Patients with chronic obstructive pulmonary disease (COPD) are predisposed to atherosclerosis and coronary artery disease, but the underlying mechanisms are unclear. Although there is wide acceptance that atherosclerosis is related to systemic inflammation, the cause(s) and mechanism(s) of pulmonary inflammation in stable COPD remain unknown. Infectious (bacterial and viral) as well as noninfectious agents can cause acute exacerbations in COPD, and they intensify local and systemic inflammation. Although it is not known how systemic inflammation develops in stable COPD, there is good evidence to suggest that it occurs and that the intensity of systemic inflammation is linked to the severity of airflow obstruction. We postulate that systemic inflammation provides the linkage between COPD and atherosclerosis. Inhaled corticosteroids have been shown to improve health outcomes in COPD, but the mechanism by which this occurs is a pivotal and challenging question that has yet to be answered. To prove the concept that inhaled corticosteroids could suppress systemic inflammation (as exemplified by serum C-reactive protein [CRP] levels), a double-blind, placebo-controlled clinical trial was conducted in a group of patients with mild to moderate COPD. We found that withdrawal of inhaled corticosteroids increased serum CRP levels, and that reintroduction of inhaled fluticasone could suppress CRP levels.