Published: Feb 3, 2014 | Updated: Feb 4, 2014
By Crystal Phend, Senior Staff Writer, MedPage Today
Action Points
- In a prospective, randomized, placebo-controlled, study, in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD), long-term use of N-acetylcysteine reduced the incidence of acute exacerbations.
- In another study, colonization by bacterial pathogens in patients with COPD was associated with a clinically significant moderate increase in daily symptoms.
Administering an anti-oxidant supplement and tackling bacteria colonizing the lungs are two separate strategies that each could be effective in chronic obstructive pulmonary disease (COPD), two studies showed.
In the first one, the antioxidant supplement N-acetylcysteine – which is also an antidote to acetaminophen (Tylenol) — cut acute exacerbations by 22% in the Chinese PANTHEON trial.
The drug reduced the number of acute exacerbations per patient year to 1.16 compared with 1.49 on placebo (risk ratio 0.78, 95% CI 0.67-0.90), Nan-Shan Zhong, MD, of China’s First Affiliated Hospital of Guangzhou Medical University, and colleagues reported online in Lancet Respiratory Medicine.
Results for the drug have been mixed in prior COPD trials.
Zhong’s PANTHEON trial randomized 1,006 moderate-to-severe COPD patients at 34 hospitals in China to double-blind treatment with N-acetylcysteine (one 600-mg tablet, twice daily) or matched placebo for 1 year.
The researchers called N-acetylcysteine well-tolerated, with not much difference in adverse event rates compared with placebo (29% versus 26%, serious events 48 versus 46).
The most common serious adverse event — acute exacerbation of COPD — wasn’t more common compared with placebo (6% among those on N-acetylcysteine versus 7% among those on placebo). No study drug-related deaths or notable laboratory abnormalities occurred.
“Patients with mild COPD (GOLD I), might also benefit from treatment with N-acetylcysteine and this group is worth investigating in future trials,” they concluded.
In the second study, another strategy — one that might be a little farther from the clinic — was described by Himanshu Desai, MD, of Virginia’s Chesapeake Pulmonary and Critical Care Medicine, and colleagues in the Annals of the American Thoracic Society.
Symptom scores adjusted for exacerbations and other factors were higher (average 5.28 versus 4.46 on the Breathlessness, Cough, and Sputum Scale, P=0.008) during periods of colonization with four pathogens:
- Nontypeable Haemophilus influenzae
- Moraxella catarrhalis
- Streptococcus pneumoniae
- Pseudomonas aeruginosa
Airway inflammation marked by sputum interleukin-8 levels correlated with bacterial colonization, although the longitudinal observational study of 41 COPD patients followed daily for symptoms and biweekly for sputum cultures couldn’t determine causality.
These findings suggested prophylactic antibiotics would cut COPD symptoms, but “concerns about the emergence of antibiotic resistance should temper such an approach,” Desai’s group cautioned.
“Therapies that augment innate lung defence mechanisms, making the airway milieu less hospitable to bacterial colonization, could have significant impact on the daily symptom burden and unreported exacerbations of COPD,” they suggested instead. “Development of such therapies would be welcome and could have these additional benefits besides reducing clinical exacerbations.”
Zhong’s trial was sponsored by Hainan Zambon Pharmaceutical, which also paid for study medication, travel to attend an investigators’ meeting for the study, and editorial assistance.
Several co-authors on that study reported employment with the sponsor or MedKey (Shanghai) Med-Tec Development.
Zhong reported having no conflicts of interest to declare.
Desai’s study was funded by the Department of Veterans Affairs.
Additional 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.
Additional source: Annals of the American Thoracic Society
Source reference:Desai H, et al “Bacterial colonization increases daily symptoms in patients with chronic obstructive pulmonary disease” Ann Am Thorac Soc 2014.