Lung Transplantation

What’s new in lung Transplantation

During the last decade there has been a significant increase in the number of lung transplants performed in the US and Europe. In 1999, there were just under 1500 lung transplants performed in the US & Europe, while in 2009 there were about 3000 performed in the US and Europe, and almost 1700 performed in the US. Historically fibrotic lung disease (pulmonary fibrosis) accounted for about 30% of all lung transplants worldwide. It is now the leading indication (close to 40% worldwide) and in many US centers accounts for over 50% of all lung transplants (see figure 3). In this article we will review some of the changes that have accounted for this. In two companion articles we will also discuss some exciting new developments, which may expand the availability of lungs for transplant (Ex Vivo Perfusion) and expand the recipient pool (Ambulatory ECMO). The Foundation also recently held a very informative ― webinar with the Lung Transplant Program at Columbia-Presbyterian Hospital and a link is located on our website.

Indications:
In order to be considered for a transplant, an individual has to have a chronic and irreversible debilitating disease process. For patients with IPF this can often be indicated by histological (a biopsy) or radiographic (usually high resolution CT) evidence of severe disease, significantly impaired oxygen diffusion (DLco), or low oxygen saturation during a 6 minute walk test. Indications for transplantation may vary from institution to institution. A concern in patients with IPF is that the disease does not progress in a consistent, predicable manner, which can make referral for transplantation problematic (i.e. a relatively stable individual can suddenly, without warning, deteriorate quite rapidly). It is hoped in the near future that the with the discovery and elucidation of blood biomarkers that the course of disease progression will be better defined, and that referral for transplantation can proceed in a more predictable manner.

Contraindications:
In the past patients over the age of 70 were not considered candidates for transplantation. At present, however, in some institutions, patients over 80, without significant co-morbidities, have been successfully transplanted! Thus age is only a ― relative‖ contraindication. Other conditions that may preclude transplantation are recent malignancy, active, non-curable infection (HIV, hepatitis B & C), and advanced, irreversible dysfunction of another major organ system (heart, liver, kidney). Also active or recent cigarette smoking, alcohol or drug abuse, inability to adhere or follow through with medical therapy, untreatable psychiatric disorders, and an absence of a reliable social support system may also preclude an individual from receiving a transplant.

Pre-transplant:
Once the decision has been made to proceed with a transplant, the individual undergoes a thorough pre-transplant evaluation. It is important to determine if there are any significant untreated or unrecognized medical problems (cardiac, kidney, diabetic, infectious etc.). The transplant candidate should attempt to achieve ideal body weight, engage in pulmonary/respiratory rehab, attend education seminars and participate in transplant support groups. Patients are placed on a wait list with UNOS (United Network for Organ Sharing). All individuals are assigned a Lung Allocation Score (LAS) based on their clinical characteristics: age, severity of disease, lung, heart and kidney function, and laboratory values. Patients are assigned a score ranging from 0 (less ill) to 100 (gravely ill). Prior to LAS, allocation was based on the time that a patient had accrued on the waiting list. Thus patients who were severely ill, but had only been on the list for a short period, might not receive a transplant. With the LAS system, transplants are allocated on the basis of need and the ―wait periods‖ are generally quite reasonable.

Transplant Procedure:
As institutions and physicians have gained more experience and expertise, results have improved. Many surgeons are now able to perform lung transplants through much smaller, less invasive incisions. This often results in much less pain and discomfort allowing patients to breathe more deeply and recover more quickly.

Success of the transplant also depends on proper organ selection and recovery. Critical in this process are the lung preservation techniques that have evolved and improved during the last few years. Prior to harvesting the lung, attempts are made to improve the donor’s metabolic and hemodynamic state. After recovery of the lung, specific preservation techniques are utilized which can enhance the function of the donor lung and perhaps expand the number of donor lungs that can be utilized. (This will be discussed in more de-tail in article on Ex Vivo Perfusion).

Whether the individual should undergo a single or bilateral lung transplant is an extremely complicated issue. Many factors are involved including patient’s age, co-morbidities, and severity of underlying lung disease. Excellent results have been achieved with either single or bilateral transplant.

Post-transplant:
Acute rejection, primary graft dysfunction (PDG), and infection are concerns during the early post-operative procedure. Generally with newer immunosuppressive regimens acute rejection is rarely a serious problem. With improved preservation techniques, which are discussed in more detail in the article on Ex Vivo Perfusion, PGD (the transplanted lung does not oxygenate properly) has also be-come a less common post-operative problem.

Long term concerns following transplantation include side effects and adverse reactions from immunosuppressant agents (hypertension, diabetes, impaired kidney function, and skin sensitivity), infection, and bronchiolitis obliterans syndrome (BOS). BOS is a condition in which there is excessive fibroproliferation (build up of scar tissue) in the airways (bronchioles). The airways progressively narrow and oxygen exchange becomes increasingly difficult. The exact cause or etiology is unknown but is probably multifactorial including low grade, chronic rejection, early graft dysfunction (PGD), viral and bacterial infections, and an abnormal immune response. Management includes aggressive anti-rejection therapy, aggressive treatment for low-grade infection, and improved preservation techniques.

Generally most individuals get back to a relatively normal active lifestyle with minimal restrictions. One year survival in most insti-tutions is close to 95% with most mortalities in extremely high risk individuals, and the long term results continue to improve.

References:
Orens JB, Estenne M, Arcasoy S, et. al. International guidelines for the selection of lung transplant candidates: 2006 Update – A consensus report from the pulmonary scientific council of the International Society for Heart and Lung Transplantation. The J of Heart and Lung Trans 2006; 25: 745-755.

Lama VN. Update in lung transplantation 2008. Am J Respir Crit Care Med 2009; 179: 759-764.

Kreider M, Kotloff RM. Selection of Candidates for Lung Transplantation. Proc Am Thorac Soc 2009; 6: 20-27.
Estenne M, Hertz MI. Bronchiolitis Obliterans after Human Lung Trans-plantation. Am J Respir Crit Care Med 2002; 166: 440-444.