Investigating Sinonasal Inflammatory Profiles, Histopathological Features, and Remodeling Factors in Chronic Rhinosinusitis Patients With Nasal Polyposis
Overview
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- St. Paul's Sinus Centre
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Change in sinonasal inflammatory cytokine concentrations measured in nasal secretions using multiplex immunoassay
Overview
Brief Summary
This study aims to examine three key aspects of chronic rhinosinusitis with nasal polyps (CRSwNP): inflammation, tissue structure (histopathology), and remodeling.
Detailed Description
By analyzing these tissue samples before and after treatment with intranasal corticosteroids (INCS), investiagtors hope to better understand how the nasal tissue changes and whether those changes are linked to improvements in symptoms. This information could help doctors create more personalized treatment plans for people with CRSwNP in the future.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 19 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Must be ≥19 of age at the time of signing the informed consent form
- •Capable of giving signed informed consent.
- •Having CRSwNP based on clinical symptoms and/or radiographic or endoscopic evidence of inflammation in their upper airways (Diagnosis consistent with EPOS 2020)2 and nasal polyp score (NPS) of at least 2 on each side
- •Not expecting to have surgery within the next 7 months
Exclusion Criteria
- •A history of organ transplantation such as lung transplantation
- •Previously or currently using immunomodulator or allergy medications or (including The allergy medications such as: a) First and second generations of Antihistamines (H1 blockers); b) Oral/Topical Decongestants; c) Oral or systemic corticosteroids; d) Leukotriene Receptor Antagonists; e) Mast Cell Stabilizers.
- •Autoimmune medications such as: a) Systemic Steroids, b) Disease-modifying antirheumatic drugs (DMARDs) (non-biologic); c) Biologics such as anti-TNF, anti-IL, anti-B cell, anti-T cell; and d) Small molecules.
- •A history of auto-immune diseases such as Rheumatoid arthritis and Systemic lupus erythematosus,
- •Current or past sinonasal or bronchial tumors
- •Currently using systemic or oral corticosteroids (such as Prednisone, Methylprednisolone)
- •Current participation in any interventional treatment trials
- •Diagnosed or suspected malignant or premalignant nasal disease (e.g. Schniderian Papilloma, unilateral nasal polyposis)
- •Fungal rhinosinusitis (CT/Histology), positive Aspergillus skin prick testing and/or positive Aspergillus IgE RAST (Radioallergosorbent) testing
- •Malignant neoplasm within 5 years (from screening) excluding basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterinecervix treated locally and without metastatic disease for 3 years.
Arms & Interventions
Budesonide
Participants will use budesonide for 6 months to treat CRSwNP
Intervention: Budesonide (Drug)
Outcomes
Primary Outcomes
Change in sinonasal inflammatory cytokine concentrations measured in nasal secretions using multiplex immunoassay
Time Frame: Baseline to 6 months
Sinonasal secretions will be collected via endoscopy-guided intranasal brushing using nasosorption sponges. Samples will be analyzed using the Luminex Bio-Plex Pro Human Cytokine Multiplex Assay and Luminex Human Magnetic Assay. Concentrations of inflammatory biomarkers will be quantified in pg/mL. The panel includes, but is not limited to: Interleukins (e.g., IL-4, IL-5, IL-6, IL-13) Interferon-gamma (IFN-γ) Transforming growth factor beta-1 (TGF-β1) Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) Monocyte chemoattractant protein (MCP) Macrophage inflammatory proteins (MIP) Chemokine ligands (CCLs) Granulocyte colony-stimulating factor (G-CSF) Granulocyte-macrophage colony-stimulating factor (GM-CSF) Myeloperoxidase (MPO) will be measured separately using enzyme-linked immunosorbent assay (ELISA)
Change in sinonasal histopathological score assessed using semi-quantitative histopathological evaluation of nasal biopsy specimens
Time Frame: Baseline to 6 months
Nasal biopsy specimens will be analyzed using standard histopathological techniques, including hematoxylin and eosin (H\&E) staining. Histopathological features will be evaluated by a qualified pathologist using a predefined semi-quantitative scoring system. The following parameters will be assessed: inflammatory cell infiltration (eosinophils, neutrophils, lymphocytes), epithelial integrity and damage, goblet cell hyperplasia, basement membrane thickening, subepithelial fibrosis, and edema. Each parameter will be scored on a scale from 0 to 3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Individual parameter scores will be summed to generate a total histopathological score, with higher scores indicating greater inflammation and tissue remodeling.
Remodeling features
Time Frame: 6 months
Sinonasal remodeling features will be evaluated using nasal endoscopy and the Modified Lund-Kennedy (MLK) scoring system. The MLK scale assesses endoscopic findings including edema, discharge, crusting, and scarring. Each parameter is scored from 0 to 2 (0 = absent, 1 = mild, 2 = severe), with a total score ranging from 0 to 8. Higher scores indicate worse sinonasal disease severity and greater remodeling.
Secondary Outcomes
- SNOT-22(6 months)
- Smell test(6 months)
Investigators
Dr. Andrew Thamboo, MD
MD
St. Paul's Sinus Centre