Obliterative bronchiolitis after lung and heart-lung transplantation

Abstract

With a prevalence of 34% (55/162 at-risk recipients) and a mortality of 25% (14/55 affected recipients), obliterative bronchiolitis is the most significant long-term complication after pulmonary transplantation. Because of its importance, we examined donor-recipient characteristics and antecedent clinical events to identify factors associated with development of obliterative bronchiolitis, which might be eliminated or modified to decrease its prevalence. We also compared treatment outcome between recipients whose diagnosis was made early by surveillance transbronchial lung biopsy before symptoms or decline in pulmonary function were present versus recipients whose diagnosis was made later when symptoms or declines in pulmonary function were present. Postoperative airway ischemia, an episode of moderate or severe acute rejection (grade III/IV), three or more episodes of histologic grade II (or greater) acute rejection, and cytomegalovirus disease were risk factors for development of obliterative bronchiolitis. Recipients with obliterative bronchiolitis detected in the preclinical stage were significantly more likely to be in remission than recipients who had clinical disease at the time of diagnosis: 81% (13/15) versus 33% (13/40); p < 0.05). These results indicate that acute rejection is the most significant risk factor for development of obliterative bronchiolitis and that obliterative bronchiolitis responds to treatment with augmented immunosuppression when it is detected early by surveillance transbronchial biopsy.

Current Status and Future of Lung Transplantation.

“…The pathogenesis of bronchiolitis obliterans remains poorly understood. However, the identification of acute rejection as the single mostimportant risk factor substantiates the hypothesis that this disorder is immunologically based (58,59 plantation with BLThaving a survival advantage (p<0.005).…”

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

“…In the 1980s, obliterative bronchiolitis (OB) was identified as a common pathology in chronically failing lung transplants; OB was subsequently discovered to also be a complication of bone marrow transplant recipients (90). Histologic features of lung transplant-associated OB include anatomic restriction to membranous and respiratory bronchioles, presence of both constrictive and proliferative subtypes, and potential association with mononuclear cell infiltration (91). Graft vasculopathy with progressive myointimal thickening of the pulmonary arteries and veins is also described in association with OB.…”

The Cell Biology of Cytomegalovirus: Implications for Transplantation

“…Furthermore, most studies have indicated that successful antiviral prophylaxis has a beneficial effect on long-term graft function (8). This suggests that viral replication is a component of risk, but the precise mechanisms underlying this effect are debated (9,11,(26)(27)(28)(29)(30)(31)(32)(33)(34).…”