联合检测IL-5、IL-17A、IFN-α诊断慢性阻塞性肺疾病患者急性加重预警诊断模型的建立及临床应用评价

Establishment and clinical application evaluation of early warning diagnostic model for acute exacerbation of chronic obstructive pulmonary disease by combined detection of IL-5,IL-17A and IFN-α

目的:建立应用于慢性阻塞性肺疾病(COPD)患者急性加重(AECOPD)的预警诊断模型,为临床提供简便、快速、准确的辅助诊断依据。方法:方法学建立与验证。构建受试者样本库,选取2021年9月10日至2023年7月25日就诊于解放军总医院第八医学中心的COPD患者172例。其中102例为模型建立队列,有稳定期COPD(SCOPD)组49例(男性42例,女性7例),年龄(69.71±11.16)岁、AECOPD组53例(男性49例,女性4例),年龄(72.60±10.19)岁;其余70例为模型验证队列,有SCOPD组35例(男性28例,女性7例),年龄(69.97±10.40)岁、AECOPD组35例(男性33例,女性2例),年龄(71.43±9.67)岁。空腹采集外周血样本,采用流式细胞术检测白细胞介素(IL)-1β、IL-4、IL-5、IL-6、IL-10、IL-17A、干扰素(IFN)-α和肿瘤坏死因子-α(TNF-α)表达水平,通过Mann-Whitney U检验进行差异分析。采用二元logistic回归分析筛选与急性加重期慢阻肺患者的相关危险因素。通过受试者工作特征(ROC)曲线评价模型的诊断效力。结果:模型建立队列中SCOPD组的IL-5[1.64(0.60,2.86)pg/ml]、IL-17A[1.42(0.88,2.29)pg/ml]、IFN-α[0.91(0.59,1.81)pg/ml]低于AECOPD组患者血浆中IL-5[4.68(2.34,9.40)pg/ml,Z=-5.362,P<0.001]、IL-17A[2.33(1.59,4.62)pg/ml,Z=-4.217,P<0.001]、IFN-α[2.83(0.91,3.75)pg/ml,Z=-3.913,P<0.01]水平,SCOPD和AECOPD组间二元logistic回归分析结果显示,IL-5、IL-17A、IFN-α是COPD患者急性加重的独立危险因素(P<0.05),且回归方程为Y=-2.861+0.364×IL-5+0.385×IL-17A+0.445×IFN-α,三者联合检测时曲线下面积(AUC)值可达0.866(P<0.001)。模型验证队列中SCOPD及AECOPD组人群相比,IL-5、IL-17A、IFN-α联合检测AUC为0.858(P<0.001),Kappa值为0.773(P<0.05)。结论:联合检测IL-5、IL-17A、IFN-α对急性加重期COPD患者具有较高的诊断效能,且该联合诊断模型性能可靠、与临床诊断的一致性较好、可行性高,为急性加重期COPD的临床诊断提供了新的潜在工具,具有进一步探索优化及推广应用的价值。

Objective This study aims to establish an early warning diagnosis model for acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and to provide a simple,rapid,and accurate auxiliary diagnosis basis for clinical practice.Methods The sample bank of subjects(patients admitted to the Eighth Medical Center of the PLA General Hospital from September 10,2021,to July 25,2023)was constructed,including the model establishment cohort[SCOPD group 49,42 males and 7 females,(69.71±11.16)years old;AECOPD group 53,49 males and 4 females,(72.60±10.19)years old]and the model validation cohort[SCOPD group 35,28 males and 7 females,(69.97±10.40)years old;AECOPD group 35,33 males and 2 females,(71.43±9.67)years old].Fasting peripheral blood samples were collected,and the expression levels of IL-5,IL-17A,and IFN-αwere detected by flow cytometry.Different expression levels were analyzed by Mann-Whitney U test.Binary logistic regression analysis was used to screen the related risk factors of COPD patients in acute exacerbation.The diagnostic efficacy of the model was evaluated by the receiver operating characteristic(ROC)curve.Results The levels of IL-5[1.64(0.60,2.86)pg/ml],IL-17A[1.42(0.88,2.29)pg/ml],and IFN-α[0.91(0.59,1.81)pg/ml]in the SCOPD group were significantly decreased compared with the AECOPD group IL-5[4.68(2.34,9.40)pg/ml,Z=-5.033,P<0.001],IL-17A[2.33(1.59,4.62)pg/ml,Z=-3.919,P<0.001],IFN-α[2.83(0.91,3.75)pg/ml,Z=-4.127,P<0.01]in the cohort of model establishment.The results of binary logistic regression analysis between SCOPD and AECOPD groups showed that IL-5,IL-17A,and IFN-αwere independent risk factors for acute exacerbation of patients with COPD(P<0.05).And the regression equation is Y=-2.861+0.364×IL-5+0.385×IL-17A+0.445×IFN-α.The AUC value of IL-5,IL-17A,IFN-αand combined detection was 0.866(P<0.001).Compared to the SCOPD group and the AECOPD group in the cohort of model validation,the receiver operating characteristic(ROC)curve showed that the combined model of three(AUC=0.858,P<0.001)could be used to diagnose the AECOPD.And the Kappa value was 0.773(P<0.05).Conclusion The combined detection of IL-5,IL-17A,and IFN-αhas high diagnostic efficacy for patients with acute exacerbation of COPD.This method provides a new potential tool for the clinical diagnosis of AECOPD and has the value of further exploration and optimization,promotion,and application.