Bronchial Thermoplasty in Severe Persistent Asthma

This is a multicenter, open-label, single arm study designed to demonstrate durability of the treatment effect and to evaluate the short-term and longer-term safety profile of the Alair System in the United States in the intended use population (patients 18 years and older with severe persistent asthma).

Inclusion criteria

• Subject is an adult between the ages of 18 to 65 years.
• Subject is able to read, understand, and sign a written Informed Consent to participate in the study and able to comply with the study protocol.
• Subject has asthma and is taking regular maintenance medication that includes:

• Inhaled corticosteroid (ICS) at a dosage greater than 1000μg beclomethasone per day or equivalent, AND long acting β2-agonist (LABA) at a dosage of ≥80μg per day Salmeterol or equivalent.
• Other asthma medications such as leukotriene modifiers, or anti-IgE, are acceptable (Subjects on Xolair® must have been on Xolair for greater than 1 year).
• Oral corticosteroids (OCS) at a dosage of up to, but not greater than 10mg per day are acceptable.*
• Subject has a pre-bronchodilator FEV1 of greater than or equal to 60% of predicted.
• Subject is a non-smoker for 1 year or greater (if former smoker, less than 10 pack years total smoking history).
• Subject is able to undergo outpatient (same day) bronchoscopy in the opinion of the investigator or per hospital guidelines.
• Subject has at least 2 days of asthma symptoms in the last 4 weeks.
• Subject has an AQLQ score during the baseline period of 6.25 or less.

• NOTE: Subjects on a dosage regimen of 20mg OCS every other day may be included as this is equivalent to an average daily dosage of 10mg.

Exclusion criteria

• Subject is participating in another clinical trial within 6 weeks of the Baseline Period involving respiratory intervention that could affect the outcome measures of this Study.
• Over the last 7 days of a 4 week medication stable period, subject requirement for rescue medication use other than for prophylactic use for exercise exceeds an average of:

• 8 puffs per day of short-acting bronchodilator, or
• 4 puffs per day of long-acting rescue bronchodilator, or
• 2 nebulizer treatments per day. At the discretion of the Principal Investigator, subjects considered as unstable on baseline medications may have medications adjusted and re-evaluated after a 4 week medication stabilization period.
• Subject has a post-bronchodilator FEV1 of less than 65%.
• Subject has a history of life-threatening asthma, defined by past intubation for asthma, or ICU admission for asthma within the prior 2 years.
• Subject has 3 or more hospitalizations for exacerbations of asthma in the previous year.
• Subject has had 4 or more infections of lower respiratory tract (LRTI) requiring antibiotics in the past 12 months.
• Subject has had 4 or more pulses of systemic corticosteroids (tablets, suspension or injection) for asthma symptoms in the past 12 months.
• Subject has a known sensitivity to medications required to perform bronchoscopy (such as lidocaine, atropine and benzodiazepines).
• Subject has other respiratory diseases including emphysema, cystic fibrosis, vocal cord dysfunction, mechanical upper airway obstruction, Churg-Strauss syndrome, and allergic bronchopulmonary aspergillosis (asthma, immediate cutaneous reactivity to A. fumigatus, total serum IgE of >1000ng/mL, elevated specific IgE and IgG to A. fumigatus with or without evidence of central bronchiectasis).
• Subject has segmental atelectasis, lobar consolidation, significant or unstable pulmonary infiltrate, or pneumothorax, confirmed on x-ray.
• Subject currently has clinically significant cardiovascular disease, including myocardial infarction, angina, cardiac dysfunction, cardiac dysrhythmia, conduction defect, cardiomyopathy, or stroke.
• Subject has a known aortic aneurysm.
• Subject has significant co-morbid illness such as cancer, renal failure, liver disease, or cerebral vascular disease.
• Subject has uncontrolled hypertension (>200mm Hg systolic or >100mm Hg diastolic pressure).
• Subject has an implanted electrical stimulation device (e.g., a pacemaker, cardiac defibrillator, or deep nerve or deep brain stimulator).
• Subject has coagulopathy (INR > 1.5).
• Subject has any other medical condition that would make them inappropriate for study participation, in the Investigator's opinion.