Human Heart-lung Transplantation: Physiologic Aspects of the Denervated Lung and Post-transplant Obliterative Bronchiolitis

Eighteen sequential follow-up measurements of pulmonary function were obtained over a period of 21 months after heart-lung transplantation in a patient who had undergone surgery for end-stage pulmonary lymphangioleiomyomatosis. In the early postoperative period, there was a moderate decrease in VC and TLC but gas exchange was maintained at essentially normal levels. The most conspicuous features of postoperative lung function were a very low airway resistance and an increase in FEV1/VC ratio above 95%. These alterations were associated with an unusual shape of the maximal expiratory flow-volume (MEFV) curve. Instead of showing a uniform decrease in expiratory flow as expiration proceeds to residual volume, the post-transplant MEFV curve showed a peak followed by a gently sloping plateau ending at a knee where flow suddenly fell. The knee occurred after exhalation of 80% VC. From the sixth postoperative month, the patient developed rapidly increasing air-flow obstruction, which proved to be due to obliterative bronchiolitis. As airflow obstruction worsened, the knee on the MEFV curve progressively occurred at a higher lung volume, the flow plateau shortened, and flow after the knee became smaller at a given volume. From the ninth postoperative month, it was no longer possible to identify a plateau-knee configuration on the MEFV curve, which resembled that seen in severe obstructive airway disease. Analysis of these data according to recent theories of flow limitation suggests that (1) the flow plateau configuration of the MEFV curve in the early postoperative period was related to dynamic airway compression occurring in the trachea over most of the VC (we hypothesize that lung denervation and consequent loss of airway smooth muscle tone may be implicated in this phenomenon); (2) the subsequent shortening of the flow plateau indicates a progressively earlier shift of the site of flow limitation from extrapulmonary to intrapulmonary airways. This is likely to be related to an increase in frictional pressure losses in peripheral airways caused by the development of obliterative bronchiolitis.