Diesel Exhaust and Mechanism of Asthma

Asthma Clinical Trial

Official title:

Effects of Diesel Exhaust on Airways

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01699204
• Other study ID #: H08-02288
• Status: Completed
• Phase: N/A
• First received: October 1, 2012
• Last updated: September 27, 2017
• Start date: September 2007
• Est. completion date: October 2011

Study information

• Verified date: September 2017
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 49 Years

Eligibility

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)

Related Conditions & MeSH terms

• Asthma

Intervention

Dietary Supplement:
• N-acetylcysteine
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

Other:
• Diesel exhaust
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
• Filtered air
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

Locations

Country	Name	City	State
Canada	University of British Columbia	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

References & Publications (8)

Atkinson RW, Anderson HR, Sunyer J, Ayres J, Baccini M, Vonk JM, Boumghar A, Forastiere F, Forsberg B, Touloumi G, Schwartz J, Katsouyanni K. Acute effects of particulate air pollution on respiratory admissions: results from APHEA 2 project. Air Pollution and Health: a European Approach. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1860-6. — View Citation

Braman SS. The global burden of asthma. Chest. 2006 Jul;130(1 Suppl):4S-12S. Review. — View Citation

Hashimoto S, Gon Y, Takeshita I, Matsumoto K, Jibiki I, Takizawa H, Kudoh S, Horie T. Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation. Am J Respir Crit Care Med. 2000 Jan;161(1):280-5. — View Citation

Janssen NA, Brunekreef B, van Vliet P, Aarts F, Meliefste K, Harssema H, Fischer P. The relationship between air pollution from heavy traffic and allergic sensitization, bronchial hyperresponsiveness, and respiratory symptoms in Dutch schoolchildren. Environ Health Perspect. 2003 Sep;111(12):1512-8. — View Citation

McCreanor J, Cullinan P, Nieuwenhuijsen MJ, Stewart-Evans J, Malliarou E, Jarup L, Harrington R, Svartengren M, Han IK, Ohman-Strickland P, Chung KF, Zhang J. Respiratory effects of exposure to diesel traffic in persons with asthma. N Engl J Med. 2007 Dec 6;357(23):2348-58. — View Citation

Mudway IS, Stenfors N, Duggan ST, Roxborough H, Zielinski H, Marklund SL, Blomberg A, Frew AJ, Sandström T, Kelly FJ. An in vitro and in vivo investigation of the effects of diesel exhaust on human airway lining fluid antioxidants. Arch Biochem Biophys. 2004 Mar 1;423(1):200-12. — View Citation

Rudell B, Ledin MC, Hammarström U, Stjernberg N, Lundbäck B, Sandström T. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust. Occup Environ Med. 1996 Oct;53(10):658-62. — View Citation

Stenfors N, Nordenhäll C, Salvi SS, Mudway I, Söderberg M, Blomberg A, Helleday R, Levin JO, Holgate ST, Kelly FJ, Frew AJ, Sandström T. Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel. Eur Respir J. 2004 Jan;23(1):82-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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