UNASSIGNED: To evaluate the operability and safety of bronchoscopic domestic one-way endobronchial valves (EBV) on animals.
UNASSIGNED: Nine pigs were randomly assigned (2:1) to receive domestic one-way EBV (the experimental group, n = 6) and Zephyr® EBV (the control group, n = 3). Routine blood tests, arterial blood gases, and CT scans of the lungs were performed 1 day pre-procedure in addition to 1 week and 1 month post-procedure to assess changes in blood markers and lung volumes. At 1 month post-procedure, the animals were sacrificed, followed by removal of all valves via bronchoscopy. Pathological examinations of critical organs were subsequently performed.
UNASSIGNED: A total of 15 valves were placed in the experimental group and 6 valves were placed in the control group, without serious complications. Routine blood tests and arterial blood gas examinations at 1 day pre-procedure, 1 week post-procedure, and 1 month post-procedure did not differ significantly in both groups. No EBV displacement was noted under bronchoscopy, and the valve was smoothly removable by bronchoscope at 1 month post-procedure. At 1 week post-procedure, varying degrees of target lung lobe volume reduction were observed on lung CT in both groups. Lung volume reduction was achieved at 1 month post-procedure in both groups, without significant statistical difference. Although 3 cases in the experimental group and 1 case in the control group developed varying degrees of pneumonia, the inflammatory response did not increase over time during the experimental period. Pathological examination revealed no significant abnormal changes in the critical organs for both groups.
UNASSIGNED: Our results demonstrate that domestic EBV is safe and reliable for endobronchial application in general-grade laboratory white pigs. The safety of domestic EBV is similar to that of Zephyr® EBV, with good ease of use and operability. This kind of domestic EBV can meet the safety evaluation requirements for animal testing.

UNASSIGNED: Lung volume reduction with endobronchial coils treatment (ECT), for patients with severe emphysema, has shown modest improvement in exercise capacity and lung functions in clinical trials, yet the benefit of this procedure is still unclear.
UNASSIGNED: We conducted a multicenter retrospective cohort study including all patients who underwent ECT in Israel and a propensity score matched control group of patients with chronic obstructive pulmonary disease (COPD) that were treated with usual care. The primary outcome was six-minute walk test distance (6MWTD), secondary outcomes were lung function tests and patient survival.
UNASSIGNED: Overall, 46 patients were included in the ECT group. Their mean 6MWTD at baseline and at 6 and at 24 months post procedure was 331.0±101.4, 372.9±76.8 and 338.8±104.8, respectively (overall P=0.04, pairwise comparison: baseline to 6 months (P=0.1), baseline to 24 months (P=1.0)). Mean FEV1 values at baseline and at 6 and at 24 months post procedure were 0.86±0.38, 0.92±0.37 and 0.82±0.36 liters, respectively (overall P=0.003, pairwise comparison: baseline to 6 months (P=0.04), baseline to 24 months (P=0.75)). The median 6MWTD for the ECT and control groups at 24 months were 333.0 (262.5-390) and 280 (210-405), respectively (P=0.16). There was no difference in overall survival (P=0.84). Heterogenous emphysema was a significant predictor of treatment success in univariate analysis (p=0.004).
UNASSIGNED: Lung volume reduction with endobronchial coils may improve the exercise capacity and FEV1 of COPD patients. However, the majority of the effect was diminished after 24 months. The current state of evidence does not support regulatory approval of ECT and warrant its use only after consideration of the benefit-harm ratio in a highly selected patient population.

BACKGROUND: The PneumRx endobronchial coil system for patients with severe emphysema has been shown to improve quality of life, exercise capacity, and pulmonary function in patients with emphysema. A post hoc analysis of the RENEW trial has identified patient characteristics and lobar selection methods associated with improved outcomes, which have to be confirmed prospectively.
METHODS: The ELEVATE trial is a prospective, multicenter, open label, randomized (2:1), controlled trial comparing outcomes in patients treated with endobronchial coils (treatment) to a medically managed control group (control). The trial aims to enroll 210 patients (140 in the treatment group and 70 in the control group) with severe emphysema. Control patients will be eligible to crossover to coil treatment after 6 months of follow-up. The co-primary effectiveness endpoints are percent change in forced expiratory volume in 1 s and quality of life measured by change in St. George\'s Respiratory Questionnaire from baseline to 6 months. Secondary objectives are determination of responder rates of clinical endpoints and mean change in other functional and physiologic endpoints. All patients will be followed for 24 months after initial treatment. Adverse events will be collected on an ongoing basis throughout the trial.
CONCLUSIONS: The primary objective of the ELEVATE trial is to prospectively confirm the safety and effectiveness profile of the coil system for the treatment of severe emphysema in consideration of the findings of previous randomized controlled trials. Secondary objectives are the determination of responder rates in all clinical endpoints and mean change in physiologic endpoints.

BACKGROUND: Bronchoscopic therapies are less invasive alternatives of surgical lung volume reduction for severe emphysema. Bending of lung tissue by implanting metallic coils into bronchi is one of the procedures. A new-designed device with a similar rationale, Reverser, has been developed with some improvements.
OBJECTIVE: The aim of the study was to evaluate the safety and feasibility of the Reversers.
METHODS: Twelve healthy pigs were randomly divided into 3 groups (groups A, B, and C). The Reversers were implanted bronchoscopically into the selected airways using a proprietary delivery system. Physical examination, chest fluoroscopy, computed tomography (CT) scans, and bronchoscopic observations were performed before implantation and during the follow-up period. Necropsy was performed respectively at 1 month (group A), 3 months (group B), and 6 months (group C) after implantation.
RESULTS: A total of 47 Reversers were implanted successfully. The procedure was feasible and well tolerated by all pigs. No severe complications, such as pneumothorax, abscesses, and airway hemorrhage, were found. No unintended injuries or death occurred. Mild granulation and inflammation were observed in the airway wall. Opacities around Reversers were shown on CT scans in some pigs. In the pigs with opacities, histological evaluation revealed widened alveolar septa due to inflammatory cell infiltration in the vicinity of the Reversers. On the analysis of CT data, there was a trend for volume reduction of the treated lung at 1 and 3 months after treatment compared with baseline.
CONCLUSIONS: This study showed that Reversers were safe and feasible for bronchoscopic lung volume reduction in pigs.

Although lung volume reduction surgery and bronchoscopic lung volume reduction with endobronchial valves have both been shown to improve lung function, exercise capacity and quality of life in appropriately selected patients with emphysema, there are no direct comparison data between the two procedures to inform clinical decision-making.
We describe the protocol of the CELEB study, a randomised controlled trial which will compare outcomes at 1 year between the two procedures, using a composite disease severity measure, the iBODE score, which includes body mass index, airflow obstruction, dyspnoeaand exercise capacity (incremental shuttle walk test).
Ethical approval to conduct the study has been obtained from the Fulham Research Ethics Committee, London (16/LO/0286). The outcome of this trial will provide information to guide treatment choices in this population and will be presented at national and international meetings and published in peer-reviewed journals. We will also disseminate the main results to all participants in a letter.
ISRCTN19684749; Pre-results.

Single-center randomized controlled trials of the Zephyr endobronchial valve (EBV) treatment have demonstrated benefit in severe heterogeneous emphysema. This is the first multicenter study evaluating this treatment approach.
To evaluate the efficacy and safety of Zephyr EBVs in patients with heterogeneous emphysema and absence of collateral ventilation.
This was a prospective, multicenter 2:1 randomized controlled trial of EBVs plus standard of care or standard of care alone (SoC). Primary outcome at 3 months post-procedure was the percentage of subjects with FEV1 improvement from baseline of 12% or greater. Changes in FEV1, residual volume, 6-minute-walk distance, St. George\'s Respiratory Questionnaire score, and modified Medical Research Council score were assessed at 3 and 6 months, and target lobe volume reduction on chest computed tomography at 3 months.
Ninety seven subjects were randomized to EBV (n = 65) or SoC (n = 32). At 3 months, 55.4% of EBV and 6.5% of SoC subjects had an FEV1 improvement of 12% or more (P < 0.001). Improvements were maintained at 6 months: EBV 56.3% versus SoC 3.2% (P < 0.001), with a mean ± SD change in FEV1 at 6 months of 20.7 ± 29.6% and -8.6 ± 13.0%, respectively. A total of 89.8% of EBV subjects had target lobe volume reduction greater than or equal to 350 ml, mean 1.09 ± 0.62 L (P < 0.001). Between-group differences for changes at 6 months were statistically and clinically significant: ΔEBV-SoC for residual volume, -700 ml; 6-minute-walk distance, +78.7 m; St. George\'s Respiratory Questionnaire score, -6.5 points; modified Medical Research Council dyspnea score, -0.6 points; and BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, -1.8 points (all P < 0.05). Pneumothorax was the most common adverse event, occurring in 19 of 65 (29.2%) of EBV subjects.
EBV treatment in hyperinflated patients with heterogeneous emphysema without collateral ventilation resulted in clinically meaningful benefits in lung function, dyspnea, exercise tolerance, and quality of life, with an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT02022683).

One-way endobronchial valves (EBV) insertion to reduce pulmonary air trapping has been used as therapy for chronic obstructive pulmonary disease (COPD) patients. However, local inflammation may result and can contribute to worsening of clinical status in these patients. We hypothesized that combined EBV insertion and intrabronchial administration of mesenchymal stromal cells (MSCs) would decrease the inflammatory process, thus mitigating EBV complications in severe COPD patients. This initial study sought to investigate the safety of this approach. For this purpose, a phase I, prospective, patient-blinded, randomized, placebo-controlled design was used. Heterogeneous advanced emphysema (Global Initiative for Chronic Lung Disease [GOLD] III or IV) patients randomly received either allogeneic bone marrow-derived MSCs (108 cells, EBV+MSC) or 0.9% saline solution (EBV) (n = 5 per group), bronchoscopically, just before insertion of one-way EBVs. Patients were evaluated 1, 7, 30, and 90 days after therapy. All patients completed the study protocol and 90-day follow-up. MSC delivery did not result in acute administration-related toxicity, serious adverse events, or death. No significant between-group differences were observed in overall number of adverse events, frequency of COPD exacerbations, or worsening of disease. Additionally, there were no significant differences in blood tests, lung function, or radiological outcomes. However, quality-of-life indicators were higher in EBV + MSC compared with EBV. EBV + MSC patients presented decreased levels of circulating C-reactive protein at 30 and 90 days, as well as BODE (Body mass index, airway Obstruction, Dyspnea, and Exercise index) and MMRC (Modified Medical Research Council) scores. Thus, combined use of EBV and MSCs appears to be safe in patients with severe COPD, providing a basis for subsequent investigations using MSCs as concomitant therapy. Stem Cells Translational Medicine 2017;6:962-969.

Endobronchial valves (EBVs) have been successfully used in patients with severe heterogeneous emphysema to improve lung physiology. Limited available data suggest that EBVs are also effective in homogeneous emphysema.
To evaluate the efficacy and safety of EBVs in patients with homogeneous emphysema with absence of collateral ventilation assessed with the Chartis system.
Prospective, multicenter, 1:1 randomized controlled trial of EBV plus standard of care (SoC) or SoC alone. Primary outcome was the percentage change in FEV1 (liters) at 3 months relative to baseline in the EBV group versus the SoC group. Secondary outcomes included changes in FEV1, St. George\'s Respiratory Questionnaire (SGRQ), 6-minute-walk distance (6MWD), and target lobe volume reduction.
Ninety-three subjects (age, 63.7 ± 6.1 yr [mean ± SD]; FEV1, % predicted, 29.3 ± 6.5; residual volume, % predicted, 275.4 ± 59.4) were allocated to either the EBV group (n = 43) or the SoC group (n = 50). In the intention-to-treat population, at 3 months postprocedure, improvement in FEV1 from baseline was 13.7 ± 28.2% in the EBV group and -3.2 ± 13.0% in the SoC group (mean between-group difference, 17.0%; P = 0.0002). Other variables demonstrated statistically and clinically significant changes from baseline to 3 months (EBV vs. SoC, respectively: SGRQ, -8.63 ± 11.25 vs. 1.01 ± 9.36; and 6MWD, 22.63 ± 66.63 m vs. -17.34 ± 52.8 m). Target lobe volume reduction at 3 months was -1,195 ± 683 ml (P < 0.0001). Of the EBV subjects, 97.2% achieved volume reduction in the target lobe (P < 0.0001). Procedure-related pneumothoraces occurred in 11 subjects (25.6%). Five subjects required removal/replacement of one or more valves. One subject experienced two valve migration events requiring removal/replacement of valves.
EBV in patients with homogeneous emphysema without collateral ventilation results in clinically meaningful benefits of improved lung function, exercise tolerance, and quality of life.

We describe the use of structured light plethysmography (SLP)-a novel, non-contact, light-based technique for measuring tidal breathing-among a cohort of patients undergoing lung resection. In this feasibility study, we examined whether changes in chest wall motion or in asynchrony between regions of the thoraco-abdominal wall could be identified after surgery.
Fifteen patients underwent wedge resection (n = 8) or lobectomy (n = 7). All patients underwent two SLP assessments (before surgery and on Day 1 post-surgery). Each assessment captured data during 5 min of quiet (tidal) breathing.
When data were averaged across all patients, motion on the operated side of the thorax was significantly reduced after surgery (mean change from presurgery ± standard deviation: -14.7 ± 16.5%, P = 0.01), while motion on the non-operated side increased (15.9 ± 18.5%, P = 0.01). Thoraco-abdominal asynchrony also increased (mean change ± standard deviation: 43.4 ± 55.1%, P = 0.01), but no significant difference was observed in right-left hemi-thoracic asynchrony (163.7 ± 230.3%, P = 0.08). When analysed by resection type, lobectomy was associated with reduced and increased motion on the operated and non-operated side, respectively, and with an increase in both right-left hemi-thoracic and thoraco-abdominal asynchrony. No significant changes in motion or asynchrony were identified in patients who underwent wedge resection.
SLP was able to detect changes in chest wall motion and asynchrony after thoracic surgery. Changes in this small group of patients were consistent with the side of the incision and were most apparent in patients undergoing lobectomy.