Studies of the Role of Basophils in Aspirin Exacerbated Respiratory Disease Pathogenesis.

Abstract Background Aspirin Exacerbated Respiratory Disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 (COX-1) enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type-2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear. Objective To characterize the systemic and local basophil responses in AERD compared to CRSwNP patients. Methods Sinonasal tissues including inferior turbinate (IT) and/or nasal polyps (NP) and peripheral blood were collected from controls, AERD, and CRSwNP patients. Expression of cell surface (CD45, FceRI, CD203c), activation (CD63) and intracellular (2D7) markers associated with basophils were characterized using flow cytometry. Clinical data including Lund-Mackay scores and pulmonary function were obtained. Results The mean number of basophils (CD45+CD203c+FceRI+CD117-) detected in AERD NP (147±28 cells/mg tissue) was significantly elevated compared to CRSwNP (69±20 cells/mg tissue; p=0.01). The number of circulating basophils was significantly elevated in AERD (p=0.04). Basophils in NP had significantly higher CD203c and CD63 MFI compared to blood in both conditions (p Conclusions Increased basophil numbers and extent of ongoing degranulation in NP of patients with AERD compared to CRSwNP may contribute to the exaggerated disease pathogenesis and severity unique to AERD.