COPD: mucolytics reduce exacerbations and days of disability.

Clinical bottom line (level 1a)

  1. Patients with chronic bronchitis who are given mucolytics, are more likely to have a greater reduction in exacerbations per month, than those given placebo.
  2. Patients given mucolytics are more likely to have a greater reduction in days of disability per month than those given placebo.
  3. Patients given mucolytics are less likely to have an improvement in FEV1 or FVC than those given placebo.
  4. There is no clear difference in number of adverse effects.
Poole and Black: The Cochrane Library 1999; 3: 1-10
Expires November 2003

The study

Systematic review of randomised, double blind, placebo controlled studies of
  • Patients: Adults (>20 years old) with chronic bronchitis as defined by the criteria of the American Thoracic Society or the Medical Research Council (cough and sputum on most days during at least 3 consecutive months for more than 2 successive years.
  • Intervention: oral mucolytic agents, including N-acetylcysteine, S-carboxymethlcysteine, bromhexine, ambroxol, sobrerol, cithiolone, letosteine and iodinated glycerol (administered regularly for a period of at least 2 months) compared with placebo
  • Outcome: frequency of exacerbations (defined as an increase in cough and in the volume and/or purulence of sputum) and days of disability (defined as days in bed, days off work or days where the subject was unable to undertake normal activities)


    • Articles found in ?language using MEDLINE, EMBASE, CINAHL, ?dates (search terms: chronic bronchitis or chronic obstructive pulmonary disease, and mucolytics or N-acetylcysteine or bromhexine or S-carboxymethylcysteine or ambroxol or sobrerol or iodinated glycerol ) and hand searching respiratory journals and meeting abstracts, also reference lists of relevant articles.

    Selection criteria: as above
    Appraisal criteria: detailed in text
    Articles excluded if: studies on patients with asthma or cystic fibrosis; standard deviation for the outcome measures of interest not reported

    15 studies were included.
    There was significant heterogeneity between the studies with regard to reduction in days of disability (Chi squared 44.7).

    The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NNH
    (95% CI)
    adverse effects unknown 1556/3121
    (49.86%)    		 1.01
    (0.92 to 1.12)     		402
    (NNT = 48 to infinity;
    NNH = 35 to infinity)

    • The weighted mean difference in exacerbation reduction per month was 0.11 in favour of the mucolytics (95% CI -0.11 to -0.10).
    • The mean difference in reduction of days of disability per patient per month was 0.65 in favour of mucolytics (95% CI -0.69 to -0.61)
    • The mean difference in FEV1 was 0.057 litres in favour of placebo (95% CI 0.039 to 0.075); and for FVC was a reduction of 0.04 litres in favour of placebo (95% CI 0.017 to 0.063).

    Comments

    1. It is uncertain how quality of life issues are affected by the administration of mucolytics.

    Citation

    1. Poole PJ, and Black PN: Mucolytic agents for chronic bronchitis (Cochrane review). The Cochrane Library 1999; 3: 1-10
    Search Terms: chronic bronchitis in Cochrane
    Contributor: Clare Wotton and Musab Hayatli, November 1999
    Reviewer: Mitsuhiro Kamei

    Clinical Question.
    Patient chronic bronchitis
    Intervention or Exposure mucolytics
    Comparison placebo
    Outcome number of exacerbations