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 investi gate 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 nonsmoker s (n = 22) that contained both ex-smokers (n = 17) and lifelong nonsmo kers (n = 5). Subjects were also divided into those with (n = 19) and those without (n = 20) airflow obstruction. We found an increase in to tal eosinophils (p = 0.001) and activated eosinophils (p = 0.010), an increase in the CD8(+)/CD3(+) cell ratio (p = 0.003), and a decrease i n the CD4(+)/CD8(+) cell ratio (p = 0.005) among cells infiltrating th e small-airway submucosa in an area 50 mu m deep to the basement membr ane in smokers as compared with nonsmokers. There was also an increase in neutrophils (p = 0.019) when smokers were compared with lifelong n onsmokers. Neutrophil numbers correlated with numbers of eosinophils ( p = 0.0003, r = 0.58). Furthermore, the CD8(+)/CD3(+) cell ratio was r elated to pack-years smoked (p = 0.016, r = 0.36), months since smokin g cessation (p = 0.003, r = 0.47), and number of infiltrating eosinoph ils (p = 0.007, r = 0.43) and neutrophils (p = 0.004 r = 0.44). These findings suggest that smoking induces movement of an inflammatory infi ltrate into the submucosa of the small airway, the location of the inc reased resistance to airflow in COPD.