Eosinophilic Oesophagitis (EoE) is a rare, emerging, chronic allergic disease characterized by oesophageal dysfunction and dense eosinophilia that can lead to symptoms of poor growth, vomiting, abdominal pain, difficulty swallowing, food impaction and poor quality of life. Part of the Atopic March, EoE is increasing in prevalence, impacts ~1 in 2000 US and an estimated Irish paediatric incidence of 2.0-3.3/100,000/year, (Irish Society for Gastroenterology, Hussey 2017), similar to Australian and European studies. To date, no cure exists, and in Ireland there is no study or biobank, and current treatment options are largely restricted to topical steroids.
Recent reports suggest that EoE may not resolve in all patients following steroid treatments (steroid non-responsive EoE; SNR-EoE) generating an emergent need for novel therapeutic options. Our own data shows dysregulated steroid signalling in SNR-EoE patients, suggesting a possible inherent defect in a sub-population. We hypothesize that a distinct clinical, molecular and histologic profile will differentiate steroid responsive (SR-EoE) and SNR-EoE prior to introduction of therapy. Distinguishing between these populations will provide a prognostic indicator for medical therapeutic decision making in EoE.
The overall objective of this proposal is to discover novel biomarkers of true steroid non-responsive EoE, as distinct from non-adherent patients, and elucidate potential mechanisms underlying SNR-progressive-EoE. We will measure adherence with an assessment tool and engage Public Patient Involvement to immediately tailor/improve clinical assessment and patient education tools. We will develop a Patient Care Best Practices for Ireland document within the time of this award. Our proposal uses an existing unstudied growing cohort of Irish EoE patients, immunohistochemistry, innovative cell culture, cutting edge molecular biology, state-of-the-art omic’s and carefully selected collaborations. Together our gathered resources will permit the synergy of patient oriented research (immediate effect) with mechanistic studies (medium-term effect) to serve the Irish EoE patients and their clinical care teams.
