Ethical considerations in xenotransplantation of thoracic organs - a call for a debate on value based decisions.

Xenotransplant covers a broad ethical territory and there are several ethical questions that have arisen in parallel with the technological advances that have allowed the first porcine transplants to occur. This brief communication highlights ethical considerations regarding heart and lung xenotransplantation, with an emphasis on unresolved value-based concerns in the field. The aim of this text is therefore to encourage the readers to consider the vast potential of this emerging technique to do good, but also the risk of doing harm, and to participate in a discussion. The list of questions presented here is not exhaustive but hopefully represents some of the questions that appear to be most pressing as the field advances. The focus is on the value-based, or ethical questions, not the questions related to the practical medical procedures.

Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop.

Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance of immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include the appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potentially novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report.

Public Appeals Challenging Criteria for Pediatric Organ Transplantation.

In this article, I review the ethical issues that arise in the allocation of deceased-donor organs to children and young adults. By analyzing the public media cases of Sarah Murnaghan, Amelia Rivera, and Riley Hancey, I assess whether public appeals to challenge inclusion and exclusion criteria for organ transplantation are ethical and under which circumstances. The issues of pediatric allocation with limited evidence and candidacy affected by factors such as intellectual disability and marijuana use are specifically discussed. Finally, I suggest that ethical public advocacy can coexist with well-evidenced transplant allocation if and when certain conditions (morally defensible criteria, expert evidence, nonprioritization of the poster child, and greater advocacy for organ transplantation in general) are met.

Ethical considerations regarding heart and lung transplantation and mechanical circulatory support during the COVID-19 pandemic: an ISHLT COVID-19 Task Force statement.

To understand the challenges for thoracic transplantation and mechanical circulatory support during the current coronavirus disease 2019 pandemic, we propose separating the effects of the pandemic into 5 distinct stages from a healthcare system perspective. We discuss how the classical ethical principles of utility, justice, and efficiency may need to be adapted, and we give specific recommendations for thoracic transplantation and mechanical circulatory support centers to balance their clinical decisions and strategies for advanced heart and lung disease during the current pandemic.

[Age limitation to lung transplant recipients. Ethical aspects]. / Limitación por edad en trasplante de pulmón. Aspectos éticos.

We present a review of bioethical aspects of limiting patients 65 years or older to lung transplantation. Lung transplantation is a therapeutic option in patients with severe advanced respiratory diseases, progressive despite medical treatment to prolong the expected survival. It is an aggressive surgical treatment, and the patient must complete a lifelong immunosuppressive treatment. Given the donor shortage, access to this treatment is regulated by organ transplant societies, which develop patient selection guidelines. One contraindication to transplantation has been the age of 65 years, sustained by the poor results of older patients and following utilitarian bioethics concept. For the time being there is no unified selection criteria to identify older patients susceptible to have a worse outcome after transplantation. Applying a personalist bioethics, we propose to use selection criteria based on frailty scales to identify those frail patients more likely to die after the transplant procedure.

Limitación por edad en trasplante de pulmón. Aspectos éticos / Age limitation to lung transplant recipients. Ethical aspects

Presentamos una revisión de los aspectos bioéticos de la limitación al acceso a trasplante pulmonar en pacientes mayores de 65 años. El trasplante pulmonar supone una opción terapéutica en pacientes con enfermedades respiratorias graves en fase avanzada, progresivas a pesar de tratamiento médico con el objetivo de prolongar la supervivencia esperada. Se trata de un tratamiento quirúrgico agresivo para el paciente, que deberá cumplimentar un tratamiento inmunosupresor de por vida. Dada la escasez de donantes, el acceso a este tratamiento está regulado por las sociedades de trasplante de órgano, que realizan las guías de selección de pacientes. Entre las contraindicaciones al trasplante ha existido un límite de edad fijado en 65 años, sostenido por los malos resultados de los pacientes de mayor edad y siguiendo una bioética utilitarista. No existe un criterio unificado de selección en la actualidad que permita identificar a los pacientes de mayor edad susceptibles de tener peor resultado tras el trasplante. Aplicando una bioética personalista proponemos emplear criterios de selección basados en escalas de fragilidad del paciente para identificar aquellos pacientes con mayor fragilidad y mayor posibilidad de fallecer tras el trasplante

We present a review of bioethical aspects of limiting patients 65 years or older to lung transplantation. Lung transplantation is a therapeutic option in patients with severe advanced respiratory diseases, pro-gressive despite medical treatment to prolong the expected survival. It is an aggressive surgical treatment, and the patient must complete a lifelong immunosuppressive treatment. Given the donor shortage, access to this treatment is regulated by organ transplant societies, which develop patient selection guidelines. One contraindication to transplantation has been the age of 65 years, sustained by the poor results of older patients and following utilitarian bioethics concept. For the time being there is no unified selection criteria to identify older patients susceptible to have a worse outcome after transplantation. Applying a personalist bioethics, we propose to use selection criteria based on frailty scales to identify those frail pa-tients more likely to die after the transplant procederé

Addressing lung transplant with adults with cystic fibrosis: A qualitative analysis of patients' perspectives and experiences.

Referral for lung transplantation is a complex process that typically begins with a discussion in cystic fibrosis (CF) clinic. We performed a secondary analysis of interviews conducted at the University of Washington CF Clinic as part of a study of unmet palliative care needs, June 2015 - January 2016, among adults with moderate-to-severe CF-related lung disease. Content analysis methods were used to identify themes related to discussion of lung transplant in CF clinic. Thirty-two of 48 interviews (67%) addressed transplant. An individual's willingness to discuss transplant was not necessarily related to the degree of lung function impairment. Patients reported reliance on CF physicians as a source of accurate information about transplant. Individuals with CF sometimes reported feeling too old or not worthy of transplant. Many had apprehensive or ambivalent feelings towards transplant. Patient-identified barriers and facilitators to lung transplant discussions can inform physicians as they discuss transplant in CF clinic.

Lung transplant referral for individuals with cystic fibrosis: Cystic Fibrosis Foundation consensus guidelines.

OBJECTIVE: Provide recommendations to the cystic fibrosis (CF) community to facilitate timely referral for lung transplantation for individuals with CF. METHODS: The CF Foundation organized a multidisciplinary committee to develop CF Lung Transplant Referral Consensus Guidelines. Three workgroups were formed: timing for transplant referral; modifiable barriers to transplant; and transition to transplant care. A focus group of lung transplant recipients with CF and spouses of CF recipients informed guideline development. RESULTS: The committee formulated 21 recommendation statements based on literature review, committee member practices, focus group insights, and in response to public comment. Critical approaches to optimizing access to lung transplant include early discussion of this treatment option, assessment for modifiable barriers to transplant, and open communication between the CF and lung transplant centers. CONCLUSIONS: These guidelines will help CF providers counsel their patients and may reduce the number of individuals with CF who die without consideration for lung transplant.

Combined liver-lung transplantation: Indications, outcomes, current experience and ethical Issues.

Combined liver-lung transplantation (CLLT) is a rare, life-saving procedure to treat concomitant lung and liver disease. There have been 93 combined lung and liver transplantations performed in the United States since 1994. Techniques include both lung first and liver first sequential transplants with selective extracorporeal circulation of either thoracic or abdominal portions, with either end-to-end or Roux-en-Y choledochojejunostomy for biliary reconstruction. This review evaluates the existing literature regarding combined lung and liver transplantation (CLLT), describing the candidates, operation, perioperative complications, associated management strategies, and recommendations for immunosuppressive therapy and follow up.

A personal perspective on the science, ethics, and commercialization of xenotransplantation.

A parent of a child with a fatal lung disease decides to try to save her first with improved pharmaceuticals to hold the disease at bay, and then with an unlimited supply of transplantable lungs to cure the disease and manage the consequences of eventual organ rejection. The parent needs to surmount science, ethics, and commercialization issues for organ transplantation to be a practical cure, and several of those issues are particularly difficult for xenotransplanation. After half-a-decade of effort, the parent's personal journey has resulted in a 100-fold increase in the number of hours that pulmonary xenografts are viable, but still remains significantly shy of commercial viability and still leaves some ethical issues open.

Reflexión bioética sobre trasplantes de pulmón / Bioethics reflection about lung transplant

Despite a substantial improvement in organ transplant techniques and rejections methods, Chile still exhibits an apparent lack of adequate increase of lung transplants. In particular, despite the presence of precise indicactions of lung transplant, the problem of limited donors is a very difficult reality for the receptors. In this work, we offer a comparison amongst Chile and Spain, with special emphasis on bioethical aspects of this process.

A pesar de los avances que ha experimentado la técnica de los trasplantes de órganos y la mejora en manejo del rechazo, en nuestro país no se advierte un crecimiento adecuado a las necesidades de los trasplantes del sistema respiratorio requeridos. Si bien existen indicaciones precisas de trasplante pulmonar, el problema de la escasez de donantes es una dificultad concreta para los enfermos. Se revisa y compara nuestra situación con la de España y se analizan algunos aspectos bioéticos que surgen de este proceso.

Was Sarah Murnaghan treated justly?

Lung transplantation is a potentially life-saving procedure for patients with irreversible lung failure. Five-year survival rates after lung transplantation are >50% for children and young adults. But there are not enough lungs to save everyone who could benefit. In 2005, the United Network for Organ Sharing developed a scoring system to prioritize patients for transplantation. That system considered transplant urgency as well as time on the waiting list and the likelihood that the patient would benefit from the transplant. At the time, there were so few pediatric lung transplants that the data that were used to develop the Lung Allocation Score were inadequate to analyze and prioritize children, so they were left out of the Lung Allocation Score system. In 2013, the family of a 10-year-old challenged this system, claiming that it was unjust to children. In the article, we asked experts in health policy, bioethics, and transplantation to discuss the issues in the Murnaghan case.