The study explores how chronic rhinosinusitis (CRS) and asthma share a common inflammatory process, particularly affecting patients with both conditions. Interaction between immune cells (Interleukins) and Th2 cytokines, such as TSLP, exacerbates asthma control in CRS patients, especially those with nasal polyps (CRSwNP). TSLP plays a pivotal role in initiating and maintaining airway inflammation in both diseases. Tezepelumab, a biologic therapy targeting TSLP, shows promise in reducing inflammation markers in severe asthma but its impact on CRSwNP and quality of life remains unclear. The study proposes investigating Tezepelumab's efficacy in treating CRSwNP and severe asthma to inform future biologic therapies.
The investigators hypothesize that TSLP blockade with Tezepelumab will a) reduce upper airway inflammation based on histological, inflammatory, and remodeling biomarkers, that are evident in the airway remodeling process and b) correlate to a positive clinical response. Thus, nasal samples from chronic rhinosinusitis with nasal polyps (CRSwNP) patients with Severe Asthma (SA) pre- and post-treatment will exhibit inflammatory biomarkers and histopathological evidence that could prove responsive to the Tezepelumab. The overall research objectives are to evaluate the effect of study intervention (Tezepelumab) on CRSwNP-SA outcomes through a) evaluating the sinonasal inflammatory profile, histopathological features, and remodeling biomarkers and b) investigating the impact of Tezepelumab on the CRSwNP-related clinical outcomes in the treated study subjects.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
10 patients will receive teszpire
Eosinophil Count
Measurement of eosinophil count in tissue samples. Cells per high power field (HPF) or cells per millimeter squared (cells/mm²).
Time frame: From baseline to 24 weeks
Neutrophil count
Measurement of neutrophil count in tissue samples. Cells per high power field (HPF) or cells per millimeter squared (cells/mm²).
Time frame: From baseline to 24 weeks.
Basement Membrane Thickness
Measurement of the thickness of the basement membrane in tissue samples. Micrometers (µm)
Time frame: From baseline to 24 weeks
Fibrosis
Assessment of the extent of fibrosis in tissue samples, which may involve scoring systems or quantitative measurements
Time frame: From baseline to 24 weeks
Squamous Metaplasia
Immunohistochemical staining will be used to identify the presence of squamous metaplasia, with scoring based on percentage of positive cells.
Time frame: From baseline to 24 weeks
Lymphocytic Proliferation
Lymphocytic proliferation will be assessed using immunohistochemistry (IHC) to measure the Ki-67 proliferation index in tissue samples, specifically identifying the percentage of Ki-67-positive lymphocytes
Time frame: From baseline to 24 weeks
Immunoglobulin leves
IgE, IgG, IgA,
Time frame: 24 weeks
Th2 Cytokines
Measurement of Th2 cytokines such as IL-4, IL-5, IL-13
Time frame: 24 weeks
Th1/Th17 Cytokines
Measurement of Th1/Th17 cytokines such as IFN-γ and IL-17.
Time frame: 24 weeks
Myeloperoxidase (MPO)
Measurement of MPO levels in sinonasal samples or serum.
Time frame: 24 weeks
Interferon-γ (IFN-γ)
Measurement of IFN-γ levels in sinonasal samples or serum.
Time frame: 24 weeks
SNOT-22 (Sino-Nasal Outcome Test 22-item)
Assessment of sinonasal symptoms and their impact on quality of life using a 22-item questionnaire.
Time frame: 24 weeks
Health-Related Quality of Life
Measurement of health-related quality of life using the EuroQualityOfLife 5-Dimension 5-Level (EQ-5D-5L) instrument. The EQ-5D-5L includes 5 dimensions of health (Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression) with 5 levels of severity for each dimension (no problems, slight problems, moderate problems, severe problems, and extreme problems). For the overall EQ-5D-5L index score, it typically ranges from: Minimum Value: 0 (representing death) Maximum Value: 1 (representing perfect health) In some versions, a negative score can be obtained, which represents a state "worse than death."
Time frame: 24 weeks
Asthma Control Questionnaire
Asthma control will be assessed using the 5-question Asthma Control Questionnaire (ACQ-5), which includes the following domains: symptoms, reliever medication use, and limitations on daily activities. Each question is rated on a scale from 0 (no symptoms) to 6 (maximum symptoms). The total score is the sum of the individual responses, with possible scores ranging from 0 to 30
Time frame: 24 weeks
Epithelial Changes
Measurement of epithelial changes in sinonasal tissues, including alterations in epithelial thickness, cell type, and structural modifications.
Time frame: 24 weeks
Modified Lund-Kennedy Endoscopy Score
Evaluation of sinonasal pathology using the Modified Lund-Kennedy endoscopy scoring system, which assesses factors like nasal polyp size, discharge, and mucosal appearance. Typically ranges from 0 to 24, where higher scores indicate more severe disease.
Time frame: 24 weeks
Lund-Mackay CT Scan Score
Evaluation of sinus opacifications and other CT scan findings using the Lund-Mackay scoring system, which assesses the extent of sinus disease. Typically ranges from 0 to 24. 0 (no opacification) to 2 (complete opacification)
Time frame: 24 weeks
Changes in smell
Measurement of changes in olfactory function using the University of Pennsylvania Smell Identification Test (UPSIT)
Time frame: 24 weeks
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