Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD
Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD
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DOI：
10.1136/thoraxjnl-2015-207428
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发表时间：
2016-02-01
期刊：
影响因子：
10
通讯作者：
Wilkinson, Tom M. A.
中科院分区：
文献类型：
--
作者：
Ostridge, Kristoffer;Williams, Nicholas;Wilkinson, Tom M. A.
研究背景基质金属蛋白酶（MMPs）是一种蛋白水解酶，可降解细胞外基质并驱动组织重塑，是COPD发病机制中的关键过程。小气道疾病的发展已被确定为气流阻塞早期发展的关键机制，但MMPs在人类疾病中的作用尚不明确。目的我们通过定量COPD患者和健康对照组中MMPs和炎性细胞因子的水平并确定其与COPD关键病理成分的关系来研究MMPs和炎性细胞因子在肺中的作用。方法我们分析了MMPs和炎性细胞因子的水平。来自24名COPD和8名对照受试者的支气管肺泡灌洗液中的细胞因子。每例受试者均接受肺功能测定和高分辨率CT检查。结果COPD患者肺组织中多种MMPs（MMP-1、MMP-2、MMP-3、MMP-8、MMP-9、MMP-10）和细胞因子（IL-6、IL-8）均升高。MMP-3、MMP-7、MMP-8、MMP-9、MMP-10和MMP-12与小气道疾病的CT标志物密切相关。肺气肿的严重程度也与MMP-3、MMP-7和MMP-10相关。然而，有没有很强的关系MMPs和支气管壁厚度的较大airways.Conclusions肺MMP浓度直接与气体潴留和小气道疾病的程度确定的CT扫描。这项研究表明，MMPs在小气道重塑中发挥重要作用，这是COPD发病机制的一个关键特征。
Background Matrix metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and drive tissue remodelling, key processes in the pathogenesis of COPD. The development of small airway disease has been identified as a critical mechanism in the early development of airflow obstruction but the contribution of MMPs in human disease is poorly characterised.Objectives We investigated the role of MMPs and inflammatory cytokines in the lung by quantifying levels and determining relationships with the key pathological components of COPD in patients and healthy controls.Methods We analysed levels of MMPs and inflammatory cytokines in bronchoalveolar lavage from 24 COPD and 8 control subjects. Each subject underwent spirometry and high-resolution CT. Image analysis quantitatively assessed emphysema, bronchial wall thickening and small airways disease.Results Multiple MMPs (MMP-1, -2, -3, -8, -9 and -10) and cytokines (interleukin (IL) 6 and IL-8) were elevated in lungs of subjects with COPD. MMP-3, -7, -8, -9, -10 and -12 concentrations closely associated with CT markers of small airways disease. Emphysema severity was also associated with MMP-3, -7 and -10. However, there were no strong relationships between MMPs and bronchial wall thickness of the larger airways.Conclusions Pulmonary MMP concentrations are directly associated with the extent of gas trapping and small airways disease identified on CT scan. This study suggests that MMPs play a significant role in small airways remodelling, a key feature in the pathogenesis of COPD.