Chronic obstructive pulmonary disease: an update of treatment related to frequently associated comorbidities

Chronic obstructive pulmonary disease (COPD) is associated with a pulmonary inflammatory response to inhaled substances, and individuals with COPD often have raised levels of several circulating inflammatory markers indicating the presence of systemic inflammation. Recently, there has been increasing interest in comorbidities associated with COPD such as skeletal muscle dysfunction, cardiovascular disease, osteoporosis, diabetes and lung cancer. These conditions are associated with a similar inflammation-based pathophysiology to COPD, and may represent a lung inflammatory 'overspill' to distant organs. Cardiovascular disease is a significant cause of mortality in COPD, and the concepts of an inflammatory link raise the possibility that treatment for one organ may show benefits to comorbidities in other organs. When considering treatment of COPD and its comorbidities, one approach is to target the pulmonary inflammation and hence reduce any 'overspill' effect of inflammatory mediators systemically as suggested by response to inhaled corticosteroids. Alternatively, treatment targeted towards comorbid organs may alter features of pulmonary disease as statins, angiotensin-converting enzyme (ACE) inhibitors and peroxisome proliferator-activated receptor (PPAR) agonists may have beneficial effects on COPD by reducing exacerbations and mortality. Newer anti-inflammatory treatments, such as phosphodiesterase 4 (PDE4), nuclear factor(NF)-kB, and p38 mitogen-activated protein kinase (MAPK) inhibitors, are given systemically and may confer benefits to both COPD and its comorbidities. With common inflammatory pathways it might be expected that successful anti-inflammatory therapy in one organ may also influence others. In this review we explore the concepts of systemic inflammation in COPD and current evidence for treatment of its related comorbidities.