慢性阻塞性肺疾病急性加重患者外周血微RNA-34a表达水平的临床意义

Clinical significance of the expression of miR-34a in peripheral blood of patients with acute exacerbation of chronic obstructive pulmonary disease

目的探讨慢性阻塞性肺疾病急性加重(AECOPD)患者外周血miR-34a表达水平与病情及近期预后的关系。方法2020年5月至2021年5月在本院接受治疗的AECOPD患者90例作为AECOPD组,同期在本院进行体检的健康志愿者100名作为健康对照组,对比2组研究对象外周血miR-34a表达水平、动脉血气指标、肺功能参数的差异,采用Pearson检验分析AECOPD患者外周血miR-34a表达水平与动脉血气指标、肺功能参数的相关性。根据AECOPD患者入院后28 d的死亡情况分为死亡组20例、存活组70例,采用多因素Logistic回归模型分析AECOPD患者入院近期死亡的危险因素。采用受试者工作特征(ROC)曲线分析入院后早期外周血miR-34a表达水平对AECOPD患者入院后近期死亡的预测价值。结果AECOPD组患者的外周血miR-34a表达水平高于健康对照组,差异有统计学意义(P<0.05)。AECOPD组患者的动脉血氧分压(PaO_(2))、用力肺活量(FVC)、第1秒用力呼气容积(FEV_(1))、第1秒用力呼气容积占用力肺活量比值(FEV_(1)/FVC)水平低于健康对照组,动脉二氧化碳分压(PaCO_(2))水平高于健康对照组(P<0.05)。Pearson检验发现,AECOPD患者入院早期外周血miR-34a表达水平与PaCO_(2)水平呈正相关,与PaO_(2)、FVC、FEV_(1)、FEV_(1)/FVC水平呈负相关(P<0.05)。多因素Logistic回归分析结果显示:年龄较大、入院急性生理与慢性健康状况Ⅱ系统(APACHEⅡ)评分较高、FVC较低、FEV_(1)较低、FEV_(1)/FVC较低、PaO_(2)较低、PaCO_(2)较高、miR-34a较高分别是AECOPD患者入院28 d死亡的独立危险因素(P<0.05)。ROC曲线显示,入院早期外周血miR-34a表达水平预测AECOPD患者入院28 d死亡的最佳截断值为0.780,ROC曲线下面积(95%CI)为0.830(0.758,0.902),对应的灵敏度、特异度分别为70.2%、72.2%。结论AECOPD患者外周血miR-34a表达异常增高是其入院早期死亡的独立危险因素,且对死亡结局出现具有早期预警价值。

Objective To investigate the relationship between the expression level of miR-34a in peripheral blood of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and disease condition,short-term prognosis.Methods Ninety cases with AECOPD treated in our hospital from May 2020 to May 2021 were selected as AECOPD group,and 100 healthy volunteers who underwent physical examination in our hospital during the same period were selected as normal control group.Differences in miR-34a expression level in peripheral blood,arterial blood gas indexes and pulmonary function parameters between two groups were compared.Pearson test was used to analyze the correlation between the expression level of miR-34a in peripheral blood of patients with AECOPD and arterial blood gas indexes,and lung function parameters.According to the death of AECOPD patients 28 days after admission,they were divided into death group(n=20)and survival group(n=70),and the risk factors of recent death in AECOPD patients were analyzed by the multi-factor Logistic regression model.The receiver operating characteristic(ROC)curve was used to analyze the prognostic value of miR-34a expression level in peripheral blood of AECOPD patients in the early post-admission period.Results Expression level of miR-34a in peripheral blood of patients in AECOPD group was higher than that in normal control group,the difference was statistically significant(P<0.05).Levels of PaO_(2),forced vital capacity(FVC),forced expiratory volume in 1 s(FEV_(1))and FEV_(1)/FVC in AECOPD group were lower than those in normal control group,PaCO_(2)level was higher than that in normal control group(P<0.05).Pearson test showed that the expression level of miR-34a in peripheral blood of AECOPD patients was positively correlated with PaCO_(2)in early admission,and negatively correlated with PaO_(2),FVC,FEV_(1)and FEV_(1)/FVC(P<0.05).Results of multi-factor Logistic regression analysis showed that older age,higher APACHEⅡscore on admission,lower FVC,lower FEV_(1),lower FEV_(1)/FVC,lower PaO_(2),higher PaCO_(2)and higher miR-34a were the independent risk factors for death of AECOPD patients on 28 days after admission(P<0.05).ROC curve showed that the optimal cut-off value of miR-34a expression level in peripheral blood in early admission to AECOPD for predicting 28 d death was 0.780,AUC(95%CI)was 0.830(0.758,0.902),corresponding sensitivity and specificity were 70.2%and 72.2%,respectively.Conclusion Abnormal expression of miR-34a in peripheral blood of AECOPD patients is an independent risk factor for early death on admission,which also has an early warning value for the occurrence of death outcome.