Emphysema is a progressive and irreversible disease for which there is no cure to date. The patients experience debilitating shortness of breath with repetitive exacerbations and poor quality of daily life. At present, patients with severe emphysema have limited treatment options. Endoscopic lung-volume reduction with valve implantation or using lung sealant is a treatment option for patients with severe emphysema. By our patients, we detected collateral channels, which allow airflow into the target lobe and prevent atelectasis and significant lung-volume reduction. Thus, we decided to treat the advanced emphysema of our patients with endoscopic volume reduction using lung sealant (AeriSeal). Lung-volume reduction surgery reduces hyperinflation and improves lung function by removal of emphysematous lung tissue. However, lung-volume reduction surgery is also associated with significant short-term morbidity and mortality. Results from recently published Endobronchial Valve for Emphysema Palliation Trail (VENT) and Exhale Airway Stents for Emphysema (EASE) trial showed that treatment was substantially less effective and did not consistently reduce hyperinflation or improve lung function mostly likely due to collateral ventilation present in majority of patients. There is a volume reduction therapy in case of detection of collateral flow; use of a lung sealant is a possible alternative. A novel endoscopic tissue sealant (AeriSeal; Aeris Therapeutics, Woburn, MA) is a liquid foam sealant that collapses hyperinflated lung areas destroyed by emphysema. The foam of lung sealant AeriSeal is instilled into the peripheral airways and alveoli where it polymerizes and functions as tissue glue, forming a film of material on the lung surface that seals the target region to cause durable absorption atelectasis. Two patients with advanced emphysema and hyperinflation underwent endoscopic volume reduction with endoscopic tissue sealant (AeriSeal); collateral flow was confirmed by using the Chartis System. Both patients experienced transient fever, malaise, chest discomfort, and shortness of breath for about 3 days after the procedure. Over a period of 8 and 12 weeks, the air within the sealed region was absorbed and the treated area showed atelectasis on computed tomography scan. The follow-up evaluations of those 2 patients showed improved lung function (increased FEV1, and a reduction of TLC and RV) with improved quality of life of both patients. Correlation and comparisons between changes in primary and secondary outcome measures in the lung function parameters and 6-minute walking test before and after the application of AeriSealant revealed significant reduction of hyperinflation and improvement both in the flow rates and physical capacity of our patients.