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-东南大学学报医学版

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

作者：雷芳龚霞

单位：重庆市大足区人民医院儿科, 重庆 402360

分类号：R725.6;R562.25

出版年·卷·期（页码）：2021·40·第三期（324-330）

摘要：

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 factor α (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.

参考文献：

[1] 邹艳萍, 罗小兰, 刘利.布地奈德与丙酸倍氯米松辅助特布他林雾化吸入治疗小儿哮喘急性发作的对比研究[J]. 中国药房, 2016, 27(17):2388-2391.
[2] GUILBERT T W, BACHARIER L B, FITZPATRICK A M.Severe asthma in children[J]. J Allergy Clin Immunol Pract, 2014, 2(5):489-500.
[3] 韩莹, 蔡庆宇, 张岩.泻肺定喘汤对中性粒细胞型哮喘大鼠KLF-2/RelA比例平衡及中性粒细胞凋亡的影响[J]. 中国中医急症, 2019, 28(4):607-610, 614.
[4] HORINOKITA I, HAYASHI H, OTEKI R, et al. Involvement of progranulin and granulin expression in inflammatory responses after cerebral ischemia[J]. Int J Mol Sci, 2019, 20(20):5210.
[5] POGONOWSKA M, PONIATOWSKI Ł A, WAWRZYNIAK A, et al. The role of progranulin (PGRN) in the modulation of anti-inflammatory response in asthma[J]. Cent Eur J Immunol, 2019, 44(1):97-101.
[6] 鲍一笑, 陈爱欢, 符州, 等. 儿童支气管哮喘诊断与防治指南(2016年版)[J]. 中华儿科杂志, 2016, 54(3):167-181.
[7] 孙晓丽, 张湘华, 曹晓玮.呼出气一氧化氮对支气管哮喘的诊断价值及其与疾病严重程度的关系[J]. 中国医药导报, 2020, 17(22):82-85.
[8] 盖晓燕, 常春, 王娟, 等. 中性粒细胞型哮喘患者的气道炎症与小气道重构分析[J]. 北京大学学报(医学版), 2018, 50(4):645-650.
[9] RAY A, KOLLS J K.Neutrophilic inflammation in asthma and association with disease severity[J]. Trends Immunol, 2017, 38(12):942-954.
[10] GRUNWELL J R, STEPHENSON S T, TIROUVANZIAM R, et al. Children with neutrophil-predominant severe asthma have proinflammatory neutrophils with enhanced survival and impaired clearance[J]. J Allergy Clin Immunol Pract, 2019, 7(2):516-525.
[11] CAI Y, CAO Y X, LU S M, et al. Infliximab alleviates inflammation and ex vivo airway hyperreactivity in asthmatic E3 rats[J]. Int Immunol, 2011, 23(7):443-451.
[12] PARK S Y, HONG G H, PARK S, et al. Serum progranulin as an indicator of neutrophilic airway inflammation and asthma severity[J]. Ann Allergy Asthma Immunol, 2016, 117(6):646-650.
[13] PELAIA G, VATRELLA A, BUSCETI M T, et al. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma[J]. Mediators Inflamm, 2015, 2015(7):879783.
[14] TANG W, LU Y, TIAN Q Y, et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice[J]. Science, 2011, 332(6028):478-484.
[15] 黄闯, 黄琨.颗粒蛋白前体在炎症性疾病中的作用研究进展[J]. 细胞与分子免疫学杂志, 2016, 32(2):268-271.
[16] CHEN X, LIU J, ZHU M, et al. Progranulin is a novel biomarker for predicting an acute exacerbation of chronic obstructive pulmonary disease[J]. Clin Respir J, 2018, 12(10):2525-2533.

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