BY pam mcgrath
Image courtesy of Shutterstock
Thirty-five years ago, specialists at Washington University School of Medicine and what was then Barnes Hospital played an integral role in advancing the new and developing field of lung transplantation. In January 2023, the Washington University and Barnes-Jewish Transplant Center performed its 2,000th lung transplantation. Here’s how it happened.
No. 45: That number represents one of the pivotal moments in lung transplantation history. In 1983 at the University of Toronto General Hospital, a thoracic surgery team performed the world’s 45th lung transplant: a single lung for Tom Hall, 58, a man with pulmonary fibrosis. Hall lived six years after the surgery. He is now recognized as the first long-term lung transplant survivor.
This milestone was significant because it demonstrated the potential viability of lung transplantation for people with lung disorders. It also proved to be the foundation upon which members of that Toronto thoracic surgery team would establish a pioneering lung transplantation program at Barnes-Jewish Hospital, which would become one of the earliest and largest in the world.
A tenuous start
James Hardy, MD, performed the first-ever human lung transplant surgery in 1963 at the University of Mississippi Medical Center. While the surgery itself was a success, the patient died 18 days later of renal failure. Within a few days of Hardy’s surgery, a second lung transplant surgery was performed at Presbyterian-University Hospital in Pittsburgh; the patient died within a week. In 1971, a patient in Belgium survived 10 ½ months after his lung transplant—but he was hospitalized much of that time. By 1983, 20 years after Hardy’s first attempt, only 40 patients worldwide had undergone lung transplantation, and none of them survived longer 10 ½ months.
Then came Joel Cooper, MD, and his team in Toronto; they performed Hall’s transplant surgery. One member of that team, G. Alexander Patterson, MD, is now a Washington University thoracic surgeon at Barnes-Jewish Hospital and has been for the past 32 years.
MEMBERS OF THE EARLY LUNG-TRANSPLANT TEAM AT BARNES-JEWISH HOSPITAL INCLUDED (FROM LEFT TO RIGHT): WASHINGTON UNIVERSITY PHYSICIANS ELBERT TRULOCK, MD; JOEL COOPER, MD; JOHN FRATTINI, MD; AND NEIL ETTINGER, MD.
Photo courtesy of Bernard Becker Medical Library, Washington University School of Medicine
“The major obstacle in the early days was revasculating—restoring blood flow—to the transplanted windpipe” explains Patterson. “Other transplanted organs are revascularized during surgery—the kidney by a renal artery, the liver by a hepatic artery and portal vein, the heart by the coronary circulation.”
Patterson estimates that ischemia, an inadequate blood supply, between the bronchus (air passages) of the donor lung and that of the recipient caused half of the early lung transplant failures.
“The other potential obstacle to successful lung transplantation was the nature of the lungs themselves,” says Patterson. “Unlike other transplanted organs, lungs are exposed to the external environment as they take in oxygen, which means there’s the potential for damage because the lungs may also take in harmful toxins or bacterial organisms.”
In 1981, Bruce Reitz, MD, and his colleagues at Stanford University performed the first heart-lung transplant, for a 45-year-old woman with primary pulmonary hypertension. The surgery succeeded at least in part because the donor heart attached to the lungs provided some blood circulation to the donor windpipe. This en bloc (heart and lung together) approach was used through the 1980s by several transplant centers as a strategy for people with end-stage lung disease. It was a way to lessen the risk of damage caused by breathing tubes in the trachea that had proven fatal in previous transplant recipients.
It wasn’t until 1986 that the first successful en bloc double lung transplant for emphysema was performed, with Patterson leading the Toronto thoracic surgery team. That patient, Ann Harrison, 42, lived nearly 15 years.
“Over time, technical refinements that promoted airway healing, as well as the development of various surgical approaches, contributed to the growing success of lung transplantation,” says Patterson. “The immunosuppressant drug cyclosporine, approved by the Food and Drug Administration in 1983, was another important advancement that significantly affected lung-transplant patients’ outcomes.”
Becoming a leader
In 1988, Washington University School of Medicine recruited Cooper to lead its section of general thoracic surgery. With his interest in the still-developing field of lung transplantation, and the expertise he had gained in Toronto, it was virtually inevitable that he and his new colleagues would establish a lung transplant program at Washington University and what was then Barnes Hospital. Among those co-founders was Elbert Trulock, MD, now professor emeritus at Washington University School of Medicine, who served as the program’s first medical director. Today, Trulock is recognized worldwide as an expert in managing the care of lung transplant patients.
“Establishing the program was a voyage of discovery,” says Trulock. “Lung transplantation was so new that we couldn’t anticipate complications or outcomes because we were seeing these things for the first time. But with each person we treated, we added to our cumulative experience, which snowballed in our favor over time.”
Patterson added to that knowledge when he joined Washington University in 1991. With lung transplantation pioneers Cooper and Patterson on board and pulmonologist Trulock overseeing patients’ pre- and post-medical care, the program quickly took on a leadership role nationwide, becoming one of only three large lung transplant centers in the U.S. This team made important contributions to the process of recipient and donor selection, as well as procedural technical advances, operative management and innovative application of lung transplantation for those people not considered transplant-eligible elsewhere. The protocols developed at Washington University and Barnes Hospital became the standards by which both new and existing lung transplantation programs were measured.
The patients
Trulock points out that a successful lung transplantation program requires thoracic surgeons, pulmonologists, anesthesiologists, nurses, physical therapists—and patients. But in 1988, patients were not in plentiful supply.
“Keep in mind, lung transplantation was not widely known as an option when we began our program because so few had been performed,” says Trulock. “And at the time, our criteria for selecting transplant candidates were relatively narrow compared to what we follow today.”
In those early days, only a small subset of people who needed transplantation were approved for the procedure. Candidates had to be in generally good health except for their underlying lung condition and be age 65 or younger. In addition, health parameters were used to gauge the severity and prognosis of their lung disease; people likely to succumb within a few years to their underlying lung disease were given priority.
“As we gained experience, we learned there is no real reason to use an age barrier to transplantation. Today, approximately 30% of patients receiving lung transplants are over age 65,” says Trulock. “Those having health conditions in addition to their lung disorder are no longer automatically excluded from consideration. And many more transplant candidates are seriously ill and hospitalized or even on life support. In 1988, we would have considered the likelihood of success for these people to be nearly impossible.”
He adds, “Our status as one of the first dedicated transplant programs resulted in our having a significant role in developing management strategies and protocols for recipients. Physicians and other care teams would visit to see how our program was structured: Who were our staff members, what immunosuppressive regimen did we use and how did we follow it, how did we monitor patients? It was gratifying that many programs patterned their organizational structure on ours.”
WE HAVE MADE SIGNIFICANT CONTRIBUTIONS IN TRANSLATIONAL RESEARCH— BASIC RESEARCH DIRECTLY BENEFITING PATIENTS—THAT HAS RESULTED IN IMPROVED DONOR LUNG PRESERVATION.
The donors
In 1988, the scarcity of patients was matched by the lack of donor lungs.
“In the beginning, organ procurement organizations routinely providing hearts, kidneys and livers weren’t accustomed to thinking about lungs as a potentially transplantable organ,” says Trulock. “There was some education needed in that area.”
Washington University lung transplant physicians at Barnes Hospital were among the first to publish findings regarding the criteria for suitable lung donors, including: age younger than 55 years, smoking less than 20 pack-years (a pack a day for 20 years or two packs a day for 10 years) for and a clear chest X-ray. But just as the pool of people awaiting transplants expanded over the years, so did the pool of potential acceptable donors.
“Historically, the initial criteria for donor acceptance were fairly conservative. Over time, many centers, including our own, have progressively liberated these criteria using ‘extended criteria’ donors and have had good outcomes,” says Ramsey Hachem, MD, Washington University pulmonologist at Barnes-Jewish Hospital and medical director of the lung transplant program. Today, Hachem notes, many acceptable donors are older than 55 years, some with test results that previously might have excluded them from transplantation. “There is ongoing research focused on donor management and better donor-recipient matching to improve donor utilization,” he says.
Improved techniques for readying lungs for donation and preserving them prior to transplantation has also increased the number of available lungs.
“As with all organs, the United Network for Organ Sharing, or UNOS, is responsible for matching donated lungs to transplant candidates,” says Gary Marklin, MD, chief medical and research officer for Mid-America Transplant, the organization that manages organ procurement in eastern Missouri, southern Illinois and northern Arkansas. “In the beginning, lungs were allocated on a first-come, first-served basis. Once patients were placed on the list, they began accumulating time. Those who had been on the list longest were transplanted first when suitable lungs became available.”
The result was that people on the list with diseases such as emphysema, which were debilitating but not urgently fatal, were being transplanted before those whose lung disorders would result in a limited life expectancy.
“To eliminate these disparities, in 2005 UNOS implemented its lung allocation score, which uses medical information on each transplant candidate to estimate the severity of illness and the chance of success following a transplant. Candidates are listed in the order of the score they receive, from 0 to 100,” says Marklin.
He notes that research undertaken at Mid-America Transplant—the first such organization to build an independent organ recovery center outside of a hospital, which it did in 2001—is further expanding the donor pool for lung transplantation.
By way of example, Marklin notes research at Mid-America Transplant that is aimed at helping to expand that donor pool. One study showed that new protocols could increase viable lungs for transplant from 23% of potential donors to 44%. He adds: “Over the past 10 years, lungs from one out of three of our donors are suitable for transplant compared to a national average of one out of five.”
Commitment to research—and to the future
Since its inception, a hallmark of the Washington University lung transplantation program at Barnes-Jewish Hospital has been its commitment to research.
“Today there are many large, successful lung transplant programs in the world. But few are supported by a vibrant, active research laboratory that has been funded by the National Institutes of Health for 35 years,” says Patterson. “We have made significant contributions in translational research—basic research directly benefiting patients—that has resulted in improved donor-lung preservation.”
The laboratory, overseen first by Cooper and then Patterson, is now led by Daniel Kreisel, MD, PhD, surgical director of lung transplantation at the Transplant Center.
“We are one of the leading lung transplant research programs in the world,” says Kreisel. “Through our pioneering work with mouse lung transplants, we have described numerous pathways that lead to good and bad outcomes after lung transplantation.” One of the goals, Kreisel says, is to translate those findings into larger animals and humans. Researchers want to understand why lung transplantation is prone to conditions like primary graft dysfunction, an inflammatory process that occurs immediately following transplantation, and to chronic lung allograft dysfunction, a rejection process that develops in about 40% of patients five years after their transplant.
Ongoing research also includes examining the experiences of lung transplant programs across the country and looking at ways to optimize management of donors. “The outcomes for lung transplantation are far worse than for other transplanted organs, especially as patients reach three, five, 10 years of survival. We are working to understand why and develop solutions to the problems,” says Kreisel. “For instance, the immunosuppressants prescribed for lung transplant patients are based on experiences with liver and kidney transplant recipients. Medications designed specifically for lung transplantation may influence patients’ outcomes.” The program is active in clinical trials, including one currently underway testing new immunosuppressive medication in lung transplant patients.
Kreisel sees personalized medicine as the possible answer to increasing survival rates for lung transplant patients. “Once we understand exactly what causes complications following transplantation, we may be able to alter the donor lung,” he explains. “For example, we may be able to genetically alter the lungs by deleting specific cells that lead to bad outcomes or enriching cells that promote good outcomes.” Those possibilities, Kreisel says, represent the next phase of lung transplantation, and transplantation in general. “We hope to be able to fit the donor lung or other donor organ to work well in the immunological landscape of the recipient to minimize complications.”
Watch a video about the 2,000th lung transplant at Barnes-Jewish Hospital.