Previous work has shown an increase in CD8+ T-cells, neutrophils and eosinophils in small airway subepithelium in smokers. The authors have now investigated whether similar changes occur in the large airways.Immunohistochemistry on frozen sections of bronchial biopsies were obtained at bronchoscopy in 11 nonsmokers, eight asymptomatic smokers and 11 smokers with chronic bronchitis and chronic obstructive pulmonary disease (COPD).There was an increase in the number of CD8+ cells infiltrating the bronchial subepithelium in the COPD group compared to the asymptomatic smokers (305 (109± 400) versus 92 (41±550) cells . mm -2 , p=0.030). There was a negative correlation between the number of CD8+ cells and the forced expiratory volume in one second (FEV1) %predicted (p=0.005, r=-0.62), and a positive correlation between the number of CD8+ cells and the number of pack years smoked (p=0.017, r=0.42). There was a negative correlation between the activated/total eosinophils ratio and the FEV1 % pred (p=0.017, r=-0.51). There was a negative correlation between pack years smoked and the number of neutrophils (p=0.022, r=-0.36).Smokers who develop chronic obstructive pulmonary disease have increased numbers of CD8+ T-cells in large airways when compared to asymptomatic smokers. Airway obstruction was associated with an increase in the proportion of eosinophils that were activated. Eur Respir J 2000; 15: 512±516.

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.

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