Grantee Research Project Results
2001 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, 2000 through September 30, 2001
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 also may 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 either (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.Progress Summary:
A new Buxco inhalation exposure system (whole-body plethysmography) has been setup and validated for measuring Penh as a means to assess airway hyperresponsiveness. The system also has been validated for ovalbumin (OVA) exposures. Aerosol concentration (e.g., in chamber, rise to concentration [T90], decay time, and spatial uniformity), nebulizer performance (e.g., use rate, aerosol output, and efficiency), and particle size characteristics were evaluated. Particle size characteristics were evaluated for both methacholine and OVA at three different points in the aerosol flow (e.g., nebulizer, dilution plenum, and exposure chamber). The particle sizes for methacholine were 2.27 (MMAD)/2.32 (sg), 2.72/1.8, and 2.16/1.47, respectively. Particle sizes for OVA were 2.10/2.74, 1.15/2.04, and 0.86/2.18. Methacholine aerosols were delivered wet, whereas OVA aerosols were run through a drying tube prior to delivery into the dilution plenum.A series of experiments were performed in support of the hypothesis that ultrafine particle exposure will enhance an existing allergic airway response. In addition, allergen challenge was performed prior to or after particle exposure to assess whether the presence of existing allergic lung inflammation is required to observe a particle effect. Ovalbumin sensitized (i.p. OVA-Alum) Balb/c mice were challenged with OVA either 24 hours prior to ulrafine particle exposure or immediately thereafter. Animals were exposed to aerosolized OVA (10 min; nebulized 1 percent OVA solution) in Buxco whole-body plythysmograph chambers. Ultrafine carbon particles were generated using an electric spark discharge generator with graphite electrodes (model CFG 1000; Palas Co, Karlsruhe, Germany). Ultrafine particle exposure was for a 6-hour period at an exposure concentration of 50 µg/m3 (CMAD = 22.5 ? 1.4 nm) in a nose-only exposure system. For some groups of animals, the particle concentration was increased to 200 µg/m3 (CMAD = 33.0 ? 1.5 nm) for 1 hour during the 6-hour exposure at the 1-2 or 5-6 hour period. Approximately 16 hours following the last exposure, airway hyperresonsiveness (AHR; Penh) following methacholine challenge was measured, lungs were lavaged, and blood was collected. Initial analyses of AHR data suggest that ultrafine carbon particle exposure can increase AHR independent of whether animals were challenged with OVA or not. It does not appear that the timing of the allergen challenge made a significant difference on AHR. Analyses of lavage cell differentials, lavage cytokine (IL-2, IL-4, IL-5 and IFNg) levels, and serum antibody levels are currently in progress.
Pilot experiments were carried out in collaboration with the National Environmental Respiratory Center (NERC) in which the effect of diesel exhaust exposure on the allergic airway response was examined. Studies from NERC suggested that diesel exposure prior to OVA challenge suppressed the allergic airway response (i.e., decreased AHR, decreased lung eosinophilia, decreased lung IL-5 levels, decreased serum IgE). In the collaborative studies we found that if OVA challenge was administered prior to diesel exhaust exposure, the allergic airway response was exacerbated (i.e., increased AHR, increased lung lymphocytes and eosinophils, and increased serum IgE). A significant fraction of the diesel exhaust particulate matter falls within the ultrafine particulate size fraction (e.g., < 0.01 mm). Based on our preliminary results from the ultrafine carbon particle exposures, these results suggest that this diesel effect is not due to a nonspecific particle effect. These results suggest that there is a specific component of diesel exhaust that can have divergent effects on the pulmonary immune response, depending on the timing of the exposure with respect to allergen challenge.
Future Activities:
A no-cost 1 year extension was requested and received to complete the work described in this section. Upcoming work will focus on analyzing current data, performing targeted experiments, and preparation of manuscripts. Epidemiological data in the literature suggests that the effect of ultrafine particle exposure is more noticeable (e.g., decreased FEV1) after repeated daily exposure. Thus, upcomming experiments will challenge animals for 3 days with ultrafine particles to determine whether increasing the duration of particle exposure (1 versus 3 days) will further enhance the allergic airway response. Other experiments will focus on the effect of increasing the allergen dose while maintaining a constant ultrafine particle exposure level.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.