# Molecular endotypes and manifestations of chronic rhinosinusitis

> **NIH NIH P01** · NORTHWESTERN UNIVERSITY · 2022 · $499,213

## Abstract

PROJECT SUMMARY: The overall goal of the studies in this project is to test the hypothesis that inflammatory
endotypes control clinical presentations and comorbid airway diseases in chronic rhinosinusitis (CRS). CRS is
one of the most common chronic diseases in adults in the US, affecting approximately 12.5% of Americans, and
has a severe impact on patients' quality of life and healthcare costs. Although CRS is most commonly treated
with antibiotics, steroids, and allergy medications, their efficacy is not universal. Due to poor responses to
medical therapy, over 400,000 surgical procedures are performed annually in the US. There is therefore an
urgent need for a new understanding of the pathogenic mechanisms that drive CRS phenotypes. CRS is clinically
classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Both forms are
characterized by intense inflammatory cell infiltration which drives symptoms of the disease, but CRSwNP is the
more severe form of the two and is characterized by type 2 inflammation including eosinophilia. In contrast to
CRSwNP, the mechanism of inflammation in CRSsNP is understudied and poorly understood, despite the fact
that over 75% of CRS patients have this phenotype. Although initial studies from Europe suggested that CRSsNP
is characterized by type 1 inflammation, we found that only a small subset of patients with CRSsNP did show
type 1 inflammation. We therefore hypothesized that inflammation in CRSsNP is more heterogeneous than
CRSwNP and this induces variable outcomes of medical treatment. In a preliminary study, we found the overall
frequency of CRSsNP with type 1, 2 and 3 inflammation to be 21%, 50% and 27% of patients, respectively. This
supports our initial hypothesis and suggests that a pharmaceutical agent targeting a single endotype will not
benefit all patients with CRSsNP. A central hypothesis of this project is that inflammatory endotypes control
clinical phenotypes of CRS and comorbid airway diseases, and they predict variable outcomes for
pharmacological treatments. For example, we have obtained preliminary evidence showing that type 2
inflammation is selectively associated with smell loss and comorbid asthma. In addition, we found that females
with CRSwNP have more severe disease than males with CRSwNP. We therefore also hypothesize that sex
influences endotype, phenotype and comorbid diseases in CRS. We will collaborate with Project 1
(Immunopathology at Northwestern) and Project 3 (Epidemiology at Geisinger and Johns Hopkins) to test these
hypotheses in tertiary care patients at Northwestern and to validate our hypothesis in the general population at
Geisinger. Studies in Aim 1 will identify the mechanisms of inflammation for the major endotypes of CRSsNP.
Studies in Aim 2 will test the hypothesis that inflammatory endotypes of CRS control clinical presentations and
influence comorbidity of lower airway diseases. Studies in Aim 3 will test the hypothesis that sex influenc...

## Key facts

- **NIH application ID:** 10458541
- **Project number:** 5P01AI145818-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Atsushi Kato
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $499,213
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458541

## Citation

> US National Institutes of Health, RePORTER application 10458541, Molecular endotypes and manifestations of chronic rhinosinusitis (5P01AI145818-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10458541. Licensed CC0.

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