Associations between serum mitokine levels and outcomes in stable COPD: an observational prospective study

Carlos A Amado, Paula Martín-Audera, Juan Agüero, Bernardo A Lavín, Armando R Guerra, Pedro Muñoz, Ana Berja, Ciro Casanova, Mayte García-Unzueta, Carlos A Amado, Paula Martín-Audera, Juan Agüero, Bernardo A Lavín, Armando R Guerra, Pedro Muñoz, Ana Berja, Ciro Casanova, Mayte García-Unzueta

Abstract

Mitokines (Humanin (HN), GDF15 and FGF21) are produced as a result of mitochondrial dysfunction and may have major roles in chronic inflammation, malnutrition and exercise capacity in people with COPD. Except for GDF15, studies on this subject are lacking. A total of 165 patients with stable COPD and 49 smokers without COPD were enrolled. We assessed their serum mitokine levels and clinical characteristics at baseline. We recorded moderate and severe exacerbation for the next 12 months. Baseline serum HN (p = 0.037) and GDF-15 (p = 0.013) levels were higher in the COPD group. High HN levels were independently associated with a high risk of exacerbation (HRE) (OR 2.798, 95% CI 1.266-6.187, p = 0.011), malnutrition (OR 6.645, 95% CI 1.859-23.749, p = 0.004), and 6MWD (OR 0.995, 95% CI 0.991-0.999, p = 0.008), and future moderate (HR 1.826, 95% CI 1.181-2.822, p = 0.007) and severe exacerbations (HR 3.445, 95% CI 1.357-8.740, p = 0.009). High GDF15 levels were associated with HRE (OR 3.028, 95% CI 1.134-8.083, p = 0.027), 6MWD (OR 0.995, 95% CI 0.990-0.999, p = 0.017) and predicted desaturation in 6MWT (OR 3.999, 95% CI 1.487-10.757, p = 0.006). High FGF21 levels were associated with HRE (OR 2.144, 95% CI 1.000-4.600, p = 0.05), and predicted future severe exacerbation (HR 4.217, 95% CI 1.459-12.193, p = 0.008). The mitokine levels were higher in patients with COPD than smokers without COPD, and were associated with important clinical outcomes such as exercise capacity and COPD exacerbation. Among the mitokines, HN showed the strongest association with COPD and may serve as a future risk biomarker in this disease.Trial registation NCT04449419.

Conflict of interest statement

Partially funded by GlaxoSmithKline. Carlos Amado has received speaker or consulting fees from Boehringer Ingelheim, Pfizer, AstraZeneca, Novartis, Chiesi, Faes Farma, Esteve and GlaxoSmithKline. Ciro Casanova has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, and research grants from GlaxoSmithKline, Menarini and AstraZeneca. The rest of the authors do not have any conflict of interest.

© 2022. The Author(s).

Figures

Figure 1
Figure 1
Flowchart for patient selection.
Figure 2
Figure 2
Serum HN levels as predictors of moderate COPD exacerbations.
Figure 3
Figure 3
High serum humanin levels (higher than the median) as predictors of severe COPD exacerbations.

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