COMMENTARY

Best Evidence Review: Mucolytics -- An Update on Their Use in COPD

Charles P. Vega, MD

Disclosures

July 06, 2010

In This Article

Best Evidence Reference

Poole P, Black PN. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews. 2010, Issue 2. Art. No: CD001287.

Abstract

This study was selected from Medscape Best Evidence, which uses the McMaster Online Rating of Evidence System. Of a possible top score of 7, this study was ranked as 6 for newsworthiness and 6 for relevance by clinicians who used this system.

Introduction: Mucolytics and Chronic Obstructive Pulmonary Disease

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with significant reductions in quality of life. Although inhaled corticosteroids and anticholinergic medications can reduce the frequency of exacerbations, they are far from completely effective. Mucolytics represent a safe way to further reduce exacerbations among patients with COPD and chronic bronchitis, and the current review updates the knowledge on their efficacy for this use.

Background

Chronic obstructive pulmonary disease (COPD) is a growing health concern in the United States and worldwide. The standardized rate of death secondary to COPD in the United States increased 2-fold from 1970 to 2002, and it is now the fourth leading cause of death.[1]

COPD often follows a slowly progressive course, particularly in patients who continue to smoke. As the disease progresses, COPD exacerbations become more frequent. They are generally characterized by increases in cough and sputum production, increased dyspnea, or both, and can have a significant negative effect on quality of life. One trial that followed patients with moderate or severe COPD found that patients experienced a median of 3 exacerbations per year.[2] In another study of similar patients, the mean rate of exacerbations was 1.5 per year.[3] Nearly 31% of these patients required hospitalization for COPD exacerbation during 2 years of follow-up. Among patients with moderate COPD, exacerbations significantly reduced quality-of-life scores in several domains -- symptoms, physical activity, and life impact. Of note, COPD exacerbations did not independently affect the quality of life among patients with severe COPD, but in all participants, quality of life declined during winter months, when COPD exacerbations are most frequent.

Fortunately, several medications are available that can reduce the risk for COPD exacerbation. In a 4-year placebo-controlled study of patients with moderate or severe disease, long-term use of the inhaled anticholinergic medication tiotropium was associated with a 14% relative reduction in the risk for COPD exacerbation.[4] The time to first exacerbation and time to hospitalization for exacerbation were also reduced with tiotropium vs placebo, although the overall number of exacerbations leading to hospitalization was not. However, another trial of tiotropium that was limited to patients with moderate COPD failed to demonstrate a significant benefit in the number of exacerbations compared with placebo.[5]

Inhaled corticosteroids also can improve the risk for COPD exacerbation, with fluticasone associated with a 25% reduction in the annual risk for exacerbation in one trial.[6] The combination of fluticasone with the long-acting beta2-agonist salmeterol reduced the rate of COPD exacerbations to a similar degree in another placebo-controlled trial, and this combination treatment also reduced the risk for hospitalization due to COPD exacerbation.[7] In addition, the fluticasone/salmeterol combination in this trial was superior in reducing the risk for exacerbation compared with either drug alone.

Of concern, this trial also demonstrated a higher risk for pneumonia with the use of inhaled fluticasone vs placebo. A meta-analysis confirmed a 34% increase in the risk for pneumonia among patients with COPD treated with inhaled corticosteroids for at least 6 months compared with treatment with other inhaled medications.[8] Risk factors for pneumonia from the meta-analysis included higher dosages of inhaled corticosteroids, use of combination corticosteroids plus long-acting beta2-agonists, and worse COPD at baseline. Despite the higher risk for pneumonia with inhaled corticosteroids, the rates of 1-year mortality were similar between inhaled corticosteroids and other inhaled medications.

The safety data on inhaled corticosteroids for patients with COPD are concerning, and it is clear that many patients with more advanced COPD develop exacerbations regardless of treatment with inhaled medications. Mucolytics could help reduce the number of COPD exacerbations and the overall burden of disease of COPD. The current systematic review examined the efficacy and safety of these medications among patients with COPD and chronic bronchitis.

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