【作者】 李妍；

【导师】 程哲；

【作者基本信息】 郑州大学 ， 内科学（呼吸系病学）（专业学位）， 2020， 硕士

【摘要】 背景慢性阻塞性肺疾病(Chronic obstructive pulmonary disease,COPD)是一种慢性呼吸道炎症性疾病,目前已经成为全球第四大死亡原因。COPD的常见死因与并发症有关,并发症会影响患者的疾病负担和生存率。肺动脉高压(Pulmonary hypertension,PH)是COPD的常见并发症之一,慢性阻塞性肺疾病相关肺动脉高压(chronic obstructive pulmonary disease-associated pulmonary hypertension,COPD-PH)的发病率在20%至91%,肺动脉压力的升高会增加COPD患者的急性加重、预后不良和死亡风险,加重了经济负担和社会负担。因此,尽早发现、及时干预COPD-PH对患者的预后有积极影响。此外,COPD的诊疗指南强调了评估和随访COPD并发症对控制疾病的进展、改善患者预后的重要作用,但并未指出是否所有的COPD患者在初次评估以及每次随访中都需要筛查PH,COPD-PH的人群特征、危险因素仍不清楚。因此,明确COPD患者出现COPD-PH的高危因素,尽早干预,对降低患者死亡率、提高患者的生活质量有重要意义。目的分析COPD-PH患者的临床特征及危险因素,寻找潜在的COPD-PH的预测指标,为干预COPD的进展和疾病管理提供参考。方法连续选取郑州大学第一附属医院呼吸科2018年1月至2019年1月收治的COPD患者,经纳入标准和排除标准筛选后,最终纳入482例患者,根据是否并发PH,分为COPD-PH组(132例)和COPD组(350例)。收集患者的一般资料(性别、年龄、身高、体重、合并疾病、吸烟史、病程时间)、实验室资料(血常规、炎症指标、血生化、血气分析、心肌酶及脑钠肽、凝血功能)及肺功能检查、心脏彩超、胸部CT等相关检查。应用SPSS 22.0软件进行分析,比较COPD-PH组和COPD组患者的一般资料、实验室指标、肺功能指标的差异;对以上分析结果中有统计学差异的指标(P<0.05),分析这些指标与肺动脉收缩压力(Pulmonary artery systolic pressure,PASP)的相关性;应用 Logistic 回归分析COPD-PH的危险因素;绘制受试者工作特征(ROC)曲线,分析各指标对COPD-PH的诊断效能。结果1.两组患者的一般资料:COPD-PH组的平均年龄、合并糖尿病的比例高于COPD 组,分别为(68.64±8.92 vs 64.38±9.02)岁、(28/104 vs 38/312),差异有统计学意义(P<0.05)。2.实验室结果分析:比较动脉血气分析指标,可见COPD-PH组动脉血二氧化碳分压、实际碳酸氢根浓度高于COPD组,分别为(52.60±13.93 VS 46.93±8.37)mmHg、(28.26±3.91 VS 26.82±3.21)mmol/L,差异有统计学意义(P<0.05)。与COPD组相比,COPD-PH组血常规检测中的中性粒细胞淋巴细胞比值、红细胞分布宽度较高、血小板计数水平较低,分别为[2.66(1.85,4.05)vs 3.53(2.15,5.58)]、(13.80±1.20 vs 14.21±1.28)%、(222.35±77.47 vs 204.11±67.87)10^9/L,差异有统计学意义(P<0.05)。比较炎症指标,可见COPD-PH组的C反应蛋白[8.56(3.55,30.13)mg/L]高于 COPD 组的 C 反应蛋白[4.69(1.26,15.34)mg/L],差异有统计学意义(P<0.05)。比较血生化指标,可见与COPD组相比,COPD-PH组白蛋白、白蛋白/球蛋白比值(Albumin/Globulin,A/G)较低,球蛋白较高,分别为(39.92±4.85 vs 37.96±3.98)g/L,(1.68±0.39 vs 1.49±0.31)、(24.76±4.86 vs 26.24±4.69)g/L,差异有统计学意义(P<0.05)。比较两组患者的脑利钠肽(brain natriuretic peptide,BNP)、N端脑利钠肽前体及心肌酶中各指标差异,COPD-PH组BNP、N端脑利钠肽前体高于COPD组,分别为(133.54±77.66 vs 76.18±57.35)ng/L、(570.40±266.75 vs 256.70±194.27)ng/L,差异有统计学意义(P<0.05),两组的心肌酶指标差异均无统计学意义。比较两组患者的凝血功能,COPD-PH组的D-二聚体高于COPD组[0.16(0.11,0.28)vs 0.11(0.07,0.19)]mg/L,差异有统计学意义(P<0.05)。3.比较两组的肺功能相关指标:COPD-PH组的第一秒用力呼气容积/用力肺活量、第一秒用力呼气容积占预计值的百分比(Forced expiratory volume in 1 second as percentage of predicted value,FEV1%pred)、用力肺活量占预计值的百分比、一氧化碳弥散量占预计值的百分比均低于COPD组,分别为(44.86±12.69vs 48.33±11.39)%、(44.18±22.42 vs 52.74±19.73)%、(74.69±21.31 vs 84.35±20.11)%、(52.44±27.65 vs 60.11±25.70)%,差异有统计学意义(P<0.05)。4.各指标与PASP的相关性分析,年龄与PASP呈正相关(r=0.197,P<0.001),动脉血二氧化碳分压与PASP呈正相关(r=0.208,P<0.001)、红细胞分布宽度与PASP呈正相关(r=0.182,P<0.001),A/G与PASP呈负相关(r=-0.222,P<0.001),BNP与PASP呈正相关(r=0.0.340,P<0.001),FEV1%pred与PASP呈负相关(r=-0.234,P<0.001)。5.应用二元Logistic回归分析COPD-PH的危险因素,结果提示年龄≥65岁、合并糖尿病、A/G降低、BNP升高、FEV1%pred<50%是COPD-PH的危险因素。6.通过二元Logistic回归综合计算这5个危险因素指标得出联合预测指标,比较联合预测指标与年龄、合并糖尿病、A/G、BNP水平、FEV1%pred对PH的预测准确度,结果提示联合预测指标诊断COPD-PH的AUC为0.763,灵敏度为69.9%,特异度为73.6%;年龄诊断COPD-PH的AUC为0.648,灵敏度为53.6%,特异度为71.6%;A/G诊断COPD-PH的AUC为0.662,灵敏度为80.0%,特异度为48.9%;BNP诊断COPD-PH的AUC为0.736,灵敏度为59.2%,特异度为80.9%;FEV1%pred 诊断 COPD-PH 的 AUC 为 0.651,灵敏度为 52.0%,特异度为78%,联合预测指标的诊断效能最高。结论1.年龄≥65岁、合并糖尿病、A/G比值下降、BNP水平升高、肺通气功能重度及以上障碍的COPD患者容易并发PH,对此类患者需要评估PH。2.在排除左心衰竭、肾功能衰竭等其他可引起BNP升高的疾病后,BNP对COPD-PH有一定的预测价值。更多还原

【Abstract】 BackgroundChronic obstructive pulmonary disease(COPD)is a chronic respiratory inflammatory disease,but it has become the fourth leading cause of death globally.The common cause of death of COPD is related to Complications,which can affect the patient’s disease burden and survival rate.Pulmonary hypertension(PH)is one of the common complications of COPD.The incidence of chronic obstructive pulmonary disease-associated pulmonary hypertension(COPD-PH)is 20%to 91%.The rise of pulmonary arterial pressure will increase the acute exacerbation,poor prognosis and death risk of COPD patients,greatly increasing the economic burden and social burden.Therefore,Screening PH in COPD patient,which plays an important role in controlling the progression of the disease and improving the prognosis of patients.In addition,the COPD diagnosis and treatment guidelines do not indicate whether all COPD patients need to be screened for PH in the initial evaluation and follow-ups.The population characteristics and risk factors of COPD-PH are still unclear.Therefore,identifying the risk factors for COPD-PH and intervening it as soon as possible has a positive effect on reducing patient mortality and improving patients’ quality of life.purposeAnalyze the clinical characteristics and risk factors of in COPD-PH patients,to explore potential predictors of COPD-PH,and provide basis for the intervention of COPD progression and management.methodContinuous selection of COPD patients admitted to the Department of Respiratory Medicine of the First Affiliated Hospital of Zhengzhou University from January 2018 to January 2019,after screening for inclusion and exclusion criteria,482 patients were finally included.According to whether they were combined with PH,they were divided into COPD-PH group(132 cases)and COPD group(350 cases).Collected patient’s socio-demographic characteristics(gender,age,height,weight,comorbid disease,smoking history,duration of disease),laboratory data(blood routine,inflammation indicators,blood biochemistry,blood gas analysis,myocardial enzymes and brain natriuretic peptide,coagulation function)and lung function examination,doppler echocardiography,chest CT reaults.SPSS 22.0 software was used to analyze datas.compared the differences of general information,laboratory indexes and lung function indexes between patients in COPD-PH group and COPD group;analyzed the correlation between pulmonary artery systolic pressure(PASP)with different indexes;Logistic regression analysis of risk factors for COPD-PH;drew receiver operating characteristic(ROC)curve and analyzed of the diagnostic efficacy of various indicators for COPD-PH.result1.General information of the two groups of patients:the average age and the proportion of combined diabetes of the COPD-PH group were higher than that of the COPD group,which were(68.64±8.92 vs 64.38±9.02)years old,(28/104 vs 38/312),the difference was statistically significant(P<0.05).2.Analysis of laboratory results:Blood gas analysis showed that,PaCO2 and AB in the COPD-PH group were higher than those in the COPD group,respectively(52.60±13.93 vs 46.93±8.37)mmHg,(28.26±3.91 vs 26.82±3.21)mmol/L,the difference was statistically significant(P<0.05).Compared with the COPD group,the neutrophil/lymphocyte ratio and red blood cell distribution width were higher and platelet count was lower in the COPD-PH group,which were[2.66(1.85,4.05)vs 3.53(2.15,5.58)],(13.80±1.20 vs 14.21 ± 1.28)%,(222.35±77.47 vs 204.11±67.87)10^9/L,the difference was statistically significant(P<0.05).Comparing inflammation indicators,it can be seen that c-reactive protein of COPD-PH group was higher than that of COPD group[8.56(3.55,30.13)vs 4.69(1.26,15.34)mg/L],the difference was statistically significant(P<0.05).Comparing the blood biochemical indicators,compared with the COPD group,the COPD-PH group had lower albumin and A/G and higher globulin,respectively(39.92±4.85 vs 37.96±3.98)g/L,(1.68±0.39 vs 1.49±0.31),(24.76±4.86 vs 26.24±4.69).g/L,the difference was statistically significant(P<0.05).Comparing the differences between BNP,NT-proBNP and myocardial enzymes in the two groups of patients,the COPD-PH group had higher BNP and NT-proBNP than the COPD group,which were(133.54±77.66 vs 76.18±57.35)ng/L and(570.40±266.75 vs 256.70±194.27)ng/L,the difference was statistically significant(P<0.05),the difference of myocardial enzyme index between the two groups was not statistically significant.Comparing the coagulation function of the two groups of patients,the D-dimer of COPD-PH group was higher than that of COPD group[0.16(0.11,0.28)vs 0.11(0.07,0.19)]mg/L,the difference was statistically significant(P<0.05).3.Compared the lung function test indicators of the two groups:FEV1/FVC,FEV1%pred,FVC%pred,DLCO%pred of the COPD-PH group were lower than that of the COPD group,which were(44.86±12.69 vs 48.33± 11.39)%、(44.18±22.42 vs 52.74±19.73)%、(74.69±21.31 vs 84.35±20.11)%、(52.44±27.65 vs 60.11±25.70)%,the difference was statistically significant(P<0.05).4.Correlation analysis of various indicators and PASP,age was positively correlated with PASP(r=0.197,P<0.001),PaCO2 was positively correlated with PASP(r=0.208,P<0.001),RDW was positively correlated with PASP(r=0.182,P<0.001),A/G was negatively correlated with PASP(r=-0.222,P<0.001),BNP was positively correlated with PASP(r=0.0.340,P<0.001),FEV1%pred was negatively correlated with PASP(r=-0.234,P<0.001).5.The use of binary logistic regression analysis of risk factors of COPD-PH,the results suggested that age≥65 years old,with diabetes,A/G decreased,BNP increased,FEV1%pred<50%was risk factors of COPD-PH.6.Comprehensive calculation of these five high-risk factor indicators through binary logistic regression to obtain joint prediction indicators,compared the combined prediction indicators with age,combined diabetes,A/G ratio,BNP level,FEV1%pred indicators for PH prediction accuracy,The results suggested that the AUC for the diagnosis of COPD-PH with the combined predictors was 0.763,the sensitivity was 69.9%,and the specificity was 73.6%;the AUC for age diagnosis of the COPD-PH is 0.648,the sensitivity was 53.6%,and the specificity was 71.6%;the AUC for A/G diagnosis of COPD-PH was 0.662,sensitivity was 80.0%,specificity was 48.9%;the AUC for BNP diagnosis of COPD-PH was 0.736,sensitivity was 59.2%,specificity was 80.9%;the AUC for FEV1%pred diagnosis of COPD-PH was 0.651,the sensitivity was 52.0%,the specificity was 78%,and the diagnostic efficacy of the combined predictor was the highest.conclusion1.patients with age≥65 years old,diabetes mellitus,decreased A/G ratio,increased BNP level,severe pulmonary ventilation function obstacles or above are more likely to combine with PH.PH screening is more necessary for patients with this type of COPD patients.2.After excluding left heart failure,renal failure and other diseases that can increase BNP,BNP has a certain predictive value for COPD-PH.更多还原