肺功能和血浆IL-5及IL-8在不同表型哮喘间的差异性分析及风险预测

目的：分析支气管哮喘急性期患者不同气道炎症表型在临床特征、肺功能和血浆炎症因子方面的差异，探索炎症表型分型的风险因素。方法：前瞻性选取洛阳市中心医院2019年5月至2020年7月符合纳入排除标准的109例急性期哮喘患者作为哮喘组，根据诱导痰将其分为嗜酸性粒细胞型哮喘（eosinophilic asthma, EA）、中性粒细胞型哮喘（neutrophilic asthma, NA）、混合粒细胞型哮喘（mixedgranulocytic asthma, MA）和寡细胞型哮喘（paucigranulocytic asthma, PA），另纳入同期30例健康者作为对照组。收集受试者一般情况、哮喘控制测试（ACT）评分、肺功能、呼出气一氧化氮（FeNO）值，ELISA法检测血浆IL-5、IL-8水平。结果：对照组与哮喘组在过敏史、肺功能、FeNO、血浆炎症因子方面均有差异（P均<0.05）。与NA比，EA有过敏史比例及FeNO水平明显高，但吸烟患者比例明显低（P均<0.05）。PA肺功能（FEV1%及PEF%）和ACT评分均高于其他3组（P均<0.05），NA、MA组肺功能（FEV1/FVC、FEV1%、PEF%）均分别较EA、PA组差（P均<0.05）。嗜酸性炎症哮喘组（EA和MA）血浆IL-5含量高于非嗜酸性组（NA和PA），嗜中性炎症哮喘组（NA和MA）血浆IL-8含量高于非嗜中性组（EA和PA，P均<0.05）。分别按是否为嗜酸性炎症或嗜中性炎症对哮喘组行Logistic回归，提示FeNO及血浆IL-5含量增加、伴有过敏是嗜酸性炎症哮喘的危险因素（P均<0.05）；肺功能严重程度和血浆IL-8含量增加、ACT评分降低是嗜中性炎症哮喘的危险因素（P均<0.05）。结论：肺功能和血浆IL-5、IL-8在哮喘表型间有明显差异，肺功能分级、IL-5、IL-8、FeNO、伴过敏史和ACT评分是表型的风险因素。

Difference analysis and risk prediction of lung function and plasma IL-5 and IL-8 among different phenotypes of asthma

Objective: To analyze the differences of various airway inflammatory phenotypes in clinical features, pulmonary function and plasma inflammatory factors in patients with acute bronchial asthma, and to explore the risk factors for phenotypic classification. Methods: A total of 109 patients with acute asthma who met the inclusion and exclusion criteria from May 2019 to July 2020 in Luoyang Central Hospital were prospectively selected as asthma group. According to induced sputum, the subjects were divided into eosinophilic asthma （EA）, neutrophil asthma （NA）, mixed granulocytic asthma （MA） and oligocytic asthma （PA）. Meanwhile, 30 healthy persons were included as the control group. The general condition, asthma control test （ACT）, pulmonary function, and exhaled nitric oxide （FeNO） of subjects were recorded, and plasma IL-5 and IL-8 levels were measured by ELISA. Results:  There were significant difference in allergies, lung function, and plasma inflammation factors between control group and asthma group（all P<0.05）. The proportion of EA with allergic history and FeNO level was higher than those in NA group, but the proportion of smoking patients was lower （all P<0.05）. The scores of PA pulmonary function （FEV1% and PEF%） and ACT were higher than those of the other three groups （all P<0.05）. The pulmonary function （FEV1/FVC, FEV1%, PEF%） in NA and MA groups was worse than that in EA and PA groups. The content of plasma IL-5 in eosinophilic inflammatory asthma group （EA and MA） was higher than that in non-eosinophilic group （NA and PA）, and the level of plasma IL-8 in neutrophilic inflammatory asthma group （NA and MA） was higher than that in non-neutrophilic group （EA and PA, all P<0.05）. Logistic regression was performed in asthma group according to whether it was eosinophilic inflammation or neutrophilic inflammation. The results suggest that the increase of FeNO and serum IL-5 level and allergy are the risk factors for eosinophilic inflammatory asthma, and the severity of lung function, the increase of plasma IL-8 level and the decrease of ACT score are the risk factors of neutrophilic inflammatory asthma （all P<0.05）. Conclusion:  Pulmonary function and plasma IL-5 and IL-8 were significantly different among asthma phenotypes. Pulmonary function grade, IL-5, IL-8, FeNO, history of allergy and ACT score were risk factors for phenotype variation. ［Key words］asthma；inflammatory phenotype; IL-5; IL-8; FeNO; pulmonary function