Differential distribution of inflammatory cells in large and small airways in smokers

Background: Smoking induces structural changes in the airways, and is considered a major factor in the development of airflow obstruction in chronic obstructive pulmonary disease. However, differences in inflammatory cell distribution between large airways (LA) and small airways (SA) have not been systematically explored in smokers. Hypothesis: The content of cells infiltrating the airway wall differs between LA and SA. Aims: To compare the content of neutrophils, macrophages, lymphocytes and mast cells infiltrating LA and SA in smokers who underwent surgery for lung cancer. Methods: Lung tissue from 15 smokers was analysed. Inflammatory cells in the lamina propria were identified by immunohistochemical analysis, quantified by digital image analysis and expressed as number of cells per surface area. Results: The number of neutrophils infiltrating the lamina propria of SA (median 225.3 cells/mm(2)) was higher than that in the lamina propria of LA (median 60.2 cells/mm(2); p < 0.001). Similar results were observed for mast cells: 313.3 and 133.7 cells/mm(2) in the SA and LA, respectively (p < 0.001). In contrast, the number of CD4 cells was higher in LA compared with SA (median 217.8 vs 80.5 cells/mm(2); p = 0.042). Conclusions: These findings indicate a non-uniform distribution of neutrophils and mast cells throughout the bronchial tree, and suggest that these cells may be involved in the development of smoking-related peripheral lung injury.