High-dose oral N-acetylcysteine fails to improve respiratory health status in patients with chronic obstructive pulmonary disease and chronic bronchitis: a randomized, placebo-controlled trial
Authors Johnson K, McEvoy C, Naqvi S, Wendt C, Reilkoff R, Kunisaki K, Wetherbee E, Nelson D, Tirouvanziam R, Niewoehner D
Received 12 December 2015
Accepted for publication 1 February 2016
Published 21 April 2016 Volume 2016:11(1) Pages 799—807
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Richard Russell
Kara Johnson,1,2 Charlene E McEvoy,3 Sakina Naqvi,1,4 Chris Wendt,1 Ronald A Reilkoff,4,5 Ken M Kunisaki,1 Erin E Wetherbee,1 David Nelson,6 Rabindra Tirouvanziam,7 Dennis E Niewoehner1
1Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, MN, 2Sanford Health, Fargo, ND, 3Pulmonary Section, HealthPartners Research Foundation, St Paul, 4HealthEast Maplewood Clinic, Maplewood, 5Pulmonary Section, University of Minnesota Medical Center, 6Center for Chronic Disease Outcomes Research, Minneapolis VA Health Care System, Minneapolis, MN, 7Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine, Atlanta, GA, USA
Background: Clinical outcomes are worse in patients with COPD and chronic bronchitis. N-acetylcysteine (NAC) is commonly prescribed for such patients but with uncertain clinical benefits. We postulated that oral NAC, at much larger doses than those ordinarily prescribed, would improve clinical outcomes in a subset of patients with COPD and chronic bronchitis.
Objective: The aim of this study was to determine whether very high-dose NAC would improve respiratory health status in patients with COPD and chronic bronchitis.
Methods: Patients with COPD and chronic bronchitis were enrolled in a randomized, controlled, double-blinded trial. Patients received oral NAC (1,800 mg) or matching placebo twice daily for 8 weeks in addition to their usual respiratory medications. The primary outcome, respiratory health status, was assessed by changes in the St George’s Respiratory Questionnaire. The effects of NAC on lung function and circulating markers of oxidative stress and inflammation were also evaluated.
Results: We terminated the study prematurely because new external information suggested the possibility of a safety issue. Of the planned 130 patients, 51 were randomized and 45 (22 in the placebo arm and 23 in the NAC arm) completed the study. There was no statistically significant difference between changes in the St George’s Respiratory Questionnaire total score, comparing NAC to placebo (adjusted mean difference, 0.1 U; 95% CI, -7.8 to 8.18 U; P=0.97). There were also no significant NAC-related improvements in any of the secondary outcomes.
Conclusion: In this 8-week trial, we were unable to show any clinical benefit from a very high dose of NAC in patients with COPD and chronic bronchitis.
Keywords: COPD, chronic bronchitis, N-acetylcysteine