Polosukhin Vasiliy V, Gutor Sergey S, Du Rui-Hong, Richmond Bradley W, Massion Pierre P, Wu Pingsheng, Cates Justin M, Sandler Kim L, Rennard Stephen I, Blackwell Timothy S
Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Thorax. 2021 Nov;76(11):1079-1088. doi: 10.1136/thoraxjnl-2020-216037. Epub 2021 Apr 7.
Although a variety of pathological changes have been described in small airways of patients with COPD, the critical anatomic features determining airflow limitation remain incompletely characterised.
We examined lung tissue specimens from 18 non-smokers without chronic lung disease and 55 former smokers with COPD for pathological features of small airways that could contribute to airflow limitation. Morphometric evaluation was performed for epithelial and subepithelial tissue thickness, collagen and elastin content, luminal mucus and radial alveolar attachments. Immune/inflammatory cells were enumerated in airway walls. Quantitative emphysema scoring was performed on chest CT scans.
Small airways from patients with COPD showed thickening of epithelial and subepithelial tissue, mucus plugging and reduced collagen density in the airway wall (in severe COPD). In patients with COPD, we also observed a striking loss of alveolar attachments, which are connective tissue septa that insert radially into the small airway adventitia. While each of these parameters correlated with reduced airflow (FEV), multivariable regression analysis indicated that loss of alveolar attachments was the major determinant of airflow limitation related to small airways. Neutrophilic infiltration of airway walls and collagen degradation in airway adventitia correlated with loss of alveolar attachments. In addition, quantitative analysis of CT scans identified an association between the extent of emphysema and loss of alveolar attachments.
In COPD, loss of radial alveolar attachments in small airways is the pathological feature most closely related to airflow limitation. Destruction of alveolar attachments may be mediated by neutrophilic inflammation.
尽管慢性阻塞性肺疾病（COPD）患者的小气道存在多种病理变化，但决定气流受限的关键解剖学特征仍未完全明确。
我们检查了18名无慢性肺部疾病的非吸烟者和55名曾吸烟的COPD患者的肺组织标本，以寻找可能导致气流受限的小气道病理特征。对上皮和上皮下组织厚度、胶原蛋白和弹性蛋白含量、管腔内黏液及肺泡径向附着进行形态学评估。对气道壁中的免疫/炎症细胞进行计数。对胸部CT扫描进行定量肺气肿评分。
COPD患者的小气道显示上皮和上皮下组织增厚、黏液阻塞以及气道壁胶原蛋白密度降低（重度COPD患者）。在COPD患者中，我们还观察到肺泡附着显著丧失，肺泡附着是径向插入小气道外膜的结缔组织间隔。虽然这些参数均与气流减少（第一秒用力呼气容积[FEV]）相关，但多变量回归分析表明，肺泡附着丧失是与小气道相关的气流受限的主要决定因素。气道壁中性粒细胞浸润和气道外膜胶原蛋白降解与肺泡附着丧失相关。此外，CT扫描定量分析确定肺气肿程度与肺泡附着丧失之间存在关联。
在COPD中，小气道肺泡径向附着丧失是与气流受限最密切相关的病理特征。肺泡附着破坏可能由中性粒细胞炎症介导。
