Investigating the Role of ATP Production by Airway Epithelium in Patients With Refractory and Unexplained Chronic Cough (RCC/UCC).
- Conditions
- Chronic Cough (CC)
- Interventions
- Diagnostic Test: Bronchoscopy
- Registration Number
- NCT06600646
- Lead Sponsor
- McMaster University
- Brief Summary
Chronic cough is a common troublesome symptom which has a global prevalence of approximately 10%, but with wide variations across continents. Patients with refractory and unexplained chronic cough (RCC/UCC) often exhibit dysregulated vagal pathways, necessitating a neuronal biomarker for targeted treatment. ATP, involved in the ATP/P2X3 pathway, may serve as a potential biomarker due to its role in the cough reflex. The study aims to discover if ATP production by the airway epithelium is greater in RCC/UCC patients compared with healthy controls, if the epithelium is a source of ATP, whether gene and protein expression related to ATP production differs between these groups and whether ATP release is triggered by mechanical and chemical stimulation. Additionally, the study seeks to determine if biomarker gene expression signatures can differentiate RCC/UCC patients from healthy controls.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
- Participants who are currently established on treatment and their chronic cough is well controlled.
- Unable to perform acceptable and reproducible spirometry.
- Participants with a positive covid-19 test within 2 weeks of screening.
- Current smoker or ex-smoker with ≥20 pack year smoking history and abstinence of ≤6 months
- Symptoms of upper respiratory tract infection in the last 1 month which have not resolved
- Lower respiratory tract infection or pneumonia in the last 1 month
- Asthma exacerbation in the previous month requiring an increase or start of an inhaled corticosteroid (ICS) or oral corticosteroid (OCS)
- Significant other primary pulmonary disorders in particular; pulmonary embolism, pulmonary hypertension, lung cancer, cystic fibrosis, significant radiologically proven emphysema, interstitial lung disease or bronchiectasis.
- History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial.
- Allergy or intolerance to sedation medication including fentanyl and midazolam, or a history of complications during procedural sedation
- Severe coagulopathy, bleeding disorder, or medical need for anti- coagulation that would increase the risk of endobronchial biopsy as determined by the investigator
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Refractory or Unexplained Chronic Cough Bronchoscopy - Healthy Controls Bronchoscopy -
- Primary Outcome Measures
Name Time Method Difference in expressed genes At baseline Expression of genes involved in intracellular ATP production, transport, extracellular metabolism in the airway epithelium will be compared in both RCC/UCC and healthy controls.
- Secondary Outcome Measures
Name Time Method Difference Immune Cells and Cytokines 12 months Investigate differences in the levels of neuroinflammatory mediators and immune cells from the respiratory airways and distal alveoli.
Gene Expression At baseline To compare the differences in RCC/UCC and healthy control in gene expression profiling in bronchial biopsies (sub-epithelial dominant).
Difference in Nerve Morphology baseline Investigate differences in nerve length, nerve branch points, nerves expressive P2X3 receptors on airway sensory nerves expressing P2X3 receptor in RCC/UCC compared with healthy controls.
Difference in ATP release 5,15,30 minutes ATP release from the cultured bronchial epithelial cells (BEC) taken from RCC/UCC and healthy controls after exposure to dynamic mechanical stretch and environmental exposures (cigarette smoke and NO2).
Trial Locations
- Locations (1)
Imran Satia
🇨🇦Hamilton, Ontario, Canada