Lung transplantation is increasingly used as therapy for patients with chronic obstructive pulmonary disease (COPD). The goal of this research is to improve outcome in lung transplantation by understanding and manipulating the relationship between lung expansion and chest wall expansion. In health, the sizes of lungs and chest wall are matched so that each operates in its optimal volume range. Transplantation, like disease, can alter the relationship between the sizes of lungs and chest wall, causing dysfunction. For example, transplanting large lungs into a small chest causes the chest wall to operate at greater than optimal volumes (overexpansion) and the lungs to operate at less than optimal volumes (underexpansion). Overexpansion of the chest wall limits the ability of inspiratory muscles to lower pleural pressure and expand the lungs; fatigue and hypoventilation may result. Underexpansion of the lungs predisposes them to airway closure, atelectasis and hypoxemia. Pulmonary underexpansion also limits maximum expiratory flow-rates, reducing the effectiveness of cough and leading to accumulation of secretions and infection. We propose a series of investigations in patients before and after lung transplantation to assess the importance of matching optimal lung and chest wall volumes. Data will be interpreted with the aid of a computational model of respiratory mechanics that simulates dynamic breathing maneuvers in patients before and after transplantation. There are 5 Specific Aims: 1) to determine the relative expansion of the lungs and chest wall (i.e., the relationship between predicted volumes and operating volumes) from thoracic tomographs in patients before and after lung transplantation; 2) to find how relative expansion of the lungs affects pulmonary mechanics in the same patients; 3) to find how relative expansion of the chest affects chest wall mechanics and respiratory muscle function in the same patients; 4) to describe morphological adaptations of the rib cage in chronic and acute over- or underexpansion before and after transplantation by analysis of thoracic CT; and 5) to correlate outcome variables such as respiratory symptoms, exercise capacity, and significant infection with physiological, clinical and psychosocial data to test the possibility that chronic underexpansion of the allograft can lead to respiratory symptoms and disease. Findings will lead to specific recommendations about matching sizes of donor lungs with patients' chests and will guide the choice between double lung transplantation and single lung transplantation with or without volume reduction of the remaining lung.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Respiratory and Applied Physiology Study Section (RAP)
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Beth Israel Deaconess Medical Center
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