Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by lung inflammation that persists after smoking cessation. This inflammation is heterogeneous but the key inflammatory cell types involved are macrophages, neutrophils and T cells. Other lung cells may also produce inflammatory mediators, particularly the epithelial cells. The main inflammatory mediators include tumor necrosis factor alpha, interleukin-1, interleukin-6, reactive oxygen species and proteases. COPD is also associated with systemic inflammation and there is a markedly increased risk of cardiovascular disease (particularly coronary artery disease) and lung cancer in patients with COPD. There is strong associative evidence that the inflammatory cells/mediators in COPD are also relevant to the development of cardiovascular disease and lung cancer. There are a large number of potential inhibitors of inflammation in COPD that may well have beneficial effects for these comorbidities. This is a not well-understood area and there is a requirement for more definitive clinical and mechanistic studies to define the relationship between the inflammatory process of COPD and cardiovascular disease and lung cancer.

Fig. 1

Potential targets for anti-inflammatory therapy The inflammatory process in COPD is associated with cardiovascular disease and lung cancer and is a potential therapeutic target to reduce these comorbidities. In additional to broad spectrum therapies such as corticosteroids specific anitinflammatory therapies could be directed towards a the primary factors driving inflammation in COPD, b intracellular signaling pathways including NF-κβ and STAT3 e.g. by tyrosine kinase inhibitors, c inhibition of specific inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukins (IL) 1 and 6 and the generation of d reactive oxygen species (ROS) and e proteases such as neutrophil elastase (NE) and matrix metalloproteinases 9 and 12 (MMP9/12).