Frontier Program Redefines Treatment for Severe Swallowing, Feeding, Breathing Problems

The Esophageal and Airway Treatment Center, a new Frontier Program at CHOP led by Dr. Michael Manfredi (center) and Dr. Thomas Hamilton (second from left), will set new standards in EA care.

A new Frontier Program is developing groundbreaking antifibrotic therapies, personalized care plans, and innovative devices to prevent and treat abnormal narrowing of the airway caused by scar tissue in patients with esophageal atresia (EA).

EA fibrosis is one of the most common and vexing problems related to the treatment of this patient population, as it can lead to persistent or recurring blockages. No therapeutic interventions have been identified to effectively target and disrupt this pathological process.

By leveraging existing expertise in advanced imaging and bioinformatics, the Esophageal and Airway Treatment Center Frontier team aims to enhance diagnostic accuracy, tailor treatments, and reduce the need for repeat interventions and hospitalizations. The robust research infrastructure will support translational studies and the rapid adoption of innovative therapies for patients.

"The Esophageal and Airway Treatment Center will set new standards in EA care, globally cementing CHOP as the leader in both clinical excellence and research advancements," said Co-director Thomas Hamilton, MD, an Attending Pediatric Surgeon at CHOP.

Dr. Hamilton is leading this new Frontier Program with Michael Manfredi, MD, a Gastroenterologist in the Division of Gastroenterology, Hepatology and Nutrition. Research endeavors are spearheaded by Emily Partridge, MD, PhD, MHS, Pediatric and Fetal Surgeon in the Division of Pediatric General, Thoracic and Fetal Surgery and Amanda Muir, MD, Attending Physician in the Division of Gastroenterology, Hepatology, and Nutrition at CHOP.

Groundbreaking Research Translates to Antifibrotic Therapies

Severe feeding, swallowing, and breathing issues are common among children with EA, with or without tracheoesophageal fistula, a congenital malformation in which the esophagus is disrupted during fetal development. Instead of the esophagus forming as a continuous tube from mouth to stomach, it splits into two separate segments.

While surgery in the neonatal period is essential for this life-threatening disorder, many children face lifelong challenges, including severe feeding difficulties, strictures, and respiratory complications that require ongoing, coordinated care.

Scientific investigators within the Esophageal and Airway Treatment Center are focused on the underlying biological mechanisms driving fibrosis and stricture formation, or narrowing of the esophagus, to development new therapies.

"That's a big problem to study in little babies," Dr. Partridge said.

Dr. Amanda Muir and her team in the Muir Lab are working to develop novel antifibrotic drugs to prevent or reduce esophageal stricture formation following EA repair. By targeting key pathways in fibrosis, these therapeutic drugs could minimize scar formation, decrease the need for repeated interventions, and improve long-term esophageal function and outcomes.

Together, Drs. Partridge and Muir are working to identify the mechanistic underpinnings of fibrosis using complementary basic science techniques, which aim to deepen their understanding of EA pathophysiology. They have extensive data demonstrating a novel clinical pathway for targeted therapeutics to reduce or prevent fibrosis in EA. Working with a novel animal model of fetal EA, they will study various preclinical interventions.

"These breakthrough treatments will decrease the number and frequency of re-intervention for anastomotic sequelae, greatly improving clinical and patient perceived outcomes," Dr. Hamilton said.

Developing an Innovative Device to Prevent Esophageal Strictures

Once a stricture forms in the esophagus, it can cause pro-inflammatory tissue and repeated trips to the OR. The mainstay treatment is esophageal dilation using a stent, a hollow cylinder-tube placed in the esophagus to try to keep it open for a prolonged period of time. The current stents on the market are not very effective, according to Dr. Manfredi. Due to the shape and design, these stents put pressure on the esophagus, restricting blood supply to the area.

Dr. Manfredi and his team are working on a novel stent with a unique shape. It's designed to self-expand and exert a constant, gradual outward force to dilate and maintain the openness of a narrowed esophagus with minimal touch points to the esophagus to minimize ischemia.

"So two-fold, doing the dilation and minimizing ischemia," Dr. Manfredi said. "Even an improvement by 20% would have a significant effect on the quality of life of our patients. With decreased anesthetics and decreased trips to the OR, this device has a lot of potential upside."

Personalized Care Plans

Depending on the patient's specific risk profile, the care team will create a plan to mitigate adverse events and optimize survival and quality of life. Every patient will undergo a thorough diagnostic evaluation of the esophagus and airway by the Frontier Program's multidisciplinary team.

With a family-centered care and engagement approach, this Frontier Program will enhance family support services, including financial assistance for travel and lodging, educational resources, remote patient monitoring, and the establishment of a patient and family advisory board to ensure care strategies align with patient needs.

Training Future EA Leaders

Next year, the Esophageal and Airway Treatment Center will launch the Pediatric Aerodigestive Fellowship in Gastroenterology, a first-of-its-kind training program. Future expansion includes an additional pulmonology fellowship.

"We will train the future leaders in EA care at CHOP to ensure research advancements and the best clinical care continue for our patients," Dr. Hamilton said.