嗜酸性粒细胞哮喘的研究进展

doi:10.19983/j.issn.2096-8493.20220073

摘要/Abstract

摘要：

哮喘是临床常见的异质性慢性气道炎症性疾病,其中嗜酸性粒细胞哮喘(eosinophilic asthma,EA)是最常见的临床表型。持续性气道嗜酸性粒细胞炎症极易促使哮喘进展为重症,是导致哮喘高致残率及高致死率的原因之一。变应性EA与非变应性EA在临床特征、发病机制方面具有明显区别,深入认识EA发病机制对疾病的管理和改善患者预后具有重要意义。作者对EA的研究进展进行综述。

关键词: 嗜酸粒细胞, 哮喘, 疾病特征, 发病机制, 诊断

Abstract:

Asthma is a heterogenous chronic airway inflammatory disease with various phenotypes,among which eosinophilic asthma (EA) is the most common one. Persistent eosinophilic airway inflammation may lead to severe asthma, and thus accounts for the high morbidity and mortality rates. Allergic EA and non-allergic EA subtypes varied significantly in terms of their clinical characteristics and pathogenesis. Recognizing pathogenic mechanism of EA is of great significance for disease management and for improving patient’s prognosis. In this review, we summarized the research progress on EA.

Key words: Eosinophils, Asthma, Disease attributes, Pathogenic mechanism, Diagnosis

中图分类号:

R562.2+5

林慧敏, 符昱, 方章福, 谢佳星. 嗜酸性粒细胞哮喘的研究进展[J]. 结核与肺部疾病杂志, 2022, 3(4): 328-333. doi: 10.19983/j.issn.2096-8493.20220073

Lin Huimin, Fu Yu, Fang Zhangfu, Xie Jiaxing. Research progress on eosinophilic asthma[J]. Journal of Tuberculosis and Lung Disease, 2022, 3(4): 328-333. doi: 10.19983/j.issn.2096-8493.20220073

图/表 2

图1

变应性EA与非变应性EA发病机制注图中黑色虚线左侧为变应性嗜酸性粒细胞哮喘(eosinophilic asthma,EA)的免疫学机制通路,即变应原被树突状细胞(dendritic cell,DC)识别,并诱导DC分化,DC通过释放白细胞介素(interleukin,IL)-4诱导CD4+T细胞分化为2型辅助性T淋巴细胞(T helper lymphocytes 2,Th2);此外,变应原可通过刺激气道上皮细胞释放警报因子,如IL-33、IL-25及胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin,TSLP),警报因子能够促进Th2细胞的活化。活化的Th2通过释放IL-4、IL-5、IL-13、IL-9等2型炎症因子,其中IL-4和IL-13能够促进B细胞分化为浆细胞,最后产生免疫球蛋白E(immunoglobulin E,IgE);IgE与肥大细胞表面受体结合后形成致敏状态,当再次暴露于变应原时,肥大细胞通过脱颗粒释放多种炎症介质,如组胺、半胱氨酸白三烯(cysteinyl leukotriene,cysLT)和前列腺素D2(prostaglandin D2,PGD2),诱导变应性气道炎症;黑色虚线右侧概括了非变应性EA的发生机制,即环境中的非变应原(PM2.5、臭氧及病原体等)刺激气道上皮细胞释放警报素,后者能够与2型固有淋巴细胞(type 2 innate lymphocytes,ILC2)相应的受体结合,激活的ILC2能够释放大量IL-5、IL-13、IL-9等炎症因子,介导气道嗜酸性粒细胞炎症发生。两种表型EA都是以IL-5作为关键炎症因子,IL-5能够促进Eos的存活及分化,并诱导Eos释放主要碱性蛋白(major basic protein,MBP)、嗜酸性粒细胞阳离子蛋白(eosinophil cationic protein,ECP)、嗜酸性粒细胞过氧化物酶(EPO)和嗜酸性粒细胞衍生神经毒素(eosinophil derived neurotoxin,EDN)、cysLT、PDG2和血小板激活因子(platelet activating factor,PAF)等炎症介质,引起气道黏液分泌增加、平滑肌细胞增生、气道高反应性(airway hyperresponsiveness,AHR)、气道重塑等病理改变;此外,Eos释放的毒性蛋白颗粒(如MBP、ECP、EPO及EDN)能形成嗜酸性粒细胞胞外陷阱(eosinophil extracellular trap,EET),而Eos发生细胞溶解时可在气道内形成夏科-雷登结晶(Charcot-Leyden crystal,CLC),以上因素进一步加重了哮喘气道炎症;TCR:T细胞受体(T cell receptor);HLA:人白细胞抗原(human leukocyte antigen)

图1

表1

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临床指标	变应性EA	非变应性EA
诱因	变应原(多为吸入变应原)	非过敏因素(PM2.5、臭氧及微生物等)
发病年龄	多为早发性(儿童)	多为迟发性(成人)
疾病发展进程	进展相对缓慢	起病症状重,进展速度快
伴发疾病	常伴其他变应性疾病(变应性皮炎、变应性鼻炎等)	慢性鼻炎-鼻窦炎伴或不伴鼻息肉
过敏史	多为过敏体质,有食物药物过敏史或吸入性、接触性过敏史	多无
预后	规律使用抗炎药物能较好控制	难控制,容易发生激素抵抗,或进展为重症
外周血总IgE	升高	多数为正常水平