【作者】 李瑞；

【导师】 刘剑波；

【作者基本信息】 郑州大学 ， 内科学（专业学位）， 2021， 硕士

【摘要】 背景与目的慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD,简称慢阻肺）是一种以渐进性呼吸困难及肺功能下降为特征的慢性呼吸系统疾病,由于其患病率高、生存期及预后差、社会经济负担重,已成为一个重要的全球健康卫生问题。慢阻肺急性加重（acute exacerbation of chronic obstructive pulmonary disease,AECOPD）是影响慢阻肺患者生活质量、引起肺功能损害及造成经济负担的重要原因。因此,做好慢阻肺患者病程分期的早诊断、早治疗是慢阻肺管理的重要环节。肺功能检测是临床上诊断慢阻肺、评估气流受限程度的金标准,但是其测定值容易受多种因素的影响,且当患者存在急性呼吸困难、活动性咯血、生命体征不稳定等情况时,都无法完成肺功能测试,影响病情评估。因此有必要找出简便易行、可重复测量的常规检验指标,以协助评估慢阻肺病情、辨别慢阻肺不同病程分期及评估气流受限,满足不同情况的慢阻肺患者临床管理的需求。纤维蛋白原与前白蛋白比值（Fibrinogen-to-Prealbumin ratio,FPR）是一项综合了凝血状态和营养状况的新的炎性指标,多项研究证实FPR与急性胰腺炎、胃癌、肝癌等的疾病活动度、严重程度相关,由此推测FPR与炎症反应相关。本研究依据是否患有慢阻肺、处于慢阻肺的哪种病程分期将纳入的研究对象分组,比较其炎性指标、肺功能,探讨FPR与慢阻肺诊断、慢阻肺病程分期及气流受限的关系。对象与方法回顾性收集2017年06月至2020年10月在郑州大学第二附属医院住院治疗的急性加重期慢性阻塞性肺疾病患者（AECOPD组）、门诊复查的稳定期慢性阻塞性肺疾病患者（SCOPD组）及同时期的健康体检者（健康组）的一般资料:性别、年龄、病史、身高、体重、吸烟史等;炎性指标:入院24小时以内检测的白介素-6（interleukin-6）、降钙素原（PCT）、C反应蛋白（C-reactive protein,CRP）、纤维蛋白原（Fibrinogen,FIB）、前白蛋白（prealbumin,PA）,并根据收集到的数据计算体质指数（BMI）、FPR;肺功能指标:第1秒用力呼气量（FEV1）、FEV1占预计值的百分比（FEV1%pred）、用力肺活量（FVC）。探讨健康组、SCOPD组及AECOPD组患者一般资料、炎性指标及肺功能指标的水平;将AECOPD组患者根据FEV₁%pred分为轻度气流受限组（FEV₁%pred≥80%及50%≤FEV₁%pred<80%,109例）、中度气流受限组（30%≤FEV₁%pred<50%,51例）及重度气流受限组（FEV₁%pred<30%,20例）,比较三组患者的一般资料、炎性指标及肺功能;绘制ROC曲线,分析IL-6、PCT、CRP及FPR在慢阻肺诊断中的作用,进一步绘制ROC曲线,分析IL-6、PCT、CRP及FPR在慢阻肺不同病程分期诊断的作用。结果（1）健康组、SCOPD组和AECOPD组患者性别构成、年龄、BMI及吸烟史的差异无统计学意义（P>0.05）,AECOPD组患者的IL-6、PCT、CRP、FIB、PA、FPR水平高于SCOPD组患者,差异具有统计学意义（P<0.05）;SCOPD组患者的IL-6、PCT、CRP、FIB、FPR水平高于健康组患者,差异具有统计学意义（P<0.05）,PA的差异无统计学意义（P>0.05）;AECOPD组-SCOPD组、AECOPD组-健康组、SCOPD组-健康组两两比较,IL-6、PCT、CRP、FIB、FPR的差异均具有统计学意义（P<0.05）,PA在SCOPD组-健康组组间的差异无统计学意义（P>0.05）。AECOPD组患者的FEV1、FEV1%pred、FVC水平低于SCOPD组患者,差异具有统计学意义（P<0.05）;SCOPD组患者的FEV1、FEV1%pred、FVC水平低于健康组患者,差异具有统计学意义（P<0.05）,AECOPD组-SCOPD组、AECOPD组-健康组、SCOPD组-健康组两两比较,FEV1、FEV1%pred、FVC的差异具有统计学意义（P<0.05）。（2）轻度气流受限组、中度气流受限组及重度气流受限组患者的性别构成、年龄、BMI及吸烟史的差异无统计学意义（P>0.05）。比较炎性指标,结果示IL-6、PCT、CRP、FIB及FPR在三组间的差异均有统计学意义（P<0.05）,PA（P=0.584>0.05）的差异无统计学意义。轻度-中度、中度-重度、轻度-中度组间两两比较,结果示IL-6、PCT、CRP、FIB及FPR在各组间的差异均有统计学意义（P<0.05）,轻度-中度PA（P=0.384）、中度-重度PA（P=0.901）、轻度-重度PA（P=0.458）在各组间两两比较,差异均无统计学意义（P>0.05）。（3）诊断慢阻肺的ROC曲线示:IL-6（AUC和95%CI分别为0.810,（0.764,0.855））、PCT（AUC和95%CI分别为0.787,（0.729,0.845））、CRP（AUC和95%CI分别为0.831,（0.758,0.867））、FPR（AUC和95%CI分别为0.857,（0.816,0.897））对于慢阻肺均有较好的诊断作用。各项指标诊断慢阻肺的最佳截断值、敏感性和特异性分别为IL-6 8.414（78.0%,76.8%）、PCT 0.126（87.5%,55.1%）、CRP 7.878（72.7%,81.2%）、FPR15.089（67.4%,95.7%）,其约登指数分别为0.548、0.426、0.539、0.631。判断慢阻肺不同病程分期的ROC曲线示:IL-6（AUC和95%CI分别为0.66,（0.596,0.724））、PCT（AUC和95%CI分别为0.735,（0.677,0.793））、CRP（AUC和95%CI分别为0.704,（0.639,0.769））、FPR（AUC和95%CI分别为0.795,（0.742,0.848））对于慢阻肺病程分期均有较好的诊断作用。各项指标诊断慢阻肺不同病程的最佳截断值、敏感性和特异性分别为IL-6 16.084（78.0%,89.3%）、PCT0.737（45.6%,91.4%）、CRP 9.512（62.8%,76.2%）、FPR18.681（65.6%,83.3%）,其约登指数分别为0.360、0.456、0.390、0.489。结论（1）急性加重期慢阻肺患者的FPR水平高于稳定期慢阻肺患者,稳定期慢阻肺患者的FPR水平高于健康人群;（2）气流受限程度严重患者的FPR水平高于气流受限程度低的患者,可以将FPR用于判断无法实施肺功能的患者的气流受限程度;（3）在患者无法完成肺功能测试时,FPR可以作为慢阻肺诊断的一项参考指标;（4）FPR可以用于判断慢阻肺患者的稳定期和急性加重期。更多还原

【Abstract】 Background and ObjectiveChronic obstructive pulmonary disease（COPD）is a chronic respiratory disease characterized by progressive breathing difficulties and decreased lung function,which has becomed an important global health problem due to its high prevalence,poor survival and prognosmation,and heavy socio-economic burden.Acute exacerbation of COPD（AECOPD）is an important cause affecting the quality of life of COPD patients,causing damage to lung function and causing financial burden,so early diagnosis and early treatment of COPD patients is an important part of COPD management.Lung function testing is the gold standard for clinical diagnosis of slow-blocking lungs and assessment of the degree of air flow restriction,but the measurement value of lung function is easily affected by a variety of factors,and when patients have acute breathing difficulties,active hemoptysis,unstable vital signs,etc,can not complete the lung function test,affecting the assessment of the disease.Therefore,it is necessary to identify the conventional test indicators that can be used to assist in the diagnosis of COPD,to identify the different course stages of COPD and to assess airflow constraints to meet the clinical management needs of COPD patients in different situations.Fibrinogen-to-Prealbumin ratio（FPR）is a new inflammatory index that combines fibrinogen and pre-albumin to reflect the body’s blood clotting and nutritional status,and several studies have confirmed that FPR is associated with the activity and severity of diseases such as acute pancreatitis,stomach cancer,liver cancer,and so on.Based on whether or not there is a chronic pulmonary disease,which disease stage will be included in the study group,collect the patient’s inflammatory index,lung function,explore the relationship between FPR and COPD diagnosis,slow-blocking lung disease phased and limited airflow.Objects and MethodsRetrospective Collection Patients with Acute Aggravated Chronic Obstructive Pulmonary Disease（AECOPD Group）and Patients with Stable Period chronic Obstructive Pulmonary Disease（SCOPD Group）hospitalized at the Second Affiliated Hospital of Zhengzhou University from June 2017 to October 2020 General information on health check-ups（health groups）in the same period:age,sex,medical history,height,weight and smoking history,etc.Inflammation indicators:interlethional-6,procalcitonin（PCT）,C-reactive protein,fibrinogen,prealbumin,lung function indicators:1st second force exhalation（FEV1）,force lung capacity（FVC）,FEV1 as a percentage of the expected value（FEV1%pred）,The fibrinogen-to-prealbumin ratio（FPR）is calculated based on the data collected.The levels of general data,inflammatory index and lung function index of patients in health group,SCOPD group and AECOPD group were discussed,and patients in AECOPD group were grouped according to FEV1%pred,and mild airflow restricted group（FEV1%pred≥80%and 50%≤FEV₁%pred<80%,109 cases）,moderate airflow restricted group（30%≤FEV₁%pred<50%,51 cases）,severe airflow restricted group（FEV1%pred<30%,20 cases）,comparing general data,inflammatory indicators and lung function of three groups of patients,mapping ROC curve,analyzing the efficacy of IL-6,PCT,CRP and FPR diagnosis of slow-blocking lungs,further mapping ROC curve,analyzing the effectiveness of IL-6,PCT,CRP and FPR diagnosis of different courses of COPD.Results（1）The differences in sex composition,age,BMI and smoking historyin patients in the health group,SCOPD group and AECOPD group were not statistically significant（P>0.05）,and the levels of IL-6,PCT,CRP,FIB,PA,and FPR in patients in the AECOPD group were higher than those of SCOPD In the group of patients,the difference was statistically significant（P<0.05）,and the difference in the SCOPD group was statistically significant（P<0.05）and the difference in PA was not statistically significant in patients with IL-6,PCT,CRP,FIB,and FPR levels（P>0.05）;AECOPD group-SCOPD group,AECOPD group-health group,SCOPD group-health group two-two comparison,IL-6,PCT,CRP,FIB,FPR differences are statistically significant（P<0.05）,PA differences between SCOPD group-health groups are not statistically significant（P>0.05）.The differences were statistically significant（P<0.05）in patients in the AECOPD group in patients with FEV1,FEV1%pred,and FVC levels were lower than in the SCOPD group,FVC level is lower than health group patients,the difference is statistically significant（P<0.05）,AECOPD group-SCOPD group,AECOPD group-health group,SCOPD group-health group two-two comparison,The differences between FEV1,FEV1%pred,and FVC are statistically significant（P<0.05）.（2）The differences in sex composition,age,BMI and smoking history of patients in the mild airflow restricted group,the moderate airflow restricted group,and the severe airflow restricted group were not statistically significant（P>0.05）.Comparing inflammatory indicators,the results showed that the differences between IL-6,PCT,CRP,FIB and FPR were statistically significant（P<0.05）and PA（P=0.584>0.05）were not statistically significant.Mild-moderate,moderate-heavy,mild-moderate groups were compared between two or two,and the results showed that the differences between IL-6,PCT,CRP,FIB and FPR were statistically significant（P<0.05）,when compared between the two groups,mild-moderate PA（P=0.384）,moderate-heavy PA（P=0.901）,and mild-heavy PA（P=0.458）,the differences were not statistically significant（P>0.05）.（3）ROC curve for diagnosis of COPD:IL-6（AUC and are 95%CI 0.81,（0.764,0.855））,PCT（AUC and 95%CI are 0.787,（0.729,0.845））,CRP（AUC and 95%CI are 0.831,（0.758,0.867））,FPR（AUC and 95%CI are 0.857,（0.816,0.897））respectively for slow-blocking lungs have good diagnostic performance.The diagnostic best truncation values,sensitivity and specificity of the indicators were IL-6 8.414（78.0%,76.8%）,PCT 0.126（87.5%,55.1%）,CRP 7.878（72.7%,81.2%）,FPR15.089（67.4%,95.7%）,and the Jordon index was 0.548,0.426,0.539 and 0.631.ROC curve for determining the stages of different stages of COPD:IL-6（AUC and 95%CI are 0.66,（0.596,0.724））,PCT（AUC and 95%CI are 0.735,（0.677,0.793））,respectively CRP（AUC and 95%CI are 0.704,（0.639,0.769））,FPR（AUC and 95%CI are 0.795,（0.742,0.848））respectively for the chronic pulmonary disease phased have better diagnostic performance.The diagnostic best truncation values,sensitivity and specificity of the indicators were IL-6 16.084（78%,89.3%）,PCT 0.737（45.6%,91.4%）,CRP 9.512（62.8%,76.2%）,FPR18.681（65.6%,83.3%）,and the Jordon index was 0.360,0.456,0.390 and 0.489.Conclusions（1）The FPR level of patients with acute exacerbation period was higher than that of patients with chronic pulmonary resistance during stabilization period,and the level of FPR in patients with stability period was higher than that of healthy population;（2）The FPR level of patients with severe airflow restriction is higher than that of patients with low airflow restriction,which can be used to determine the degree of air flow restriction in patients who are unable to perform lung function;（3）FPR can be used as a reference index for the diagnosis of slow-blocking lung when the patient is unable to complete the lung function test;（4）FPR can be used to determine the stabilization and acute exacerbation periods of patients with chronic pulmonary resistance.更多还原