Olfactory mucosal inflammation and barrier disruption correlate with perceived CRSwNP-associated olfactory...

This study aimed to characterize the local inflammatory and histopathological features of the olfactory mucosa (OM) in patients with CRSwNP and to clarify how these local changes are associated with perceived olfactory dysfunction.

OM specimens were collected from patients with CRSwNP during FESS and from control subjects undergoing endoscopic transnasal skull base surgery, with sampling restricted to the olfactory region under endoscopic guidance. qRT-PCR was performed in 30 CRSwNP and 13 control samples to quantify inflammatory mediators, and immunofluorescence staining was performed in 18 CRSwNP and 10 control samples to assess epithelial cell composition, tight junction proteins, and inflammatory cell infiltration. Clinical symptoms were evaluated using VAS and SNOT-22.

Compared with controls, the OM of patients with CRSwNP showed significantly increased expression of TNF-α, IFN-γ, IL-5, IL-13, CLC, CCL11, and CCL18. More severe smell loss was associated with a type 2 inflammatory endotype, eosinophilic CRSwNP, and older age. Among the inflammatory mediators examined, IL-5 showed the clearest positive association with smell loss severity, while IL-13, CLC, and CCL11 provided additional support for a type 2 inflammatory pattern linked to olfactory dysfunction. Patients with severe smell loss also exhibited a greater local inflammatory burden, particularly increased IL-5, CLC, and CCL11. Histologically, CRSwNP OM demonstrated reduced OMP-positive olfactory sensory neurons and KRT18-positive sustentacular cells, increased KRT5-positive basal cells, decreased Golf expression, and downregulation of ZO-1, Occludin, Claudin-1, and Claudin-3, together with increased infiltration of CD45⁺ cells, CD3⁺ T cells, CD4⁺ T cells, and eosinophils.

Perceived olfactory dysfunction in CRSwNP was closely associated with an active local immune-inflammatory microenvironment in the olfactory mucosa, characterized by predominant type 2/eosinophilic inflammation, epithelial injury, abnormal repair, barrier disruption, and immune cell infiltration. Among the inflammatory markers examined, IL-5 showed the strongest association with the severity of olfactory dysfunction, while CLC and CCL11 may serve as candidate local tissue markers of inflammatory burden in CRSwNP-associated olfactory dysfunction.