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

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

Study Overview

• Status: Completed
• Conditions: Sinusitis, Chronic
• Intervention / Treatment: Procedure: Sinus surgery

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Center for Environmental Medicine, Asthma and Lung Biology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects who are patients at UNC Healthcare ENT clinics

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CRS subjects; CRS subjects who have sinus surgery	Procedure: Sinus surgery; Standard Clinical Sinus Surgery

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Flight Attendant Medical Research Institute
• Investigators: Principal Investigator: Ilona Jaspers, Ph.D., UNC SOM

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): December 10, 2018
• Study Completion (Actual): December 20, 2019

Study Registration Dates

• First Submitted: August 10, 2017
• First Submitted That Met QC Criteria: August 10, 2017
• First Posted (Actual): August 15, 2017

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 4, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases; Nose Diseases; Sinusitis
• Other Study ID Numbers: 17-1499

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No