Inhaled Steroid Reduces Systemic Inflammation in COPD
Inhaled Steroid Reduces Systemic Inflammation in COPD
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 patients aged 45 to 80 years, who had stable symptoms of COPD in the previous 3
 months before study entry. All patients had a forced expiratory volume in one second (FEV1)
 after bronchodilation with 400 mcg salbutamol that was 25 to 90% of predicted, a change of
 less than 20% of predicted FEV1, 30 minutes following bronchodilation, and a FEV1/forced
 vital capacity (FVC) of less than 75%. Patients also had a history of at least 10 pack-years
 of smoking or prolonged exposure (>10 years) to noxious gases (e.g. diesel fumes).

 At the first visit, patients, who were taking inhaled corticosteroids, were asked to
 immediately discontinue the use of these medications. They were allowed to take other
 anti-COPD medications. None of the patients took theophyllines at the time of study entry and
 no new medications were commenced between the first and second visits. The patients returned
 4 weeks later for a second visit, at which point, they were randomized into one of the three
 arms of the trial: placebo capsules and a placebo puffer, fluticasone (500 mcg twice daily)
 and placebo capsules, or prednisone (30 mg once daily) and a placebo puffer. The trial period
 lasted 2 weeks. Patients were then assigned to fluticasone (500 mcg twice daily) for 8 weeks
 in an un-blinded fashion, followed by an additional 8 weeks of fluticasone at 1000 mcg twice
 daily. At each visit, we measure the participants' serum C-reactive protein (CRP) level using
 nephelometry in accordance with recommendations from Center for Disease Control and the
 American Heart Association. We also measured serum concentrations of interleukin-6 (IL-6) and
 monocyte chemoattractant protein-1 (MCP-1). IL-6 was measured because it is a powerful
 signaling cytokine for CRP expression by the liver and is a known, independent risk factor
 for cardiovascular events.22,23 MCP-1 was measured because it may play a central role in the
 pathogenesis of COPD24 and by itself is a known risk factor for atherosclerosis, myocardial
 infarction and cardiac deaths. All samples were analyzed in duplicate.

 For analytic purposes, continuous variables that were not normally distributed (including CRP
 values) were log-transformed to achieve normality. We used a paired t-test to compare the
 log-transformed CRP values between visit 2 (i.e. at the time of randomization) and visit 3
 (at the end of the randomized trial phase) within each treatment group. Similarly, using
 visit 2 as the referent CRP value, we used paired t-tests to compare log-transformed CRP
 values across the visits. To assess whether there was a gradient in the log-transformed CRP
 values between placebo, fluticasone and prednisone groups, we also used a Mantel-Haenszel
 test for trend. We reasoned a priori that oral prednisone, a more potent systemic
 corticosteroid than inhaled fluticasone, would have the largest effect on CRP, followed by
 fluticasone. Linear regression was used to examine the association between changes in
 interleukin-6 and log-transformed CRP values between visit 1 and 2 and between visit 2 and 3.
 Continuous variables are expressed as meanSD, unless otherwise specified.
Inclusion Criteria:

 -  stable symptoms of COPD in the previous 3 months before study entry; forced expiratory
 volume in one second (FEV1) after bronchodilation with 400 mcg salbutamol that was 25
 to 90% of predicted, a change of less than 20% of predicted FEV1, 30 minutes following
 bronchodilation, and a FEV1/forced vital capacity (FVC) of less than 75%; history of
 at least 10 pack-years of smoking or prolonged exposure (>10 years) to noxious gases
 (e.g. diesel fumes).

 Exclusion Criteria:

 -  active malignancy; unable to follow instructions; patients taking any
 anti-inflammatory medications