Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study
Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study
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轻中度慢性阻塞性肺疾病小气道病变的横断面研究
DOI：
10.1016/s2213-2600(18)30196-6
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发表时间：
2018-08-01
影响因子：
76.2
通讯作者：
Hackett, Tillie-Louise
中科院分区：
文献类型：
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作者：
Koo, Hyun-Kyoung;Vasilescu, Dragos M.;Hackett, Tillie-Louise
背景直径小于2 mm的小传导气道是慢性阻塞性肺疾病（COPD）气流阻塞的主要部位，这一概念在科学文献中得到了很好的确立，并且已知最后一代小传导气道（终末细支气管）在非常严重的COPD患者中被破坏。我们的目的是确定终末和移行细支气管的破坏是否（第一代呼吸道）发生在肺气肿组织破坏之前或与肺气肿组织破坏同时发生。我们将一种新的多分辨率CT成像方案应用于使用系统均匀采样方法获得的组织样本，以获得具有正常肺的吸烟者的整个肺或肺叶的代表性无偏样本。功能（对照）和轻度COPD（慢性阻塞性肺疾病全球倡议[GOLD] 1期）、中度COPD（GOLD 2）或极重度COPD（GOLD 4）患者。GOLD 1或GOLD 2 COPD患者和肺功能正常的吸烟者接受了肺叶切除术和全肺切除术，GOLD 4 COPD患者接受了肺移植术。肺组织样本被用于体视学评估的数量和形态的终端和过渡性细支气管，空域大小（平均线性截距），和alveolar surface area.Findings的34例患者包括在这项研究中，10个对照组（吸烟者肺功能正常），10例患者有黄金1慢性阻塞性肺病，8个黄金2慢性阻塞性肺病，和6个黄金4慢性阻塞性肺病与小叶中心肺气肿。34例肺标本提供了262个肺样本。与对照组吸烟者相比，GOLD 1级COPD患者终末细支气管数目减少40%（p=0.014），GOLD 2级COPD患者中为43%（p=0.036），GOLD 1级COPD患者的移行细支气管数量减少了56 GOLD 1 COPD患者的肺泡表面积减少33%（p = 0.019），GOLD 2 COPD患者的肺泡表面积减少45%（p =0.0021）。发现这些病理变化与肺功能下降相关。我们还发现，在具有正常肺泡表面积的GOLD 1或GOLD 2 COPD患者的肺样本中，终末和移行细支气管显著缺失。发现剩余的小气道壁增厚、管腔狭窄，随着COPD GOLD分期的增加，这些气道变得更加阻塞。解释这些数据表明小气道疾病是轻度和中度COPD的病理特征。重要的是，这项研究强调，轻度或中度COPD患者可能需要早期干预以改善疾病。版权所有（C）2018 Elsevier Ltd.保留所有权利。
Background The concept that small conducting airways less than 2 mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the scientific literature, and the last generation of small conducting airways, terminal bronchioles, are known to be destroyed in patients with very severe COPD. We aimed to determine whether destruction of the terminal and transitional bronchioles (the first generation of respiratory airways) occurs before, or in parallel with, emphysematous tissue destruction.Methods In this cross-sectional analysis, we applied a novel multiresolution CT imaging protocol to tissue samples obtained using a systematic uniform sampling method to obtain representative unbiased samples of the whole lung or lobe of smokers with normal lung function (controls) and patients with mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1), moderate COPD (GOLD 2), or very severe COPD (GOLD 4). Patients with GOLD 1 or GOLD 2 COPD and smokers with normal lung function had undergone lobectomy and pneumonectomy, and patients with GOLD 4 COPD had undergone lung transplantation. Lung tissue samples were used for stereological assessment of the number and morphology of terminal and transitional bronchioles, airspace size (mean linear intercept), and alveolar surface area.Findings Of the 34 patients included in this study, ten were controls (smokers with normal lung function), ten patients had GOLD 1 COPD, eight had GOLD 2 COPD, and six had GOLD 4 COPD with centrilobular emphysema. The 34 lung specimens provided 262 lung samples. Compared with control smokers, the number of terminal bronchioles decreased by 40% in patients with GOLD 1 COPD (p=0.014) and 43% in patients with GOLD 2 COPD (p=0.036), the number of transitional bronchioles decreased by 56% in patients with GOLD 1 COPD (p=0.0001) and 59% in patients with GOLD 2 COPD (p=0.0001), and alveolar surface area decreased by 33% in patients with GOLD 1 COPD (p=0.019) and 45% in patients with GOLD 2 COPD (p=0.0021). These pathological changes were found to correlate with lung function decline. We also showed significant loss of terminal and transitional bronchioles in lung samples from patients with GOLD 1 or GOLD 2 COPD that had a normal alveolar surface area. Remaining small airways were found to have thickened walls and narrowed lumens, which become more obstructed with increasing COPD GOLD stage.Interpretation These data show that small airways disease is a pathological feature in mild and moderate COPD. Importantly, this study emphasises that early intervention for disease modification might be required by patients with mild or moderate COPD. Copyright (C) 2018 Elsevier Ltd. All rights reserved.