A pRospective, multicenter, single-arm study EvaLuating the safety and feasIbility of Targeted Lung Denervation (TLD) for the trEatment of severe asthma.

1. Adult; age *21 to *65;
2. Patient has provided written informed consent using a form that has been reviewed and
approved by the Ethics Committee;
3. Diagnosis of severe asthma as defined by the 2017 GINA Report, and are taking regular maintenance medication that includes: a) Inhaled corticosteroid (ICS) at a dosage >1000*g beclomethasone per day or equivalent, AND b) Long-acting *-agonist (LABA) at a dosage of *100*g Salmeterol per day or equivalent (MDI prn); -or- a) Inhaled corticosteroid (ICS) at a dosage >1000*g beclomethasone per day or equivalent, AND b) Leukotriene receptor antagonist (LTRA) or theophylline; And may be taking other add-on medications including (but not limited to): * Tiotropium; *Oral corticosteroids (OCS) at a dosage of *10mg per day. Note: Subjects on a dosage regimen of 20mg OCS every other day may be included as this averages to a daily dose of 10mg.
4. Pre-bronchodilator FEV1 *60% predicted on stable therapy after a 4-week medication run-in of an inhaled corticosteroid (>1000*g beclomethasone per day or equivalent) and a long-acting *-agonist (*100 *g Salmeterol per day or equivalent MDI prn);
5. Subject has at least two days of asthma symptoms during the 4-weeks of the Baseline Diary Period;
6. Women of child bearing potential must have a negative pregnancy test (serum or urine) at screening and agree not to become pregnant for the duration of the study;
7. Non-smoker for at least 6 months (if former smoker, less than 10 pack years total smoking history) and agree to continue not smoking for duration of the study;
8. Patient is a candidate for bronchoscopy in the opinion of the physician or per hospital
guidelines;
NOTE: Examples of suitability of patients for bronchoscopy include, but are not limited to:
* Cardiovascular fitness
* Ability of patient to be intubated
* Ability to oxygenate patient
* Absence of previously diagnosed high-grade tracheal obstruction
* Absence of uncorrectable coagulopathy
9. Patient is a candidate to undergo methacholine challenge testing in the opinion of the physician;(e.g., does not have uncontrolled hypertension, history of MI or stroke within 3 months prior to the test, aortic or cerebral aneurysm);
10. The patient is willing, able and agrees to complete all protocol required baseline and
follow up testing assessments and comply with medication requirements.

1. In the 24 months prior to enrollment, the subject has:
* Been intubated for asthma
* Had intensive Care Unit admission(s) for asthma
* Been treated with immunosuppressant therapy for any reason (steroids excluded)
2. In the 12 months prior to enrollment, the subject has had:
* * 3 lower respiratory tract infections requiring antibiotics
* * 3 hospitalizations for asthma exacerbations
3. In the 3 months prior to enrollment, the subject has taken/used an opioid(s)
4. In the 6 weeks prior to enrollment the subject had a lower respiratory tract infection or
asthma exacerbation that required:
* antibiotics
* unscheduled physician visits for asthma care
* changes in use of asthma maintenance medication
* taking of rescue medication over normal dose in a 24-hour period for asthma symptoms
* a steroid burst (pulse)
NOTE: Prophylactic use of rescue medication for exercise is not counted in daily totals.
5. Current use of oral steroids >10mg at the time of enrollment;
6. History of poor medication compliance;
7. Prior lung or chest procedure (i.e. bronchial thermoplasty, metal stent, median sternotomy, etc.);
8. Other chronic pulmonary disorders associated with asthma-like symptoms, including (but not limited to) cystic fibrosis, chronic obstructive pulmonary disease, chronic bronchitis, vocal cord dysfunction eosinophilic granulomatosis with polyangiitis (EGPA), previously called the Churg-Strauss syndrome (CSS), or interstitial lung disease that is the sole cause of asthma symptoms, severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways;
9. Pre-existing diagnosis of pulmonary hypertension, defined as a sustained elevation of the mean pulmonary artery pressure greater than or equal to 25 mm Hg at rest by right heart
catheterization or estimated by echocardiogram to be greater than 40 mm Hg;
10. Uncontrolled diabetes as evidenced by an HbA1c >7%;
11. Patient has an implantable electronic device;
12. Known contraindication or allergy to anticholinergic drugs or components;
13. Known contraindication or allergy to medications required for bronchoscopy or general
anesthesia (such as lidocaine, atropine, propofol, sevoflurane, etc.) or peri-procedural therapy (i.e. prednisone, azithromycin) that cannot be medically
controlled;
14. Based on investigator judgment, the patient is unable to stop taking blood thinning
medication (with the exception of aspirin) 7 days before and not re-start until 7 days after the study procedure;
15. Documented history of untreated severe (AHI index >30/hr) obstructive sleep apnea;
16. The patient has any disease or condition that might interfere with completion of a procedure or this study or patient safety (e.g., structural esophageal disorder, bronchiectasis, pneumothorax, pleural effusion, life expectancy <3 years);
17. Screening Chest CT Scan reveals bronchi anatomy cannot be fully treated with the available catheter sizes or discovery of a pulmonary nodule requiring follow-up or intervention unless proven benign;
18. Patients who had abdominal surgical procedures on stomach, esophagus or pancreas
(esophagectomy, gastrostomy, gastrectomy, bariatric surgery, fundoplication, vagotomy, etc.);
19. Patients with a GCSI score *18.0 prior to treatment;
20. Patient is currently enrolled in another clinical trial that has not completed follow-up.