Lung Transplantation

Marisa Magaña and Gordon L. Yung

Lung transplantation has a relatively short history: the first successful human single and double lung transplants were performed in 1983 and 1986, respectively. Organ availability remains the major obstacle to the number of lung transplants, with only 15% to 20% of all potential donors’ lung(s) being suitable for transplant. With better donor management and better public awareness, there has been a small but steady increase in the number of patients receiving lung transplantation, despite an increasing number of double lungs over single lung transplants (which would, theoretically, result in a decrease in the total number of patients receiving lung transplant). In 2011, 1,822 adult lung transplants were performed in 60 adult and 3 pediatric transplant centers in the United States, including one living donor transplant. Compared to a total of 3,519 lung transplants reported from 178 centers worldwide to the International Society of Heart and Lung Transplantation in 2010, the United States continues to lead the world in this treatment. Encouragingly, the median posttransplant survival has increased from 4.7 years in the 1990s to 5.7 years for the past decade.

The most common indications for lung transplantation worldwide are chronic obstructive pulmonary disease (COPD) (including α-1 antitrypsin deficiency, ∼40%), interstitial lung disease (including idiopathic pulmonary fibrosis [IPF], ∼27%), and cystic fibrosis (∼17%). Other less common indications, each constituting approximately 1% to 3% of all cases, include pulmonary arterial hypertension (PAH), sarcoidosis, bronchiectasis, and lymphangioleiomyomatosis. In addition, 1% to 2% of all lung transplants were performed in patients who had a previous lung transplant, usually due to chronic rejection (bronchiolitis obliterans). In the United States, due to a new prioritizing allocation system established in 2005 that favors interstitial lung disease, the proportion of patients with this group of conditions approaches that of patients with COPD.

PATIENT SELECTION

Because of limited organ availability, there are often conflicts during recipient selection between individual patient needs and societal benefits. For example, “high risk” patients who might benefit from transplant but who have a low chance of posttransplant survival may be denied transplant in favor of other patients with a better chance of survival. In addition, in developed countries, where rationing of resources is not a normal societal expectation, physicians may face significant ethical dilemmas. For example:

1. Should patients be allowed to have repeat transplants for a second or third time, even though they are sicker than others who have not had their first one?

2. Should a 25-year-old patient with cystic fibrosis (a disease he or she has no control over) who is the sole source of income for a family with young children be chosen over a 78-year-old retired individual with COPD who was a life-long smoker?

3. Should there be limits on the number of transplants for foreign nationals, including illegal immigrants, when there are not enough organs for legal residents/citizens?

EXCLUSION CRITERIA

Ethical issues and society considerations aside, selection of patients should be based primarily on potential benefits for the patient, either in terms of improved survival, quality of life or both. The significant perioperative and postoperative risks for morbidity and mortality, as well as the scarcity of donor organs, necessitates a vigorous selection process for suitable recipients that is critical to successful outcomes that benefit the largest number of patients for the longest period of time. The ideal patient should be healthy enough to undergo the surgery safely with the least risk of postoperative complications (both immediate and long-term), yet sick enough (i.e., high expected mortality and sufficiently impaired quality of life) to justify the considerable risks. Every patient is, therefore, required to undergo an extensive evaluation to determine transplant candidacy. This includes a detailed history and physical examination, testing for latent infections or organ dysfunction, cardiac and pulmonary function testing, imaging with chest radiograph and CT scan, as well as a careful psychosocial assessment.

Although every transplant center has its own guidelines regarding recipient selection, there is a general consensus that patients with the following conditions should not be considered for transplant until these issues are resolved: active tobacco, drug, or alcohol abuse; severe psychiatric illness that impairs the patient’s ability to comply with medical care; documented current history of medical nonadherence; lack of a significant social support system; active infection with hepatitis B or C, especially with histologic evidence of liver disease; untreatable advanced dysfunction of another major organ; significant chest wall/spinal deformities; and recent malignancy with the exception of nonmelanoma skin cancers. It is important to recognize that experience in lung transplants is still relatively limited and some of the “conventional” practices and guidelines are constantly being challenged and undergoing change. For example, most transplant centers still consider infection with HIV to be an absolute contraindication; however, with advances in antiviral therapies, it is possible that patients with HIV or chronic viral hepatitis may be candidates in the future if these infections can be treated successfully. Age is considered a relative contraindication due to evidence of worse outcomes in patients over the age of 65 years. However, increasingly, there is an emphasis on physiologic age, so that if a patient over 65 years is physically strong and healthy aside from the lung disease, consideration can be given to transplantation. In fact, in 2011, more than 25% of all lung transplants in United States were performed on patients older than 64 years. Long-term outcome data on lung transplants in “elderly” patients are inconclusive, but it is likely that, even in well-selected patients, long-term (5 year) survival of patients over 70 years of age would be significantly worse that those younger than 65 years. Finally, selected patients with multi-organ failure may have successful multi-organ transplants, most commonly heart–lung and lung–kidney transplants.

Other conditions may increase posttransplant mortality and should also be taken into account when considering a patient’s transplant candidacy, including: symptomatic osteoporosis, poor functional status with poor potential for rehabilitation, hemodynamic instability, and active and untreated extrapulmonary infections.

Although patients with cystic fibrosis and pan-resistant Pseudomonas aeruginosa have worse transplant outcomes than those with sensitive strains, they are similar to non–cystic fibrosis patients, presumably due to the younger age of this population. Thus, one may argue that colonization with pan-resistant P. aeruginosa should not preclude transplantation. On the other hand, patients colonized with Burkholderia cepacia type III have significantly decreased 1 year survival posttransplant, prompting some centers to consider colonization with this organism a contraindication to transplantation.

Selected patients on chronic home ambulatory ventilator support have comparable survival outcomes, but those with acute respiratory failure requiring mechanical ventilation and urgent lung transplant generally have significantly worse outcomes. Extreme high or low body weight (±20%–30% of ideal body weight) is associated with worse outcome; aggressive approaches, including dietary restriction or placement of a feeding tube, are often necessary. Some centers use a body mass index of 30 as a “cut-off” for transplant consideration, although one should also take into account the distribution of fat and relative muscle/fat proportion in making the final decision. Increasingly, gastroesophageal reflux disease (GERD) has been associated with worse transplant outcomes due to its association with chronic lung rejection, and some transplant centers now recommend definitive surgical treatment in severe cases either prior to, or soon after, lung transplantation.

Inclusion Criteria

To select the right patients, physicians should consider several factors:

1. Survival after transplant: While no one can accurately predict how long an individual patient will live after a transplant, the most comprehensive data are available from the annual report from the Registry of the International Society of Heart and Lung Transplantation. In the 2012 report of self-reported data of almost 33,000 lung transplants performed between 1994 to 2010, the average survival after lung transplant was about 5½ years (single lung: 4.6 years, double lung: 6.7 years). The survival difference in single versus double lung transplant may, in part, be a result of selection bias: most older patients, who would be expected to have shorter posttransplant survival, typically receive single rather than double lung transplants. Similar survival data have also been reported in the United States by the Scientific Registry for Transplant Recipients (which operates under the Department of Health and Human Services to collect all transplant data in the United States). Different diagnoses may also have different transplant outcomes, in part because of age at the time of transplant. The shortest survival is associated with IPF (4.5 years). Previously, idiopathic PAH had the lowest 1-year survival, but this has improved to an average of 4.9 years. Patients with COPD have an average posttransplant survival of 5.3 years, while those with the similar disease of emphysema due to α1 antitrypsin deficiency survive an average of 6.3 years. Patients with cystic fibrosis have the longest average survival of 7.4 years. It is likely that age and, possibly, single versus double lung transplant plays a significant role in the reported differences in survival.

2. Survival without transplant: To evaluate the benefits of transplant, one should compare post-transplant survival to the expected survival of patients without transplant. To achieve this goal, one has to estimate individual patient survival without transplant. Because most lung diseases are associated with a wide range of survival, it is important for transplant physicians to take into account an individual patient’s condition and disease progression, and not simply look at the average survival for each disease. For example, a patient with COPD who quit smoking 20 years previously and has had stable lung function for the past 5 years may have significantly better survival than another patient with α1 antitrypsin deficiency and similar pulmonary function tests, but who just quit smoking only 6 months earlier. Similarly, a patient with pulmonary hypertension who has not yet received optimal medical therapy might have a very different prognosis than another patient with similar pulmonary hemodynamics, but who was already receiving maximal medical therapy. Guidelines were developed in 2006 by the International Society for Heart and Lung Transplantation (Table 75-1), which provide a framework for patient selection for lung transplant, but these do not substitute for an individual physician’s judgment, especially with regard to disease progression and consideration of quality of life. Because different countries may have very different systems of prioritizing organ allocation, and waiting time can vary considerably among different transplant centers in the same country, it is important for physicians to work with their local transplant centers to optimize the timing for transplant referrals.