In people hospitalized for a COPD flare, most mitochondrial peptides change, but the level of the peptide humanin (HN) stays the same compared to stable patients. However, higher-than‑average HN levels were linked to a greater chance of being readmitted to the hospital later.

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. A total of 51 consecutive patients admitted to our hospital for ECOPD were included and followed for 1&#xa0;year; in addition, 160 participants with stable COPD from our out-patient clinic were recruited as controls. Serum FGF-21 (<i>p</i> &lt; .001), MOTS-c (<i>p</i> &lt; .001) and Romo1 (<i>p</i> = .002) levels were lower, and GDF-15 (<i>p</i> &lt; .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, <i>p</i> &lt; .001) and GDF-15 (AUC 0.735, 95% CI 0.670-0.793, <i>p</i> &lt; .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, <i>p</i> &lt; .001). FGF-21 (AUC 0.700, 95% CI 0.633-0.761, <i>p</i> &lt; .001) and Romo1 (AUC 0.645 95% CI 0.573-0.712, <i>p</i> = .001) had lower diagnostic accuracy. HN levels did not differentiate patients with ECOPD versus stable COPD (<i>p</i> = .557). In Cox regression analysis, HN (HR 2.661, CI95% 1.009-7.016, <i>p</i> = .048) and MOTS-c (HR 3.441, CI95% 1.252-9.297, <i>p</i> = .016) levels exceeding mean levels were independent risk factors for re-admission. 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.