Objectives: Eosinophilic esophagitis (EoE) is an increasingly prevalent chronic disease arising from an allergy/immune-mediated process. Generally, the risk of atopic disease differs in rural and urban environments. The relationship between population density and EoE is unknown. Our aim was to assess the relationship between EoE and population density. Methods: We conducted a cross-sectional, case-control study of patients with esophageal biopsies in a US national pathology database between January 2009 and June 2012 to assess the relationship between population density and EoE. Using geographic information systems, the population density (individuals per square mile) was determined for each patient zip code. The odds of esophageal eosinophilia and EoE were estimated for each quintile of population density and adjusted for potential confounders. Sensitivity analyses were conducted with varying case definitions and to evaluate the potential for bias from endoscopy volume and patient factors. Results: Of 292,621 unique patients in the source population, 89,754 had normal esophageal biopsies and 14,381 had esophageal eosinophilia with ≥15 eosinophils per high-power field. The odds of having esophageal eosinophilia increased with decreasing population density (P for trend <0.001). Compared with those in the highest quintile of population density, odds of having esophageal eosinophilia were significantly higher among those in the lowest quintile of population density (adjusted odds ratio (aOR) 1.27, 95% confidence interval (CI): 1.18, 1.36). A similar dose-response trend was observed across case definitions with increased odds of EoE in the lowest population density quintile (aOR 1.59, 95% CI: 1.45-1.76). Estimates were robust to sensitivity analyses. Conclusions: Population density is strongly and inversely associated with esophageal eosinophilia and EoE. This association is robust to varying case definitions and adjustment factors. Environmental exposures that are more prominent in rural areas may be relevant to the pathogenesis of EoE.
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