title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, MN, USA; Sanford Health, Fargo, ND, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Johnson
authors.affiliation: Pulmonary Section, HealthPartners Research Foundation, St Paul, Minneapolis, MN, USA.
authors.forename: Charlene E
authors.initials: CE
authors.lastname: McEvoy
authors.affiliation: Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, MN, USA; HealthEast Maplewood Clinic, Maplewood, Minneapolis, MN, USA.
authors.forename: Sakina
authors.initials: S
authors.lastname: Naqvi
authors.affiliation: Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, MN, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Wendt
authors.affiliation: HealthEast Maplewood Clinic, Maplewood, Minneapolis, MN, USA; Pulmonary Section, University of Minnesota Medical Center, Minneapolis, MN, USA.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Reilkoff
authors.affiliation: Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, MN, USA.
authors.forename: Ken M
authors.initials: KM
authors.lastname: Kunisaki
authors.affiliation: Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, MN, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Wetherbee
authors.affiliation: Center for Chronic Disease Outcomes Research, Minneapolis VA Health Care System, Minneapolis, MN, USA.
authors.forename: David
authors.initials: D
authors.lastname: Nelson
authors.affiliation: Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Rabindra
authors.initials: R
authors.lastname: Tirouvanziam
authors.affiliation: Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, MN, USA.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Niewoehner
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000368:Aged; D029481:Bronchitis, Chronic / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy*; D017211:Treatment Failure
chemical_list: D000111:Acetylcysteine
keywords: COPD; N-acetylcysteine; chronic bronchitis