Lams B E, Sousa A R, Rees P J, Lee T H
Department of Allergy and Respiratory Medicine, Guy's Hospital, London, United Kingdom.
Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1518-23. doi: 10.1164/ajrccm.158.5.9802121.
The airflow obstruction in chronic obstructive pulmonary disease (COPD) occurs mainly at the level of the small airways. In order to investigate the effect of smoking on small-airway submucosal immunopathology, we used immunohistochemistry in peripheral lung sections obtained at surgery from a group of smokers (n = 22) and from a group of nonsmokers (n = 22) that contained both ex-smokers (n = 17) and lifelong nonsmokers (n = 5). Subjects were also divided into those with (n = 19) and those without (n = 20) airflow obstruction. We found an increase in total eosinophils (p = 0.001) and activated eosinophils (p = 0.010), an increase in the CD8(+)/CD3(+) cell ratio (p = 0.003), and a decrease in the CD4(+)/CD8(+) cell ratio (p = 0.005) among cells infiltrating the small-airway submucosa in an area 50 micrometers deep to the basement membrane in smokers as compared with nonsmokers. There was also an increase in neutrophils (p = 0.019) when smokers were compared with lifelong nonsmokers. Neutrophil numbers correlated with numbers of eosinophils (p = 0.0003, r = 0.58). Furthermore, the CD8(+)/CD3(+) cell ratio was related to pack-years smoked (p = 0.016, r = 0.36), months since smoking cessation (p = 0.003, r = 0.47), and number of infiltrating eosinophils (p = 0.007, r = 0.43) and neutrophils (p = 0.004, r = 0.44). These findings suggest that smoking induces movement of an inflammatory infiltrate into the submucosa of the small airway, the location of the increased resistance to airflow in COPD.
慢性阻塞性肺疾病（COPD）中的气流阻塞主要发生在小气道水平。为了研究吸烟对小气道黏膜下免疫病理学的影响，我们对一组吸烟者（n = 22）和一组非吸烟者（n = 22）手术获取的外周肺组织切片进行免疫组织化学检测，其中非吸烟者包括既往吸烟者（n = 17）和终身不吸烟者（n = 5）。受试者还被分为有气流阻塞者（n = 19）和无气流阻塞者（n = 20）。我们发现，与非吸烟者相比，吸烟者基底膜下50微米深处小气道黏膜下浸润细胞中的总嗜酸性粒细胞数量增加（p = 0.001）、活化嗜酸性粒细胞数量增加（p = 0.010）、CD8(+)/CD3(+)细胞比值增加（p = 0.003）以及CD4(+)/CD8(+)细胞比值降低（p = 0.005）。与终身不吸烟者相比，吸烟者的中性粒细胞数量也增加（p = 0.019）。中性粒细胞数量与嗜酸性粒细胞数量相关（p = 0.0003，r = 0.58）。此外，CD8(+)/CD3(+)细胞比值与吸烟包年数相关（p = 0.016，r = 0.36）、与戒烟后的月数相关（p = 0.003，r = 0.47）、与浸润嗜酸性粒细胞数量相关（p = 0.007，r = 0.43）以及与中性粒细胞数量相关（p = 0.004，r = 0.44）。这些发现表明，吸烟会诱导炎症浸润进入小气道黏膜下层，而小气道黏膜下层正是COPD中气流阻力增加的部位。
