# Understanding CPAP Effects in the Developing Airway

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $611,096

## Abstract

Abstract:
Supplemental O2 therapy and non-invasive ventilation (e.g. continuous positive pressure
support, CPAP) are two major life-saving modalities of respiratory care for the treatment of
preterm infants with respiratory distress syndrome. Unfortunately, there are significant
unintended consequences associated with clinical care. Supplemental O2 therapy specifically
has long been recognized as a potent contributor to the pathogenesis of wheezing and asthma
of former preterm infants – these observations have led to efforts to titrate and minimize the
usage of O2 in the NICU setting and a shift toward increased use of CPAP. The dilemma,
however, is that virtually nothing is known about whether there are also any adverse side-effects
of CPAP. In this proposal, we will utilize a novel neonatal mouse model of CPAP (developed in
our lab) to test the hypothesis that there are indeed, long-term adverse consequences
associated with CPAP, manifest as an increase in airway hyperreactivity (AHR). We further
hypothesize that the mechanistic basis underlying the effects of CPAP on AHR involves a
stretch-induced increase in low-molecular weight hyaluronan (HALMW) expression in airway
smooth muscle. HALMW is a major component of the extracellular matrix and our data show that
it initiates downstream signaling pathways leading to increased calcium signaling,
hyperreactivity, and smooth muscle proliferation. In parallel studies, we also show that the HA-
Ca2+ pathway is functional in age-appropriate (for preterm infants) human fetal airway smooth
muscle cells. Interestingly, offsetting or counter-balancing the increased HALMW by exogenous
delivery of high molecular weight HA (HAHMW) prevents the adverse effects of CPAP. The
clinical safety of HAHMW has been tested in a variety of settings ranging from treating eye
abnormalities in preterm infants to children with cystic fibrosis, and adults with asthma.
Therefore, this proposal will utilize a novel mouse model of neonatal CPAP to highlight the
mechanistic basis for the unintended consequences it has on airway function, and provide
evidence demonstrating tremendous promise for HAHMW administration as a viable therapy for
the treatment and prevention of wheezing and asthma in former preterm infants.

## Key facts

- **NIH application ID:** 9962478
- **Project number:** 5R01HL138402-04
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Peter MacFarlane
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $611,096
- **Award type:** 5
- **Project period:** 2017-08-10 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962478

## Citation

> US National Institutes of Health, RePORTER application 9962478, Understanding CPAP Effects in the Developing Airway (5R01HL138402-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9962478. Licensed CC0.

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