Relationship between Antithrombin III Activity and Mortality in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

We aimed to explore the role of antithrombin III (AT-III) activity in diagnosing patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and chronic bronchitis, and its relationship with all-cause mortality of AECOPD patients. We performed univariate and multivariate Cox regression analyses of the factors determining all-cause mortality. We recruited 279 patients with AECOPD and 91 with chronic bronchitis. On admission, patients with AECOPD had lower AT-III activity (80.7 vs. 86.35%, <i>p</i> = 0.002) and higher neutrophil percentages (70.12 vs. 66.40%, <i>p</i> = 0.02) than those with chronic bronchitis. The patients who died were older (78 vs. 73 years, <i>p</i> &lt; 0.001); had higher CRP (39.05 vs. 5.65 mg/L, <i>p</i> &lt; 0.001), D-dimer (1.72 vs. 0.46 mg/L, <i>p</i> &lt; 0.001), FIB (3.56 vs. 3.05 g/L, <i>p</i> = 0.01) levels; and exhibited lower AT-III activity (71.29 vs. 82.94%, <i>p</i> &lt; 0.001) than the survivors. The AT-III area under the receiver operating characteristic curve for predicting COPD all-cause mortality was 0.75 (<i>p</i> &lt; 0.001), optimal cutoff point 79.75%, sensitivity 86.8%, and specificity 57.1%. Multivariate Cox regression analyses showed that increased levels of CRP (HR = 1.005, <i>p</i> = 0.02), D-dimer (HR = 1.17, <i>p</i> = 0.01), WBC count (HR = 1.11, <i>p</i> = 0.002), and reduced AT-III activity (HR = 0.97, <i>p</i> = 0.02) were independent prognostic factors for all-cause mortality. Patients with AT-III ≤ 79.75% were 4.52 times (<i>p</i> = 0.001) more likely to die than those with AT-III &gt; 79.75%. AT-III activity was lower in patients with AECOPD than in those with chronic bronchitis and is potentially useful as an independent predictor of all-cause mortality in patients with AECOPD: reduced AT-III activity and increased CRP and D-dimer levels indicate a higher risk of all-cause mortality.

本研究旨在探讨抗凝血酶Ⅲ（antithrombin III, AT-Ⅲ）活性在慢性阻塞性肺疾病急性加重期（acute exacerbation of chronic obstructive pulmonary disease, AECOPD）与慢性支气管炎患者诊断中的作用，及其与AECOPD患者全因死亡率的关联。本研究针对全因死亡率的影响因素开展单因素及多因素Cox回归分析，共纳入279例AECOPD患者及91例慢性支气管炎患者。入院时，与慢性支气管炎患者相比，AECOPD患者的AT-Ⅲ活性更低（80.7% vs. 86.35%，p=0.002），中性粒细胞百分比更高（70.12% vs. 66.40%，p=0.02）。与存活患者相比，死亡患者年龄更大（78岁 vs. 73岁，p<0.001）；C反应蛋白（C-reactive protein, CRP）、D-二聚体（D-dimer）、纤维蛋白原（fibrinogen, FIB）水平更高，分别为39.05mg/L vs. 5.65mg/L（p<0.001）、1.72mg/L vs. 0.46mg/L（p<0.001）、3.56g/L vs. 3.05g/L（p=0.01）；且AT-Ⅲ活性更低（71.29% vs. 82.94%，p<0.001）。用于预测AECOPD患者全因死亡率的AT-Ⅲ受试者工作特征曲线（receiver operating characteristic curve, ROC）下面积为0.75（p<0.001），最佳截断值为79.75%，灵敏度为86.8%，特异度为57.1%。多因素Cox回归分析显示，CRP水平升高（风险比（hazard ratio, HR）=1.005，p=0.02）、D-二聚体水平升高（HR=1.17，p=0.01）、白细胞计数（white blood cell count, WBC）升高（HR=1.11，p=0.002），以及AT-Ⅲ活性降低（HR=0.97，p=0.02）均为全因死亡率的独立预后因素。AT-Ⅲ活性≤79.75%的患者，其死亡风险是AT-Ⅲ活性>79.75%患者的4.52倍（p=0.001）。AECOPD患者的AT-Ⅲ活性低于慢性支气管炎患者，且AT-Ⅲ活性有望成为AECOPD患者全因死亡率的独立预测指标：AT-Ⅲ活性降低、CRP与D-二聚体水平升高均提示全因死亡风险更高。