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Although ways to treat allergic rhinitis exist, improved therapies would have a great impact on the health of the more than 30 million Americans who suffer from this problem. Despite the great prevalence of allergic rhinitis, surprisingly little is known abut the events which occur in allergic subjects between antigen inhalation and the development of symptoms. By examining the nasal secretions for the presence of inflammatory mediators and cells before and after exposing the nasal mucosa of volunteers to pollen antigens, this proposal plans to improve the human model of allergic rhinitis in order to better understand the pathophysiology of allergic inflammation. Since the immediate anaphylactic reaction to nasal challenge with antigen does not fully explain the clinical disease, this proposal focuses on the inflammation which occurs after the immediate response. Specific Aim 1 evaluates the spontaneous recurrence of symptoms and mediators which occurs in approximately 40% of allergic subjects during the first ten hours after nasal challenge. Aim 2 addresses the issue of the response of subjects to rechallenge with antigen hours after the initial challenge. Recent exposure to antigen reduces the threshold for response to another challenge and may better mimic the response to the repetitive challenges which occur during natural exposure. Aim 3 is designed to determine if the sensitivity of the nasal mucosa to nonsensitizing, nonantigenic stimuli changes after antigen stimulation. A common denominator of all the specific aims is the evaluation of existing therapies, including antihistamines, topical and systemic corticosteroids, cyclooxygenase inhibitors and immunotherapy, to determine their effect on the response to nasal challenge. Most importantly, this proposal will relate an individual's response to nasal challenge with his symptoms during natural exposure. Development of an in vivo human, nasal laboratory model which accurately predicts a subject's response to seasonal exposure will lead to more rapid understanding of the pathophysiology of allergic rhinitis and to the development of new treatments for this common disorder.
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