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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Croxton, Thomas
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Medicine
Saint Louis
United States
Zip Code
McDonough, John E; Yuan, Ren; Suzuki, Masaru et al. (2011) Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N Engl J Med 365:1567-75
Choong, Cliff K; Macklem, Peter T; Pierce, John A et al. (2008) Airway bypass improves the mechanical properties of explanted emphysematous lungs. Am J Respir Crit Care Med 178:902-5
Woods, Jason C; Choong, Cliff K; Yablonskiy, Dmitriy A et al. (2006) Hyperpolarized 3He diffusion MRI and histology in pulmonary emphysema. Magn Reson Med 56:1293-300
Choong, Cliff K; Phan, Loc; Massetti, Patrick et al. (2006) Prolongation of patency of airway bypass stents with use of drug-eluting stents. J Thorac Cardiovasc Surg 131:60-4
Choong, Cliff K; Haddad, Fabio J; Gee, Elaine Y et al. (2005) Feasibility and safety of airway bypass stent placement and influence of topical mitomycin C on stent patency. J Thorac Cardiovasc Surg 129:632-8
Choong, Cliff K; Haddad, Fabio J; Martinez, Carlo et al. (2005) A simple, reproducible, and inexpensive technique in the preparation of explanted emphysematous lungs for ex vivo studies. J Thorac Cardiovasc Surg 130:922-3
Woods, Jason C; Yablonskiy, Dmitriy A; Chino, Kimiaki et al. (2004) Magnetization tagging decay to measure long-range (3)He diffusion in healthy and emphysematous canine lungs. Magn Reson Med 51:1002-8
Chino, Kimiaki; Choong, Cliff K; Toeniskoetter, P Diane et al. (2004) A canine model for production of severe unilateral panacinar emphysema. Exp Lung Res 30:319-32
Lausberg, Henning F; Chino, Kimiaki; Patterson, G Alexander et al. (2003) Bronchial fenestration improves expiratory flow in emphysematous human lungs. Ann Thorac Surg 75:393-7; discussion 398