Discrimination value of serum irisin, HSP-27 and D-D in acute exacerbation of chronic obstructive pulmonary disease with pulmonary embolism and their relationship with prognosis
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摘要: 目的 观察并探讨血清鸢尾素、热休克蛋白27(HSP27)和D-二聚体(D-D)水平在慢性阻塞性肺疾病急性加重期(AECOPD)合并肺栓塞(PE)中的变化意义及临床价值。方法 选取大连医科大学附属第二医院呼吸内科2018年1月-2020年12月期间住院的AECOPD患者共500例，其中未合并PE的AECOPD患者(AECOPD组)420例，AECOPD合并PE患者(AECOPD+PE组)80例，对AECOPD合并PE患者根据PE严重指数评分和危险分级，分为高、中、低危3个组；以截止末次随访患者是否死亡，将AECOPD合并PE患者分为存活组和死亡组；另选取体检中心的健康体检者80例为对照组。记录其性别、年龄、BMI、吸烟史及研究指标的数据，检测所有研究对象血清鸢尾素、HSP27、D-D水平，并进行对比分析。结果 AECOPD+PE组血清HSP27和D-D水平高于AECOPD组和对照组，且AECOPD组也高于对照组(P < 0.05)，而AECOPD+PE组血清鸢尾素水平低于AECOPD组和对照组，且AECOPD组也低于对照组(P < 0.05)；Spearman相关性分析显示，AECOPD合并PE患者血清HSP27和D-D水平与PE危险程度呈显著正相关，而血清鸢尾素水平与PE危险程度呈显著负相关(P < 0.05)。受试者工作特征曲线分析发现血清鸢尾素、HSP27和D-D单独应用及联合应用鉴别AECOPD合并PE的受试者工作特征曲线下面积分别为0.774、0.716、0.721、0.804。Logistic回归分析结果显示：血清鸢尾素水平是预后的重要保护因素，而HSP27和D-D水平是预后的重要危险因素(P < 0.05)。结论 血清HSP27、D-D水平在AECOPD尤其是合并PE患者中升高，而血清鸢尾素水平则降低，且与PE危险程度有相关性，具有一定的鉴别价值，联合检测3个血清指标可能有助于及时判断患者的病情严重程度及评估预后。Abstract: Objective To observe and explore the changes of serum irisin, heat shock protein 27(HSP27) and D-dimer(D-D) levels in acute exacerbation of chronic obstructive pulmonary disease(AECOPD) complicated with pulmonary embolism(PE) significance and clinical value.Methods A total of 500 AECOPD patients who were hospitalized in the Department of Respiratory Medicine in The Second Affiliated Hospital of Dalian Medical University from January 2018 to December 2020 were selected, including 420 AECOPD patients without PE(AECOPD group) and 80 AECOPD patients with PE(AECOPD+PE group). Patients with AECOPD combined with PE were divided into high, medium and low risk groups according to the PE severity index score and risk classification. Patients with AECOPD combined with PE were divided into survival group and death group according to whether the patients died at the last follow-up up to discharge. 80 healthy subjects from the hospital's physical examination center were selected as the control group. Basic information such as gender, age, body mass index(BMI), smoking history and research indicators were recorded, and serum irisin, HSP27 and D-D of all subjects were detected and compared and analyzed.Results The serum HSP27 and D-D in the AECOPD+PE group were higher than those in the AECOPD group and the control group, and the AECOPD group was also higher than the control group(P < 0.05), while the serum irisin in the AECOPD+PE group was lower than that in the AECOPD group and the control group, and the AECOPD group was also lower than the control group(P < 0.05). Spearman correlation analysis showed that serum HSP27 and D-D in AECOPD patients with PE were significantly positively correlated with the risk of PE, the degree of irisin was significantly negatively correlated(P < 0.05). ROC curve analysis found that the AUC of serum irisin, HSP27 and D-D single and combined application were 0.774, 0.716, 0.721, 0.804 respectively. Logistic regression analysis showed that serum irisin level was an important protective factor for prognosis, while HSP27 and D-D levels were important risk factors(P < 0.05).Conclusion Serum HSP27 and D-D are elevated in AECOPD, especially in patients with PE, and are significantly correlated with the risk of PE, while serum irisin is the opposite, which may help to judge the severity of the disease in time and prognosis assessment.
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表 1 3组受试者的一般资料比较
例(%)，X±S 一般资料 对照组(n=80) AECOPD组(n=420) AECOPD+PE组(n=80) F/χ2 P 性别 男 68(85.00) 352(83.80) 70(87.50) 0.707 0.702 女 12(15.00) 68(16.20) 10(12.50) 年龄/岁 68.15±6.04 71.58±7.15 72.13±6.84 13.284 0.122 BMI 22.64±2.17 22.88±2.42 22.73±2.34 0.234 0.792 吸烟史 50(62.50) 269(64.05) 51(63.75) 0.039 0.981 
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表 2 3组受试者血清鸢尾素、HSP27和D-D水平的比较
X±S 检测指标 对照组(n=80) AECOPD组(n=420) AECOPD+PE组(n=80) F P 鸢尾素/(ng·mL-1) 52.17±5.63 30.35±4.291) 23.04±3.631)2) 603.321 < 0.001 HSP27/(ng·mL-1) 7.32±2.04 9.06±3.371) 10.42±3.651)2) 11.894 < 0.001 D-D/(mg·L-1) 0.31±0.07 0.48±0.442) 2.62±1.011)2) 377.963 < 0.001 与对照组比较，1)P < 0.05；与AECOPD组比较，2)P < 0.05。
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表 3 AECOPD合并PE患者不同PE危险程度血清鸢尾素、HSP27和D-D水平的比较
X±S 检测指标 低危组(n=36) 中危组(n=24) 高危组(n=20) F P 鸢尾素/(ng·mL-1) 26.35±3.97 21.68±3.511) 18.71±2.741)2) 32.694 < 0.001 HSP27/(ng·mL-1) 9.84±3.07 10.31±3.361) 11.60±4.141)2) 4.293 0.017 D-D/(mg·L-1) 1.48±0.57 2.86±0.851) 4.38±1.421)2) 63.598 < 0.001 与低危组比较，1)P < 0.05；与中危组比较，2)P < 0.05。
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表 4 血清鸢尾素、HSP27和D-D单独应用及联合应用鉴别AECOPD合并PE的效能
检测指标 AUC(95%CI) 阈值 敏感度 特异度 约登指数 准确度 鸢尾素 0.716(0.450~0.977) 26 ng/mL 0.713(57/80) 0.700(56/80) 0.413 0.706(113/160) HSP27 0.721(0.461~0.973) 9 ng/mL 0.700(56/80) 0.725(58/80) 0.425 0.713(114/160) D-D 0.774(0.556~0.981) 0.4 mg/L 0.788(63/80) 0.750(60/80) 0.538 0.769(123/160) 联合应用 0.804(0.634~0.977) 0.838(67/80) 0.775(62/80) 0.613 0.806(129/160)
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表 5 不同预后AECOPD合并PE患者血清鸢尾素、HSP27和D-D水平的变化
例(%)，X±S 因素 存活组(n=63) 死亡组(n=17) t/χ2 P 性别 男 56(88.89) 14(82.35) 0.096 0.757 女 7(11.11) 3(17.65) 年龄/岁 72.35±6.84 71.31±6.84 0.556 0.580 BMI 22.91±2.34 22.06±2.34 1.329 0.188 吸烟史 40(63.49) 11(64.71) 0.009 0.926 鸢尾素/(ng·mL-1) 24.22±3.84 18.67±2.20 7.706 < 0.001 HSP27/(ng·mL-1) 9.34±3.47 14.42±2.25 5.706 < 0.001 D-D/(mg·L-1) 2.37±0.46 3.55±0.91 5.171 < 0.001
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表 6 AECOPD合并PE预后影响因素的logistic回归分析
因素 赋值 β SE Wald χ2 P OR 95%CI 常数 -0.039 0.021 3.422 0.064 0.962 0.923~1.002 血清鸢尾素 1=≥23.13 ng/mL，0=否 -0.609 0.248 6.015 0.014 0.544 0.334~0.885 血清HSP27 1=≥10.40 ng/mL，0=否 0.578 0.188 9.440 0.002 1.783 1.233~2.578 血清D-D 1=≥2.63 mg/L，0=否 0.655 0.184 12.714 < 0.001 1.926 1.343~2.761
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