The complex relationship between inflammation and lung function in severe asthma.
The complex relationship between inflammation and lung function in severe asthma.
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作者：
哮喘是一种常见的呼吸道疾病，影响全球约3亿人。气道炎症被认为是哮喘发病机制的一部分，但炎症与气道高反应性之间的直接关系尚不清楚。本研究探讨了炎症在类固醇不敏感的严重过敏性气道疾病模型和按炎症特征分层的严重哮喘中的作用。首先，我们利用TH17细胞过继转移哮喘小鼠模型诱导肺部炎症，通过TNFα中和或中性粒细胞耗竭减轻炎症。虽然TNFα中和和中性粒细胞耗竭后气道炎症减少挽救了肺顺应性，但与对照组相比，两种干预均未改善气道对乙酰甲胆碱的高反应性，组织炎症仍然升高。此外，从41名严重哮喘患者中收集痰液样本并进行分析。在痰液中性粒细胞水平升高，但嗜酸性粒细胞水平低的重度哮喘患者中，炎性标志物升高与肺功能恶化无关。与其他具有其他炎症表型的严重哮喘患者相比，该哮喘患者亚组的痰液中TH17相关细胞因子的水平也显著更高。总的来说，这项工作表明，肺顺应性可能与空气中的细胞炎症有关，而T细胞驱动的气道高反应性可能与组织炎症和其他肺部因素有关。
Asthma is a common respiratory disease affecting approximately 300 million people worldwide. Airway inflammation is thought to contribute to asthma pathogenesis, but the direct relationship between inflammation and airway hyperresponsiveness remains unclear. This study investigates the role of inflammation in a steroid-insensitive, severe allergic airway disease model and in severe asthmatics stratified by inflammatory profile. First, we utilized the TH17 cell adoptive transfer mouse model of asthma to induce pulmonary inflammation, which was lessened by TNFα neutralization or neutrophil depletion. While decreased airspace inflammation following TNFα neutralization and neutrophil depletion rescued lung compliance, neither intervention improved airway hyperresponsiveness to methacholine, and tissue inflammation remained elevated when compared to control. Further, sputum samples were collected and analyzed from 41 severe asthmatics. In severe asthmatics with elevated levels of sputum neutrophils, but low levels of eosinophils, increased inflammatory markers did not correlate with worsened lung function. This subset of asthmatics also had significantly higher levels of TH17-related cytokines in their sputum compared to other severe asthmatics with other inflammatory phenotypes. Overall, this work suggests that lung compliance may be linked with cellular inflammation in the airspace, while T cell-driven airway hyperresponsiveness may be associated with tissue inflammation and other pulmonary factors.
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DOI：
10.1016/j.jaci.2007.10.028
发表时间：
2008-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Brightling C;Berry M;Amrani Y
通讯作者：
Amrani Y
影响因子：
9.6
作者：
Gibson, PG;Simpson, JL;Saltos, N
通讯作者：
Saltos, N
DOI：
10.1164/rccm.200702-334oc
发表时间：
2007-11-15
影响因子：
24.7
作者：
Alcorn, John F.;Rinaldi, Lisa M.;Irvin, Charles G.
通讯作者：
Irvin, Charles G.
影响因子：
10
作者：
Howarth, PH;Babu, KS;Holgate, ST
通讯作者：
Holgate, ST
影响因子：
10
作者：
Green, RH;Brightling, CE;Pavord, ID
通讯作者：
Pavord, ID