# Determinants of Olfactory Dysfunction in Chronic Rhinosinusitis

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $612,191

## Abstract

PROJECT SUMMARY: Olfactory deficit is a defining symptom of chronic rhinosinusitis (CRS) by current
consensus guidelines, but olfactory dysfunction is typically under-reported by patients and under-appreciated
by treating clinicians. Previous research has found olfactory deficit in 68% of patients with CRS and 20% with
complete anosmia, affecting over 25 million individuals in the United States (US). The ability to predict which
patients will have olfactory improvement after treatment of CRS is critical to clinical treatment decision-making.
Recent studies suggest that localized inflammation of the olfactory cleft could be associated with to olfactory
deficits in CRS, resulting in the presence of sinonasal edema, airflow restriction, and alterations in mucus
translocation and olfactory receptor neuron activation. Untreated inflammation may even promote metaplasia,
wherein specialized olfactory epithelium is replaced by respiratory epithelium incapable of olfaction. There are
no current robust methods to categorize olfactory dysfunction in CRS. This lack of categorization is
problematic clinically because, at present, all patients are essentially grouped together despite variations in
disease characteristics and treatment outcomes. The result is an inability to provide personalized treatment
recommendations and disease prognostication from an olfactory standpoint. Categorization enhances
mechanistic insight for clinical studies aimed at evaluating treatments for olfactory dysfunction and increases
the likelihood that ideal patients are enrolled in clinical trials based their precise disease characteristics, a
particularly important concept as medicine shifts toward targeted therapies and personalized medicine.
 The studies proposed herein are all hypothesis-testing or hypothesis-generating in nature. Specific
Aim 1 utilizes unsupervised cluster analysis to identify olfactory-specific patient clusters based on an extensive
array of clinical and biologic characteristics. Specific Aim 2 will incorporate multivariate linear modeling and
cluster analysis to assess improvement in olfactory function to identify determinants of olfactory function
following either medical or surgical intervention for CRS and predict which patient groups will experience
improvement and to what degree. Specific Aim 3 will further incorporate proteomic and cytokine analysis to
explore molecular characteristics of identified olfactory-specific patient cluster groups to provide further insight
into disease mechanisms and pathophysiology. These aims will be completed by initiating an unprecedented
multi-center, prospective, observational cohort study to enroll approximately 1,000 subjects undergoing
treatment for CRS and olfactory deficit in US between 2016 and 2021. All study participants meeting inclusion
criteria will be evaluated using objective olfactory testing and olfactory-specific quality of life instruments, as
well as for indicators of inflammation severity within the...

## Key facts

- **NIH application ID:** 9954041
- **Project number:** 5R01DC005805-15
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** TIMOTHY L SMITH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $612,191
- **Award type:** 5
- **Project period:** 2004-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954041

## Citation

> US National Institutes of Health, RePORTER application 9954041, Determinants of Olfactory Dysfunction in Chronic Rhinosinusitis (5R01DC005805-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9954041. Licensed CC0.

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