Journal Club - Endobronchial Valve Bronchoscopic Lung Volume Reduction.

Abstract

It is estimated that approximately 3.5 million American adults have been diagnosed with emphysema, an irreversible destruction of the alveolar lung parenchyma. In advanced cases, the lung damage is so severe that significant air trapping occurs and does not improve with the use of bronchodilators and other conventional medicines used for chronic obstructive pulmonary disease (COPD). Viable surgical options include bullectomy, lung volume reduction surgery (LVRS), and lung transplantation but many patients may not be appropriate candidates for these procedures and/or there are long wait times for transplantation. Recently, the U.S. Food and Drug Administration (FDA) approved the Zephyr® endobronchial valve (EBV) (Zephyr Valve EBV; Pulmonx Corporation, Redwood City, California) for bronchoscopic lung volume reduction for patients with severe emphysema who are not responsive to medical therapy. This 1-way valve, the size of a pencil eraser, is inserted into the targeted diseased portion of the lung. Typically, 4 to 8 valves are inserted into the chosen emphysematous lobe and will allow air to escape out of that region but prevent any further air from entering, leading to deflation, and ultimately, total lobar collapse over a matter of weeks. An earlier study with the Zephyr® valves, the “Endobronchial Valve for Emphysema Palliation Trial, (VENT)” study,1 was a multicenter trial with 321 participants (220 with EBV insertion) that demonstrated statistically significant improvements in forced expiratory volume in 1 second (FEV1) and the 6-minute walk distance test (6MWD) between EBV and standard of care (SoC) groups but these were not clinically meaningful differences (mean change in FEV1 was 60 mL and median difference from baseline 6MWD 19.1 m).1 Post hoc analysis indicated that the best responders were those who demonstrated the following criteria: little to virtually no collateral ventilation to ipsilateral adjacent lobes, complete lobar occlusion achieved with the correct occlusive positioning of the valves in all segmental and sub-segmental airways and complete intact fissures between lobes.2,3 With this information, Pulmonx developed a unique technology-- Chartis (Pulmonx Corporation, Redwood City, California) a device that tests for collateral ventilation to judge the appropriateness of valve insertion.4 The Chartis system consists of a console connected to a balloon catheter with a central channel that is used to occlude the target lobe and to subsequently measure pressure and flow to calculate resistance to airflow and hence to quantify collateral ventilation in that lobe.4 More recently, advanced computed tomography (CT) scan analysis techniques have been developed that can virtually eliminate the need for testing with the Chartis system.5,6 Advanced CT analysis techniques have become a key element of deciding on the appropriateness of candidates. This has been confirmed with several short-term single center studies.2,7,8 The FDA actually granted the Zephyr® valve “breakthrough device” designation, allowing the FDA to provide guidance on efficient device development and to expedite evidence generation and review of the device. This designation generally signals the recognition that there are relatively few viable options for treating the targeted patient population. Indeed, the first study we review by Criner and colleagues, LIBERATE (below) is the first large, prospective, randomized controlled, multicenter study to evaluate the effectiveness, safety and durability of the benefit out to 12 months in patients with severe heterogeneous emphysema and with little to no collateral ventilation in the target lung. In order to expedite approval, the FDA required that, compared to previous studies, the primary endpoints show a greater magnitude of difference between Zephyr valve insertion and SoC versus a sham procedure and then SoC. In this Journal Club we will review this pivotal study that led to the approval of the Zephyr® valve in the United States and other recent studies that have evaluated the efficacy and safety of this device. Note: Abstracts are presented in their original, published format and have not been edited to match JCOPDF style.