# Eicosanoid Networks in Aspirin Hypersensitivity

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $549,828

## Abstract

Project Summary
Aspirin-exacerbated respiratory disease (AERD) is a common, severe idiopathic disorder
characterized by asthma, recurrent nasal polyposis, and marked eosinophilic inflammation of
the sinonasal and bronchial mucosa. The disease is consistently associated with markedly
dysregulated cysteinyl leukotriene production, and with cryptic over-activation of platelets. This
proposal will focus on understanding how these two features drive the pathophysiology of the
disease. The central hypothesis is that an autocrine, LTC4-mediated platelet activation pathway
plays a critical role in driving the exaggerated type 2 immunopathology associated with AERD,
and is central to pathognomonic reactions to ASA. Platelet-associated CysLT2R and HMGB1
are each necessary for these features. A corollary hypothesis is that neutralization of platelet
HMGB1 by salicylic acid (SA) contributes to the therapeutic effect of ASA therapy in AERD. We
will use newly created transgenic mice, a novel model of AERD, and cells and tissues from
carefully characterized human subjects to test the hypothesis. The studies proposed will reveal
potential causative mechanisms in AERD and identify therapeutic targets that could restore
normal homeostasis, and are the first to integrate CysLT2R into AERD pathophysiology.

## Key facts

- **NIH application ID:** 10062848
- **Project number:** 5R01AI136041-08
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Joshua A Boyce
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $549,828
- **Award type:** 5
- **Project period:** 2017-12-04 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062848

## Citation

> US National Institutes of Health, RePORTER application 10062848, Eicosanoid Networks in Aspirin Hypersensitivity (5R01AI136041-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10062848. Licensed CC0.

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