Exacerbations of Chronic Obstructive Pulmonary Disease and Cardiac Events. A Post Hoc Cohort Analysis from the SUMMIT Randomized Clinical Trial.

Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, associated with acute inflammation, and may increase subsequent cardiovascular disease (CVD) risk.

Objectives: Determine whether AECOPD events are associated with increased risk of subsequent CVD.

Methods: We performed a secondary cohort analysis of the SUMMIT (Study to Understand Mortality and Morbidity) trial, a convenience sample of current/former smokers with moderate COPD from 1,368 centers in 43 countries.

Serum bilirubin and the risk of chronic obstructive pulmonary disease exacerbations.

Background: Bilirubin is a potent anti-oxidant and higher serum concentrations of bilirubin have been associated with better lung function, slower lung function decline, and lower incidence of chronic obstructive pulmonary disease (COPD). We sought to determine whether elevated bilirubin blood concentrations are associated with lower risk for acute exacerbations of COPD (AECOPD).

Methods: We performed a secondary analyses of data in the Simvastatin for Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE) and the Azithromycin for Prevention of Exacerbations of COPD (MACRO) studies.

Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial.

Background: Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals.

Methods: We did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries.

High-dose oral N-acetylcysteine fails to improve respiratory health status in patients with chronic obstructive pulmonary disease and chronic bronchitis: a randomized, placebo-controlled trial.

Background: Clinical outcomes are worse in patients with COPD and chronic bronchitis. N-acetylcysteine (NAC) is commonly prescribed for such patients but with uncertain clinical benefits. We postulated that oral NAC, at much larger doses than those ordinarily prescribed, would improve clinical outcomes in a subset of patients with COPD and chronic bronchitis.

Self-reported alcohol intake and risk of acute exacerbations of chronic obstructive pulmonary disease: a prospective cohort study.

Objective: To evaluate the relationship between alcohol consumption and the risk of acute exacerbation of COPD (AECOPD).

Methods And Measurements: We conducted a secondary analysis of data previously collected in a large, multicenter trial of daily azithromycin in COPD. To analyze the relationship between amount of baseline self-reported alcohol consumption in the past 12 months and subsequent AECOPD, we categorized the subjects as minimal (<1 drink/month), light-to-moderate (1-60 drinks/month), or heavy alcohol users (>60 drinks/month).

Simvastatin for the prevention of exacerbations in moderate-to-severe COPD.

Background: Retrospective studies have shown that statins decrease the rate and severity of exacerbations, the rate of hospitalization, and mortality in chronic obstructive pulmonary disease (COPD). We prospectively studied the efficacy of simvastatin in preventing exacerbations in a large, multicenter, randomized trial.

Methods: We designed the Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations (STATCOPE) as a randomized, controlled trial of simvastatin (at a daily dose of 40 mg) versus placebo, with annual exacerbation rates as the primary outcome.

Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study.

Background: We evaluated the effect of dual, longacting inhaled bronchodilator treatment on exacerbations in patients with severe and very severe chronic obstructive pulmonary disease (COPD).

Methods: In this parallel-group study, 2224 patients (aged ≥40 years, Global Initiative for Chronic Obstructive Lung Disease stages III-IV, and one or more moderate COPD exacerbation in the past year) were randomly assigned (1:1:1; via interactive voice response or web system; stratified for smoking status) to once-daily QVA149 (fixed-dose combination of indacaterol 110 μg and glycopyrronium 50 μg), glycopyrronium 50 μg, or tiotropium 18 μg for 64 weeks. Assignment to QVA149 and glycopyrronium was double-blind; tiotropium was open-label.

A post hoc pooled analysis of exacerbations among US participants in randomized controlled trials of tiotropium.

Background: Exacerbations are a defining outcome of chronic obstructive pulmonary disease (COPD). We evaluated the effect of tiotropium on COPD exacerbations and related hospitalizations among patients from the USA enrolled in clinical trials.

Methods: Data were pooled from six randomized, double-blind, placebo-controlled trials (6 to ≥ 12 months' duration) of tiotropium in patients with COPD.

Long-term comparative immunogenicity of protein conjugate and free polysaccharide pneumococcal vaccines in chronic obstructive pulmonary disease.

Background: Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years.

A comprehensive care management program to prevent chronic obstructive pulmonary disease hospitalizations: a randomized, controlled trial.

Background: Improving a patient's ability to self-monitor and manage changes in chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes.

Objective: To determine the efficacy of a comprehensive care management program (CCMP) in reducing the risk for COPD hospitalization.

Design: A randomized, controlled trial comparing CCMP with guideline-based usual care.

Influence of lightweight ambulatory oxygen on oxygen use and activity patterns of COPD patients receiving long-term oxygen therapy.

Lightweight ambulatory oxygen devices are provided on the assumptions that they enhance compliance and increase activity, but data to support these assumptions are lacking. We studied 22 patients with severe chronic obstructive pulmonary disease receiving long-term oxygen therapy (14 men, average age = 66.9 y, FEV(1) = 33.

Vitamin D levels and risk of acute exacerbations of chronic obstructive pulmonary disease: a prospective cohort study.

Rationale: Low blood levels of 25-hydroxyvitamin D (25[OH]D) have been associated with a higher risk of respiratory infections in general populations and higher risk of exacerbations of lung disease in people with asthma. We hypothesized that low blood levels of 25(OH)D in patients with chronic obstructive pulmonary disease (COPD) would be associated with an increased risk of acute exacerbations of COPD (AECOPD).

Objectives: To determine if baseline 25(OH)D levels relate to subsequent AECOPD in a cohort of patients at high risk for AECOPD.

Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD.

Background: Combining maintenance medications with different mechanisms of action may improve outcomes in COPD. In this study we evaluated the efficacy and safety of fluticasone/salmeterol (FSC) (250/50 mcg twice daily) when added to tiotropium (18 mcg once daily) (TIO) in subjects with symptomatic moderate to severe COPD.

Methods: This was a 24-week, randomized, double-blind, parallel group, multi-center study.

Azithromycin for prevention of exacerbations of COPD.

Background: Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases.

Methods: We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval.

Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization.

Rationale: Leukotrienes have been implicated in the pathogenesis of acute exacerbations of COPD, but leukotriene modifiers have not been studied as a possible therapy for exacerbations.

Objective: We sought to test the safety and efficacy of adding oral zileuton (a 5-lipoxygenase inhibitor) to usual treatment for acute exacerbations of COPD requiring hospitalization.

Methods: Randomized double-blind, placebo-controlled, parallel group study of zileuton 600 mg orally, 4 times daily versus placebo for 14 days starting within 12 hours of hospital admission for COPD exacerbation.

Disease management program for chronic obstructive pulmonary disease: a randomized controlled trial.

Rationale: The effect of disease management for chronic obstructive pulmonary disease (COPD) is not well established.

Objectives: To determine whether a simplified disease management program reduces hospital admissions and emergency department (ED) visits due to COPD.

Methods: We performed a randomized, adjudicator-blinded, controlled, 1-year trial at five Veterans Affairs medical centers of 743 patients with severe COPD and one or more of the following during the previous year: hospital admission or ED visit for COPD, chronic home oxygen use, or course of systemic corticosteroids for COPD.

Therapeutic conversion of the combination of ipratropium and albuterol to tiotropium in patients with chronic obstructive pulmonary disease.

Background: Ipratropium and albuterol, combined in a single formulation, is widely used as three to four times daily maintenance therapy in COPD. This trial compared tiotropium, once daily, as a potential alternative to patients already taking the ipratropium/albuterol combination.

Methods: 676 patients with moderate to very severe stable COPD (mean FEV(1)=39% of predicted) maintained on ipratropium/albuterol were randomized to receive over an 84 day period either tiotropium (18 mcg) each morning, or continue with ipratropium (26 mcg)/albuterol (206 mcg), 2 actuations 4 times daily, using a parallel group, double-blind, double-dummy design.

TORCH and UPLIFT: what has been learned from the COPD "mega-trials"?

TORCH and UPLIFT are amongst the largest and most ambitious COPD trials ever undertaken. In terms of the primary outcomes, both trials were negative. Compared with placebo, combined salmeterol and fluticasone therapy did not significantly reduce all cause mortality over 3 years in TORCH, and tiotropium did not slow the decline in lung function over 4 years in UPLIFT.

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

Background: A subset of patients with chronic obstructive pulmonary disease (COPD) may respond more favorably to inhaled corticosteroids (ICS), but no simple method is currently utilized to predict the presence or absence of ICS responses in patients with COPD.We evaluated the ability of exhaled nitric oxide (FENO) and serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], and interleukin-8 [IL-8]) to independently predict spirometric responses to ICS in patients with COPD.

Methods: Among 60 ex-smokers with severe COPD (mean FEV1 1.