Pathogenesis of Chronic Rhinosinusitis

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): Chronic Rhinosinusitis (CRS) is the most
frequently reported chronic disease in the U.S. The etiology of CRS is not well
understood. CRS patients are often difficult to treat effectively; even with
aggressive medical and surgical therapies, many patients continue to have
persistent or recurrent disease. The long-term goal of this project is to
understand the causes and pathophysiologic mechanisms of CRS through both
clinical and basic research. The specific objective is to delineate the
mechanisms causing chronic antigenic stimulation and eosinophilic inflammation
in sinus and nasal cavities of CRS patients. The underlying hypothesis to be
tested is that immune cells in CRS patients respond to fungi colonized in nasal
and sinus cavities and produce large amounts of IL-5 and other inflammatory
cytokines, resulting in persistent eosinophilic inflammation of the upper
airways. In Aim 1, the altered immunologic responses of CRS patients to fungal
antigens are defined. We will examine whether CRS patients' lymphocytes produce
more IL-5 and IFN-gamma compared to normal subjects or atopic controls when
exposed to fungal antigen(s). The clinical correlation of eosinophil mediators
with sinus inflammation and disease severity in patients will be determined. In
Aim 2, we will ask why and how eosinophil degranulation occurs in sinus
cavities of patients with CRS. We will test the hypothesis that fungal
antigen(s) activate and induce eosinophil degranulation through
protease-activated receptors (PARs) expressed on eosinophils. The observations
in Aim 1 and Aim 2 will be culminated in Aim 3. We will directly ask whether
fungal organisms colonized in nasal and sinus cavities cause or exacerbate the
disease in CRS patients. By instillation of an antifungal agent, we will remove
the colonized fungi from the nasal/sinus cavities of patients and will examine
eosinophilic inflammation and clinical outcomes. We believe these studies will
lead to a better understanding of the pathophysiologic mechanisms of CRS,
especially the underlying causes of antigenic stimulation of immune cells in
patients. Elucidation of the causes and mechanisms of inflammation may help to
develop specific and effective therapies for this common, costly, and
incapacitating disorder.
StatusFinished
Effective start/end date3/1/016/30/14

Funding

  • National Institute of Allergy and Infectious Diseases: $426,492.00
  • National Institute of Allergy and Infectious Diseases: $414,744.00
  • National Institute of Allergy and Infectious Diseases: $438,591.00
  • National Institute of Allergy and Infectious Diseases: $487,845.00
  • National Institute of Allergy and Infectious Diseases: $478,487.00
  • National Institute of Allergy and Infectious Diseases: $403,339.00
  • National Institute of Allergy and Infectious Diseases: $278,281.00
  • National Institute of Allergy and Infectious Diseases: $468,781.00
  • National Institute of Allergy and Infectious Diseases: $483,395.00
  • National Institute of Allergy and Infectious Diseases: $477,365.00
  • National Institute of Allergy and Infectious Diseases: $451,056.00

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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