# Type-2 inflammation mediates olfactory loss in Chronic Rhinosinusitis: mechanisms and therapeutic opportunities

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $606,712

## Abstract

Project Summary
This is a request to the NIH for an Investigator-Initiated Research Project Grant (R01) for Bruce K. Tan, MD,
MS, Assistant Professor of Otolaryngology at Northwestern University.
The sense of smell in humans is pivotal for stimulating appetite, guiding food selection, avoiding spoiled foods
and noxious chemicals, and enhancing overall quality of life. Unfortunately, many patients with chronic
rhinosinusitis (CRS) suffer from extended periods of smell loss despite medical and surgical treatment. We
further find that patients with type 2 inflammation of the nasal mucosa are more frequently and severely
affected by smell loss before and after sinus surgery. CRS patients with type 2 inflammation are also more
likely to experience recurrence of their symptoms and require repeated surgery. The Principal Investigator is a
surgeon-scientist whose clinical interests focus on CRS patients but has completed extensive mentored
training in mucosal immunity. This proposal seeks to translate a recent novel discovery in our laboratory that
found that airway epithelial cell responses to IL-4 and -13, critical type 2 cytokines causing the most severe
forms of chronic sinusitis, require action of an ion pump called the non-gastric H+/K+ATPase. Specific
experiments will: (1) evaluate mechanisms by which the non-gastric H+/K+ATPase causes airway
inflammation using drug inhibitors and genetic knockout cell lines; (2) evaluate how to use smell loss to
accurately identify patients with active type 2 inflammation after sinus surgery; and (3) perform clinical studies
to find out how to effectively use proton pump inhibitors to reduce airway eosinophilic inflammation and test
whether they can reduce type 2 inflammation and improve smell function in patients with CRS. If successful,
these studies will firmly establish a novel mechanism that disrupts the airway barrier in type 2 inflammatory
conditions. Additionally, the results of this study may identify less invasive methods to identify type 2
inflammation in the nasal airway. Finally, the clinical studies may discover new drugs to treat persistent type 2
inflammation and smell loss in patients after sinus surgery- problems for which there are currently no effective
medical treatments.

## Key facts

- **NIH application ID:** 9948628
- **Project number:** 5R01DC016645-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Bruce K Tan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $606,712
- **Award type:** 5
- **Project period:** 2018-07-23 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948628

## Citation

> US National Institutes of Health, RePORTER application 9948628, Type-2 inflammation mediates olfactory loss in Chronic Rhinosinusitis: mechanisms and therapeutic opportunities (5R01DC016645-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9948628. Licensed CC0.

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