Supplementary Material for: Bronchoscopic Lung Volume Reduction with Endobronchial Zephyr Valves for Severe Emphysema: A Systematic Review and Meta-Analysis

Background: Endoscopic lung volume reduction using Zephyr® valves has been recently adopted as a treatment option for patients with severe emphysema without collateral ventilation (CV). Objectives: To assess the efficacy and safety of Zephyr valves in such a population. Methods: Studies were identified from MEDLINE and EMBASE databases. All searches were current until June 2018. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of Zephyr. We defined as outcome: change in forced expiratory volume in 1 s (FEV1), in the 6-min walking test (6MWT), in the St George’s Respiratory Questionnaire (SGRQ), and in residual volume (RV). Safety analysis included relative risk (RR) of pneumothorax. We assessed the quality of the evidence using GRADE. Results: 7 RCTs reported on Zephyr valves and 5 RCTs included only patients without CV. Zephyr improved FEV1 with a mean difference (MD) of 17.36% (CI, 9.28–25.45, I2 = 78%). Subgroup analysis showed significant FEV1 improvement following Zephyr placement in patients with heterogeneous distribution: MD = 21.78% (CI, 8.70–34.86, I2 = 89%) and 16.27% (CI, 8.78–23.76, I2 = 0%) in patients with homogeneous emphysema. Studies with a follow-up of 3 months reported FEV1 MD = 17.19% (CI, 3.16–31.22, I2 = 89%) compared to studies with a follow-up of 6–12 months, which showed a consistent improvement of FEV1 MD = 17.90% (CI, 11.47–24.33, I2 = 0%). Zephyr also showed improvement of SGRQ, 6MWT, and RV. RR of pneumothorax was 6.32 (CI, 3.74–10.67, I2 = 0%). Conclusion: In this population, Zephyr valves provided significant and clinically meaningful short-term improvements in either homogeneous or heterogeneous emphysema without CV but with an increase in adverse events