditions. Here, we aimed to evaluate the pathophysiologic, diagnostic and prognostic value of measuring serum mitochondrial peptides at hospital admission in patients with ECOPD.MethodsA total of 51 consecutive patients admitted to our hospital for ECOPD were included and followed for 1 year; in addition, 160 participants with stable COPD from our out-patient clinic were recruited as controls.ResultsSerum FGF-21 (p < .001), MOTS-c (p < .001) and Romo1 (p = .002) levels were lower, and GDF-15 (p < .001) levels were higher, in patients with ECOPD than stable COPD, but no differences were found in HN. In receiver operating characteristic analysis, MOTS-c (AUC 0.744, 95% CI 0.679-0.802, p < .001) and GDF-15 (AUC 0.735, 95% CI 0.670-0.793, p < .001) had the best diagnostic power for ECOPD, with a diagnostic accuracy similar to that of C-RP (AUC 0.796 95% IC 0.735-0.848, p < .001). FGF-21 (AUC 0.700, 95% CI 0.633-0.761, p < .001) and Romo1 (AUC 0.645 95% CI 0.573-0.712, p = .001) had lower diagnostic accuracy. HN levels did not differentiate patients with ECOPD versus stable COPD (p = .557). In Cox regression analysis, HN (HR 2.661, CI95% 1.009-7.016, p = .048) and MOTS-c (HR 3.441, CI95% 1.252-9.297, p = .016) levels exceeding mean levels were independent risk factors for re-admission.ConclusionsMost mitochondrial peptides are altered in ECOPD, as compared with stable COPD. MOTS-c and GDF15 levels have a diagnostic accuracy similar to C-RP for ECOPD. HN and MOTS-c independently predict future re-hospitalization.

Keywords

• COPD; MOTS-c; humanin; FGF-21; GDF-15; Romo1 mitochondria; exacerbation