Primary graft dysfunction, a common complication that affects up to 25 percent of lung transplant patients shortly after surgery, constitutes a significant risk factor for later deadly bronchiolotis obliterans syndrome (BOS).
This research appears in the first issue for March 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.
Ramsey R. Hachem, M.D., of the Division of Pulmonary and Critical Care at Washington University School of Medicine in St. Louis, and eight associates examined the impact of primary graft dysfunction on the development of BOS in 320 lung transplant recipients.
BOS, a chronic scarring process that affects the small airways of the lungs years after transplant surgery, results in the progressive obliteration of the small airways with resulting obstructive lung disease. BOS is a leading cause of death after the one-year anniversary of a lung transplant.
"We found that primary graft dysfunction is associated with an increased risk of BOS independent of certain other risk factors, including acute rejection and community-acquired respiratory viral infections," said Dr. Hachem.
Clinically and pathologically, primary graft dysfunction is a devastating form of acute lung injury that affects transplant patients in the first hours after they receive transplanted organs. The complication, which mimics adult respiratory distress syndrome, can be fatal for up to 50 percent of affected transplant patients.
"Among the 320 recipients studied, 161 developed BOS, with the median time to onset at close to four years," said Dr. Hachem. "Lung transplant recipients who did not have primary graft dysfunction had significantly greater freedom from BOS than those who developed any grade of primary graft dysfunction."
The researchers graded the severity of subjects' primary graft dysfunction according to the International Society for Heart and Lung Transplantation (ISHLT) definition. Those who did not have primary graft dysfunction immediately after transplantation were classified grade 0, while those with more severe graft dysfunction received a 1, 2 or 3.
In their analysis, the investigators found that all grades of primary graft dysfunction were associated with a significantly increased risk of BOS. Recipients with primary graft dysfunction grade 1 had the relative risk of 1.73; those with grade 2 had a relative risk of 2.13; and those with grade 3 were 2.53 times more likely to experience the later problem.
"This association has important clinical implications and suggests that the immunosuppressive regimen should be optimized and that lung function should be monitored closely for patients who develop primary graft dysfunction," said Dr. Hachem.
The researchers noted that additional studies are needed to further investigate the molecular mechanisms of primary graft dysfunction and its relationship to BOS.
According to the ISHLT, this area of study is becoming increasingly important, as the number of lung transplants performed in the U.S. was a record 1,815 last year. They reported that survival was 78 percent at one year, 61 percent at three years, 49 percent at five years, and 25 percent at 10 years.