Endotypes of Chronic Rhinosinusitis; relationships to disease phenotypes, pathogenesis, clinical findings and treatment approaches.

Abstract

Chronic rhinosinusitis (CRS) is a common clinical syndrome that produces significant morbidity and costs to our health system. The study of CRS has progressed from an era focused on phenotype to include endotype based information. Phenotypic classification has identified clinical heterogeneity in CRS based on endoscopically observed features such as presence of nasal polyps, presence of comorbid or systemic diseases and timing of disease onset. More recently, laboratory-based findings have established CRS endotype based upon specific mechanisms or molecular biomarkers. Understanding the basis of widespread heterogeneity in the manifestations of CRS is advanced by findings that the three main endotypes, Type 1, 2 and 3, orchestrate the expression of three distinct large sets of genes. The development and use of improved methods of endotyping disease in the clinic is ushering in an expansion of the use of biological therapies targeting Type 2 inflammation now and perhaps other inflammatory endotypes in the near future. The purpose of this review is to discuss the phenotypic and endotypic heterogeneity of CRS from the perspective of advancing the understanding of the pathogenesis and improvement of treatment approaches and outcomes.

Sweet taste receptor agonists attenuate macrophage IL‐1β expression and eosinophilic inflammation linked to autophagy deficiency in myeloid cells

“…ECRS is a persistent sinonasal inflammatory condition attributed to dominant eosinophilia driven by Th2 cytokines (e.g., IL‐4, IL‐5, IL‐13) 49 . Due to its frequent association with refractory disease and NP recurrence following therapeutic intervention, 50,51 eosinophilia is an important target in CRS patients 3,9 . In general, ECRS is first treated with corticosteroids in an oral or topical route, which is frequently inefficacious and related to adverse systemic effects 52–54 .…”

“…[2][3][4] A range of inflammatory mediators and effector cells orchestrate in a complex manner, leading to the development of CRS with varying inflammatory endotypes and clinical phenotypes. [3][4][5] Amongst the various inflammatory cells infiltrating the sinonasal mucosa of CRS patients, primary attention has been paid to the regulation of eosinophils due to their frequent association with refractory and recurrent CRS. 6,7 Accordingly, strategies that target eosinophil survival and migration in addition to topical or oral corticosteroids have been pursued as a promising treatment modality to resolve eosinophilic inflammation.…”

Epidemiology of Chronic Rhinosinusitis: Prevalence and Risk Factors

“…1 This recommendation is based on numerous studies that illustrate that for most individuals the major division lies between type 2 and nonetype 2 responses. 47,48 The biomarkers of CRS inflammatory endotypes are directly ascertained from patients' biological tissues that can include blood, nasal mucus, and sinonasal mucosal tissue. The sinonasal mucosa is the gold standard tissue to sample because it is the site of the disease, although nasal mucus and blood biomarkers are correlated with varying degrees.…”

Increased B Cell-Activating Factor Expression Is Associated with Postoperative Recurrence of Chronic Rhinosinusitis with Nasal Polyps

“…Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the upper respiratory tract which results in clinical syndromes, including nasal discharge, nasal obstruction, and reduction and loss of smell [1,2]. Previous epidemiologic studies showed that CRS is one of the most common disorders with an estimated prevalence of 2-4% according to the geographic region surveyed [3,4].…”