# Project 3: Therapeutic Control of AERD

> **NIH NIH U19** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $460,159

## Abstract

This Project will determine the role of T prostanoid (TP) receptors in the pathophysiology of aspirin
exacerbated respiratory disease (AERD). TP receptors bind thromboxane A2 (TXA2) with high affinity, and also
mediate bronchoconstriction induced by prostaglandin (PG)D2. Using a double blinded, placebo controlled
crossover trial of ifetroban, a potent and selective TP receptor antagonist, we will test the central hypothesis
that TP receptor signaling on platelets, endothelial cells, and airway smooth muscle promotes persistent
eosinophilic respiratory inflammation, drives cysteinyl leukotriene (cysLT) overproduction, facilitates release of
innate type 2 cytokines downstream of cysLTs and platelets, and mediates bronchoconstriction in response to
TXA2 and PGD2 released by mast cells (MCs) during reactions to aspirin in AERD. As such, TP receptor
blockade will interfere with both the cysLT-dependent and -independent features of AERD pathophysiology
and interrupt a feed-forward loop that drives the disease. Aim 1 will determine the efficacy of ifetroban as a
treatment for patients with AERD. Aim 2 will determine the relevance of TP receptor signaling, and the effect of
TP receptor blockade, on platelet and MC activation, mediator generation, release of IL-33, and cell
recruitment in subjects with AERD at baseline and during clinical reactions to aspirin. The studies are central to
the AADCRC, as they seek to validate central hypothetical disease-causing mechanisms inferred by the other
two projects, while providing cells and tissues necessary for the completion of these projects.

## Key facts

- **NIH application ID:** 10171015
- **Project number:** 5U19AI095219-10
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Elliot Israel
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $460,159
- **Award type:** 5
- **Project period:** — → 2021-07-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171015

## Citation

> US National Institutes of Health, RePORTER application 10171015, Project 3: Therapeutic Control of AERD (5U19AI095219-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10171015. Licensed CC0.

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