In the last decade, the analysis of bronchial biopsies and lung parenchyma obtained from chronic obstructive pulmonary disease (COPD) patients compared with those from smokers with normal lung function and non-smokers has provided new insights on the role of the different inflammatory and structural cells, their signalling pathways and mediators, contributing to a better knowledge of the pathogenesis of COPD. This review summarizes and discusses the lung pathology of COPD patients with emphasis on inflammatory cell phenotypes that predominate in different clinical conditions. In bronchial biopsies, a cascade of events takes place during progression from mild-to-severe disease. T lymphocytes, particularly CD8+ cells and macrophages are the prevalent inflammatory cells in the lung of healthy smokers and patients with mild COPD, while total and activated neutrophils predominate in severe COPD. The number of CD4+, CD8+ cells and macrophages expressing nuclear factor-kappa B (NF-kappaB), STAT-4 and IFN-gamma proteins as well as endothelial adhesion molecule-1 in endothelium is increased in mild/moderate disease. In contrast, activated neutrophils (MPO+ cells) and increased nitrotyrosine immunoreactivity develops in severe COPD. In bronchial biopsies obtained during COPD exacerbations, some studies have shown an increased T cell and granulocyte infiltration. Regular treatment with high doses of inhaled glucocorticoids does not significantly change the number of inflammatory cells in bronchial biopsies from patients with moderate COPD. The profile in lung parenchyma is similar to bronchial biopsies. 'Healthy' smokers and mild/moderate diseased patients show increased T lymphocyte infiltration in the peripheral airways. Pulmonary emphysema is associated with a general increase of inflammatory cells in the alveolar septa. The molecular mechanisms driving the lymphocyte and neutrophilic prevalence in mild and severe disease, respectively, needs to be extensively studied. Up-regulation of pro-inflammatory transcription factors NF-kappaB and STAT-4 in mild, activated epithelial and endothelial cells in the more severe disease may contribute to this differential prevalence of infiltrating cells.

CC-chemokines are chemotactic factors expressed in a wide range of cell types and tissues. The aim of this study was to evaluate the involvement of CCchemokines in the airways inflammation of patients affected by chronic bronchitis.The study evaluated, with an immunoassay, the concentrations of monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1a (MIP-1a) and macrophage inflammatory protein-1b (MIP-1b), in the bronchoalveolar lavage fluid (BALF) of 12 smokers affected by chronic bronchitis and 14 smoking, 15 nonsmoking and six exsmoking healthy subjects.MCP An increase of monocyte chemotactic protein-1 is related to smoking habit and seems consistent with a lung inflammatory reaction. On the contrary, an increase in macrophage inflammatory protein-1b levels is restricted to smokers developing chronic obstructive pulmonary disease. These data suggest a role of CC-chemokines in the pathogenesis of chronic bronchitis.

Activation of the transcription factor signal transducer and activator of transcription (STAT)-4 is critical for the differentiation of T-helper 1 cells/type-1 cytotoxic T-cells and the production of interferon (IFN)-c.Expression of STAT4, phospho-STAT4, IFN-c and T-box expressed in T-cells (Tbet) proteins in bronchial biopsies and bronchoalveolar lavage (BAL)-derived lymphocytes, obtained from 12 smokers with mild/moderate chronic obstructive pulmonary disease (COPD) (forced expiratory volume in one second (FEV1) 59¡16% predicted), 14 smokers with normal lung function (FEV1 106¡12% pred) and 12 nonsmoking subjects (FEV1 111¡14% pred), was examined by immunohistochemistry and immunocytochemistry.In bronchial biopsies of COPD patients, the number of submucosal phospho- 6103 ). In all smokers who underwent lavage, phospho-STAT4z lymphocytes correlated with airflow obstruction and the number of IFNcz lymphocytes. T-bet expression was not altered in bronchial biopsies and BAL-derived lymphocytes between the three groups.In conclusion, this study suggests that stable mild/moderate chronic obstructive pulmonary disease is associated with an active T-helper 1 cell/type-1 cytotoxic T-cell inflammatory process involving activation of signal transducer and activator of transcription 4 and interferon-gamma production.

Tobacco smoking (TS) is a major cause of lung diseases. This study aimed to determine: 1) the prevalence of TS among chest physicians; 2) the influence of the personal smoking habit on clinical practice; and 3) what training about tobacco-related issues (TI) doctors received in medical school. A total of 983 attendees at the National Meeting of the Italian National Thoracic Society (AIPO) received a questionnaire about TI, which also contained the Fagerstroem Tolerance Questionnaire, and 605 (61.5%) answered. An independent assessment of the prevalence of smokers was carried out to minimize the bias of self-selection. The numbers of smokers was 151 (25%), never-smokers 246 (40.7%) and exsmokers 208 (34.4%). Smoking chest physicians underestimate the health hazards of smoking (p<0.001) and disregard their educational role (p=0.005) more than nonsmoking chest physicians. Compliance with smoking restrictions inside hospitals is frequently poor (30.1% smoke in clinics). In 33.1% of smokers a high nicotine addiction was found, which influenced their behaviour in hospital but not their ability to cope with tobacco-related problems. This ability was generally low: 39.1% of responders reported no training about TI. Smoking is frequent among Italian chest physicians, who are poorly trained about the health effects of tobacco smoking and are poorly skilled in treating smokers.

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