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Original Articles: General Thoracic

Invited Commentary

Division of Cardiothoracic Surgery, The Ohio State University Medical Center, N835 Doan Hall, 410 W 10th Ave, Columbus, OH 43210

(Email: susan.moffatt-bruce{at}osumc.edu).

Lung transplantation is the ultimate therapy for advanced lung disease. The first lung transplant was performed more than 2 decades ago, and since that time, our technical and immunosuppressive expertise has improved. First-year survival statistics have improved, whereby more than 75% of recipients are expected to be alive after 1 year [1]. However, the International Society of Heart and Lung Transplantation Registry reveals that only 51% of patients are alive at 5 years, and even more discouraging is that only 28% of patients are alive at 10 year.

After the first year, the most common cause of morbidity and death is bronchiolitis obliterans syndrome (BOS). This form of chronic allograft dysfunction is truly the most significant obstacle to long-term well-being for lung transplant recipients. Research on the etiology of BOS is extensive and yet to date remains inconclusive. Several suggestions have included cytomegalovirus infection, early acute rejection, human leukocyte antigen mismatches, organizing pneumonias, nonuse of induction therapy, and most important, ischemia-reperfusion injury.

Ischemia-reperfusion injury is recognized as primary graft failure and, depending on the severity, affects not only the patient early in the postoperative period but also, potentially, the long-term outcome. As such, the article by Sugita and colleagues [2] reveals very exciting results that may serve to improve both early and late outcomes in lung transplant recipients.

The authors chose a large-animal model that has the potential to render the results translational to the clinical situation. Ischemia-reperfusion injury is likely to result from both a nonspecific inflammatory syndrome as well as an alloimmune-mediated process. Understanding this, they tested two agents: (1) phentolamine, which has been shown to modulate oxidative stress and alveolar liquid clearance in lung injury, and (2) FK506, which is currently the most commonly used immunosuppressant in lung transplantation and serves to down-regulate the allogeneic T-cell response. Not surprisingly, these agents did not individually improve outcomes, but instead appeared to work synergistically.

The phentolamine was administered to the donor to stave off the initiation of the nonspecific ischemia-reperfusion injury and the FK506 was administered to the donor to address the more specific T-cell response. The administration of these agents was deliberate, well thought out, and immediately clinically applicable. These authors have provided a very reasonable approach to improve early success in lung transplantation that truly has the potential to affect long-term outcomes.

	References

Top References

 

1. Christie JD, Edwards LB, Aurora P, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-fifth official adult lung and heart/lung transplantation report–2008 2008;27:957-969.
2. Sugita M, Berthiaume Y, VanSpall M, Dagenais A, Ferraro P. Pharmacologic modulation of alveolar liquid clearance in transplanted lungs by phentolamine and FK506 Ann Thorac Surg 2009;88:958-965.[Abstract/Free Full Text]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Susan Moffatt-Bruce Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moffatt-Bruce, S. Search for Related Content PubMed PubMed Citation Articles by Moffatt-Bruce, S. Related Collections Lung - transplantation Related Article