Effects of Fluticasone on Systemic Markers of Inflammation in Chronic Obstructive Pulmonary Disease

Abstract

Systemic inflammation is present in chronic obstructive pulmonary disease (COPD), which has been linked to cardiovascular morbidity and mortality. We determined the effects of oral and inhaled corticosteroids on serum markers of inflammation in patients with stable COPD. We recruited 41 patients with mild to moderate COPD. After 4 weeks during which inhaled corticosteroids were discontinued, patients were assigned to fluticasone (500 mcg twice a day), oral prednisone (30 mg/day), or placebo over 2 weeks, followed by 8 weeks of fluticasone at 500 mcg twice a day and another 8 weeks at 1,000 mcg twice a day. Withdrawal of inhaled corticosteroids increased baseline C-reactive protein (CRP) levels by 71% (95% confidence interval [CI], 16-152%). Two weeks with inhaled fluticasone reduced CRP levels by 50% (95% CI, 9-73%); prednisone reduced it by 63% (95% CI, 29-81%). No significant changes were observed with the placebo. An additional 8 weeks of fluticasone were associated with CRP levels that were lower than those at baseline (a 29% reduction; 95% CI, 7-46%). Inhaled and oral corticosteroids are effective in reducing serum CRP levels in patients with COPD and suggest their potential use for improving cardiovascular outcomes in COPD.

Exhaled nitric oxide, systemic inflammation, and the spirometric response to inhaled fluticasone propionate in severe chronic obstructive pulmonary disease: A prospective study

“…We did not confirm the work of Sin and colleagues, who demonstrated a 50% decrease in serum CRP following only two weeks of the same dose of inhaled fluticasone [Sin et al 2004]. Our subjects had substantially more advanced COPD (FEV 1 of 1.07 L vs. 1.67 L, respectively) and were slightly older (71 years vs. 64 years, respectively) than those in Sin and colleagues' study.…”

Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis

“…As these medications are widely prescribed as anti-inflammatory agents to patients with CF, it was not possible to exclude patients who were receiving this therapy. In adults with chronic obstructive pulmonary disease, inhaled glucocorticoids have been shown to have systemic anti-inflammatory activity [44]. We are not aware of previous serum cytokine measurements in patients with CF following treatment with these agents.…”

Systemic manifestations and comorbidities of COPD

“…ICS, even in high doses, fail to suppress inflammation in COPD lungs and airways and this may be due to an active resistance mechanism linked to a reduction in histone deacetylase 2 expression [161]. Observational studies suggested that ICS reduces all causes of mortality in COPD patients, including cardiovascular mortality [162], and ICS have been shown to reduce markers of systemic inflammation, such as CRP [163]. However, a prospective study of high-dose ICS in COPD patients (TORCH study) showed a minimal reduction in all causes of mortality, indicating that it is unlikely that there is a significant clinical benefit of ICS on COPD comorbidities such as cardiovascular disease or lung cancer, which are the commonest causes of death [93].…”