Oral mucolytic drugs for exacerbations of chronic
obstructive pulmonary disease: systematic review
Phillippa J Poole, Peter N Black
Objective To assess the effects of oral mucolytics in
adults with stable chronic bronchitis and chronic
obstructive pulmonary disease.
Design Systematic review of randomised controlled
trials that compared at least two months of regular
oral mucolytic drugs with placebo.
Studies Twenty three randomised controlled trials in
outpatients in Europe and United States.
Main outcome measures Exacerbations, days of
illness, lung function, adverse events.
Results Compared with placebo, the number of
exacerbations was significantly reduced in subjects
taking oral mucolytics (weighted mean difference
− 0.07 per month, 95% confidence interval − 0.08 to
− 0.05, P < 0.0001). Based on the annualised rate of
exacerbations in the control subjects of 2.7 a year, this
is a 29% reduction. The number needed to treat for
one subject to have no exacerbation in the study
period would be 6. Days of illness also fell (weighted
mean difference − 0.56, − 0.77 to − 0.35, P < 0.0001).
The number of subjects who had no exacerbations in
the study period was greater in the mucolytic group
(odds ratio 2.22, 95% confidence interval 1.93 to 2.54,
P < 0.0001). There was no difference in lung function
or in adverse events reported between treatments.
Conclusions In chronic bronchitis and chronic
obstructive pulmonary disease, treatment with
mucolytics is associated with a reduction in acute
exacerbations and days of illness. As these drugs have
to be taken long term, they could be most useful in
patients who have repeated, prolonged, or severe
exacerbations of chronic obstructive pulmonary
bronchitis,1and up to 15% will develop limiting symp-
toms from chronic obstructive pulmonary disease.2
People with chronic bronchitis or chronic obstructive
pulmonary disease may experience recurrent exacer-
bations with worsening symptoms or greater volume
or purulence of sputum. These exacerbations contrib-
ute to morbidity and poorer health3as well as to
increased healthcare costs.4
Although these exacerbations can be treated with
antibiotics or steroids, it would be useful to have other
treatments that reduced the frequency and duration of
acute exacerbations. Mucolytics increase the expecto-
hypersecretion.5Some are also antioxidants.6These
drugs might be of benefit in reducing exacerbations of
chronic obstructive pulmonary disease. In some Euro-
pean countries, mucolytics are widely prescribed in the
belief that they reduce the frequency of exacerbations
or symptoms in patients with chronic bronchitis. How-
ever, in the United Kingdom and Australasia, mucolyt-
ics are used infrequently because they are perceived to
be ineffective. Two oral mucolytics are currently
available in the United Kingdom (carbocisteine and
mecysteine)7and one in New Zealand (bromhexine).
These drugs,however,are not funded in either country
for adults with chronic obstructive pulmonary disease.
We conducted a systematic review to determine,
firstly, if treatment with mucolytics reduced the
frequency of exacerbations or days of illness in people
with chronic bronchitis or chronic obstructive pulmo-
nary disease and, secondly, to determine if mucolytics
improve lung function or increase adverse events.
We did the first Cochrane systematic review on this
topic in 1997 and updated it in 1999 using similar
methods.8We identified abstracts using the Cochrane
Airways Group register.The register has been compiled
from Medline, Embase, CINAHL, and hand searching
of respiratory journals and meeting abstracts. We
searched the register using the following terms:
(chronic bronchitis or chronic obstructive pulmonary
disease) and (mucolytics or N-acetylcysteine or brom-
hexine or S-carboxymethylcysteine or ambroxol or
sobrerol or iodinated glycerol).
From the abstracts of studies identified by this
search strategy, we identified studies for full text review.
In addition, we checked the reference lists of all the
papers and reviews we obtained for any other relevant
articles. We contacted researchers in the field and
material. We each independently selected trials for
inclusion in the review. Disagreement over inclusion
was resolved by discussion. Papers published in
languages other than English were assessed with the
help of four translators.When we needed more data or
clarification, we wrote at least twice to authors and
Phillippa J Poole
Peter N Black
P J Poole
BMJ VOLUME 32226 MAY 2001bmj.com
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(Accepted 28 February 2001)
BMJ VOLUME 32226 MAY 2001bmj.com