Original Research: COPD |

High-Dose N-Acetylcysteine in Stable COPDEffect of High-dose N-Acetylcysteine in COPD: The 1-Year, Double-Blind, Randomized, Placebo-Controlled HIACE Study

Hoi Nam Tse, MBChB, FCCP; Luca Raiteri, MD; King Ying Wong, MBBS; Kwok Sang Yee, MBBS; Lai Yun Ng, MBChB; Ka Yan Wai, MBBS; Ching Kong Loo, MBBS; Ming Houng Chan, MBBS
Author and Funding Information

From the Kwong Wah Hospital (Drs Tse, Ng, Wai, Loo, and Chan), Hong Kong, China; Wong Tai Sin Hospital (Drs Wong and Yee), Hong Kong, China; and Medical Department (Dr Raiteri), Innovation & Medical Sciences, Zambon Company SpA, Bresso, Italy.

Correspondence to: Hoi Nam Tse, MBChB, FCCP, Medical and Geriatric Department, Kwong Wah Hospital, Waterloo Road, Yau Ma Tei, Hong Kong, China; e-mail: drhoinam@gmail.com

Funding/Support: The study was sponsored by the Tung Wah Group of Hospitals Research Fund. Both the N-acetylcysteine and placebo used in this study were manufactured by Zambon Switzerland Ltd and provided by Zambon S.p.A, Bresso, Italy.

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

Chest. 2013;144(1):106-118. doi:10.1378/chest.12-2357
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Background:  The mucolytic and antioxidant effects of N-acetylcysteine (NAC) may have great value in COPD treatment. However, beneficial effects have not been confirmed in clinical studies, possibly due to insufficient NAC doses and/or inadequate outcome parameters used. The objective of this study was to investigate high-dose NAC plus usual therapy in Chinese patients with stable COPD.

Methods:  The 1-year HIACE (The Effect of High Dose N-acetylcysteine on Air Trapping and Airway Resistance of Chronic Obstructive Pulmonary Disease—a Double-blinded, Randomized, Placebo-controlled Trial) double-blind trial conducted in Kwong Wah Hospital, Hong Kong, randomized eligible patients aged 50 to 80 years with stable COPD to NAC 600 mg bid or placebo after 4-week run-in. Lung function parameters, symptoms, modified Medical Research Council (mMRC) dyspnea and St. George’s Respiratory Questionnaire (SGRQ) scores, 6-min walking distance (6MWD), and exacerbation and admission rates were measured at baseline and every 16 weeks for 1 year.

Results:  Of 133 patients screened, 120 were eligible (93.2% men; mean age, 70.8 ± 0.74 years; %FEV1 53.9 ± 2.0%). Baseline characteristics were similar in the two groups. At 1 year, there was a significant improvement in forced expiratory flow 25% to 75% (P = .037) and forced oscillation technique, a significant reduction in exacerbation frequency (0.96 times/y vs 1.71 times/y, P = .019), and a tendency toward reduction in admission rate (0.5 times/y vs 0.8 times/y, P = .196) with NAC vs placebo. There were no significant between-group differences in mMRC dypsnea score, SGRQ score, and 6MWD. No major adverse effects were reported.

Conclusion:  In this study, 1-year treatment with high-dose NAC resulted in significantly improved small airways function and decreased exacerbation frequency in patients with stable COPD.

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

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