Diesel Exhaust and Mechanism of Asthma

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

Detailed Description
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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).

Official Title
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Effects of Diesel Exhaust on Airways

Conditions
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Asthma

Intervention / Treatment
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* Dietary Supplement: N-acetylcysteine
* Other: Diesel exhaust
* Other: Filtered air


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Filtered air with placebo<br>Exposure for 2 hours to filtered air and placebo tablets 3 times daily for 6 days | Other: Filtered air<br>* 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<br>|
| Active Comparator: Diesel exhaust with placebo<br>Exposure for 2 hours to diesel exhaust and placebo tablets 3 times daily for 6 days | Other: Diesel exhaust<br>* 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<br>|
| Experimental: Diesel exhaust with N-acetylcysteine<br>Exposure for 2 hours to diesel exhaust and N-acetylcysteine tablets (600 mg) 3 times daily for 6 days | Dietary Supplement: N-acetylcysteine<br>* 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<br>Other: Diesel exhaust<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Human airway reactivity | Establish that oxidative stress is responsible for changes in human airway reactivity induced by DE (300 µg/m3 inhaled for two hours). | 50 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Air pollution, Diesel exhaust, Airway responsiveness, Anti-oxidant