title: Effect of N-acetylcysteine in COPD patients with different microsomal epoxide hydrolase genotypes.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Jia-Qiang
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Respiratory Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Zhi-Huan
authors.initials: ZH
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Li-Zhou
authors.initials: LZ
authors.lastname: Fang
authors.affiliation: Department of Respiratory Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Respiratory Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Fu
authors.affiliation: Department of Respiratory Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Jing-Kui
authors.initials: JK
authors.lastname: Shu
authors.affiliation: Department of Respiratory Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Jia-Gang
authors.initials: JG
authors.lastname: Feng
authors.affiliation: Department of Respiratory Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
authors.forename: Lu-Ming
authors.initials: LM
authors.lastname: Dai
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D018450:Disease Progression; D004334:Drug Administration Schedule; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D020127:Recovery of Function; D012720:Severity of Illness Index; D013147:Spirometry; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human; D000111:Acetylcysteine
keywords: N-acetylcysteine; chronic obstructive pulmonary disease; microsomal epoxide hydrolase; polymorphism