Nasal and Peripheral Blood Biomarkers of CRS Patients Before and After Surgical Intervention

Study Overview
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Brief Summary
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To characterize inflammatory cells in the nose of patients with Chronic Rhinosinusitis (CRS) before and after sinus surgery.

Detailed Description
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Rhinosinusitis (RS) is a heterogenous disease, with variable etiologies, manifestations, and progression. Generally, RS can be divided into acute, subacute, and chronic RS, depending on the symptoms and duration of the disease. Most commonly, acute RS is caused by a viral infection (viral RS), which starts in the nasal passages and progresses to inflammation of the sinuses. When this inflammation of the paranasal sinuses does not resolve and lasts for at least 12 weeks, the disorder is broadly defined as chronic RS (CRS), which is usually accompanied by bacterial infections. This inflammatory disease pathophysiology is further subdivided into CRS with (CRSwNP) and without (CRSsNP) nasal polyps. Recently, several studies aimed at phenotyping the diverse pathophysiology among patients suffering from CRS characterized subgroups based on the presence of inflammatory clusters. CRSsNP is marked by pro-inflammatory neutrophilic inflammation of the nasal mucosa and a nasal cytokine profile that is characterized by increased levels of TGFβ1 and IFNγ and low or undetectable levels of IL-5. In contrast, patients with CRSwNP demonstrate eosinophilic inflammation of the nasal mucosa, low levels of TGFβ1, but high levels of Th2/Th17-type cytokines such as IL-17 and IL-5, higher levels of eosinophil cationic protein (ECP) and mast cell tryptase, and lower levels of IL-10. Currently biomarkers associated with physician diagnosed disease severity and patient-perceived quality of life impairments are lacking. Analysis of markers of inflammation in the nasal mucosa and peripheral blood leukocytes in combination with quality of life symptom scoring will enable us to identify biomarkers associated with CRS disease severity. This study will determine if biomarkers identified in the nasal mucosa and peripheral blood leukocytes correlate with physician diagnosed and patient-perceived disease severity.

Official Title
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Nasal and Peripheral Blood Biomarkers of CRS Patients Before and After Surgical Intervention

Conditions
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Sinusitis, Chronic

Intervention / Treatment
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* Procedure: Sinus surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Physician diagnosed CRS with surgical requirement for treatment Exclusion Criteria: Subjects with physician-diagnosed: cystic fibrosis, vasculitis, any type of nasal tumor receiving ongoing immunosuppressant therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CRS subjects<br>CRS subjects who have sinus surgery | Procedure: Sinus surgery<br>* Standard Clinical Sinus Surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Inflammatory mediators in the nasal mucosa | Detection and analysis of inflammatory mediators previously characterized in CRS subgroups, including but not limited to Transforming growth factor beta 1 (TGFβ1), Interferon gamma (IFNγ), Interleukin 5 (IL-5), Interleukin 17 (IL-17), eosinophil cationic protein (ECP), mast cell tryptase, and Interleukin (IL-10) from the nasal mucosa. | Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Inflammatory mediators in the peripheral blood | Detection and analysis of inflammatory mediators previously characterized in CRS subgroups, including but not limited to TGFβ1, IFNγ, IL-5, IL-17, ECP, mast cell tryptase, and IL-10 from the peripheral blood. | Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery) | 
| Change in Rhinosinusitis Disability Index (RSDI) Scores | The RSDI is a disease-specific health-related quality of life instrument with 3 domains (physical, functional, and emotional impacts of rhinosinusitis) using a 5-point Likert scale ranging from 0 to 4 where 0 is never and 4 is always a problem. Higher scores indicate more significant impact on quality of life. | Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery) | 
| Change in gene expression profile | Analyze cells for gene expression of inflammatory mediators including but not limited to TGFβ1, IFNγ, IL-5, IL-17, ECP, mast cell tryptase, and IL-10 | Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery) | 
| Change in Nasal lavage fluid cell count | Count cell types present in nasal lavage fluid cells. | Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery) |