“The availability of suitable donor lungs for transplantation continues to be a major obstacle to increasing the number of lung transplants performed annually, and this study demonstrated that reasonable outcomes are possible with the use of advanced age donors,” said William Micah Whited, MD, University of Louisville Department of Surgery. “Research such as this that explores the means of expanding the donor pool is of critical importance.”

Whited, along with senior author Matthew Fox, MD, of the Department of Cardiovascular and Thoracic Surgery and other colleagues from UofL, queried the United Network of Organ Sharing thoracic transplant database to identify lung transplant recipients age 18 years or older.

Between January 2005 and June 2014, 14,222 lung transplants were performed. Of these lung transplant recipients, 26 percent were age 50 years or younger, with 2 percent receiving lungs from donors older than age 60. Among this group of younger patients who received older donor lungs, there was no significant difference in five-year survival when compared to patients who received lungs from younger donors.

The researchers also examined the impact of double versus single lung transplant on long-term survival, finding that younger patients who received older donor lungs experienced much better outcomes when a double versus a single transplantation was performed.

The study showed that in younger patients who received a single lung transplant using organs from older versus younger donors, there was a lower five-year survival: 15 percent versus 50 percent. However, with a double lung transplant, there was no significant difference in five-year survival: 53 percent versus 59 percent.

“Ideal donor” criteria vary by hospital, but the researchers said that the criteria generally consist of brain death, age less than 45 to 50 years, minimal smoking history, and no evidence of pneumonia or trauma. Donor organs that do not meet all of the ideal donor criteria are sometimes accepted, but not always.

Whited said that while the use of extended criteria donor lungs varies from program to program, most surgeons should be willing to accept non-ideal donors, especially those who are older but otherwise good candidates.

“The vast majority of potential donors do not meet the relatively strict donor criteria,” he said. “As a result, we need to continue exploring options that would expand the donor pool and more aggressively utilize extended criteria donors. Much like the general population, the donor pool has continued to grow older. Now more than ever, we have to rely on older donors.”

The U.S. Organ Procurement & Transplant Network reports that 1,399 people currently are waiting for a lung transplant in the United States. The overall median waiting time for candidates on the wait list is four months, while more than 200 people die annually waiting for a lung transplant, according to an OPTN report.

The UofL Center is one of only 20 in the nation. It’s funding score for the grant was the best in the nation, and it is the only center with a nutrition focus.

“We are going to take a unique focus into organ injury associated with alcohol use,” said Dr. Gregory C. Postel, interim executive vice president for health affairs at UofL. “Our researchers are going to examine the interactive role of nutrition and alcohol in the deleterious, as well as beneficial, effects of alcohol on the human body.”

Through four different projects, the research team led by Dr. Craig McClain, associate vice president for translational research and associate vice president for health affairs/research, has three specific aims:

1. Facilitate interdisciplinary approaches and serve as a regional/national resource for the study of nutrition and alcohol-induced organ injury;
2. Provide a robust pilot project program and comprehensive education and research training in order to develop the next generation of alcohol investigators; and
3. Develop potential therapeutic targets/interventions for alcohol-induced organ injury based on the mechanistic research of the center and translate knowledge/interventions to the community.

“This funding will allow us to look at the problems that alcohol abuse causes, as well as the potential benefits of alcohol,” McClain said. “Our focus on dietary nutrition and abuse is unique. For example, only a small proportion of people who abuse alcohol will develop liver disease. We believe that the type of dietary fat intake is critical in the development of alcohol-induced organ injury.”

To find answers, the center will initially focus on four projects.

Project 1 will evaluate the role of dietary unsaturated fat in the development/progression of alcoholic liver disease.

Project 2 will evaluate alcohol-induced alterations in the gut-liver axis. Researchers will examine the role of histone deacetylases (HDACs) in both the intestine and liver in alcohol-induced gut-barrier dysfunction and steatohepatitis and the role of probiotics and dietary HDAC inhibitors in preventing/treating experimental ALD.

Project 3 will determine mechanisms by which maternal alcohol consumption causes mental retardation in the offspring. Researchers will evaluate epigenetic mechanisms by which alcohol induces apoptosis and teratogenesis, and by which the nutraceutical, sulforaphane, provides epigenetic protection.

Project 4 will evaluate mechanisms by which alcohol causes increased susceptibility to acute lung injury. They postulate that chronic alcohol intake triggers extracellular matrix remodeling resulting in “repavement” of lung tissue with a proinflammatory extracelluar matrix and that this process can be modulated by dietary intervention.

“Our studies are designed to look at a number of organ systems, not just the liver,” McClain said. “Additionally, we are very interested in gaining a better understanding of the role alcohol may play during fetal development and the mechanisms associated with fetal alcohol syndrome.”

The research team spans 13 departments at UofL in six schools/colleges.

“One of the keys to developing the breadth of information we hope to achieve is bringing together people with expertise in areas that often are not combined,” McClain said. “It is important that we look at these issues from a broad perspective if we are to examine the overall impacts of alcohol.”

Here is more information about the Alcohol Research Center: