N-acetylcysteine for COPD: another trial shows benefit (PANTHEON)

Image: pipingrock.com

Can N-acetylcysteine help prevent exacerbations of chronic obstructive pulmonary disease (COPD)? Another randomized trial says yes.

N-acetylcysteine, or NAC, is a nutritional supplement with antioxidant and anti-inflammatory properties. After ingestion, N-acetylcysteine is metabolized into glutathione, a key antioxidant with effects throughout the body. In the lungs, glutathione deficiency (common in alcoholics) is linked to a higher risk for ARDS. People with COPD and smokers without COPD tend to have lower glutathione levels, which correlate with worse lung function.

Oral N-acetylcysteine is safe and has a good physiologic rationale as a supportive treatment for COPD. Does it work?

• The largest trial to date (BRONCUS, n=523 in 2005) did not show any benefit of 600 mg N-acetylcysteine daily for COPD, but some argued that dose was too low.

• In a randomized trial (n=120) published in Chest in 2013, 600 mg N-acetylcysteine twice daily prevented exacerbations in mild to moderate COPD.

• In a meta-analysis of 11 randomized trials published in COPD in 2013, high-dose NAC (600 mg bid or more) reduced the severity and frequency of COPD exacerbations.

• Meta-analyses by Cochrane in 2010 and by Grandjean et al in 2000 also suggested NAC might reduce COPD exacerbations.

In the latest news, Zheng et al reported the results of their PANTHEON trial in Lancet Respiratory Medicine in January 2014. They randomized 1006 Chinese patients at 34 centers with moderate-to-severe COPD to receive either N-acetylcysteine 600 mg b.i.d. or placebo for one year. Those treated with NAC had significantly fewer exacerbations (~1.5 vs. ~1.2 per year), with a number needed to treat of 3 to prevent one exacerbation in a year.

If real, that's a huge benefit: Advair had a number needed to treat of about 4 to prevent a COPD exacerbation in randomized trials including TORCH. Given the equivocal results in the past, it seems appropriate to be optimistic but skeptical of this magnitude of benefit. A large multicenter randomized trial in North America and Europe would seem like a moral imperative, given the suggestion of benefit, the magnitude of the problem of COPD, and the ready availability of a nontoxic and inexpensive potential therapy. Are our fearless leaders performing or planning one? Not yet, as listed on clinicaltrials.gov (where there are just a few mom-and-pops described at single centers, n = 40-60).

You can always direct your COPD patients to the local or online supplement store, where NAC costs about $9 for a month's supply. But supplements aren't regulated by the FDA, and there's no way to guarantee the actual dose. Don't prescribe the liquid form of NAC (Mucomyst) -- it smells and tastes terrible, like rotten eggs.

Zheng et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. The Lancet Respiratory Medicine, Volume 2, Issue 3, Pages 187 - 194, March 2014.