Abstract
BACKGROUND: Congenital olfactory disorders (CODs) are rare but impactful conditions that impair the sense of smell from birth. These disorders can significantly affect a child's appetite, nutrition, safety awareness, and overall quality of life. Despite their clinical importance, treatment options for CODs remain limited and largely ineffective, with no established therapies capable of restoring olfactory function in pediatric patients. Recent advances in regenerative medicine and stem cell therapy offer promising avenues for addressing sensory deficits. Nasal epithelial stem cells have emerged as a viable candidate for therapeutic intervention due to their accessibility and intrinsic ability to differentiate into olfactory sensory neurons. Preliminary studies suggest their potential in promoting the regeneration of the olfactory epithelium and functional recovery. However, long-term data on the efficacy and safety of such approaches in children are lacking. AIM: To evaluate the long-term efficacy and safety of autologous nasal epithelial stem cell transplantation for the treatment of CODs in children. METHODS: This prospective, single-center study enrolled 50 children aged 3-15 years with CODs. All patients underwent autologous nasal epithelial stem cell transplantation and were followed up for 3 years. The primary outcome measure was change in olfactory function, assessed using the Sniffin' Sticks test and the University of Pennsylvania Smell Identification Test - Children's Version. Secondary outcomes included quality of life (measured by the Pediatric Quality of Life Inventory™ and a custom olfaction-specific questionnaire), safety, endoscopic evaluation, and electro-olfactogram measurements. Data were analyzed using repeated measures analysis of variance, Friedman's test, and multiple regression analysis. RESULTS: The mean composite olfactory score increased from 8.3 ± 4.7 at baseline to 52.6 ± 18.9 at the 3-year follow-up (P < 0.001). Significant improvement (≥ 50% increase in score) was observed in 60% of patients, with 24% showing moderate improvement. Quality of life scores improved significantly across all domains (P < 0.001). No serious adverse events were reported. Minor complications occurred in 16% of patients, which resolved within 2 weeks. Endoscopic evaluation revealed normal-appearing olfactory epithelium in 84% of patients at 3 years, compared to 24% at baseline (P < 0.001). Electro-olfactogram amplitudes increased from 0.11 ± 0.08 mV to 0.67 ± 0.31 mV (P < 0.001). Age at intervention (β = 0.31, P = 0.02) and baseline residual olfactory function (β = 0.45, P < 0.001) were positively associated with treatment outcomes. CONCLUSION: Autologous nasal epithelial stem cell transplantation demonstrates significant and sustained improvements in olfactory function and quality of life in children with CODs, with a favorable safety profile over a 3-year follow-up period. This approach represents a promising advancement in the treatment of pediatric sensory disorders.