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Location of Pulmonary Mast Cells Predicts Asthma Outcomes

Journal of Allergy and Clinical Immunology(2019)SCI 1区

Univ Pittsburgh | Dept Environm & Occupat Hlth

Cited 0|Views48
Abstract
Pulmonary mast cells (MC) have been associated with asthma pathogenesis. We have previously shown differences in MC phenotype by location in the lung (submucosa and epithelium) [Balzar, AJRCCM, 2011]. Little is known regarding the relative importance of luminal MCs to asthma. We hypothesized that distal/luminal MCs would better predict more severe clinical outcomes than proximal/epithelial MCs. In 102 University of Pittsburgh asthmatics enrolled in NHLBI trials, bronchial epithelial brushings, bronchoalveolar (BAL) cells and fluid were obtained at bronchoscopy. Expression of the MC protease, tryptase mRNA was determined by qRT-PCR. Using the median tryptase mRNA values for epithelial brushings and BAL cells, subjects were classified as proximal and distal MC "Hi" or "Lo." Regression analysis was performed to assess the effect of MC "Hi" on the outcomes of history of recent exacerbation, baseline FEV1% predicted and FEV1/FVC. Distal MCHi asthma significantly predicted exacerbation [OR=3.6, p=0.004], while proximal MCHi asthma did not [OR=1.7, p=0.2]. Distal MCHi asthma negatively associated with baseline FEV1% predicted [Beta= -12.5, p=0.006, R2=0.07] and baseline FEV1/FVC [Beta= -0.06, p=0.019, R2=0.05]. This relationship was not seen with proximal MCHi asthma [p for FEV1% predicted=0.6, p for FEV1/FVC=0.8]. In matched samples from asthmatic subjects, the distal/BAL cell MC signature better predicted asthma exacerbation, lower FEV1%predicted and decreased FEV1/FVC than the proximal/epithelial MC signature. In asthma, this suggests an important difference in MC function based on the location in the lung. Use of distal MC biomarkers should better identify more clinically severe asthma.
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要点】:研究发现肺部不同位置的肥大细胞(MC)对预测哮喘严重程度有显著差异,其中远端/腔内MC比近端/上皮MC更能预测哮喘的严重临床结果。

方法】:通过对102名匹兹堡大学哮喘患者在NHLBI试验中进行的支气管镜检查,收集支气管上皮刷片、支气管肺泡(BAL)细胞和液体样本,通过qRT-PCR方法测定MC蛋白酶tryptase mRNA的表达量。

实验】:将研究对象根据上皮刷片和BAL细胞的中位tryptase mRNA值分类为近端和远端MC "高"或"低",并通过回归分析评估MC "高"对近期加重史、基线FEV1%预计值和FEV1/FVC的影响。结果显示,远端MCHi哮喘显著预测了加重的风险,而近端MCHi哮喘则没有显著预测效果。同时,远端MCHi哮喘与基线FEV1%预计值和基线FEV1/FVC的降低有负相关性,而近端MCHi哮喘则没有这种相关性。在匹配的哮喘患者样本中,远端/BAL细胞MC特征比近端/上皮MC特征更好地预测了哮喘加重、较低的FEV1%预计值和降低的FEV1/FVC。数据集名称未在文中提及。