Irritant-Induced Asthma: Epidemiology and Pathogenesis

Details

• Personal Author:
  Gautrin D ; Malo JL ; Martin, Jennifer E.
• Description:
  It has been recently recognized that exposure to irritant materials can cause asthma, a type of asthma called Irritant-Induced asthma (IrIA). One of the most dramatic manifestations of this condition was the bronchopulmonary disease that occurred in the survivors of the World Trade Center (1). When this syndrome occurs at work, it is a type of occupational asthma (2). The general aim of this proposal was to explore the following questions related to IrIA from both epidemiological and physiopathological approaches: 1) Do single irritant exposures (Reactive Airways Dysfunction Syndrome--RADS--) and multiple irritant exposures (IrIA) 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? We examined and followed 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 sub-sample, we also examine induced sputum. In a mouse model, we: 1) explored the mechanisms of airway damage following chlorine exposure; 2) determined the time course of airway damage and repair after chlorine exposure. We found that: 1) Subjects who undergo the most significant changes in airway caliber and hyper-responsiveness generally have more numerous episodes of accidental inhalations and have suggestive evidence of airway remodeling (increased metalloproteinase activities in induced sputum); moreover, there is suggestion that subjects with lower airway caliber and higher responsiveness are at increased risks of lung function deterioration; 2) in the mouse model, chlorine causes dose-dependent changes in pulmonary function and histopathological dames as indicated by altered lung mechanics and epithelial cell sloughing, increased protein in bronchoalveolar lavage fluid. Repair of the damaged airways is characterized by a large increase in epithelial and subepithelial cell proliferation, which peaked five days post-exposure. There is evidence of oxidative stress in airway tissues as indicated, by the findings of an increase in carbonyl residues and the nitration of tyrosine residues. There is also evidence of the induction of the iNOS isoform in airway epithelial cells and in alveolar macrophages after chlorine exposure. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Air Pollution, Indoor Asthma Asthma, Occupational Chlorine Compounds Irritants Lung Lung Diseases Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Air-contamination Airborne-particles Bronchial-asthma Chlorine-compounds Inhalation-studies Irritant-gases Lung-cells Lung-disease Lung-disorders Lung-irritants Pulmonary-system-disorders Respiratory-system-disorders

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• Series:
  Grant Final Reports
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Final Grant Report
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-54
• NIOSHTIC Number:
  nn:20023743
• NTIS Accession Number:
  PB2005-105203
• Citation:
  NIOSH 2003 Mar; :1-54
• Contact Point Address:
  Jean-Luc Malo,MD, Department of Chest Medicine Sacre-Coeur Hospital, 5400 West Gouin Boulevard, Montreal, Canada, H4J 1C5
• Email:
  malojl@meddir.umontreal.ca
• Federal Fiscal Year:
  2003
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Performing Organization:
  Hospital du Sacre-Coeur, Montreal, Quebec
• Peer Reviewed:
  False
• Start Date:
  19990930
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20021229
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fd0b33cc1ffb7c9ebee7cc2b21fb2f418f137b20802709bedb9e9a1aa6987dcad3e240345b0b4c39f326cde060a77ae3db18dacb20e73eb83eb47d7df5f590fe
• Download URL:
  https://stacks.cdc.gov/view/cdc/218101/cdc_218101_DS1.pdf
• File Type:
  [PDF - 1.84 MB ]