Why is living donor lobar lung transplantation necessary?
Over the past decade there has been a marked increase in the life span of people with CF due to improved paediatrics, special centre care, new methods of physiotherapy, improved nutrition and new antibiotics regimes. The average survival now exceeds 32 years. However, even with the best care available many young adults will still experience a decline in lung function until they are in end-stage respiratory failure. For these patients and their families, lung transplantation has brought hope.
“…outcomes of transplantation for CF are as good as for any other patient group”
The first successful cadaveric transplants for CF were performed in the UK in 1985. The medical management of CF patients before and after transplantation is complex, but these problems have largely been overcome and outcomes of transplantation for CF are as good as for any other patient group. The problem is a lack of suitable donor organs. Many CF patients are small, which can make matching recipients with potential donors difficult.
The usual sources of organs for transplantation are donated organs from cadavers. Even though varied efforts have been made to educate the public to allow the organs of a brain dead relative be used for transplantation, this has only increased the donor supply to a small extent. ‘Required Request’ has been suggested as a potential way forward with doctors required by law to ask the relatives about organ donation when the patient was certified as brain dead.
Transplantation from animals has been discussed for many years but it is still some way off due to the theoretical risk of transfer of animal viruses and other microbes to humans. Transplantation from human to human presents many challenges in stopping the organs from being rejected. This challenge would be much greater if one was transplanting across animal species.
“…many young CF patients were dying on the waiting list for a cadaveric donation”
Since the 1950’s it has been possible for some family member or friend to be able to give a kidney to someone who is on dialysis with renal failure. The transplant results from these family members have proved better than from brain dead donors. This may be because they are often from genetically related individuals, such as parents, brothers, sisters, cousins, uncles or aunts. Given that as many as 50% of young CF patients, at some centres, were dying on the waiting list for a cadaveric donation, surgeons in the USA considered using living donor lobar lung transplants (LL) for patients with CF.
“…survival was similar to that of patients receiving a heart/lung
or a bilateral sequential lung transplant (CL)”
Professor Starnes from Los Angeles carried out the first successful transplant using living lobe donors in 1990. Initially this option was chosen as a last resort for young people about to die on the transplant waiting list and the results were not encouraging. However as selection of cases, preparation for surgery and post-operative care improved, so did survival of the cases treated with LL transplant. In 1996 Prof Starnes reported a 75% one-year survival rate for 20 patients with CF. This survival was similar to that of patients receiving a heart/lung or a bilateral sequential lung transplant (CL). He reported no mortality among the donors. The great advantage of using this technique is that the CF patient has a chance to be transplanted instead of a 50% chance of dying on the waiting list.
Human beings have five lung lobes, three in the right lung and two in the left lung. Two donors give one lobe each. The donor is left with four lung lobes. The donors donate either a left or right lower lobe each. The recipient has a bilateral pneumonectomy, (removal of both lungs) and receives two new lung lobes, one from each donor.
Human lung showing five lobes
From: Blackiston’s NEW Gould Medical Dictionary 2nd ed 1956
Surprisingly lung function at two years appears to be comparable with that from patients receiving five lobes from a conventional transplant. There is a shorter time during which tissue is deprived of blood supply and oxygen when living donors are used, than when brain dead donors are used where it is usually 3-4 hours while the donor organs are being transported to the hospital where the recipient is waiting.
“...Living lobe donation also has the advantage that the operation
can be planned in advance”
Living lobe donation also has the advantage that the operation can be planned in advance and does not need to take place in the middle of the night when surgeons and theatre staff may be tired. It is also possible that transplantation from genetically related individuals might achieve better results, as happens in the case of renal transplants. Obliterative bronchiolitis (OB) thought to be due to some form of chronic rejection, is a condition that affects many lung transplant recipients. The airways in the transplanted lung become obstructed over time leading to increasing breathlessness. It would be very advantageous if there was less OB using the LL technique.
Selection of Donors
Initially, a senior member of staff interviews interested volunteers with the same blood group as the recipient. If the blood group is not compatible with the potential recipient, there is no point in proceeding further. If the potential donors wish to proceed further, and have no obvious major health problems, a detailed medical history, examination and multiple investigations must be performed to make certain that the potential donors are fit, and any risk to them is kept to a minimum. They must also be fully informed so that they know the risks and potential benefits of this type of surgery.
Volunteers will be asked about their age and occupation, for example someone whose occupation requires them to be physically very fit with regular medicals (such as a pilot) may not be suitable as a donor. Details of previous medical and surgical history are required. Any addiction to drugs, alcohol or smoking must be discussed. Current medications are recorded. A history of any symptoms referable to the respiratory system, alimentary tract, central nervous system, cardiovascular system, urogenital system, skin, joints, bleeding disorders or psychiatric illness are recorded. Some of the investigations include lung, liver, renal and cardiac function as well as ventilation perfusion scans and exercise tolerance tests.
In our centre, if the potential donor still wishes to proceed after these tests and discussions have taken place, they are seen by an independent psychiatrist to make certain that he or she understands the risks of what they are doing. An independent physician considers all the medical test results to confirm that the potential donor is completely fit.
“…treating one patient with LL transplant makes for one less on the waiting list”
The reasons for a living donor lobar lung transplant are fully discussed. The international results and the centre’s results should be given in detail. Family structure is discussed. Is there more than one CF child? Are both children on the waiting list for a transplant? If both donors are the parents, this can create additional difficulties. Not only do they have the continued care of both children with somewhat diminished health themselves, they may have to choose between two of their children. Pressure from other family members in particular, must not be allowed to influence their decision.
Clinicians should explain to the potential donors that this is a relatively new procedure and that despite their donation of a lobe, the recipient may still die. Donors should be given the opportunity to change their mind at any time from the initial discussion until surgery.
Risks to the Donor
Initially surgeons found it difficult to accept this procedure due to the possible risks to the healthy donors. It should be explained to donors that they can only do this once, and this is particularly important if there is more than one CF child in a family. They may find themselves with a dying relative when they themselves are recovering from surgery. It must be emphasised that there is a 1-2% mortality risk in the surgery and anaesthetic to healthy donors. There are to date, no recorded donor deaths but as more of these operations are performed it is inevitable that there will eventually be a fatality. Donors are told of the risk of chest and wound infections. They are advised that when they wake up they will have an intercostal tube (a rubber tube between the ribs) and they may be in hospital for 1-2 weeks, or possibly longer.
“…The loss of a lobe involves the loss of about 20% of lung function”
Most of our donors have been able to walk around and were ready for discharge in about four days. It is, however, 2-3 months before normal activity can be resumed. The loss of a lobe involves the loss of about 20% of lung function. Walking and gentle sports can be performed, but it may not be possible for the donor to take part in very active or aerobic sports. Potential donors should be warned that there may be an increased risk of chest infection in the future, and if they develop lung disease they will have less reserve. It is advantageous for them to have detailed follow-up for about five years. It will be necessary for them to bring a relative or friend to hospital to support them during their recovery because there maybe be three family members involved in the one operation.
Outcomes of the first few cases of living lobe donor transplants were poor, probably because surgery was done as a last resort when they were already extremely sick. Prof. Sir Magdi Yacoub performed the first LL transplantation for CF in the UK in July 1995. Only one of the first four patients survived to leave hospital and this patient lived for a further 4-5 years. From the next five patients treated, three survivors are currently at 3, 4, and 5 years and are doing well. Starnes’s original paper in 1994 reported a one-year survival of 75%. By 1997 at the same centre, 41 recipients of LL were experiencing similar survival rates as those of conventional lung transplants (CL).
“…transplants in children from live donors result in less obliterative bronchiolitis”
At another centre in North Carolina survival after lobe donor grafts was not as good when compared to CL but numbers were very small. Early results however indicate that transplants in children from live donors resulted in less obliterative bronchiolitis (OB) and better pulmonary function at two years after surgery. If this decrease in OB rates holds true for long term survivors of LL transplants then this procedure will increase in popularity.
Changes in after care for LL transplants
There is absolutely no doubt that surgeons have had to modify their techniques to deal with this operation, in particular the post-operative management in the intensive care unit is different.
“...there is a greater tendency for severe pulmonary oedema to occur”
What are the Ethical Dilemmas?
Some of the issues relating to choosing the recipient if there is more than one CF child in the family are covered in the paragraph under Informed Consent. The reluctance of surgeons to perform this procedure and potentially risk the lives of three people is understandable. It was only as a result of insistence by the relatives of seriously sick patients with CF, and due to the number of deaths on the transplant waiting list, that this procedure was initiated. Possible pressure from family members to persuade someone to donate is a matter requiring extremely careful investigation. No surgeon would be prepared to operate on a donor who has been pressurised to participate.
However there have been some benefits to potential donors. The average adult who is fit does not get extensive investigations. At our centre during the course of volunteering as a potential lobe donor, three individuals were found who needed urgent medical treatment. They therefore benefited from exploring the possibility of lobe donation although they did not actually participate. Even when surgery has taken place and the recipient dies, a number of the donors have told us that there were glad that they did everything possible to try and save the life of their loved one.
Friends and Spouses
Some centres accept friends and spouses of CF patients as donors, in other places this is not done. If two mentally fit adults wish to give a lung lobe to save a young person’s life, do the doctors or the “regulatory authority” have the right to say no? This procedure is in many ways little different from donating a kidney to a patient with end-stage renal failure. A recent survey of renal transplant centres in the US, showed that 88% out of 126 centres accepted spouses and 83% accepted friends as potential donors. It is the altruistic stranger who is the real challenge. In the UK it is against the law to offer money, or other form of reward, in exchange for an organ.
The regulations regarding living organ donation vary from country to country and must be observed. Clinicians have become more comfortable with this procedure with the passage of time especially when they see patients doing well at four and five years. Indeed, to give something which you can live without, to help save the life of another person does seem entirely acceptable, not only from the modern secular view point but also from a Christian viewpoint.
Questions Still to be Answered
We do not yet know the long-term results of living donor lobar lung transplantation. We know that with conventional transplantation many patients are now living over 10 years with a good quality of life. We need to study the pulmonary reserve of patients who have had lobar transplants to see if this is the same as following conventional transplantation. It will be very interesting to see if genetically related adult recipients continue to experience less obliterative bronchiolitis and better pulmonary function than patients conventionally transplanted. If this is so, it is very important and will prolong survival. We also need to study the long-term risks to those who have acted as donors.
Not all patients with CF will have relatives who are fit enough, are of the correct blood group and are willing to be lobe donors. However if 20% of the CF patients needing life saving transplantation could be treated using this method there would be more organs left for conventional transplantation for the remaining candidates. Living donor lobar lung transplantation is an acceptable option that should be considered for selected CF adults as well as children with end-stage disease.
Margaret E Hodson MD MSc FRCP DA
Professor of Respiratory Medicine
Royal Brompton & Harefield NHS Trust and Imperial College School of Medicine London