title: Anti-oxidant N-acetylcysteine diminishes diesel exhaust-induced increased airway responsiveness in person with airway hyper-reactivity.
abstract: BACKGROUND
  Inhalation of diesel exhaust (DE) at moderate concentrations causes increased airway responsiveness in asthmatics and increased airway resistance in both healthy and asthmatic subjects, but the effect of baseline airway responsiveness and anti-oxidant supplementation on this dynamic is unknown.
  
  
  OBJECTIVE
  We aimed to determine if changes in airway responsiveness due to DE are attenuated by thiol anti-oxidant supplementation, particularly in those with underlying airway hyper-responsiveness.
  
  
  METHODS
  Participants took N-acetylcysteine (600 mg) or placebo capsules three times daily for 6 days. On the last of these 6 days, participants were exposed for 2 h to either filtered air (FA) or DE (300 μg/m(3) of particulate matter smaller than 2.5 microns). Twenty-six non-smokers were studied under each of three experimental conditions (filtered air with placebo, diesel exhaust with placebo, and diesel exhaust with N-acetylcysteine) using a randomized, double-blind, crossover design, with a 2-week washout between conditions. Methacholine challenge was performed pre-exposure (baseline airway responsiveness) and post-exposure (effect of exposure).
  
  
  RESULTS
  Anti-oxidant supplementation reduced baseline airway responsiveness in hyper-responsive individuals by 20% (p = 0.001). In hyper-responsive individuals, airway responsiveness increased 42% following DE compared with FA (p = 0.03) and this increase was abrogated with anti-oxidant supplementation (diesel exhaust with N-acetylcysteine vs. filtered air with placebo, p = 0.85).
  
  
  CONCLUSIONS
  Anti-oxidant (N-acetylcysteine) supplementation protects against increased airway responsiveness associated with DE inhalation and reduces need for supplement bronchodilators in those with baseline airway hyper-responsiveness. Individuals with variants in genes of oxidative stress metabolism when exposed to DE are protected from increases in airway responsiveness if taking anti-oxidant supplementation.
authors.affiliation: Department of Medicine, Respiratory Division.
authors.forename: Chris
authors.initials: C
authors.lastname: Carlsten
authors.forename: Meaghan J
authors.initials: MJ
authors.lastname: MacNutt
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Francesco
authors.initials: F
authors.lastname: Sava
authors.forename: Mandy M
authors.initials: MM
authors.lastname: Pui
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000517:prevention & control*; D001335:Vehicle Emissions / Q000633:toxicity*; D055815:Young Adult
chemical_list: D000975:Antioxidants; D016085:Bronchoconstrictor Agents; D001335:Vehicle Emissions; D016210:Methacholine Chloride; D000111:Acetylcysteine
keywords: air pollution; airway responsiveness; anti-oxidant; asthma; diesel exhaust