Prospective study measuring serum humanin, FGF-21, GDF-15, MOTS-c, and Romo1 at hospital admission in COPD exacerbation patients, evaluating their diagnostic and prognostic value compared to CRP. Assesses whether mitochondrial peptides improve exacerbation severity assessment and outcome prediction in COPD. Establishes a multi-mitochondrial-peptide biomarker panel for COPD exacerbations—evaluating MOTS-c's contribution to exacerbation risk stratification in a disease where better biomarkers are needed for guiding intensity of treatment and predicting readmission.
Abstract
BACKGROUND: Chronic 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.
METHODS: A 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.
RESULTS: Serum FGF-21 (< .001), MOTS-c (< .001) and Romo1 (= .002) levels were lower, and GDF-15 (< .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,< .001) and GDF-15 (AUC 0.735, 95% CI 0.670-0.793,< .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,< .001). FGF-21 (AUC 0.700, 95% CI 0.633-0.761,< .001) and Romo1 (AUC 0.645 95% CI 0.573-0.712,= .001) had lower diagnostic accuracy. HN levels did not differentiate patients with ECOPD versus stable COPD (= .557). In Cox regression analysis, HN (HR 2.661, CI95% 1.009-7.016,= .048) and MOTS-c (HR 3.441, CI95% 1.252-9.297,= .016) levels exceeding mean levels were independent risk factors for re-admission.
CONCLUSIONS: Most 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.