RATIONALE: Despite advancements in emphysema treatment, high morbidity and mortality rates highlight the need for innovative therapies. A novel self-expanding nitinol airway scaffold was designed to alleviate lung hyperinflation by connecting emphysematous parenchyma with central bronchi, releasing trapped air. OBJECTIVES: To assess the feasibility, safety, and initial outcomes of airway scaffolds in treating emphysema-related hyperinflation. METHODS: We conducted a pooled analysis of two first-in-human studies (NCT05949645, NCT05854550) involving patients with heterogeneous or homogeneous emphysema treated bronchoscopically with up to three permanent airway scaffolds per lung. MEASUREMENTS: The primary outcome was safety, measured by procedure and/or device-related serious adverse events (SAEs) over six months. Secondary outcomes were technical feasibility, pulmonary function, quality of life, symptoms and exercise capacity at 3 and 6-months, and airway patency assessment by high-resolution computed tomography. MAIN RESULTS: 60 severe emphysema patients (33F/27M
mean age 66±8 years
mean residual volume (RV) percent predicted 255±47%) were included. 98 procedures were performed and 328 airway scaffolds were successfully placed. 21.7% of patients experienced at least one related SAE within 6-months including pneumonia (10.0%) and COPD exacerbation (5.0%), but no pneumothoraxes. RV improved (decreased) from baseline by a mean [95% confidence interval] of 866 [626, 1106] ml at 3-months and 753 [512, 994] ml at 6-months. Clinically meaningful improvements were further observed in spirometry, quality of life, symptoms and exercise capacity. CONCLUSIONS: This study provides the first clinical evidence of the feasibility, safety and initial outcomes after treatment with airway scaffolds in patients with emphysema-related hyperinflation. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT05949645, NCT05854550.