Adalberto S. Rubin

Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial.

RATIONALE Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle. OBJECTIVES To evaluate the effectiveness and safety of BT versus a sham procedure in subjects with severe asthma who remain symptomatic despite treatment with high-dose inhaled corticosteroids and long-acting beta(2)-agonists. METHODS A total of 288 adult subjects (Intent-to-Treat [ITT]) randomized to BT or sham control underwent three bronchoscopy procedures. Primary outcome was the difference in Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to average of 6, 9, and 12 months (integrated AQLQ). Adverse events and health care use were collected to assess safety. Statistical design and analysis of the primary endpoint was Bayesian. Target posterior probability of superiority (PPS) of BT over sham was 95%, except for the primary endpoint (96.4%). MEASUREMENTS AND MAIN RESULTS The improvement from baseline in the integrated AQLQ score was superior in the BT group compared with sham (BT, 1.35 +/- 1.10; sham, 1.16 +/- 1.23 [PPS, 96.0% ITT and 97.9% per protocol]). Seventy-nine percent of BT and 64% of sham subjects achieved changes in AQLQ of 0.5 or greater (PPS, 99.6%). Six percent more BT subjects were hospitalized in the treatment period (up to 6 wk after BT). In the posttreatment period (6-52 wk after BT), the BT group experienced fewer severe exacerbations, emergency department (ED) visits, and days missed from work/school compared with the sham group (PPS, 95.5, 99.9, and 99.3%, respectively). CONCLUSIONS BT in subjects with severe asthma improves asthma-specific quality of life with a reduction in severe exacerbations and healthcare use in the posttreatment period. Clinical trial registered with www.clinialtrials.gov (NCT00231114).

Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma

BACKGROUND Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. OBJECTIVE We sought to assess the effectiveness and safety of BT in asthmatic patients 5 years after therapy. METHODS BT-treated subjects from the Asthma Intervention Research 2 trial (ClinicalTrials.govNCT01350414) were evaluated annually for 5 years to assess the long-term safety of BT and the durability of its treatment effect. Outcomes assessed after BT included severe exacerbations, adverse events, health care use, spirometric data, and high-resolution computed tomographic scans. RESULTS One hundred sixty-two (85.3%) of 190 BT-treated subjects from the Asthma Intervention Research 2 trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and emergency department (ED) visits and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months before BT treatment (average 5-year reduction in proportions: 44% for exacerbations and 78% for ED visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in years 2 through 5 compared with the first year after BT. Prebronchodilator FEV₁ values remained stable between years 1 and 5 after BT, despite a 18% reduction in average daily inhaled corticosteroid dose. High-resolution computed tomographic scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. CONCLUSIONS These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ED visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking inhaled corticosteroids and long-acting β₂-agonists.

Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial

BackgroundBronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure.MethodsPatients enrolled in the Asthma Intervention Research Trial were on inhaled corticosteroids ≥200 μg beclomethasone or equivalent + long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-β2-agonist withdrawal. Following initial evaluation at 1 year, subjects were invited to participate in a 4 year safety study. Adverse events (AEs) and spirometry data were used to assess long-term safety out to 5 years post-BT.Results45 of 52 treated and 24 of 49 control group subjects participated in long-term follow-up of 5 years and 3 years respectively. The rate of respiratory adverse events (AEs/subject) was stable in years 2 to 5 following BT (1.2, 1.3, 1.2, and 1.1, respectively,). There was no increase in hospitalizations or emergency room visits for respiratory symptoms in Years 2, 3, 4, and 5 compared to Year 1. The FVC and FEV1 values showed no deterioration over the 5 year period in the BT group. Similar results were obtained for the Control group.ConclusionsThe absence of clinical complications (based on AE reporting) and the maintenance of stable lung function (no deterioration of FVC and FEV1) over a 5-year period post-BT in this group of patients with moderate to severe asthma support the long-term safety of the procedure out to 5 years.

Persistence of effectiveness of bronchial thermoplasty in patients with severe asthma

BACKGROUND Bronchial thermoplasty (BT) has been demonstrated to be safe and effective in the treatment of severe persistent asthma out to at least 1 year. Preclinical studies have demonstrated that the reduction in airway smooth muscle after bronchial thermoplasty persists out to at least 3 years. OBJECTIVES To examine the persistence of effectiveness of BT 2 years posttreatment in subjects with severe asthma. METHODS Subjects participating in the long-term safety follow-up phase of the Asthma Intervention Research 2 (AIR2) Trial were evaluated by comparing the proportion of subjects who experienced exacerbations, adverse events, or healthcare utilization during the first year (year 1) after BT treatment with the proportion of subjects who experienced the same during the subsequent 12 months (year 2). RESULTS Severe exacerbations, respiratory adverse events, emergency department visits for respiratory symptoms, and hospitalizations for respiratory symptoms (proportion of subjects experiencing and rates of events), and stability of pre- and post-bronchodilator forced expiratory volume in 1 second (FEV(1)), were comparable between years 1 and 2. The proportion of subjects experiencing severe exacerbations in year 2 after BT was 23.0%, compared with 30.9% in year 1. CONCLUSIONS The reduction in the proportion of subjects experiencing severe exacerbations after BT is maintained for at least 2 years. Bronchial thermoplasty provides beneficial long-term effects on asthma outcomes in patients with severe asthma. TRIAL REGISTRATION clinicaltrials.gov, Identifier: NCT00231114.

Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma

Journal. American J Respir Crit Care Medicine 2010; 181:116–124. Rationale. The treatment of severe asthma has been expanded with the introduction of a recent bronchoscopic procedure entitled bronchial thermoplasty in which controlled heat energy is impacted on the airway wall to produce a decline in smooth muscle. The objectives of the authors was to assess the effectiveness and safety of bronchial thermoplasty versus a sham protocol in individuals with severe asthma who continue to be symptomatic despite conventional therapy with high dose inhaled corticosteroids and long-acting beta agonists. Methods. A total of 288 adult with severe asthma using an intent to treat analysis were randomized to bronchial thermoplasty or sham control. Each subject was evaluated with three bronchoscopic procedures. The primary outcome was the difference in asthma quality-of-life questionnaire scores from baseline to average of 6, 9 and 12 months (integrated AQLQ). Adverse events and health care utilization were determined to evaluate safety. Statistical design and analysis of the primary endpoint was Bayesian. The target posterior probability of superiority of bronchial thermoplasty over sham was 95% except for the primary endpoint (96.4%). Results and outcomes. The amelioration from baseline in the integrated AQLQ score was superior in the bronchial thermoplastic group when compared with sham (bronchial thermoplasty 1.35 plus or −1.10; sham 1.16 plus or −1.23)(PPS, 96% intention to treat and 97.9% per protocol). 79% of the bronchial thermoplasty and 64% of sham subjects developed changes in the AQLQ of 0.5 or greater (PPS, 99.6%). Six percent more of bronchial thermoplasty individuals were hospitalized in the treatment period up to six weeks after bronchial thermoplasty. In the post therapy period, which was 6 to 52 weeks after bronchial thermoplasty, the bronchial thermoplasty group experienced fewer severe exacerbations, ER visits and absence from work or school when compared with the sham group (PPS 95.5, and 99.9 and 99.3% respectively). Conclusions of the authors. Bronchial thermoplasty in individuals with severe asthma ameliorates asthma specific quality of life with a decline in severe exacerbations, in health care utilization in the post treatment period. Reviewers comments. The strengths of the study were the relatively large number of subjects as well as the multicenter, randomized, double blind with sham study design. The findings of the study hold that bronchial thermoplasty provides clinically significant amelioration of severe exacerbations requiring corticosteroids, ED visits and time lost from work and school during the post treatment therapy in individuals with severe asthma or those with inadequately controlled asthma, together with an improvement in quality of life. The authors conclude that increased risk of adverse events in the short-term after bronchial thermoplastic is outweighed by the benefits of bronchial thermoplastic that continues for at least one year. Bronchial thermoplasty provides a novel supplementary procedure that provides additional therapy beyond conventional utilization of high-dose inhaled steroids and long-acting beta agonist to decrease the morbidity from severe asthma. Further large prospective studies randomized with sham are needed to confirm the authors findings. An associated editorial in the same issue indicates that long-term clinical morphologic research in various severe asthma phenotypes is still needed to obtain required information for clinical decisions regarding this procedure.Journal. American J Respir Crit Care Medicine 2010; 181:116–124. Rationale. The treatment of severe asthma has been expanded with the introduction of a recent bronchoscopic procedure entitled bronchial thermoplasty in which controlled heat energy is impacted on the airway wall to produce a decline in smooth muscle. The objectives of the authors was to assess the effectiveness and safety of bronchial thermoplasty versus a sham protocol in individuals with severe asthma who continue to be symptomatic despite conventional therapy with high dose inhaled corticosteroids and long-acting beta agonists. Methods. A total of 288 adult with severe asthma using an intent to treat analysis were randomized to bronchial thermoplasty or sham control. Each subject was evaluated with three bronchoscopic procedures. The primary outcome was the difference in asthma quality-of-life questionnaire scores from baseline to average of 6, 9 and 12 months (integrated AQLQ). Adverse events and health care utilization were determined ...

Asthma and lower airway diseaseBronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma

BACKGROUND Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. OBJECTIVE We sought to assess the effectiveness and safety of BT in asthmatic patients 5 years after therapy. METHODS BT-treated subjects from the Asthma Intervention Research 2 trial (ClinicalTrials.govNCT01350414) were evaluated annually for 5 years to assess the long-term safety of BT and the durability of its treatment effect. Outcomes assessed after BT included severe exacerbations, adverse events, health care use, spirometric data, and high-resolution computed tomographic scans. RESULTS One hundred sixty-two (85.3%) of 190 BT-treated subjects from the Asthma Intervention Research 2 trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and emergency department (ED) visits and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months before BT treatment (average 5-year reduction in proportions: 44% for exacerbations and 78% for ED visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in years 2 through 5 compared with the first year after BT. Prebronchodilator FEV₁ values remained stable between years 1 and 5 after BT, despite a 18% reduction in average daily inhaled corticosteroid dose. High-resolution computed tomographic scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. CONCLUSIONS These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ED visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking inhaled corticosteroids and long-acting β₂-agonists.

Long term safety and effectiveness in patients with severe persistent asthma.

BACKGROUND Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. OBJECTIVE We sought to assess the effectiveness and safety of BT in asthmatic patients 5 years after therapy. METHODS BT-treated subjects from the Asthma Intervention Research 2 trial (ClinicalTrials.govNCT01350414) were evaluated annually for 5 years to assess the long-term safety of BT and the durability of its treatment effect. Outcomes assessed after BT included severe exacerbations, adverse events, health care use, spirometric data, and high-resolution computed tomographic scans. RESULTS One hundred sixty-two (85.3%) of 190 BT-treated subjects from the Asthma Intervention Research 2 trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and emergency department (ED) visits and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months before BT treatment (average 5-year reduction in proportions: 44% for exacerbations and 78% for ED visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in years 2 through 5 compared with the first year after BT. Prebronchodilator FEV₁ values remained stable between years 1 and 5 after BT, despite a 18% reduction in average daily inhaled corticosteroid dose. High-resolution computed tomographic scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. CONCLUSIONS These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ED visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking inhaled corticosteroids and long-acting β₂-agonists.