This document addresses the use of bronchial thermoplasty as a treatment option for adults whose severe persistent asthma is not well controlled with inhaled corticosteroids and long-acting beta-agonists.
Note: Please see the following documents for additional information related to the treatment of asthma:
Investigational and Not Medically Necessary:
Bronchial thermoplasty is considered investigational and not medically necessary for the treatment of asthma and all other conditions.
The safety and effectiveness of bronchial thermoplasty for the treatment of severe persistent asthma in adults was evaluated in three randomized controlled trials (RCTs) supported by the manufacturer of the Alair® Bronchial Thermoplasty System (Boston Scientific Corporation, Natick, MA [Asthmatx, Inc., Sunnyvale, CA]). The system received U.S. Food and Drug Administration (FDA) premarket approval (PMA) in April 2010 for use in adults with severe and persistent asthma whose symptoms are not adequately controlled with inhaled corticosteroids (ICSs) and long-acting beta-antagonists (LABAs).
Research in Severe Asthma (RISA) Trial
Pavord and colleagues (2007) evaluated the safety and effectiveness of bronchial thermoplasty in adults (18 years of age or older) with symptomatic, severe asthma in a multicenter study conducted at eight centers in the United Kingdom, Brazil, and Canada. Individuals eligible for participation included those with uncontrolled asthma symptoms despite treatment with high-dose ICSs (at least 750 µg fluticasone propionate per day or equivalent) and LABAs (at least 100 µg salmeterol per day or equivalent), with or without other medications (including oral prednisone, leukotriene modifiers, or theophylline); prebronchodilator forced expiratory volume in 1 second (FEV1 ) ≥ 50% of predicted; demonstrated airway hyperresponsiveness by challenge with methacholine or reversible bronchoconstriction during the prior 12 months; uncontrolled symptoms despite taking maintenance medication; abstinence from smoking for 1 year or greater; and past history of smoking < 10 packs of cigarettes per year. After a 2-week run-in period, subjects were randomized to a control group (n=17) that received continued medical management alone or medical management plus treatment with the Alair Bronchial Thermoplasty System (n=17). The bronchial thermoplasty group received three procedures at least 3 weeks apart (Weeks 0 to 6). During the 16-week phase (Weeks 6 to 22), all subjects remained on a stable dose of steroids followed by a 14-week steroid wean phase (Weeks 22 to 36) when an attempt was made to reduce the dose of oral corticosteroids (or ICSs for subjects not taking the oral medication). Between Weeks 36 to 52, subjects took the reduced dose of steroids.
The primary outcomes of the study measured the rate of adverse events and serious adverse events, the latter defined as any event that was fatal, required hospitalization or prolonged hospitalization, caused substantial immediate risk of death, resulted in permanent or significant disability/incapacity, or required intervention to prevent permanent impairment. A total of 32 of the 34 subjects (94%) completed the study. During the initial treatment period, 4 subjects in the bronchial thermoplasty group experienced 7 serious adverse events requiring hospitalization; none occurred in the control group. In the bronchial thermoplasty group, 2 subjects had five severe respiratory adverse events and 2 subjects in the control group had two severe respiratory adverse events that were medically treated and did not result in hospitalization. In the post-treatment period, 3 subjects in the bronchial thermoplasty group experienced five serious adverse events and 1 subject in the control group experienced four serious adverse events; all of these events required hospitalization. The investigators noted this difference was not statistically significant (p=0.32).
The investigators also reported a number of efficacy variables as secondary outcomes. At the end of the study (Week 52), bronchial thermoplasty subjects had a significantly greater improvement in beta-agonist use than control subjects (decrease of 26 puffs vs. 6 puffs per week, p<0.05). There were no significant differences between groups in other efficacy variables including morning and evening peak expiratory flow (PEF), symptom scores, number of symptom-free days, improvement in FEV1 predicted and several quality of life measures. The authors stated:
In considering the potential long-term role for bronchial thermoplasty in the treatment of severe asthma, the increased short-term risk of procedure-related adverse events needs to be weighed against the preliminary evidence of improvement in a range of measures of asthma control.
The study was limited in its ability to accurately evaluate the safety of the procedure as it "was a small study with a high potential for placebo effect and there were differences in baseline values, which although not statistically significant, could have influenced the response to treatment" (Pavord, 2007). The investigators concluded that appropriately powered studies with blinded sham treatment are critical in order to interpret the real risk-benefit balance of the bronchial thermoplasty procedure in the treatment of adults with symptomatic, severe asthma.
Asthma Intervention Research (AIR) Trial
Cox and colleagues (2007) evaluated the effect of bronchial thermoplasty on the control of moderate or severe persistent asthma in adults (ages 18-65): requiring daily therapy with ICSs to maintain reasonable asthma control (equivalent to a dose of 200 µg or more of beclomethasone) and LABAs (at a dose of 100 µg or more of salmeterol or the equivalent); an FEV1 of 60% to 85% of the predicted value; airway hyperresponsiveness and stable asthma in the 6 weeks before enrollment; no current respiratory infection; and not more than two lower respiratory infections requiring treatment in the past year. An additional criterion was worsening asthma control during a 2-week baseline test period during which time LABAs were withheld. A total of 112 individuals met eligibility following the baseline test phase and were randomized to receive medical management with ICSs and LABAs (n=56) or the same medical management strategy plus bronchial thermoplasty (3 sessions approximately 3 weeks apart, n=56). After follow-up visits at 3, 6, and 12 months, there was a 2-week period of abstinence from LABAs, during which time data on exacerbations were collected. Between data collection periods, subjects could use all maintenance therapies. The primary outcome was the difference between the 2 groups in the change in the rate of mild exacerbations between the baseline and the 2-week abstinence period. An exacerbation was defined as the occurrence on 2 consecutive days of a reduction in the morning PEF of at least 20% below the average value (recorded during the week before the abstinence period), the need for more than three additional puffs of rescue medication compared to the week before the abstinence period or nocturnal awakening caused by asthma symptoms. The study was powered to detect a difference between groups of eight mild exacerbations per subject per year. Data was available at 3 months for 100 of 112 subjects (89%) and at 12 months for 101 subjects (90%). All subjects were included in the safety analysis.
The mean rate of mild exacerbations, as compared with baseline, was reduced in the bronchial thermoplasty group but was unchanged in the control group (change in frequency per subject per week, -0.16 ± 0.37 vs. 0.04 ± 0.29, p=0.005). At 12 months, there were significantly greater improvements in the bronchial thermoplasty group than in the control group in the morning PEF (39.3 ± 48.7 vs. 8.5 ± 44.2 liters per minute).
Changes in secondary outcomes included airflow, airway hyperresponsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) in subjects receiving usual care at 3 months and when LABAs were withdrawn at 3, 6, and 12 months. At 12 months, values for airway responsiveness and FEV1 did not differ significantly between the two groups. There were significantly greater improvements in the bronchial thermoplasty group than in the control group in scores on the AQLQ (1.3 ± 1.0 vs. 0.6 ± 1.1) and ACQ (reduction, 1.2 ± 1.0 vs. 0.5 ± 1.0), the percentage of symptom-free days (40.6 ± 39.7 vs. 17.0 ± 37.9), and symptom scores (reduction, 1.9 ± 2.1 vs. 0.7 ± 2.5). In addition, the bronchial thermoplasty group required fewer puffs of rescue medication.
The rate of adverse events was higher in the bronchial thermoplasty group during the active treatment period, but the proportion of adverse events was similar in the two groups in the post-treatment period. Post-treatment, 3 subjects in the bronchial thermoplasty group required hospitalization and 2 subjects in the control group required a total of three hospitalizations. A limitation of the study is the lack of a sham intervention and consequently, an inability to blind subjects to the treatment group.
Asthma Intervention Research 2 (AIR2) Trial
Castro and colleagues (2010) conducted a randomized, double-blind, sham-controlled trial at 30 sites in 6 countries including the United States. Eligibility criteria in the AIR2 trial were similar to those in the AIR trial; key differences were that a higher initial dose of ICSs was required (equivalent to at least 1000 µg beclomethasone) and subjects were required to have experienced at least 2 days of asthma symptoms during the 4-week baseline period and have a baseline score on the AQLQ of no more than 6.25 (possible range of the AQLQ score is 1 to 7, with a higher number representing a better quality of life). Also different from the AIR trial, subjects were not required to experience worsening symptoms during a period of abstinence from LABAs. Subjects were on stable maintenance asthma medications for at least 4 weeks before entry and continued their medication regimen during the study. The primary outcome was the difference between groups in the change from baseline in the AQLQ score, with scores from the 6-, 9-, and 12-month follow-ups averaged (integrated AQLQ score). A related outcome was the proportion of subjects who achieved a change in their AQLQ score of 0.5 or greater, generally considered the minimally important difference for this scale. All endpoints were analyzed using Bayesian statistics. The target posterior probability of superiority (PPS) of bronchial thermoplasty over sham was 95%, except for the primary AQLQ endpoint, where in that instance, the target was 96.4% to adjust for two interim reviews of the data.
A total of 297 individuals were randomized, 196 to a bronchial thermoplasty group and 101 to a sham control group. The intervention for all subjects consisted of three bronchoscopy procedures, performed 3 weeks apart. Subjects and outcome assessment were blinded, but the intervention team was unblinded. The sham intervention was identical to the active treatment except that no radiofrequency energy was delivered. A total of 9 subjects withdrew consent before beginning treatment and 288 subjects underwent bronchoscopy and were included in the intention to treat (ITT) population. A total of 185 subjects in the treatment group and 97 subjects in the sham control group attended the second bronchoscopy and the same numbers of subjects had the third bronchoscopy (it is not clear whether these were exactly the same subjects). A total of 278 out of the 297 enrolled subjects (94%) completed the 12-month visit, 181 subjects in the treatment group and 97 subjects in the sham control group.
In the ITT population, the mean change in the integrated AQLQ score (the primary effectiveness outcome) was 1.35 (standard deviation [sd]=1.10) in the bronchial thermoplasty group and 1.16 (sd=1.23) in the sham control group. Using Bayesian analysis, the PPS was 96% which did not surpass the target PPS of 96.4%. However, in the ITT population, the percentage of subjects achieving an AQLQ score change of 0.5 or greater (the minimally important difference) was 79% in the bronchial thermoplasty group and 64% in the control group. The PPS of 99.6% surpassed the target probability for secondary outcomes of 95%. Additional analysis of data from the active treatment group suggests that responders (defined as a change in AQLQ score of at least 0.5) were more likely to have a lower baseline score than non-responders (mean of 4.1 compared to 5.1, respectively). Several secondary outcomes favored bronchial thermoplasty over the sham control group. These include a reduction in the proportion of subjects reporting asthma worsening during follow-up (27.3% compared to 42.9%, respectively; PPS, 99.7%) and a reduction in the number of emergency room visits (0.07 compared to 0.43 visits per subject per year, respectively; PPS, 99.9%). Moreover, there was a reduction in severe exacerbations of 0.47 per subject per year in the bronchial thermoplasty group compared to 0.70 per subject per year in the control group (PPS, 95.5%). There was no significant difference between groups in other secondary efficacy outcomes including morning PEF, number of symptom-free days, symptom score and rescue medication use.
Safety outcomes reported during the treatment phase included a higher rate of respiratory adverse events in the active treatment group (85% of subjects, mean of 1 event per bronchoscopy) compared to the sham group (76% of subjects, mean of 0.7 events per bronchoscopy). A total of 16 subjects (8.4%) in the active treatment group required 19 hospitalizations for respiratory symptoms during the treatment phase compared to 2 subjects (2%) in the sham group who required 1 hospitalization each. However, during the post-treatment period, 70% of subjects in the bronchial thermoplasty group and 80% of subjects in the sham group reported adverse respiratory events. During this phase of the study, 5 subjects (2.6%) in the bronchial thermoplasty group had a total of 6 hospitalizations for respiratory symptoms and 4 subjects (4.1%) in the sham group had 12 hospitalizations (1 subject had 9 hospitalizations). In the AIR2 study, the sham group had a relatively high rate of response, in that 69% experienced a clinically significant increase in the AQLQ. Blinding appeared to be initially successful and remained so for the sham group. After the first bronchoscopy, subjects in both groups were unable to correctly guess their treatment group. During subsequent assessments, this continued among subjects in the sham group, whereas in the bronchial thermoplasty group, a larger proportion guessed correctly.
Long-term Safety and Effectiveness
Thomson and colleagues (2011) described safety and effectiveness outcomes up to 5 years after bronchial thermoplasty from a subset of AIR trial participants with moderate to severe asthma. Participants were assessed for adverse events and spirometric stability. The authors concluded there was no evidence of clinical complications (based on adverse event reporting) and maintenance of stable lung function (no deterioration of FVC and FEV1 ). However, the study had significant methodological limitations. The subset of participants followed were self-selected volunteers which represented only a small number of the actual treatment group. Thus, it is not possible to conclude that bronchial thermoplasty demonstrates long term safety; rather, it is appropriate to conclude that, in this small cohort, there was no increase in adverse events. It is also unclear whether the bronchial thermoplasty had any lasting effect or whether a single bronchial thermoplasty treatment would be effective for such an extended period of time. The method of collecting adverse events was unconventional. The authors used one method of collecting and reporting adverse events for the first year and a different method for subsequent years. In addition, controls were only followed for 3 years and in the active treatment group, there were a number of individuals lost to follow-up. After Year 1, adverse events were based in part on subject recollection, and were therefore subject to recall bias. Last, the data was limited to records available at the authors' institutions; there was a lack of data collection from other facilities including emergency department visits and hospitalizations.
Castro and colleagues (2011) evaluated the durability of bronchial thermoplasty beyond 1 year in subjects who participated in the follow-up phase of the AIR2 trial. This posttreatment observational study compared the percentage of subjects who experienced severe exacerbations, respiratory adverse events, stability of pre- and post-bronchodilator FEV1 , or healthcare utilization including emergency department admissions and respiratory-related hospitalizations during Year 1 (n=181) and Year 2 (n=166) after bronchial thermoplasty treatment. The authors concluded that the percentage of bronchial thermoplasty subjects experiencing severe exacerbations, defined as those requiring treatment with oral or intravenous corticosteroid, or a doubling of the baseline IHC dose for at least 3 days, or any temporary increase in the dosage of oral corticosteroids for a subject taking maintenance oral corticosteroids at entry into the AIR2 trial, were comparable between Years 1 and 2, at 30.9 and 23.0, respectively. The percentage of subjects reporting emergency department visits was 5 (9 subjects) at Year 1 and 6.6 (11 subjects) at Year 2. The percentage of subjects reporting respiratory-related hospitalizations was comparable for subjects at Year 1 and Year 2 in the posttreatment group at 3.3 (n=6) and 4.2 (n=7), respectively. Methodological limitations of this study include lack of a comparable sham-controlled group beyond Year 1, as subjects in the sham-control group in the AIR2 trial exited from the study at 1-year post bronchial thermoplasty. In addition, 15 of the 166 subjects (9.0%) did not complete the Year 2 evaluation. Finally, adverse event reporting for bronchial thermoplasty treated individuals was subject to recall bias as data was collected from quarterly telephone calls and during an annual in-office evaluation.
Pavord and colleagues (2013) evaluated the 5-year safety data on 14 of the 17 (82%) subjects randomized to the bronchial thermoplasty group in the RISA study. All 14 subjects completed the 3-year evaluation and 12 participants completed evaluations at 4 and 5 years. In Year 1 of the study, each asthma symptom was considered an adverse event and in subsequent years, multiple asthma symptoms were considered to be a single adverse event. For those with available follow-up data, 5 (36%), 7 (50%), 2 (17%) and 5 (42%) subjects experienced asthma adverse events in Years 2, 3, 4 and 5, respectively. A total of 11 respiratory-related hospitalizations in 5 subjects were reported during Years 2 to 5 after bronchial thermoplasty. Measures of lung function showed no deterioration for 5 years. The number of subjects with data available was too small to draw meaningful conclusions concerning the long-term safety of bronchial thermoplasty. In addition, no long-term data were available on subjects in the control group.
Wechsler and colleagues (2013) reported 5-year safety and effectiveness data on 162 (85.3%) of 190 bronchial thermoplasty-treated subjects from the AIR2 study. Matched-pairs analysis comparing the 162 subjects completing the Year 5 evaluations with the same group in previous years showed a similar proportion of subjects having a severe exacerbation in Years 1, 2, 3, 4 and 5, that is, 30.9%, 23.5%, 34.0%, 36.4% and 21.6%, respectively. The proportion of subjects experiencing severe exacerbations in Years 2, 3, 4 and 5 did not differ significantly from the number of exacerbations in Year 1. The proportion of subjects who experienced any asthma adverse events (multiple symptoms) were 28.7%, 27.9%, 29.6%, 31.4% and 24.7%, respectively. In the 12 months before bronchial thermoplasty, the rate of hospitalization for respiratory symptoms in this group was 4.2%. Limitations of this study include lack of follow-up data collected on subjects randomized to the sham group beyond 1 year; therefore, outcomes such as rate of exacerbations and hospitalizations cannot be compared in subjects who did and did not receive bronchial thermoplasty.
To date, three industry-sponsored RCTs on bronchial thermoplasty have been published in the peer-reviewed medical literature. The largest RCT with the most rigorous methodology was the AIR2 trial, the only published double-blind, sham-controlled trial with sites in the United States. Over 1 year, bronchial thermoplasty was not found to be superior to sham treatment on the investigator-designated primary efficacy outcome, a mean change in quality of life score, but was found to be superior on a related outcome, an improvement in quality of life of at least 0.5 points on the AQLQ scale. The high rate of response in the sham group of the AIR2 suggests a large placebo effect, particularly for subjective outcomes such as quality of life which calls into question conclusions about efficacy in the earlier trials that did not have a sham control. In the AIR2 trial, bronchial thermoplasty provided benefit in terms of quality of life and some, but not all, secondary outcomes. Therefore, it is unclear which individuals are most likely to respond to bronchial thermoplasty. Data from the AIR2 trial suggests that those with more severe asthma may experience the greatest improvement. In the AIR and RISA trials, improvements were reported in quality of life for the bronchial thermoplasty group. However, given the lack of benefit in the AIR2 trial, it is possible that the differences in quality of life for these other trials were due to placebo effect.
Three-year comparative data published from the AIR trial reporting rates of hospitalizations and respiratory adverse events did not differ significantly in the groups that received bronchial thermoplasty versus medication in Years 2 and 3. Data up to 5 years in the bronchial thermoplasty group did not suggest delayed complications. For the sham-controlled AIR2 trial, 2-year follow-up data are available, but only for bronchial thermoplasty group. In Year 2, subjects did not experience an increase in severe exacerbations or asthma adverse events compared to Year 1.
Adverse events reported from the three trials suggest that bronchial thermoplasty is associated with a relatively high rate of adverse events including hospitalizations during the treatment period, but not in the post-treatment period. Safety data up to 5 years have been reported for the subjects treated with bronchial thermoplasty in the RCTs but not for control subjects. Rates of adverse events in Years 2 to 5 were similar to those in the first year following treatment. The uncertain degree of benefit and presence of substantial adverse events suggests a significant degree of uncertainty exists concerning the potential of bronchial thermoplasty to improve net health outcomes. In addition, it is not possible to determine which individuals receive the most benefit as there is a lack of data on selection factors for appropriate candidates for bronchial thermoplasty.
In a Cochrane review, Torrego and colleagues (2014) performed a pooled analysis of the three RCTs (429 participants) comparing bronchial thermoplasty to any active control in adults with moderate or severe asthma. The primary outcomes evaluated quality of life, asthma exacerbations and adverse events. The authors concluded that bronchial thermoplasty provided a modest clinical benefit in quality of life and lower rates of asthma exacerbation, but no significant difference in asthma control scores. The quality of life findings, however, are at risk of bias, as the main benefits were seen in the two studies that did not include a sham treatment arm. Bronchial thermoplasty had a reasonable safety profile after completion of the bronchoscopies, despite the increased risk of adverse events during treatment. The overall quality of evidence regarding bronchial thermoplasty was "moderate." The authors recommend systematically collecting data from individuals in independent clinical registries and performing further research to "provide a better understanding of the mechanisms of action of bronchial thermoplasty, as well as its effect in different asthma phenotypes or in patients with worse lung function."
Zhou and colleagues (2016) performed a systematic review and meta-analysis of the literature on the long-term efficacy and safety of bronchial thermoplasty in individuals with moderate to severe asthma. Three RCTs and extension studies met the inclusion criteria (n=6). The authors pooled data on the long-term effects in bronchial thermoplasty-treated individuals (n=216, those not in comparison groups) with 5 years of follow-up. No significant decline was found in spirometry-detected prebronchodilator FEV1 (percent predicted) compared with 1 year findings (weighted mean difference [WMD], 0.75; 95% CI, -3.36 to 1.85; p=0.57). Similarly, there was no significant decline in postbronchodilator FEV1 (WMD=0.62; 95% CI, -3.32 to 2.08; p=0.65). The rates of respiratory adverse events and emergency department visits for adverse events and hospitalizations did not differ significantly after the 1- and 5-year follow-ups. There are several limits to this review, in that almost all of the studies included in the meta-analysis did not have a control group (sham treatment group) for the 5-year follow-up. In addition, the current studies are based only on clinical manifestations and outcomes. It was suggested by the authors that histological assessment after bronchial thermoplasty treatment could provide more evidence to support their findings.
Pretolani and colleagues (2017) examined the effect of bronchial thermoplasty on bronchial structures and explored the association with clinical outcomes in individuals who met the American Thoracic Society/European Respiratory Society criteria for severe, refractory asthma. Ten of 15 individuals met the criteria for receiving omalizumab for 6 months before entry into the study protocol without successful clinical outcome. For these participants, omalizumab was discontinued at least 6 months prior to the first bronchial thermoplasty procedure. All 15 participants underwent three sessions of bronchial thermoplasty separated by 1-month intervals. The pre-specified primary outcome was a reduction in airway smooth muscle (ASM) surface area at 3 months. A total of 300 bronchial biopsy specimens were collected (from 15 participants) from 4 different lobes of the lungs (n=3, right lower lobe; n=2, each upper lobe; n=2, middle lobe; n=3, left lower lobe) 15 days before the first bronchial thermoplasty procedure and 3 months after the last bronchial thermoplasty procedure. Immunostained sections were assessed for ASM area, subepithelial basement membrane (SBM) thickness, nerve fibers, and epithelial neuroendocrine cells. Clinical and airway functional parameters were examined prior to and 3 and 12 months after bronchial thermoplasty. Histopathologic findings were correlated with clinical parameters. At the pre-specified intervals, all participants underwent assessment of FEV1 and forced vital capacity (FVC) before and after inhalation of 400 mg of salbutamol. Asthma Control Test (ACT) (response scale, 1-25) and AQLQ (response scale, 1-7) scores, the number of exacerbations, hospitalizations for asthma and intensive care unit (ICU) visits, emergency department visits, and treatments were recorded throughout the study. A total of 6 of 15 (40%) bronchial thermoplasty-treated participants still experienced uncontrolled asthma at 3 months; however, the investigators reported overall significantly higher scores on the ACT and AQLQ (p<0.001 for both comparisons) and a lower number of severe exacerbations (p<0.001), visits to the emergency department (p<0.001), hospitalization for asthma (p<0.01), and ICU visits (p<0.001) than those measured before bronchial thermoplasty. A significant decrease in the number of exacerbations (p<0.001), hospitalizations for asthma (p<0.001), ICU visits (p=0.008), and emergency department visits (p<0 .001) and an increase in ACT and AQLQ scores (p<0.001, both comparisons) were observed at 12 months compared with values obtained before bronchial thermoplasty. At 12 months, 8 of 10 (80%) participants still required regular oral corticosteroids with a mean daily dose of oral prednisone significantly lower compared with that administered at study onset (13.8 vs. 31.5 mg/d, 12 months after compared with before bronchial thermoplasty; p=0.002). In addition, at 12 months after bronchial thermoplasty, 4 of 15 (27%) participants continued to experience symptoms of uncontrolled asthma (mean ACT score of 7.8; AQLQ score of 2.4). Participants were considered unresponsive to bronchial thermoplasty when ACT scores at 3 and 12 months after the procedures remained lower than 15. Bronchial thermoplasty was not associated with changes in subepithelial mucous glands, blood eosinophil and neutrophil counts at 3 and 12 months after bronchial thermoplasty. Neither the proportion of regenerating bronchial epithelium or normal stratified columnar, metaplastic, or squamous epithelium nor goblet cell hypertrophy/hyperplasia were modified by bronchial thermoplasty. The relationship between the components of airway remodeling that were altered 3 months after bronchial thermoplasty and clinical parameters measured at 3 and 12 months were reported as follows: 3 months after bronchial thermoplasty, ASM correlated significantly with ACT scores (p=0.003) and numbers of severe exacerbations (p<0.001), emergency department visits (p=0.003), and hospitalizations for asthma (p=0.03). Similar associations were reported when considering submucosal and ASM-associated nerves and numbers of epithelial neuroendocrine cells, whereas SBM thickening correlated exclusively with ACT scores. These correlations were prospectively analyzed and reported as maintained at 12 months. However, the histopathologic parameters investigated did not correlate with pulmonary function tests of prebronchodilator and postbronchodilator FEV1 , FVC, and FEV1 /FVC ratio at 3 months. Limitations of this study include lack of a sham control group; thus, it cannot be ruled out that participants were more adherent to treatments while undergoing bronchial thermoplasty compared with the 12 months before study enrollment. It was reported that autonomic nerve fibers, both in the bronchial submucosa and within the ASM bundles, were drastically decreased 3 months after bronchial thermoplasty, and this reduction was significantly associated with the decrease in the number of severe exacerbations. The investigators suggested that damage of autonomic-innervated structures induced by bronchial thermoplasty downregulated airway excitability and thus improved asthma control; however, "whether these airway structural abnormalities need to be downregulated simultaneously by bronchial thermoplasty to deliver a therapeutic advantage remains to be answered." Finally, as favorable clinical outcomes after bronchial thermoplasty were inconsistent in 4 of the 15 participants, additional study is needed to determine which individuals with severe asthma may respond to bronchial thermoplasty, and what the relationship is to both long-term clinical and histopathologic corrections of benefit to treatment with the procedure.
The Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA, 2017) has evaluated the evidence on bronchial thermoplasty. For management of individuals with severe, uncontrolled asthma, that is "persistent symptoms or exacerbation despite correct inhaler technique and good adherence with treatment and in whom other controller options have been considered," higher level care and/or add-on treatment is required. The preferred option is referral to a specialist with expertise in management of severe asthma (Evidence D). Treatment options that may be considered (if not already tried) include bronchial thermoplasty. The current GINA recommendation concerning bronchial thermoplasty states:
Add-on treatment with bronchial thermoplasty: may be considered for some adult patients with severe asthma (Chung, 2015) (Evidence B). Evidence is limited and in selected patients. The long term effects compared with control patients, including in lung function, are not known.
As a non-pharmacological intervention, GINA's advice/recommendation states:
The American College of Chest Physicians (CHEST™, 2014) has issued a position statement for bronchial thermoplasty stating:
Based on the strength of the clinical evidence, bronchial thermoplasty offers an important treatment option for adult patients with severe asthma who continue to be symptomatic despite maximal medical treatment and, therefore should not be considered experimental. Randomized controlled clinical trials of bronchial thermoplasty for severe asthma have shown a reduction in the rate of severe exacerbations, emergency department visits, and days lost from school or work.
The position statement references the 5-year follow-up data from the AIR2 study (Wechsler, 2013), stating the reported outcomes further demonstrate the "safety, effectiveness, and durability" of bronchial thermoplasty.
A joint task force of the European Respiratory Society/American Thoracic Society (Chung, 2014) has published guidelines on the definition, evaluation and treatment of severe asthma, stating:
We recommend that bronchial thermoplasty is performed in adults with severe asthma only in the context of an Institutional Review Board approved independent systematic registry of a clinical study…This is a strong recommendation, because of the very low confidence in the available estimates of effects of bronchial thermoplasty in patients with severe asthma. Both potential benefits and harms may be large and the long-term consequences of this new approach to asthma therapy utilizing an invasive physical intervention are unknown. Specifically designed studies are needed to define its effects on relevant objective primary outcomes such as exacerbation rates, and on long-term effect on lung function.
Description, Prevalence, and Pharmacologic Treatment of Asthma
According to the Centers for Disease Control and Prevention (CDC, 2017), asthma affected approximately 7.6% of adults and 8.4% of children in the United States in 2015. Asthma is a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation. The airway hyperresponsiveness is reversible either spontaneously or through therapy. Symptoms include wheezing, cough, and dyspnea, which can vary widely in severity and duration, although a typical attack does not last for more than several hours. The onset of asthma for most individuals begins early in life with the pattern of disease persistence determined by early, recognizable risk factors including atopic disease, recurrent wheezing, and a parental history of asthma (Akinbami, 2012). In some individuals, persistent changes in airway structure occur, including sub-basement fibrosis, mucus hypersecretion, injury to epithelial cells, and smooth muscle hypertrophy (NAEPP, 2007). Attacks can be triggered by a number of factors, including allergic triggers, smoke and pollution, cold air, colds and other respiratory infections, exercise, and strong emotions.
Guidelines from the National Heart, Lung and Blood Institute (NHLBI) (National Institutes of Health [NIH]) define 6 pharmacologic steps for treatment of intermittent asthma (Step 1), and persistent asthma (Steps 2-6):
Step 1: Short-acting beta-agonists (such as albuterol) as needed;
Step 2: Low-dose ICS;
Step 3: ICS and LABA or medium-dose ICS;
Step 4: Medium dose ICS and LABA;
Step 5: High-dose ICS and LABA; and
Step 6: High dose ICS and LABA, and oral corticosteroids.
In 2007, the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma was issued with: 1) a new focus on monitoring asthma control as the goal for asthma therapy and distinguishing between classifying asthma severity and monitoring asthma control; and 2) a new focus on impairment and risk as the two key domains of severity and control, and multiple measures for assessment. According to this NAEPP document, based on symptoms, the classification of asthma severity for severe persistent and moderate persistent asthma for individuals who are not currently taking long-term control medications is as follows:
Description of Bronchial Thermoplasty
The Alair System is the first medical device using radiofrequency energy to treat severe and persistent asthma in certain adults. The Alair System is a tool used to perform bronchial thermoplasty, a procedure indicated for the treatment of severe persistent asthma in individuals 18 years of age and older whose asthma is not well controlled with ICSs and LABAs. The device is composed of a catheter with an electrode tip that delivers a form of electromagnetic energy (radiofrequency energy) directly to the airways, resulting in a prolonged reduction in airway smooth muscle (ASM) mass. A controller unit generates and controls the energy. The treatment is performed in the outpatient setting (as a minimally invasive procedure) during a series of bronchoscopy procedures scheduled at least 3 weeks apart. The catheter is inserted through a bronchoscope with the individual under conscious sedation. The catheter is first positioned in the most distal targeted airway and the electrode array is extended. Once the array basket is in contact with the airway wall, radiofrequency energy is delivered through the catheter to heat tissue to 65°C over the 5 millimeter area of exposed (uninsulated) electrode wire. Complete treatment of any given airway requires delivery of radiofrequency energy along the entire accessible length of the airway, so the catheter must be repositioned and the electrode redeployed several times. The procedure takes approximately 1 hour to complete. Use of the treatment is contraindicated in individuals with implantable devices and those with sensitivities to lidocaine, atropine or benzodiazepines. It should also not be used while individuals are experiencing an asthma exacerbation, active respiratory infection, bleeding disorder, or within 2 weeks of making changes in their corticosteroid regimen. The same area of the lung should not be treated more than once with bronchial thermoplasty.
Asthma Quality of Life Questionnaire (AQLQ): A 32-item disease-specific questionnaire used to reflect areas of function important to adults with asthma; available in both interviewer- and self-administered forms. The 4 domains measured by the AQLQ include activity limitations, emotional function, exposure to environmental stimuli, and symptoms.
Dyspnea: Shortness of breath; subjective difficulty or distress in breathing.
Forced expiratory volume in 1 second (FEV1 ): A measure of airway obstruction determined using spirometry; individual FEV1 values are compared to predicted values based on age, height, sex and race.
Hyperresponsiveness: Also referred to as the early phase of asthma, when the airways of the lungs get smaller when exposed to certain allergens or environmental triggers, making it more difficult to breathe.
Inflammatory response: Also referred to as the late phase of asthma. Swelling and irritation of the lining of the lung that can cause bronchoconstriction and increased mucus that leads to asthma symptoms.
Inhaled corticosteroid(s) (ICS or ICSs): A class of medications also referred to as inhaled steroids; used for the treatment of asthma and chronic obstructive pulmonary disease (COPD). A potent anti-inflammatory medication that improves asthma control more effectively than any other agent used as a single treatment; helps to prevent chronic asthma symptoms such as wheezing, chest tightness, shortness of breath, and chronic cough.
Long-acting beta-agonist(s) (LABA or LABAs): Also referred to as long-acting beta2 -adrenergic agonists. A type of bronchodilator whose effects last for 12 hours or more when used as adjunctive treatment for the prevention of asthma symptoms such as wheezing, chest tightness, shortness of breath, and cough; improves asthma symptoms by increasing airflow through the lungs.
Peak expiratory flow (PEF): Often described as a percent of personal best measurement; personal best PEF is the highest PEF value attained after 2 to 3 weeks of testing when asthma is in good control.
Radiofrequency (RF) energy: Energy that travels as radio waves; electrical energy used in medical procedures for sculpting, shrinking or removing soft-tissue.
The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.
When services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.
|31660||Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with bronchial thermoplasty, 1 lobe|
|31661||Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with bronchial thermoplasty, 2 or more lobes|
When services are also Investigational and Not Medically Necessary:
|0B538ZZ||Destruction of right main bronchus, via natural or artificial opening endoscopic|
|0B548ZZ||Destruction of right upper lobe bronchus, via natural or artificial opening endoscopic|
|0B558ZZ||Destruction of right middle lobe bronchus, via natural or artificial opening endoscopic|
|0B568ZZ||Destruction of right lower lobe bronchus, via natural or artificial opening endoscopic|
|0B578ZZ||Destruction of left main bronchus, via natural or artificial opening endoscopic|
|0B588ZZ||Destruction of left upper lobe bronchus, via natural or artificial opening endoscopic|
|0B598ZZ||Destruction of lingula bronchus, via natural or artificial opening endoscopic|
|0B5B8ZZ||Destruction of left lower lobe bronchus, via natural or artificial opening endoscopic|
Peer Reviewed Publications:
Government Agency, Medical Society, and Other Authoritative Publications:
|Websites for Additional Information|
Alair Bronchial Thermoplasty System
The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.
|Reviewed||08/03/2017||Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Rationale, Background, References, and Websites for Additional Information sections.|
|Reviewed||08/04/2016||MPTAC review. Updated Description, Rationale, Background, References, and Websites for Additional Information sections. Removed ICD-9 codes from Coding section.|
|Reviewed||08/06/2015||MPTAC review. Updated Rationale, References, and Websites for Additional Information sections.|
|Reviewed||08/14/2014||MPTAC review. Updated Description, Rationale, Background, References, and Websites for Additional Information sections.|
|Reviewed||08/08/2013||MPTAC review. Updated Rationale, References, and Websites for Additional Information sections.|
|01/01/2013||Updated Coding section with 01/01/2013 CPT changes; removed 0276T, 0277T deleted 12/31/2012.|
|Reviewed||08/09/2012||MPTAC review. Updated Description, Rationale, Background/Overview, References, Websites for Additional Information and Index.|
|01/01/2012||Updated Coding section with 01/01/2012 CPT and HCPCS changes; removed codes C9730, C9731 deleted 12/31/2011.|
|Reviewed||08/18/2011||MPTAC review. Updated Rationale and References.|
|07/01/2011||Updated Coding section with 07/01/2011 HCPCS changes|
|New||08/19/2010||MPTAC review. Initial document development.|