Dept of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway
Dept of Clinical Science, University of Bergen, Bergen, Norway.
Eur Respir J. 2017 Mar 15;49(3). doi: 10.1183/13993003.01298-2016. Print 2017 Mar.
Increased levels of growth differentiation factor-15 (GDF15) are associated with cachexia, cardiovascular disease and all-cause mortality. The role of GDF15 in chronic obstructive pulmonary disease (COPD) is unknown.The study included 413 patients with COPD from the Bergen COPD Cohort Study. All patients had a forced expiratory volume in 1 s (FEV) <80% predicted, a FEV to forced vital capacity (FVC) ratio <0.7 and a history of smoking. Spirometry, fat free mass index, blood gases and plasma GDF15 were measured at baseline. Patients were followed for 3 years regarding exacerbations and changes in lung function, and 9 years for mortality. Yearly exacerbation rate, survival and yearly change in FEV/FVC were evaluated with regression models.Median plasma GDF15 was 0.86 ng·mL (interquartile range 0.64-1.12 ng·mL). The distribution was not normal and GDF15 was analysed as a categorical variable. High levels of GDF15 were associated with a higher exacerbation rate (incidence rate ratio 1.39, 95% CI 1.1-1.74, p=0.006, adjusted values). Furthermore, high levels of GDF15 were associated with higher mortality (hazard ratio 2.07, 95% CI 1.4-3.1, p<0.001) and an increased decline in both FEV (4.29% 3.25%) and FVC (2.63% 1.44%) in comparison to low levels (p<0.01 for both).In patients with COPD, high levels of GDF15 were independently associated with a higher yearly rate of exacerbations, higher mortality and increased decline in both FEV and FVC.
生长分化因子 15（GDF15）水平升高与恶病质、心血管疾病和全因死亡率有关。GDF15 在慢性阻塞性肺疾病（COPD）中的作用尚不清楚。该研究纳入了来自卑尔根 COPD 队列研究的 413 名 COPD 患者。所有患者的第 1 秒用力呼气量（FEV）<80%预计值、FEV 与用力肺活量（FVC）比值<0.7 且有吸烟史。在基线时测量了肺活量、去脂体重指数、血气和血浆 GDF15。对患者进行了 3 年的随访，观察其急性加重和肺功能变化情况，并随访 9 年观察其死亡率。采用回归模型评估每年急性加重率、生存率和 FEV/FVC 的每年变化率。血浆 GDF15 的中位数为 0.86ng·mL（四分位距 0.64-1.12ng·mL）。分布并不呈正态，因此将 GDF15 作为分类变量进行分析。高水平的 GDF15 与更高的急性加重率相关（发病率比 1.39，95%CI 1.1-1.74，p=0.006，校正值）。此外，高水平的 GDF15 与更高的死亡率相关（风险比 2.07，95%CI 1.4-3.1，p<0.001），与低水平相比，FEV（4.29% 3.25%）和 FVC（2.63% 1.44%）的下降速度更快（p<0.01）。在 COPD 患者中，高水平的 GDF15 与每年急性加重率更高、死亡率更高以及 FEV 和 FVC 下降速度更快独立相关。
