晚发型重度难治性哮喘气道炎症表型与激素疗效的临床研究  

Clinical study on airway inflammation phenotype and steroid effect in adult late-onset severe refractory asthma

作　　者：刘振千[1] 王凡[1] 陈韦[1] 韩志海[1] Liu Zhenqian;Wang Fan;Chen Wei;Han Zhihai(Department of Respiratory Medicine,The PLA Navy General Hospital,Beijing 100048,China)

机构地区：[1]中国人民解放军海军总医院呼吸内科,北京100048

出　　处：《中华肺部疾病杂志（电子版）》2018年第1期72-77,共6页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：军队后勤科研计划重点项目(BHJ14C009)

摘　　要：目的探讨成人晚发型重度难治性哮喘患者的气道炎症类型及对激素治疗的反应,以期阐明该型哮喘的发病机制和治疗策略。方法连续收集正常对照者(A组)、确诊的成人晚发型轻中度(B组)、重度哮喘患者(C组),分别采集哮喘患者治疗前以及激素治疗后的诱导痰液,进行炎性细胞分类计数,采用酶联免疫吸附测定法检测痰中IL-17、IL-8、IL-6、IL-5浓度及中性粒细胞弹性蛋白酶水平,并记录患者治疗前后的肺功能、哮喘控制评分等基线情况。比较三组患者间的不同以及治疗前后的差别,并采用相关分析及多元直线回归方程筛选与气道炎症和哮喘控制评分相关的指标。结果在全部146例哮喘患者中,重度哮喘所占比例将近1/3。与轻中度哮喘相比,重度哮喘患者有着较低的特应质比例、FEV1值和哮喘控制评分,但年龄及体质指数均较高。诱导痰细胞检查显示,治疗前的重度哮喘诱导痰嗜酸细胞比例低于轻中度哮喘(4.59%vs.7.74%,P<0.01),而中性粒细胞比例则明显增加(63.22%vs.22.8%,P<0.01)。轻中度哮喘的气道炎症类型以嗜酸性粒细胞型为主,重度哮喘则以中性粒细胞型为最多(P<0.01)。与正常对照和轻中度哮喘相比,重度哮喘患者诱导痰中的炎症介质IL-17、IL-8、IL-6及中性粒细胞弹性蛋白酶浓度亦显著升高(P<0.01)。相关分析显示,哮喘患者痰中性粒细胞比例与IL-17浓度正相关(r=0.545,P<0.01)。而直线回归分析提示,哮喘控制评分与IL-17和体质指数呈负回归关系(P<0.01)。激素治疗可明显降低轻中度哮喘诱导痰内嗜酸性粒细胞和中性粒细胞比例及炎症介质浓度,提高哮喘控制评分和FEV1(P<0.01),而重度哮喘仅有诱导痰嗜酸细胞计数及IL-5浓度的降低,余炎性介质浓度、中性粒细胞比例及哮喘控制评分无改善(P<0.05)。结论成人晚发型重度哮喘是不同于轻中度哮喘的一种特殊亚型,其气道炎症成分复杂,以Objective To investigate airway inflammation phenotype and responses to steroid treatment in adult late-onset severe asthma,and further highlight the underlying mechanisms as well as therapy strategy for this asthma phenotype.Methods Healthy control subjects and adults diagnosed with late-onset mild,moderate and severe asthma were consecutively enrolled.Induced sputum were collected and processed for inflammatory cell differential respectively before and after steroid treatment in asthmatic patients.Sputum IL-17,IL-8,IL-6,IL-5 concentrations and neutrophil elastase levels were determined by enzyme-linked immunosorbent assay.Demographic information,Asthma control test(ACT)score and data of pulmonary function test were recorded and compared in three groups.B ivariate Correlate and Linear Regression were used to analyze risk factors for airway inflammation and ACT.Results Almost one third of patients were severe asthmatic in total 146 subjects.Apart from the expected lower FEV 1,poor ACT,older age and higher BMI level,patients with adult onset severe asthma were more often nonatopic compared with mild and moderate asthma.On the basis of induced sputum cell analysis,different phenotypes of airway inflammation were determined that mild to moderate asthma was eosinophilic,but severe asthma was neutrophilic(P<0.01).Compared with healthy control and mild to moderate asthma,percent sputum eosinophils was lower in severe asthma(4.59%vs.7.74%,P<0.01),but percent sputum neutrophils was significantly increased with elevated IL-17,IL-8,IL-6 and neutrophil elastase levels at initial treatment(63.22%vs.22.8%,P<0.01).IL-17 concentration was positively correlated with percent sputum neutrophils(r=0.545,P<0.01)by bivariate correlate in asthmatic patients.Nevertheless,in multiple regression analysis of subjects with asthma,IL-17 concentration was significantly negative predictor of ACT score.After 4-week steroid inhalation or systemtic use,concentrations of all inflammatory factors were remarkably decreased with increased ACT score

关 键 词：支气管哮喘 重度难治性 气道炎症 激素 

分 类 号：R562[医药卫生—呼吸系统]