The Role of Eosinophils in Aspirin Exacerbated Respiratory Disease Pathogenesis

Statement of the Problem: Eosinophilia is a major histological hallmark of Aspirin Exacerbated Respiratory Disease (AERD), a disease defined by the clinical triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and sensitivity to inhibitors of the cyclooxygenase-1 enzyme. Patients with AERD have the highest level of airway eosinophilia and have unique clinical characteristics, including more severe upper and lower respiratory tract disease than patients with CRSwNP or asthma alone. Additionally, AERD is associated with significant morbidity, large socioeconomic burden, and negative impact on quality of life. However, the molecular mechanisms driving disease pathogenesis and how eosinophils contribute remain unclear. Specific Aims: The central hypothesis of this proposal is that AERD patients have elevated eosinophil granule proteins in their nasal polyps (NP) as a result of enhanced eosinophil recruitment and activation and this, in turn, leads to accelerated fibrin deposition and NP growth contributing to the rapid rate of NP growth and recurrence. The proposed hypothesis will be addressed in 2 specific aims: 1) characterizing the mechanisms responsible for the recruitment and activation of eosinophils in AERD NP; and 2) evaluating the relationship between enhanced fibrin deposition and elevated eosinophils in AERD NP.