How Does Inflammation Affect the Development and Progression of Eosinophilic Esophagitis?

Principal Investigator: Marie-Pier Tétreault, PhD The epithelial lining of the esophagus serves as the first line of defense to protect the underlying tissue from various external insults. Upon injury and inflammation, a rapid and efficient restoration of the esophageal epithelial barrier is needed. Failure to restore this barrier ultimately leads to pathological consequences. To date, most studies of inflammation have focused in immune cells because they are the paradigmatic inflammatory cell type. Yet immune cells are not the only cell type involved in inflammation and immunity. Epithelial cells sense and initiate inflammation, and also play a key role in the production of inflammatory molecules. It still remains unclear, though, how epithelial cells contribute to inflammation in patients with Eosinophilic Esophagitis (EoE). The investigators will determine how epithelial cells control inflammation and fibrosis in eosinophilic esophagitis. The Tétreault laboratory will also test how blocking mediators of inflammation can prevent the development and progression of...

Inflammatory Lipid Signaling and Eosinophilic Esophagitis

Principal Investigator: Guang-Yu Yang, MD, PhD Most patients with Eosinophilic Esophagitis (EoE) experience an abnormal immune-mediated response to food antigens. Identifying unique biomarkers involved in the pathogenesis of allergic inflammation could significantly improve treatments. The conversion of cell membrane arachidonic acid to ω-6 prostaglandin and ω-6 leukotriene eicosanoids during the inflammatory cascade provides many potential drug targets to impede the inflammatory process in patients with EoE. ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) have opposing influences on inflammation. Currently, there is no study on PUFA metabolism and the role these PUFAs metabolites play in the pathogenesis of EoE. Dr. Yang’s study aims to determine the ω-3 and ω-6 PUFAs metabolites/eicosanoids profile in eosinophilic esophagitis using a liquid chromatography tandem mass spectrometry (LC-MS/MS)-based metabolomics approach and to identify the unique eicosanoids or biomarker/s for diagnosis, prognosis and monitoring the therapeutic effect on...

Understanding Immune Signature of Foods in Eosinophilic Esophagitis

In Eosinophilic Esophagitis (EoE), a variety of foods trigger inflammation in the esophagus.  Diet elimination remains a mainstay treatment approach, with the number and type of food triggers varying between patients. Some respond well to eliminating a single food while others require the removal of multiple foods. Although no biomarkers or testing currently exist to help pinpoint specific triggers, previous studies have found a key role for white blood cells known as T-cells. This study will assess the novel association between individual food triggers and T-cell clonality. Dr. Wechsler and his team intend to examine esophageal biopsies for evidence of the specificity of immune response of white blood cells to specific foods. The researchers will use deep sequencing of the T-lymphocyte receptor to identify how frequently unique types of T-cells appear. The team hopes this data will help explain how the immune system “learns” to respond to specific foods and, ultimately, provide a potential...

A Clinical Trial of Standard Repair Versus a Novel Repair for Hiatal Hernia

Principal Investigator: Eric S. Hungness, MD Muscular weakness at the junction of the diaphragm and esophagus (hiatal hernia) is a common problem that may result in heartburn, difficulty swallowing, or anemia. Current surgical repair techniques have an unacceptably high hernia recurrence rate. A novel surgical material was developed at Northwestern University and has demonstrated promising results in animal and human studies. This project will investigate the efficacy of an innovative mesh suture in hiatal hernia repair, as compared to the current gold standard material. The principle outcome of interest will be measured by a non-invasive x-ray examination 6 months following surgery. The hope is that patients undergoing repair with the novel material will have...

Programmer Analyst to Improve Digestive Health Quality at Northwestern Medicine

Principal Investigator: Rajesh N. Keswani, MD Among the busiest digestive disease centers in the country, Northwestern Medicine (NM) manages some 35,000 GI endoscopy procedures and more than 42,000 outpatient clinic visits a year. NM clinicians strive to deliver high quality, patient-centered cost-effective care with every patient encounter. Improving the quality of care relies on measuring clinical performance (i.e., “quality metrics”), implementing interventions to improve care delivery, and then re-measuring quality following the interventions. Our group utilized this approach to markedly improve the quality of colonoscopy at Northwestern thereby reducing the risk of colon cancer death after colonoscopy in the patients we serve, and subsequently published this innovative work in a leading journal (American Journal of Gastroenterology, 2015). Although the NM digestive health group has considerable quality improvement expertise, each initiative requires an analyst who has the computer and statistical skills to collect patient and procedure data from the electronic health record and interpret that data in a continuous fashion. The lack of a dedicated analyst has been a persistent bottleneck to replicating this approach to quality improvement research. Funding of the programmer analyst position will now allow the group to support multiple novel quality improvement projects and improve the efficiency of current research...