Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial.
BACKGROUND
Increased oxidative stress is important in the pathogenesis of chronic obstructive pulmonary disease (COPD). We postulated that treatment with the antioxidant N-acetylcysteine would reduce the rate of lung-function decline, reduce yearly exacerbation rate, and improve outcomes.


METHODS
In a randomised placebo-controlled study in 50 centres, 523 patients with COPD were randomly assigned to 600 mg daily N-acetylcysteine or placebo. Patients were followed for 3 years. Primary outcomes were yearly reduction in forced expiratory volume in 1 s (FEV1) and the number of exacerbations per year. Analysis was by intention to treat.


RESULTS
The yearly rate of decline in FEV1 did not differ between patients assigned N-acetylcysteine and those assigned placebo (54 mL [SE 6] vs 47 mL [6]; difference in slope between groups 8 mL [9]; 95% CI -25 to 10). The number of exacerbations per year did not differ between groups (1.25 [SD 1.35] vs 1.29 [SD 1.46]; hazard ratio 0.99 [95% CI 0.89-1.10, p=0.85]). Subgroup analysis suggested that the exacerbation rate might be reduced with N acetylcysteine in patients not treated with inhaled corticosteroids and secondary analysis was suggestive of an effect on hyperinflation.


CONCLUSIONS
N-acetylcysteine is ineffective at prevention of deterioration in lung function and prevention of exacerbations in patients with COPD.
Decramer
Marc
M
Respiratory Division, University Hospital, Katholieke Universiteit Leuven, Belgium. marc.decramer@uz.kuleuven.ac.be
Rutten-van Mölken
Maureen
M
Dekhuijzen
P N Richard
PN
Troosters
Thierry
T
van Herwaarden
Cees
C
Pellegrino
Riccardo
R
van Schayck
C P Onno
CP
Olivieri
Dario
D
Del Donno
Mario
M
De Backer
Wilfried
W
Lankhorst
Ida
I
Ardia
Alfredo
A
D000111:Acetylcysteine / Q000009:adverse effects / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000975:Antioxidants / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D014797:Vital Capacity
D000975:Antioxidants; D005938:Glucocorticoids; D000111:Acetylcysteine