Background: Biologic lung volume reduction ( BLVR) is an experimental endobronchial treatment for advanced emphysema that reduces lung volume by remodeling damaged areas of hyperinflated lung. This article summarizes the first experience using BLVR to treat unilateral bullous disease.Methods: A 67-year-old man with very severe chronic obstructive pulmonary disease owing to advanced emphysema underwent BLVR at 8 right upper lobe (RUL) subsegmental sites during 2-treatment sessions 6 weeks apart. Response to therapy was assessed 6 weeks after initial treatment, and 6 and 12 weeks after the second treatment.Results: Six weeks after initial BLVR treatment at 4 subsegments, small improvements in spirometry, dyspnea [Modified Medical Research Council Dyspnea (MRCD) score= -1U change], and a 6-minute walk distance (6MWD=+ 76m change) were observed. Improvements at 6 and 12 weeks after repeat treatment in FEV1 (+ 20.0%, + 22.1%), FVC (+ 33.1%, + 27.6%), DLco (+ 6.4%, + 6.3%), RV/ TLC ratio (- 9.8%, - 5.1%), MRCD (- 1U, - 1 U), 6MWD (79 m, 77 m), and St George's Respiratory Questionnaire score ( total score= -5.9 U, - 2.2 U) were observed. Quantitative analysis of computed tomography imaging demonstrated a 357mL reduction in RUL lung volume, and corresponding increases in volumes of adjacent, less damaged areas of lung tissue.Conclusions: BLVR produced effective targeted lung volume reduction of a RUL bullous and improvements in spirometry, symptoms, exercise capacity, and diffusing capacity. This novel bronchoscopic technique may provide a safe alterative to bullectomy in selected patients.