Type 2/Th2‐driven inflammation impairs olfactory sensory neurogenesis in mouse chronic rhinosinusitis model

Rouyar, Angéla; Classe, Marion; Gorski, Raphael; Bock, Marie-Dominique; Le-Guern, Joelle; Roche, Sandrine; Fourgous, Valerie; Rémaury, Anne; Paul, Pascal; Ponsolles, Clara; Françon, Dominique; Rocheteau-Beaujouan, Laurence; Clément, Margerie; Haddad, El-Bdaoui; Guillemot, Jean‐Claude; Didier, Michel; Biton, Bruno; Orsini, Cécile; Mikol, Vincent; Leonetti, M.

doi:10.1111/all.13559

Cited by 46 publications

(44 citation statements)

References 42 publications

(77 reference statements)

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“…This was largely due to collinearity of both IL‐5 and IL‐13 with other variables in the model, suggesting that these cytokines may be markers of more severe disease. This hypothesis was partially supported by a recent study in mice, which showed that allergic inflammation associated with elevated olfactory epithelium Th2 cytokines reduced the number of immature olfactory neurons, but dis not affect the number of mature olfactory neurons or olfactory function …”

Section: Discussionmentioning

confidence: 71%

Patterns of olfactory dysfunction in chronic rhinosinusitis identified by hierarchical cluster analysis and machine learning algorithms

Morse

Shilts

Ely

et al. 2018

Int Forum Allergy Rhinol

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Background: Olfactory dysfunction is a common symptom of chronic rhinosinusitis (CRS). We previously identified several cytokines potentially linked to smell loss, potentially supporting an inflammatory etiology for CRSassociated olfactory dysfunction. In the current study we sought to validate pa erns of olfactory dysfunction in CRS using hierarchical cluster analysis, machine learning algorithms, and multivariate regression.Methods: CRS patients undergoing functional endoscopic sinus surgery were administered the Smell Identification Test (SIT) preoperatively. Mucus was collected from the middle meatus using an absorbent polyurethane sponge and 17 inflammatory mediators were assessed using a multiplexed flow-cytometric bead assay. Hierarchical cluster analysis was performed to characterize inflammatory patterns and their association with SIT scores. The random forest approach was used to identify cytokines predictive of olfactory function. Results:One hundred ten patients were enrolled in the study. Hierarchical cluster analysis identified 5 distinct CRS clusters with statistically significant differences in SIT scores observed between individual clusters (p < 0.001). A majority of anosmic patients were found in a single cluster, which was additionally characterized by nasal polyposis (100%) and a high incidence of allergic fungal rhinosinusitis (50%) and aspirin-exacerbated respiratory disease (AERD) (33%). A random forest approach identified a strong association between olfaction and the cytokines interleukin (IL)-5 and IL-13. Multivariate modeling identified AERD, computed tomography (CT) score, and IL-2 as the variables most predictive of olfactory function. Conclusion:Olfactory dysfunction is associated with specific CRS endotypes characterized by severe nasal polyposis, tissue eosinophilia, and AERD. Mucus IL-2 levels, CT score, and AERD were independently associated with smell loss. C 2018 ARS-AAOA, LLC. How to Cite thisArticle: Morse JC, Shilts MH, Ely KA, et al. Pa erns of olfactory dysfunction in chronic rhinosinusitis identified by hierarchical cluster analysis and machine learning algorithms. Int Forum Allergy Rhinol. 2019;9:255-264.O lfactory dysfunction is among the most common symptoms of chronic rhinosinusitus (CRS) with a prevalence of between 30% and 80%. 1, 2 Unfortunately, the etiology of CRS-associated olfactory dysfunction remains poorly understood. Olfactory loss in CRS has previously been attributed to an inability of odorants to effectively reach the olfactory cleft, due either to structural abnormalities or presence of nasal polyps. 3, 4 Recent research has suggested that sinonasal inflammation may directly or indirectly affect olfactory neurons and olfactory function. 5 In animal models, certain cytokines have the ability to adversely affect olfactory neuron function, turnover, and regeneration. 5-8 An association between olfactory cleft cytokine levels and olfactory function has been partially

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Section: Discussionmentioning

confidence: 71%

Patterns of olfactory dysfunction in chronic rhinosinusitis identified by hierarchical cluster analysis and machine learning algorithms

Morse

Shilts

Ely

et al. 2018

Int Forum Allergy Rhinol

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“…75 Recent work in mice suggests that type 2 inflammation decreases the number of immature olfactory neurons, but not the mature olfactory neurons, indicating that it may interfere with the process of olfactory neurogenesis. 76 After some time, this may lead to reduced mature olfactory neuron populations, resulting in reduced OMP+ cells, as mentioned above.…”

Section: Mechanisms For Olfactory Loss In Crsmentioning

confidence: 99%

Olfaction: Sensitive indicator of inflammatory burden in chronic rhinosinusitis

Xing

Whitcroft

Hummel

2020

Laryngoscope Investig Oto

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Background and Objective: Olfactory dysfunction has a high prevalence in chronic rhinosinusitis (CRS) patients and significantly affects quality of life. CRS is recognized as a complex disorder encompassing heterogeneous inflammatory processes in the nose and paranasal sinuses. Olfactory dysfunction in CRS patients is associated with the level of inflammatory mediators and the efficiency of inflammatory control. Learning about the association between CRS-related inflammation and olfactory function will provide clues to the pathogenesis of CRS. Structure: The first section of this review describes the assessment of olfactory function using various measures, from ratings to MR based imaging. Then, we discuss the conductive and inflammatory mechanisms related to olfactory dysfunction in CRS: olfaction is associated with certain inflammatory patterns and is potentially a marker of CRS subtype. Finally, we review anti-inflammatory therapies including conservative and surgical approaches, and their effectiveness in olfactory dysfunction in CRS. Conclusion: Assessment of olfactory function should be considered in the clinical evaluation of CRS patients, not only for detecting and quantifying patients' symptom, but also because it appears to be useful to objectively assess the efficacy of CRS treatment over time. In addition, olfaction can be expected to expand the library of CRS phenotypes and endotypes and, hence, pave the way for more precise, tailored treatment options.

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“…AR, CRS, and asthma all characterize the basic pathophysiological changes in chronic inflammatory injury and abnormal remodeling in the airway. Many studies revealed that asthma patients’ bronchial walls were thickened due to epithelial injuries, subepithelial fibrosis, augmented extracellular matrix protein depositions, angiogenesis, goblet cell, and mucosal/submucosal gland hyperplasia, and enhanced airway smooth muscle masses, which were caused by repeated episodes of allergic inflammations 22‐25 . Similarly, there is also evidence showing goblet cell hyperplasia, excessive mucus productions, basal cell hyperplasia, and basement membrane thickening in the upper airways of patients with CRS with nasal polyp (CRSwNP) 26‐28 .…”

Section: Introductionmentioning

confidence: 99%

Role of IL‐25, IL‐33, and TSLP in triggering united airway diseases toward type 2 inflammation

Hong

Liao

Chen

et al. 2020

Allergy

121

107

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Under the concept of "united airway diseases," the airway is a single organ wherein upper and lower airway diseases are commonly comorbid. The upper and lower airways are lined with respiratory epithelium that plays a vital role in immune surveillance and modulation as the first line of defense to various infective pathogens, allergens, and physical insults. Recently, there is a common hypothesis emphasizing epithelium‐derived cytokines, namely IL‐25, IL‐33, and TSLP, as key regulatory factors that link in immune‐pathogenic mechanisms of allergic rhinitis (AR), chronic rhinosinusitis (CRS), and asthma, mainly involving in type 2 inflammatory responses and linking innate and adaptive immunities. Herein, we review studies that elucidated the role of epithelium‐derived triple cytokines in both upper and lower airways with the purpose of expediting better clinical treatments and managements of AR, CRS, asthma, and other associated allergic diseases via applications of the modulators of these cytokines.

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Type 2/Th2‐driven inflammation impairs olfactory sensory neurogenesis in mouse chronic rhinosinusitis model

Cited by 46 publications

References 42 publications

Patterns of olfactory dysfunction in chronic rhinosinusitis identified by hierarchical cluster analysis and machine learning algorithms

Patterns of olfactory dysfunction in chronic rhinosinusitis identified by hierarchical cluster analysis and machine learning algorithms

Olfaction: Sensitive indicator of inflammatory burden in chronic rhinosinusitis

Role of IL‐25, IL‐33, and TSLP in triggering united airway diseases toward type 2 inflammation

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