Clinical Question

Are oral mucolytics safe and effective at reducing the number of acute exacerbations, days of disability, and hospital admissions in patients with chronic bronchitis or chronic obstructive pulmonary disease (COPD)?

Evidence-Based Answer

Oral mucolytic agents may reduce the number of acute exacerbations in patients with chronic bronchitis or COPD (number needed to treat [NNT] = 8 over an average of nine months; 95% CI, 7 to 10). Although mucolytics do not appear to impact lung function or quality of life, they are associated with a small reduction in days of disability per month (mean difference [MD] = −0.43 days; 95% CI, −0.56 to −0.30) and decreased hospital admissions (NNT for 17 months = 19; 95% CI, 12 to 59). Mucolytics are not associated with an increase in adverse effects.¹ (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

COPD is the fourth leading cause of death in the United States, with the majority of cases attributed to tobacco use.^1,2 COPD is characterized by persistent respiratory symptoms and chronic airflow limitation due to a mixture of small airway disease and parenchymal destruction.³ Current clinical practice guidelines require spirometry to establish the diagnosis of COPD.³ Many patients with chronic bronchitis have COPD. Acute exacerbations are the largest contributor to health care costs related to COPD and are characterized by an increase in the volume or purulence of sputum.¹ The authors of this review sought to determine the potential role of mucolytics in the treatment of chronic bronchitis or COPD.

This Cochrane review included 38 randomized controlled trials (published between 1976 and 2017) involving 10,377 participants.¹ The authors looked for placebo-controlled trials investigating a range of oral mucolytic therapy given for at least two months in adults with chronic bronchitis or COPD. The mean age of participants ranged from 40 years to 71 years. A total of 15 studies investigated the use of mucolytics in participants with COPD only, whereas the remaining 23 studies involved participants with chronic bronchitis, COPD, or both. In 13 studies conducted from 1980 to 1999, the diagnosis of chronic bronchitis was made using the British Medical Research Council definition, which does not require spirometry.⁴ The primary outcome measured was a reduction in acute exacerbations and/or days of disability. Secondary outcomes included quality of life, lung function, and adverse effects. Studies investigating children or persons with other pulmonary conditions such as asthma and cystic fibrosis were excluded.

This review showed that patients receiving oral mucolytic therapy had a small reduction in the number of acute exacerbations (odds ratio [OR] = 1.73; 95% CI, 1.56 to 1.91; NNT = 8; 95% CI, 7 to 10; 28 studies; 6,723 participants). These results should be interpreted with caution because of high heterogeneity between studies, with larger effects seen in older studies of mucolytics in chronic bronchitis and smaller effects noted in more recent studies. Of note, the severity of COPD as well as the dose and type of mucolytic agent did not alter the effect size of this primary outcome. Mucolytic use was also associated with fewer days of disability per participant per month (MD = −0.43; 95% CI, −0.56 to −0.30; nine studies; 2,259 participants) and a reduction in the number of participants with one or more hospital admissions over the course of 17 months (OR = 0.68; 95% CI, 0.52 to 0.89; NNT = 19; 95% CI, 12 to 59; five studies; 1,833 participants). Subgroup analysis showed no significant difference in groups of participants being treated concurrently with inhaled corticosteroids. This suggests that the effect of mucolytics is independent of inhaled corticosteroid use.

Forced vital capacity was evaluated in 12 studies, with results favoring mucolytics over placebo; however, results were not statistically significant. Pooled results from studies that measured health-related quality of life using the validated St. George's Respiratory Questionnaire favored mucolytics over placebo; however, the effect did not meet the minimum clinically important difference of −4 units, and the MD for this secondary outcome was not statistically significant. Mucolytic agents did not appear to be associated with a significant increase in adverse effects.

Current clinical practice guidelines offer a range of recommendations regarding the use of mucolytic agents in the treatment of COPD.^3,5–8 Most clinical practice guidelines recommend that mucolytic therapy be considered for certain patients with COPD to reduce the number of exacerbations.^3,5–7 This recommendation is consistent with the findings of this Cochrane review. Further research is needed to assess the role of mucolytics in the treatment of chronic bronchitis and COPD with regard to symptom severity, quality of life, disease progression, and mortality.

The practice recommendations in this activity are available at http://www.cochrane.org/CD001287.

This article reflects the opinions of the authors alone and does not reflect the opinion of the Department of the Army, the Department of the Air Force, the Department of the Navy, the Defense Health Agency, the Department of Defense, or the U.S. government.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army, Department of the Air Force, Department of Defense, or the U.S. government. This document was created free of branding or market affiliations. The author is operating solely as a contributor.