Emphysema affects approximately 2 million individuals in the US and is the fourth leading cause of death. Once medical therapy has been maximized, further therapeutic strategies are limited, apart from lung transplantation, and lung volume reduction surgery, both of which are applicable to only a small subsegment of end-stage patients. The crippling effects of end-stage emphysema, including severe dyspnea, relate not only to loss of lung substance but also to the dynamic hyperinflation of the lungs associated with loss of elastic recoil and a marked increase in the size of the lungs. The concomitant enlargement of the thorax, and flattening of the diaphragm, render the inspiratory muscles inefficient, increase the work of breathing, and contribute significantly to the feeling of breathlessness. The patient is trapped in a state of hyperinflation and no amount of forced effort can empty the lungs since the same force exerted to empty the lungs, is transmitted to the small airways which collapse and obstruct the outflow of gas. There is clear evidence that the normal collateral ventilation present in human lungs is markedly increased in emphysema due to extensive breakdown of alveolar walls. In fact, it has been demonstrated that airflow from one region of the lung to another in the emphysematous patient can exceed air flow through the nonnal air passages. We hypothesize that the extensive collateral ventilation existing in emphysematous lungs, can be utilized to decrease the hyperinflation and air trapping which is responsible for a significant portion of the dyspnea in such patients. We propose to create new passageways from the lung substance to large airways in order to bypass the small, obstructed airways. This will allow the lungs to deflate more completely on exhalation, relieving breathlessness and increasing the patients' tolerance for exertion. To accomplish this we propose: 1) to create a dog model of severe emphysema; 2) to develop a simple, safe, and effective endoscopic technique for creation of broncho-pulmonary conduits, using methods applicable for humans; 3) to evaluate the radiologic, physiologic, and functional consequences of alleviating dynamic hyperinflation with this method.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL062194-07
Application #
7187840
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Smith, Robert A
Project Start
1999-04-01
Project End
2008-03-31
Budget Start
2006-03-23
Budget End
2008-03-31
Support Year
7
Fiscal Year
2005
Total Cost
$282,150
Indirect Cost
Name
University of Pennsylvania
Department
Surgery
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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