Field Of Lung Transplantation Research Articles

Progress of Clinical Application for Ex Vivo Lung Perfusion (EVLP) in Lung Transplantation.

In recent years, medical advances make lung transplantation become a standard treatment for terminal lung diseases (such as emphysema, pulmonary fibrosis, pulmonary cystic fibrosis, and pulmonary arterial hypertension) that cannot be cured by drugs or surgery (Lund et al., J Heart Lung Transplant 34:1244, 2015). However, the current number of donor lungs that meet the transplant criteria is no longer sufficient for transplanting, causing some patients to die while waiting for a suitable lung. Current methods for improving the situation of shortage of lung transplant donors include the use of donation after cardiac death (DCD) donors, smoker donors, and Ex Vivo Lung Perfusion (EVLP). Among them, EVLP is a technique for extending lung preservation time and repairing lung injury in the field of lung transplantation. By continuously assessing and improving the function of marginal donor lungs, EVLP increases the number of lungs that meet the transplant criteria and, to some extent, alleviates the current situation of shortage of donor lungs. This chapter reviews the clinical application and research progress of EVLP in the field of lung transplantation.

The role of the immune system in lung transplantation: towards improved long-term results.

Over the past 35 years, lung transplantation has evolved from an experimental treatment to the treatment of choice for patients with end-stage lung disease. Beyond the immediate period after lung transplantation, rejection and infection are the leading causes of death. The risk of rejection after lung transplantation is generally higher than after other solid organ transplants, and this necessitates more intensive immunosuppression. However, this more intensive treatment does not reduce the risk of rejection sufficiently, and rejection is one of the most common complications after transplantation. There are multiple forms of rejection including acute cellular rejection, antibody-mediated rejection, and chronic lung allograft dysfunction. These have posed a vexing problem for clinicians, patients, and the field of lung transplantation. Confounding matters is the inherent effect of more intensive immunosuppression on the risk of infections. Indeed, infections pose a direct problem resulting in morbidity and mortality and increase the risk of chronic lung allograft dysfunction in the ensuing weeks and months. There are complex interactions between microbes and the immune response that are the subject of ongoing studies. This review focuses on the role of the immune system in lung transplantation and highlights different forms of rejection and the impact of infections on outcomes.

Statement From the Society for the Advancement of Transplant Anesthesia: White Paper Advocating Desirable Milestones and Competencies for Anesthesiology Fellowship Training in the Field of Lung Transplantation.

The clinical, educational, and research facets of lung transplantation have advanced significantly since the first lung transplant in 1963. The formation of the International Society for Heart and Lung Transplantation (ISHLT) and subsequent Registry has forged a precedent of collaborative teamwork that has significantly affected current lung transplantation outcomes. The Society for the Advancement of Anesthesia (SATA) is dedicated to developing educational platforms for all facets of transplant anesthesia. Additionally, we believe that the anesthetic training for lung transplantation has not kept pace with other advances in the field. As such, SATA presents for consideration these educational milestones and competencies for anesthetic fellowship training in the field of lung transplantation. The proposed milestones were designed on the framework of 6 core competencies created by the Accreditation Council on Graduate Medical Education. The milestones were identified by combining the expert opinion of our Thoracic Transplant Committee, our experience as educators, and literature review. We offer this White Paper to the anesthesiology and transplant communities as a starting point for the discussion and evolution of perioperative anesthetic care in the field of lung transplantation.

Predictors of Mortality Post Lung Transplantation: Systematic Review and Meta-Analysis

Purpose In the field of lung transplantation , prognostic factors help in identifying characteristics of recipients and donors that may influence the survival of the transplanted organ or the patient's life. Understanding such factors can guide clinical decision making and better matching of recipients and donors. Our systematic review and meta-analysis aimed to provide best estimates of the association between possible predictors and 1-year all-cause mortality in adult primary lung transplant recipients. Methods We systematically searched 5 bibliographic databases for eligible primary studies assessing the association between any potential risk factor (related to lung donor, recipient, or the transplant operation), and 1-year recipient mortality. We pooled effect estimates using a random effects or fixed effects framework, as appropriate, according to a pre-specified protocol. This review utilized the GRADE approach to assess the quality of the evidence. Results High quality evidence identified older recipient age (HR 1.19 per 10-year increase, 95% CI 1.12 to 1.26), higher recipient BMI (HR 1.05 per 5-kg/m2 increase, 95% CI 1.01 to 1.10), female donor sex (HR 1.09, 95% CI 1.01 to 1.18), single vs bilateral lung transplant (HR 1.25, 95% CI 1.19 to 1.32) and post-transplant use of dialysis (HR 7.96, 95% CI 6.87 to 9.22) as predictors of 1-year mortality (Table 1). High quality evidence also excluded associations of pre-transplant lung disease etiology, recipient diabetes , pre-transplant systolic pulmonary artery pressure (PAP), pre-transplant mean PAP, donor age, blood type compatibility, and height mismatch between recipient and donors with 1-year mortality. Conclusion Recipient age, recipient BMI, post-transplant dialysis, donor sex, and transplant type predict 1-year graft survival . With the exception of post-transplant need for dialysis, the impact of each factor is, however, modest, suggesting the potential value for a predictive model that would incorporate multiple factors.

Can Lung Transplant Surgeons Still Be Scientists? High Productivity Despite Competitive Funding

Today's declining federal budget for scientific research is making it consistently more difficult to become federally funded. We hypothesized that even in this difficult era, surgeon-scientists have remained among the most productive and impactful researchers in lung transplantation. Grants awarded by the NIH for the study of lung transplantation between 1985 and 2015 were identified by searching NIH RePORTER for 5 lung transplantation research areas. A grant impact metric was calculated for each grant by dividing the sum of impact factors for all associated manuscripts by the total funding for that grant. We used nonparametric univariate analysis to compare grant impact metrics by department. We identified 109 lung transplantation grants, totaling approximately $300 million, resulting in 2304 papers published in 421 different journals. Surgery has the third highest median grant impact metric (4.2 per $100,000). The department of surgery had a higher median grant impact metric compared to private companies (P <.0001). There was no statistical difference in the grant impact metric compared to all other medical specialties, individual departments with multiple grants, or all basic science departments (all P >.05). Surgeon-scientists in the field of lung transplantation have received fewer grants and less total funding compared to other researchers but have maintained an equally high level of productivity and impact. The dual-threat academic surgeon-scientist is an important asset to the research community and should continue to be supported by the NIH.

Cystic fibrosis in Canada: A historical perspective

Cystic Fibrosis Canada (CF Canada) is a productive model of collaboration between families and the scientific and medical communities. The impetus for this response to a rare and then poorly unders...

Recent advances in lung transplantation.

Lung transplantation can improve quality of life and prolong survival for individuals with end-stage lung disease, and many advances in the realms of both basic science and clinical research aspects of lung transplantation have emerged over the past few decades. However, many challenges must yet be overcome to increase post-transplant survival. These include successfully bridging patients to transplant, expanding the lung donor pool, inducing tolerance, and preventing a myriad of post-transplant complications that include primary graft dysfunction, forms of cellular and antibody-mediated rejection, chronic lung allograft dysfunction, and infections. The goal of this manuscript is to review salient recent and evolving advances in the field of lung transplantation.

Banff Lung Report: Current knowledge and future research perspectives for diagnosis and treatment of pulmonary antibody-mediated rejection (AMR).

The Lung session of the 2017 14th Banff Foundation for Allograft Pathology Conference, Barcelona focused on the multiple aspects of antibody-mediated rejection (AMR) in lung transplantation. Multidimensional approaches for AMR diagnosis, including classification, histological and immunohistochemical analysis, and donor- specific antibody (DSA) characterization with their current strengths and limitations were reviewed in view of recent research. The group also discussed the role of tissue gene expression analysis in the context of unmet needs in lung transplantation. The current best practice for monitoring of AMR and the therapeutic approach are summarized and highlighted in this report. The working group reached consensus of the major gaps in current knowledge and focused on the unanswered questions regarding pulmonary AMR. An important outcome of the meeting was agreement on the need for future collaborative research projects to address these gaps in the field of lung transplantation.

Acute postoperative management after lung transplantation

Despite many advances in the field of lung transplantation, lung transplant recipients have the lowest median survival of any solid organ transplant population. Complications such as reperfusion injury, graft rejection, infection, and anastomotic breakdown increase morbidity and mortality during the immediate postoperative period. Ventilator management with lung protective strategies can not only minimize ventilator time and mitigate the risk of ventilator-associated pneumonia, but it may also decrease the risk of primary graft dysfunction and graft failure. Maintaining fluid balance, pain control, and preserving renal function also decrease postoperative complications. Advancements in immunotherapy with the use of calcineurin inhibitors and monoclonal antibodies have been shown to decrease the incidence of acute rejection. However, when unexpected complications occur, appropriately timed rescue therapies such asthe initiation of extra-corporeal membrane oxygenation, retransplantation, and plasmapheresis are important considerations geared toward a positive transplant outcome.

Ex Vivo Lung Perfusion: A Key Tool for Translational Science in the Lungs

Exvivo lung perfusion (EVLP) promises to be a comprehensive platform for assessment, reconditioning, and preservation of donor lungs and has been dramatically changing the face of clinical lung transplantation. Besides its increasing role in lung transplantation, EVLP has also been recognized as a useful tool for translational research involving the lungs. Based on recent remarkable evidence and experience using EVLP in lung transplantation, there is growing interest in, and expectations for, the use of EVLP beyond the field of lung transplantation. By combining EVLP with advances in regenerative medicine, stem cell biology, and oncology, the evolving technology of EVLP has tremendous potential to advance pulmonary medicine and science. In this review, we revisit recent advances in EVLP technology and research and discuss the future translation of EVLP applications into life-changing medicine.

Medical complications after lung transplantation

In recent years, the field of lung transplantation has seen incremental advances in surgical technique and medical management, resulting in improved graft survival and an overall increase in the number of lung transplants performed worldwide. Lung transplantation is now performed in older patients with greater comorbidities and more pulmonary dysfunction prior to transplant than in past eras. Consequently, we have greater knowledge of the significant medical complications that occur after lung transplant including cardiovascular disease, renal insufficiency, gastroesophageal reflux, blood dyscrasias, neurologic disease, and malignancies. This article focuses on noninfectious, nonpulmonary medical complications seen postoperatively and discusses their impact on overall morbidity and mortality after lung transplantation.

Quantitative Evaluation of Native Lung Hyperinflation After Single Lung Transplantation for Emphysema Using Three-Dimensional Computed Tomography Volumetry

ObjectiveAlthough double lung transplantation is performed more frequently for emphysema, single lung transplantation (SLT) continues to be performed owing to limited donor organ availability. Native lung hyperinflation (NLH) is a unique complication following SLT for emphysema. Three-dimensional computed tomography (3D-CT) volumetry has been introduced into the field of lung transplantation, which we used to assess NLH in emphysema patients undergoing SLT. The primary purpose of this study was to confirm the effectiveness of 3D-CT volumetry in the evaluation of NLH following SLT for emphysema. MethodsIn 5 emphysema patients undergoing SLT at Kyoto University Hospital, 3D-CT volumetry data, pulmonary function test results, and clinical and radiological findings were retrospectively evaluated. ResultsThree patients did not develop a significant mediastinal shift, whereas the other 2 patients developed a mediastinal shift. In the 3 patients without a mediastinal shift, 3D-CT volumetry did not show a significant increase in native lung volume. These patients had a history of sternotomy prior to lung transplantation and firm adhesion on the mediastinal side was detected during lung transplantation. One of 2 patients with a mediastinal shift developed severe dyspnea with significantly decreased pulmonary function, and 3D-CT volumetry showed a significant increase in the native lung volume. However, the other patient did not show any dyspnea and his native lung volume decreased postoperatively (preoperatively to 6 months postoperatively: +981 mL and −348 mL, respectively). ConclusionAlthough bilateral lung transplantation has become preferable for emphysema patients owing to postoperative NLH with SLT, patients with a history of sternotomy prior to lung transplantation might be good candidates for SLT. 3D-CT volumetry may be a useful method for detection of NLH.

Practical guidelines: lung transplantation in patients with cystic fibrosis.

There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation.

Recipient risk factors and lung transplant outcomes

Scientific and technical developments in the field of lung transplantation have allowed it to become a successful treatment option for various end-stage lung diseases. As the demand for lung allografts increases and waitlists expand, it is vital that lung transplant centers optimize use of this limited resource by selecting recipients who have the best prospects of positive long-term outcomes. Recipient selection criteria vary across transplant selection committees. We review the most recent body of literature for recipient consideration and describe potential effects on morbidity and mortality posttransplantation. Although prior guidelines for contraindications to lung transplantation have been described, the benchmarks for recipient selection are constantly being challenged. Age, weight, and psychologic condition of recipients pretransplant have more recently been shown to have significant influence on posttransplant outcomes. Advancements in human leukocyte antigen antibody testing and use of extracorporeal membrane oxygenation as a bridge to lung transplantation have additionally impacted recipient selection standards. Recipient selection criteria continue to evolve because of advances in mechanical bridging to transplant and postoperative management. This review will cover some of the new concepts in lung transplant recipient selection and their potential effect on posttransplant outcomes.

Lobar Lung Transplantation: Emerging Evidence for a Viable Option

The field of lung transplantation has seen an exciting evolution recently, with novel approaches to increasing the number of organs available for patients with end-stage lung disease. We review 2 recent reports describing the approach of lobar lung transplant as a successful and viable option for those recipients who are challenged by size mismatch and clinical course decline while on the transplant waiting list.

Lung transplantation

Lung transplantation may be the only intervention that can prolong survival and improve quality of life for those individuals with advanced lung disease who are acceptable candidates for the procedure. However, these candidates may be extremely ill and require ventilator and/or circulatory support as a bridge to transplantation, and lung transplantation recipients are at risk of numerous post-transplant complications that include surgical complications, primary graft dysfunction, acute rejection, opportunistic infection, and chronic lung allograft dysfunction (CLAD), which may be caused by chronic rejection. Many advances in pre- and post-transplant management have led to improved outcomes over the past decade. These include the creation of sound guidelines for candidate selection, improved surgical techniques, advances in donor lung preservation, an improving ability to suppress and treat allograft rejection, the development of prophylaxis protocols to decrease the incidence of opportunistic infection, more effective therapies for treating infectious complications, and the development of novel therapies to treat and manage CLAD. A major obstacle to prolonged survival beyond the early post-operative time period is the development of bronchiolitis obliterans syndrome (BOS), which is the most common form of CLAD. This manuscript discusses recent and evolving advances in the field of lung transplantation.

Are three patients better than one?

Lung transplantation represents the only effective strategy for treatment of end stage respiratory failure. Nevertheless its clinical application remains quite limited and a significant discrepancy between the number of LTx performed and its real need still remains evident [1]. Therefore patients wait for LTx for a long period with a high mortality rate while on the waiting list. For this reason we wrote a review with a provocative title in which we wondered if LTx was a clinical reality or should be conversely considered an experimental procedure [2]. In the recent period, we are witnessing epochal changes at different levels in the field of lung transplantation. On the side of donor management, application of particular ventilatory strategies may be effective in increasing the rate of lung suitability [3]. After the initial experience published by Steen [4], very recently an important article from the Toronto Lung Transplant Program showed how initially rejected or sub-optimal grafts can be successfully transplanted after the recovery of a normal pulmonary function, obtained by ex-vivo lung perfusion [5]. ECMO and interventional lung assist devices have been introduced in the clinical armamentarium for the management of lung transplant recipients suffering from severe deterioration of pulmonary function. As it happens for heart and kidney recipients, novel technological advances of the devices nowadays available allow their applications as a bridge to transplant also for LTx. These technologies not only increase the life expectancy of patients in the waiting list but also avoid the necessity of mechanical ventilation and lead these patients to LTx in better conditions even without the need of an intensive care unit stay [6–8]. Waiting time for LTx is highly dependent from somatic characteristics of recipients and very small patients may wait for a suitable graft for a longer period. For these patients, living lobar lung transplant may be one of the possible strategies to overcome this issue. Chen et al. describe excellent results regarding pulmonary function on living lobar lung transplant donors. This is an important message but a word of caution is mandatory. In comparison with other solid transplant performed using living donor graft (e.g. kidney), living lobar lung transplant is a highly demanding procedure performed on ‘healthy’ patients (the donor). In fact, the procedure Correspondence Massimo Boffini, Cardiac Surgery Department, San Giovanni Battista Hospital, University of Turin, Corso Bramante 88, Turin 18100, Italy. Tel.: +39 011 6335511; fax: +39 011 6336130; e-mail: massimo.boffini@unito.it

Challenges in lung transplantation

Lung transplantation is an established therapy for end-stage pulmonary disorders in selected patients without significant comorbidities. The particular constraints associated with organ transplantation from deceased donors involve specific allocation rules in order to optimise the medical efficacy of the procedure. Comparison of different policies adopted by national transplant agencies reveals that an optimal and unique allocation system is an elusive goal, and that practical, geographical and logistic parameters must be taken into account. A solution to attenuate the imbalance between the number of lung transplant candidates and the limited availability of organs is to consider marginal donors. In particular, assessment and restoration of gas exchange capacity ex vivo in explanted lungs is a new and promising approach that some lung transplant programmes have started to apply in clinical practice. Chronic lung allograft dysfunction, and especially bronchiolitis obliterans, remains the major medium- and long-term problem in lung transplantation with a major impact on survival. Although there is to date no cure for established bronchiolitis obliterans, new preventive strategies have the potential to limit the burden of this feared complication. Unfortunately, randomised prospective studies are infrequent in the field of lung transplantation, and data obtained from larger studies involving kidney or liver recipients are not always relevant for this purpose.

Guidelines for the Selection of Lung Transplantation Candidates

The present guidelines have been prepared with the consensus of at least one representative of each of the hospitals with lung transplantation programs in Spain. In addition, prior to their publication, these guidelines have been reviewed by a group of prominent reviewers who are recognized for their professional experience in the field of lung transplantation. Within the following pages, the reader will find the selection criteria for lung transplantation candidates, when and how to remit a patient to a transplantation center and, lastly, when to add the patient to the waiting list. A level of evidence has been identified for the most relevant questions. Our intention is for this document to be a practical guide for pulmonologists who do not directly participate in lung transplantations but who should consider this treatment for their patients. Finally, these guidelines also propose an information form in order to compile in an organized manner the patient data of the potential candidate for lung transplantation, which are relevant in order to be able to make the best decisions possible.

Normativa para la selección de pacientes candidatos a trasplante pulmonar

The present guidelines have been prepared with the consensus of at least one representative of each of the hospitals with lung transplantation programs in Spain. In addition, prior to their publication, these guidelines have been reviewed by a group of prominent reviewers who are recognized for their professional experience in the field of lung transplantation. Within the following pages, the reader will find the selection criteria for lung transplantation candidates, when and how to remit a patient to a transplantation center and, lastly, when to add the patient to the waiting list. A level of evidence has been identified for the most relevant questions. Our intention is for this document to be a practical guide for pulmonologists who do not directly participate in lung transplantations but who should consider this treatment for their patients. Finally, these guidelines also propose an information form in order to compile in an organized manner the patient data of the potential candidate for lung transplantation, which are relevant in order to be able to make the best decisions possible.