中性粒细胞型哮喘患儿急性发作期血清颗粒蛋白前体与疾病严重程度及气道炎症的关系

Relationship between serum progranulin and severity of disease,airway inflammation in children with acute neutrophilic asthma exacerbation

目的:探讨中性粒细胞型哮喘患儿急性发作期的血清颗粒蛋白前体(PGRN)与疾病严重程度及气道炎症的关系。方法:选取2019年1月至10月期间在我院儿科就诊的185例哮喘患儿,包括115例急性发作期患儿(急性组)和70例临床缓解期患儿(缓解组),另外选取30例健康儿童的血样作为对照组,用以检测血清PGRN水平。将哮喘患儿根据痰涂片进行气道炎症分型;另外检测两组哮喘患儿血清PGRN、肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)、全血中性粒细胞(NEU)计数、肺功能参数[用力肺活量(FVC)、第1秒用力呼气容积(FEV1)、最大呼气峰值流速(PEF)、FEV1占预计值的百分比(FEV1%pred)和FEV1/FVC]。采用多因素Logistic回归分析法和受试者工作特征(ROC)曲线评估血清PGRN水平诊断重度哮喘的价值。结果:急性组和缓解组患儿血清PGRN水平低于对照组,尤其是急性组患儿血清PGRN水平降低更明显(P<0.001)。急性组中性粒细胞型患儿血清PGRN水平低于嗜酸粒细胞型患儿(P<0.05)。经Pearson相关性分析,中性粒细胞型哮喘急性发作期患儿血清PGRN水平与FEV1%pred、FEV1/FVC、PEF均呈正相关(r=0.756、0.703、0.411,P<0.001),并且与血清TNF-α水平、IL-8水平、全血NEU计数均呈负相关(r=-0.537,-0.541,-0.413,P<0.001)。经多因素Logistic回归分析,血清PGRN是中性粒细胞型哮喘急性发作期患儿重度疾病的独立保护因素(OR=0.886,95%CI:0.847~0.958,P<0.001),且血清PGRN水平诊断中性粒细胞型哮喘急性发作期患儿重度疾病的ROC曲线下面积为0.876(95%CI:0.781~0.972),灵敏度和特异度分别为73.90%和88.50%。结论:检测中性粒细胞型哮喘患儿急性发作期时的血清PGRN水平可以反映疾病严重程度,其有望成为新的抑制中性粒细胞气道炎症反应加重的潜在靶点。

Objective:To evaluatethe the relationship between serum progranulin(PGRN)and severity of asthma,airway inflammation in children with acute neutrophilic asthma exacerbation.Methods:A total of 185 children in pediatric department of our hospital from January to October in 2019 were selected,including 115 children with acute asthma exacerbation(acute group)and 70 children with asthma at clinical remission stage(remission group).All the children underwent sputum induction,and the cellular composition of the sputum was evaluated.Then 30 healthy children were selected as the control group,and the serum PGRN level was detected.The serum PGRN level,tumor necrosis factorα(TNF-α),interleukin-8(IL-8),whole blood neutropenia(NEU)and pulmonary function parameters[forced vital capacity(FVC),forced expiratory volume in one second(FEV1),percentage of forced expiratory volume in one second in the projected value(FEV1%pred),forced expiratory volume in one second/forced vital capacity(FEV1/FVC),peak expiratory flow(PEF)]were detected.The value of serum PGRN level in diagnosing severity of disease was evaluated by multivariate Logistic regression analysis and receiver operating characteristic(ROC)curve.Results:The serum PGRN level of the acute group and the remission group was lower than that of the control group,especially the serum PGRN level of the acute group was more significantly decreased(P<0.05).In the acute group,the serum PGRN level of children with neutrophilic asthma was lower than that of children with eosinophilic asthma(P<0.05).By the Pearson correlation analysis,the serum PGRN level was positive correlation with FEV1%pred,FEV1/FVC,PEF in children with acute neutrophilic asthma exacerbation(r=0.756,0.703,0.411,P<0.001),and the serum PGRN level was negative correlation with the level of serum TNF-α,IL-8,complete blood NEU count(r=-0.537,-0.541,-0.413,P<0.001).Multivariate Logistic regression analysis showed that increased serum PGRN level was an independent protective factor for the severe asthma in children with acute neutrophilic asthma exacerbation(OR=0.886,95%CI:0.847-0.958,P<0.001),and ROC curve analysis showed that the predicted area under the curve of the serum PGRN level for diagnosing the severe asthma in children with acute neutrophilic asthma exacerbation was 0.876(95%CI:0.781-0.972),and the sensitivity and specificity were respectively 73.90%and 88.50%.Conclusion:The detection of serum PGRN level in children with acute neutrophilic asthma exacerbation can reflect the severity of asthma disease,and it is expected to be a new potential target for inhibiting neutrophilic airway hyperreactivity.