Retronasal olfactory recovery during biologic therapy for chronic rhinosinusitis with nasal polyps: a prospective longitudinal study with parallel orthonasal assessment

Olfactory dysfunction is a key feature of chronic rhinosinusitis with nasal polyps (CRSwNP). While biologics improve orthonasal olfaction, longitudinal data on retronasal function and differences between inflammatory targets remain limited. This study evaluated retronasal olfactory recovery over time during biologic therapy and compared IL-4/IL-13 versus IL-5 pathway blockade.

In this prospective longitudinal study, adults with severe CRSwNP starting biologics were assessed at baseline and after 4, 12, and 24 weeks. Orthonasal olfaction was measured using Sniffin' Sticks (TDI), and retronasal function with a validated 20-item identification test. Clinical outcomes included nasal polyp score (NPS), peak nasal inspiratory flow, and SNOT-22. Repeated-measures ANOVA was used to evaluate longitudinal changes and time-by-treatment interactions.

Sixty-nine patients were included (44 dupilumab, 25 mepolizumab). At baseline, mean TDI was 15.0 and retronasal score 7.2, indicating severe impairment. All outcomes improved significantly over time. Retronasal function improved rapidly within 4 weeks (7.2 to 10.4). TDI increased progressively (15.0 to 26.0 at 24 weeks). Significant time-by-treatment interactions were observed for retronasal identification, TDI, SNOT-22, and NPS, indicating non-parallel recovery patterns with dupilumab being associated with greater improvements in retronasal function and symptoms compared with mepolizumab.

Biologic therapy leads to substantial recovery of both retronasal and orthonasal olfaction in CRSwNP, with distinct considetemporal dynamics. Retronasal function shows rapid improvement and may be particularly sensitive to IL-4/IL-13 blockade, supporting its potential role as an early functional marker of response to biologic therapy.