By Ramsey Hachem, M.D.
Washington University School of Medicine Barnes-Jewish Hospital
Division of Pulmonary and Critical Care
July, 2016
In this column, I will address some questions that are frequently asked by patients and their family members.
1. How long will I have to wait for the transplant once I am put on the waiting list, and what factors influence the waiting time?
The average waiting time for lung transplantation in the U.S. is approximately 4 months. This can vary slightly from center to center depending on the population density in the center’s region and the number of lung transplant centers within a city. The lung allocation score (LAS) is the biggest factor that influences waiting time. The LAS is meant to reflect medical urgency for a transplant and the likelihood of living 1 year after transplant, and this is based on objective factors including the underlying lung disease, lung function, the amount of oxygen that is necessary, and other test results. The higher the LAS, the higher the expected transplant benefit, and in turn the shorter the waiting time for transplant. For example, a patient who has severe disease requiring life support in the intensive care unit would generally have a high LAS and would wait a short time for transplant. On the other hand, a patient with less severe disease would have a lower LAS and would wait a longer time for transplant.
2. What are antibodies and how do they affect waiting time for transplant?
Before a patient is put on the waiting list for transplant, they are screened for antibodies to human leukocyte antigens (HLA). HLA essentially represent tissue types, and everyone has their unique HLA. Some patients develop antibodies, or immune proteins, towards some HLA after exposure to these antigens, most commonly because of previous pregnancy or blood transfusions. There are other reasons why some patients develop antibodies, and these include infections and vaccinations. Preformed antibodies can cause rapid rejection of the transplanted lungs early after transplant. As a result, patients are screened for the presence of HLA antibodies, and donors with those HLA are generally avoided to decrease the risk of early rejection. The calculated panel reactive antibodies (CPRA) is an estimate of the proportion of donors in the general public that have the HLA that a given patient has antibodies against. Not surprisingly, having HLA antibodies narrows the donor pool and extends the waiting time to transplantation.
3. Is there an age limit for patients to have a lung transplant?
Historically, lung transplantation was not considered an appropriate treatment for patients older than 65 years. In fact, 60 years of age was considered the upper limit for a bilateral transplant and 65 was considered the upper limit for a single lung transplant. However, over time, many patients who were older than 65 years were deemed good candidates because they had no comorbidities, and they underwent both single and bilateral transplants with good results. As experience has grown, chronological age has become a less important factor in patient selection, and many programs do not have an age limit for selecting patients. However, survival after transplantation is significantly shorter for older patients because of the combined effects of advancing age and post-transplant comorbidities.
4. Is a bilateral (double) lung transplant better than a single lung transplant?
This has been a controversial topic in the field for the past 30 years. Initially, single lung transplantation was the more common procedure, but the number of bilateral transplants quickly increased and today approximately 75% of all transplants are bilateral. Single lung transplantation is a shorter operation that allows a more rapid recovery and may be appropriate for frail patients. In addition, single lung transplants may expand the donor pool as one donor can donate 2 lungs to 2 recipients. However, single lung transplantation provides less lung function resulting in a lower lung reserve compared to bilateral transplantation. In a large international registry, survival after bilateral transplantation is significantly better than after single lung transplantation. In the most recent analysis, the median survival after bilateral transplantation was 7.1 years while the median survival after single lung transplantation was 4.6 years. However, it should be noted that this survival difference may not be solely due to the operation performed because factors that influence the decision to perform a single lung transplant, such as frailty, may also influence survival after transplantation.
5. Are there different kinds of rejection and what do they mean?
There are different forms of rejection after lung transplantation. Acute rejection is a common form of rejection that occurs in the first 6-12 months after transplantation. The term acute refers to the chronicity of lung injury that is seen on biopsies. Acute rejection often does not cause any respiratory symptoms or changes in pulmonary function tests. As a result, most transplant programs have a surveillance bronchoscopy protocol to look for rejection. It is graded on a scale of 0-4; grade 0 is no rejection, grade 1 is minimal rejection, grade 2 is mild rejection, grade 3 is moderate rejection, and grade 4 is severe rejection. Acute rejection usually responds well to high-dose steroids, but episodes of acute rejection are strong risk factors for chronic rejection. Chronic rejection is the leading obstacle to better outcomes and the leading cause of death beyond the first year after lung transplantation. It is generally detected by decreases in spirometry, and although it may not cause any symptoms in the early stages, it tends to follow a progressive course and is more resistant to therapy. There are numerous treatments for chronic rejection, but none completely reverses the resultant scarring. Finally, antibody-mediated rejection is a form of rejection that can occur at any time point after transplant and generally results in the rapid onset of shortness of breath, infiltrates on chest x-ray, and low oxygen levels. In some cases, this form of rejection can be reversed, but there is persistent lung dysfunction in many cases. This remains a difficult challenge in caring for lung transplant patients.