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Background: Only a few studies have evaluated microvascular changes and proangiogenetic mediators in the bronchial mucosa of patients with chronic obstructive pulmonary disease (COPD), and the results have been discordant. Furthermore, the role of inhaled corticosteroids (ICS) in COPD has not been extensively studied. A study was undertaken to evaluate vascular remodelling, its relationship with inflammatory cells and treatment effects in the bronchial mucosa of patients with COPD., Methods: The study comprised three groups: (1) 10 non-treated patients with COPD (COPD); (2) 10 patients with COPD treated with nebulised beclomethasone dipropionate 1600-2400 mug daily (equivalent to 800-1200 mug via metered dose inhaler) (COPD/ICS); and (3) 8 control subjects (CS). Bronchial biopsies were evaluated for number and size of vessels and vascular area. Specimens were also examined for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta) expression and inflammatory cell counts were performed., Results: Vascular area, vessel size, VEGF+ cells, bFGF+ cells and TGF-beta+ cells were significantly increased in the COPD group compared with the COPD/ICS and CS groups (all p<0.05). In addition, bFGF+ cells were significantly increased in the COPD/ICS group compared with the CS group, and CD8+ and CD68+ cells were significantly increased in the COPD group compared with the COPD/ICS and CS groups (p<0.05). In the COPD group the VEGF+ cells correlated with the number of vessels (p<0.05), vascular area (p<0.01) and vessel size (p<0.05), and TGF-beta+ cells correlated significantly with vascular area (p<0.05)., Conclusion: Bronchial vascular remodelling in patients with COPD is mainly related to morphological changes of the mucosal microvessels rather than to new vessel formation, and may be reduced in patients treated with steroids.

Background: The role of transforming growth factor-beta1 (TGF-beta1) in chronic obstructive pulmonary disease is still controversial, but it has been proposed that it may protect from mucus hypersecretion since it is able to downregulate mucin production. A study was undertaken to investigate the expression of TGF-beta1 and its type II receptor (TGF-beta RII) in the bronchial glands of smokers with COPD., Methods: The expression of TGF-beta(1) and TGF-beta RII were examined immunohistochemically in the bronchial glands of 24 smokers undergoing lung resection for solitary peripheral nodules: 12 with airflow limitation (smokers with COPD) and 12 with normal lung function., Results: The expression of TGF-beta1 in bronchial glands was similar in the two groups of subjects while that of TGF-beta RII was lower in smokers with COPD than in smokers with normal lung function (p=0.004). TGF-beta RII expression was inversely correlated with the values of Reid's index, a measure of gland size (p=0.02, r=-0.50)., Conclusions: In the bronchial glands of smokers with COPD there is decreased expression of TGF-beta RII which is associated with bronchial gland enlargement. These findings support the view that the absence of TGF-beta signalling may induce structural changes in the bronchial glands which, in turn, may promote mucus hypersecretion.

Background: COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role., Methods: To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways., Results: Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted)., Conclusions: Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation.