ToAST:Investigating the Effect of Bronchial Thermoplasty on Cough in Patients With Severe Asthma

Study Overview
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Brief Summary
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ToAST study is a pilot study aiming to establish the safety profile of using inhaled capsaicin challenge in patients with severe asthma. The investigators will also explore the differences in cough symptoms and threshold in patients with and without bronchial thermoplasty.

Detailed Description
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ToAST is designed as a two-visit observational study. During visit 1, written consent and measurements of baseline asthma characteristics were completed; history and examination, questionnaires (Asthma Control Questionnaires and Leicester Cough Questionnaire, and basic lung physiological assessment were performed. At the end of visit 1, a cough monitor was attached to the subject to monitor cough frequency for the next 24 hours and this was returned at visit 2. Visit 2 followed within two weeks after visit 1, during which a full dose capsaicin cough challenge was performed. Emergency contact details were given towards end of visit 2 should any adverse events occur. Telephone call within 48 hours, Day 3 and Day 7: The purpose of these phone calls was to ensure that the patient had not developed any adverse effects to the capsaicin challenge.

Official Title
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ToAST: Investigating the Effect of Bronchial Thermoplasty on Cough in Patients With Severe Asthma

Conditions
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Asthma Chronic, Cough

Intervention / Treatment
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* Other: Inhaled capsaicin cough challenge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥18 Person with an established diagnosis of severe asthma All patients should be on British Thoracic Society (BTS) steps 4 or 5 Patients who have had bronchial thermoplasty (BT) should be at least 2 months after their treatment Historical evidence of one of the following: Airway reversibility to a short acting beta-2 agonist of ≥12% Bronchial hyper-responsiveness (PC20<8mg/ml) Fractional exhaled nitric oxide ≥50ppb Peak flow variability >8% Raised serum (≥0.45) or sputum eosinophilia (>3%) Variability in spirometry over 24 months of >20% Exclusion Criteria: Unable to give informed consent FEV1<50% predicted or < 1 litre Known allergy or intolerance to capsaicin Symptoms of upper respiratory tract infection in the last 1 month which have not resolved. Lower respiratory tract infection or pneumonia in the last 6 weeks. Current smoker or ex-smoker with ≥10 pack year smoking history, abstinence of ≤6 months Asthma exacerbation in the previous month requiring an increase or starting of an ICS or OCS Subject has changed asthma medication within the past 4 weeks prior to screening A previous asthma exacerbation requiring Intensive Care Unit (ICU) admission. Significant other pulmonary disorders as the major diagnosis, in particular: pulmonary embolism, pulmonary hypertension, interstitial lung disease, lung cancer, cystic fibrosis, emphysema or bronchiectasis. Evidence of vocal cord dysfunction Pregnancy or breast-feeding Use of ACE inhibitors Any centrally acting medication which in the view of the investigator could alter the sensitivity of the cough reflex* History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Patients without BT<br> | Other: Inhaled capsaicin cough challenge<br> <br> |
| Other: Post BT<br> | Other: Inhaled capsaicin cough challenge<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who has had significant fall in FEV1 (defined as >20%) within the challenge period | By measuring spirometry immediately before and after challenge | Through study completion, an average of 6 months | 
| Number of participants who require bronchodilator treatment during capsaicin challenge period | Defined as rescue medications - 2 puffs of salbutamol inhaler via spacer | Through study completion, an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in %FEV1 predicted during capsaicin challenge period in all subjects | By measuring spirometry immediately before and after challenge | Through study completion, an average of 6 months | 
| The tolerability of inhaled capsaicin in severe asthma | By exploring the pattern of termination of challenge in severe asthma | Through study completion, an average of 6 months | 
| The number of adverse events in all subjects during and after capsaicin evoked cough challenge | by follow up phone calls at 48 hours, 3 days and 7 days to assess AE and SAE | Through study completion, an average of 6 months | 
| Degree of breathlessness during capsaicin challenge period assessed by using modified Borg scale (mBorg). | By calculating Borg immediately before and after challenge to assess level of breathlessness. | Through study completion, an average of 6 months | 
| Degree of breathlessness during capsaicin challenge period assessed by using dysnoea Visual Analogue Score (dVAS). | By calculating dVAS immediately before and after challenge to assess level of breathlessness. | Through study completion, an average of 6 months | 
| Differences in capsaicin dose response curves (Maximum cough response evoked by any concentration of capsaicin- Emax and Capsaicin dose inducing half-maximal response - ED50) between subjects who have had BT versus those have not | by comparing post-BT and no-BT patients | Through study completion, an average of 6 months | 
| The differences in 24-hour cough frequency between patients who have had BT and those who have not. | by comparing post-BT and no-BT patients | Through study completion, an average of 6 months | 
| The differences in Leicester cough questionnaire (LCQ) between patients who have had BT and those who have not. | by comparing post-BT and no-BT patients | Through study completion, an average of 6 months | 
| The differences in asthma control questionnaire(ACQ) between patients who have had BT and those who have not. | by comparing post-BT and no-BT patients | Through study completion, an average of 6 months | 
| The differences of the dose response curves in patients with severe asthma with existing data of capsaicin challenge in patients with healthy and mild/moderate asthma (in Emax and ED50). | By comparing with existing data. | Through study completion, an average of 6 months |