血清脑钠肽、白细胞介素-6、外泌体环状RNA BPTF对慢性阻塞性肺疾病急性加重期患者的预后分析

Predictive values of serum BNP, IL-6, and extracellular vesicle-derived circular RNA BPTF for prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease

摘要:

目的 分析血清脑钠肽（BNP）、白细胞介素-6（IL-6）、外泌体环状RNA BPTF（circRNA BPTF）在慢性阻塞性肺疾病（COPD）急性加重期患者中的表达水平，以及对患者预后的预测价值。方法 选取2021年5月—2023年5月常州市妇幼保健院收治的118例COPD急性加重期患者（急性加重期组），另取同期该院80例COPD稳定期患者（稳定期组）和80例健康体检成人（对照组）。比较3组血清BNP、IL-6和circRNA BPTF的表达差异。分析疾病炎症程度与血清BNP、IL-6和circRNA BPTF的相关性。应用多因素一般Logistic回归模型分析COPD急性加重期患者预后不良的危险因素，并通过受试者工作特征（ROC）曲线评价BNP、IL-6和circRNA BPTF对预后的预测价值。结果 急性加重期组、稳定期组血清BNP、IL-6、circRNA BPTF相对表达量均高于对照组（P <0.05），急性加重期组又均高于稳定期组（P <0.05）。疾病严重程度与血清BNP、IL-6、circRNA BPTF呈负相关（r_s =-0.733、-0.918和-0.926，均P <0.05）。多因素一般Logistic回归分析显示：肺功能Ⅲ、Ⅳ级［O^R=55.649（95% CI：10.429，296.939）］、APACHE Ⅱ评分高［O^R=1.213（95% CI：1.020，1.444）］、Charlson合并症指数≥ 3［O^R=81.696（95% CI：15.888，420.076）］、PCT高水平［O^R=4.629（95% CI：1.198，17.888）］、BNP高水平［O^R=1.025（95% CI：1.009，1.042）］、IL-6高水平［O^R=1.429（95% CI：1.021，1.999）］和circRNA BPTF高水平［O^R=20.942（95% CI：2.772，158.200）］是COPD急性加重期患者死亡的危险因素（P <0.05）。ROC曲线结果表明，血清BNP、IL-6、circRNA BPTF联合预测的曲线下面积为0.943（95% CI：0.875，1.000），敏感性为91.7%（95% CI：0.861，0.972），特异性为94.7%（95% CI：0.924，0.969）。结论 血清BNP、IL-6和circRNA BPTF的表达与COPD急性加重期患者的病情严重程度和预后密切相关，可作为有效的预后评估生物标志物。

Abstract:

Objective To investigate the levels of serum brain natriuretic peptide (BNP), interleukin-6 (IL-6), and extracellular vesicle-derived circular RNA BPTF (circRNA BPTF) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD), and to assess their predictive values for the prognosis of patients.Methods Between May 2021 and May 2023, 118 patients experiencing acute exacerbation of COPD were selected from Changzhou Maternal and Child Health Care Hospital as the acute exacerbation group. Additionally, 80 patients in the stable phase of COPD were included as the stable phase group, and 80 healthy adults undergoing routine checkups during the same period were selected as the control group. Differences in the expressions of serum BNP, IL-6, and circRNA BPTF among the three groups were compared, and the correlations between the disease severity and serum levels of BNP, IL-6, and circRNA BPTF were analyzed. Multivariable regression analysis was utilized to identify risk factors for poor prognosis in patients with acute exacerbation of COPD, and predictive values of BNP, IL-6, and circRNA BPTF for the prognosis were assessed through the receiver operating characteristic (ROC) curve analysis.Results The levels of BNP, IL-6, and circRNA BPTF were found to be higher in both the acute exacerbation group and the stable phase group compared to those in the control group (P < 0.05), and those in the acute exacerbation group were even higher than those in the stable phase group (P < 0.05). The disease severity was negatively correlated with the serum levels of BNP, IL-6, and circRNA BPTF (r_s = -0.733, -0.918, and -0.926, all P < 0.05). Multivariable Logistic regression analysis indicated that grade Ⅲ and Ⅳ pulmonary function [O^R = 55.649 (95% CI: 10.429, 296.939) ], high APACHE Ⅱ scores [O^R = 1.213 (95% CI: 1.020, 1.444) ], Charlson Comorbidity Index ≥ 3 [O^R = 81.696 (95% CI: 15.888, 420.076) ], and high levels of PCT [O^R = 4.629 (95% CI: 1.198, 17.888) ], BNP [O^R = 1.025 (95% CI: 1.009, 1.042) ], IL-6 [O^R = 1.429 (95% CI: 1.021, 1.999) ], and circRNA BPTF [O^R = 20.942 (95% CI: 2.772, 158.200) ] were independent risk factors for death of patients with acute exacerbation of COPD (P < 0.05). ROC curve analysis showed that the area under the curve of the combined detection of serum BNP, IL-6, and circRNA BPTF for predicting the poor prognosis of patients with acute exacerbation of COPD was 0.943 (95% CI: 0.875, 1.000), with a sensitivity of 91.7% (95% CI: 0.861, 0.972), and a specificity of 94.7% (95% CI: 0.924, 0.969).Conclusion The serum levels of BNP, IL-6, and circRNA BPTF are closely related to the disease severity and prognosis of patients with acute exacerbation of COPD, and can serve as effective prognostic biomarkers.