Revisiting Asian chronic rhinosinusitis in the era of type 2 biologics

Abstract

Chronic rhinosinusitis (CRS) is defined as the inflammation of the mucosa of the nose and paranasal sinuses over 12 weeks, occurring in 11%-12% of adults in Europe and the United States, 1 and approximately 8% of adults in China and Korea. 2,3 CRS frequently presents with other inflammatory airway conditions such as asthma and allergic rhinitis (AR), and imposes huge global health and economic burdens. 1,2 CRS is a highly heterogeneous disorder with diverse inflammatory profiles. [4][5][6] Based on endoscopic examination finding, CRS is clinically subclassified into CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). 4,5 Studies in Caucasian patients have shown that CRSwNP is characterized by type 2 (T2) [high interleukin (IL)-4, IL-5, IL-13 and IgE expression] and eosinophilic inflammation, whereas CRSsNP is primarily characterized by type 1 (T1) [high interferon (IFN)γ expression] and type 3 (T3) (high IL-17A expression) inflammation. 1,4,6 Conventional anti-inflammatory treatments of CRS include intranasal and systemic corticosteroids. 1,4 Endoscopic sinus surgery is considered when medical therapy fails. 1,4 However, it has been shown that approximately 20% of CRSsNP and 40% of CRSwNP patients relapse 1-2 years after surgery. [7][8][9] Eosinophilic inflammation and T2 immune response have been identified as important risk factors for disease relapse in CRS patients, 1,4,6,10,11 thus stimulating the study of T2 biologics in Caucasian patients with severe CRSwNP. Four multicentre and international phase 3 trials have demonstrated promising effect of omalizumab (anti-IgE), dupilumab (anti-IL-4Rα), mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in reducing nasal polyp (NP) size and relieving symptoms in patients with refectory and severe CRSwNP. [12][13][14][15]

Effects of Neutrophil and Eosinophil Extracellular Trap Formation on Refractoriness in Chronic Rhinosinusitis With Nasal Polyps

“…The same trend was reported in previous studies conducted in China. 43 EETosis is known to be the basis of CLCs, which are found at the site of eosinophil infiltration and promote neutrophilic inflammation as well as NETosis. 16 44 45 This is a possible explanation of why most patients with severe type 2 CRS show mixed neutrophilic-eosinophilic inflammation, and the formation of NETs ultimately aggravates type 2 inflammation.…”

“… 9 Studies in Asia reported that the prevalence of severe type 2 CRS was generally less than 10% (4.4%–11.2%), and our results are similar to those of previous studies. 28 43 When investigating mixed eosinophilic-neutrophilic CRS in Asia, it is necessary to find causes of mixed inflammation other than autocrystallized CLCs.…”

Endotypes of Asian chronic rhinosinusitis with nasal polyps: A narrative review

“…Geographic differences in endotypes affected the clinical characteristics of patients with CRSwNP (Table 1). In Asian CRSwNPs, the prevalence of eosinophilic or type 2 inflammation is relatively lower and the burden of inflammation is less than Western CRSwNPs [32]. Also, the incidence of comorbidities such as asthma or AERD/NERD is low.…”

“…There are potential targets for other cytokines and nontype 2 inflammation in CRS [32]. A clinical trial with biologics for epithelial cell-derived cytokines, including thymic stromal lymphopoietin and IL-33, is underway.…”

Application of Biologics in Treating Chronic Rhinosinusitis With Nasal Polyps in Asian Populations

“…New therapeutic strategies, such as biologics or reboot surgery, were introduced as a response to treat the recalcitrant nature of severe type 2 CRSwNP, which often shows a poor response to traditional treatment. The prevalence of type 2 inflammation in CRSwNP and severe type 2 inflammation related to severe infiltration of eosinophils and neutrophils with staphylococcal enterotoxin-specific immunoglobulin E in Asian population is below 50% and 4.4%–11.2%, respectively [ 3 ], much lower than in Western populations [ 4 ]. In addition, a study proposed that the response of type 2 CRSwNP to surgery is very much different from that of non-type 2 CRSwNP [ 5 ], and as a result, the role of biologics in treating CRSwNP in Asian populations seemed to be limited.…”