Bronchial 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.
Patients 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.
45 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.
The 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.
Asthmatic exacerbations result in part from constriction of airway smooth muscle. In this controlled trial, the use of bronchoscopically delivered thermoplasty to reduce the mass of airway smooth ...muscle resulted in fewer exacerbations among subjects with moderate or severe asthma. The incidence of adverse events was higher among subjects undergoing bronchial thermoplasty than among control subjects during the first 3 weeks after treatment.
The use of bronchoscopically delivered thermoplasty to reduce the mass of airway smooth muscle resulted in fewer exacerbations among subjects with moderate or severe asthma.
Many of the variable symptoms of asthma are thought to be due to the contraction of airway smooth muscle, leading to bronchoconstriction.
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Increased airway smooth-muscle mass is a characteristic feature of asthma, particularly in persons with severe or fatal asthma.
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Bronchial thermoplasty is a novel intervention in which controlled thermal energy is delivered to the airway wall during a series of bronchoscopies, resulting in a prolonged reduction of airway smooth-muscle mass.
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In previous studies, we determined the amount and duration of energy to be delivered that result in modest thermal injury.
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The treatment in humans of airways . . .
Bronchial thermoplasty (BT) is designed to reduce airway smooth muscle and improve asthma control.
This study was conducted to determine the safety and efficacy of this procedure in subjects with ...symptomatic, severe asthma.
Adults who were symptomatic despite treatment with fluticasone or equivalent at more than 750 mug/day, a long-acting beta(2)-agonist, and other medications, which could include 30 mg or less of oral prednisolone/day, were randomized to BT or to a control group. After treatment, subjects entered a 16-week steroid stable phase (Weeks 6-22), a 14-week steroid wean phase (Weeks 22-36), and a 16-week reduced steroid phase (Weeks 36-52).
BT resulted in a transient worsening of asthma symptoms. Seven hospitalizations for respiratory symptoms occurred in 4 of 15 BT subjects during the treatment period. Five hospitalizations were within 3 days of treatment. Two subjects had segmental collapse involving the most recently treated lobe; one required bronchoscopy and aspiration of a mucus plug. There were no hospitalizations during this period in the 17 control subjects. The rate of hospitalizations was similar in both groups in the post-treatment period. At 22 weeks, BT subjects had significant improvements versus control subjects in rescue medication use (-26.6 +/- 40.1 vs. -1.5 +/- 11.7 puffs/7 d, P < 0.05), prebronchodilator FEV(1)% predicted (14.9 +/- 17.4 vs. -0.94 +/- 22.3%, P = 0.04), and Asthma Control Questionnaire scores (-1.04 +/- 1.03 vs. -0.13 +/- 1.00, P = 0.02). Improvements in rescue medication use and Asthma Control Questionnaire scores remained significantly different from those of controls at 52 weeks.
BT is associated with a short-term increase in asthma-related morbidity. However, there is preliminary evidence of long-lasting improvement in asthma control. Clinical trial registered with www.clinicaltrials.gov (NCT 00214539).
Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle.
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.
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%).
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).
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).
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.gov NCT01350414 ) 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.
The purpose of this study was to evaluate the use of MDCT to assess response to bronchial thermoplasty treatment for severe persistent asthma.
MDCT data from 26 patients with severe persistent asthma ...who underwent imaging before and after bronchial thermoplasty were analyzed retrospectively. Changes in the following parameters were assessed: total lung volume, mean lung density, airway wall thickness, CT air trapping index (attenuation < -856 HU), and expiratory-inspiratory ratio of mean lung density (E/I index). Asthma Quality of Life Questionnaire score changes were also assessed.
Median total lung volumes before and after bronchial thermoplasty were 2668 mL (range, 2226-3096 mL) and 2399 mL (range, 1964-2802 mL; p = 0.08), respectively. Patients also showed a pattern of obstruction improvement in air trapping values (median before thermoplasty, 14.25%; median after thermoplasty, 3.65%; p < 0.001 and in mean lung density values ± SD (before thermoplasty, -702 ± 72 HU; after thermoplasty, -655 ± 66 HU; p < 0.01). Median airway wall thickness also decreased after bronchial thermoplasty (before thermoplasty, 1.5 mm; after thermoplasty, 1.1 mm; p < 0.05). There was a mean Asthma Quality of Life Questionnaire overall score change of 1.00 ± 1.35 (p < 0.001), indicating asthma clinical improvement.
Our study showed improvement in CT measurements after bronchial thermoplasty, along with Asthma Quality of Life Questionnaire score changes. Thus, MDCT could be useful for imaging evaluation of patients undergoing this treatment.
Background
Lebrikizumab is a monoclonal antibody that modulates activity of interleukin‐13. The Phase 3 ACOUSTICS study assessed lebrikizumab efficacy and safety in adolescents with uncontrolled ...asthma despite standard‐of‐care treatment.
Methods
Adolescents (aged 12–17 years) with uncontrolled asthma, prebronchodilator forced expiratory volume in 1 s 40%–90% predicted, and stable background therapy were randomised 1:1:1 to receive lebrikizumab 125 or 37.5 mg or placebo subcutaneously once every 4 weeks. Primary efficacy endpoint was asthma exacerbation rate over 52 weeks.
Results
Between August 2013 and July 2016, 579 patients were screened and 346 were randomised; 224 (65%) completed the study with 52 weeks of treatment. Lebrikizumab 125 mg (n = 116) reduced the exacerbation rate at 52 weeks versus placebo (n = 117; adjusted rate ratio RR 0.49 95% CI 0.28–0.83; 51% rate reduction). Lebrikizumab 37.5 mg (n = 113) was less effective at reducing exacerbations (RR 0.60 95% CI 0.35–1.03; 40% rate reduction). In patients with blood eosinophil counts ≥300 cells/μl, both lebrikizumab doses reduced exacerbations (125 mg: RR 0.44 95% CI 0.21–0.89; 37.5 mg: 0.42 95% CI 0.19–0.93). Treatment‐emergent adverse events, serious adverse events, and adverse events leading to study discontinuation occurred in 155 (68%), 7 (3%), and 5 (2%) of 229 patients who received lebrikizumab (both 125 and 37.5 mg doses) and in 72 (62%), 4 (3%), and 1 (1%) of 117 who received placebo, respectively. No deaths occurred.
Conclusion
Lebrikizumab 125 mg reduced asthma exacerbation rates in adolescents with uncontrolled asthma. However, the study was prematurely terminated (sponsor's decision) potentially limiting interpretation of results.
Clinical trial registration
NCT01875003 (www.ClinicalTrials.gov).
To compare the survival of patients with IPF treated retrospectively with corticosteroids alone, to survival of patients treated with immunosuppressive and corticosteroids combined.
Non-randomized ...retrospective cohort study.
Three tertiary centers in Brazil.
Eighty-two IPF patients were included. The diagnosis was confirmed by open lung biopsy in 48. Patients received either corticosteroids alone (group I) or cytotoxic agents in addition to corticosteroids (group II).
The primary end-point was mortality. Secondary outcome included longitudinal changes in FVC. Mean age was 66±8 years. FVC was 71±17% of predicted. There were 48 deaths during the study period (59%), 44 secondary to respiratory causes. From preliminary univariate analysis, for the group as a whole, worse survival was found to be associated with FVC% <70% of predicted (
P
=
0.0
0
4
), evidence of disease progression by follow-up FVC measurements (
P
=
0.0
1
), and pharmacologic treatment (
P
=
0.0
1
4
). Median survival was 25 months for the group I, and 45 months for the group II (Log-Rank=6.45,
P
=
0.0
1
). After adjusting for FVC⩾70% and<70% of predicted, there was evidence to indicate that survival was associated with recommended pharmacologic treatment only in patients with FVC⩾70% (Log Rank=6.84,
P
=
0.0
0
9
).
The combination of immunosuppressive agents and prednisone results in better survival when compared to prednisone alone in patients with IPF. The benefit seems to occur only in patients with less severe disease, as reflected by FVC⩾70%.
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