Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study.
BACKGROUND
FEV(1) is used for the classification of disease severity and is a good predictor of COPD mortality. However, it is a poor predictor of clinical symptoms, exercise tolerance, and response to bronchodilators in COPD. Progressive reduction in inspiratory capacity (IC) during exercise reflects dynamic hyperinflation and is a good predictor of decreased exercise ability as well as increased exertional dyspnea. In animal models of COPD, N-acetylcysteine (NAC), an antioxidant/mucous modifier, has been shown to modify small airways, which mainly causes lung hyperinflation.


OBJECTIVE
Our goal was to examine the effect of 1,200 mg/d of NAC on lung hyperinflation at rest and after exercise in patients with moderate-to-severe COPD.


METHODS
This was a randomized, double-blind, cross-over study that included 24 eligible patients > 40 years of age with a diagnosis of COPD, a FEV(1) < 70% of predicted, FEV(1)/FVC ratio < 0.70, and a functional residual capacity > 120% of predicted normal. Patients were randomized to placebo treatment or NAC treatment twice daily for 6 weeks. This was followed by a 2-week washout period, and then patients were crossed over to alternate therapy for an additional 6 weeks. Evaluation was performed after each 6 weeks of each treatment.


RESULTS
IC and FVC were higher especially after exercise after NAC treatment compared with placebo treatment. In addition, the relationship of residual volume to total lung capacity was reduced in a similar pattern. Furthermore, endurance time was longer after NAC treatment compared with placebo treatment.


CONCLUSIONS
NAC treatment of patients with stable, moderate-to-severe COPD has a beneficial effect on physical performance, probably due to a reduction in air trapping.


BACKGROUND
Clinicaltrials.gov Identifier: NCT00476736.
Stav
David
D
Pulmonary Institute, Assaf Harofeh Medical Center, Zerifin, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: dstav@post.tau.ac.il.
Raz
Meir
M
Maccabi Health Care Services, Tel Aviv, Israel.
D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D011336:Probability; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000188:drug therapy*; D012016:Reference Values; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012720:Severity of Illness Index; D014109:Total Lung Capacity / Q000187:drug effects*; D016896:Treatment Outcome
D000111:Acetylcysteine