Differential donor management of pediatric vs adult organ donors and potential impact on pediatric lung transplantation.

BACKGROUND: Despite clinical progress over time, a shortage of suitable donor organs continues to limit solid organ transplantation around the world. Lungs are the organs most likely to be assessed as unsuitable during donor management among all transplantable organs. Although the number of lung transplants performed in children is limited, death on the wait list remains a barrier to transplant success for many potential transplant candidates. Optimizing organ donor management can yield additional organs for transplant candidates. METHODOLOGY: We accessed the Donor Management Goal (DMG) Registry to evaluate the efficiency and efficacy of donor management in the procurement of lungs for transplantation. Further, we stratified donors by age and compared pediatric age cohorts to adult cohorts with respect to attainment of donor management target goals and successful pathway to transplantation. We utilized recipient data from the Organ Procurement Transplantation Network (OPTN) to put this data into context. The DMG bundle consists of nine physiologic parameters chosen as end-points guiding donor management for potential organ donors. The number of parameters fulfilled has been regarded as an indication of efficacy of donor management. RESULTS: We noted a markedly lower number of organ donors in the pediatric age group compared to adults. On the other hand, the number of donors greatly exceeds the number of infants, children and adolescents who undergo lung transplantation. Organs transplanted per donor peaks in the adolescent age group. At initial donor referral, DMG bundle attainment is lower in all age groups and improves during donor management. With respect to oxygenation, there is less overall improvement in younger donors compared to older donors during donor management. When donors who yield lungs for transplantation are compared to those whose lungs were not transplanted, oxygenation improved more substantially during donor management. Furthermore, improved oxygenation correlated with the total number of organs transplanted per donor. CONCLUSIONS: In the face of continued wait list mortality on the pediatric lung transplant wait list, the number of young donors may not be a limiting factor. We believe that this dataset provides evidence that management of young pediatric donors is not as consistent or efficient as the management of older donors, potentially limiting the number of life-saving organs for pediatric lung transplant candidates. Across all ages, optimizing donor lung management may increase the potential to transplant multiple other organs.

ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part III: Pharmacology, medical and surgical management of post-transplant extrapulmonary conditions statements.

Patients with connective tissues disease (CTD) are often on immunomodulatory agents before lung transplantation (LTx). Till now, there's no consensus on the safety of using these agents perioperative and post-transplant. The International Society for Heart and Lung Transplantation-supported consensus document on LTx in patients with CTD addresses the risk and contraindications of perioperative and post-transplant management of the biologic disease-modifying antirheumatic drugs (bDMARD), kinase inhibitor DMARD, and biologic agents used for LTx candidates with underlying CTD, and the recommendations and management of non-gastrointestinal extrapulmonary manifestations, and esophageal disorders by medical and surgical approaches for CTD transplant recipients.

ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part I: Epidemiology, assessment of extrapulmonary conditions, candidate evaluation, selection criteria, and pathology statements.

Patients with connective tissue disease (CTD) and advanced lung disease are often considered suboptimal candidates for lung transplantation (LTx) due to their underlying medical complexity and potential surgical risk. There is substantial variability across LTx centers regarding the evaluation and listing of these patients. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization aims to clarify definitions of each disease state included under the term CTD, to describe the extrapulmonary manifestations of each disease requiring consideration before transplantation, and to outline the absolute contraindications to transplantation allowing risk stratification during the evaluation and selection of candidates for LTx.

Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation.

Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation.

ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part II: Cardiac, surgical, perioperative, operative, and post-operative challenges and management statements.

Patients with connective tissue disease (CTD) present unique surgical, perioperative, operative, and postoperative challenges related to the often underlying severe pulmonary hypertension and right ventricular dysfunction. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization addresses the surgical challenges and relevant cardiac involvement in the perioperative, operative, and postoperative management in patients with CTD.

Cystic fibrosis foundation consensus statements for the care of cystic fibrosis lung transplant recipients.

Cystic fibrosis (CF) is the indication for transplantation in approximately 15% of recipients worldwide, and Cystic Fibrosis Lung Transplant Recipients (CFLTRs) have excellent long-term outcomes. Yet, CFLTRs have unique comorbidities that require specialized care. The objective of this document is to provide recommendations to CF and lung transplant clinicians for the management of perioperative and underlying comorbidities of CFLTRs and the impact of transplantation on these comorbidities. The Cystic Fibrosis Foundation (CFF) organized a multidisciplinary committee to develop CF Lung Transplant Clinical Care Recommendations. Three workgroups were formed to develop focused questions. Following a literature search, consensus recommendations were developed by the committee members based on literature review, committee experience and iterative revisions, and in response to public comment. The committee formulated 32 recommendation statements in the topics related to infectious disease, endocrine, gastroenterology, pharmacology, mental health and family planning. Broadly, the committee recommends close coordination of care between the lung transplant team, the cystic fibrosis care center, and specialists in other disciplines with experience in the care of CF and lung transplant recipients. These consensus statements will help lung transplant providers care for CFLTRs in order to improve post-transplant outcomes in this population.

Performance Changes Following the Revision of Organ Allocation System of Lung Transplant: Analysis of Korean Network for Organ Sharing Data.

BACKGROUND: There is currently a lack of data on the impact of the recent revision of the domestic lung allocation system on transplant performance. METHODS: We conducted a retrospective analysis of transplant candidates and transplant patients registered in Korean Network for Organ Sharing between July 2015 and July 2019. Study periods were classified according to the introduction of the revised lung allocation system as follows: period 1 from July 2015 to June 2017 and period 2 from August 2017 to July 2019. RESULTS: During the study period, a total of 627 patients were on the waiting list, of which 398 lung transplantations were performed. Total waiting list size increased by 98.6%, from 210 in period 1 to 417 in period 2. The number of transplant patients also increased by 32.7%, from 171 in period 1 to 227 in period 2. The number of donors decreased from 1,042 to 878, whereas the usage rate, i.e., the number of lung donors used for transplantation among the total number of reported lung donors, increased from 16.4% to 25.9%. The proportion of patients with high urgent status at transplantation increased from 45% to 60.4%, whereas those with urgent status decreased from 46.8% to 35.7% (P = 0.006). The use of marginal donor lungs increased from 29.8% to 53.7% (P < 0.001). To adjust urgency status and marginal donor usage between two groups, we conducted a propensity score matching analysis. No significant differences were detected in 1-year survival rates between the two periods after propensity score matching. As well, no significant difference was observed in mortality on the waiting list between the two periods. CONCLUSION: The recent revision of the lung allocation system in Korea did not change the performance of lung transplant in terms of waiting list mortality and 1-year survival. The rapid increase in the volume of waiting list between the two periods increased the waiting time, transplantation of high-urgency patients, and use of marginal lung donors.

Impact of surgical technique and analgesia on clinical outcomes after lung transplantation: A STROBE-compliant cohort study.

There is paucity of data on the impact of surgical incision and analgesia on relevant outcomes.A retrospective STROBE-compliant cohort study was performed between July 2007 and August 2017 of patients undergoing lung transplantation. Gender, age, indication for lung transplantation, and the 3 types of surgical access (Thoracotomy (T), Sternotomy (S), and Clamshell (C)) were used, as well as 2 analgesic techniques: epidural and intravenous opioids. Outcome variables were: pain scores; postoperative hemorrhage in the first 24 hours, duration of mechanical ventilation, and length of stay at intensive care unit (ICU).Three hundred forty-one patients were identified. Thoracotomy was associated with higher pain scores than Sternotomy (OR 1.66, 95% CI: 1.01; 2.74, P: .045) and no differences were found between Clamshell and Sternotomy incision. The median blood loss was 800 mL [interquartile range (IQR): 500; 1238], thoracotomy patients had 500 mL [325; 818] (P < .001). Median durations of mechanical ventilation in Thoracotomy, Sternotomy, and Clamshell groups were 19 [11; 37] hours, 34 [IQR 16; 57.5] hours, and 27 [IQR 15; 50.5] hours respectively. Thoracotomy group were discharged earlier from ICU (P < .001).Thoracotomy access produces less postoperative hemorrhage, duration of mechanical ventilation, and lower length of stay in ICU, but higher pain scores and need for epidural analgesia.

[Perioperative infection prevention strategies for double-lung transplantation in elderly patients with COVID-19].

OBJECTIVE: To summarize the experience of perioperative prevention during double-lung transplantation for elderly patients with coronavirus disease 2019 (COVID-19). METHODS: Clinical data of 2 elderly patients with COVID-19 who underwent double-lung transplantation in the First Affiliated Hospital of Zhejiang University School of Medicine in March 2020 were retrospectively reviewed. Perioperative protective measures were introduced in terms of medical staffing, respiratory tract, pressure injuries, air in operating room, instruments and equipment, pathological specimens, and information management. RESULTS: Two cases of double-lung transplantation were successfully completed, and the patients had no operation-related complications. Extracorporeal membrane oxygenator was successfully removed 2 to 4 days after surgery and the patients recovered well. There was no infection among medical staff. CONCLUSIONS: Adequate preoperative preparation, complete patient transfer procedures, proper placement of instruments and equipment, strengthening of intraoperative care management, and attention to prevention of pressure injury complications can maximize the safety of COVID-19 patients and medical staff.

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.

Pretransplant Opioid Use and Survival After Lung Transplantation.

BACKGROUND: The impact of opioid use in lung transplant candidates on posttransplant outcomes is unknown. Studies on opioid therapy in kidney and liver transplant candidates have suggested increased risk of graft failure or death. We sought to analyze the relationship between pretransplant opioid use in lung transplant candidates and retransplant-free survival. METHODS: We retrospectively reviewed adult patients transplanted consecutively between November 2004 and August 2015. The exposure was any opioid use at time of transplant listing and primary outcome was retransplant-free survival, analyzed via Cox regression model adjusted for recipient age, gender, ethnicity, diagnosis, and bridging status. Secondary outcomes included duration of ventilation, intensive care unit and hospital length of stay, 3-month and 1-year survival, continuing opioid use at 1 year, and time to onset of chronic lung allograft dysfunction. RESULTS: The prevalence of opioid use at time of listing was 14% (61/425). Median daily oral morphine equivalent dose was 31 mg (18-54). Recipient ethnicity was associated with pretransplant opioid use. Opioid use at time of listing did not increase risk of death or retransplantation in an adjusted model (hazard ratio 1.12 [95% confidence interval 0.65-1.83], P = 0.6570). Secondary outcomes were similar between groups except hospital length of stay (opioid users 35 versus nonusers 27 d, P = 0.014). Continued opioid use at 1-year posttransplant was common (27/56, 48%). CONCLUSIONS: Pretransplant opioid use was not associated with retransplant-free survival in our cohort and should not necessarily preclude listing. Further work stratifying opioid use by indication and the association with opioid use disorder would be worthwhile.

International Society for Heart and Lung Transplantation consensus statement for the standardization of bronchoalveolar lavage in lung transplantation.

Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International Society for Heart and Lung Transplantation-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics.

Chronic Obstructive Pulmonary Disease and Lung Transplantation.

Lung transplantation (LTx) has been a viable option for patients with end-stage chronic obstructive pulmonary disease (COPD), with more than 20,000 procedures performed worldwide. Survival after LTx lags behind most other forms of solid-organ transplantation, with median survival for COPD recipients being a sobering 6.0 years. Given the limited supply of suitable donor organs, not all patients with end-stage COPD are candidates for LTx. We discuss appropriate criteria for accepting patients for LTx, as well as contraindications and exclusionary criteria. In the first year post-LTx, infection and graft failure are the leading causes of death. Beyond this chronic graft rejection-currently referred to as chronic lung allograft dysfunction-represents the leading cause of death at all time points, with infection and over time malignancy also limiting survival. Referral of COPD patients to a lung transplant center should be considered in the presence of progressing disease despite maximal medical therapy. As a rule of thumb, a forced expiratory volume in 1 second < 25% predicted in the absence of exacerbation, hypoxia (PaO2 < 60 mm Hg/8 kPa), and/or hypercapnia (PaCO2 > 50 mm Hg/6.6 kPa) and satisfactory general clinical condition should be considered the basic prerequisites for timely referral. We also discuss salient issues post-LTx and factors that impact posttransplant survival and morbidity such as infections, malignancy, renal insufficiency, and complications associated with long-term immunosuppression.

Hyperinflation With Pulmonary Dysfunction in Donor Lungs With Smoking History During Lung Perfusion.

BACKGROUND: Donor lungs with smoking history are perfused in ex vivo lung perfusion (EVLP) to expand donor lung pool. However, the impact of hyperinflation of perfused lungs in EVLP remains unknown. The aim of this study was to investigate the significance of hyperinflation, using an ex vivo measurement delta VT, during EVLP in smoker's lungs. MATERIALS AND METHODS: Seventeen rejected donor lungs with smoking history of median 10 pack-years were perfused for 2 h in cellular EVLP. Hyperinflation was evaluated by measuring delta VT = inspiratory - expiratory tidal volume (VT) difference at 1 h. All lungs were divided into two groups; negative delta VT (n = 11, no air-trapping pattern) and positive delta VT (n = 6, air-trapping pattern). Transplant suitability was judged at 2 h. By using lung tissue, linear intercept analysis was performed to evaluate the degree of hyperinflation. RESULTS: The positive delta VT group had significantly lower transplant suitability than the negative delta VT group (16 versus 81%, P = 0.035). The positive delta VT group was significantly associated with lower partial pressure of oxygen/fraction of inspired oxygen ratio ratio (278 versus 356 mm Hg, P = 0.049), higher static compliance (119 versus 98 mL/cm H2O, P = 0.050), higher lung weight ratio (1.10 versus 0.96, P = 0.014), and higher linear intercept ratio (1.52 versus 0.93, P = 0.005) than the negative delta VT group. CONCLUSIONS: Positive delta VT appears as an ex vivo marker of ventilator-associated lung hyperinflation of smoker's lungs during EVLP.

[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.

Gait-speed and oxygen flow during six-minute walk test predicts mortality in patients with advanced lung disease.

The six-minute walk test (6MWT) is a useful tool to predict outcomes in patients with advanced lung diseases. Greater distance walked has been shown to have more favorable prognostic value compared to other recorded variables.  We reviewed the medical records of 164 patients with advanced lung disease who underwent lung transplant evaluation. Results of the 6MWT (distance walked, oxygen required, and mean gait speed) were recorded and analyzed with respect to mortality. 6MWT mean oxygen (O2) flow via nasal cannula was 3.5 ± 3.7 L/min. The distance walked in meters (m) and % predicted were inversely associated with mortality, OR: 0.995 (0.992-0.998) and 0.970 (0.950-0.990), respectively. Patients who walked < 200 meters (OR: 2.1 (1.1-4.0)) or < 45% of predicted, OR: 2.7 (1.2-5.7) had higher mortality. O2 flow during the test had a direct association with mortality (OR: 1.1 (1.0-1.2). In multivariate analysis, O2 flow > 3.5 L/min remained predictive of mortality, OR: 1.1 (1.0-1.2). Mean gait speed was higher in patient who lived compared with patients who died (mean 0.83 ± 0.35 m/mim vs mean 0.69 ± 0.33 m/min, respectively, p= 0.03). Gait speed was a predictor of survival, OR 3.4 (1.1, 10.6). O2 flow during the 6MWT was an independent predictor of mortality in patients with advanced lung disease. The patients that required more than 3.5 L/m of O2 had a higher mortality. Faster gait speed during the 6MWT was also associated with better survival.

Cellular Ex Vivo Lung Perfusion Beyond 1 Hour May Improve Marginal Donor Lung Assessment.

BACKGROUND: Ex vivo lung perfusion (EVLP) permits extended evaluation of donor lungs for transplant. However, the optimal EVLP duration of Lund protocol is unclear. Using human lungs rejected for clinical transplant, we sought to compare the results of 1 versus 2 h of EVLP using the Lund protocol. METHODS: Twenty-five pairs of human lungs rejected for clinical transplant were perfused with the Lund EVLP protocol. Blood gas analysis, lung compliance, bronchoscopy assessment, and perfusate cytokine analysis were performed at both 1 and 2 h. Recruitment was performed at both time points. Donor lung transplant suitability was determined at both time points. RESULTS: All cases were divided into four groups based on transplant suitability assessment at 1 h and 2 h of EVLP. In group A (n = 10), lungs were judged suitable for transplant at both 1 and 2 h of EVLP. In group B (n = 6), lungs were suitable at 1 h but nonsuitable at 2 h. In group C (n = 2), lungs were nonsuitable at 1 h but suitable at 2 h. Finally, in group D (n = 7), lungs were nonsuitable for transplant at both time points. In both groups B and C (n = 8), the transplant suitability assessment changed between 1 and 2 h of EVLP. CONCLUSIONS: In human lungs rejected for transplant, transplant suitability differed at 1 versus 2 h of EVLP in 32% of lungs studied. Evaluation of lungs with Lund protocol EVLP beyond 1 h may improve donor organ assessment.