MicroRNA-155、microRNA-146a水平评估慢性阻塞性肺疾病急性加重期疾病严重程度的价值

Value of microRNA-155 and microRNA-146a levels in assessing disease severity in acute exacerbation of COPD

摘要:

目的 探讨microRNA-155（miR-155）、microRNA-146a（miR-146a）水平与慢性阻塞性肺疾病（COPD）急性加重期疾病严重程度及频繁发作风险的关系。方法 选取2021年5月—2023年5月在吕梁市第一人民医院接受治疗的152例COPD患者，稳定期COPD患者94例纳入稳定组，急性加重期COPD患者58例纳入加重组，另取同期该院46例健康体检者作为对照组。比较疾病不同严重程度下miR-155、miR-146a水平的变化，同时探讨急性加重患者发作频繁的影响因素，评估miR-155、miR-146a水平在COPD急性加重期的价值。结果 加重组与稳定组患者miR-155水平均高于对照组（P <0.05），加重组患者miR-155水平高于稳定组（P <0.05）。加重组与稳定组患者miR-146a水平均低于对照组（P <0.05），加重组患者miR-146a水平低于稳定组（P <0.05）。Spearman相关性分析结果显示：miR-155水平与疾病严重程度呈正相关（r_s =0.602，P <0.05）；miR-146a水平与疾病严重程度呈负相关（r_s =-0.588，P <0.05）。加重组不同严重级别患者miR-155水平和miR-146a水平比较，差异均有统计学意义（P <0.05）。频繁组年龄≥60岁占比、吸烟史率、冠心病史率、糖尿病史率、病情评估C/D级占比、COPD评估测试（CAT）评分和miR-155水平均高于非频繁组，miR-146a水平低于非频繁组（P <0.05）。多因素一般Logistic回归分析结果显示：年龄≥60岁［O^R=6.713（95% CI：1.770，25.461）］、病情评估为C/D级［O^R=3.039（95% CI：1.237，7.464）］、高CAT评分［O^R=15.152（95% CI：2.865，80.137）］、高miR-155水平［O^R=8.975（95% CI：1.625，49.551）］、低miR-146a水平［O^R=0.212（95% CI：0.063，0.710）］均是COPD加重期患者频繁发作的危险因素（P <0.05）。miR-155与miR-146a联合预测的诊断效能最佳，曲线下面积为0.906（95% CI：0.829，0.982），敏感性为76.9%（95% CI：0.647，0.875），特异性为89.5%（95% CI：0.813，0.948）。结论 miR-155、miR-146a水平可作为评估COPD急性加重期疾病严重程度的生物标志物，对于指导临床治疗决策具有重要意义。

Abstract:

Objective To investigate the relationship between microRNA-155 (miR-155) and microRNA-146a (miR-146a) levels and disease severity and the risk of frequent exacerbations in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD).Methods A total of 152 patients with COPD who received treatment at Lvliang First People's Hospital between May 2021 and May 2023 were enrolled. Among them, 94 patients with stable COPD were assigned to the stable group, and 58 patients with acute exacerbation of COPD were assigned to the exacerbation group. In addition, 46 healthy individuals who underwent health checkups during the same period were selected as the control group. Changes in miR-155 and miR-146a levels among patients with different disease severities were compared. Factors influencing frequent exacerbations in patients with acute exacerbation were analyzed, and the value of miR-155 and miR-146a levels during acute exacerbation of COPD was evaluated.Results The miR-155 levels in both the exacerbation group and the stable group were significantly higher than those in the control group (P < 0.05), and the miR-155 level in the exacerbation group was significantly higher than that in the stable group (P < 0.05). The miR-146a levels in both the exacerbation group and the stable group were significantly lower than those in the control group (P < 0.05), and the miR-146a level in the exacerbation group was significantly lower than that in the stable group (P < 0.05). Spearman correlation analysis showed that miR-155 levels were positively correlated with disease severity (r_s = 0.602, P = 0.000), whereas miR-146a levels were negatively correlated with disease severity (r_s = -0.588, P = 0.000). There were statistically significant differences in miR-155 and miR-146a levels among patients in Groups A, B, C, and D (P < 0.05). Compared with the non-frequent exacerbation group, the frequent exacerbation group had higher proportions of patients aged ≥60 years, with a smoking history, a history of coronary heart disease, a history of diabetes mellitus, and GOLD group C/D classification, as well as higher COPD Assessment Test (CAT) scores and miR-155 levels, while miR-146a levels were lower. Multivariable logistic regression analysis showed that age ≥60 years [O^R = 6.713 (95% CI: 1.770, 25.461) ], GOLD group C/D classification [O^R = 3.039 (95% CI: 1.237, 7.464) ], high CAT score [O^R = 15.152 (95% CI: 2.865, 80.137) ], high miR-155 level [O^R = 8.975 (95% CI: 1.625, 49.551) ], and low miR-146a level [O^R = 0.212 (95% CI: 0.063, 0.710) ] were risk factors for frequent exacerbations in patients with acute exacerbation of COPD (P < 0.05). The combination of miR-155 and miR-146a showed the best diagnostic performance, with an area under the curve (AUC) of 0.906 (95% CI: 0.829, 0.982), sensitivity of 76.9% (95% CI: 64.7%, 87.5%), and specificity of 89.5% (95% CI: 0.813, 0.948).Conclusion The levels of miR-155 and miR-146a can serve as valuable biomarkers for assessing the severity of disease in the acute exacerbation stage of COPD and are of great significance for guiding clinical treatment decisions.