Increased levels of cell death and proliferation in alveolar wall cells in patients with pulmonary emphysema

BACKGROUND: Pulmonary emphysema, a major component of COPD, is pathologically characterized by destructive alterations in pulmonary architectures as a result of persistent inflammation. However, alterations in the turnover of pulmonary cells are less well understood. This study was designed to examine whether the turnover of alveolar wall cells is altered in patients with emphysema. PATIENTS AND MEASUREMENTS: We obtained lung tissue specimens from patients with emphysema who had undergone lung volume reduction surgery (13 patients) as well as asymptomatic smokers (7 patients) and nonsmokers (9 patients) undergoing lung resections for solitary lung cancers. Paraffin-embedded lung tissue sections were evaluated for apoptosis and proliferation using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) or immunohistochemistry for Bax, proliferation cell nuclear antigen (PCNA), and topoisomerase IIalpha. Tissue sections were also immunostained for epithelial membrane antigen, surfactant protein A, and CD31. RESULTS: The percentages of alveolar wall cells undergoing apoptosis and proliferation of the total number of alveolar wall cells were significantly higher in patients with emphysema than in asymptomatic smokers and nonsmokers (p < 0.05). The percentage of TUNEL-positive alveolar wall cells was positively correlated with the percentage of PCNA-positive alveolar wall cells. Most of the TUNEL-positive and PCNA-positive cells were alveolar epithelial cells. CONCLUSIONS: These results suggest that the turnover of alveolar wall cells is enhanced in emphysematous lungs, compared to healthy lungs. Emphysema may be a dynamic disease process in which alveolar wall cell death and proliferation are repeated.