Diesel Exhaust and Mechanism of Asthma

This experiment is designed to test the hypothesis that oxidative stress is responsible for changes in airway responsiveness in humans exposed to diesel exhaust.

The specific aim is to test the hypothesis that diesel exhaust (DE) increases airway reactivity via oxidative stress, particularly in asthmatics. To test this hypothesis, we use a crossover in vivo experimental model in mild asthmatics and normal controls using a state-of-the-art diesel exhaust exposure facility. Participants took N-acetylcysteine (600 mg) or placebo capsules three times daily for six days. On the final morning of supplementation, participants were exposed for 2 hours to either filtered air or diesel exhaust (300 µg·m-3 of particulate matter smaller than 2.5 microns). Twenty-six non-smokers between 19-49 years were studied under three experimental conditions (filtered air with placebo, diesel exhaust with placebo and diesel exhaust with N-acetylcysteine) using randomized, double-blind, crossover design, with a two week minimum washout between conditions. Methacholine challenge was performed pre-exposure (to determine baseline airway responsiveness) and post-exposure (to determine the effect of exposure).

Exposure for 2 hours to diesel exhaust and N-acetylcysteine tablets (600 mg) 3 times daily for 6 days

N-acetylcysteine 600mg taken orally 3 times daily for 6 days prior to exposure to diesel exhaust for 2 hours. The last supplement was taken the morning of the exposure

A placebo tablet taken 3 times daily for 6 days prior to exposure to diesel exhaust for 2 hours. The last supplement was taken the morning of the exposure

A placebo tablet taken 3 times daily for 6 days prior to exposure to filtered air for 2 hours. The last supplement was taken the morning of the exposure

Establish that oxidative stress is responsible for changes in human airway reactivity induced by DE (300 µg/m3 inhaled for two hours).

Inclusion Criteria: Between 19-49 years, non smokers, asthmatics, healthy controls Exclusion Criteria: Smokers, pregnant or co-existing medical condition for which diesel exhaust would confer significant risk (i.e. coronary artery disease)

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