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.

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.

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.