Pioneering Lung Transplantation in Toronto

Pioneering Lung Transplantation in Toronto

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By: Petri Takkala

Joel D. Cooper, MD, FACS
Chief of Thoracic Surgery, Department of Surgery, University of Pennsylvania Health System
Emeritus Professor of Surgery, Perelman School of Medicine, University of Pennsylvania
Former Clinician-Scientist, Institute of Medical Science, Faculty of Medicine, University of Toronto (1972-1988)

Lung transplantation is a relatively new approach to treating end-stage lung diseases. The first lung transplant was attempted by Dr. James Hardy in 1963, but the patient died 18 days later. Subsequently, lung transplants were attempted unsuccessfully in 44 patients, making it clear that a number of challenges had to be overcome before lung transplantation could be possible—for example, immunological complications that led to organ rejection, and failed wound healing in lung transplant recipients. Indeed, failure of the bronchus connection to heal properly has often been called the “Achilles’ heel” of lung transplants. Through the 1970’s and 1980’s, a group of surgeons in Toronto—including former Institute of Medical Science (IMS) clinician-scientist, Dr. Joel Cooper—devised strategies to solve this problem.

Dr. Joel Cooper came to Toronto in 1972 after obtaining his medical degree from Harvard Medical School and completing his clinical training. At the time, Dr. Griffith Pearson was a leading figure in his field: as head of thoracic surgery in Toronto, he established a thoracic surgery research lab and recruited Dr. Cooper to work on extracorporeal membrane oxygenation (ECMO)—the artificial heart-lung system. Several years later, Dr. Pearson invited Brazilian clinician Dr. Oriane Lima to join his lab under the mentorship of Dr. Cooper. To be allowed to supervise a graduate student, Dr. Cooper joined the IMS, which provided structure for the PhD training.

In 1978, Drs. Cooper and Bill Nelems—another clinician working on Dr. Pearson’s team—performed an autopsy on a lung transplant patient who had died shortly after the operation after being removed from their artificial ventilator. They determined that death resulted from bronchial dehiscence—wound rupture at the bronchial connection between the donor organ and recipient. Thus, the “Achilles’ heel” was identified: they postulated that this failure in wound healing could be due to the effects of immunosuppression, or ischemia (insufficient blood supply) of the donor bronchus.

In the lab, Drs. Cooper and Lima devised a set of experiments to investigate the wound-healing problem. In the first set of experiments, Dr. Cooper and his team removed and replaced the lungs of individual dogs, to avoid the issue of donor lung rejection. Next, they gave the dogs prednisone and azathioprine, two types of steroid immunosuppressants commonly used in lung transplantation. Drs. Coopers and Lima observed that compared to dogs that did not receive steroid immunosuppressants, the airway connection of immunosuppressed dogs did not heal properly. Therefore, they concluded that steroid immunosuppression had been preventing wound healing. As a substitute for high dose steroids, cyclosporine—an experimental drug used in some heart transplants—was found to significantly improve wound healing while still exerting beneficial immunosuppressant effects.

The next problem to solve was ischemia of the donor bronchus, which appeared to cause stenosis of the airway. In initial lung transplant surgeries, the donor bronchus had its arterial blood supply cut, leaving its only remaining blood supply from collaterals from the pulmonary circulation. This was reasoned to be insufficient, and led to ischemia that increased progressively up the bronchus. The solution to this problem was to use the omentum—a section of the peritoneum attached to the stomach—and wrap it around the bronchial anastomosis. This would bring the systemic circulation up and form collaterals around the bronchus. Similar to the previous set of experiments, this solution was tested in dogs, with much success.

After demonstrating the feasibility of successful lung transplantation in dogs, in the late summer of 1982, Dr. Cooper submitted a proposal to the Toronto General Hospital to perform experimental lung transplants in humans. Dr. Cooper asked the hospital be allowed to perform unilateral lung transplant operations in patients with end-stage, disabling pulmonary pathology. Specifically, patients would be selected who were expected to have less than six months to live. Ultimately, the decision was made to perform this procedure in patients who had idiopathic pulmonary fibrosis (IPF)—a progressive, and ultimately fatal, disease involving scarring of lung tissue.

On November 7, 1983, the world’s first human single lung transplant was successfully performed at the Toronto General Hospital. The patient, 58-year old Tom Hall, would go on to become world famous as the first successful lung transplant recipient, and would live for six more years before passing away due to renal failure. In Dr. Cooper’s view, “the mark of success [in lung transplantation] is to give a patient at least two years of life with good health.” The success of the procedure was reproduced in several other patients with IPF, and the team of surgeons in Toronto would go on to perform the first successful bilateral lung transplantation in 1986 for a patient with emphysema. Then in 1988, the first successful bilateral lung transplantation was performed in a patient with cystic fibrosis. In light of these procedures, Dr. Cooper and his team demonstrated that lung transplantation could be successful in patient groups with varying pulmonary pathologies.

Toronto General Hospital Division of Thoracic Surgery (1987): (left to right) Drs. Thomas Todd, Joel Cooper, Alec Patterson, and Griffith Pearson (seated).

The success of lung transplantation is still limited by the availability of healthy donor lungs. Researchers in lung transplantation, and from the Toronto Lung Transplant Program team, are developing innovative ways to improve the health and availability of donor lungs for recipients, and to ultimately increase the success of lung transplantation.

Dr. Joel Cooper has since moved back to the United States, and is currently the head of thoracic medicine at the Hospital of the University of Pennsylvania.