Inhaled Steroid Reduces Systemic Inflammation in COPD
Condition: Chronic Obstructive Pulmonary Disease; Emphysema; Chronic Bronchitis
MeSH terms: Bronchitis; Bronchitis, Chronic; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Inflammation; Emphysema
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): inhaled fluticasone 500 mcg b.i.d.
Intervention type(s): Drug
Intervention MeSH terms: Fluticasone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: inflammation; trial; fluticasone