慢性阻塞性肺疾病患者并发肺间质纤维化的血清学预测指标研究

Prediction of serum markers in patients with chronic obstructive pulmonary disease complicated with pulmonary fibrosis

目的分析血清转化生长因子β1(TGF-β1)、碱性成纤维细胞生长因子(b FGF)、血管紧张素Ⅱ(AngⅡ)水平对慢性阻塞性肺疾病(COPD)患者并发肺间质纤维化的预测价值。方法选取河北省胸科医院2017年6月至2019年5月收治的128例COPD患者(COPD组)和120例健康志愿者(健康组)。比较2组血清TGF-β1、b FGF、AngⅡ水平;随访1年,计算COPD组肺间质纤维化的发生率,对比发生与未发生肺间质纤维化的COPD患者(并发组与未并发组)的肺功能;分析血清TGF-β1、bFGF、AngⅡ水平与COPD并发肺间质纤维化的关系及对其预测效能。结果 COPD组随访期间3例失访、2例确诊为肺癌脱落。COPD组血清TGF-β1、bFGF、AngⅡ水平均高于健康组[(42±10)μg/L比(28±5)μg/L、(24±4) ng/L比(17±4) ng/L、(30±5) ng/L比(21±4) ng/L](均P <0.001)。COPD组肺间质纤维化发生率为25.2%(31/123),并发组第1秒用力呼气容积(FEV1)、FEV1与用力肺活量比值、二氧化碳弥散量均低于未并发组,功能残气容积/肺总量高于未并发组(均P <0.001),年龄、烟龄、COPD病程、急性加重期、肺功能3~4级、烟雾/粉尘工作环境、血清TGF-β1、bFGF、AngⅡ水平、急性加重发作频率均是COPD并发肺间质纤维化的危险因素,治疗依从是其保护因素(均P <0.05);血清TGF-β1、bFGF、AngⅡ联合检测预测COPD并发肺间质纤维化的敏感度和曲线下面积均高于单独检测(均P <0.05)。结论血清TGF-β1、bFGF、AngⅡ水平升高的COPD患者并发肺间质纤维化风险高,3项指标联合可预测COPD患者肺间质纤维化的发生情况。

Objective To analyze the predictive value of serum transforming growth factor-β1( TGF-β1),basic fibroblast growth factor( b FGF) and angiotensin Ⅱ( Ang Ⅱ) levels in patients with chronic obstructive pulmonary disease( COPD) complicated with pulmonary fibrosis. Methods From June 2017 to May 2019,128 COPD patients admitted to Hebei Chest Hospital( COPD group) and 120 healthy volunteers undergoing physical examination( healthy group) were selected. The serum levels of TGF-β1,b FGF and AngⅡ were compared between the two groups. After 1-year follow-up,the incidence of pulmonary fibrosis in COPD group was calculated;the pulmonary function were compared between patients who did and did not develop pulmonary fibrosis. The relationships between serum TGF-β1,b FGF,AngⅡ levels and COPD complicated with pulmonary fibrosis and their predictive efficacy were analyzed. Results In COPD group,3 cases were lost to follow-up and 2 cases were drop out as lung cancer. The levels of TGF-β1,b FGF and AngⅡin COPD group were higher than those in healthy group[( 42 ± 10) μg/L vs( 28 ± 5) μg/L,( 24 ± 4) ng/L vs( 17 ± 4) ng/L,( 30 ± 5) ng/L vs( 21 ± 4) ng/L]( all P < 0. 001). The incidence of pulmonary fibrosis in COPD group was 25. 2%( 31/123),and the forced expiratory volume in the first second( FEV1),ratio of FEV1 to forced vital capacity,diffusion capacity of carbon dioxide in complicated group were lowerer than those in non complicated group,the functional residual volume/total lung capacity in complicated group was higher than that in non complicated group( all P < 0. 001). Age,smoking age,duration of COPD,acute exacerbation,grade 3-4 pulmonary function,smoke/dust working environment,serum levels of TGF-β1,b FGF,AngⅡ and frequency of acute exacerbation were all risk factors of COPD complicated with pulmonary fibrosis,and treatment compliance was a protective factor( all P < 0. 05). The sensitivity and the area under the curve of combined detection of serum TGF-β1,b FGF and AngⅡ in predicting COPD complicated with pulmonary fibrosis were higher than those of single detection( all P < 0. 05). Conclusions COPD patients with high serum levels of TGF-β1,b FGF and Ang Ⅱ have high risk to complicate pulmonary fibrosis. The combination of the three factors can predict the occurrence of pulmonary fibrosis.