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痰中肥大细胞与哮喘临床和炎症特征的关系。

Relationship of sputum mast cells with clinical and inflammatory characteristics of asthma.

机构信息

Priority Research Centre for Healthy Lungs, The University of Newcastle, Newcastle, NSW, Australia.

National Health and Medical Research Council Centre of Excellence in Severe Asthma, Newcastle, NSW, Australia.

出版信息

Clin Exp Allergy. 2020 Jun;50(6):696-707. doi: 10.1111/cea.13609. Epub 2020 May 4.

DOI:10.1111/cea.13609
PMID:32291815
Abstract

BACKGROUND

Mast cells (MCs) are innate immune cells that regulate atopic and non-atopic inflammation in the airways. MCs play a critical role in the pathogenesis of asthma, yet their relationship to airway and systemic inflammation and clinical characteristics of asthma is poorly understood.

OBJECTIVE

To quantify MCs in induced sputum samples and understand their relationship to airway and circulatory immune cells, and clinical variables in asthma.

METHODS

We employed flow cytometry of sputum samples to quantify MCs, basophils and other immune cells in 51 participants (45 asthma and 6 non-asthma controls). Relationship of MCs to airway (n = 45) and blood (n = 19) immune cells, participant demographics, asthma history, spirometry and airways hyperresponsiveness (AHR) to hypertonic saline was determined by correlation and comparison of cut-off-based sputum MC high vs low participants.

RESULTS

Mast cells, basophils and eosinophils were increased in asthma vs non-asthma control sputum. In asthma sputum, MCs, basophils and eosinophils were significantly intercorrelated, and MCs and basophils were elevated in participants with eosinophilic asthma. MCs and basophils, but not eosinophils, correlated with AHR. Sputum MC high asthma was characterized by an increased proportion of participants with uncontrolled asthma and reduced FEV and FVC. Trends towards similar clinical associations with elevated MCs were observed in a paucigranulocytic subpopulation (n = 15) lacking airway eosinophilia or neutrophilia. Receiver operator characteristic (ROC) analysis showed peripheral blood eosinophil (PBE) count predicted elevated sputum eosinophils and basophils, but not MCs.

CONCLUSIONS AND CLINICAL RELEVANCE

Sputum MCs are elevated in asthma, and their measurement may be useful as they relate to key clinical features of asthma (spirometry, asthma control, AHR). PBE count did not predict airway MC status, suggesting direct measurement of airway MCs by sensitive methods such as flow cytometry should be further developed.

摘要

背景

肥大细胞(MCs)是先天免疫细胞,可调节气道中的过敏性和非过敏性炎症。MCs 在哮喘发病机制中起关键作用,但它们与气道和全身炎症以及哮喘的临床特征之间的关系尚未得到充分了解。

目的

定量检测诱导痰样本中的 MCs,并了解其与气道和循环免疫细胞以及哮喘临床变量之间的关系。

方法

我们采用流式细胞术检测 51 名参与者(45 名哮喘患者和 6 名非哮喘对照者)痰样本中的 MCs、嗜碱性粒细胞和其他免疫细胞。通过相关性和基于截止值的高 MC 与低 MC 参与者的比较,确定 MCs 与气道(n=45)和血液(n=19)免疫细胞、参与者人口统计学、哮喘病史、肺功能和高渗盐水诱导的气道高反应性(AHR)之间的关系。

结果

与非哮喘对照组相比,哮喘患者的痰中 MCs、嗜碱性粒细胞和嗜酸性粒细胞增加。在哮喘患者的痰中,MCs、嗜碱性粒细胞和嗜酸性粒细胞之间呈显著相关性,且嗜酸性粒细胞性哮喘患者的 MCs 和嗜碱性粒细胞升高。MCs 和嗜碱性粒细胞与 AHR 相关,而嗜酸性粒细胞与 AHR 无关。高 MC 哮喘患者中,未控制的哮喘和 FEV 和 FVC 降低的患者比例增加。在缺乏气道嗜酸性粒细胞或中性粒细胞增多的少数粒细胞亚群(n=15)中,观察到与 MC 升高具有相似临床关联的趋势。受试者工作特征(ROC)分析显示,外周血嗜酸性粒细胞(PBE)计数可预测痰嗜酸性粒细胞和嗜碱性粒细胞的升高,但不能预测 MCs。

结论和临床相关性

哮喘患者的痰中 MCs 升高,其测量可能有用,因为它与哮喘的关键临床特征(肺功能、哮喘控制、AHR)相关。PBE 计数不能预测气道 MC 状态,这表明应进一步开发通过流式细胞术等敏感方法直接测量气道 MCs。

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