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 are 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

“… 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 , 53 , 54 Monoclonal biologics targeting T2 inflammation are increasingly used but only approved in patients with established T2 polyps due to challenges in identifying T2 inflammation in CRS without nasal polyps (CRSsNP) and in classifying distinct endotypes over variations in time, treatment and interpretation.…”

“… 1 , 2 Due to its multifactorial etiology, CRS has a high degree of heterogeneity in inflammatory endotypes, clinical traits, and treatment outcomes. 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.…”

“… 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.…”

“… 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. 3 , 8 , 9 However, the phenotypic and endotypic heterogeneity of CRS confound precise classification of the disease (e.g., often a mixed or alternative endotype instead of distinct T1 and T2 that is unrelated to polyp status) and thus challenge the predictions as to the best medical therapy being used for an individual patient. 4 , 10 , 11 , 12 , 13 …”

XBP1 Regulates the Transcription of HIF-1a in BALB/c Mice with Chronic Rhinosinusitis without Polyps

“…Both phenotypes are characterized by an overwhelming burden and an overlapping spectrum of symptoms, including facial pain or pressure, nasal discharge, congestion, and hyposmia or anosmia [ 3 ]. It has been suggested that CRSwNP is related to underlying T helper 2- (Th2-) driven inflammation (producing IFN- γ ), while CRSsNP is precipitated by T helper 1- (Th1-) driven inflammation (secreting IL-4, IL-5, and IL-13) [ 4 , 5 ]. However, type 2 immune responses were also observed in CRSsNP following similar patterns but less pronounced in CRSwNP [ 2 ].…”