Edinburgh Lung and the Environment Group Initiative (ELEGI), Centre for Inflammation and Research, Queens' Medical Research Institute, Edinburgh, UK
Respiratory Therapy Area Unit, GSK, King of Prussia, PA, USA.
Eur Respir J. 2016 May;47(5):1365-73. doi: 10.1183/13993003.01824-2015. Epub 2016 Mar 23.
Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality.pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic-femoral pulse wave velocity.pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=-0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05).In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.
弹性蛋白降解是肺气肿的一个关键特征,可能在与慢性阻塞性肺疾病(COPD)相关的动脉粥样硬化发病机制中起作用。循环中的脱氧异肽是弹性蛋白降解的特异性生物标志物。我们研究了血浆脱氧异肽(pDES)与肺气肿严重程度/进展、冠状动脉钙评分(CACS)和死亡率之间的关系。在两个独立的队列中,对 1177 名 COPD 患者和 110 名健康对照者进行了 pDES 测量。通过胸部计算机断层扫描评估肺气肿。作为主动脉-股动脉脉搏波速度来测量动脉僵硬程度。患有心血管疾病的患者的 pDES 升高(p<0.005),并与年龄(rho=0.39,p<0.0005)、CACS(rho=0.19,p<0.0005)、改良的医学研究委员会呼吸困难评分(rho=0.15,p<0.0005)、6 分钟步行距离(rho=-0.17,p<0.0005)和体重指数、气流阻塞、呼吸困难、运动能力指数(rho=0.10,p<0.01)相关,但与肺气肿、肺气肿进展或 1 秒用力呼气量下降无关。pDES 可独立于多种混杂因素预测全因死亡率(p<0.005)。在一个由 186 名 COPD 患者和 110 名对照者组成的独立队列中,患有心血管疾病的 COPD 患者的 pDES 水平更高,并且与动脉僵硬相关(p<0.05)。在 COPD 中,弹性蛋白过度降解与心血管合并症、动脉粥样硬化、动脉僵硬、全身炎症和死亡率有关,但与肺气肿或肺气肿进展无关。pDES 是 COPD 患者心血管风险和死亡率的良好生物标志物。