# Identifying mechanisms and reversibility of eosinophil-induced airway hyperinnervation in asthma

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $651,934

## Abstract

Asthma is characterized by excessive bronchoconstriction and a heightened sensitivity to inhaled irritants.
Airway nerves control these responses. Recently, we found that eosinophils, which are a defining feature of
airway inflammation in a majority of asthmatics, increased sensory nerve density in humans with asthma and in
mice. Increased innervation produced exaggerated neuronally-mediated reflex bronchoconstriction. These
data show that eosinophil-induced nerve remodeling has a key role in the development of excessive
bronchoconstriction in asthma. The central hypothesis of this proposal is that eosinophils increase
airway nerve density in asthma by releasing granule proteins that induce neurotrophins, which in turn
promote nerve growth and potentiate nerve-mediated reflex bronchoconstriction. We will test this
hypothesis in three aims that will 1) determine the role of eosinophil granule proteins EPX and MBP in sensory
and parasympathetic nerve remodeling, neurotrophin expression and nerve-mediated reflex
bronchoconstriction 2) test which neurotrophins mediate eosinophil-induced nerve remodeling and reflex
bronchoconstriction and 3) determine whether airway hyperinnervation is reversed in humans with asthma by
measuring airway nerves in bronchoscopic airway biopsies before and after initiation of the anti-IL5 antibody
mepolizumab. Effects of eosinophil depletion will also be tested in mice with established hyperinnervation. The
ultimate goals of this study are to discover new asthma mechanisms and to identify drug targets that will
prevent and/or reverse effects of nerve dysfunction in asthma.

## Key facts

- **NIH application ID:** 10330954
- **Project number:** 5R01HL155623-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Matthew G. Drake
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $651,934
- **Award type:** 5
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330954

## Citation

> US National Institutes of Health, RePORTER application 10330954, Identifying mechanisms and reversibility of eosinophil-induced airway hyperinnervation in asthma (5R01HL155623-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10330954. Licensed CC0.

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