Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study

Chest. 2009 Aug;136(2):381-386. doi: 10.1378/chest.09-0421. Epub 2009 May 15.


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.

Trial registration: Clinicaltrials.gov Identifier: NCT00476736.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Adult
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Exercise Test
  • Exercise Tolerance / drug effects*
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Probability
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Reference Values
  • Respiratory Function Tests
  • Risk Assessment
  • Severity of Illness Index
  • Total Lung Capacity / drug effects*
  • Treatment Outcome


  • Acetylcysteine

Associated data

  • ClinicalTrials.gov/NCT00476736