Eosinophilic esophagitis (EoE) is an increasingly recognized rare disease of children and adults characterized by symptoms including nausea, vomiting, abdominal pain, dysphagia and food impaction that occur in conjunction with esophageal eosinophilia. To date, the only method to make EoE diagnoses and follow treatment responses in EoE is invasive endoscopy with biopsy. While endoscopy is generally safe, an accurate, less invasive, inexpensive, comprehensive and durable test is urgently needed to determine therapeutic efficacy. To address this need, we will use a novel application of an existing technology, the Enterotest"""""""" (a string-based test used to detect intestinal Giardiasis), to measure esophageal inflammation (herein termed the Esophageal String Test - EST). Our recent publication provides proof-of-principle for the ability of ESTs to capture esophageal inflammatory mediators (biomarkers) in luminal samples from patients affected with EoE, and that these biomarkers correlate with those found in tissue. Our novel Preliminary Data support the rationale and feasibility of sampling EoE-associated inflammatory protein biomarkers in a 1-hour collection time point. These findings provide strong support for using ESTs as novel minimally invasive instruments to monitor therapeutic efficacy in EoE. The global objective of this project is therefore to bring the """"""""Esophageal String Test"""""""" (EST) to commercialization, so that it can be used to monitor therapeutic efficacy in children and adults with EoE. We hypothesize that ESTs will capture an EoE Biomarker Panel (EBP) reflective of disease activity.
The Specific Aims are to: (1) Identify an EoE Biomarker Panel (EBP) that will improve the sensitivity and specificity of the EST for monitoring disease activity, and (2) Validate the ability of the EST EBP to monitor therapeutic efficacy in a 1-hour sampling time. Our supportive published and Preliminary Data demonstrate the feasibility of using ESTs in both children and adults with EoE to measure disease activity (esophageal inflammation) in an overnight (12-hour) test, and shorter time periods, currently performed before a scheduled endoscopy with biopsy. In this project, we propose to shorten this time frame to a 1-hour test, a clinically relevant time point that will markedly facilitate its use and potential impact in the outpatient clinic setting. Public Health Relevance/Impacts: At least four major impacts should result from these studies: (1) Identification of an EBP will permit monitoring of esophageal inflammation in EoE;(2) the EBP will be relevant to following disease progression, treatment responses, management and pathogenesis of EoE, (3) validation of the EST EBP will enable development of rapid and inexpensive assays to follow treatment responses, thus reducing the number of follow-up endoscopies with biopsy that are currently performed, and (4) provide a device to monitor EoE disease activity where endoscopy with biopsy may not be available or affordable.
Eosinophilic Esophagitis (EoE) is an increasingly recognized rare allergic disease that affects both children and adults. EoE is characterized by symptoms such as vomiting, abdominal pain, trouble swallowing, and food impaction. In EoE, the esophageal lining develops an increased number of white blood cells called eosinophils. Eosinophils are white blood cells associated with other allergic diseases such as asthma and eczema. Evidence to date suggests that EoE affects children with a prevalence of ~1:10,000. If untreated, children and adults with EoE can develop esophageal narrowings that can lead to esophageal food impactions that may require emergency medical intervention. The cause of EoE and how these complications develop is uncertain. Currently, the only method to monitor the activity of this disease is to perform an endoscopy with biopsy, an invasive procedure that requires putting a flexible tube into the esophagus and taking a piece of tissue. Thus, a better understanding of the causes, and less invasive, inexpensive and better-tolerated tests are urgently needed to improve the lives of patients with EoE. This proposal seeks to address both these issues. The global objective of this project is therefore to bring a new device, the Esophageal String Test (EST) to commercialization, so that it can be used by physicians to monitor treatment success (or failure) in children and adults with EoE. Here, we hypothesize that the EST captures a selective group of proteins or biomarkers that reflect disease activity. The Esophageal String Test (EST) is based on an old test that was originally used to make the diagnosis of an intestinal infection. This test consists of using a capsule that is filled with a nylon string;one end of the string is pulled out of the small capsule and this end is taped to the cheek. The capsule is then swallowed and the capsule dislodges the string as it goes into the esophagus and upper intestinal tract. After being in place for a few hours, the tape is removed and the string containing the liquid esophageal secretions is pulled out of the mouth. This liquid is removed and analyzed for the EoE biomarkers. Our recent publication showed that ESTs can capture proteins that are increased in patients with EoE after the EST is in the esophagus for 12-hours. In this project, we will use ESTs in a more clinically relevant 1-hour collection period to obtain esophageal samples that will: (1) establish a panel of specific proteins that are present in the esophagus of patients with EoE with active inflammation, and will call this the EoE Biomarker Panel (EBP), and (2) determine whether the EBP can be used to monitor how well the treatment is working. At least three Public Health Impacts should result from these studies: (1) ESTs may be used as safe, inexpensive, and minimally invasive tools to monitor esophageal inflammation in EoE during treatment instead of using endoscopy with biopsy;(2) ESTs may allow the identification of biomarkers relevant to disease progression and treatment responses in EoE;and (3) provide a device to monitor EoE disease activity where endoscopy with biopsy may not be available or affordable.
| Khoury, Paneez; Akuthota, Praveen; Ackerman, Steven J et al. (2018) Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD). J Leukoc Biol 104:69-83 |
| Metcalfe, Dean D; Pawankar, Ruby; Ackerman, Steven J et al. (2016) Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases. World Allergy Organ J 9:7 |
| Ackerman, Steven J; Park, Gye Young; Christman, John W et al. (2016) Polyunsaturated lysophosphatidic acid as a potential asthma biomarker. Biomark Med 10:123-35 |
