People with chronic obstructive pulmonary disease (COPD) have a slightly reduced risk of having a flare-up of symptoms if they take mucolytic drugs. The number of days on which they are too ill to perform their normal activities is also slightly reduced, from 1.57 days to 1.14 days per month.
A review of placebo-controlled trials, including 10,377 people taking a variety of mucolytic drugs, for between two months to three years, found improvements in exacerbations, days of disability, and hospital admissions. However, the improvements were small and more recent trials were likely to show less benefit than older trials. The results for hospitalisation suggested an improvement but were not consistent.
Mucolytics may be useful for some COPD patients, but their benefits are likely to be small. The review supports current guidance not to prescribe them routinely for patients with stable COPD.
Why was this study needed?
Around 1.2 million people in the UK have COPD, making it the second most common respiratory disease after asthma. Exacerbation of symptoms such as breathlessness and sputum production can lead to emergency hospital treatment and account for much of the cost of managing COPD.
Reducing exacerbations is a major aim of COPD treatment. Inhaled bronchodilators and steroids are the main drug treatments which are used to keep the airways open and reduce inflammation. Mucolytic drugs, on the other hand, aim to thin mucus to make it easier to cough up.
So far, it has been unclear how well mucolytic drugs such as carbocysteine and N-acetylcysteine reduce exacerbations. Guidelines differ in their recommendations about the place of mucolytic drugs in COPD treatment. This review aimed to summarise the evidence to show whether mucolytics reduce exacerbations or days of disability for COPD patients.
What did this study do?
This was an updated Cochrane systematic review and meta-analysis of randomised controlled trials of oral mucolytic drugs compared to placebo in adults with chronic bronchitis or COPD.
Four new studies were added, giving a total of 38 trials with 10,377 participants. They did not include people with asthma or cystic fibrosis. Most studies were conducted in Europe, including four in the UK. There were four studies in China, two in India, two in the US, and one in Japan.
The average study length was 8.8 months (range two months to three years). Mucolytics tested included N-acetylcysteine, carbocysteine, and erdosteine. They were taken by mouth one to three times per day.
No data was provided on bronchodilator inhaler or other medication use, and there was a wide variation between the studies, which reduces the reliability of the results.
What did it find?
- People receiving mucolytic drugs were more likely to remain free of exacerbation of symptoms (50.9%) than people receiving placebo (38.6%) during the study period (odds ratio [OR] for being exacerbation-free 1.73, 95% confidence interval [CI] 1.56 to 1.91; 28 trials, 6,723 participants).
- People receiving mucolytic drugs had slightly fewer days of disability, where they were unable to do their usual activities, each month: 1.14 days, compared to 1.57 days for people taking a placebo (mean difference 0.43 days, 95% CI 0.30 to 0.56; 9 trials, 2,259 participants).
- Fewer people were admitted to hospital (13.8%) on mucolytic drugs compared with placebo (18.7%) over 16.6 months of follow-up (OR 0.68, 95% CI 0.52 to 0.89; 5 trials, 1,833 participants).
- There was no difference in the results when the use of inhaled corticosteroids was taken into account.
- Researchers said the results were based on moderately certain evidence. However, the review found larger effects in earlier studies of mucolytics for chronic bronchitis and smaller effects in more recent studies of COPD.
What does current guidance say on this issue?
The NICE 2018 guideline only recommends considering mucolytic drug therapy for people with a chronic cough productive of sputum. Mucolytic drugs should be stopped if there is no improvement in symptoms such as cough frequency or sputum production. The guideline does not recommend their routine use to prevent exacerbations for all people with COPD.
What are the implications?
This updated Cochrane review suggests that the NICE guideline hits the right balance in its recommendation that mucolytics may be of help for some people with COPD, but should not be prescribed routinely.
It confirms that mucolytics may offer a small reduction in risk of an exacerbation of COPD symptoms, with few adverse effects, but authors add that the results may be driven by older studies that could have been subject to publication bias.
Citation and Funding
Poole P, Sathananthan K and Fortescue R. Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2019;(5):CD001287.
Cochrane UK and the Cochrane Airways Review Group are supported by NIHR infrastructure funding.
NICE. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. NG115. London: National Institute of Health and Care Excellence; 2018.
British Lung Foundation. Chronic obstructive airways disease (COPD) statistics. London: British Lung Foundation; 2019.
Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre