Immunopathology of the small-airway submucosa in smokers with and without chronic obstructive pulmonary disease

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 mu m 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.