COPD and N-acetylcysteine: Questions Remain


COPD patients treated with N-acetylcysteine had significantly fewer exacerbations than patients treated with placebo, but more data is needed before the compound can be made an integral component of treatment guidelines.

COPD patients treated with N-acetylcysteine had significantly fewer exacerbations than patients treated with placebo, but more data is needed before the compound can be made an integral component of treatment guidelines.

Patients who have chronic obstructive pulmonary disease (COPD) often suffer acute exacerbations. Patients’ acute exacerbations are immediately visible; they breathe rapidly, perspire profusely, develop a bluish tinge, and strain their neck muscles to breathe. Patients may report rapid heart rate, and in extreme cases, family and caregivers observe that patients may become confused or combative. Each exacerbation erodes lung function and exercise tolerance. Patients’ overall health declines and care costs spiral upward as hospital admission and readmission become a pattern. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strongly recommends aggressively addressing exacerbations.

Many prescribers use N-acetylcysteine (acetylated L-cysteine) to reduce risk of acute exacerbations in patients at all GOLD stages of COPD regardless of age or concomitant therapies. The January 2014 GOLD Global Strategy for Diagnosis, Management, and Prevention of COPD (available free of charge here) recently added the following language to its guideline narrative: “Drugs like N-acetylcysteine may have antioxidant effects, leading to the speculation that these medications could have a role in the treatment of patients with recurrent exacerbations. … There is some evidence that in COPD patients not receiving inhaled corticosteroids, treatment with mucolytics such as carbocysteine and N-acetylcysteine may reduce exacerbations.” The guideline falls short of making a recommendation to use N-acetylcysteine routinely, and does not identify specific populations in which it may be most beneficial.

A study published online on January 30, 2014, in the Lancet Respiratory Medicine, begins to address N-acetylcysteine’s potential in patients with moderate-to-severe COPD. In it, the authors report on the PANTHEON study, which included 1006 patients in Chinese hospitals aged 40 to 80 years with moderate-to-severe COPD, randomized to receive N-acetylcysteine or placebo for 1 year. The results indicated that patients who received N-acetylcysteine had significantly fewer exacerbations than those treated with placebo. Patients in the N-acetylcysteine arm experienced 497 acute exacerbations, while those in the placebo arm experienced 641 acute exacerbations. This translates to 1.16 and 1.49 exacerbations per patient-year in the N-acetylcysteine and placebo arms, respectively. Patients with moderate disease tended to have better treatment responses than those with severe disease.

Previous studies have addressed N-acetylcysteine use in patients who were not receiving corticosteroids or smoking. This study included patients who were taking steroids as well as smokers, and the researchers found that patients who received inhaled corticosteroids or smoked were as likely to respond to N-acetylcysteine as those who did not.

In an accompanying editorial, a pair of COPD experts suggests that the study’s results are insufficient to make N-acetylcysteine an integral component of COPD treatment guidelines. They argue that more data is needed in specific patient groups (those with emphysema, chronic bronchitis, exacerbations, and overlap COPD—asthma) to determine which are most likely to respond to N-acetylcysteine. They also indicate that the PANTHEON study fails to confirm N-acetylcysteine’s mechanism of action, and note that the compound may have antioxidant, anti-inflammatory, mucolytic drug, or combined actions.

In sum, PANTHEON increases our understanding of N-acetylcysteine’s role in COPD, but further studies are needed to answer additional questions.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.

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