Bronchial thermoplasty: A new treatment for severe refractory asthma
ABSTRACTBronchial thermoplasty was recently approved for treating severe refractory asthma that is not well controlled by high-dose inhaled corticosteroids and long-acting bronchodilator therapy. This article reviews its indications, evidence of efficacy, and protocols.
KEY POINTS
- Bronchial thermoplasty involves the application of radiofrequency energy to the airways distal to the mainstem bronchi down to airways as small as 3 mm in diameter.
- Treatments are done in three separate sessions, with careful monitoring before and after for respiratory complications that can occur in severe asthma. Airway complications and asthma exacerbations can occur up to 6 weeks after the last procedure, thus requiring close patient follow-up.
- In clinical trials, including a randomized trial in which the control group underwent sham thermoplasty, bronchial thermoplasty had an acceptable safety profile while improving asthma quality-of-life scores, symptoms, and health care utilization.
BRONCHIAL THERMOPLASTY PROTOCOLS
Patients are assessed before and on the day of the procedure to make sure their disease is stable (ie, their postbronchodilator FEV1 is within 15% of baseline values, and they have no evidence of asthma exacerbation or active infection), similar to the protocol used in the AIR2 trial,6 before proceeding with the treatment.
Patients are given 50 mg of prednisone 3 days before and again on the day of the procedure. Nebulized albuterol (2.5–5.0 mg) is given before the patients undergo screening spirometry and again before the procedure. If the preprocedure FEV1 is lower than 15% below baseline, we postpone the procedure to another day.
The procedure is performed with the patient under moderate conscious sedation, typically using fentanyl (Sublimaze), midazolam (Versed), and topical lidocaine in a monitored environment. The bronchoscope is inserted via either the mouth or nose, and supplemental oxygen is provided.
Thermoplasty is performed with the Alair system (Asthmatx, Inc., Sunnyvale, CA), which delivers a specific amount of radiofrequency (thermal) energy through a dedicated catheter. The catheter is deployed through a 2.0-mm channel of a flexible bronchoscope, starting in distal airways as small as 3 mm in diameter and working proximally to sequentially treat all airways to the mainstem lobar bronchi. The sites treated are meticulously recorded on a bronchial airway map to ensure that treatment sites are not skipped or overlapped (FIGURE 1).
An array of four electrodes is manually expanded to make contact with the airway walls; each electrode has 5 mm of exposed wire. As the energy is delivered, the control unit measures electrical resistance converted to thermal energy and turns off the current when an appropriate dosage is given. This thermal energy is what is responsible for altering the airway smooth muscle.
A full course of treatment requires three separate bronchoscopy sessions, each separated by 2 to 3 weeks. The left lower lobe and the right lower lobe are treated in separate procedures, and then both upper lobes are treated in a third procedure to minimize any respiratory symptoms. Each procedure usually requires 50 to 75 activations of the device and takes up to 60 minutes.
After each procedure the patient should be observed for 3 to 4 hours, and spirometry should be repeated to make sure the FEV1 (percent predicted) is within 20% of the baseline value. An additional 50-mg dose of prednisone is prescribed for the day after the procedure.24
FDA CLEARANCE AND LONG-TERM FOLLOW-UP
The FDA approved the Alair device for treating severe refractory asthma in early 2010.3 The indications for it are based on the study populations in the published trials. Patients can be evaluated for this treatment if they have well-documented severe persistent asthma not well controlled on inhaled corticosteroids and long-acting beta agonists and have no significant contraindications to bronchoscopy.
As part of the conditions of approval, the FDA required a postapproval study based on the long-term follow-up of the AIR2 trial. They specifically wanted to compare patients who have desirable long-term outcomes and those in whom any treatment effect wanes with time. Since we have only a few years of follow-up data, we still do not know all the possible late effects of the treatment; we have an opportunity to learn more.
Another question that needs to be studied is whether thermoplasty will help other forms of bronchospastic lung disease, such as chronic obstructive pulmonary disease.
A second postapproval study will be a prospective, open-label, single-arm, multicenter study conducted in the United States to assess the treatment effect and short-term and long-term safety profile of thermoplasty in asthma.
As experience with the procedure increases, we will be better able to characterize which patients may benefit from it. In addition, the knowledge gained by the longer-term study of airway smooth muscle function alterations will potentially drive the discovery of other innovative therapies for severe asthma.
