Risk factors for chronic rejection in heart and lungs – Why do hearts and lungs rot?

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Abstract
The major cause of graft loss and patient death during the 1st yr after heart transplantation is progressive coronary occlusive disease. All survival curves show progressive and persistent graft loss over time. To improve the overall results of heart transplantation, attention must be directed to the etiology, prevention, and treatment of coronary occlusive disease. This condition affects both small and large vessels, and most probably results from a continuous immune insult that generates smooth muscle proliferation and subsequent development of atheromatous plaque. Multivariate analysis suggests that highly significant risk factors for the development of coronary occlusive disease include preoperative diagnosis of ischemic heart disease, age of recipient, and age of donor. Other risk factors, notably cytomegalovirus (CMV) infection, have not proved to be independent causes of coronary occlusive disease in our series. Diagnosis before the occlusive disease sets in, as well as the development of new therapeutic strategies, may prevent or delay the onset of coronary artery disease, thereby improving overall results of heart transplantation. Graft loss from lung transplantation after the 1st yr is associated with obliterative bronchiolitis. This final end‐stage progressive loss of small airways can be seen not only in transplanted lungs but in lungs with chronic infection. It appears to be a final common pathway for lung injury, but following transplantation it is most likely to be mediated by rejection. Risk factor analysis in our series indicates that severe or persistent rejection in the first few months is associated with the subsequent development of obliterative bronchiolitis. CMV does not appear to be an independent causal variable in obliterative bronchiolitis, although it may have a role through its association with the development of rejection. Another possible etiology is damage to the bronchopulmonary vasculature; this would be of particular importance in isolated lung transplantation without revascularization of the bronchial arteries, in which case the bronchial circulation is reliant on collaterals through the pulmonary circulation. It is yet to be seen whether this is a significant issue in the development of obliterative bronchiolitis.