Grantee Research Project Results
2002 Progress Report: Effects of Airborne Particles on Allergic Airway Disease
EPA Grant Number: R829216Title: Effects of Airborne Particles on Allergic Airway Disease
Investigators: Harkema, Jack , Sioutas, Constantinos
Institution: Michigan State University , University of Southern California
EPA Project Officer: Chung, Serena
Project Period: October 31, 2001 through October 30, 2004 (Extended to October 30, 2006)
Project Period Covered by this Report: October 31, 2001 through October 30, 2002
Project Amount: $854,702
RFA: Health Effects of Particulate Matter (2001) RFA Text | Recipients Lists
Research Category: Human Health , Particulate Matter , Air
Objective:
People with preexisting respiratory disease may be at increased risk from the toxic effects of airborne particulate matter (PM). Childhood asthma currently is a major public health problem, especially among urban and minority populations that are exposed to high levels of air pollutants (e.g., Los Angeles, Detroit). Although recent epidemiologic studies suggest that children with asthma are one of the major susceptible populations to the toxic effects of PM, little is known about the physicochemical character of PM to which asthmatic children are exposed or the underlying toxicologic mechanisms responsible for the PM-induced adverse effects.
The overall objective of this research project is to conduct atmospheric and toxicologic research designed to understand the adverse effects of airborne PM of various size fractions (coarse, fine, and ultrafine particles) on pulmonary airways with preexisting allergic airway disease. We will test the following hypotheses: (1) PM exposure exacerbates the airway injury associated with allergic airway disease; (2) the magnitude of PM-induced airway toxicity is dependent on particle size; (3) PM in transported ("aged") air pollution is more toxic to airways than that in locally generated air pollution; and (4) PM-induced airway toxicity is most severe during periods of intense photochemical activity.
Progress Summary:
In October 2001, we conducted our first inhalation toxicology studies in Claremont, CA, in the northeast Los Angeles Basin ([LAB] our receptor site for transported PM). The potential health effects of inhalation co-exposures of urban air pollutants and airborne allergens have not been thoroughly investigated. The purpose of this initial study was to determine the effects of inhalation exposure of various size fractions of concentrated ambient particles (CAPs) on the lungs of rats that were concurrently exposed to a pulmonary allergen (ovalbumin [OVA]). A state-of-the-art mobile air research laboratory, equipped with inhalation exposure chambers and ambient particle concentrators, was used to conduct the inhalation toxicology studies. The mobile laboratory was parked in a residential site in Claremont, CA. OVA-sensitized, male, Brown Norway rats (10-12 weeks of age) were exposed to filtered air (controls), concentrated ambient coarse (2.5-10 µm; CCAPs), fine (0.15-2.5 µm; FCAPs), or ultrafine (0.01-0.15 µm; UFCAPs) particles, 5 hours/day (11 a.m.-4 p.m.), for 3 consecutive days. Immediately prior to each daily inhalation exposure, the rats were intranasally challenged with saline alone or a 0.5 percent solution of OVA in saline. Rats were exposed to average mass concentrations of 554, 515, and 45 µg/m3 for CCAPs, FCAPs, and UFCAPs, respectively. Twenty-four hours after the end of the exposures, rats were sacrificed, their pulmonary airways were lavaged with saline, and their lung lobes were processed for light microscopic or mRNA analyses. OVA-instilled rats had an allergic bronchiolitis with mucous cell hyperplasia (increase in the number of mucus-producing secretory cells lining the pulmonary airways) and an allergic alveolitis with marked increases in eosinophils in the bronchoalveolar lavage fluid (BALF). OVA-instilled and air-exposed rats had 538 percent more eosinophils in the BALF, 104 percent more stored mucosubstances in the bronchiolar epithelium, and a six-fold increase in mucin-specific gene expression in bronchiolar airways than saline-instilled/air-exposed controls. Using this specific exposure regime of daily allergen and CAPs exposure, we observed a marked particle-induced suppression, rather than enhancement, of the pulmonary inflammatory and epithelial responses to the inhaled allergen. Exposures to FCAPs or UFCAPs, but not CCAPs, caused a marked attenuation (50-100 percent) of the OVA-induced allergic alveolitis, and mucous cell hyperplasia and mucin-specific gene expression in bronchiolar epithelium. These results indicate that fine (or ultrafine) ambient airborne particles may significantly interfere with allergen-induced airway responses during co-exposure of these airborne agents.
In January 2002, we conducted our second inhalation toxicology study at the same site in Claremont, CA. The experimental design was similar to that conducted in October 2001. Like the first study, male, Brown Norway rats (10-12 weeks of age) were exposed to filtered air, CCAPs, FCAPs, or UFCAPs particles, 5 hours/day (11 a.m.- 4 p.m.), for 3 consecutive days. Immediately prior to each daily inhalation exposure, the rats were again intranasally challenged with saline alone or a 0.5 percent solution of OVA in saline. However, in this winter study, rats were exposed to average mass concentrations of 86, 103, and 25 µg/m3 for CCAPs, FCAPs, and UFCAPs, respectively. These average mass concentrations were markedly lower than those to which rats were exposed in the first Claremont study in October 2001 (see above). In contrast to the results of the October study, no FCAP-, UFCAP-, or CCAP-related effects on OVA-induced allergic alveolitis, mucous cell hyperplasia, or mucin-specific gene expression were observed in these rats exposed to the much lower concentrations of CAPs. These results, in relation to the first study, suggest that these lower mass concentrations were not sufficient to modulate the pulmonary responses induced by the allergen challenge. Additional chemical analyses of the CAPs from the first and second studies will be conducted to determine if differences in the chemical makeup of the CAPs also may have contributed, in part, to the marked differences in the pulmonary responses observed between the late summer and winter studies.
In October 2002, we conducted our third inhalation toxicology study of CAPs-exposed Brown Norway rats with and without OVA airway instillations. In this study, our mobile research laboratory was parked in Los Angeles, CA, near the main campus of the University of Southern California and highways with heavy motor vehicle traffic (i.e., our source site with locally generated PM). We used the same experimental design and exposure regime as described above for the first and second studies in Claremont, CA. In this Los Angeles study, rats in this winter study were exposed to average mass concentrations of 310, 324, and 31 µg/m3 for CCAPs, FCAPs, and UFCAPs, respectively. We presently are in the process of analyzing the BALF and pulmonary tissues taken from these exposed rats.
Future Activities:
In 2003 and 2004, we will conduct similar inhalation toxicology studies using the mobile laboratory in Los Angeles, CA, near the main campus of the University of Southern California (our source site for locally generated PM) in the LAB. Specifically designed studies will be conducted to determine if the sensitized rats that are challenged to OVA 1 or 2 days prior to the CAPs exposure exhibit the same FCAPs-induced attenuation of allergen-induced airway disease observed in the previous allergen and CAPs co-exposure study in October 2001.
Journal Articles:
No journal articles submitted with this report: View all 2 publications for this projectSupplemental Keywords:
particulate matter, PM, inhalation toxicology, asthma, Los Angeles Basin, LAB, allergen, source/receptor sites., RFA, Health, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, Geographic Area, particulate matter, Toxicology, air toxics, Health Risk Assessment, Chemistry, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Allergens/Asthma, Disease & Cumulative Effects, Environmental Monitoring, Children's Health, genetic susceptability, tropospheric ozone, Molecular Biology/Genetics, Biology, West Coast, Risk Assessment, asthma, health effects, particle size, sensitive populations, particulates, urban air, minority population, exposure and effects, stratospheric ozone, airway epithelial cells, fine particles, human health effects, air pollutants, cytokines, exposure, human airway epithelial calls, particulate emissions, airway disease, allergic airway disease, children, air pollution, particles, pariculate matter, human exposure, inhalation, particle pollutants, particulate exposure, airborne pollutants, immunology, urban air pollution, environmentally caused disease, PM, environmental effects, human health, Los Angeles Basin (LAB), allergen, disease, respiratory, ultrafine particles, air quality, environmental hazard exposures, toxics, exposure assessmentProgress 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.