Simulation of lung function evolution after heart-lung transplantation using a numerical model.

A morphometry-based computational model for expiratory flow in humans was used to study the unusual configuration of the maximum expiratory flow-volume (MEFV) curve associated with alterations in lung function after heart-lung transplantation (HLT). The postoperative MEFV curve showed a peak, followed by a gently sloping plateau over the midvolume range, ending in a knee where the flow suddenly fell, instead of the usual observed uniform decrease in expiratory flow. We have tested several hypotheses about the relationship between the pattern of changes in the configuration of the MEFV curve and pathological changes in the airway mechanics through computer simulations. Principally, effects of lung denervation and airway obstruction, associated with the development of bronchiolitis obliterans in the lung periphery, have been investigated. The calculated curves are similar in appearance to the measured postoperative flow-volume curves and confirm reliability of the earlier hypotheses. We conclude that the plateau-knee configuration of the MEFV curve can result from flow limitation in one of the first airway generations, that this flow limitation coupled with an increase in peripheral airway resistance results in plateau shortening, and that flows exceeding predicted values during the second part of expiration may be produced by lung denervation. Additionally our results demonstrate that airways larger than the transitional and respiratory bronchioles can be involved in pulmonary function deterioration observed in patients affected with obliterative bronchiolitis. Our findings indicate that the computational model, based on a symmetrical dichotomous branching structure of the bronchial tree, along with pathological data, can be employed to evaluate the effects of heterogeneous changes in the lung periphery. Index Terms-Airway mechanics, forced expiration, lung transplantation, mathematical modeling, maximal expiratory flow-volume curve.