Title: A mixed methods feasibility study into the use of physiological assessment in eosinophilic oesophagitis
Funder: Health Education England

Abstract: Background Eosinophilic oesophagitis (EoE) is an antigen-mediated, inflammatory condition of the oesophagus with increasing prevalence. Frequently, EoE causes dysphagia and in severe cases food bolus obstruction, but in others, EoE is associated with symptoms including heartburn and chest pain. Diagnosis is based on histological findings acquired during endoscopy, in conjunction with oesophageal symptoms. Despite treatment effectively achieving histological remission in most cases, many patients remain symptomatic. Oesophageal physiology investigations are used routinely to assess primary motility disorders and gastro-oesophageal reflux disease, but their role in EoE assessment is unestablished. Aim This study aims to investigate the use of physiological assessments of oesophageal function in identifying symptom causes in EoE, whilst simultaneously exploring patient-perspectives and acceptability of tests. This will inform feasibility of implementation of more extensive, pathophysiological assessments of EoE within the NHS. Objectives Describe oesophageal motility in EoE when swallowing food and assess motility during symptomatic episodes occurring contemporaneously during eating. Investigate practicability of mucosal impedance as a novel method of monitoring inflammation in EoE, before and after standard therapy. Determine the feasibility of performing oesophageal physiology investigations within the patient pathway and understand challenges associated with acceptability, using qualitative interviews. Describe clinical factors to improve understanding of different EoE symptom profiles, including objective (test information) and subjective data (symptom reports).Methods This mixed-methods feasibility study encompasses a serial diagnostic study with embedded qualitative design, addressing four objectives using three work-packages (WPs). Nasogastric catheter-based approaches will be used for physiological assessment (WP1,2), with each test performed twice (before and following standard therapy). Patient-reported outcome measures will be collected before each set of tests to understand symptom profiles. The research is embedded within the normal clinical care pathway. WP1: Oesophageal motility will be assessed using high-resolution manometry (HRM), comparing novel solid bolus swallow assessment methods to traditional water swallow methods. As symptoms more frequently occur when eating, this approach is expected to provide more insight into causes of ongoing symptoms in EoE. (Objective 1,3,4) WP2: The use of pH/impedance monitoring of oesophageal mucosal response to treatment will be investigated. Mucosal impedance is used to assess mucosal integrity in reflux disease; this study will assess whether this technique may be useful in monitoring EoE, providing an alternative to biopsies. (Objective 2,3,4) WP3: Semi-structured interviews will be conducted with a subset of individuals following initial physiological assessments. Thematic analysis will explore perspectives on living with EoE and acceptability of undergoing tests to monitor the condition. (Objective 3) Impact There is a clear message from patients with EoE that faster diagnosis, better management, treatment tailored to disease manifestation (as opposed to going on a 'voyage of discovery') and reduction in number of required endoscopies are needed to improve living with EoE. To address this, this project uses novel modes of physiological assessment to see if we can enhance understanding of the cause of persistent symptoms. Ultimately this could result in treatments tailored to specific disease manifestations, faster remission and reduced burden on stretched endoscopy services.

Lay abstract: Aim and needThis study aims to improve understanding of the cause of symptoms in eosinophilic oesophagitis (EoE), an inflammatory condition of the oesophagus/gullet (food pipe to stomach). Tests will be used to see if the oesophagus is working properly and symptoms will be recorded, both before and after a course of treatment. This work is needed to help understand why, despite treatment, 1/3 patients with EoE continue to have distressing symptoms, making activities such as eating and staying nourished a daily challenge.BackgroundEoE is found in adults and children and affects approximately 29/100,000 people. This number is increasing, with EoE linked to allergies, triggered by environmental factors or foods. It is known as 'the asthma of the oesophagus' and requires lifelong treatment and monitoring. Symptoms include food sticking in the oesophagus. In serious cases, stuck food needs removing during emergency endoscopy (camera test). One in four patients coming to hospital with this acute problem has EoE. EoE is diagnosed if increased eosinophils (cells often involved in allergic responses) are found in tissue samples taken during endoscopy. However, treatment currently only addresses whether eosinophils are controlled, not whether the oesophagus is working properly.DesignSixty patients with EoE diagnosed during endoscopy will be asked to participate. Two tests that are not currently used in EoE will be used to study the oesophagus: Manometry: a test measuring how the muscles in the oesophagus squeeze and clear swallowed material during eating. Mucosal pH/impedance: a test to monitor inflammation in the oesophagus, commonly used to detect reflux.Participants will have each test both before and after receiving treatment. The study will not influence treatment decisions and participants will still have their usual follow-up endoscopy with tissue samples to document treatment response.Both tests involve passing a thin tube through the nose into the oesophagus. It is not painful, but can be uncomfortable. Manometry takes approximately 20 minutes and is done in hospital. Mucosal pH/impedance testing involves the person going home with the tube (2 mm diameter) in place for 24-hours, with information recorded during quiet periods/sleep. The researcher will remove this the following day; however, participants will be shown how to remove it, if needed.The test results will provide unique insight into the causes of symptoms in EoE. Manometry and mucosal pH/impedance results will be compared to tissue samples from endoscopies. This will show how inflammation affects gullet muscle function, the passage of food and symptoms.Additionally, 20 patients will be invited for interview to explore how acceptable these tests are in monitoring EoE. Experiences of living with EoE and undergoing tests will be discussed. This qualitative approach will help understand the feasibility of assessing EoE differently in the NHS, making the first steps towards improving quality of life for those affected.Patient/public involvementWhen designing the study, I conducted an online survey of 68 people with EoE to understand their priorities and concerns. People described fear of symptom episodes and their desire to understand the condition better. Subsequently, I met with a group of individuals with EoE to discuss this project directly. Participants were supportive of the project and its goals to improve the current situation, where they 'randomly bounce around' trying to get a diagnosis and then struggle to manage the condition.The study will be supported by an advisory group: three representatives with EoE, the founder of the EoE charity 'EOS Network' and an individual without direct experience of EoE. This group will be compensated for involvement. Research findings will be presented to the public and healthcare professionals via platforms including the EOS Network and scientific meetings.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL;INFLAMMATORY AND IMMUNE SYSTEM