Olfactory Function as a Candidate Endpoint of Type 2 (Th2) Inflammation: Translational Rationale from Humans to Dogs

Type 2 inflammation is a central immunopathogenic driver of chronic immune-mediated disease, characterized by IgE polarization, eosinophilia, epithelial barrier disruption, and tissue remodeling. In veterinary medicine, especially in canine atopic and allergic disorders, the absence of validated functional endpoints hampers disease monitoring and therapeutic assessment. In humans, this endotype underlies a spectrum of linked conditions, including asthma, allergic rhinitis, atopic dermatitis, and chronic rhinosinusitis with nasal polyps (CRSwNP), where olfactory dysfunction is common, quantifiable, and clinically meaningful. In this narrative review, we examine the relationship between type 2 inflammation and olfactory outcomes in human disease and consider its translational relevance in dogs within a reverse translational One Health framework. Evidence from human studies, particularly in CRSwNP, shows a strong association between type 2 inflammatory burden and olfactory loss, while biologics targeting these pathways yield clinically meaningful gains in smell function. Comparable clinical evidence is still lacking in dogs. Olfactory function should therefore be regarded as a promising, yet unvalidated, translational endpoint in canine type 2 disease and a priority for prospective clinical investigation and methodological validation.