The last 20 years have seen lung transplantation emerge from an experimental surgical technique to an established and respected form of therapy for end-stage lung disease. There have been over 20,000 lung transplants performed worldwide to date and, for many chronic end-stage respiratory diseases, such as cystic fibrosis and idiopathic pulmonary fibrosis, it is the only therapy proven to offer a survival advantage. However, this therapeutic option is only available to a highly selected group of patients and the potential demand for the procedure far outstrips supply of suitable donor organs. This widening gap between demand and supply of donor organs accounts for a significant waiting-list mortality. The decision on whether or not a patient with end-stage respiratory disease is a suitable candidate for lung transplantation is reached after a careful multidisciplinary assessment. Surgeons, physicians, anesthesiologists, microbiologists, nurse co-ordinators, physiotherapists, psychologists and social workers all play important roles in the assessment team.
The team has three key areas of responsibility when performing assessment for lung transplantation. The first area of responsibility is to the patient under assessment, to ensure that lung transplantation is the correct treatment option for that individual. This requires detailed knowledge of the prognosis and management of their advanced lung disease and careful evaluation of their psychosocial status. The team must be sure that all other therapeutic options have been exhausted and must explore whether other surgical options, such as lung volume reduction surgery in chronic obstructive pulmonary disease, or improved medical management are more appropriate.
The second area of responsibility is to the transplant unit and the population it serves, to ensure use of human and financial resources in an effective manner. Getting a patient successfully through lung transplantation is a very resource-intense option in terms of both staff time and costs. This resource use can increase dramatically if the lung-transplant recipient has a prolonged intensive care unit stay and encounters complications requiring interventions, such as extracorporeal membrane oxygenation and hemofiltration. Such complications may also lead to a prolonged period of rehabilitation. It is therefore vital that an individual’s risk of developing major postoperative complications and their ability to rehabilitate quickly and effectively after transplant are assessed carefully by the team on an ongoing basis. Transplanting individuals at high risk of prolonged postoperative complications with consequent prolonged intensive care unit stay and low chance of successful rehabilitation has a significant effect on staff morale and is a poor use of limited resources. Any patient has the potential to be transplanted but the challenge is to identify those in whom there is a high chance of a successful outcome.
The third area of responsibility is to the donor and in particular their next of kin. They have gifted their loved one’s organs for transplantation and must be safe in the knowledge that these organs will be used in a responsible manner to obtain the maximum benefit. It is very common for donor families to ask how the gifted organs were used and how individual recipients benefited. Many next of kin write anonymously to the recipient several weeks or months after their transplant and get comfort from the knowledge of the good their gift has achieved. Therefore, the assessment team must aim to achieve the most effective use of the scarce donor resource by identifying potential candidates likely to obtain the most benefit.
The key to achieving these three areas of responsibilities by the transplant team is the careful assessment of each individual’s level of risk to undergo lung transplantation. Risk is a term in widespread use by healthcare professionals; published studies talk of relative risks of certain outcomes and how this changes with therapeutic interventions; practitioners taking informed consent for a procedure or for a potentially toxic therapy discuss the risk of adverse events with the patient. In virtually all these cases, the average risks for the particular intervention are quoted and it is very unusual for risks to be individualized. However, in determining the suitability of a potential candidate for lung transplantation it is essential that risk is individualized and then balanced against the potential benefit before a decision is reached. The ability to do this is more art than science and requires experience, clinical skill and an ability to draw together expert opinion from a wide range of disciplines within the assessment team.
To patients, however, risk is a difficult concept to grasp and conveying it accurately and in a way that guarantees understanding is difficult. The easiest way to demonstrate individualized risk is to give a potential candidate an idea of where their risk lies compared with the average. For example, the chance of being alive at the end of the first year after transplant or expected long-term survival can be expressed as a mean for a historical population of lung-transplant recipients. After assessment, these survival rates can be individualized for a specific candidate.
In order to give referring physicians a guide to those patients likely to be lung-transplant candidates, the International Society of Heart and Lung Transplantation has issued guidelines on candidate referral and selection Citation[1]. These include a number of general indications and also generic contraindications to be considered in a candidate. Generally, patients should have end-stage lung disease, have exhausted all therapeutic options and have an expected survival of 50% at 2 years. Candidates should be nonsmokers or have stopped for at least 6 months by assessment and should be free of any major or uncontrolled extrapulmonary disease. In addition, there are a number of disease-specific guidelines that alert the referring clinician and the transplant physician to factors that convey a poor prognosis in that condition. These are really designed to help with timing of referral and timing of listing suitable individuals and should not be confused with the assessment of suitability, which is much more involved than following a prescriptive list of indicators.
Some aspects of the lung-transplant-assessment process are more frequently open to scrutiny and criticism. One area that attracts a lot of opinion is with regards to candidate age. Use of age as a selection indicator is considered unacceptable in most forms of medicine, yet this is common practice in selecting lung-transplant candidates. Most centers internationally use 65 years as an upper age limit guide for single lung transplantation and 60 years as a guide for bilateral lung transplantation or for heart–lung transplantation. Unlike other fields of medicine, where expensive therapy is limited solely by costs, in transplantation the limit is predominantly on supply of donor organs. Moreover, increasing age is an independent risk factor for a poorer outcome and transplantation in patients aged over 55 years significantly increases the risk of 1- and 5-year mortality Citation[2]. In a recent study examining outcomes after lung transplantation, patients over 60 years of age had a worse outcome even when fully matched for transplant indication and comorbidity with another group aged under 60 years Citation[3]. As a result, many centers insist that patients aged over 55 years have no relative contraindications to transplantation before they will consider them and, as such, age should be considered an equal relative contraindication to this procedure as any other, such as significant heart disease or renal disease.
Another area where possible candidates and their families may find difficulty is in accepting that as well as being ‘sick enough’ to need lung transplantation, it is essential that patients are ‘fit enough’ to get through the procedure safely. One of the key responsibilities of the assessment team is to identify when a patient has moved beyond the window of opportunity for transplantation and to suggest that palliation may be more appropriate. Unfortunately, owing to late referral to the transplant center and a fear by the referring physician of activating palliative care, especially in younger patients, this is not an uncommon scenario.
Assessment of the psychosocial status of potential candidates is important and yet may be considered a soft indicator by some. It is my belief that this aspect of assessment is as important as any other, more clinical, part of the process. Candidates must demonstrate that they are capable of dealing with a complex post-transplant treatment regime and to take responsibility for attending follow-up reliably as part of their essential post-transplant care. Poor compliance with treatments such as immunosuppressants or prophylactic antimicrobials can have a significant impact on long-term survival. Future compliance can obviously be very difficult to assess and past history is not always a predictor of future behavior, especially in younger patients who may be maturing around the time lung transplantation is being considered. In the same way, however, a past history of reckless behavior, drug taking and poor attendance has, in my experience, been associated with a similar behavior pattern after transplant in a number of individuals in our center. These patients pose difficult choices as they may demonstrate improved compliance and behavior when they are under scrutiny by the transplant team only to abandon this after transplant.
The provision of a dedicated carer who can support the potential candidate through the assessment process and transplantation (if they are accepted) is an essential prerequisite to being a suitable candidate. Again, there may be a temptation to consider the absence of such support as less important than other contraindications but a robust social-support network appears from experience to be crucial to a good outcome after transplant. A very common situation that arises during assessment is the identification of a number of relative contraindications but no absolute contraindication to transplant. It is worth noting that multiple relative contraindications can combine to give a cumulative increase in risk that is unacceptable. Deciding on when these combine to become unacceptable is part of the art of balancing risks that characterizes the way lung-transplant candidates are selected.
As part of this discussion, as well as selecting suitable candidates, it is essential to determine the optimal timing for adding a patient to the waiting list. Not all patients deemed suitable lung-transplant candidates need to be placed on the waiting list immediately. As transplanted lungs have a finite lifespan, it is essential that the procedure is performed at the optimal time for each individual: too early and the survival advantage the procedure may offer will be lost; too late and the patient may not survive long enough for donor organs to become available and may die on the waiting list. This period, termed the transplant window, opens when the risk of death while undergoing lung transplantation is less than the risk of death due to the underlying lung disease. The transplant window closes when the risk of dying during the procedure or in the period shortly afterwards increases to the degree that the organ could be more effectively used in another individual. The decision on when to place a patient on the waiting list is not subject to a mathematical model and relies on clinical excellence and experience, as well as the wishes of the candidate.
The process of identifying suitable candidates for lung transplantation is involved and complex. Performing this process well is a specific challenge to the lung-transplant community but one that is critical to the continued success of this therapeutic intervention in the future. An understanding of the complexities of the process and the way in which risks are balanced will hopefully help referring physicians to select and prepare patients they refer more effectively.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
References
- Orens JB, Estenne M, Arcasoy S et al. International Guidelines for the Selection of Lung Transplant Candidates: 2006 update. J. Heart Lung Transplant.25(7), 745–755 (2006).
- Trulock EP, Christie JD, Edwards LB et al. Registry of the International Society for Heart and Lung Transplantation: twenty-fourth official adult lung and heart–lung transplantation report – 2007. J. Heart Lung Transplant.26(8), 782–795 (2007).
- Gutierrez C, Al-Faifi S, Chaparro C et al. The effect of recipient’s age on lung transplant outcome. Am. J. Transplant.7(5), 1271–1277 (2007).