RISA.

Methods	Design: randomised controlled trial (NCT00214539) Number of participating centres: eight from United Kingdom, Canada and Brazil
Participants	Inclusion criteria: Participants with asthma aged 18 to 65 years Requirement of high‐dose inhaled corticosteroid (ICS) and LABA with or without oral prednisone (< 30 mg/d), leukotriene modifiers or theophylline Pre‐bronchodilator FEV1 > 50% of predicted Airway hyperresponsiveness by challenge with methacholine or reversible bronchoconstriction during prior 12 months Uncontrolled symptoms despite taking maintenance medication Abstinence from smoking for at least one year and past smoking history of less than 10 pack‐years Exclusion criteria (not specified in the main publication (Pavord 2007); obtained from clinicaltrials.gov): Participation in another clinical trial involving respiratory intervention that could affect the outcome measures of this study, within six weeks before randomisation. Participants will be disqualified from the study if they enter another study or fail to comply with prescribed asthma medications Use of immunosuppressant therapy (e.g. methotrexate) Current or recent lower respiratory tract infection (resolved within six weeks of enrolment testing) History of recurrent (no more than three in the last three months) lower respiratory tract infections requiring antibiotics Presence of other respiratory diseases including emphysema, cystic fibrosis, vocal cord dysfunction, mechanical upper airway obstruction, obstructive sleep apnoea, Churg‐Strauss syndrome, cardiac dysfunction or allergic bronchopulmonary aspergillosis DLCO (diffusion capacity) < 70% predicted Uncontrolled sinus disease Uncontrolled gastroesophageal reflux disease Use of implanted electronic device such as a pacemaker or internal cardiac defibrillator Use of external pacemaker Significant co‐morbid illness such as cancer, renal failure, liver disease or cerebral vascular disease Post‐bronchodilator FEV1 of less than 55% predicted Known systemic hypersensitivity or contraindication to methacholine chloride or other parasympathomimetic agents Known sensitivity to medications required to perform bronchoscopy, including lidocaine, atropine, benzodiazepines and opioids Use of a systemic beta‐adrenergic blocking agent Other medical criteria. No. of randomly assigned participants: 34 (17 BT vs 17 control group) Age (mean (SD)): BT group: 39.1 (13) versus control group: 42.1 (12.6) Sex (% male): BT group: 40 versus control group: 59 PC20 mg/mL (geometric mean (95% CI)): BT group: 0.19 (0.05 to 0.76) versus control group: 0.31 (0.08 to 1.26) Pre‐bronchodilator FEV1 (% predicted; mean (SD)): BT group: 69.9 (12.2) versus control group: 66.4 (17.8) Dose OCS (mg/d; mean (SD)): BT group: 14.4 (6.2) versus control group: 18.6 (9.8) Dose ICS (µg/d; mean (SD)): BT group: 1166.7 (408.3) versus control group: 1058.9 (336.9) Dose LABA (µg/d; mean (SD)): BT group: 125 (60.5) versus control group: 136.7 (45.5) Asthma severity (percentage of participants with severe persistent asthma according to criteria of the Global Initiative for Asthma (GINA) and the American Thoracic Society (ATS)): BT group: 100 (GINA) versus control group: 100 (GINA) AQLQ score (mean (SD)): BT group: 3.96 (1.34) versus control group: 4.72 (1.06)
Interventions	Intervention: bronchial thermoplasty plus medical management Control: medical management
Outcomes	Main outcome: Respiratory adverse events per participant Secondary outcomes: Use of maintenance medications Use of rescue medications Total symptom score Morning and evening peak expiratory flow (PEF) Pre‐bronchodilator FEV1 (percentage predicted) Post‐bronchodilator FEV1 (percentage predicted) Asthma Control Questionnaire (ACQ) score Asthma Quality of Life Questionnaire (AQLQ) score Symptom‐free days
Notes	Funded by Asthmatx Inc
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Centrally generated computer randomisation sequence in blocks of four participants
Allocation concealment (selection bias)	Low risk	Randomisation provided to each participating centre in sealed envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open trial
Blinding of outcome assessment (detection bias) All outcomes	High risk	Outcomes collected by participants in diaries monitored by the research staff at medical meetings or in telephone interviews
Incomplete outcome data (attrition bias) All outcomes	Low risk	The trial publication did not provide details about the plan needed to perform the analysis of results 34 participants randomly assigned (17 to each group) Participants lost to follow‐up: two participants in the bronchial thermoplasty group withdrawn from the study before receiving treatment in keeping with a recommendation to not treat them from the study Data and Safety Monitoring Board 15 participants in the bronchial thermoplasty group and 17 in the control group included in the final analysis
Selective reporting (reporting bias)	Low risk	Outcomes described in the study protocol (NCT00214539) were reported in the main publication (Pavord 2007)

BT: bronchial thermoplasty.