UCSF Medical Center is at the forefront of successfully treating patients with end-stage lung disease who have exhausted traditional medical therapies. The UCSF Lung Transplant Program is one of three in the nation with higher-than-expected one-year patient survival rates, even though UCSF transplants some of the most complex patients. The program has performed 468 lung transplants since 1991, and is pioneering new approaches to improve outcomes and make transplantation available to more patients.
"Teamwork is critical to the success of our program," said Jasleen Kukreja, M.D., MPH, surgical director of the program. "This includes our pulmonologists, surgical housestaff, operating room staff, anesthesiologists, intensive care unit nursing staff, physical therapists, respiratory therapists and many others." Kukreja and the team perform 40 to 50 lung transplants annually.
"We continue to have excellent outcomes, while providing lung transplants for a very challenging patient population," said Steven Hays, M.D., the program's medical director. "Reasons for our success include our integrated team approach with our Advanced Lung Disease Program, our aggressive long-term medical management, and our focus on patient education. We push the envelope in terms of performing very active surveillance of our patients. We are very aggressive about treating infections and rejection."
Lung transplant can be an effective treatment for a wide spectrum of patients, including those with pulmonary fibrosis, bronchiectasis, cystic fibrosis, COPD, emphysema, alpha-1 antitrypsin deficiency and pulmonary hypertension. UCSF is also one of only a handful of programs that will transplant patients with scleroderma — associated interstitial lung disease; although these patients can be difficult to manage after surgery because they are at high risk for aspiration, UCSF monitors them rigorously and can refer them for gastric fundoplication and other interventions as needed.
At UCSF, one-year survival for lung transplant recipients is 90 to 94 percent, compared with 82 to 83 percent nationally. Three — and five-year survival rates are also higher than the national averages. Median survival at UCSF is about 6.8 years.
"The lung is a complex organ to deal with from an immunosuppression and infection standpoint," said Hays. "Survival has improved each decade, but we still have continued room for improvement. Most patients undergoing lung transplantation are not expected to survive another year, so it is a great option for those who are dying of lung disease."
Kukreja and her team are leading the way in bringing advanced technology to the program. "One of the limiting factors for long-term success in lung transplant is that lungs develop chronic rejection," said Kukreja. One likely contributing cause is ischemia reperfusion injury.
Transplant surgeons in other countries have pioneered the use of ex vivo lung perfusion, in which donor lungs are connected to a device that functions like a heart-lung machine — supplying the lungs with oxygen, removing carbon dioxide and ventilating the lungs. UCSF is participating in an international, multicenter, randomized clinical trial that will allow transplant surgeons to immediately connect donor lungs to this portable device at the procurement center and transport the organs back to UCSF while the lungs continue to "breathe." This may reduce the likelihood of primary graft dysfunction, which is the leading cause of mortality in the first 30 days. It may also ultimately allow UCSF to obtain donor lungs from more distant locations, such as Alaska and Hawaii, which are currently too far away from San Francisco to transport lungs before they begin to deteriorate. The device will also allow the surgical team to closely monitor the donor lungs, assessing their quality and functionality prior to transplant.
Eventually, the device could also be used to increase the number of acceptable donor lungs. "Right now, eight out of 10 donor lungs are rejected over the phone because they do not meet transplant criteria," said Kukreja. "Some of those rejected organs could now potentially be rehabilitated." For example, the transplant team can administer antibiotics, steroids and other medications to marginal donor lungs connected to the ex vivo lung perfusion device to reduce pneumonia, inflammation and swelling. After four to six hours of rehabilitative treatment and careful monitoring, transplant surgeons can then determine whether the lungs are suitable for transplantation.
A recent Canadian study published in the New England Journal of Medicine demonstrated that 20 out of 23 high-risk donor lungs were physiologically stable enough to transplant after following this protocol, and that recipients experienced similar outcomes to patients who received conventionally selected lungs. At UCSF, Kukreja believes that this new technology could eventually double the supply of donor lungs that are currently available. "The way that we surgically perform the operation five years from now is going to be very different from where we are now," she said. "I think this device is really going to change the way we perform lung transplants."
Another innovation is the use of extracorporeal membrane oxygenation (ECMO), which uses a pump to circulate blood through an artificial lung. UCSF Medical Center was one of the first centers in the country to deploy this technology as a bridge to transplant. A whole team is required to successfully use ECMO, and UCSF Medical Center staff are on duty 24/7 to monitor the equipment and the patient. With ECMO, patients have survived for over a month while donor lungs are identified. ECMO also allows patients to exercise and walk under the supervision of a physical therapist. This pretransplant conditioning reduces recovery time and improves outcomes. UCSF has performed more than two dozen transplants on such patients, with excellent outcomes.
UCSF also has the ability to use a portable form of ECMO. A surgeon or physician at a community hospital may request help if they have a patient with acute lung injury whose condition is not improving. UCSF lung transplant surgeons can go to the community hospital, place the patient on ECMO, then transport the patient to UCSF for further care and evaluation. Some patients are able to recover, and others have successfully received lung transplants.
UCSF faculty are also leading a number of research initiatives in lung transplantation, including investigations using stem cell therapy to rehabilitate donor lungs, identifying factors that affect quality of life in lung transplant recipients, developing better ways to predict outcomes based on measurements of frailty, studying risk factors for the development of skin cancer in lung transplant recipients, and identifying biomarkers associated with lung rejection.
Kukreja believes that innovations such as ex vivo lung perfusion will support the growth of the program, and in the next three years hopes to significantly increase the number of lung transplants per year and reduce the mortality on the waiting list. "I want UCSF to be the top, not only in outcomes, but also in lung transplant research," she said. "We have the desire, intellect, support and the critical mass to make it happen."
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