Evidence-Based Review

Endobronchial Valves

Endobronchial valves were among the frst devices to be developed for ELVR. They have been widely studied and results from well-­designed randomized trials are available and continue to enrich our understanding of how ELVR might beneft selected patients with severe emphysema. The landmark endobronchial valve for emphysema palliation trial (VENT), a multicenter randomized controlled trial, demonstrated that endobronchial valves can achieve modest statistically signifcant improvements in a variety of endpoints, including lung function, exercise capacity, and quality of life [15]. The study was completed in 2007 and enrolled 321 patients. It compared the safety and effcacy of endobronchial valve therapy employing a unilateral lobar approach in patients with heterogeneous emphysema with optimal medical care. Despite achieving statistical signifcance, the results were considered by many, including the U.S. Food and Drug Administration (FDA), underwhelming [16]. Improvements in FEV1 (60 mL), the 6 min walk distance (19 m), and reductions in the St. George’s respiratory questionnaire (SGRQ) scores with treatment (3.4 points) have been considered by some clinically insig-

nifcant. Careful scrutiny of VENT results, however, left much room for optimism. Improvements in the body mass index, obstruction, dyspnea, exercise, index (BODE) index, more common among valve treated patients, are provocative since this index correlates well with prognosis in COPD [17]. In addition, patients with complete fssures who achieved a greater than 50% reduction in lobar volume demonstrated clinically relevant improvements in FEV1 (23%) which may have survival implications as demonstrated in a subsequent report from a group of investigators using the same valves as the VENT [18]. These authors found a survival beneft in a small cohort of patients among those who achieved atelectasis at the expense of more pneumothoraces, suggesting that ELVR may match surgical results in some patients with heterogeneous emphysema. The BeLieVeR HIFi single-center study confrmed the hypothesis that patients with intact interlobar fssures beneft from ELVR using endobronchial valves [19]. In that randomized, sham bronchos- copy-controlled trial, unilateral lobar occlusion with endobronchial valves placed in patients with heterogeneous emphysema and intact interlobar fssures as measured by CT was associated with signifcant improvements in lung function and quality of life. Results of the STELVIO randomized trial which assessed collateral ventilation

using the Chartis™ system provided further evidence supporting this strategy [20]. In that study, patients treated with endobronchial valves showed a statistically signifcant beneft with improvements in FEV1, FVC, and 6MWT distance that were clinically relevant. The overall responder rate was 75% when the interlobar fssure was largely intact precluding signifcant collateral ventilation. Two subsequent multicenter studies known as TRANSFORM and LIBERATE demonstrated the beneft of ELVR with endobronchial valves with 55% and 47%, respectively, of treated patients benefting from valve placement [21, 22].

In its original ruling denying approval for the Zephyr device (Fig. 35.3) employed in the VENT (a self-expanding nitinol stent with a silicon one-­ way duckbill valve), the FDA expressed concern regarding the complications of ELVR, including a major increase in the number of hospitalizations for COPD exacerbations in the treatment arm (17 vs 1) and other complications such as hemoptysis [16]. Fear of the risks undermined the modest benefts of the trial. As a result, more research was requested. Evidence is now available regarding patient selection and the role of collateral ventilation and fssure integrity in pneumothorax susceptibility. Furthermore, three studies, including long term follow-up of patients treated with endobronchial valves, have shown a signifcant survival beneft in ELVR responders [18, 23, 24].

Results from a randomized sham bronchoscopy controlled trial using the Spiration IBV system (an umbrella-shaped, self-expanding device) were reported some years ago (Fig. 35.4). This smaller trial kept patients blinded for 3 months [25]. The treatment strategy differed signifcantly from the VENT, since it focused on a bilateral approach purposefully avoiding lobar occlusion by sparing a segmental or subsegmental bronchus in the right upper lobe as well as the lingula on the left side. The trial failed to achieve clinically relevant improvements in hard outcomes such as FEV1, gas exchange, or exercise capacity, but demonstrated statistically signifcant improvements in a combined endpoint including quality of life and regional lung volume changes as measured by CT. At the conclusion of the Spiration trial, 31% of the treated patients demonstrated an improvement of eight points in the SGRQ score, and a signifcant regional lung volume reduction in the treated upper lobes. The companion and larger US trial using the IBV system but prolonging blinded follow-up to 6 months was also underwhelming [26]. In that trial, only 6 out of 121 patients in the treatment arm were considered responders. Although lobar volume changes were signifcantly better in the treated arm vs control (−224 mL vs −17 mL), there were no signifcant differences in quality of life as measured by the St. George’s Respiratory Questionnaire. As