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Effect of N-acetylcysteine in COPD patients with different microsomal epoxide hydrolase genotypes

Authors Zhang JQ, Zhang JQ, Liu H, Zhao ZH, Fang LZ, Liu L, Fu WP, Shu JK, Feng JG, Dai LM

Received 23 December 2014

Accepted for publication 6 March 2015

Published 13 May 2015 Volume 2015:10(1) Pages 917—923

DOI https://doi.org/10.2147/COPD.S79710

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Richard Russell

Jian-Qing Zhang,1 Jia-Qiang Zhang,1 Hua Liu,2 Zhi-Huan Zhao,1 Li-Zhou Fang,1 Ling Liu,1 Wei-Ping Fu,1 Jing-Kui Shu,1 Jia-Gang Feng,1 Lu-Ming Dai1

1Department of Respiratory Critical Care Medicine, 2Department of Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China

Background: The role of the antioxidant N-acetylcysteine (NAC) in the treatment of chronic obstructive pulmonary disease (COPD) has not been clarified as yet. In early studies, we found that the proportion of smokers with COPD having extremely slow/slow microsomal epoxide hydrolase (EPHX1) enzyme activity is significantly higher than that in healthy smokers. The purpose of this study was to evaluate whether different EPHX1 enzyme activity is related to differential therapeutic effects of treatment with NAC in COPD.
Methods: A total of 219 patients with COPD were randomly allocated to an extremely slow/slow EPHX1 enzyme activity group (n=157) or a fast/normal EPHX1 enzyme activity group (n=62) according to their EPHX1 enzyme activity. Both groups were treated with NAC 600 mg twice daily for one year. The main study parameters, including forced expiratory volume in one second (FEV1), St George’s Respiratory Questionnaire (SGRQ), and yearly exacerbation rate, were measured at baseline and at 6-month intervals for one year.
Results: Both FEV1 and SGRQ symptom scores were improved after treatment with NAC in the slow activity group when compared with the fast activity group. Further, changes in FEV1 and SGRQ symptom score in patients with mild-to-moderate COPD were more significant than those in patients with severe-to-very severe COPD. The yearly exacerbation rates were reduced in both groups, but the reduction in the slow activity group was significantly lower than in the fast activity group.
Conclusion: NAC treatment in COPD patients with extremely slow/slow EPHX1 enzyme activity improves FEV1 and the SGRQ symptom score, especially in those with mild-to-moderate COPD, and polymorphism in the EPHX1 gene may have a significant role in differential responses to treatment with NAC in patients with COPD.

Keywords: N-acetylcysteine, chronic obstructive pulmonary disease, microsomal epoxide hydrolase, polymorphism

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