Górka Karolina, Soja Jerzy, Jakieła Bogdan, Plutecka Hanna, Gross-Sondej Iwona, Ćmiel Adam, Mikrut Sławomir, Łoboda Piotr, Andrychiewicz Anna, Jurek Paulina, Sładek Krzysztof
Pol Arch Med Wewn. 2016 Jun 30;126(6):402-10. doi: 10.20452/pamw.3461.
INTRODUCTION Airway remodeling plays an important role in the development of chronic obstructive pulmonary disease (COPD). Imaging methods, such as computed tomography (CT) and endobronchial ultrasound (EBUS), may be useful in the assessment of structural alterations in the lungs. OBJECTIVES The aim of this study was to evaluate a relationship between the severity of emphysema assessed by chest CT, the thickness of bronchial wall layers measured by EBUS, and the markers of remodeling in bronchoalveolar lavage fluid (BALF) in patients with COPD. PATIENTS AND METHODS The study included 33 patients with COPD who underwent pulmonary function tests, emphysema score assessment by chest CT, as well as bronchofiberoscopy with EBUS in order to measure the total bronchial wall thickness and, separately, layers L1, L2, and L3-5. Selected remodeling (matrix metalloproteinase 9 [MMP-9], tissue inhibitor of metalloproteinase 1, transforming growth factor β1 [TGF-β1]) and inflammatory markers (neutrophil elastase, eosinophil cationic protein) were measured in BALF samples using an enzyme-linked immunosorbent assay. RESULTS MMP-9 levels in BALF were significantly higher in patients with very severe bronchial obstruction than in those with moderate and mild bronchial obstruction (P = 0.02), and showed a negative correlation with forced expiratory volume in 1 second (r = -0.538, P = 0.002). The thickness of L1 and L2, which histologically correspond to the mucosa, submucosa, and smooth muscle, demonstrated a positive correlation with TGF-β1 levels in BALF (r = 0.366, P = 0.046 and r = 0.425, P = 0.02) and the thickness of L1 showed a negative association with neutrophil elastase levels (r = -0.508, P = 0.004). There was no significant correlation between the analyzed markers in BALF and the emphysema score. CONCLUSIONS Significant correlations of TGF-β1 and elastase with the thickness of bronchial wall layers, and of MMP-9 with the severity of obstruction, may suggest the involvement of these markers in airway remodeling in patients with COPD.
引言 气道重塑在慢性阻塞性肺疾病（COPD）的发展中起着重要作用。成像方法，如计算机断层扫描（CT）和支气管内超声（EBUS），可能有助于评估肺部结构改变。
目的 本研究旨在评估COPD患者中通过胸部CT评估的肺气肿严重程度、通过EBUS测量的支气管壁层厚度与支气管肺泡灌洗液（BALF）中重塑标志物之间的关系。
患者和方法 该研究纳入了33例COPD患者，他们接受了肺功能测试、通过胸部CT评估肺气肿评分，以及进行了带有EBUS的纤维支气管镜检查，以测量总支气管壁厚度，以及分别测量L1、L2和L3-5层。使用酶联免疫吸附测定法在BALF样本中测量选定的重塑标志物（基质金属蛋白酶9 [MMP-9]、金属蛋白酶组织抑制剂1、转化生长因子β1 [TGF-β1]）和炎症标志物（中性粒细胞弹性蛋白酶、嗜酸性粒细胞阳离子蛋白）。
结果 BALF中MMP-9水平在极重度支气管阻塞患者中显著高于中度和轻度支气管阻塞患者（P = 0.02），并且与第1秒用力呼气量呈负相关（r = -0.538，P = 0.002）。组织学上对应于黏膜、黏膜下层和平滑肌的L1和L2层厚度与BALF中TGF-β1水平呈正相关（r = 0.366，P = 0.046和r = 0.425，P = 0.02），并且L1层厚度与中性粒细胞弹性蛋白酶水平呈负相关（r = -0.508，P = 0.004）。BALF中分析的标志物与肺气肿评分之间无显著相关性。
结论 TGF-β1和弹性蛋白酶与支气管壁层厚度之间、MMP-9与阻塞严重程度之间的显著相关性，可能表明这些标志物参与了COPD患者的气道重塑。
