Eosinophilic esophagitis (EOE) is an allergic inflammation of the mucosa of the esophagus. One or more of the common food constituents (milk, egg, soy, wheat, peanuts, tree nuts, fish, and shellfish) in a susceptible host (people with history of atopic dermatitis or asthma) is the cause of allergic inflammation in EOE. It is a Th-2 immune cell mediated allergic inflammation that leads to infiltration of the esophageal mucosa with eosinophils (\> 15/high power field/HPF), which leads to submucosal fibrosis, esophageal stricture, narrow esophageal lumen, and reduced distensibility of the esophagus. Patients present with symptoms of dysphagia, food impaction, heartburn, and other non-descript symptoms. The condition can start in childhood and continue in adulthood; however, patients may present at any age. Current incidence estimates range from 5 to 10 cases per 100,000, and current prevalence estimates range from 0.5 to 1 case per 10001. Some of the EOE patients respond to acid inhibition therapy and it may be that acid reflux is the cause of EOE in some patients.

The inflammatory damage to the esophageal epithelium results in symptoms of esophageal dysfunction, such as dysphagia. Chronic inflammation of the esophagus may also lead to remodeling, stricture formation, and fibrosis6. The fibrotic aspect of progressed disease is not well understood, and whether or not this can be reversed with treatment is unknown. Current therapeutic approaches include chronic dietary elimination, swallowed topical formulation of corticosteroids and esophageal dilation. Emergency endoscopy for prolonged and/or painful food impaction is associated with a risk of severe esophageal injury, and it does not alter the underlying pathogenesis or progression of the disease. Although swallowed topical corticosteroids have been reported in clinical trials to induce partial clinical responses and histologic remission, they are not uniformly effective and can be associated with fungal infections as well as disease recurrence after discontinuation. Studies shows that Dupilumab, a monoclonal antibody against IL4 and IL13 is an effective treatment in patients with EOE.

Few years ago, the investigators observed an additional mechanism of dysphagia in EOE patients, which relates to the esophageal motor function. The latter is best assessed by esophageal manometry study, which is normal in the majority (80%) of EOE patients. However, esophageal manometry records only the function of inner, i.e., circular muscle layer of the esophagus, which is only 50% of the total esophageal muscles mass (muscularis propria). The other 50%, i.e., longitudinal muscle is the outer of the 2 muscle layers of the esophagus. A series of studies from my laboratory reveal that the longitudinal muscle layer is responsible for the descending relaxation of the peristaltic reflex. Descending relaxation is critical because it allows esophagus to distend and bolus to proceed in aboral direction with minimal resistance to the flow of swallowed contents. The investigators found that patients with EOE have, 1) dysfunctional longitudinal muscle which manifests as a lower amplitude of contraction as compared to normal subjects and, 2) temporal discoordination between the contractions of the two muscle layers15. Both of the above scenarios can lead to impaired descending relaxation that can results in a smaller luminal CSA of the esophagus during peristalsis as compared to normal subject, which will appear as a narrow lumen esophagus on the barium swallow study, a scenario similar to an esophageal stricture, well described in patients with EOE. A narrow lumen esophagus will result in resistance to the passage of bolus or in other words difficulty swallowing (dysphagia).

Patients with EOE have reduced distensibility of the esophagus, as measured by Endoflip technique. The Endoflip study requires placement of a bag inside the esophagus and distending it with saline to measure pressure and the bag luminal CSA. While Endoflip is an important advancement to measure the luminal CSA, it does not record distensibility under physiological condition of swallowing, i.e., swallow-induced peristalsis. Using intraluminal impedance technique, the investigators have pioneered a methodology to measure the luminal CSA during peristalsis. Using above methodology, the investigators found that in many participant groups, i.e., nutcracker esophagus, esophagogastric junction outflow obstruction and functional dysphagia, the luminal CSA during peristalsis is significantly smaller as compared to normal healthy subjects. The luminal CSA ahead of contraction during peristalsis is an indirect measure of the descending relaxation of the peristaltic reflex. Recent studies published in the New England Journal of Medicine and Gastroenterology show that a 24-week treatment with Dupilumab leads to an approximately 50% reduction in dysphagia symptoms, \>90% reduction in the eosinophil count, 70% reduction in the histologic scoring system and 18% improvement in the esophageal distensibility. The goal of the study is to determine if treatment with Dupilumab will result in reversal of the longitudinal muscle dysfunction during peristalsis seen in patients with EOE.

The Dupilumab is an FDA approved study for the treatment of EOE. The current investigation is not intended to support, 1) a significant change in the advertising for the drug, 2) does not involve a change of route of administration, dose, participant population, or other factor that significantly increases the risk (or decreases the acceptability of the risk) associated with the use of the drug product. The investigation will be conducted in compliance with the requirements for review by an IRB and with the requirements for informed consent. 3) A previously reported study has showed a significant inflammation reduction in 60% EoE patients when taking Dupilumab for 12 weeks. This study aims to study its effects on restoring peristalsis in EoE participants when taken for 12 weeks. 4) Participants after study completion will be continuing standard treatment guidelines as indicated by the study PI or participant's physician.