Introduction
The role of eosinophils in unexplained gastrointestinal diseases is an area of increasing interest. However, there remains a lack of quality data available to determine the relationship between eosinophilic oesophagitis (EoE) and DGBIs (e.g., functional dyspepsia (FD), associated with duodenal eosinophilia). Several other gastrointestinal diseases are also characterised by an increased number of tissue eosinophils, including gastro-oesophageal reflux, inflammatory bowel disease and rumination syndrome. Risk factors for EoE still remain to be clearly defined in large population-based studies. The aim of this study was to determine the relationship between EoE and DGBIs as well as other potential risk factors for EoE, and mortality in EoE.
Aims & Methods
General practice electronic medical records were sourced from the United Kingdom (UK) via The Health Improvement Network which collates and cleans records from across the UK. EoE was identified through Read codes. DGBIs were similarly identified via Read codes and the first date of first record of each was noted.
Results
A total of 1.274 million unique patients were available for analysis. There were 389 EoE cases (0.03%) from the cohort, with age at first diagnoses being mean 21 years (SD=18), and 74% female.
Statistically significant univariate risk factors for EoE included female sex (OR: 3.69, 95%CI: 2.94-4.63), Crohn’s disease (OR: 3.85, 95%CI: 1.44-10.31), Helicobacter pylori infection (OR: 3.35, 95%CI: 1.84-6.10), gluten sensitivity (OR: 10.59, 95%CI: 1.48-75.59), allergy (OR: 2.99, 95%CI: 2.37-3.78), reflux (OR: 3.05, 95%CI: 2.43-3.83), GI Infection (OR: 2.07, 95%CI: 1.55-2.77), asthma (OR: 2.97, 95%CI: 2.37-3.72), rhinitis (OR: 2.46, 95%CI: 1.94-3.12), antibiotics (OR: 2.79, 95%CI: 1.74-4.48), and proton pump inhibitors (PPIs) (OR: 11.78, 95%CI: 8.02-17.31). Significant factors that had a reduced risk were IBS (OR: 0.36, 95%CI: 0.23-0.56) and FD (OR: 0.74, 95%CI: 0.57-0.97).
We conducted three separate multiple logistic regression models. The first consisted of all univariate risk factors of which the following were independent: female sex (OR: 4.10, 95%CI: 3.27-5.15), H. pylori (OR: 2.48, 95%CI: 1.35-4.56), gluten sensitivity (OR: 9.10, 95%CI: 1.25-66.46), allergy (OR: 1.74, 95%CI: 1.36-2.21), reflux (OR: 1.63, 95%CI: 1.28-2.07), asthma (OR: 1.72, 95%CI: 1.36-2.17), and prior PPI use to diagnosis of EoE (OR: 13.29, 95%CI: 10.27-17.20). Independent factors that reduced risk were IBS (OR: 0.19, 95%CI: 0.12-0.30) and FD (OR: 0.22, 95%CI: 0.17-0.30). ROC/AUC 0.86 (95%CI: 0.84-0.88).
Second model assessed IBS and FD (adjusting for sex, age at first contact, anxiety, and depression): both IBS and FD remained statistically significant and less likely to be associated with EoE (IBS OR: 0.35, 95%CI: 0.22-0.54; FD OR: 0.74, 95%CI: 0.56-0.97). ROC/AUC 0.79 (95%CI: 0.77-0.81).
Final model assessed mortality (adjusting for sex/ age at first contact): mortality (OR: 0.15, 95%CI: 0.03-0.59) was less likely in EoE. ROC/AUC 0.78 (95%CI: 0.76-0.81).
Conclusion
Individuals with EoE were less likely to have DGBIs (IBS and FD), whereas they were more likely to have other gastrointestinal diseases (e.g. gluten sensitivity, reflux, H. pylori). They were more likely to have had allergies and asthma and much more likely to have used PPIs before diagnosis of EoE. Mortality is not increased.
Disclosure
GD Eslick, MP Jones, MM Walker have no conflicts of interest. Nicholas J. Talley is supported by funding from the National Health and Medical Research Council (NHMRC) to the Centre for Research Excellence in Digestive Health and he holds an NHMRC Investigator grant. Dr Talley reports nonfinancial support from Norgine (2021) (IBS interest group); reports research grants from Allakos, Astra Zeneca; personal fees from Allakos (eosinophilic disease) (2021), Bayer (IBS) (2020), Planet Innovation (Gas capsule IBS) (2020), twoXAR Viscera Labs, (USA 2021) (IBS-diarrhea), Dr Falk Pharma (2020) (eosinophilic esophagitis), Sanofi-Aventis, Glutagen (2020) (celiac disease), IsoThrive (2021) (esophageal microbiome), BluMaiden (microbiome advisory board) (2021), Rose Pharma (IBS) (2021), Intrinsic Medicine (2022) (human milk oligosaccharide), Comvita Mānuka Honey (2021) (digestive health), Astra Zeneca (2022), and Glaxo (2022) outside the submitted work. In addition, Dr Talley has a patent on Nepean Dyspepsia Index (NDI) 1998 and Biomarkers of IBS licensed, a patent on Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo/Talley, a patent on Nestec European Patent licensed, a Singapore Provisional Patent “Microbiota Modulation of BDNF Tissue Repair Pathway” issued, and “Diagnostic marker for functional gastrointestinal disorders,” Australian Provisional Patent Application 2021901692. Committees: NHMRC member, Asia Pacific Association of Medical Journal Editors, Rome V Working Team Member (gastroduodenal committee), International Plausibility Project co-chair (Rome Foundation funded), COVID-19 vaccine forum member (by invitation only). Community groups: advisory board, International Foundation for Functional GI Disorders and ausEE Inc. Editorial: Mayo Clinic Proceedings (Associate Editor), UpToDate (section editor), Precision and Future Medicine, Sungkyunkwan University School of Medicine, South Korea (Journal of Cell Press).