Bronchial thermoplasty: Device therapy for asthmaJune 11, 2019
Asthma is a complex inflammatory disorder of the airways characterized by airway hyper-responsiveness (AHR) and variable airflow obstruction. Although advances in clinical and basic research over the past few decades have led to the development of effective treatments and dissemination of detailed disease management guidelines, difficult-to-treat asthma continues to affect 5-10% of adults with this disorder.
Bronchial thermoplasty (BT) is a modality for treating asthma and is thought to prevent the chronic structural changes that occur in airway smooth muscle (ASM) in individuals with asthma. BT targets ASM via the delivery of a controlled specific amount of radiofrequency (RF) energy (RF ablation [RFA]) to the airway wall through a dedicated catheter.
It is an innovative treatment whose clinical efficacy and safety are beginning to be better understood. Since this is a device-based therapy, the overall evaluation of risk-benefit is unlike that of pharmaceutical products; safety aspects, regulatory requirements, study design and effect size assessment may be unfamiliar. The mechanisms of action and optimal patient selection need to be addressed in further rigorous clinical and scientific studies.
Candidates for bronchial thermoplasty include adults with severe persistent asthma who require regular maintenance medications of inhaled corticosteroids (>1000 µg/day of beclomethasone or the equivalent) and a long-acting beta agonist (≥100 µg/day of salmeterol or the equivalent). These patients would have received add-on therapies such as leukotriene modifiers, omalizumab, or oral corticosteroids (≤10 mg/day).
These patients should be on stable maintenance asthma medications according to accepted guidelines, should have a pre-bronchodilator forced expiratory volume in 1 second (FEV1) of 60% or more of predicted, and should have a stable asthma status (FEV1 within 10% of the best value, no current respiratory tract infection, and no severe asthma exacerbation within the preceding 4 weeks).
Patients are usually selected on the basis of the AIR 2 trial. The patient should be stable in terms of asthma status, defined as a post bronchodilator FEV1 within 15% of baseline values with no respiratory tract infection or asthma exacerbations within the preceding 14 days.
Contraindications for BT include the following:
- Presence of an implantable electronic device
- Known hypersensitivity to drugs used during bronchoscopy
- Severe comorbid conditions that would increase the risk of adverse events
Patients are not considered candidates for BT if they had three or more hospitalisations for asthma, three or lower respiratory tract infections and four or more oral corticosteroids used for asthma in the previous year.
Although the benefits of BT may be large, the potential harm may be large as well, and the long-term side effects are unknown. Studies are still needed to assess exacerbation rates and long-term effects on lung function. It remains to be determined which phenotypes will respond best to BT, what the effects may be on obstructed patients with an FEV1 higher than 60%, and what the applicability of the procedure may be in patients receiving systemic steroid therapy
BT is performed via fibreoptic bronchoscopy in three separate procedures, separated by approximately 3 weeks, as demonstrated by previous studies.] Dividing the treatments into three bronchoscopy sessions minimizes the risk of inducing an asthma exacerbation or diffuse airway oedema. It also avoids excessive procedural length. BT takes longer (30-60 minutes) than a standard fiber-optic bronchoscopy (5-20 minutes) does, and the longer duration implies the use of larger doses of medication for sedation.
All accessible airways are treated, with the exception of the right middle lobe, because of the theoretical concern about the risk of inducing right-middle-lobe syndrome.]
Oxygen delivery should be started via a nasal or oral cannula during the procedure, with appropriate monitoring of vital signs. Heart rate, pulse oximetry, and noninvasive blood pressure should be continuously monitored.
Patients may experience respiratory-related adverse events such as cough, wheezing, and chest tightness during the treatment period. Most of these symptoms occur within 1 day of the procedure and resolve in an average of 7 days with standard therapy.
It is unclear why an intervention aiming at a reduction of smooth-muscle mass would not affect FEV1. Given that the number of exacerbations is reduced with no change in FEV1, it may be that altered response to the inflammatory triggers plays a role in addition to the reduction in smooth-muscle mass.
Recurrent lung atelectasis secondary to fibrin plugs has been reported as an early complication of BT. In the susceptible patient, high thermal stimulation may lead to an inflammatory reaction with microvascular alteration, induced either by heat or by the release of inflammatory mediators. Lung abscess has also been described as a direct complication; thus, collecting and publishing safety data continue to be important. A prospective cohort study performed as part of the TASMA trial reported a high incidence of acute radiologic abnormalities after BT. Postprocedural CT of the chest identified four different radiologic patterns: (1) peribronchial consolidations with surrounding ground-glass opacities (94%), (2) atelectasis (38%), (3) partial bronchial occlusions (63%), and (4) bronchial dilatations (19%). These complications resolved without clinical impact in virtually all cases.
The author is Head, Department of Respiratory Medicine, Medical Trust Hospitals, Cochin