• Safety
  

• Reduction in maintenance Medications
  
• Change in Asthma Symptoms
  
• Asthma Control Questionnaire (ACQ)
  
• Spirometry
  
• Asthma Quality of Life (AQLQ)
  
• Use of rescue medications
  

Inclusion Criteria:

• Ambulatory adult; age 18-65 years
• Asthma requiring regular maintenance medication that includes high dose inhaled corticosteroid AND long acting β2 agonist (LABA) with or without other asthma maintenance medications. Oral prednisone < 30 mg/day, leukotriene modifiers, theophylline or other asthma control drugs may be prescribed at the physician’s discretion.
• Pre-bronchodilator FEV1 >50% predicted (patients stabilized on inhaled corticosteroids (ICS) and long acting β2 agonists)
• PC20 < 4 mg/ml per methacholine inhalation test using standardized methods, for patients with pre-bronchodilator FEV1 > 60% predicted (or FEV1 > lower limit defined by individual hospital protocol)
• Reversible bronchoconstriction during the 12 months prior to enrollment, as demonstrated by an increase in FEV1 of at least 12% 30 minutes after 4 puffs of short-acting β2 agonist, for patients with pre-bronchodilator FEV1 < 60% predicted (or FEV1 < lower limit defined by individual hospital protocol)

• Patient must be symptomatic, despite medication with high dose inhaled corticosteroids and LABA, by at least one of the following:

  1. Use of rescue medication (short-acting β2 agonist) at least 8 of the 14 days prior to enrollment OR
  2. Daytime symptoms at least 10 of the 14 days prior to enrollment
• Non-smoker x 1 year or greater (if former smoker, less than 10 pack years total smoking history)
• Patient must be suitable for bronchoscopy in the opinion of the investigator or per hospital guidelines
• Willingness and ability to give written Informed Consent
• Willingness and ability to comply with the study protocol, including requirements for taking and abstaining from medications

Exclusion Criteria:

• Participation in another clinical trial involving respiratory intervention that could affect the outcome measures of this study, within 6 weeks prior to randomization. Patients 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 less than 6 weeks from enrollment testing)
• History of recurrent (no more than three in the last three months) lower respiratory tract infection requiring antibiotics
• Presence of other respiratory diseases including emphysema, cystic fibrosis, vocal cord dysfunction, mechanical upper airway obstruction, obstructive sleep apnea, Churg-Strauss syndrome, cardiac dysfunction, allergic bronchopulmonary aspergillosis
• DLCO < 70% predicted
• Uncontrolled sinus disease
• Uncontrolled gastro-esophageal 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 b-adrenergic blocking agent
• Other medical criteria.