Department of Pulmonology, Hospital Universitario Marqués de Valdecilla, Av Valdecilla SN, 39005, Santander, Spain.
University of Cantabria, Santander, Spain.
Sci Rep. 2022 Oct 15;12(1):17315. doi: 10.1038/s41598-022-21757-5.
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.
线粒体衍生因子（人类素（HN）、GDF15 和 FGF21）是线粒体功能障碍的产物，可能在 COPD 患者的慢性炎症、营养不良和运动能力中发挥重要作用。除了 GDF15，这个领域的研究还很缺乏。共纳入了 165 名稳定期 COPD 患者和 49 名无 COPD 的吸烟者。我们在基线时评估了他们的血清线粒体衍生因子水平和临床特征。我们记录了接下来 12 个月的中度和重度恶化情况。COPD 组基线血清 HN（p=0.037）和 GDF-15（p=0.013）水平较高。高水平的 HN 与高风险的恶化（HRE）（OR 2.798，95%CI 1.266-6.187，p=0.011）、营养不良（OR 6.645，95%CI 1.859-23.749，p=0.004）和 6MWD（OR 0.995，95%CI 0.991-0.999，p=0.008）相关，并且与未来的中度（HR 1.826，95%CI 1.181-2.822，p=0.007）和重度恶化（HR 3.445，95%CI 1.357-8.740，p=0.009）相关。高水平的 GDF15 与 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）和 6MWT 中的低氧饱和度（OR 3.999，95%CI 1.487-10.757，p=0.006）相关。高水平的 FGF21 与 HRE（OR 2.144，95%CI 1.000-4.600，p=0.05）相关，并且预测未来的重度恶化（HR 4.217，95%CI 1.459-12.193，p=0.008）。COPD 患者的线粒体衍生因子水平高于无 COPD 的吸烟者，与重要的临床结局相关，如运动能力和 COPD 恶化。在这些线粒体衍生因子中，HN 与 COPD 的相关性最强，可能成为该疾病的未来风险生物标志物。试验注册号：NCT04449419。
