Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Oral mucolytic agents reduce exacerbations and sick days in chronic bronchitis

ACP J Club. 1999 July-Aug;131:14. doi:10.7326/ACPJC-1999-131-1-014

Source Citation

Poole PJ, Black PN. The effect of mucolytic agents on exacerbation frequency in chronic bronchitis. Cochrane Review, latest version 15 May 1998. In: The Cochrane Library. Oxford: Update Software.



Do oral mucolytic agents reduce the frequency of exacerbations and disability days in adults with chronic bronchitis?

Data sources

Studies were identified by searching the Cochrane Airways Group Register (which includes citations identified from searches of MEDLINE, EMBASE/Excerpta Medica, and CINAHL and from hand searches of respiratory journals and meeting abstracts) using the terms chronic bronchitis or chronic obstructive pulmonary disease combined with the terms mucolytics, N-acetylcysteine, bromhexine, S-carboxymethylcysteine, ambroxol, sobrerol, or iodinated glycerol. Bibliographies of retrieved studies were also reviewed.

Study selection

Studies were selected if they were randomized, double-blind, placebo-controlled trials of oral mucolytic agents (N-acetylcysteine, S-carboxymethylcysteine, bromhexine, ambroxol, sobrerol, cithiolone, letosteine, and iodinated glycerol) administered regularly for 2 months to adults > 20 years of age with chronic bronchitis (defined as cough and sputum on most days during 3 consecutive months for more than 2 successive years) and if outcomes included acute exacerbations (increase in cough and volume or purulence of sputum) or disability days (e.g., days in bed or off work). Studies were excluded if patients had asthma or cystic fibrosis or if they were studies of inhaled mucolytic agents, deoxyribonuclease or proteases, or combinations of mucolytic agents and antibiotics or bronchodilators.

Data extraction

Data were extracted on study duration, country, participant characteristics, intervention, and outcomes. Studies were assessed for methodologic quality.

Main results

15 studies were included in the review. 9 studies were done in Italy, 3 in Scandinavia, 2 in the United Kingdom, and 1 in the United States. The mean age of participants ranged from 40 to 65 years, and the proportion of current or former smokers ranged from 64% to 100%. Significant heterogeneity existed among studies.

Meta-analysis was done using a fixed-effects model. Compared with placebo, oral mucolytic agents reduced the number of exacerbations per patient per month (14 studies, weighted mean difference [WMD] 0.105 exacerbations, 95% CI 0.10 to 0.11), the number of disability days per patient per month (7 studies, WMD 0.65 d, CI 0.61 to 0.69), and the number of days receiving antibiotics per patient per month (3 studies, WMD 0.68 d, CI 0.64 to 0.71).


Oral mucolytic agents reduce the frequency of exacerbations, disability days, and antibiotic use in patients with chronic bronchitis.

Source of funding: No external funding.

For correspondence: Dr. P.J. Poole, University of Auckland, Private Bag 92019, Auckland, New Zealand. FAX 64-9-3022101.


In this meta-analysis of oral mucolytic agents for chronic bronchitis, Poole and Black found a beneficial effect that is probably too small to warrant the widespread use of this therapy for chronic bronchitis. Mucus hypersecretion defines the pathology and permits clinical recognition of chronic bronchitis. Although less important than smoking and airway obstruction as a prognostic indicator, mucus hypersecretion is associated with an increased rate of loss of lung function, hospitalization for chronic obstructive pulmonary disease (relative risk 2.4) (1), and increased death from respiratory tract infection (2). Consequently, mucus hypersecretion is a relevant treatment outcome.

The host clearance mechanisms of cough and mucociliary transport are usually not impaired in chronic bronchitis. Rehabilitation programs reinforce the use of these methods of mucus clearance and typically show significant quality of life gains that are greater than those reported with oral mucolytic agents (3).

In this study, oral mucolytic agents reduced exacerbations by 22% in patients who had an unusually high baseline rate of 5.5 exacerbations/y. The typical patient with 2 or 3 exacerbations/y could expect 1 less exacerbation by taking mucolytic agents daily for 2 or 3 years. The reduction in disability (sick days) from an average of 4 d/mo to 3.4 d/mo suggests that these agents have a limited place in the treatment of chronic bronchitis. Of note, no effect was observed for FEV1, which is the most important prognostic indicator in this disease.

Clinicians should manage chronic bronchitis by encouraging smoking cessation, optimizing functional status through exercise rehabilitation, and treating airway obstruction. The benefit from oral mucolytic agents is too small to justify routine use. Patients with mucus hypersecretion who have frequent exacerbations or severe disability or are unable to use conventional therapy may experience limited gains from daily therapy with oral mucolytic agents.

Peter G. Gibson, MD
John Hunter HospitalNewcastle, New South Wales, Australia


1. Vestbo J, Prescott E, Lange P. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group. Am J Respir Crit Care Med. 1996;153:1530-5.

2. Prescott E, Lange P, Vestbo J. Chronic mucus hypersecretion in COPD and death from pulmonary infection. Eur Respir J. 1995;8:1333-8.

3. Lacasse Y, Wong E, Guyatt GH, et al. Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. Lancet. 1996;348:1115-9.