# Chronic Rhinosinusitis Integrative Studies Program 2 (CRISP2)

> **NIH NIH P01** · NORTHWESTERN UNIVERSITY · 2020 · $1,881,553

## Abstract

The Chronic Rhinosinusitis Integrative Studies Program 2 (CRISP2) is an integrated program of epidemiologists,
otolaryngologists, allergists and immunologists with highly collaborative studies to better understand the
molecular and cellular mechanisms of disease heterogeneity and how these mechanisms translate into clinical
phenotypes, natural history and long term outcomes. There is a compelling need for more research in chronic
rhinosinusitis (CRS). Patients with CRS experience a dramatic decrement in quality of life, CRS has a prevalence
approaching 12%, nearly half a million patients per year undergo surgery and the estimated total costs of CRS
in the US are $22-32 billion per year. Hypotheses and themes of CRISP2 are: 1.) Heterogeneous underlying
pathogenic mechanisms yield variable clinical phenotypic manifestations; 2.) Comorbidity of sinus disease and
lung disease tracks with selected molecular endotypes; 3.) There are profound differences between mechanisms
and manifestations of CRS in men and women; 4.) Pathogenic mechanisms of CRSsNP, the more prevalent
form of disease, have not been well studied; 5.) There is a significant need to study CRS in primary care
populations; 6.) New assays are needed to evaluate molecular endotypes in an outpatient setting. This grant
addresses all of these hypotheses and themes. Relating molecular endotypes to clinical manifestations, natural
history, comorbidity and outcomes of disease is an overarching goal of this program. Three projects and two
cores (Administrative Core A and Clinical, Laboratory and Data Management Core B) comprise the CRISP2
program. The three main project main aims are: Project 1-To study the mechanisms of epithelial barrier
dysfunction and tissue hyperplasia in CRS. Project 1 will use a novel microparticle (MP) based assay of epithelial
differentiation and will assay components of the coagulation and fibrinolytic systems to test the hypothesis that
fibrin deposition, barrier dysfunction and epithelial mesenchymal transition (EMT) play important pathogenic
roles in CRS. These responses will be related to immunological endotypes, clinical phenotypes, comorbidity and
clinical outcomes. Project 2-To dissect molecular endotypes and relate them to manifestations of CRS. Project
2 will test the hypothesis that inflammation in CRS is heterogeneous and that inflammatory endotypes control
clinical phenotypes of CRS. Preliminary results implicate select endotypes as inducers of certain symptom
constellations and have led to hypotheses about the cells and molecules that drive the main immunological
endotypes, type 1, 2 and 3. Both Project 1 and Project 2 will utilize large sample sets from patients at both
Geisinger (Project 3) and NU (Core B). Project 3-To use population-based CRS epidemiology to evaluate sex
differences, natural history, and long-term outcomes based on clinically-defined phenotypes and biologically-
based endotypes. Large retrospective cohort and longitudinal epidemiologica...

## Key facts

- **NIH application ID:** 9996480
- **Project number:** 5P01AI145818-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Robert P Schleimer
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,881,553
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996480

## Citation

> US National Institutes of Health, RePORTER application 9996480, Chronic Rhinosinusitis Integrative Studies Program 2 (CRISP2) (5P01AI145818-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9996480. Licensed CC0.

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