The general aim of this proposal is to explore the following questions related to irritant-induced asthma from both epidemiological and physiopathological approaches: 1) Do single irritant exposures (Reactive Airways Dysfunction Syndrome--RADS- and multiple irritant exposure (Irritant-Induced-Asthma--IrIA--) exposures result in equivalent consequences for airway structure and function? 2) Are baseline characteristics (atopy, airway caliber and responsiveness) relevant to susceptibility of developing IrIA and RADS? RADS and IrIA represent up to 15 percent of all cases of occupational asthma. It is also a condition of general interest for asthma per se. It has been estimated that 60 000 inhalational accidents occurring at home and identified as RADS are reported in U.S. emergency rooms on a yearly basis. RADS was originally defined as the development of respiratory symptoms in the minutes or hours after a single accidental inhalation of high concentrations of gas, aerosol, or particles, after which subjects are left with asthma like symptoms and airway hyperresponsiveness. Multiple exposures to high concentrations of products such as chlorine in pulp and paper mills can also cause IrIA, a more general term to describe an asthmatic syndrome that results from single or multiple exposures to irritant products. We will examine and follow new employees at risk of acute exposure to chlorine and serially assess their characteristics (atopy, airway caliber and responsiveness, smoking, nasal symptoms) and exposure events. In a subsample, we will also examine induced sputum. In a rat model, we will 1) examine the response to single and multiple exposures to chlorine vapor; 2) test the importance of background characteristics of the rat strain (atopy, airway muscle) to the response; 3) quantify the degree of airway remodelling in a susceptible and resistant rat strain; 4) assess the effects of neurokinin antagonists on the airway damage; 5) evaluate the role of airway epithelial chemokines such as RANTES and eotaxin in the inflammatory response. This work will identify, both in an epidemiological survey and in an animal model, the effect of single and multiple exposures to a respiratory irritant and the host predisposing factors. It will also further our understanding of the physiopathology of RADS and IrIA as well on the natural history and physiopathology of occupational asthma and of asthma induced by irritants.

Agency
National Institute of Health (NIH)
Institute
National Institute for Occupational Safety and Health (NIOSH)
Type
Research Project (R01)
Project #
5R01OH004058-03
Application #
6446030
Study Section
Special Emphasis Panel (ZOH1-MJG (07))
Program Officer
Kelty, Miriam F
Project Start
1999-09-30
Project End
2002-12-29
Budget Start
2001-09-30
Budget End
2002-12-29
Support Year
3
Fiscal Year
2001
Total Cost
$125,000
Indirect Cost
Name
Hopital Du Sacre'-Coeur de Montreal
Department
Type
DUNS #
City
Montreal
State
PQ
Country
Canada
Zip Code
Maghni, K; Malo, J-L; L'Archeveque, J et al. (2010) Matrix metalloproteinases, IL-8 and glutathione in the prognosis of workers exposed to chlorine. Allergy 65:722-30
Tuck, Stephanie A; Ramos-Barbon, David; Campbell, Holly et al. (2008) Time course of airway remodelling after an acute chlorine gas exposure in mice. Respir Res 9:61