Anti-oxidant N-acetylcysteine diminishes diesel exhaust-induced increased airway responsiveness in person with airway hyper-reactivity.

TitleAnti-oxidant N-acetylcysteine diminishes diesel exhaust-induced increased airway responsiveness in person with airway hyper-reactivity.
Publication TypeJournal Article
Year of Publication2014
AuthorsCarlsten, C, Macnutt, MJ, Zhang, Z, Sava, F, Pui, MM
JournalToxicol Sci
Volume139
Issue2
Pagination479-87
Date Published2014 Jun
ISSN1096-0929
KeywordsAcetylcysteine, Adult, Antioxidants, Bronchoconstrictor Agents, Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Methacholine Chloride, Middle Aged, Respiratory Function Tests, Respiratory Hypersensitivity, Vehicle Emissions, Young Adult
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.OBJECTIVES: 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.

DOI10.1093/toxsci/kfu040
Alternate JournalToxicol. Sci.
PubMed ID24814479