D3.455 - Comparative Characterization of Olfactory Dysfunction in Mouse Models of Eosinophilic Chronic Rhinosinusitis

Eosinophilic chronic rhinosinusitis (eCRS) is a respiratory condition frequently associated with debilitating olfactory dysfunction (OD). Despite its high prevalence, the mechanisms underlying OD remain poorly understood. Several CRS models have been described, but their olfactory phenotypes are poorly characterized. In this study, we compared the most frequent used mouse model of eCRS at the level of inflammation, functional smell testing, sex and anatomy in order to standardize in vivo research on eCRS-related OD.

In the first model, male and female mice underwent intraperitoneal and intranasal sensitization with ovalbumin (OVA), followed by combined intranasal administration of OVA with Staphylococcus aureus enterotoxin B (SEB) for 13 weeks. In the second model, male and female mice received intranasal instillation of Aspergillus protease (AP) with OVA for either 6 or 12 weeks. Olfactory function was assessed using the buried food test and habituation/dishabituation test. After sacrifice, integrity and inflammation of the olfactory epithelium was assessed on coronal skull sections at different anatomical sites by means of (immune)histological analysis. Sex differences were evaluated across all experiments.

Both models exhibited impaired olfactory function and reduced olfactory epithelium surface area and thickness. Inflammation was evident in tissue sections, with eosinophils present in all models and neutrophils mainly in AP model. Notably, the AP 12 weeks model exhibited a significantly higher neutrophil count compared with the SEB and AP 6 weeks models, highlighting a stronger inflammatory response. Sex differences were absent except for epithelial thickness in OVA/SEB control mice. Overall, the AP 12 weeks male model displayed the most pronounced effects.

Both models are suitable for mechanistic studies of OD in CRS. The 12 weeks AP male mouse model showed the greatest olfactory dysfunction corresponding to the most pronounced olfactory epithelium inflammation and disruption, making it particularly valuable for investigating the inflammatory mechanisms underlying OD.