title: Immunopathology of the small-airway submucosa in smokers with and without chronic obstructive pulmonary disease.
abstract: 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.
authors.affiliation: Department of Allergy and Respiratory Medicine, Guy's Hospital, London, United Kingdom.
authors.forename: B E
authors.initials: BE
authors.lastname: Lams
authors.forename: A R
authors.initials: AR
authors.lastname: Sousa
authors.forename: P J
authors.initials: PJ
authors.lastname: Rees
authors.forename: T H
authors.initials: TH
authors.lastname: Lee
mesh_terms: D000368:Aged; D000403:Airway Resistance; D001485:Basement Membrane / Q000473:pathology; D001980:Bronchi / Q000473:pathology*; D017252:CD3 Complex / Q000032:analysis; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002465:Cell Movement; D004804:Eosinophils / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008173:Lung Diseases, Obstructive / Q000473:pathology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D011650:Pulmonary Alveoli / Q000473:pathology*; D012907:Smoking / Q000473:pathology*; D016540:Smoking Cessation; D013601:T-Lymphocytes / Q000473:pathology; D013997:Time Factors
chemical_list: D017252:CD3 Complex