Benefits of High-Dose N-Acetylcysteine to Exacerbation-Prone Patients With COPD

doi:10.1378/chest.13-2784

Chest

Volume 146, Issue 3, September 2014, Pages 611-623

https://doi.org/10.1378/chest.13-2784 Get rights and content

BACKGROUND

Although high-dose N-acetylcysteine (NAC) has been suggested to reduce COPD exacerbations, it is unclear which category of patients with COPD would benefit most from NAC treatment. The objective of this study was to compare the effect of high-dose NAC (600 mg bid) between high-risk and low-risk Chinese patients with COPD.

METHODS

Patients with spirometry-confirmed stable COPD were randomized to treatment with either NAC 600 mg bid or placebo in addition to their usual treatments. Patients were followed up every 16 weeks for a total of 1 year. Further analysis was performed according to each patient's exacerbation risk at baseline as defined by the current GOLD (Global Initiative for Chronic Obstructive Lung Disease) strategy to analyze the effect of high-dose NAC in high-risk and low-risk patients.

RESULTS

Of the 120 patients with COPD randomized (men, 93.2%; mean age, 70.8 ± 0.74 years; prebronchodilator FEV₁, 53.9 ± 2.0%; baseline characteristics comparable between treatment groups), 108 (NAC, 52; placebo, 56) completed the 1-year study. For high-risk patients (n = 89), high-dose NAC compared with placebo significantly reduced exacerbation frequency (0.85 vs 1.59 [P= .019] and 1.08 vs 2.22 [P= .04] at 8 and 12 months, respectively), prolonged time to first exacerbation (P= .02), and increased the probability of being exacerbation free at 1 year (51.3% vs 24.4%,P= .013). This beneficial effect of high-dose NAC vs placebo was not significant in low-risk patients.

CONCLUSIONS

High-dose NAC (600 mg bid) for 1 year reduces exacerbations and prolongs time to first exacerbation in high-risk but not in low-risk Chinese patients with COPD.

TRIAL REGISTRY

ClinicalTrials.gov; No.: NCT01136239; URL: www.clinicaltrials.gov

Section snippets

Study Design

This study was a 1-year, double-blind, randomized placebo-controlled trial conducted in the Kwong Wah Hospital, Hong Kong. Full details of the methodology have been published previously.⁷

Patients with stable COPD were recruited from the COPD clinic or the COPD ambulatory rehabilitation clinic from March 1, 2010, to February 28, 2011, in Kwong Wah Hospital if they had spirometry-confirmed COPD showing a postbronchodilator FEV₁/FVC < 0.70. Patients were excluded from the study if they refused to

Study Population and Baseline Characteristics

Of the 133 eligible patients with COPD screened, 120 were recruited after the 4-week run-in period. Among the high-risk group, 83.1% had two or more exacerbations in the past year, 52.8% had FEV₁< 50%, and 41.7% met both criteria. Of these high-risk patients, 44 and 45 received NAC and placebo, respectively, whereas in the low-risk group, 14 and 17 patients received NAC and placebo, respectively (Fig 1).

In total, 12 patients dropped out of the study (seven from the high-risk group and five from

Discussion

This study showed that for patients with a high risk of exacerbation, high-dose NAC significantly reduced exacerbation frequency, prolonged time to first exacerbation, and increased the likelihood of being exacerbation free at 1 year compared with placebo, but these beneficial effects of high-dose NAC over placebo were not significant in low-risk patients. The frequency of exacerbations is considered an important outcome for the clinical history of COPD. Exacerbations become more frequent and

Conclusions

The findings from this study suggest that 1-year treatment with high-dose NAC (600 mg bid) reduces exacerbation in high-risk but not in low-risk Chinese patients with COPD. Unlike previous studies proposing that the effect of mucolytics was only prominent in patients with COPD not using ICSs, the present study suggests that high-dose NAC could exert its effect even in patients with COPD using ICS or a combination of ICS with LABA or LAMA. To our knowledge, this study is the first to show that

Acknowledgments

Author contributions: L. R. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. H. N. T. served as principal author. H. N. T. and K. Y. W. contributed to the study concept and design; K. S. Y. contributed to the study supervision; H. N. T., K. Y. W., and L. Y. N. contributed to the data acquisition; H. N. T. and K. Y. W. contributed to the data interpretation; H. N. T. contributed to the data analysis; H.

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Funding/Support: Zambon SpA donated the study drugs. This work was supported by the Tung Wah Group of Hospitals Research Fund.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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Chest

Original Research: COPDBenefits of High-Dose N-Acetylcysteine to Exacerbation-Prone Patients With COPD

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

TRIAL REGISTRY

Section snippets

Study Design

Study Population and Baseline Characteristics

Discussion

Conclusions

Acknowledgments

Pulm Pharmacol Ther

Lancet

Chest

Chest

Chest

Am J Med

Chest

Lancet

Free Radic Biol Med

J Free Radic Biol Med

J Infect Chemother

Respir Physiol Neurobiol

Free Radic Biol Med

Int J Immunopharmacol

Pulm Pharmacol Ther

Pulm Pharmacol Ther

Respir Med

Exacerbation rate, health status and mortality in COPD—a review of potential interventions

Int J Chron Obstruct Pulmon Dis

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary

Am J Respir Crit Care Med

Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease

Cochrane Database Syst Rev

Original Research: COPD
Benefits of High-Dose N-Acetylcysteine to Exacerbation-Prone Patients With COPD