An adjusted and time-saving method to measure collateral ventilation with Chartis

INTRODUCTION: Bronchoscopic lung volume reduction with endobronchial valves is an important treatment option in selected patients with severe emphysema and absence of collateral ventilation in the treatment target lobe. The Chartis system provides an important physiological assessment of the presence or absence of collateral ventilation. We aimed to evaluate a new feature and determine whether low flow during a Chartis measurement is predictive for the absence of collateral ventilation, and whether this allows for a procedure to be shortened by earlier terminating the Chartis measurement. This is measured with the “volume trend for the previous 20 s” (VT20). METHODS: We retrospectively evaluated 249 Chartis assessments of patients scheduled for bronchoscopic lung volume reduction procedures. The VT20 was calculated, and several thresholds were compared between patients with collateral ventilation (CV positive) and without collateral ventilation (CV negative). RESULTS: 100% of the CV negative patients reached a threshold of VT20 ≤6 mL, whereas all CV positive patients reached a VT20 ≥7 mL. The median “time saved” between VT20=6 mL and end of assessment was 60 s (range 5–354 s). CONCLUSION: The threshold of VT20 ≤6 mL is a reliable method to exclude the presence of collateral ventilation when air flow rates are low and can therefore reduce bronchoscopic lung volume procedure times

A multicenter, prospective, single-arm clinical investigation of a modified staged treatment algorithm using the AeriSeal system:The STAGE trial

Introduction: Treatment with AeriSeal is an alternate treatment option to achieve lung volume reduction in patients with severe COPD and emphysema who are not eligible for valve treatment. This study aimed to assess the safety and mode of action of a modified staged treatment algorithm with a staged treatment with lower dose of AeriSeal. Methods: We performed a prospective, multicenter feasibility study. AeriSeal was administered during two sequential bronchoscopies: 2 subsegments of a lobe treated with two 5 mL doses, followed by two 10 mL doses in a contralateral lobe after 6 weeks. Results: A total of 14 patients (36% male, mean FEV1 28.4% ± 6.7% of predicted) were enrolled. Ten patients completed both treatments, four were treated unilaterally. AeriSeal treatment resulted in significant TLVR (median 220.5 mL) at 3 months follow up. There were no significant changes from baseline at 12 months in lung function, exercise capacity and quality of life. During the 3-month post-treatment period, respiratory SAEs included 5 COPD exacerbations in 4 (28.6%) subjects, post-treatment acute inflammatory response (PAIR) in 2 (14.3%) subjects, and 1 respiratory failure event in 1 (7.1%) subject. Conclusion: The staged and lower dosed administration of AeriSeal does not impact the overall safety profile in terms of reducing the type and frequency of respiratory SAEs previously reported for a single-stage treatment. A larger volume of AeriSeal than used in this study may be necessary to provide meaningful clinical benefits

Endobronchial Valve (Zephyr) Treatment in Homogeneous Emphysema:One-Year Results from the IMPACT Randomized Clinical Trial

RATIONALE: The long-term safety and effectiveness of bronchoscopic lung volume reduction with Zephyr endobronchial valves in subjects with severe homogeneous emphysema with little to no collateral ventilation beyond 3 months have yet to be established. METHODS: Ninety-three subjects were randomized to either bronchoscopic lung volume reduction with Zephyr valves or standard of care (SoC) (1:1). Zephyr valve subjects were assessed at 3, 6, and 12 months. SoC subjects were assessed at 3 and 6 months; they were then offered crossover to Zephyr valve treatment. RESULTS: The mean group difference (Zephyr valve − SoC) for change in FEV1 from baseline to 6 months was 16.3 ± 22.1% (mean ± SD; p < 0.001). Secondary outcomes showed the mean between-group difference for the six-minute walk distance of +28.3 ± 55.3 m (p = 0.016); St. George's Respiratory Questionnaire, −7.51 ± 9.56 points (p < 0.001); modified Medical Research Council, −0.42 ± 0.81 points (p = 0.019); BODE index, −0.85 ± 1.39 points (p = 0.006); and residual volume of −430 ± 830 mL (p = 0.011) in favor of the Zephyr valve group. At 6 months, there were significantly more responders based on the minimal clinically important difference for these same measures in the Zephyr valve versus the SoC group. The clinical benefits were persistent at 12 months. The percentage of subjects with respiratory serious adverse events was higher in the Zephyr valve group compared to SoC during the first 30 days post-procedure but not statistically different for the Zephyr valve and SoC groups from 31 days to 6 months, and stable in the Zephyr valve group out to 12 months. There were 2 deaths in the SoC group in the 31-day to 6-month period and none in the Zephyr valve group out to 12 months. CONCLUSIONS: Bronchoscopic lung volume reduction with Zephyr valves in subjects with severe homogeneous emphysema and little to no collateral ventilation provides clinically meaningful change from baseline in lung function, quality of life, exercise capacity, dyspnea, and the BODE index at 6 months, with benefits maintained out to 12 months

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

&lt;b&gt;Background:&lt;/b&gt; 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. &lt;br&gt;&lt;/br&gt; &lt;br&gt;&lt;/br&gt; &lt;b&gt;Methods:&lt;/b&gt; 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. &lt;br&gt;&lt;/br&gt; &lt;br&gt;&lt;/br&gt; &lt;b&gt;Results:&lt;/b&gt; 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. &lt;br&gt;&lt;/br&gt;&lt;br&gt;&lt;/br&gt; &lt;b&gt;Conclusions:&lt;/b&gt; 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

Effect of Zephyr Endobronchial Valves on Dyspnea, Activity Levels, and Quality of Life at One Year Results from a Randomized Clinical Trial

Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation. Objectives: Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported. Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool-PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George's Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy). Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains (P, 0.05 and P, 0.001, respectively). Reduction in CAT was through improvements in breathlessness (P, 0.05), energy level (P, 0.05), activities (P, 0.001), and increased confidence when leaving home (P, 0.05). The TDI measures of effort, task, and functional impairment were uniformly improved (P, 0.001). The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT)-PRO, dyspnea domain, was significantly improved in the Zephyr Valve group. Improvements correlated with changes in residual volume and residual volume/TLC ratio. Conclusions: Patients with severe hyperinflated emphysema achieving lung volume reductions with Zephyr Valves experience improvements in multidimensional scores for breathlessness, activity, and psychosocial parameters out to at least 12 months

Bronchial thermoplasty: a novel technique in the treatment of severe asthma

New therapies are needed for patients with severe persistent asthma who cannot achieve control with current therapy of inhaled corticosteroids and long-acting β 2 -agonists. Bronchial thermoplasty is a novel intervention for asthma that delivers controlled thermal energy to the airway wall during a series of bronchoscopies, resulting in a prolonged reduction in airway smooth muscle mass. We review the method of performing bronchial thermoplasty with the Alair System, how to appropriately select and manage patients undergoing bronchial thermoplasty, and the clinical experience to date with this treatment. Randomized, controlled clinical trials with bronchial thermoplasty in subjects with severe asthma have resulted in improvements in overall asthma control as demonstrated by significant improvement in quality of life, asthma symptoms, severe exacerbations requiring corticosteroids, days lost from work/school/other daily activities due to asthma, and healthcare utilization

Indirect comparison of bronchial thermoplasty versus omalizumab for uncontrolled severe asthma

<p><i>Objective:</i> Bronchial thermoplasty (BT) as an add-on therapy for uncontrolled severe asthma is an alternative to biologic therapies like omalizumab (OM). We conducted an indirect treatment comparison (ITC) to appraise comparative effectiveness of BT and OM. <i>Methods</i>: A systematic literature review identified relevant randomized controlled trials. The ITC followed accepted methodology. <i>Results</i>: The ITC comprised a sham-controlled trial of BT (AIR2) and two placebo-controlled trials of OM (INNOVATE; EXTRA). Comparing the BT post-treatment period to ongoing treatment with OM, showed no significant differences in the rate ratios (RRs) for severe exacerbations (RR of BT versus OM = 0.91 [95% CI: 0.64, 1.30]; <i>p</i> = 0.62) or hospitalizations (RR = 0.57 [95% CI: 0.17, 1.86]; <i>p</i> = 0.53); emergency department visits were significantly reduced by 75% with BT (RR = 0.25 [95% CI: 0.07, 0.91]; <i>p</i> = 0.04); the proportions of patients with clinically meaningful response on the asthma quality-of-life questionnaire were comparable (RR = 1.06 [95% CI: 0.86, 1.34]; <i>p</i> = 0.59). The RR for exacerbations statistically favours OM over the total study period in AIR2 (RR = 1.50 [95% CI: 1.11, 2.02]; <i>p</i> = 0.009) likely reflecting a transient increase in events during the BT peri-treatment period. <i>Conclusions</i>: The ITC should be interpreted cautiously considering the differences between patient populations in the included trials. However, based on the analysis, BT compares well with a potentially more costly pharmacotherapy for asthma. Clinicians evaluating the relative merits of using these treatments should consider the totality of evidence and patient preferences to make an informed decision.</p

Indirect comparison of bronchial thermoplasty versus omalizumab for uncontrolled severe asthma

Objective: Bronchial thermoplasty (BT) as an add-on therapy for uncontrolled severe asthma is an alternative to biologic therapies like omalizumab (OM). We conducted an indirect treatment comparison (ITC) to appraise comparative effectiveness of BT and OM. Methods: A systematic literature review identified relevant randomized controlled trials. The ITC followed accepted methodology. Results: The ITC comprised a sham-controlled trial of BT (AIR2) and two placebo-controlled trials of OM (INNOVATE; EXTRA). Comparing the BT post-treatment period to ongoing treatment with OM, showed no significant differences in the rate ratios (RRs) for severe exacerbations (RR of BT versus OM = 0.91 [95% CI: 0.64, 1.30]; p = 0.62) or hospitalizations (RR = 0.57 [95% CI: 0.17, 1.86]; p = 0.53); emergency department visits were significantly reduced by 75% with BT (RR = 0.25 [95% CI: 0.07, 0.91]; p = 0.04); the proportions of patients with clinically meaningful response on the asthma quality-of-life questionnaire were comparable (RR = 1.06 [95% CI: 0.86, 1.34]; p = 0.59). The RR for exacerbations statistically favours OM over the total study period in AIR2 (RR = 1.50 [95% CI: 1.11, 2.02]; p = 0.009) likely reflecting a transient increase in events during the BT peri-treatment period. Conclusions: The ITC should be interpreted cautiously considering the differences between patient populations in the included trials. However, based on the analysis, BT compares well with a potentially more costly pharmacotherapy for asthma. Clinicians evaluating the relative merits of using these treatments should consider the totality of evidence and patient preferences to make an informed decision.</p