Eapen Mathew S, McAlinden Kielan, Tan Daniel, Weston Steven, Ward Chris, Muller Hans K, Walters Eugene H, Sohal Sukhwinder S
NHMRC Centre of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Respirology. 2017 Aug;22(6):1125-1132. doi: 10.1111/resp.13021. Epub 2017 Mar 22.
The objective of this study was to enumerate total cells and the number of inflammatory cell differentials in large airways (LAs) versus small airways (SAs) of mild-moderate COPD, and against appropriate controls.
For LA, we used endobronchial biopsies and for SA resected lung tissues. Immunostaining was enumerated (cells per mm ) for macrophages, neutrophils, CD4 and CD8 T cells in the lamina propria (LP) up to 150 µM deep for LA and full wall thickness for SA.
We confirmed hypocellularity in the LA and in the SA wall in smokers and COPD (P < 0.001). LA cellularity was least in current smokers with COPD (COPD-CS) (P < 0.01), while SA cellularity was similar across smoker/COPD groups. LA neutrophils were decreased in COPD-CS (P < 0.01), while SA neutrophil counts were unchanged. Compared with controls, LA macrophage numbers in COPD were significantly lower (P < 0.05), with SA macrophage numbers unchanged. A significant increase was observed in SA CD8+ cells in both normal smokers (P < 0.01) and COPD-CS (P < 0.001) but not in LA.
These unique data indicate that the current model for airway wall inflammation in COPD is oversimplified, and contrast with innate inflammatory activation in the lumen, at least in mild-moderate disease. Any abnormalities in airway wall cell differentials are small, although exaggerated in percentage terms.
本研究的目的是对轻度至中度慢性阻塞性肺疾病（COPD）患者的大气道（LA）和小气道（SA）中的总细胞数及炎性细胞分类计数进行统计，并与适当的对照组进行对比。
对于大气道，我们采用支气管活检；对于小气道，则使用切除的肺组织。对固有层（LP）中巨噬细胞、中性粒细胞、CD4和CD8 T细胞进行免疫染色计数（每毫米细胞数），大气道计数深度达150μm，小气道计数全壁厚度。
我们证实吸烟者和COPD患者的大气道及小气道壁细胞减少（P < 0.001）。当前吸烟者合并COPD（COPD-CS）时大气道细胞数最少（P < 0.01），而小气道细胞数在各吸烟/COPD组中相似。COPD-CS患者大气道中性粒细胞减少（P < 0.01），而小气道中性粒细胞计数无变化。与对照组相比，COPD患者大气道巨噬细胞数量显著降低（P < 0.05），小气道巨噬细胞数量无变化。在正常吸烟者（P < 0.01）和COPD-CS患者（P < 0.001）的小气道中均观察到CD8 +细胞显著增加，但大气道中未观察到。
这些独特的数据表明，目前COPD气道壁炎症模型过于简化，与管腔内的先天性炎症激活形成对比，至少在轻度至中度疾病中如此。气道壁细胞分类的任何异常都很小，尽管在百分比方面有所夸大。
