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Analysis of time-dependent risks for infection, rejection, and death after pulmonary transplantation
K Bando1, I L Paradis, K Komatsu
1Divsion of Cardiothoracic Surgery, University of Pittsburgh School of Medicine, Pa.
Abstract:
Infection and rejection remain the greatest threats to the survival of pulmonary allograft recipients. Furthermore, a relationship may exist between these events, because the occurrence of one may predispose to the other. By using multivariate analysis for repeated events, we analyzed the risk factors for bacterial, fungal, and viral infection, grade II or greater acute rejection, and death among 239 lung transplant recipients who received 250 allografts between January 1988 and September 1993. A total of 90 deaths, 491 episodes of acute rejection, and 542 infectious episodes occurred during a follow-up of 6 to 71 months. The hazard or risk patterns of death, infection, and rejection each followed an extremely high risk during the first 100 days after transplantation, a second modest risk period at 800 to 1200 days, and a lower constant risk. Infection and graft failure manifested by diffuse alveolar damage were the major causes of early death (< 100 days), whereas infection and chronic rejection were primary causes of later death after pulmonary transplantation. By multivariate analysis, cytomegalovirus mismatching risk for primary infection was the most significant risk factor for death, rejection, and infection. Absence of cytomegalovirus prophylaxis was also a risk factor for early and late death and late infection. Survival of recipients who received cytomegalovirus prophylaxis was significantly improved. Immunosuppression based on cyclosporine versus FK 506 was a risk factor for late death and late infection. Graft failure manifested by diffuse alveolar damage/adult respiratory distress syndrome was a significant risk for death late after transplantation. These data suggest the following: (1) The hazard for death, infection, and rejection after pulmonary transplantation appears biphasic; (2) lower survival is associated with ischemia-reperfusion lung injury represented by diffuse alveolar damage/adult respiratory distress syndrome; (3) cytomegalovirus mismatch, absence of cytomegalovirus prophylaxis, and development of cytomegalovirus disease are significant threats for death, rejection, and infection after pulmonary transplantation; (4) prevention of cytomegalovirus disease should improve survival by decreasing the prevalence of infection and rejection.
Insights
Lung transplant recipients face high early risks of infection and rejection. Cytomegalovirus (CMV) infection and prophylaxis absence significantly increase death and complications, highlighting CMV prevention
Area of Science:
- Pulmonary transplantation
- Transplant immunology
- Infectious diseases
Background:
- Infection and rejection are primary threats to lung transplant recipient survival.
- A potential link exists where one event may increase susceptibility to the other.
Purpose of the Study:
- To identify risk factors for infection, acute rejection, and death in lung transplant recipients.
- To analyze the relationship between infection, rejection, and mortality.
Main Methods:
- Multivariate analysis for repeated events was employed.
- Data from 239 lung transplant recipients (250 allografts) between 1988-1993 were analyzed.
- Risk factors for bacterial, fungal, viral infection, grade II+ acute rejection, and death were assessed over 6-71 months.
Main Results:
- A biphasic risk pattern for death, infection, and rejection was observed: high early risk (<100 days), a second modest risk (800-1200 days), and lower constant risk.
- Cytomegalovirus (CMV) mismatch was the most significant risk factor for death, rejection, and infection. Absence of CMV prophylaxis increased early and late death and late infection.
- Graft failure (diffuse alveolar damage/adult respiratory distress syndrome) and CMV disease were major causes of early and late mortality. CMV prophylaxis significantly improved survival.
Conclusions:
- Pulmonary transplant outcomes are influenced by a biphasic hazard for death, infection, and rejection.
- Ischemia-reperfusion injury (diffuse alveolar damage/adult respiratory distress syndrome) is linked to lower survival.
- CMV mismatch, lack of prophylaxis, and CMV disease are critical threats; CMV prevention is crucial for improving survival by reducing infection and rejection prevalence.