A Prospective Observational Study of Biopredictors of Bronchial Thermoplasty Response in Patients With Severe Refractory Asthma (BTR Study)

Subject Population - Severe Refractory Asthma

Inclusion Criteria:

1. Males or females age 18 or greater and less than 65

2. Subject has asthma and is taking regular maintenance medication for past 12 months that includes:

   • Inhaled corticosteroid (ICS) at a dosage greater than 1000μg beclomethasone per day or equivalent, AND long acting ß2-agonist (LABA) at a dosage of ≥100μg 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).
3. Asthma confirmed by: (a) b-agonist reversibility of FEV1 ≥ 12 % following 360mcg albuterol OR (b) methacholine FEV1 PC20 ≤ 8 mg/ml if not receiving an ICS or ≤ 16 mg/ml if receiving an ICS.
4. FEV1 ≥ 50% predicted pre-bronchodilator.
5. Asthma symptoms on at least two days or one night per week over the last 2 weeks.
6. Subject is a non-smoker for 1 year or greater (if former smoker, less than 10 pack years total smoking history).
7. Ability to undergo bronchoscopy in the opinion of the investigator.
8. Ability and willingness to provide informed consent.
9. For women of childbearing potential: not pregnant, non-lactating, and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study.

Exclusion Criteria:

1. Asthma exacerbation (ED visit, hospitalization, course of increased systemic steroids, or urgent health care visit for asthma) during the prior four weeks.
2. Subject has 3 or more hospitalizations for exacerbations of asthma in the previous year or 1 or more ICU admission for asthma in the previous year.
3. Chronic oral steroid therapy greater than 30 mg per day
4. Respiratory tract infection within past 4 weeks
5. Subject has a known sensitivity to medications required to perform bronchoscopy (such as lidocaine, atropine and benzodiazepines).
6. Subject is undergoing immunosuppressant therapy (e.g., methotrexate).
7. Subject is on anticoagulant medication.
8. Subject has bleeding diathesis, platelet dysfunction, and thrombocytopenia with platelet count less than 125,000/mm2 or known coagulopathy (INR > 1.5).
9. Subject has other respiratory diseases including interstitial lung disease, emphysema, cystic fibrosis, vocal cord dysfunction, mechanical upper airway obstruction, obstructive sleep apnea, Churg-Strauss syndrome, cardiac dysfunction, and allergic bronchopulmonary aspergillosis (total IgE of >1000 Units/mL with positive specific IgE to aspergillus and evidence of central bronchiectasis).
10. Subject has segmental atelectasis, lobar consolidation, significant or unstable pulmonary infiltrate, or pneumothorax, confirmed on x-ray.
11. Subject has clinically significant cardiovascular disease, including myocardial infarction, angina, cardiac dysrhythmia, conduction defect, cardiomyopathy, aortic aneurysm, or stroke.
12. Subject has uncontrolled hypertension (>200mm Hg systolic or >100mm Hg diastolic pressure).
13. Subject uses an internal or external pacemaker or cardiac defibrillator.
14. Chronic diseases (other than asthma) that in the opinion of the investigator would prevent participation in the trial or put the participant at risk by participation, e.g. chronic diseases of the lung (other than asthma), heart, liver, kidney, or nervous system, or immunodeficiency
15. History of cigarette smoking with > 10 pack years total
16. Use of investigative drugs or intervention trials in the 30 days prior to enrollment or during the duration of the study
17. Any condition or compliance issue which in the opinion of the investigator might interfere with participation in the study