# Role of altered response to volumetric distension in esophageal disease

> **NIH NIH P01** · NORTHWESTERN UNIVERSITY · 2022 · $372,864

## Abstract

PROJECT SUMMARY
 Swallowing difficulties are extremely common and result in a substantial reduction in the quality of life
and increased morbidity and mortality related to malnutrition and complications related to regurgitation and
aspiration. Unfortunately, our understanding regarding the pathophysiology of dysphagia and GERD has been
hampered by focusing predominantly on circular muscle activity and ignoring the biomechanical properties of
the esophageal wall that promote normal emptying. Our initial work explored the relationship between intrabolus
pressure (IBP) and esophagogastric junction (EGJ) compliance as a metric for outflow resistance. This work
highlighted the direct relationship between IBP and EGJ opening and was the foundation for the development of
a new classification scheme for esophageal motor disorders, “the Chicago Classification.” Despite this improved
understanding focused on bolus transit dynamics, there are still significant unresolved issues centered on the
lack of a true correlate for symptoms or a predictive model for adverse outcomes. Given these limitations, we
have evolved our focus toward a more directed assessment of how wall distensibility and the response of the
esophageal body to volumetric distention will alter normal bolus transit. We hypothesize that the mechanical
properties of the esophageal wall will likely alter bolus transport by disturbing the normal low pressure state that
is required for asymptomatic bolus transit through the esophagus.
 In order to test our hypothesis that wall mechanics are a major determinant of esophageal diseases, we
have had to develop new approaches and new technology to directly measure mechanical wall state. Using
impedance techniques combined with manometry, we are now capable of assessing IBP and diameter changes
across a space-time continuum (4D-IM). This approach will allow us to study the mechanics of bolus transport
beyond the isometric circular muscle contraction quantified by manometry and allow us to assess the ability of
the esophagus to accommodate the propagating bolus via isotonic relaxation and passive distention and the
ability of the esophagus to propel the bolus via passive recoil and auxotonic contraction. Additionally, we have
also modified FLIP techniques to assess the response of the esophageal wall to volumetric distention using
FLIP-panometry analysis. The response of the esophageal wall to bolus retention or reflux is one of the most
important functions of the esophagus in preventing complications of aspiration, reflux injury, or symptoms related
to bolus retention. We recently reported that the normal response to volumetric distention is associated with
repetitive antegrade contractions (RACs) and that this response was altered in specific disease states. Our
overarching goal will be to study well-defined patient populations before and after interventions targeting wall
distensibility to determine whether abnormalities in distensibility and response ...

## Key facts

- **NIH application ID:** 10439752
- **Project number:** 5P01DK117824-05
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** JOHN E PANDOLFINO
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $372,864
- **Award type:** 5
- **Project period:** 2018-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439752

## Citation

> US National Institutes of Health, RePORTER application 10439752, Role of altered response to volumetric distension in esophageal disease (5P01DK117824-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10439752. Licensed CC0.

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