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Emphysema is a severe and debilitating lung disease that results from smoking cigarettes. Patients with emphysema suffer from destruction of the lung tissue with symptoms of severe shortness of breath. The symptoms can progress to complete disability and death. Medical treatment of emphysema has little effect on disease symptoms or progression. Recently, new surgical techniques are being investigated to improve breathing function and symptoms for patients with severe emphysema. This surgery is called lung volume reduction surgery LVRS ; and involves removal of poorly functioning lung tissue. LVRS techniques must be improved in order to provide the greatest possible benefit and lowest possible risks to patients. Animal studies are needed in order to make substantial improvement in LVRS surgical treatments. We have developed animal models of emphysema that are very similar to human emphysema. We are studying lung volume reduction surgical techniques assessed using sophisticated heart and lung function measurement methods in these emphysematous animals. In accordance with the California TRDRP request for research into the effects of smoking and treatment of smoking related disease, we plan to study ways of substantially improving LVRS using this animal model. There are a number of mechanisms by which LVRS effects lung function and symptoms in patients with emphysema. Some of the benefits from LVRS results from: 1 ; removal of poorly functioning areas of the lung, allowing more normal lung regions to expand and ventilate more effectively, 2 ; improving the balance between the regions of air flow and blood flow during breathing, 3 ; improving the position of the diaphragm, chest wall, and breathing muscles, and 4 ; tightening up loose lung tissue and allowing the lungs to exhale more quickly. The resistance slowing exhalation of emphysematous lungs can be improved following the LVRS surgery as well. Many of these effects are most noticeable during rapid breathing with exercise or stress. LVRS involves removal of regions of poorly functioning lung regions. The major questions in this study involve finding the optimal amount of lung tissue to remove during surgery and the best methods for removal. Obviously, if too little lung tissue is removed, there will be no benefit from the surgery. If too much lung tissue is removed, there will be too little remaining lung to perform necessary breathing tasks. Therefore, methods need to be developed for optimizing the amount of lung tissue removal during LVRS. Therefore, we will try to answer the following questions in this study: 1 ; What aspects of lung function breathing rate, blood flow, or gas transfer ; determine the preferred amount of lung to remove during LVRS? 2 ; What measures can be performed during surgery to guide the optimal extent of tissue removal for the surgeon? 3 ; What surgical techniques results in the greatest benefit and lowest risks from surgery are staple tissue removal procedures, or combined staple and laser procedures preferable ; ? 4 ; Is better to operate on one side at a time, or perform LVRS on both lungs simultaneously? We will attempt to answer these questions using animal models of emphysema to determine the optimal LVRS response. The findings from this study should help improve surgical treatment for patients with severe emphysema. In addition, some patients with severe emphysema and lung cancer cannot be operated upon in attempt to cure their cancers because their lung function is too poor. By improving lung function with LVRS, many of these patients could then undergo surgery to potentially cure their lung cancer and
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