The pathobiology of COPD

Chronic obstructive pulmonary disease (COPD) is characterised by a chronic inflammation in the pulmonary tissue. The disease is associated with a switch from a self-limiting inflammatory response, mainly initiated by smoke inhalation, to a chronic persistent inflammatory response after prolonged interaction with cigarette smoke. The development and progression of chronic obstructive pulmonary disease have been associated with increased oxidative stress and reduced antioxidant resources. As a result, the antioxidant capacity decreases in COPD patients. Additionally, there is an imbalance between the release of proteases and of endogenous antiprotease enzymes that prevent elastin digestion. The inflammatory basis of COPD is now well established. In patients with COPD increased numbers of macrophages and neutrophils have been found in induced sputum, the former predominating in mild disease. Biopsy data confirm these observations but also demonstrate increased numbers of CD8-positive T-lymphocytes in the airway wall, which may have a role in the regulation of the inflammatory response to cigarette smoke. The extent of the inflammatory reaction is correlated with the severity of the disease. An imbalance between pro-and anti-inflammatory cytokines may favour this process. Several mediators are involved in COPD including leukotriene B4 (LTB4), tumor necrosis factor alpha (TNF-alpha), and interleukin8 (IL-8). They are selective attractants of neutrophils and regulate the ongoing inflammatory process. The whole process would be predicted to be self-perpetuating leading to a chronic inflammatory state with associated airway remodelling and progressive lung function decline.