BPI-ANCA、MMP-9和TIMP-1检测在AECOPD患者合并PA感染中的临床应用价值

Clinical Value of BPI-ANCA,MMP-9 and TIMP-1 Detection in Patients with AECOPD Complicated by PA Infection

目的探讨杀菌/通透性增加蛋白抗体(BPI-ANCA)、基质金属蛋白酶9(MMP-9)及组织基质金属蛋白酶抑制剂1(TIMP-1)检测在慢性阻塞性肺疾病急性加重期(AECOPD)合并铜绿假单胞菌(PA)感染中的临床应用价值。方法收集2017年6月至2020年10月阜阳市肿瘤医院收治的AECOPD患者200例,根据痰培养PA检测结果分为PA(+)组90例、PA(-)组110例,选择同期健康体检者50例为对照组;根据BPI-ANCA检测结果将90例PA(+)患者分为BPI-ANCA(+)组39例、BPI-ANCA(-)组51例。比较PA(+)组、PA(-)组及对照组3组BPI-ANCA阳性率,比较BPI-ANCA(+)组与BPI-ANCA(-)组2组血清MMP-9、TIMP-1、MMP-9/TIMP-1、中性粒细胞百分比(NEU%)、C反应蛋白(CRP)水平及肺功能指标水平。血清BPI-ANCA、MMP-9及TIMP-1水平采用ELISA法检测;患者肺功能于临床稳定期测量,指标包括第1秒用力呼气容积占预计值百分比(FEV1%pred)、第一秒用力呼气量占所有呼气量比例(FEV1/FVC%)及COPD气流受限严重程度。结果PA(+)组病程显著长于PA(-)组,BPI-ANCA阳性率显著高于PA(-)组、对照组,差异均有统计学意义(P<0.05)。与BPI-ANCA(-)组相比,BPI-ANCA(+)组FEV1%pred、FEV1/FVC%、TIMP-1水平明显降低,MMP-9、MMP-9/TIMP-1、NEU%、CRP水平及肺功能气流受限极重度人数占比明显升高,差异均有统计学意义(P<0.05)。与COPD气流受限轻度、中度及重度患者相比,气流受限极重度患者血清MMP-9水平、MMP-9/TIMP-1显著升高,TIMP-1水平明显下降,差异均有统计学意义(P<0.05)。结论BPI-ANCA、MMP-9、TIMP-1与AECOPD患者合并PA感染的炎症程度及肺功能受损明显相关,能作为病情预测及监测的潜在生物标志物。

Objective To investigate the clinical value of antineutrophil cytoplasmic autoantibodies against neutrophil granule bactericidal/permeability-increasing protein(BPI-ANCA),matrix metalloproteinase-9(MMP-9)and tissue inhibitor of metalloproteinase 1(TIMP-1)detection in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)complicated by Pseudomonas aeruginosa(PA)infection.Methods A total of 200 AECOPD patients admitted to Fuyang Tumor Hospital from June 2017 to October 2020 were divided into PA(+)group(n=90)and PA(-)group(n=110)according to the sputum culture results.In addition,50 healthy subjects were selected as the control group.The PA(+)patients were further divided into BPI-ANCA(+)group(n=39)and BPI-ANCA(-)group(n=51).The positive rate of BPI-AN CA was compared among PA(+)group,PA(-)group and control group.Serum MMP-9,TIMP-1,MMP-9/TIMP-1,neutrophil percentage(NEU%),C-reactive protein(CRP)expression and lung function indexes were compared between BPI-ANCA(+)group and BPI-ANCA(-)group.The levels of BPI-ANCA,MMP-9 and TIMP-1 were detected by ELISA.The forced expiratory volume in one second/predicted value ratio(FEV1%pred),FEV1/forced vital capacity(FVC)ratio,and severity of airflow limitation were measured during the clinically stable period.Results PA(+)group had a longer course of disease and a higher positive rate of BPI-ANCA than PA(-)group(P<0.05).Compared with BPI-ANCA(-)group,the FEV1%pred,FEV1/FVC ratio and TIMP-1 level decreased,but MMP-9 content,MMP-9/TIMP-1 ratio,NEU%,CRP expression and proportion of patients with extremely severe airflow limitation increased in BPI-ANCA(+)group(P<0.05).Compared with COPD patients with mild,moderate or severe airflow limitation,MMP-9 level and MMP-9/TIMP-1 ratio increased,but TIMP-1 content decreased in COPD patients with extremely severe airflow limitation(P<0.05).Conclusion BPI-ANCA,MMP-9 and TIMP-1 are closely related to lung function and inflammatory state in patients with AECOPD complicated by PA infection,suggesting that they can be used as potential biomarkers for disease prediction and monitoring.