Lung Retransplantation Research Articles

Lung Transplantation After Ex Vivo Lung Perfusion in High-Risk Recipients: A Propensity Matched Analysis of a National Database

PurposeWe report outcomes associated with EVLP lungs in high-risk lung transplant recipients utilizing a national database. MethodsWe performed a retrospective analysis of the UNOS Database (1/1/2018-3/31/2024). High-risk status was defined as mean pulmonary arterial pressure > 35 mmHg, lung retransplantation, or bridge to transplant. In addition to univariable analysis, propensity score matched analysis was performed on predictors of donor and recipient characteristics. ResultsRisk of dying on the waitlist was significantly higher for high-risk candidates (HR: 1.69 [1.51 – 1.89], p < 0.001). Following matching, 203 EVLP cases were matched to 609 standard procurement recipients. The EVLP group was associated with higher rates of postoperative acute kidney injury requiring renal replacement therapy (27% vs 16%, p < 0.001), higher mortality on index admission (13% vs. 8%, p = 0.04), and longer length of stay (29 vs 25 days, p = 0.006). EVLP modality was associated with survival time (p < 0.001) with portable EVLP having significantly shorter survival (2.7 years) relative to standard cases (4.7 years, p < 0.02). A subgroup analysis found that this survival effect was limited to bridge and retransplant recipients. ConclusionsEVLP lungs were associated with higher rates of postoperative AKI and portable EVLP was associated with shorter survival in high-risk lung transplant recipients. However, given the high waitlist mortality in this candidate population, EVLP lungs should still be considered an alternative.

Survival After Extracorporeal Membrane Oxygenation Bridge to Lung Retransplantation

BackgroundExtracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation. Despite success in select populations, candidates requiring ECMO bridge to retransplantation have historically had poor 1-year survival. This study aimed to examine the characteristics of the recipient, donor, and transplant procedure type to guide selection of candidates for ECMO bridge to retransplantation. MethodsThis was a retrospective cohort study of all US adult lung retransplant recipients between May 5, 2005, and December 31, 2022. We evaluated 1-year survival of ECMO-bridged retransplant patients, stratified by time from initial transplant, procedure type (single or bilateral retransplant), and ECMO era (2005-2017 vs 2018-2022). ResultsIn this national cohort, 111 of 1296 (8.6%) retransplant recipients underwent ECMO bridge. One-year survival was worse for ECMO bridge retransplant recipients (52.2% vs 74.0%; P < .001) and has worsened in the contemporary era (2018-2022) of ECMO bridge to retransplantation compared with prior years (P = .03). Time from initial transplantation and use of bilateral retransplant after an initial bilateral transplant were most strongly associated with improved 1-year survival of ECMO-bridged retransplant recipients. Of bilateral recipients bridged to bilateral transplant more than 1 year after primary transplantation, survival was 65.9% in ECMO-bridged patients as opposed to 77.2% in nonbridged patients. ConclusionsCareful selection of candidates and surgical procedure type remains essential in determining candidacy for ECMO bridge to retransplantation.

Pulmonary Artery Endograft Implantation Using a Parallel Stent Grafting Technique to Enable the Treatment of a Bronchial Anastomosis Complication After Lung Transplantation.

Bronchial stenosis associated with bronchial anastomosis dehiscence after lung transplantation is a catastrophic complication following lung transplantation with a paucity of therapeutic solutions. To describe an adaptation of the parallel stent grafting technique in the pulmonary arterial territory to treat this challenging situation. This is a case report of a 52-year-old patient who presented bronchus stenosis and bronchial anastomosis dehiscence after lung transplantion. Bronchial stenting and lung retransplantation were contraindicated. Therefore, an endovascular approach using pulmonary artery endograft placement to prevent bleeding during repeated right bronchial balloon dilation was propposed. The technique consists of the deployment of an aortic extender endoprosthesis in the right main pulmonary artery and a balloon expandable stent in the upper lobe pulmonary artery (using a parallel graft configuration) through the common femoral and right internal jugular veins, respectively. Intraoperative transesophageal echocardiogram and one-lung ventilatory ventilation are needed. The patient underwent a new bronchoscopy 16 days after the procedure, that showed epithelization at the previous eroded zone, enabling bronchocopic balloon dialtion to be safely performed. A post-operative contrast-enhanced CT scan revealed an adequate positioning of the stent grafts. Despite all eforts, the patient succumbed to ventilator associated pneumonia on postoperative day 108. The technique's advantages include its feasibility even in situations in which other techniques may be contraindicated and its potential use in emergencies. Its limitations include the need for experienced interventionists to perform it, and the potential risk of acute tricuspid regurgitation. This study illustrates the early feasibility of the parallel stent grafting technique applied to the pulmonary artery territory. However, it's safety profile regarding infectious risk was not demontrated.

Outcomes of single vs double lung retransplantation in patients with cystic fibrosis

ObjectivePatients requiring lung transplant for cystic fibrosis (CF) may require retransplant due to limited graft survival and otherwise excellent life expectancy. Optimal transplant strategy for this population, including single vs. double lung retransplant, has not been established. MethodsWe performed a retrospective analysis of the UNOS/OPTN database to identify adult lung retransplant recipients from 2005-2021 with a primary diagnosis of CF. Patients were stratified by retransplant type (single lung [re-SLTx] vs. double lung [re-DLTx] retransplant). Descriptive statistics, Kaplan-Meier survival analysis, and multivariable Cox regression were performed. ResultsFrom 2005-2021, 384 recipients underwent retransplant after an initial transplant for an indication of CF; more recipients underwent re-DLTx (N=337 [87.8%]) than re-SLTx (N=47 [12.2%]). The median (IQR) time from initial transplant to retransplant was similar between re-SLTx and re-DLTx recipients (4.4 [2.9-8.6] vs. 4.6 [2.6-7.4] years, p=0.73). Ischemic time was shorter and lung allocation score was lower for re-SLTx than re-DLTx recipients. Median survival after retransplant was significantly shorter for re-SLTx vs. re-DLTx recipients (2.0 [95% CI 1.2-3.5] vs. 4.3 [95% CI 3.5-6.1] years post-retransplant, p=0.008). Median survival for adults with CF undergoing primary transplant for CF in the same period was 9.1 (8.5-9.9) years. After adjusting for donor and recipient characteristics, re-SLTx in patients with CF was associated with 88% higher hazard of mortality than re-DLTx (aHR=1.88 [95% CI 1.28-2.78], p=0.001). ConclusionsIn this analysis of lung retransplant in recipients with CF, re-SLTx was associated with a higher hazard of mortality compared to re-DLTx, supporting re-DLTx as treatment for this population.

Outcomes of single-lung retransplantation after double-lung transplantation

ObjectiveTo compare outcomes of single-lung retransplantation (SLRTx) and double-lung retransplantation (DLRTx) after an initial double-lung transplantation. MethodsThe Organ Procurement and Transplantation Network/United Network for Organ Sharing database between May 2005 and December 2022 was retrospectively analyzed. Multiorgan transplantations, repeated retransplantations, and lung retransplantations when the status of the initial transplantation was unknown were excluded. ResultsA total of 891 patients were included in the analysis, included 698 (78.3%) with DLRTx and 193 (21.7%) with SLRTx. The mean lung allocation score was higher in the DLRTx group (59.6 ± 20.7 vs 55.1 ± 19.3; P = .007). The use of extracorporeal membrane oxygenation (ECMO) bridge to lung transplantation was similar in the 2 groups (P = .125), as was waitlist time (P = .610). The need for mechanical ventilation (54.6% vs 35.8%; P = .005) and ECMO (17.9% vs 9.0%; P = .069) at 72 hours post-transplantation was greater in the DLRTx group. However, median post-transplantation hospital stay (21.5 [interquartile range (IQR), 12-35] days versus 20 [IQR, 12-35] days; P = .119) and in-hospital mortality (10.9% [n = 76/698] vs 12.4% [n = 24/193]; P = .547) were comparable in the 2 groups. Long-term survival was significantly better in the DLRTx group (P < .001, log-rank test). In the propensity score–weighted multivariable model, the DLRTx group had 28% lower risk of mortality at any point during follow-up compared to the SLRTx group (hazard ratio, 0.72; 95% confidence interval, 0.57-0.91; P = .006). ConclusionsThe less invasiveness of single-lung transplantation in the retransplantation setting has minimal short-term benefit and is associated with significantly worse long-term survival. Double-lung retransplantation should remain the standard for lung retransplantation after initial double-lung transplantation.

Ethical considerations in lung re-transplantation.

Patients undergoing re-transplantation constitute a growing proportion of annual lung transplants. It is necessary to consider ethical considerations of re-transplantation in parallel with clinical progress. Most clinical data demonstrate patients undergoing re-transplantation have worse survival outcomes; however, there is limited discussion of the ethical principles surrounding re-transplantation. Ethical guidance in re-transplantation trails clinical advancement. The four-box model offers a valuable framework for assessing the ethical considerations in re-transplantation. This includes an analysis of medical indications, patient preferences, quality-of-life and contextual factors to support the ethical use of scarce donor lungs.

Outcomes of lung transplantation in cystic fibrosis.

Lung transplantation (LTX) has transformed care for people with cystic fibrosis (pwCF) suffering from advanced cystic fibrosis lung disease (ACFLD), and it has evolved into an accepted therapy for patients with ACFLD across all ages. We review cystic fibrosis as a major indication for LTX, particularly highlighting outcomes including survival, a changing landscape over time, and factors affecting sequelae following LTX in cystic fibrosis. Although some populations such as those undergoing lung retransplantation exhibit inferior posttransplant outcomes, LTX for pwCF provides an excellent long-term survival that has significantly improved over time, likely due to specialized cystic fibrosis center care and recognition of common comorbidities in pwCF post-LTX. There are gaps in post-LTX outcomes for pwCF, including that identified between Canada and the United States, and that seen in adolescents - both of which are likely multifactorial. In particular, the revolution in cystic fibrosis medical therapy with CFTR modulator therapy has resulted in a dramatic decline in programs performing LTX for cystic fibrosis. How durable this effect will remains to be seen. Overall, LTX remains a well accepted ultimate therapy option in patients with ACFLD if compatible with the individual's goals of care, offering an improved quality of life and maximization of overall survival.

Pediatric Lung Transplantations: New Possibilities and Challenges in Treatment of Children With End-Stage Respiratory Failure

Lung transplantation (LTx) is the last treatment option for children with end-stage respiratory failure. According to the literature, cystic fibrosis remains the most common cause of pediatric LTx. The study aimed to assess the characteristics of pediatric LTx recipients as well as the outcomes of the transplantation. Our study is a single-center retrospective review of clinical data of all 11 patients who underwent a LTx before the age of 18 years between the years 2016 and 2020. Medical records were examined for patients' characteristics, general treatment, and complications. There were a total of 11 patients (8 males) with a median age 14.5 years (range: 11-17). The primary diseases that led to LTx were: cystic fibrosis in 8 patients (72.73%), hereditary hemorrhagic telangiectasia in 2 patients (18.18%), and idiopathic pulmonary arterial hypertension in 1 patient (9.09%). Median period from qualification to LTx was 235.55 days (range: 11-748). Two patients (18.18%) underwent lung retransplantation after 3 and 5 years. One patient passed away 10 months after surgery due to noncompliance. Pediatric lung transplantation is less common than lung transplantation in adults. It also differs in fields of donors accessibility, stronger immune system response and noncompliance that may lead to graft failure.

Rehabilitative goals for patients undergoing lung retransplantation.

Lung retransplantation (LRT) involves a second or subsequent lung transplant (LT) in a patient whose first transplanted graft has failed. LRT is the only treatment option for irreversible lung allograft failure caused by acute graft failure, chronic lung allograft dysfunction, or postoperative complications of bronchial anastomosis. Prehabilitation (rehabilitation before LT), while patients are on the waiting list, is recognized as an essential component of the therapeutic regimen and should be offered throughout the waiting period from the moment of listing until transplantation. LRT is particularly fraught with challenges, and prehabilitation to reduce frailty is one of the few opportunities to address modifiable risk factors (such as functional and motor impairments) in a patient population in which there is clearly room to improve outcomes. Although rehabilitative outcomes and quality of life in patients receiving or awaiting LT have gained increased interest, there is a paucity of data on rehabilitation in patients undergoing LRT. Frailty is one of the few modifiable risk factors of retransplantation that is potentially preventable. As such, it is imperative that professionals involved in the field of retransplantation conduct research specifically exploring rehabilitative techniques and outcomes of value for patients receiving LRT, because this area remains unexplored.

Performance status at the time of lung retransplant predicts long-term function.

Lung retransplantation is offered to select patients with chronic allograft dysfunction. Given the increased risk of morbidity and mortality conferred by retransplantation, post-transplant function should be considered in the decision of who and when to list. The aim of this study is to identify predictors of post-operative disability in patients undergoing lung retransplantation. Data were collected from the UNOS national dataset and included all patients who underwent lung retransplant from May 2005-March 2023. Pre- and post-operative function was reported by the Karnofsky Performance Status (KPS) and patients were stratified based on their needs. Cumulative link mixed effects models identified associations between pre-transplant variables and post-transplant function. A total of 1275 lung retransplant patients were included. After adjusting for between-group differences, pre-operative functional status was predictive of post-transplant function; patients requiring Total Assistance ( n=740) were 74% more likely than No/Some Assistance patients (n=535) to require more assistance in follow-up (OR 1.74, 95% CI 1.13-2.68, p=.012). Estimated one year survival of Total Assistance patients is lower than No/Some Assistance Recipients (72%vs. 82%, CI 69%-75%; 79%-86%) but similar to overall re-transplant survival (76%, CI 74%-79%). Both survival and regain of function in patients requiring Total Assistance prior to retransplant may be higher than previously reported. Pre-operative functional status is predictive of post-operative function and should weigh in the selection, timing and post-operative care of patients considered for lung retransplantation.

(357) - The Second Time Around: Re-Evaluating Lung Retransplant Outcomes in the Lung Allocation Score Era

(357) - The Second Time Around: Re-Evaluating Lung Retransplant Outcomes in the Lung Allocation Score Era

Various combinations of living and deceased donors for lung retransplantation-a single institutional retrospective study.

Lung retransplantation has been performed as a treatment option mainly for chronic lung allograft dysfunction; however, the outcomes of lung retransplantation have been reported to be worse than those of primary lung transplantation. Because of the scarcity of deceased donors in our country, our lung transplant experience includes both living and deceased donors. Therefore, we have experienced lung retransplantation cases with various combinations of living and deceased donors. The aim of this study was to explore technical pitfalls and outcomes of lung retransplantation in this unique environment. We performed 311 lung transplantation procedures between April 2002 and October 2022. Eight lung retransplantation cases (2.6%) were analysed retrospectively. At lung retransplantation, the age of the recipient patients ranged from 11 to 61 years (median, 33 years). The combinations of donor sources (primary lung transplantation/lung retransplantation) were as follows: 2 living/living, 2 deceased/living, 3 living/deceased and 1 deceased/deceased. Seven of 8 patients received lung retransplantation for chronic lung allograft dysfunction. Hospital death occurred in 2 patients (25.0%). The 1-, 3- and 5-year survival rates after lung retransplantation (n = 8) were 75.0%, 75.0% and 75.0%, respectively, while those after primary lung transplantation (n = 303) were 92.8%, 83.4% and 76.4%, respectively (P = 0.162). Lung retransplantation with various combinations of living and deceased donors is a technically difficult but feasible procedure with acceptable outcomes.

Worth a Double Take? An In-Depth Review of Lung Retransplantation

Provided advancements in Lung Transplantation (LT) survival, the efficacy of Lung Retransplantation (LRT) has often been debated. Decades of retrospective analyses on thousands of LRT cases provide insight enabling predictive patient criteria for retransplantation. This review used the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. The PubMed search engine was utilized for articles relating to LRT published through August 2023, and a systematic review was performed using Covidence software version 2.0 (Veritas Health Innovation, Australia). Careful patient selection is vital for successful LRT, and the benefit leans in favor of those in optimal health following their initial transplant. However, the lack of a standardized approach remains apparent. Through an in-depth review, we will address considerations such as chronic lung allograft dysfunction, timing to LRT, surgical and perioperative complexity, and critical ethical concerns that guide the current practice as it relates to this subset of patients for whom LRT is the only therapeutic option available.

Off-pump lung re-transplantation avoiding clamshell thoracotomy is feasible and safe: a single-center experience.

Lung re-transplantation (re-LTx) is the only therapeutic option for selected patients with advanced allograft dysfunction. This study aims to describe our center's experience to illustrate the feasibility and safety of off-pump re-LTx avoiding clamshell incision. We performed a retrospective analysis of 42 patients who underwent bilateral re-LTx between 2007 and 2021. Patients were classified according to their surgical approach and extracorporeal life support (ECLS)-use. Demographics, surgical technique, and short- and long-term outcomes were compared between groups. Continuous data were examined with an independent-sample t-test or non-parametric test. Pearson's chi-squared and Fisher's exact were used to analyze categorical data. Twenty-six patients (61.9%) underwent re-LTx by anterior thoracotomy without ECLS. Compared to the more invasive approach (thoracotomy with ECLS and clamshell with/without ECLS, n=16, 38.1%), clamshell-avoiding off-pump re-LTx patients had a shorter operative time (471.6±111.2 vs. 704.0±273.4 min, P=0.010) and less frequent grade 3 primary graft dysfunction (PGD-3) at 72 h (7.7% vs. 37.5%, P=0.038). No significant difference was found in PGD-3 incidence within 72 h, mechanical ventilation, intensive care unit (ICU) and hospital stay, and the incidence of reoperation within 90 days between groups (P>0.05). In the long-term, the clamshell-avoiding and off-pump approach resulted in similar 1- and 5-year patient survival vs. the more invasive approach. Our experience shows that clamshell-avoiding off-pump re-LTx is feasible and safe in selected patients on a case-by-case evaluation.

Successful management of temporary veno-venous extracorporeal membrane oxygenation for a pediatric lung transplant recipient with bronchiolitis obliterans syndrome awaiting lung re-transplantation: a case report

BackgroundThe use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation is an uncommon strategy in Japan owing to the severe donor shortage and absence of urgent allocation policy. Moreover, the use of veno-venous (VV) ECMO for immunosuppressed patients is controversial; thus, applying ECMO to patients who await lung re-transplantation is challenging.Case presentationA 16-year-old lung transplant recipient with grade 3 bronchiolitis obliterans syndrome was waitlisted for lung re-transplantation. Eleven months later, he fell into severe respiratory acidosis with hypercapnia, which were not resolved with mechanical ventilation. VV ECMO was introduced to minimize lung stress and strain. Tracheostomy was additionally performed on day 5 after the start of ECMO, and respiratory condition swiftly improved; hence, the weaning process from VV ECMO began on day 9. Rehabilitation became implementable, and bilateral re-lung transplantation was successfully performed 6 months after the ECMO treatment. No critical complication related to the precedent use of ECMO was noted.ConclusionsVV ECMO can be a feasible treatment option even for lung transplant candidates awaiting re-transplantation for a prolonged period. Introduction of ECMO and tracheostomy in the early deterioration stage may be crucial to successful subsequent patient management.

Long-term management and outcome of lung transplantation in Japan.

The long-term survival after lung transplantation (LT) is favorable in Japan. However, long-term survivors after LT are subject to late complications, including chronic lung allograft dysfunction (CLAD), malignancy, infection, and chronic kidney disease (CKD) because of the need for lifelong immunosuppression. The rates of single cadaveric LT (CLT) and living-donor lobar LT (LDLLT) are higher than that of bilateral CLT in Japan. Here, we will describe the management of late complications and long-term outcome after LT in Japan. Attention should be paid to not only the phenotype of CLAD but also the difference in CLAD after CLT and after LDLLT as well as the timing of lung re-transplantation for advanced CLAD, especially after single CLT. Since post-transplant lymphoproliferative disorder is the most common malignancy after LT, infection monitoring for infection-related malignancies and appropriate screening are keys to the early diagnosis and treatment of malignancy after LT. The long-term management of infection after LT is also important, especially with regard to community-acquired pathogens, Aspergillus, and cytomegalovirus. When providing long-term care after LT, physicians should be aware of CKD and the timing of renal replacement therapy in cases with severe CKD. The widespread use of computed tomography and dialysis in Japan are beneficial for long-term survivors of LT. The similar survival outcomes of single CLT and LDLLT, compared with bilateral CLT, might contribute to improved long-term survival in Japan. Pulmonologists are encouraged to become further involved in long-term management after LT in Japan.

(110) Effect of Clad Phenotypes on the Outcome after Lung Retransplantation - A Retrospective Single Center Data Analysis

(110) Effect of Clad Phenotypes on the Outcome after Lung Retransplantation - A Retrospective Single Center Data Analysis

(320) Predicting Long-Term Functional Status after Lung Retransplantation

(320) Predicting Long-Term Functional Status after Lung Retransplantation

(1068) Successful Lung Re-Transplantation with Perioperative Desensitization for Sensitized Recipient with Donor Specific DQ Antibody

(1068) Successful Lung Re-Transplantation with Perioperative Desensitization for Sensitized Recipient with Donor Specific DQ Antibody

Epidemiology, risk factors, and outcomes of lung retransplantation: An analysis of the International Society for Heart and Lung Transplantation Thoracic Transplant Registry.

Lung retransplantation is a complex surgical decision that represents the only potential treatment option for recipients suffering from lung allograft failure. We sought to describe the modern landscape of lung retransplantation and to compare the relative importance of selected clinical, donor, and recipient factors on mortality in the year following lung retransplantation. We conducted a retrospective cohort study of first-time adult recipients of deceased donor lung retransplants reported to the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry from May 2005 through June 2017. In addition to describing the characteristics of lung retransplant recipients, we examined 1 year survival overall, and by initial transplant-retransplant procedure type, recipient age, retransplant indication, and time-to-lung retransplantation (i.e., inter-transplant interval). We used the Somers' Dxy rank correlation statistic for censored data to assess the relative importance of several potential prognostic risk factors for mortality in the year following lung retransplantation. Our cohort included 1,597 lung retransplant recipients. 2005 was the first year with more than 100 retransplants, and since 2007, 138 to 188 retransplants (approximately 4%-6% of all transplants) were reported annually to the ISHLT Registry. The median inter-transplant interval was 3.4 years (interquartile range: 1.6-6.2 years). Forty-three percent of the cohort had an obliterative bronchiolitis retransplant indication, whereas 17% had primary graft failure. One-third (32%) were retransplanted within 2 years of their primary transplant, and 64% received a double lung transplant both times, whereas 36% received consecutive single lung transplants. Six-month and 1 year survival (82% and 76%) were higher for double-double lung retransplant recipients than for single-single recipients (76% and 69%). The 3 strongest prognostic factors for 1 year mortality were the inter-transplant interval (decreasing hazard with longer intervals), donor age (increasing hazard with older age), and need for mechanical ventilation preceding lung retransplantation. Retransplants comprise approximately 5% of annual lung transplants worldwide. The factor most strongly associated with 1 year mortality in this population was the duration of time since the primary lung transplant, with a persistent reduction in risk as more time elapses.