Grantee Research Project Results
2000 Progress Report: Effects of Inhaled Ultrafine Particles on Asthma
EPA Grant Number: R826785Title: Effects of Inhaled Ultrafine Particles on Asthma
Investigators:
Institution: Lovelace Biomedical & Environmental Research Institute
EPA Project Officer: Chung, Serena
Project Period: October 1, 1998 through September 30, 2001 (Extended to September 30, 2002)
Project Period Covered by this Report: October 1, 1999 through September 30, 2000
Project Amount: $545,147
RFA: Health Effects of Particulate Matter and Associated Air Pollutants (1998) RFA Text | Recipients Lists
Research Category: Human Health , Air , Particulate Matter
Objective:
Epidemiological studies show that hospital admissions for asthma are positively associated with the concentrations of particulate matter (PM) in the air. However, experimental data are limited to support or contradict the possibility that the inhalation of low concentrations of ultrafine PM increases asthma attacks. Immune and inflammatory cells localized to the lungs of asthmatics respond to inhaled allergens with the production and release of cytokines and mediators that play central roles in asthma attacks. Although the inhalation of allergens usually stimulates the release of these cytokines and mediators, exposures to ultrafine particles may also trigger their release in the lungs of allergic individuals. The objective of the studies described in this proposal is to test two hypotheses: inhaled ultrafine particles trigger asthma attacks: directly by stimulating the release of allergic-response cytokines in the lungs of asthmatics, or indirectly by decreasing the concentration of inhaled allergen necessary to cause asthma attacks.Progress Summary:
Epidemiological studies show that hospital admissions for asthma are positively associated with the concentrations of particulate matter (PM) in the air. However, experimental data are limited to support or contradict the possibility that the inhalation of low concentrations of ultrafine PM increases asthma attacks. Immune and inflammatory cells localized to the lungs of asthmatics respond to inhaled allergens with the production and release of cytokines and mediators that play central roles in asthma attacks. Although the inhalation of allergens usually stimulates the release of these cytokines and mediators, exposures to ultrafine particles may also trigger their release in the lungs of allergic individuals. The objective of our studies is to test two hypotheses: inhaled ultrafine particles trigger asthma attacks: (1) directly by stimulating the release of allergic-response cytokines in the lungs of asthmatics, or (2) indirectly by decreasing the concentration of inhaled allergen necessary to cause asthma attacks
Preliminary Data Results
- Determined that ovalbumin (OVA) transgenic (Tg+/-) mice will not be sensitive enough to respond to acute ovalbumin and/or particle exposures. The Tg+/- mice require six weeks (6 hrs/day and 5 days/wk) of exposure to OVA to reach their maximum response. Additionally, this response is primarily neutrophilic rather than eosinophilic. Sensitization (ip OVA-alum) of the mice is not an ideal option either since the response is still neutrophilic. The goal is to determine whether short-term (1 day) increases in particle levels trigger an asthma attack short duration OVA exposures are required. Thus, we have chosen to switch to a model that utilizes OVA sensitized wild type mice that will respond to acute exposures.
- Determined the half maximal response to acute OVA exposure in terms of airway hyperresponsiveness and total inflammatory cells bronchoalveolar lavage for wild type mice. This level of OVA exposure will be used in combination with ultrafine particle exposure to determine whether ultrafine particles can exacerbate the OVA response.
- Based on discussions with other investigators and our own investigations we have found that the generator being used to produce 99.99 percent pure inorganic carbon particles is actually producing particles with a 60-70 percent organic carbon fraction. Initial characterization of these particles shows the organic fraction to be comprised of materials from plastics. Plastic components within the generator and plastic tubing are the main suspects for the organic carbon fraction. Work is underway to identify and eliminate potential contaminating.
- Set up, test and calibrate new Buxco Electronics whole-body exposure system that will allow for the measurement of airway responsiveness in unrestrained and unanesthetized animals. This will enable us to measure changes in airway responsiveness before and after OVA and/or particle exposure in the same animal.
- Characterization of particle concentration and size distribution within the mouse colony room and within an individual mouse cage to determine background particle exposure levels.
Evaluations Made During the Reporting Period
Our progress this year has been centered on developing and characterizing a new animal exposure model. We have developed a model that will enable the measurement of responses to acute OVA and/or particle exposures. The model is also suited to test the hypothesis that an elevated background level of inflammation in the lung is required for inhaled ultrafine particles to exacerbate allergic asthma.
Future Activities:
Due to changes in the exposure model design and problems with the ultrafine particle generation system, we are not as far along as expected. Next year's efforts will focus on utilizing the new animal exposure model in combination with OVA and particle exposures. Additionally, modifications to the particle generator to reduce the amount of organic carbon are in progress.Journal Articles:
No journal articles submitted with this report: View all 5 publications for this projectSupplemental Keywords:
particles, health effects, susceptibility, genetic predisposition., RFA, Scientific Discipline, Health, Air, Toxicology, particulate matter, Environmental Chemistry, Allergens/Asthma, Atmospheric Sciences, ambient air quality, asthma, cytokine production, particulates, lungs, fine particles, human health effects, inhalability, cytokines, carbon, pulmonary disease, allergic airway, exposure, carbon black, airway inflammation, chronic health effects, human exposure, lung inflammation, airborne pollutants, inhalation, Acute health effects, allergens, respiratoryProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.