S1047 Association Between Electronic Cigarette Use and Risk of Eosinophilic Esophagitis: A Retrospective Cohort Study

Introduction: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease with rising incidence, particularly among younger populations. While conventional smoking has been associated with altered mucosal immunity, little is known about the impact of electronic cigarette (e-cigarette) use on EoE risk. We aimed to evaluate the association between e-cigarette use and incidence of EoE in a large, diverse U.S. population. Methods: We conducted a retrospective cohort study using the National Institutes of Health All of Us Research Program, which integrates electronic health records (EHR) with detailed participant survey data. E-cigarette use (ever vs never) was self-reported using standardized survey instruments. Participants with a diagnosis of EoE at baseline were excluded. The primary outcome was time to incident EoE diagnosis, identified through EHR data. Cox proportional hazards models were used to estimate the association between e-cigarette use and EoE, adjusting for age, gender, race/ethnicity, smoking history, alcohol use, gastroesophageal reflux disease, education, employment, income, and insurance status. Results: A total of 432,023 participants were included, with 431 incident EoE cases identified. The median time to EoE diagnosis was 49.6 months (interquartile range: 21.8-59.5). Compared to non-users, e-cigarette users were younger (mean age 45.3 years vs 59.3 years), more likely to be men, and had higher rates of traditional smoking. In the adjusted analysis, ever e-cigarette use was associated with a non-significant trend toward reduced EoE risk (adjusted hazard ratio [HR]: 0.74; 95% confidence interval [CI] 0.53-1.03). Traditional smoking was independently associated with lower EoE risk (HR: 0.64; 95% CI 0.50-0.81). Asian (HR: 0.21; 95% CI 0.08-0.57), Hispanic (HR: 0.44; 95% CI 0.32-0.61), and Black study participants (HR: 0.26; 95% CI 0.17-0.39) had significantly lower risks of EoE compared to non-Hispanic Whites. Conclusion: In this large, nationally representative cohort with self-reported e-cigarette use data, there was no significant association between e-cigarette use and EoE incidence. However, a trend toward a protective effect was observed. The findings could suggest a potential immunomodulatory role of nicotine. Larger longitudinal studies are needed to validate these findings and explore underlying mechanisms.