# The impact of upper gastrointestinal dysmotility on aspiration-associated aerodigestive disorders in children

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2022 · $566,864

## Abstract

PROJECT SUMMARY
 More than $17 billion dollars are spent per year on health care for children with neurologic impairment
(NI). The main driver of these high costs is aspiration pneumonias, which cause lengthy and repeated
hospitalizations, higher acuity hospitalizations, and significant mortality. The dogma has long been that these
pneumonias are caused by aspiration of refluxed acidic gastric contents and thus should be treated with acid
suppression and anti-reflux surgeries. However, these therapies not only have failed to reduce the
development of aspiration pneumonias, but also may hasten the development of lung disease by increasing
pneumonia risk by altering the aerodigestive microbiome, in the case of acid suppression, or by obstructing
esophageal outflow or delaying gastric motility, in the case of anti-reflux surgery. Esophageal and gastric
dysmotility are particularly concerning because they cause fluid stagnation with secondary changes in
chemical and microbial composition. If these altered esophageal and gastric contents are aspirated, lung
disease likely ensues. But questions remain: Which specific motility abnormalities result in fluid stasis and do
these abnormalities predispose children with NI to more frequent aspiration pneumonias? Which components
of static fluid portend worse clinical outcomes? Will correcting the dysmotility improve clinical outcomes?
 The proposed research will build on the current literature by addressing the following hypotheses: (1)
distinct esophageal and gastric motility patterns result in stasis of esophageal and gastric contents; (2) this
stasis alters the microbial and chemical milieu of esophageal and gastric fluids; (3) the stagnant gastric and
esophageal contents, when aspirated, cause measurable microbiome and inflammatory changes that
predispose patients to developing aspiration pneumonias; and (4) treatment of esophageal and gastric
dysmotility improves aspiration-related symptoms and results in measurable changes in esophageal and
gastric dysmotility. First, using a longitudinal cohort study design, the investigators will determine which unique
esophageal and gastric motility patterns cause stasis and predict the development of aspiration pneumonias in
children with NI. Second, using a randomized, blinded crossover design, investigators will test whether
prucalopride, a 5HT4 agonist, improves both aspiration-related symptoms and esophageal and gastric motility.
 This research will: 1) attack a common and costly problem, aspiration pneumonias, in a medically
vulnerable population; (2) move beyond GERD to pursue a novel, paradigm-shifting pathophysiologic
mechanism, dysmotility, underlying development of aspiration pneumonias; (3) progress beyond standard
testing to include not only motility parameters, but also the microbiome and chemical consequences of
dysmotility; and (4) offer an innovative therapeutic intervention for aspiration symptoms that may improve
health outcomes and reduce health c...

## Key facts

- **NIH application ID:** 10520130
- **Project number:** 2R01DK097112-06A1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Rachel L Rosen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $566,864
- **Award type:** 2
- **Project period:** 2015-07-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520130

## Citation

> US National Institutes of Health, RePORTER application 10520130, The impact of upper gastrointestinal dysmotility on aspiration-associated aerodigestive disorders in children (2R01DK097112-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10520130. Licensed CC0.

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