# Pilot Study of an Inhaled Treatment for Bronchopulmonary Dysplasia

> **NIH NIH R03** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $72,068

## Abstract

Abstract/Summary:
 Bronchopulmonary dysplasia (BPD) is a chronic cardiopulmonary complication among survivors of preterm
birth, with more than 10,000 new diagnoses in the US each year and healthcare costs estimated to exceed
$2.5 billion. During my NHLBI K08, I have shown that pharmacologic inhibition or genetic deletion of the S-
nitrosothiol catabolic enzyme, S-nitrosoglutathione reductase (GSNO reductase), prevents the development of
all aspects of hyperoxic murine BPD including pulmonary vascular features. Moreover, increased airway
GSNO reverses the BPD airway hyperreactivity and promotes bronchodilation in these mice. The GSNO-
repleting agent, inhaled ethyl nitrite, has been used safely and successfully to treat pulmonary hypertension in
mechanically ventilated human newborns. Here, I propose a pilot study using inhaled ethyl nitrite to treat
hypoxic respiratory failure in human infants with BPD. Unlike inhaled nitric oxide (iNO), ethyl nitrite rapidly and
robustly increases pulmonary GSNO levels in animal models, and should serve to reverse the bronchospasm
and ventilation/perfusion mismatch that characterize BPD. I believe this preliminary study will be a particularly
valuable clinical application of my K08 data, as other novel treatments for respiratory failure have not been
developed for respiratory failure in BPD.
 As our primary clinical outcome variable, we will have power (>0.9) to detect a 41% (+ 27) improvement in
pre/post oxygen saturation index with a 4 hour treatment of inhaled ethyl nitrite. We have a busy NICU at UH
Rainbow Babies and Children's Hospital, with more than 25 infants/year with BPD that would be eligible for this
two year pilot. We are also fortunate to have investigators on campus familiar with ethyl nitrite use in humans,
Drs. James Reynolds and Jonathan Stamler. Of note, Dr. Stamler was the lead investigator in the initial
neonatal ethyl nitrite study, published in The Lancet. My K08 mentor, Dr. Gaston, can perform the requisite
GSNO airway assays in his laboratory, and has an FDA regulatory core and part 11-compliant DCC as part of
his Program Project Grant that can assist with the IND and data management. The UH Clinical Research
Center will provide FDA regulatory, research staffing, and coordinator cores to support this clinical trial. We
therefore have an optimal situation for testing whether inhaled ethyl nitrite improves oxygen saturation index in
infants with BPD who have respiratory failure. At the end of this proof of principle study, we hope to be able to
apply these findings to an R01 or equivalent proposal to translate my K08 findings into a novel treatment
strategy for BPD.

## Key facts

- **NIH application ID:** 10102556
- **Project number:** 1R03HL155246-01
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Thomas Michael Raffay
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $72,068
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102556

## Citation

> US National Institutes of Health, RePORTER application 10102556, Pilot Study of an Inhaled Treatment for Bronchopulmonary Dysplasia (1R03HL155246-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10102556. Licensed CC0.

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