Chronic Cough (CC)
Conditions
Keywords
chronic cough, ATP, airway nerves
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.
Interventions
DIAGNOSTIC_TESTBronchoscopy
Bronchoscopy will be performed in patients with refractory or unexplained chronic cough and healthy controls.
Sponsors
McMaster University
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
for RCC/UCC: * Patients with a history of RCC/UCC. * Normal Chest X-ray in the last 5 years. * No Evidence of Airflow Obstruction (FEV1/FVC ratio above LLN) * Cough Severity VAS ≥ 40 mm at screening. Inclusion Criteria for Healthy Controls: * No history of chronic cough, asthma, COPD, or clinical history of bronchiectasis or interstitial lung disease * No current smokers or those with >10 pack year history. * No evidence of airflow obstruction ( FEV1/FVC ratio above LLN). * Able to understand and give written informed consent.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
Canada
Contacts
Primary ContactImran Satia, MB BChir (cantab) MRCP PhD
Outcome results
None listed