Winter 2006

Lung Transplantation Program Growing Rapidly

Last year, UCSF thoracic transplant surgeons implanted more than 50 lungs, making the UCSF program one of the largest programs in California. The rapidly growing lung transplantation program owes its strength to its research program, organ procurement organization, and surgical and medical staff, UCSF physicians say.

The success of the program is especially notable because some of those patients were sufficiently sick that they would not have been considered transplant candidates using traditional criteria for recipient candidacy.

The rate of lung transplantation has grown rapidly in the last two years, but is built upon longstanding clinical and research experience with pulmonary disorders. Over the last 25 years, Jeffrey Golden, M.D., has been studying and treating interstitial lung disease, a broad category that includes more than 130 disorders. The common feature of these diseases is that they cause pulmonary fibrosis. Eventually, stiffness and alveolar dysfunction require transplantation.

Golden's research is one reason why patients with interstitial lung disease make up about half of those getting lung transplants at UCSF, whereas in other programs, the majority of lung transplant recipients have emphysema. Significant numbers of patients at UCSF get lung transplants to treat scleroderma, cystic fibrosis and pulmonary hypertension.

Golden, who is medical director of the lung transplant program, began the program in 1991. Although the program has been growing steadily since then, Golden credits the recruitment of director of Heart and Lung Transplants Charles Hoopes, M.D.;, two years ago with tripling the size of the program. "There are a lot of factors that contribute to our success, but a large part of it is that we have a fantastic surgeon who has made a major commitment to heart and lung transplantation," Golden says.

Organ Procurement Key

Hoopes and Golden both mention a remarkable organ procurement organization (OPO) as one of the foundations of the UCSF lung transplant program. "We are blessed with the best lung OPO in the country," Hoopes says. "We set the bar much higher for our local OPO."

Hoopes and Golden say that Wayne Babcock, R.N., at the California Transplant Donor Network in Modesto has pioneered new techniques to keep the lungs in good shape for transplantation. The efforts of the lung OPO enable the use of lungs that would be rejected elsewhere. "In the rest of the country, about 17 percent of donated lungs are good enough for transplantation, whereas here, about 50 percent are high enough quality," Golden says.

Patients also are evaluated for lung transplant individually, based on criteria that fit their personal circumstances, rather than according to rigid national guidelines. Many of these patients wouldn't be considered candidates for a lung transplant at other institutions, UCSF surgeons say.

Assessing patients based on criteria tailored to their individual circumstances doesn't necessarily lead to higher-risk procedures, Hoopes says. "Some are higher-risk patients and some are lower-risk," he says.

Regardless, says Hoopes, a lung transplant is a risky procedure in which statistics can be misleading. "If our one-year survival is consistently above 90 percent, we worry that we are not offering very sick patients with end-stage disease the opportunity for lifesaving surgery. The goal of lung transplantation is to reestablish a normal quality of life in patients simply surviving with diseased lungs. It is responsible utilization of the scarce resource of donor lungs that defines the newer organ allocation system."

Raising post-transplant survival statistics has been a motivating force behind Golden's research. One key element of his work centers on finding ways of predicting or detecting early signs of obliterative bronchiolitis (OB), which has emerged as the main cause of morbidity and mortality in long-term follow-up after lung transplant.

OB is characterized by immune reactions that lead to luminal obliteration and scarring in the small airways of the lungs. Its cause is multifactorial, but acute rejection and viral infection are the main causes.

Golden's research has investigated the use of expiratory, dynamic, ultrafast, high-resolution CT scanning as a way to predict impending OB. He also has investigated using a novel endobronchial biopsy as an early assessment tool.

Another interesting line of research centers on Golden's discovery that early airway rejection correlates with increased fibroblast proliferation in serial lavage fluid. In collaboration with George Caughey, M.D., Golden has recently finished a study of the gene expression profiles of cells in serial lavage fluid and airway biopsies. They found that certain gene expression profiles in lung allograft biopsies correlate with lymphocytic bronchitis that precedes OB. Golden and his colleagues are now looking for similar protein and blood markers.

UCSF's clinical and research strengths should lead to continued growth of the lung transplant program, Hoopes and Golden say. Hoopes foresees a doubling of the current volume of lung and heart transplants in the coming years. "Thoracic transplantation is moving toward a regional model, instead of one in which local medical centers do small numbers of risk-stratified patients," Hoopes says. "I would like to see us doing 100 cardiothoracic transplants a year."

To contact Dr. Charles Hoopes, call (415) 353-1606. To contact Dr. Jeffrey Golden, call (415) 353-2935.

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