Lung Transplantation PGD, and BOS
Daus SA, Yusen RD, Meyers BF, et al.
Am J Respir Crit Care Med. 2007;175:507-513
Two of the biggest problems affecting outcomes in lung transplantation are primary graft dysfunction (PGD) and bronchiolitis obliterans syndrome (BOS). The former occurs immediately or within the first few days after transplant and is the most common early cause of mortality. BOS which is largely felt to correlate to chronic allograft rejection is the most common cause of death beyond the first year. Because the intervals between their occurrences are so long, these 2 processes, PGD and BOS, would appear to be "disconnected." The authors of this article sought to investigate the relationship of these 2 distinct entities, by examining whether PGD, occurring immediately post-transplant, predisposes patients to the subsequent development of BOS.
A retrospective review of 336 lung transplant recipients was performed. PGD was graded as per the International Society for Heart and Lung Transplantation criteria immediately after transplant. Approximately 19% of the patients did not have PGD, 39% had PGD grade 1, 21% had PGD grade 2, and 21% had PGD grade 3. PGD was found to be an independent risk factor for the subsequent development of BOS. The grade of PGD also appeared to have an influence on BOS with grade 3 PGD having the highest incidence of occurrence. The association between PGD and BOS persisted even after accounting for acute rejection, lymphocytic bronchitis, and community acquired viral infections. One might hypothesize, that if indeed there was a link between PGD and BOS, this might be provided by episodes of acute rejection, a known risk factor for BOS.
While the association between PGD and BOS is somewhat unexpected, the authors do a very nice job in raising potential mechanisms whereby this might occur. The injurious process increasing the immunogenicity of the allograft with the upregulation of major human leukocyte antigens and surface adhesion molecules or possibly through nonimmune mechanism with a disordered repair process may be a cause.
Due to the retrospective nature of the study's design, the authors were not able to assess the influence of PGD on BOS beyond time 0. How the relationship would be affected by assessing PGD beyond time 0 is subject to speculation and requires further study. Although there were some methodologic issues with this study due to its retrospective nature, it does raise some important points and concerns. Most importantly, it appears that PGD might be important to prevent, not only for its immediate impact on morbidity and mortality, but also for its long-term consequences including the risk of BOS and long-term survival.
Abstract
Supported by an independent educational grant from Actelion
Daus SA, Yusen RD, Meyers BF, et al.
Am J Respir Crit Care Med. 2007;175:507-513
Two of the biggest problems affecting outcomes in lung transplantation are primary graft dysfunction (PGD) and bronchiolitis obliterans syndrome (BOS). The former occurs immediately or within the first few days after transplant and is the most common early cause of mortality. BOS which is largely felt to correlate to chronic allograft rejection is the most common cause of death beyond the first year. Because the intervals between their occurrences are so long, these 2 processes, PGD and BOS, would appear to be "disconnected." The authors of this article sought to investigate the relationship of these 2 distinct entities, by examining whether PGD, occurring immediately post-transplant, predisposes patients to the subsequent development of BOS.
A retrospective review of 336 lung transplant recipients was performed. PGD was graded as per the International Society for Heart and Lung Transplantation criteria immediately after transplant. Approximately 19% of the patients did not have PGD, 39% had PGD grade 1, 21% had PGD grade 2, and 21% had PGD grade 3. PGD was found to be an independent risk factor for the subsequent development of BOS. The grade of PGD also appeared to have an influence on BOS with grade 3 PGD having the highest incidence of occurrence. The association between PGD and BOS persisted even after accounting for acute rejection, lymphocytic bronchitis, and community acquired viral infections. One might hypothesize, that if indeed there was a link between PGD and BOS, this might be provided by episodes of acute rejection, a known risk factor for BOS.
While the association between PGD and BOS is somewhat unexpected, the authors do a very nice job in raising potential mechanisms whereby this might occur. The injurious process increasing the immunogenicity of the allograft with the upregulation of major human leukocyte antigens and surface adhesion molecules or possibly through nonimmune mechanism with a disordered repair process may be a cause.
Due to the retrospective nature of the study's design, the authors were not able to assess the influence of PGD on BOS beyond time 0. How the relationship would be affected by assessing PGD beyond time 0 is subject to speculation and requires further study. Although there were some methodologic issues with this study due to its retrospective nature, it does raise some important points and concerns. Most importantly, it appears that PGD might be important to prevent, not only for its immediate impact on morbidity and mortality, but also for its long-term consequences including the risk of BOS and long-term survival.
Abstract
Supported by an independent educational grant from Actelion
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