Lung volume reduction by isolating a target lung portion from the rest of the lung with a mass of extracellular matrix (“ECM”) material. The procedure can be performed by locating a tube within the lumen of an airway to be obstructed and depositing an amount of flowable or other ECM in the open space until the lumen is occluded. Optionally, the procedure may be performed by delivering a plug substantially comprised of ECM material into the lumen of an airway to be obstructed. Further optionally, the ECM plug may include a one-way valve to allow air and mucous to escape from the isolated lung portion.