Endoscopy-guided bilateral olfactory mucosal biopsy: a safe and reproducible outpatient technique

BACKGROUND: Reliable access to the olfactory epithelium is important for clinical and translational research; however, data on bilateral biopsy performed in an outpatient setting are limited. OBJECTIVES: To evaluate the feasibility and procedural outcomes of endoscopy-guided bilateral olfactory epithelium biopsy performed under local anaesthesia in an outpatient setting following controlled exposure sessions. METHODS: Healthy adults participated in a randomized, double-blind, crossover exposure study. Endoscopy-guided biopsies were obtained in an outpatient setting. Primary outcomes included bilateral biopsy success, tolerability, adverse events, and nucleic acid yield. RESULTS: Twenty-nine subjects were enrolled; 26 completed the study. Bilateral biopsies were obtained more frequently after implementation of pre-endoscopic screening than without screening (75.0% vs 30.0%; odds ratio 7.0, 95% CI 1.20-40.83). No serious procedural complications were observed. One self-limiting episode of delayed epistaxis. No participant reported postoperative olfactory dysfunction. All samples yielded RNA and DNA of sufficient quantity and purity for downstream analyses. CONCLUSION: Endoscopy-guided bilateral olfactory epithelium biopsy appears feasible in a carefully screened outpatient cohort. Pre-endoscopic anatomical assessment was associated with improved procedural success. Although objective olfactory testing was not performed, and subtle functional changes cannot be excluded, this technique provides a reproducible methodological framework for future studies involving the olfactory cleft.