Patterns of Inflammatory Responses in Large and Small Airways in Smokers with and without Chronic Obstructive Pulmonary Disease

Abstract

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive and irreversible airway obstruction. Smoking causes persistent inflammation in lung tissue. However, differences in inflammatory responses between the large and small airways have not been systematically explored among smokers with and without COPD. OBJECTIVES: The aim of our research was to characterise the expression and localisation of NF-κBp65 and histone deacetylase 2 (HDAC2) as well as inflammatory cell (macrophages, lymphocytes, neutrophils) distribution in large and small airways, in nonsmokers and in smokers with and without COPD. METHODS: Nineteen nonsmokers, 20 smokers with normal lung ventilation function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate NF-κBp65 and HDAC2 expression and identify inflammatory cells in airways. RESULTS: COPD patients had increased NF-κBp65 expression compared to nonsmokers and smokers without COPD, in both large and small airways, which corresponded to increased numbers of macrophages, CD8+ T lymphocytes and neutrophils. COPD patients had more macrophages in large compared to small airways and more CD8+ T lymphocytes and neutrophils in small compared to large airways. HDAC2 expression was significantly downregulated in smokers with COPD in small compared to large airways. CONCLUSIONS: Our findings indicate a nonuniform distribution of inflammatory cells throughout the bronchial tree. However, in both smokers with and without COPD, similar patterns of inflammatory processes occur in both large and small airways. The difference between smokers with and without COPD is only quantitative.