Multiple epidemiological studies have suggested correlations exist between particulate matter (PM) pollution and the prevalence of asthma cases and their severity. Additional studies have drawn correlations between asthma and both air pollution and the proximity of homes to highways further suggesting that particulate matter and specifically mobile source derived particulate matter is involved in many of the hot spots of asthma cases. The San Joaquin Valley of California is home to some of the highest asthma rates within the country and poor air quality is a consistent environmental characteristic. The San Joaquin Valley (SJV) is a consistent nonattainment area for fine particulate matter pollution by both Federal and State standards. To examine the role of particulate matter potentially acting as an adjuvant during the sensitization phase of allergic airway inflammation we conducted multiple field and laboratory studies. Seasonal, temporal, compositional and administration method effects were studied in acute models of exacerbated allergic airway inflammation from exposure during sensitization with the use of two different allergens. Experiments utilized lab generated ultrafine particles, concentrated ambient particle exposures in the field and field collected source-oriented particles. With lab generated, combustion derived ultrafine particles we were able to demonstrate the ability to detect particulate adjuvant effects from exposure during sensitization after challenge with allergen alone. We also demonstrated the ability to detect differences with our acute model of allergic airway inflammation via both inhalation and instillation exposure routes, with potentially synergistic effects. With field studies of ambient PM exposure during allergic sensitization performed in the SJV, we were able to demonstrate a seasonal effect. Source-oriented particle studies demonstrated that while seasonal effects had been witnessed with concentrated ambient particle exposures, source oriented particles from the same season are not equally potent and suggested the key in particle toxicity may be atmospheric processing of PM. Together these findings contribute to the knowledgebase of air pollution's effects on allergic airway inflammation and support the hypothesis that chemical characteristics of particles may be more important for considering their immunomodulary effects than mass alone.
|Advisor:||Pinkerton, Kent E.|
|Commitee:||Last, Jerold A., Wexler, Anthony S.|
|School:||University of California, Davis|
|Department:||Pharmacology and Toxicology|
|School Location:||United States -- California|
|Source:||DAI-B 74/02(E), Dissertation Abstracts International|
|Subjects:||Toxicology, Surgery, Environmental Health, Immunology|
|Keywords:||Adjuvant, Alleric airway inflammation, House dust mite, Ovalbumin, Particulate matter exposure, Source-oriented|
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