In nearly half of the deaths associated with lung transplant procedures, primary graft dysfunction can be attributed as the cause, report doctors in a new study.1 And the effect of this condition can last for years following the transplant procedure.
The researchers from the University of Pennsylvania School of Medicine found that even in patients who survived through the first year after the transplant procedure, if they had primary graft dysfunction at the time of the transplant, they still faced a higher risk of death later on.
A Routine Complication
Primary graft dysfunction is a form of acute lung injury that can occur after a transplant procedure, explained Jason Christie, MD, an assistant professor of Medicine and Epidemiology, who headed this study. It's a form of injury that occurs when the blood supply to the lung, or lungs, being transplanted is temporarily halted, then later restored following a transplant.
"Occurring in the first hours to days after transplantation, the clinical course and pathophysiology of the most severe forms are most similar to acute respiratory distress syndrome (ARDS)," Christie said, in a statement.
Morbidity/Mortality Risk
In fact, other experts point out that despite advances in lung transplant procedures in the last 20 years, primary graft dysfunction remains a significant cause of illness and death in transplant recipients.2 The condition can range from a mild case of hypoxemia, in which oxygen content in the blood is below normal, to a full-blown case of ARDS, requiring artificial ventilation, and medication. Patients with this condition also face a heightened risk of acute lung rejection.2
What's the Prognosis?
To assess the long-term prognoses of patients with primary graft dysfunction, Christie and his colleagues pulled the records of more than 5,000 lung transplant recipients from a database maintained by the United Network for Organ Sharing—the organization that oversees transplantation policy and organ procurement in the United States—and the International Society of Heart and Lung Transplantation. The patients had undergone transplants between 1994 and 2000.
After analyzing the data, the research team found that the overall incidence of primary graft dysfunction in this group was about 10%. "The incidence did not vary by year over the period of observation," they wrote.
More strikingly, however, is the finding that approximately 42 percent of the patients with primary graft dysfunction had died within 1 month of their transplant, compared to just 6 percent of the transplant patients without the condition; the risk for those with the syndrome was about seven times greater, Christie's group learned.
Among those patients who died within 30 days of their lung transplant, about 43 percent had primary graft dysfunction. Further, "among patients surviving at least 1 year, those who had primary graft dysfunction had significantly worse survival [odds] over ensuing years," the researchers wrote.
The study team also examined the patients' prognoses in cases in which bronchiolitis obliterans syndrome wasn't a factor, and found no difference. (Bronchiolitis obliterans syndrome is a form of injury to the lung caused by chronic rejection.)3
Other Questions Remain to be Answered
Christie and his colleagues did not investigate the reasons why primary graft dysfunction is associated with a significantly greater risk of dying since that information was not available. He said it may be due to the lingering effects of a long ICU course, or due to greater immune rejection mounted against the lungs in the early days following transplantation.
Those issues should be addressed in future research so that those with the condition can be treated effectively, he said.
Women May be More Prone
In a similar analysis performed by a different research team from the University of Pennsylvania,4 it was learned that women face a greater risk of developing primary graft dysfunction than men.
The researchers, led by Catherine Kuntz, MD, a Pulmonary Fellow at the Hospital of the University of Pennsylvania, combed through the records of 7,500 lung transplant recipients who underwent the operation between 1994 and 2002. They found that while 10 percent of these patients were afflicted with primary graft dysfunction postoperatively, women were 60% more likely to have the condition, regardless of whether they received their new lungs from a male or female donor. This was true even after the investigators considered other potential factors, such as the recipient's age, race and reason for lung transplant.
"There are a number of possible reasons why women are at increased risk," Kuntz speculated. "It may involve women's hormones or differences in their immune systems."
Lung transplantation was first performed in 1983.2 There are currently 3,628 patients on the lung transplant waiting list in the United States. Last year, there were 1,173 lung transplants performed.5
1. Christie JD, Kotloff RM, Ahya VN et al. The effect of primary graft dysfunction on survival after lung transplantation. Am J Resp Crit Care Med 2005 Jun 1;171(11):1312-6. Epub 2005 Mar 11.
2. de Perrot M, Liu M, Waddell TK, Keshavjee S. Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med 2003 Feb 15;167(4):490-511.
3. Hachem RR, Trulock EP. Bronchiolitis obliterans syndrome: pathogenesis and management. Semin Thorac Cardiovasc Surg 2004 Winter;16(4):350-5.
4. ATS 2005. International Conference of the American Thoracic Society. 2005 May 20-25. San Diego, CA.
5. The Organ Procurement and Transplantation Network. United Network for Organ Sharing (UNOS).
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
