The antioxidant N-acetylcysteine may be popular in chronic obstructive pulmonary disease (COPD) after cutting exacerbations in some trials, but don't expect to see it in clinical guidelines any time soon, two pulmonologists argued.
Most guidelines for stable COPD have shunned the supplement -- which is also an antidote to acetaminophen (Tylenol) -- despite widespread use in the community across all stages of COPD, noted Mario Cazzola, MD, of the University of Rome Tor Vergata, and Maria Gabriella Matera, MD, PhD, of the Second University of Naples, Italy.
Their commentary accompanied the findings of a 22% relative reduction of acute exacerbations compared with placebo in the Chinese PANTHEON trial, reported online in Lancet Respiratory Medicine.
"Although we are fascinated by Zheng and colleagues' results, we believe that the evidence that emerged from the PANTHEON study is not adequate to make N-acetylcysteine an integral component of COPD treatment," Cazzola and Matera wrote.
The problem is evidence.
The positive findings have all come from either small studies at high risk of selection or publication bias, or have been done in China; on the other hand, the large BRONCUS trial in a largely white European population showed no effect on lung function or exacerbations.
Replication of PANTHEON's findings in white patients with COPD is "imperative," Cazzola and Matera suggested, noting that genetic, environmental, or dietary factors could explain a benefit in China that doesn't generalize to other populations.
It's also possible that the high dose was key in PANTHEON, double the 600-mg daily dose used in BRONCUS, they added.
The purported mechanism for N-acetylcysteine was through antioxidant action, but Cazzola and Matera likewise cast doubt on that.
"At present, little is known about whether N-acetylcysteine acts as an antioxidant, an anti-inflammatory, or a mucolytic drug, or all three, when it prevents COPD exacerbations in humans," they wrote.
"However, available evidence suggests to us that the favourable effect of N-acetylcysteine on acute exacerbations of COPD is attributable to its mucolytic action," they added. "This opinion is strengthened by the documentation that mucolytic drugs, irrespective of whether or not they are able to exert antioxidant effects, are associated with a small reduction in acute exacerbations of COPD."
N-acetylcysteine has been popular as an antioxidant among AIDS and cancer patients as well.
Antioxidant use, though, has been deemed problematic during metastatic cancer treatment as it may undermine mechanisms of action on cancer cell death.
Disclosures
Cazzola and Matera reported having no conflicts of interest to disclose.
Primary Source
Lancet Respiratory Medicine
Source Reference: Cazzola M, Matera MG "N-acetylcysteine in COPD may be beneficial, but for whom?" Lancet Respir Med 2014; DOI: 10.1016/S2213-2600(13)70294-7.