COPD is a major cause of chronic morbidity and mortality throughout
the world and is currently the fourth leading cause of death
worldwide, with expected increases in the prevalence and mortality
over the next few decades.[1] Medications for COPD have not
significantly changed over the past few years. However, the mortality
rate from COPD has increased with the aging of the smoking population.
It is not surprising that patients and physicians try medications that
might be beneficial even though the evidence to support their use is
not present.
The first thing we must be clear about is the difference between
expectorants and mucolytics. Many pharmaceutical agents that we think
of as expectorants are mucolytics and vice versa. An expectorant
medication is one that increases the output of thin respiratory tract
fluid by helping to liquefy the tenacious mucus that patients with
COPD suffer from. A mucolytic medication breaks down the mucus that is
present in the lungs, which ends up thinning the respiratory
secretions. Medications that are classified as expectorants are
guaifenesin and iodinated glycerol. The mucolytics include n-acetylcysteine
and dornase alfa (recombinant human deoxyribonuclease I - rhDNase).
Despite the differences between mucolytics and expectorants, in the
end, the purpose of these medications is to thin lung secretions,
making them easier to clear by coughing and ciliary action.
Unfortunately, the expectorants have been disappointing in treating
COPD. Guaifenesin has been in use for a long time. Yet, there are no
significant studies supporting guaifenesin's benefit in COPD patients.[2]
Iodinated glycerol has also been used as an expectorant; however,
there is a good randomized clinical trial in which it failed to show
efficacy in COPD patients.[3]
The mucolytics show more promise than the expectorants. Aerosolized
surfactant, although not classified as a mucolytic, has been shown to
have a positive effect on patients with stable chronic bronchitis (a
subcategory and consistent with the diagnosis of COPD).[4]
However, expense is certainly an issue, and the author's admittedly
small numbers would require larger studies to confirm their findings.
Dornase alfa is an enzyme that selectively cleaves DNA. Purulent
pulmonary secretions in cystic fibrosis patients contain very high
concentrations of extracellular DNA. Dornase alfa has been shown to be
effective and is FDA approved for use in cystic fibrosis.
Unfortunately, dornase alfa has not been shown to be effective in COPD
patients.[5]
Finally, there is n-acetylcysteine. Oral but not inhaled n-acetylcysteine
has been shown to have some efficacy in COPD patients. Systematic
reviews of the current trials confirm the efficacy of n-acetylcysteine
and some other mucolytics but question using them, given the modest
results and high cost.[6]
In summary, the mucolytics and expectorants, as a group, are
disappointing and, for the most part, lack efficacy. Only further
clinical trials will demonstrate more conclusively whether n-acetylcysteine
really does benefit patients. Physicians who treat patients with COPD
need to review and follow the World Health Organization Global
Initiative for Chronic Obstructive Lung Disease guidelines.[1]
They represent the best practical, evidence-based summary of current
COPD care.
