Preclinical Studies of Omalizumab in Chronic Rhinosinusitis With Nasal Polyposis

Objectives: Aim 1. The investigation will identify the specific tissue compartment distribution of immunoglobulin E (IgE) expression within human nasal polyps. Colocalization studies will examine functional interaction of IgE with effector cells. Aim 2. The investigation will examine the direct effect of omalizumab on expression of Type 2, 1, and 3 inflammatory pathways in human nasal polyp tissue from phenotypically characterized chronic rhinosinusitis with nasal polyposis (CRSwNP) patients. Study Rationale: Human nasal polyps express high local tissue IgE. However, the tissue distribution, cellular location and functional consequence of IgE accumulation within the polyp tissue is not known. Phase 3 studies of omalizumab demonstrated efficacy, with responders. However, the reason for non-responder outcomes in a subset of CRSwNP patients was not understood. Therefore, the goal of this study is to examine the mechanism of action of omalizumab in CRSwNP, such that specific responders for this treatment can be identified and therapy can be optimally directed.