Improving predictability of IgE-high type 2 chronic sinusitis with nasal polyps in the biologic era

Abstract

Background Chronic rhinosinusitis (CRS) is an inflammatory disease that may require biological therapy. Omalizumab is an anti-IgE biologic that was recently approved by the FDA and Health Canada for use in severe CRS with nasal polyps (CRSwNP) recalcitrant to intranasal corticosteroids. Dosing is based on weight and pre-treatment serum IgE, with elevated levels of the latter being an indication for biologic treatment according to EPOS and EUFOREA guidelines. The goal of this study was to identify variables that predict IgE-high type 2 inflammation and serve as indicators for biologic treatment in CRS. Methods Patients ≥ 19 yo diagnosed with CRS undergoing functional endoscopic sinus surgery were included retrospectively. Demographics, past medical history, preoperative blood work, Lund-Mackay (LM), Lund Kennedy (LK), and SNOT-22 scores were extracted. Descriptive statistics and binary logistic regression analyses were conducted. Model superiority was based on Nagelkerke R2 scores and receiver operating characteristic curves. Results Sixty-five patients, average age 49.96 ± 13.59 years, were included. Sixty-one binary logistic regression models for elevated serum IgE were created. Among the top 3 models, the best model had sensitivity, specificity, positive predictive value and negative predictive values of 82.1, 69.2, 80.0, and 72.0. All performance measures except sensitivity exceeded the Canadian Biologics Guideline model. Serum eosinophils ≥ 300 cell/uL, CRSwNP and LM ≥ 17 increased the odds of elevated IgE. Conclusions IgE-high type-2 inflammation can be predicted by a model that includes eosinophil ≥ 300 cell/uL, CRSwNP, LM ≥ 17, asthma diagnosis and SNOT-22 ≥ 40. Patients meeting these parameters have a high pretest probability for elevated IgE and would benefit from IgE serology to determine qualification for omalizumab. This could reduce unwarranted IgE serology in patients with CRSwNP but also target a patient population for further workup that will lead to optimization of resource allocation and improve healthcare equity in rural and remote areas within Canada.

Non‐Type 2 and Mixed Inflammation in Chronic Rhinosinusitis and Lower Airway Disease

“…There was limited evidence for CRSsNP ( n = 1) and asthma in this review, so it is difficult to confidently discern the impact of nasal polyposis on non‐type 2 inflammation. It is possible that nasal polyposis plays a predictive role when placed in a model consisting of multiple variables 30,45 . Interestingly, being in Taiwan may have influenced this study's type 3 endotype shift, as Staudacher 44 demonstrated a higher proportion of type 3 inflammation in patients from Beijing when compared with Europe, Australia, and the United States 44 …”

“…It is possible that nasal polyposis plays a predictive role when placed in a model consisting of multiple variables. 30,45 Interestingly, being in Taiwan may have influenced this study's type 3 endotype shift, as Staudacher 44 demonstrated a higher proportion of type 3 inflammation in patients from Beijing when compared with Europe, Australia, and the United States. 44 In patients that had a mixed endotype shift, there is likely a unique unified airway inflammatory mechanism due to Håkansson et al 29 demonstrating an association between nasal polyp and bronchial type 1 and 2 inflammatory cytokines.…”