Advances in lung transplantation: 60 years on.

Lung transplantation is a well-established treatment for advanced lung disease, improving survival and quality of life. Over the last 60 years all aspects of lung transplantation have evolved significantly and exponential growth in transplant volume. This has been particularly evident over the last decade with a substantial increase in lung transplant numbers as a result of innovations in donor utilization procurement, including the use donation after circulatory death and ex-vivo lung perfusion organs. Donor lungs have proved to be surprisingly robust, and therefore the donor pool is actually larger than previously thought. Parallel to this, lung transplant outcomes have continued to improve with improved acute management as well as microbiological and immunological insights and innovations. The management of lung transplant recipients continues to be complex and heavily dependent on a tertiary care multidisciplinary paradigm. Whilst long term outcomes continue to be limited by chronic lung allograft dysfunction improvements in diagnostics, mechanistic understanding and evolutions in treatment paradigms have all contributed to a median survival that in some centres approaches 10 years. As ongoing studies build on developing novel approaches to diagnosis and treatment of transplant complications and improvements in donor utilization more individuals will have the opportunity to benefit from lung transplantation. As has always been the case, early referral for transplant consideration is important to achieve best results.

The 20-year paradigm shift toward organ recovery centers: 2500 donors at Mid-America Transplant and broader adoption across the United States.

On March 1, 2001, Mid-America Transplant, the organ procurement organization (OPO) located in St Louis, Missouri, performed the first organ recovery of a brain-dead donor in a hospital-independent, free-standing, organ recovery center (ORC), with successful transplantation of a liver. This was the inception of a paradigm shift in donor management and organ procurement, moving away from the traditional method of using the donor hospital. In the last 20 years, many advances have occurred in the ORC. Brain-dead donors are moved within hours of authorization to fully equipped intensive care units. Some ORCs are equipped with computed tomography scanners, portable radiography, laboratory facilities, bronchoscopy, and a cardiac catheterization laboratory. ORCs have dedicated surgical suites, and operating time is frequently during the day and is rarely delayed. Donor management in an ORC is more consistent, efficient, and effective than that in a donor hospital, and studies have demonstrated increased organ yield. Multiple studies have demonstrated a cost benefit of an ORC as well as providing an ideal environment for donor research studies. Currently, there are 24 of 57 OPOs that are using an independent or hospital-based ORC to manage their donors. We review the history and describe the current state of ORCs.

Outcome measures in solid organ donor management research: a systematic review.

AIM: We systematically reviewed published outcome measures across randomised controlled trials (RCTs) of donor management interventions. METHODS: The systematic review was conducted in accordance with recommendations by the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched MEDLINE, Embase, CENTRAL, Web of Science, and trial databases from 1980 to February 2021 for RCTs of donor management interventions. RESULTS: Twenty-two RCTs (n=3432 donors) were included in our analysis. Fourteen RCTs (63.6%) reported a primary outcome relating to a single organ only. Eight RCTs primarily focused on aspects of donor optimisation in critical care. Thyroid hormones and methylprednisolone were the most commonly evaluated interventions (five and four studies, respectively). Only two studies, focusing on single organs (e.g. kidney), evaluated outcomes relating to other organs. The majority of studies evaluated physiological or biomarker-related outcomes. No study evaluated recipient health-related quality of life. Only one study sought consent from potential organ recipients. CONCLUSIONS: The majority of RCTs evaluating donor management interventions only assessed single-organ outcomes or effects on donor stability in critical care. There is a need for an evaluation of patient-centred recipient outcomes and standardisation and reporting of outcome measures for future donor management RCTs.

Hypertonic Saline Modulates Heart Function and Myocardial Inflammatory Alterations in Brain-Dead Rats.

BACKGROUND: Brain death (BD) in potential organ donors is responsible for hemodynamic instability and organ hypoperfusion, leading to myocardial dysfunction. Hypertonic saline (HS) is a volume expander with positive effects on hemodynamics and immunomodulation and was tested in this study to prevent left ventricular (LV) dysfunction and myocardial injury. METHODS: BD was induced in anesthetized Wistar rats by inflating a subdural balloon catheter, except in sham-operated animals (n = 6). After BD induction, Control animals received only normal saline solution (NaCl 0.9%, 4 mL/kg; n = 6), and treated animals were divided to receive HS (NaCl, 7.5% 4 mL/kg) at 1 min (HS1, n = 6) or 60 min (HS60, n = 6) thereafter. We continuously assessed cardiac function for 6 h with LV pressure-volume analysis. Inflammatory response, markers of myocardial injury, and cellular apoptosis-related proteins were investigated. RESULTS: BD was associated with decreased LV systolic and diastolic function. In comparison with the Control group, HS treatments improved LV ejection fraction (HS1, 51% [40-66]; HS60, 71% [28-82]; Control, 46% [23-55]; P < 0.05) and other parameters of LV systolic function 6 h after BD induction. However, no ventricular relaxation advantages were observed during the same period. HS treatments increased antiapoptotic protein expression and decreased vascular adhesion molecule and tumor necrosis factor alpha expression. No significant differences in histologic or structural protein changes were observed between groups. CONCLUSIONS: The observed data suggest that HS ameliorates LV systolic dysfunction and seems to reduce myocardial tissue compromise in BD rats, even when the treatment is performed during the process triggered by this event.

Variation in Pediatric Organ Donor Management Practices Among US Organ Procurement Organizations.

INTRODUCTION: Reports of actual pediatric organ donor management practice among US organ procurement organizations are sparse, and the use of standardized management guidelines is unknown. A recent consensus statement from the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations offers guidelines for the management of the pediatric organ donor. RESEARCH QUESTION: To describe the use of guidelines and routine practices in the management of the pediatric organ donor with respect to hemodynamics, lung and ventilator management, fluid and electrolytes, hormonal replacement therapy, the use of blood products, thermoregulation, and prophylactic antibiotics. DESIGN: Cross-sectional observational study using a survey and follow-up telephone interview with respondents from all 58 US organ procurement organizations. RESULTS: All 58 US Organ Procurement Organizations participated. A majority employed written guidelines for the management of pediatric donor hemodynamics, thermoregulation, fluids, and electrolytes. Management of blood products, the lung, and mechanical ventilation were less commonly committed to written guidelines, but common practices were described. All used various forms of hormonal replacement therapy and the majority administered empiric antibiotic therapy. Wide variation was observed in the management of the lung, mechanical ventilation, and glycemic control. DISCUSSION: Most OPOs used forms of standardized donor management for the pediatric organ donor although variation in the content of that management exists. Barriers to an evidence-based approach to the pediatric donor need to be determined and addressed.

Early declaration of death by neurologic criteria results in greater organ donor potential.

BACKGROUND: Aggressive management of patients prior to and after determination of death by neurologic criteria (DNC) is necessary to optimize organ recovery, transplantation, and increase the number of organs transplanted per donor (OTPD). The effects of time management are understudied but potentially pivotal component. The objective of this study was to analyze specific time points (time to DNC, time to procurement) and the time intervals between them to better characterize the optimal timeline of organ donation. METHODS: Using data over a 5-year time period (2011-2015) from the largest US OPO, all patients with catastrophic brain injury and donated transplantable organs were retrospectively reviewed. Active smokers were excluded. Maximum donor potential was seven organs (heart, lungs [2], kidneys [2], liver, and pancreas). Time from admission to declaration of DNC and donation was calculated. Mean time points stratified by specific organ procurement rates and overall OTPD were compared using unpaired t-test. RESULTS: Of 1719 Declaration of Death by Neurologic Criteria organ donors, 381 were secondary to head trauma. Smokers and organs recovered but not transplanted were excluded leaving 297 patients. Males comprised 78.8%, the mean age was 36.0 (±16.8) years, and 87.6% were treated at a trauma center. Higher donor potential (>4 OTPD) was associated with shorter average times from admission to brain death; 66.6 versus 82.2 hours, P = 0.04. Lung donors were also associated with shorter average times from admission to brain death; 61.6 versus 83.6 hours, P = 0.004. The time interval from DNC to donation varied minimally among groups and did not affect donation rates. CONCLUSIONS: A shorter time interval between admission and declaration of DNC was associated with increased OTPD, especially lungs. Further research to identify what role timing plays in the management of the potential organ donor and how that relates to donor management goals is needed.

Organ donor management: Eight common recommendations and actions that deserve reflection.

Despite major advances in our understanding of the physiopathology of brain death (BD), there are important controversies as to which protocol is the most appropriate for organ donor management. Many recent reviews on this subject offer recommendations that are sometimes contradictory and in some cases are not applied to other critically ill patients. This article offers a review of the publications (many of them recent) with an impact upon these controversial measures and which can help to confirm, refute or open new areas of research into the most appropriate measures for the management of organ donors in BD, and which should contribute to discard certain established recommendations based on preconceived ideas, that lead to actions lacking a physiopathological basis. Aspects such as catecholamine storm management, use of vasoactive drugs, hemodynamic objectives and monitoring, assessment of the heart for donation, and general care of the donor in BD are reviewed.

Safe orthotopic transplantation of hearts harvested 24 hours after brain death and preserved for 24 hours.

OBJECTIVES: The aim of this study was to demonstrate safe orthotopic transplantation of porcine donor hearts harvested 24 hours after brain death and preserved for 24 hours before transplantation. DESIGN: Circulatory normalization of brain dead (decapitated) pigs was obtained using a new pharmacological regimen (n = 10). The donor hearts were perfused at 8 °C in cycles of 15 min perfusion followed by 60 min without perfusion. The perfusate consisted of an albumin-containing hyperoncotic cardioplegic nutrition solution with hormones and erythrocytes. Orthotopic transplantation was done in 10 recipient pigs after 24 hours' preservation. Transplanted pigs were monitored for 24 hours, then an adrenaline stress test was done. RESULTS: All transplanted pigs were stable throughout the 24-hour observation period with mean aortic pressure around 80 mmHg and normal urine production. Mean right and left atrial pressures were in the range of 3-6 and 5-10 mmHg, respectively. Blood gases at 24 hours did not differ from baseline values. The adrenaline test showed a dose dependent response, with aortic pressure increasing from 98/70 to 220/150 mmHg and heart rate from 110 to 185 beats/min. CONCLUSION: Orthotopic transplantation of porcine hearts harvested 24 hours after brain death and preserved for 24 hours can be done safely.

Extended criteria donor organ use for heart-lung transplantation in the modern era.

BACKGROUND: Demand for donor hearts and lungs exceeds their supply. Extended Criteria Donor (ECD) organs are used to help meet this demand, but their impact on heart-lung transplantation outcomes is poorly characterized. METHODS AND RESULTS: The United Network for Organ Sharing was queried for data on adult heart-lung transplantation recipients (n = 447) from 2005‒2021. Recipients were stratified based on whether they received ECD hearts and/or lungs. Morbidity was analyzed using Kruskal-Wallis, chi-square, and Fisher's exact tests. Mortality was analyzed using Kaplan-Meier estimation, log-rank tests and Cox regression. Sixty-five (14.5%) patients received two ECD organs, 134 (30.0%) received only an ECD lung, and 65 (14.5%) only an ECD heart. Recipients of two ECD organs were older, more likely to have diabetes, and more likely transplanted from 2015‒2021 (p < 0.05). Groups did not differ by pre-transplant diagnosis, intensive care unit disposition, life support use, or hemodynamics. Group five-year survival rates ranged from 54.5% to 63.2% (p = 0.428). Groups did not differ by 30-day mortality, strokes, graft rejection, or hospital length of stay. CONCLUSIONS: Using ECD hearts and/or lungs for heart-lung transplantation is not associated with increased mortality and is a safe strategy for increasing donor organ supply in this complex patient population.

Anesthetic Considerations of Organ Procurement After Brain and Cardiac Death: A Narrative Review.

Organ donation procedures have become more frequent in the US as the need for transplants is increasing. Defining the anesthesiologist's role in organ donations after brain and cardiac death is important, as is understanding its ethics and practical physiologic and perioperative implications. Despite this, there are few papers specifically addressing the anesthetic management of organ donors. This review summarizes the preoperative, intraoperative, and postmortem considerations for the anesthesiologist involved in organ donation after either brain or cardiac death. A search of the published literature was performed using PubMed, Excerpta Medica dataBASE (EMBASE), and Google Scholar in March of 2022 for articles addressing anesthetic considerations of organ procurement surgeries after brain and cardiac death. This review demonstrates that anesthesiologists play a significant role in the organ procurement process. Their role in the perioperative management of the donor may affect the outcomes of organ transplantation. The gap between the number of organs harvested and the number of patients awaiting organ transplantation remains high despite continued efforts to increase the number of available organs. Perioperative management of organ donors aims at counteracting the associated unique physiologic derangements and targets optimization of oxygenation of the organs intended for procurement. Optimizing care after death can help ensure the viability of organs and the best outcomes for recipients. As organ donation after cardiac death (DCD) becomes more frequent in the US, anesthesiologists should be aware of the DCD classifications of donors and emerging novel perfusion techniques.

Whole Blood Thiamine in Organ Donors After the Neurologic Determination of Death.

INTRODUCTION: Metabolic resuscitation of organ donors and the attenuation of oxidative stress incurred by organs following brain death and transplantation have the potential to improve organ yield and allograft function. Thiamine (vitamin B1) is a vital coenzyme in both energy metabolism and the production of antioxidants that has not been studied in the donor population. RESEARCH AIM: To determine the frequency of subclinical thiamine deficiency in brain-dead organ donors and its correlation with demographics, length of hospitalization, donor management, lactic acidosis, and the requirement for vasoactive support. DESIGN: Prospective cohort study of brain-dead donors managed at a single organ procurement organization's organ recovery facility. RESULTS: A total 64 donors were enrolled; 24 donors had thiamine levels drawn upon arrival and 40 donors had levels drawn at the time of organ procurement. Whole blood thiamine levels were inversely correlated with the time from death (P = .007) and 20% (8/40) of donors had levels below the normal range at the time of organ procurement. Demographic features of the donor were not associated with thiamine levels although longer hospital stays prior to death were associated with lower levels (P < .05). The presence and resolution of lactic acidosis was not associated with whole blood thiamine level. Higher thiamine levels were associated with earlier discontinuation of vasoactive support (P = .04). DISCUSSION: Whole blood thiamine deficiency was not uncommon at the time of organ procurement. Thiamine may be associated with the requirement for hemodynamic support.

Economic evaluation of the specialized donor care facility for thoracic organ donor management.

BACKGROUND: Over the last decade two alternative models of donor care have emerged in the United States: the conventional model, whereby donors are managed at the hospital where brain death occurs, and the specialized donor care facility (SDCF), in which brain dead donors are transferred to a SDCF for medical optimization and organ procurement. Despite increasing use of the SDCF model, its cost-effectiveness in comparison to the conventional model remains unknown. METHODS: We performed an economic evaluation of the SDCF and conventional model of donor care from the perspective of U.S. transplant centers over a 2-year study period. In this analysis, we utilized nationwide data from the Scientific Registry of Transplant Recipients and controlled for donor characteristics and patterns of organ sharing across the nation's organ procurement organizations (OPOs). Subgroup analysis was performed to determine the impact of the SDCF model on thoracic organ transplants. RESULTS: A total of 38,944 organ transplants were performed in the U.S. during the study period from 13,539 donors with an observed total organ cost of $1.36 billion. If every OPO assumed the cost and effectiveness of the SDCF model, a predicted 39,155 organ transplants (+211) would have been performed with a predicted total organ cost of $1.26 billion (-$100 million). Subgroup analysis of thoracic organs revealed that the SDCF model would lead to a predicted 156 additional transplants with a cost saving of $24.6 million. CONCLUSIONS: The U.S. SDCF model may be a less costly and more effective means of multi-organ donor management, particularly for thoracic organ donors, compared to the conventional hospital-based model.

Warm retrograde perfusion can remove more fat from lung grafts with fat embolism in a porcine model.

OBJECTIVE: In lung transplantation, unexpected pulmonary emboli, including thrombi and fat, have been observed with high probability and are associated with potential primary graft dysfunction. We evaluated a new perfusion method using warm retrograde flushing that removes more fat than conventional cold retrograde flushing. METHODS: We developed a novel porcine donor model for pulmonary fat embolism by administering autologous fat in the left pulmonary artery. The left pulmonary artery and the left superior and inferior pulmonary veins were cannulated for flushing and collecting these solutions. After flushing, the left lung was reperfused under observation for 3 h. Two groups underwent warm and cold additional retrograde flush (WS; warm solution group, CS; cold solution group). RESULTS: The fat removal rate in the antegrade flush was equal in both groups (3.0 ± 0.6% vs 3.0 ± 0.4%, p = 0.46); however, the rate was significantly greater in the WS group in retrograde flush (25.2 ± 3.2% vs 8.0 ± 1.4%, p = 0.01). Histology with Oil Red O staining and its software analysis showed more residual fat in the CS group (0.12 ± 0.01% vs 0.38 ± 0.07%, p = 0.01). There was no significant difference in the pulmonary function and hemodynamics during the 3-h period after reperfusion. CONCLUSION: Warm retrograde perfusion can remove more fat from lung grafts with fat embolism in a porcine donor model.

Development of a Pulmonary Workshop for Organ Recovery Coordinators' Continuing Medical Education.

Organ recovery coordinators (ORCs) have varied professional education backgrounds; however, based on their specialized education, their training may not have included in-depth mechanical ventilation and pulmonary management. An 8-hour pulmonary workshop was developed in collaboration between an organ procurement organization and a university-based respiratory care department. The workshop focused on pulmonary management and hands-on laboratory exercises using mechanical ventilators. A program assessment questionnaire was completed by participants following the workshop, which requested their self-reported comfort/familiarity with pulmonary management skills before and after the workshop on a 5-point Likert scale. Following the pulmonary workshop, the mean ORC comfort/familiarity for all pulmonary management skills increased significantly (P < .01). This program suggests ORCs can develop a greater awareness and comfort with pulmonary management by participating in a continuing education pulmonary workshop. Continuing education initiatives focused on pulmonary management of donor patients using hands-on competencies should be part of the ORCs practice improvement efforts.

Transplantation of a three-lobed donor left lung: A case report.

A true left middle lobe (lingular lobe) is very rare, but accessory fissures can be unexpectedly found at transplant. Pre-transplant knowledge of accessory lobes and accessory fissures aids in preparation, transplantation, postoperative assessment, and long-term care planning; however, fissures and accessory lobes can be overlooked by radiologists during routine evaluation of images. Here, we describe the first left lung with three anatomical lobes that was successfully transplanted into a 63-year-old patient with idiopathic pulmonary fibrosis. This anatomical variation did not change our surgical plan or technique, but surgeons should be aware of this possibility, especially when planning postoperative care.

Pediatric Donor Management Goals in Use by US Organ Procurement Organizations.

INTRODUCTION: A recent study of pediatric organ donation after the neurologic determination of death (DNDD) demonstrated an association between the use of donor management goals (DMGs) by organ procurement organizations (OPOs) and organ yield. OBJECTIVE: To describe the pediatric DMGs used by OPOs and any association between specific DMGs and organ yield. DESIGN: Query of US OPOs who utilized DMGs in the care of pediatric DNDD organ donors from 2010 to 2013. RESULTS: All 23 OPOs using DMGs for pediatric DNDD organ donors during the study period participated (100%). The OPOs pursued an average 9.6 goals (standard deviation: 3.9; range: 5-22) with 113 unique definitions that targeted 33 aspects of donor hemodynamics, gas exchange/mechanical ventilation, electrolytes/renal function, blood products, thermoregulation, and infection control. The DMGs used by >50% of OPOs included blood pressure, oxygenation (partial pressure of arterial oxygen (PaO2), oxygen saturation of hemoglobin by pulse oximetry, or PaO2/fractional concentration of inspired oxygen [FiO2] ratio), pH, central venous pressure, serum sodium, urine output, limitations on inotropic support, and serum glucose. There was no significant correlation between the number of DMGs pursued by OPOs and organ yield. There was a difference in the observed/expected organs transplanted in the 0- to 10-year age-group for OPOs that included serum creatinine among their DMGs ( P = .046). CONCLUSIONS: The pediatric DMGs used by OPOs were generally measurable but diverse in definition and the number of goals pursued. There was no benefit in organ yield from larger DMG bundles. There may be a benefit in organ yield through the use of serum creatinine as a DMG in pediatric donors aged 0 to 10 years.

Extended criteria donor organ use for heart-lung transplantation in the modern era

Abstract Background: Demand for donor hearts and lungs exceeds their supply. Extended Criteria Donor (ECD) organs are used to help meet this demand, but their impact on heart-lung transplantation outcomes is poorly characterized. Methods and results: The United Network for Organ Sharing was queried for data on adult heart-lung transplantation recipients (n = 447) from 2005‒2021. Recipients were stratified based on whether they received ECD hearts and/or lungs. Morbidity was analyzed using Kruskal-Wallis, chi-square, and Fisher's exact tests. Mortality was analyzed using Kaplan-Meier estimation, log-rank tests and Cox regression. Sixty-five (14.5%) patients received two ECD organs, 134 (30.0%) received only an ECD lung, and 65 (14.5%) only an ECD heart. Recipients of two ECD organs were older, more likely to have diabetes, and more likely transplanted from 2015‒2021 (p < 0.05). Groups did not differ by pre-transplant diagnosis, intensive care unit disposition, life support use, or hemodynam-ics. Group five-year survival rates ranged from 54.5% to 63.2% (p = 0.428). Groups did not differ by 30-day mortality, strokes, graft rejection, or hospital length of stay. Conclusions: Using ECD hearts and/or lungs for heart-lung transplantation is not associated with increased mortality and is a safe strategy for increasing donor organ supply in this complex patient population.

Heart transplantation using a donor with partial anomalous pulmonary venous connection and atrial septal defect.

Over the last decade, the shortage of donors has led to increased waiting time prior to transplantation and its related mortality. Therefore, extended criteria for donor hearts have been proposed. In this report, we describe a successful transplantation despite a diagnosis of partial abnormal pulmonary venous return associated with an atrial septal defect sinus venosus and persisting left-sided superior vena cava. Knowledge in congenital cardiac disease can broaden the definition of 'marginal' donor hearts and allow their use without increasing the risk of transplantation.

Organ donation education initiatives: A report of the Donor Management Task Force.

PURPOSE: It is essential that hospitals and health professionals establish systems to facilitate patients' organ donation wishes. Donation education has been neither standardized nor systematic, and resources related to donation processes have not been widely accessible. This report describes 2 free, publicly available educational resources about the organ donation process created to advance the mission of basic education and improve donation processes within hospitals and health care systems. MATERIALS AND METHODS: Members of the Donor Management Task Force of the Organ Donation and Transplantation Alliance (the Alliance) and the Health Resources and Services Administration of the US Department of Health and Human Services convened annually in person and by teleconferencing during the year to develop 2 educational vehicles on organ donation. RESULTS: Two educational products were developed: the Organ Donation Toolbox, an online repository of documents and resources covering all aspects of the donation process, and the Educational Training Video that reviews the basic foundations of a successful hospital donation system. CONCLUSIONS: There is a need for more research and education about the process of organ donation as it relates to the medical and psychosocial care of patients and families before the end of life. The educational products described can help fill this critical need.

Predictive equations for lung volumes from computed tomography for size matching in pulmonary transplantation.

OBJECTIVE: Size matching for lung transplantation is widely accomplished using height comparisons between donors and recipients. This gross approximation allows for wide variation in lung size and, potentially, size mismatch. Three-dimensional computed tomography (3D-CT) volumetry comparisons could offer more accurate size matching. Although recipient CT scans are universally available, donor CT scans are rarely performed. Therefore, predicted donor lung volumes could be used for comparison to measured recipient lung volumes, but no such predictive equations exist. We aimed to use 3D-CT volumetry measurements from a normal patient population to generate equations for predicted total lung volume (pTLV), predicted right lung volume (pRLV), and predicted left lung volume (pLLV), for size-matching purposes. METHODS: Chest CT scans of 400 normal patients were retrospectively evaluated. 3D-CT volumetry was performed to measure total lung volume, right lung volume, and left lung volume of each patient, and predictive equations were generated. The fitted model was tested in a separate group of 100 patients. The model was externally validated by comparison of total lung volume with total lung capacity from pulmonary function tests in a subset of those patients. RESULTS: Age, gender, height, and race were independent predictors of lung volume. In the test group, there were strong linear correlations between predicted and actual lung volumes measured by 3D-CT volumetry for pTLV (r = 0.72), pRLV (r = 0.72), and pLLV (r = 0.69). A strong linear correlation was also observed when comparing pTLV and total lung capacity (r = 0.82). CONCLUSIONS: We successfully created a predictive model for pTLV, pRLV, and pLLV. These may serve as reference standards and predict donor lung volume for size matching in lung transplantation.