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The lung and winding road
Editorial
Lung transplants are primarily used to prolong life, and rarely to improve symptoms, in patients with chronic respiratory diseases, after other treatment options have been exhausted. Chronic obstructive pulmonary disease (COPD) patients are the most common recipients (33·5% of transplants done between 1995 and 2012), with idiopathic pulmonary fibrosis and cystic fibrosis (CF) patients receiving 23·7% and 16·6% of lung transplants, respectively. According to the International Society for Heart and Lung Transplantation (ISHLT) in 2010, 3519 lung transplants were done in 2010, with 79% of patients reportedly still alive 1 year after transplant. These data are impressive, but the story is different for the patients who spend many years on a transplant waiting list; currently, one in six patients will die while on the list. In March, 2014, the UK Cystic Fibrosis Trust released their Hope for more report that calls for fairer access to donated lungs. In the UK, one in three CF patients will die while on the waiting list, partly because of an unfair allocation system in which donor lungs are given to the geographically nearest matched recipient. Contrastingly, the USA, and countries operating within the Eurotransplant organisation, use an impartial and reproducible Lung Allocation Score (LAS, 0–100, with a higher score representing the patients with the most urgent medical need). This score is based on clinical measurements and probability of success after transplantation. Patients with the highest LAS go to the top of the transplant list, and everyone is re-assessed at regular intervals. Since the introduction of LAS in the USA in 2005, the number of transplants has increased and the number of deaths of people on the waiting list has fallen. This month the UK will introduce the super-urgent group—a subgroup of most needy patients on the waiting list who will receive the first lung available, irrespective of location, but this move is unlikely to benefit many patients. There are also shortcomings with the US system. The transplant community is undecided about how to allocate paediatric lungs. In the USA, children younger than 12 years old are not registered on the adult waiting list whereas those in countries with the Eurotransplant system are automatically given a LAS of 100. Such ambiguity can lead to patient distress, and clinician vulnerability. In 2013, the parents of a 10-year old CF www.thelancet.com/respiratory Vol 2 April 2014
patient in Pennsylvania, USA, successfully challenged the lung allocation system and a court ruled that the child should be added to the adult transplant list. The patient eventually received a double lung transplant from an adult donor, whose lungs were surgically reduced before transplantation. Lung resizing is a new technique that many hope will increase the number of lungs used—in the UK, less than 25% of lungs from donors after brain death are transplanted. Lung resizing is particularly beneficial for CF patients who are often children or women of small stature, yet few UK surgeons are trained in the technique. The definition of whether a lung is suitable for transplantation is controversial. There is increasing evidence that lungs designated as “marginal” by the ISHLT can be clinically effective. Current guidance is based on ATS/ERS guidelines from 1998. These recommendations should be revised to ensure harvesting and transplanting clinicians are appropriately informed, and that patients are correctly advised. Unfortunately, even when a transplantation is successful, difficulties persist. Latest data show that 34% of adult lung recipients had at least one episode of acute rejection between discharge and 1 year of followup. Lung transplants have a higher rejection rate than do other solid-organ transplants, partly due to the organ’s individual immunocompetence. In March, 2014, Alexander Krupnick and colleagues reported revolutionary data using mouse models to show proliferation of memory CD8-positive T cells in lung allografts aids transplant acceptance. Because current posttransplantation immunosuppressive therapies inhibit this pathway, the findings suggest that existing strategies might be doing more harm than good. The first lung transplant recipient in 1963 survived 18 days. Today, 88% of all lung transplant recipients survive the first 3 months, with 30% still alive 10-years post-transplantation. This radical procedure has prolonged and improved thousands of lives, and transformed the outlook for many people living with a chronic respiratory disease. The challenge now is how to best use this technique to ensure that no donated lung is wasted but given to the most clinically appropriate recipient, using the most successful and progressive surgical technique, with the optimum posttransplantation care. ■ The Lancet Respiratory Medicine
Michelle Del Guercio/Science Photo Library
The lung and winding road
See Review Lancet Respir Med 2013; 1: 318–28 For the Hope for more report see http://www.cysticfibrosis.org.uk/ media/443623/PAFF9 %20-%20Transplant%20 report%20-%20online.pdf For the study by Alexander Krupnick and colleagues see J Clin Invest 2014; 124: 1130–43 For more lung transplant statistics and information on the Lung Allocation Score see http://www.ishlt.org/
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Lung transplants are primarily used to prolong life, and rarely to improve symptoms, in patients with chronic respiratory diseases, after other treatment options have been exhausted. Chronic obstructive pulmonary disease (COPD) patients are the most common recipients (33·5% of transplants done between 1995 and 2012), with idiopathic pulmonary fibrosis and cystic fibrosis (CF) patients receiving 23·7% and 16·6% of lung transplants, respectively. According to the International Society for Heart and Lung Transplantation (ISHLT) in 2010, 3519 lung transplants were done in 2010, with 79% of patients reportedly still alive 1 year after transplant. These data are impressive, but the story is different for the patients who spend many years on a transplant waiting list; currently, one in six patients will die while on the list. In March, 2014, the UK Cystic Fibrosis Trust released their Hope for more report that calls for fairer access to donated lungs. In the UK, one in three CF patients will die while on the waiting list, partly because of an unfair allocation system in which donor lungs are given to the geographically nearest matched recipient. Contrastingly, the USA, and countries operating within the Eurotransplant organisation, use an impartial and reproducible Lung Allocation Score (LAS, 0–100, with a higher score representing the patients with the most urgent medical need). This score is based on clinical measurements and probability of success after transplantation. Patients with the highest LAS go to the top of the transplant list, and everyone is re-assessed at regular intervals. Since the introduction of LAS in the USA in 2005, the number of transplants has increased and the number of deaths of people on the waiting list has fallen. This month the UK will introduce the super-urgent group—a subgroup of most needy patients on the waiting list who will receive the first lung available, irrespective of location, but this move is unlikely to benefit many patients. There are also shortcomings with the US system. The transplant community is undecided about how to allocate paediatric lungs. In the USA, children younger than 12 years old are not registered on the adult waiting list whereas those in countries with the Eurotransplant system are automatically given a LAS of 100. Such ambiguity can lead to patient distress, and clinician vulnerability. In 2013, the parents of a 10-year old CF www.thelancet.com/respiratory Vol 2 April 2014
patient in Pennsylvania, USA, successfully challenged the lung allocation system and a court ruled that the child should be added to the adult transplant list. The patient eventually received a double lung transplant from an adult donor, whose lungs were surgically reduced before transplantation. Lung resizing is a new technique that many hope will increase the number of lungs used—in the UK, less than 25% of lungs from donors after brain death are transplanted. Lung resizing is particularly beneficial for CF patients who are often children or women of small stature, yet few UK surgeons are trained in the technique. The definition of whether a lung is suitable for transplantation is controversial. There is increasing evidence that lungs designated as “marginal” by the ISHLT can be clinically effective. Current guidance is based on ATS/ERS guidelines from 1998. These recommendations should be revised to ensure harvesting and transplanting clinicians are appropriately informed, and that patients are correctly advised. Unfortunately, even when a transplantation is successful, difficulties persist. Latest data show that 34% of adult lung recipients had at least one episode of acute rejection between discharge and 1 year of followup. Lung transplants have a higher rejection rate than do other solid-organ transplants, partly due to the organ’s individual immunocompetence. In March, 2014, Alexander Krupnick and colleagues reported revolutionary data using mouse models to show proliferation of memory CD8-positive T cells in lung allografts aids transplant acceptance. Because current posttransplantation immunosuppressive therapies inhibit this pathway, the findings suggest that existing strategies might be doing more harm than good. The first lung transplant recipient in 1963 survived 18 days. Today, 88% of all lung transplant recipients survive the first 3 months, with 30% still alive 10-years post-transplantation. This radical procedure has prolonged and improved thousands of lives, and transformed the outlook for many people living with a chronic respiratory disease. The challenge now is how to best use this technique to ensure that no donated lung is wasted but given to the most clinically appropriate recipient, using the most successful and progressive surgical technique, with the optimum posttransplantation care. ■ The Lancet Respiratory Medicine
Michelle Del Guercio/Science Photo Library
The lung and winding road
See Review Lancet Respir Med 2013; 1: 318–28 For the Hope for more report see http://www.cysticfibrosis.org.uk/ media/443623/PAFF9 %20-%20Transplant%20 report%20-%20online.pdf For the study by Alexander Krupnick and colleagues see J Clin Invest 2014; 124: 1130–43 For more lung transplant statistics and information on the Lung Allocation Score see http://www.ishlt.org/
247