By Ramsey Hachem, M.D.
Washington University School of Medicine Barnes-Jewish Hospital
Division of Pulmonary and Critical Care
September 23, 2016
The first human lung transplant was performed in 1963 in Jackson, Mississippi. Unfortunately, the recipient died 3 weeks after the transplant because of kidney failure. Nonetheless, this early experience was encouraging because the recipient was liberated from ventilatory support, the transplanted lung was functioning normally, and there was no evidence of rejection during the short post-transplant period. However, over the ensuing 15 years, few lung transplants were performed worldwide and none resulted in long-term success. Many patients who underwent lung transplantation during this time period were moribund and would not have been considered good candidates by today’s criteria. Respiratory failure, rejection, pneumonia, and airway anastomotic complications were common causes of death, and few recipients survived to hospital discharge. Experience with heart transplantation and combined heart-lung transplantation led to refinement of surgical techniques for lung transplantation. In addition, cyclosporine A was developed in the late 1970s and began clinical testing in kidney transplantation. This revolutionized immunosuppressive management after transplantation and allowed lower doses of steroids, which promoted airway anastomotic and surgical wound healing. These advances led to the first successful lung transplant in 1983 in Toronto, Canada. The recipient was a 58 year-old man with idiopathic pulmonary fibrosis (IPF); he received a singe lung transplant and survived for 6 ½ years. This early success heralded a new beginning in the management of end-stage lung disease. The technique for bilateral lung transplantation was subsequently developed.
The number of lung transplants performed rapidly increased by the late 1980s and early 1990s. Initially, donor lungs were allocated based solely on waiting time in the U.S. However, in 1990, patients with IPF were awarded an additional 90 days of waiting time when they were listed because it became apparent that their disease was more rapidly progressive and they had an increased risk of dying while waiting for transplantation. The leading indication for lung transplantation throughout the 1990s was chronic obstructive pulmonary disease (COPD). In fact in 2000, 40% of patients undergoing lung transplantation worldwide had COPD and an additional 9% had emphysema due to alpha-1 antitrypsin deficiency. In that year, 15% of patients had IPF and 16% had cystic fibrosis (CF). Between 1990 and 2000, approximately half of all transplants were single lung transplants, and half were bilateral.
Not surprisingly, as the number of lung transplants performed increased the number of patients added to the waiting list grew rapidly. At the end of 1990, fewer than 500 people were waiting for lung transplantation in the U.S., but by the end of 2000, over 3500 patients were on the waiting list. This resulted in a dramatic increase in waiting time, and by 2000, the median waiting time for lung transplantation was almost 4 years. It was quickly recognized that patients needed to be listed early to accrue enough waiting time to have a transplant when their disease became severe enough. However, this was not feasible for patients with rapidly progressive lung disease and those who were diagnosed late. Furthermore, there was no way to account for medical urgency under this allocation system. Indeed, patients with IPF had a significantly higher risk of dying while waiting than those with COPD. This led to the lung allocation score, which was implemented in 2005. Under this allocation system, donor lungs are allocated based on medical urgency and expected outcomes after transplantation to maximize the transplant benefit.
The lung allocation score has significantly changed the demographics of patients undergoing lung transplantation. IPF and other interstitial lung diseases are now the leading indications for lung transplantation accounting for approximately 50% of all transplants in the U.S., while COPD accounts for approximately 30% of transplants. Because patients with IPF are often older, there has been a significant increase in recipients’ median age, and in 2012, over 25% of lung transplant recipients were 65 or older. Importantly, the waiting time has decreased significantly. The median time to transplant in 2004 was 2 years, and this has consistently been approximately 4 months over the past several years. This resulted in a decrease in the number of deaths on the waiting list, although patients with IPF and interstitial lung disease continue to have the highest risk of dying on the waiting list. However, there has been an increase in the number of deaths on the waiting list over the past 2-3 years; this has been attributed to listing an increasing number of patients with more advanced disease and many who are critically ill. Importantly, outcomes after transplantation have continued to improve, and the median survival is approaching 6 years.
Lung transplantation is still faced with many challenges, and chronic rejection remains the leading obstacle to better outcomes. However, the field has evolved quickly from an experimental procedure to a viable treatment option for patients with advanced lung disease. The trend of improving outcomes over the past 20 years is encouraging and provides hope for the future.