Use of Expectorants

David M. Quillen, MD

Disclosures

February 03, 2003

Question

Is there evidence that expectorants are effective for any condition other than cystic fibrosis? In my 25 years of experience in Canada, these were hardly ever used for the treatment of chronic obstructive pulmonary disease (COPD) -- bronchodilators were always the mainstay. What is the current evidence related to the use of expectorants?

Harvey Solomon, MD

Response from David M. Quillen, MD

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.

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