Defining the Allergic Endotype of Chronic Rhinosinusitis by Structured Histopathology and Clinical Variables

Abstract

Atopy has a strong association with chronic rhinosinusitis (CRS). To understand whether patients with atopy and CRS can be defined by markers of tissue histopathology, systemic biomarkers, and clinical factors, which may guide their response to new pharmacologic agents. In a retrospective cohort of CRS patients who underwent functional endoscopic sinus surgery, a structured histopathology report consisting of 12 variables, comorbid conditions, preoperative total serum IgE levels, and preoperative modified Lund-Kennedy endoscopic and sinonasal outcome test (SNOT-22) scores were compared between atopic CRS (aCRS) and non-aCRS control patients in a multivariable model. A total of 380 CRS patients were enrolled, 286 of whom had comorbid atopy (aCRS). Compared with non-aCRS, aCRS patients had significantly higher preoperative total SNOT-22 scores (40.45 ± 22.68 vs 29.70 ± 20.68, P= .015) and symptom-specific SNOT-22 scores in all domains except psychological dysfunction. Relative to non-aCRS, aCRS patients had increased tissue eosinophilia (P < .0001), eosinophil aggregates (P < .0001), Charcot-Leyden crystals (P < .04), fibrosis (P < .02), total serum IgE levels (P < .04), polyploid disease (P < .001), and a prevalence of comorbid asthma (P<.0001) and aspirin exacerbated respiratory disease (AERD) (P < .003). Patients with aCRS demonstrated increased tissue eosinophilia compared with non-aCRS patients even after controlling for polypoid disease, asthma, and AERD. In the context of CRS, atopy appears to be a specific predictor of CRS severity linked to specific histopathologic variables, including enhanced eosinophilic aggregates. Moving forward, allergic status may be a useful way to identify an atopic endotype of CRS patients. Furthermore, after surgery, patients are often maintained on intranasal corticosteroids. In patients whose disease is unresponsive to steroids, we may look to atopic status to identify another management therapy. Atopic CRS patients, irrespective of polypand asthmatic status, could be optimal candidatesforbiologicagents such as T-helper cell, eosinophil, and/or IgE-targeted therapies.