What is the problem to be addressed? Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular events. Indeed, ischemic heart disease is one of the leading causes of mortality and hospitalization among patients with mild to moderate COPD. For every 10% decrease in forced expiratory volume in one second (FEV1), cardiovascular mortality increases by ~28%, and nonfatal coronary event increases by ~20% in mild to moderate COPD. How COPD increases the risk of poor cardiovascular outcomes is largely unknown. However, there is growing evidence that persistent low-grade systemic inflammation is present in COPD and that this may contribute to the pathogenesis of atherosclerosis and cardiovascular disease among COPD patients. Circulating levels of C-reactive protein (CRP), which has been strongly linked with poor cardiovascular outcomes in the general population, has been demonstrated to be elevated in COPD. Moreover, an elevated level of CRP has been associated with myocardial injury in COPD. Reduction in the level of CRP, on the other hand, has been shown to be associated with improved outcomes in various populations. Other cytokines such as interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), which are potent regulators of CRP, have also been associated with cardiovascular events. If this linkage between systemic inflammation and atherosclerosis holds true for COPD, then systemic inflammation and/or its markers may provide a new and very important therapeutic target for COPD management. Corticosteroids (CS) can reduce CRP and other circulating inflammatory cytokine levels in acute pro-inflammatory states. They can also down-regulate certain inflammatory cells and cytokine expression in the airways of COPD patients and attenuate airway hyperresponsiveness related to COPD. More importantly, in large clinical studies, they have been shown to reduce clinical exacerbations, improve health status and may even reduce mortality in COPD. The mechanism by which such improvement occurs is not known. Recently, our group has demonstrated in a relatively small study that short-term inhaled corticosteroid (ICS) therapy can repress serum CRP levels in stable COPD patients. Conversely, withdrawal of ICS leads to a marked increase in serum CRP levels. Although very promising, these data cannot be considered definitive because the study was small in size and scope (N=41 patients). Additionally, this study did not address the potential effects of combination therapy with ICS and long-acting β2 agonists (LABA).This is an important short-coming because combination therapy has been shown to produce improved clinical outcomes over ICS monotherapy and is commonly used by clinicians in the treatment of moderate to severe COPD. In-vitro studies suggest that steroids and LABAs may “synergistically” down-regulate inflammation in COPD. Whether this occurs in-vivo remains largely unknown and untested.