Awaiting Lung Transplantation Research Articles

Prognostic factors in lung transplantation after extracorporeal membrane oxygenation bridging therapy: a systematic review and meta-analysis.

Extracorporeal membrane oxygenation (ECMO) has recently emerged as a critical support system for lung function in patients awaiting lung transplantation. This meta-analysis investigates the prognostic factors of lung transplantation following ECMO bridging therapy. A comprehensive search was conducted in PubMed, Cochrane Library, Embase, CINAHL, Web of Science, Scopus, and ProQuest databases from inception to August 11, 2023. Included were cohort or case-control studies focusing on prognostic factors of lung transplantation with ECMO bridging therapy. Data extraction was performed independently, and study quality was assessed. A meta-analysis was carried out using RevMan 5.4 and Stata17.0 software to aggregate mortality rates and pertinent prognostic factors of ECMO as a bridge to lung transplantation. The search identified eight trials encompassing 1,086 participants. The prognosis of patients undergoing lung transplantation with ECMO bridging was significantly associated with several factors: prolonged ECMO support [odds ratio 1.07, 95% confidence interval (CI): 1.02-1.12, I2=77%], deterioration in liver and kidney function (odds ratio 3.62, 95% CI: 2.37-5.54, I2=0%), and complications during ECMO (odds ratio 2.24, 95% CI: 1.45-3.44, I2=5%). Prolonged ECMO support, declining liver and kidney functions, and complications during ECMO are vital prognostic factors in lung transplantation following ECMO bridging therapy.

Frailty as a Prognostic Indicator in Lung Transplantation: A Comprehensive Analysis

Introduction: Frailty is a complex pathobiological process characterized by diminished physiological reserve and increased vulnerability to stressors, which has been associated with unfavorable outcomes before and after lung transplantation. Methods: We undertook an extensive narrative review, encompassing a thorough exploration of original papers, observational studies, case reports, and meta-analyses published between 1990 and July 2023, in various databases, including PubMed, Embase, Cochrane Library, Wiley Online Library databases, and Google Scholar. The search terms [frailty] AND [lung transplant] were utilized. Additionally, the reference lists of retrieved articles were examined. Inclusion criteria comprised studies written in English and involving human subjects. The identified studies were categorized into pre-transplant and post-transplant populations, and the measurement tools used to assess frailty were analyzed, along with the clinical implications reported in the studies. Results: From 1 January 1990 to 1 July 2023, a total of 10 studies on frailty and lung transplantation were identified through online sources and bibliographic searches, involving a total of 2759 patients. Among these studies, six focused on the pre-transplant population, while four examined the post-transplant population. The Fried Frailty Phenotype (FFP) and the Short Physical Performance Battery (SPPB) were the most employed tools for measuring frailty. A table presents additional frailty assessment instruments and the clinical implications described in the studies. Conclusions: Frailty is prevalent both in patients with end-stage respiratory diseases awaiting lung transplantation and in postoperative lung transplant recipients. Most transplant centers recognize the value of assessing frailty in the evaluation of potential candidates for lung transplantation. Frailty has been shown to impact mortality on the waitlist and in the post-transplant period. However, the most effective methods for measuring frailty in lung transplant candidates and recipients have yet to be determined. Strategies to reverse frailty are available and show promising results on outcomes.

A narrative review on the management of patients awaiting lung transplantation in Japan.

The number of lung transplantations performed in Japan is increasing, and post-transplant outcomes are relatively favorable. A major concern is the extremely long waiting time and the high mortality rate on the waitlist. The management of patients before transplantation is very important and essential for further improvement of outcomes. In this review, we summarize the management of patients awaiting lung transplantation in Japan. A literature search was conducted via PubMed in November 2022 using the following keywords: lung transplantation, waiting, management, recipient, and Japan. Peer-reviewed academic journal articles published in English were also included. A growing number of studies have evaluated the management of pre-transplant patients. This includes infection control, vaccination, respiratory disease-specific treatment, malignancy, nutrition, rehabilitation, psychosocial assessment, and health-related quality of life (HRQOL) for patients on the waitlist. Each is important, and various evaluation methods and strategies to improve outcomes have been reported. Proper and multifaceted management of pretransplant patients is extremely important to reduce the mortality of candidates for lung transplantation. Integrated management is crucial to the success and survival of lung transplant recipients.

Recovery of extracorporeal lungs using cross-circulation with injured recipient swine

ObjectiveLung transplantation remains limited by the shortage of healthy organs. Cross-circulation with a healthy swine recipient provides a durable physiologic environment to recover injured donor lungs. In a clinical application, a recipient awaiting lung transplantation could be placed on cross-circulation to recover damaged donor lungs, enabling eventual transplantation. Our objective was to assess the ability of recipient swine with respiratory compromise to tolerate cross-circulation and support recovery of donor lungs subjected to extended cold ischemia. MethodsSwine donor lungs (n = 6) were stored at 4 °C for 24 hours while recipient swine (n = 6) underwent gastric aspiration injury before cross-circulation. Longitudinal multiscale analyses (blood gas, bronchoscopy, radiography, histopathology, cytokine quantification) were performed to evaluate recipient swine and extracorporeal lungs on cross-circulation. ResultsRecipient swine lung injury resulted in sustained, impaired oxygenation (arterial oxygen tension/inspired oxygen fraction ratio 205 ± 39 mm Hg vs 454 ± 111 mm Hg at baseline). Radiographic, bronchoscopic, and histologic assessments demonstrated bilateral infiltrates, airway cytokine elevation, and significantly worsened lung injury scores. Recipient swine provided sufficient metabolic support for extracorporeal lungs to demonstrate robust functional improvement (0 hours, arterial oxygen tension/inspired oxygen fraction ratio 138 ± 28.2 mm Hg; 24 hours, 539 ± 156 mm Hg). Multiscale analyses demonstrated improved gross appearance, aeration, and cellular regeneration in extracorporeal lungs by 24 hours. ConclusionsWe demonstrate that acutely injured recipient swine tolerate cross-circulation and enable recovery of donor lungs subjected to extended cold storage. This proof-of-concept study supports feasibility of cross-circulation for recipients with isolated lung disease who are candidates for this clinical application.

Handgrip Strength in Lung Transplant Candidates and Recipients.

Handgrip strength is increasingly used to assess muscle strength in various conditions. In this review, we investigated handgrip strength in patients receiving or awaiting lung transplant. For this integrative review, we searched 8 databases from inception through February 2023. Two keyword entries, "handgrip strength" and "lung transplantation," were matched using the Boolean operator, AND. No filters were applied for document type, age, sex, publication date, language, and subject. The searched databases returned 73 citations. Nine articles considering 487 patients (49% female) were included in the final analysis; 7 studies were observational, and 2 were randomized controlled trials. In 7 of 9 studies, handgrip strength was measured with a hydraulic dynamometer. In candidates for lung transplant, handgrip strength ranged from 27.1 kg (before rehabilitation) to 31.2 kg (after rehabilitation). In lung transplant recipients, handgrip strength ranged from 21.1 kg (before rehabilitation) to 35.7 kg (after rehabilitation). Handgrip strength in lung transplant candidates with chronic obstructive pulmonary disease was higher (89 ± 18% predicted) versus patients with interstitial lung disease (79 ± 18% predicted). Improvements in maximal inspiratory pressure and maximal expiratory pressure were observed in those patients whose handgrip strength improved after rehabilitation. Nonsarcopenic patients walked longer distances for the 6-minute walking test (>450 m) versus sarcopenic patients (<310 m) and had higher handgrip strength (>20 kg) versus sarcopenic patients (<20 kg). Handgrip strength testing should be implemented both in preoperative and postoperative contexts to evaluate physical potential of patients and drive rehabilitative activities toward the most impaired domains.

Frailty: A Strong Impact on Lung Transplant Outcomes?

Frailty: A Strong Impact on Lung Transplant Outcomes?

Use of Berlin EXCOR cannulas in both venovenous and venoarterial central extracorporeal membrane oxygenation configurations overcomes the problem of cannula instability while bridging infants and young children to lung transplant

Infants and young children awaiting lung transplantation present challenges that often preclude successful extracorporeal membrane oxygenation support as a bridge to transplantation. Instability of neck cannulas often results in the need for intubation, mechanical ventilation, and muscle relaxation creating a worse transplant candidate. With the use of Berlin Heart EXCOR cannulas (Berlin Heart, Inc) in both venoarterial and venovenous central cannulation configurations, 5 pediatric patients were successfully bridged to lung transplant. We performed a single-center retrospective case review of central extracorporeal membrane oxygenation cannulation used as a bridge to lung transplantation cases performed at Texas Children's Hospital between 2019 and 2021. Six patients, 2 with pulmonary veno-occlusive disease (15-month-old male and 8-month-old male), 1 with ABCA3 mutation (2-month-old female), 1 with surfactant protein B deficiency (2-month-old female), 1 with pulmonary arterial hypertension in the setting of D-transposition of the great arteries after repair as a neonate (13-year-old male), and 1 with cystic fibrosis and end-stage lung disease, were supported for a median of 56.3days on extracorporeal membrane oxygenation while awaiting transplantation. All patients were extubated after initiation of extracorporeal membrane oxygenation, participating in rehabilitation until transplant. No complications due to central cannulation and use of the Berlin Heart EXCOR cannulas were observed. One patient with cystic fibrosis developed fungal mediastinitis and osteomyelitis resulting in discontinuation of mechanical support and death. Novel use of Berlin Heart EXCOR cannulas for central cannulation eliminates the problem of cannula instability allowing extubation, rehabilitation, and bridge to lung transplant for infants and young children.

Red Blood Cell Transfusion Prior to Lung Transplantation: Impact on Patient Outcomes.

There is an established association between red blood cell (RBC) transfusion and increased mortality and morbidity in cardiac surgery; however, there is little data demonstrating the influence of blood transfusion while awaiting lung transplantation. Therefore, our study compared the impact of pretransplant RBC transfusion on patient survival and post-transplantation adverse events. Adult lung transplant patient data were extracted retrospectively using the United Network for Organ Sharing thoracic database. Patients were stratified into two groups based on pretransplant transfusion status. In total, 28,217 patients were analyzed in our study (transfused: n = 1,415 and not transfused: n = 26,802). There was an increasing trend in pretransplant transfusion rates from 2006 to 2020. Transfused patients had a higher incidence of adverse events post-transplantation, including dialysis, stroke, and acute organ rejection before discharge. Multivariable survival analysis found an increased mortality risk in patients who required pretransplant transfusion(s) compared to those who did not have a transfusion (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.17-1.41; p < 0.001). There was no significant difference in bronchiolitis obliterans syndrome development between groups (HR: 0.92; 95% CI: 0.82-1.04; p = 0.185). To conclude, our study provides data to suggest that RBC transfusion(s) before lung transplantation are associated with increased patient morbidity and mortality, but have no association with chronic graft rejection development.

Expectations of patients awaiting lung transplantation: A qualitative study.

The main aim of the present study is to examine the expectations and feelings of people awaiting lung transplantation. The assessment of the benefits of lung transplant should consider, among other things, the subjective perceptions of patients about the procedure, especially in relation to the context and to their values, goals and expectations. This is an issue that has not been studied in depth, especially in Spain. Exploratory qualitative study. Data were collected through semi-structured interviews during the period of being on the waiting list for transplantation. Thematic analysis of the data was supported by the Atlas.ti software. The study population comprised 16 patients awaiting lung transplant, a number sufficient to reach data saturation. Four categories were identified to describe patients' feelings and expectations: (1) reasons for undergoing the transplant, (2) expectations about life post-transplant, (3) emotional state, and (4) relationship with the healthcare team. Patients have high expectations of lung transplantation. They see it as offering them a second chance at life, although the future creates uncertainty. The healthcare professionals are identified as key actors, providing essential support and information throughout the various stages of the process. Future research should explore recipients' experiences of lung transplant at later stages. It is important to adapt care through all the lung transplant process, which is accompanied by intense and complex emotions since the beginning. Thus, providing social and psychological support from the beginning may contribute to their health status, helping them deal with all the emotions and feelings experienced, and find balance between expectations and reality. Sixteen patients awaiting lung transplant were interviewed. Interview transcripts were returned to participants to check for accuracy with their experiences.

Immune checkpoint analysis of T-cell responses to pp65 and IE-1 antigens in end-stage lung diseases.

Lung transplant (LTX) patients are at high risk of cytomegalovirus (CMV) infection, which is often associated with high mortality and morbidity. Reactivation of CMV causes cell injury due to the cytopathic effect of viral replication and triggering of T cell immunity. The aim of this study was to compare expression of immune checkpoints (ICs) (PD-1, CTLA-4, LAG-3 and TIGIT) in CD4, CD8 and CD56 and activation markers CD137, CD154 and CD69 of end-stage patients awaiting lung transplant. Eighteen pre-LTX positive for anti-CMV IgG titres and 18 healthy subjects were enrolled. IC and activation markers have been evaluated through flow cytometric analysis in HC and pre-LTX patients. Reactive (QF+) and unreactive (QF-) patients were stratified according to QuantiFERON-CMV assays. ICs' and activation markers' expression were determined before and after in vitro stimulation with pp-65 and IE-1 antigens. Lower expression of PD-1 was observed in CD4 and CD8 cells of pre-LTX patients than controls, whereas CTLA4 appeared upregulated in CD56 and CD8 cells. TIGIT is increased on the surface of CD4, CD8 and NK cells after peptide stimulation in QF-negative patients and PD-1 is only downregulated after stimulation in the QF-positive patients. This study provides new evidence of immune dysregulation in patients with end-stage lung disorders, particularly in relation to immune checkpoint cell biology. The change in QF+ mostly happens on cytotoxic cells NK and CD8, while the changes in QF- were observed in adaptive immune cells, including CD4 and CD8.

Nutrición en fibrosis pulmonar idiopática: el trabajo multidisciplinario como abordaje del futuro

Idiopathic pulmonary fibrosis (IPF) is the most common interstitial pneumonia and has undergone significant diagnostic and therapeutic advances in recent years. However, little has been investigated so far regarding the nutritional alterations associated with the disease. The prevalence of malnutrition associated with IPF has been estimated around 30%, but it can reach up to 60% in patients awaiting lung transplantation. Malnutrition is an independent predictor of mortality in patients with IPF, and often manifests through weight reduction and/or changes in body composition, which can lead to a deterioration in muscle and/or bone mass. The origin of malnutrition in IPF is multifactorial and not entirely known. Some patients with advanced IPF, even having a preserved body weight, tend to have a loss of lean mass, which is associated with muscle dysfunction and poor physical performance. The resulting muscle weakness leads to physical deconditioning and greater dyspnea, reduced exercise tolerance and deterioration in quality of life. Consequently, in order to improve the approach to IPF, the nutritionist should be incorporated into the multidisciplinary team with the aim of making an early diagnosis of nutritional status, which will allow the identification of early alterations and the appropriate nutritional intervention.

Bilateral Lung Transplantation With Donor Positive for COVID-19 Infection on Bronchoalveolar Lavage: A Case Report

Initial experience with lung transplant of COVID-19-positive donors was marked by disappointing results, including a reported case of mortality through donor to recipient transmission of infection. However, since that time a number of improvements in preventative and therapeutic measures against COVID-19 have been developed. We present the case of a 51-year-old woman with scleroderma-associated interstitial lung disease who was awaiting lung transplant. A potential donor with excellent lung physiology was located; however, initial testing on bronchoalveolar lavage (BAL) was positive for COVID-19. The donor had tested positive 2 weeks prior and had symptomatically recovered. Our patient had been fully vaccinated but not seroconverted. Given the history of a donor with recovering COVID infection and a fully immunized recipient, our multidisciplinary team elected to proceed with the transplant. The patient successfully underwent bilateral lung transplant with standard induction immunosuppression. Bebtelovimab was given post-transplant day 1 because the recipient remained seronegative to COVID-19. Serial bronchoalveolar lavages post transplant have been negative for COVID-19. The patient has done well after transplant. She was seen in the clinic 2 months post transplant and is ambulatory without supplemental oxygen requirements. To our knowledge, this represents the first reported successful case of lung transplant with a donor positive for COVID-19 on lower respiratory tract sampling.

A two-circuit strategy for intraoperative extracorporeal support during single lung transplantation in a patient bridged with venovenous extracorporeal membrane oxygenation.

Venovenous extracorporeal membrane oxygenation is increasingly used as a bridging strategy in decompensating patients awaiting lung transplantation. Various approaches for continuing support intraoperatively have been previously described. A two-circuit strategy that uses the in situ venovenous extracorporeal membrane oxygenation circuit supplemented with peripheral cardiopulmonary bypass allows for diversion of native cardiac output away from the transplanted lung as well as seamless continuation of venovenous extracorporeal membrane oxygenation postoperatively.

Venovenous extracorporeal membrane oxygenation promotes alveolar epithelial recovery by activating Hippo/YAP signaling after lung injury.

The preferred configuration for bridging patients with respiratory failure while awaiting lung transplantation is venovenous extracorporeal membrane oxygenation (VV ECMO). However, the protective effect of VV ECMO on the lung, as well as the underlying mechanisms, are still unknown. We investigated the role of VV ECMO in preventing lung injury in vivo using a rat model. Additionally, the effects of Hippo/YAP signaling on alveolar epithelial type II cells (AT2)-mediated alveolar epithelial recovery in VV ECMO rats were also investigated. In the bronchoalveolar lavage fluid (BALF) and lung tissue, RNA sequencing, lung injury, edema, and cytokine expression were evaluated. VV ECMO significantly improved severe hypoxemia, reduced lung edema, and inflammatory response, and altered alveolar epithelial function, as indicated by reduced protein concentrations in BALF. This was associated with Hippo/YAP signaling activation, according to RNA sequencing analysis. Furthermore, we discovered that after VV ECMO, AT2 cells proliferated and differentiated, and this increase in AT2 cell activity was correlated to the increased nuclear expression of YAP, which is critical for alveolar epithelial recovery from lung injury. During VV ECMO, verteporfin-induced YAP inhibition and the loss of the oxygenator delayed lung alveolar epithelial recovery and led to a prolonged inflammatory response. These findings suggest that VV ECMO protects against lung injury by activating the Hippo/YAP signaling pathway. Strategies aimed at increasing YAP activity in AT2 cells could thus aid alveolar epithelial recovery, making VV ECMO easier for lung transplantation.

Characterization of NKG2-A/-C, Kir and CD57 on NK Cells Stimulated with pp65 and IE-1 Antigens in Patients Awaiting Lung Transplant

Introduction: Cytomegalovirus (CMV) is the leading opportunistic infection in lung transplant (LTx) recipients. CMV is associated with graft failure and decreased survival. Recently, new antiviral therapies have been proposed. The present study aimed to investigate NK and T cell subsets of patients awaiting LTx. We analyzed the cellular populations between reactive and non-reactive QuantiFERON (QF) CMV patients for the prediction of immunological response to infection. Methods: Seventeen pre-LTx patients and 15 healthy controls (HC) have been enrolled. QF and IFN-γ ELISA assay detections were applied. NK cell subsets and T cell and proliferation assay were detected before and after stimulation with pp-65 and IE-1 CMV antigens after stratification as QF+ and QF−. Furthermore, we quantified the serum concentrations of NK− and T-related cytokines by bead-based multiplex analysis. Results: CD56brCD16lowNKG2A+KIR+ resulted in the best discriminatory cellular subsets between pre-LTx and HC. Discrepancies emerged between serology and QF assay. Better proliferative capability emerged from patients who were QF+, in particular in CD8 and CD25-activated cells. CD56brCD16low, adaptive/memory-like NK and CD8Teff were highly increased only in QF+ patients. Conclusions: QF more than serology is useful in the detection of patients able to respond to viral infection. This study provides new insights in terms of immunological responses to CMV in pre-LTX patients, particularly in NK and T cells biology.

Outcomes of patients awaiting lung transplantation after the implementation of donation after brain death at a single Chinese center.

Voluntary contribution has become the only source of donor lungs in China since 2015. To elaborate the outcomes of patients awaiting lung transplantation (LTx) after the implementation of donation after brain death, we performed a retrospective study that encompassed 205 patients with end-stage lung disease who registered for LTx at Shanghai Pulmonary Hospital from January 1, 2015 to January 1, 2021. A total of 180 patients were enrolled in the study. The median waiting time was 1.25 months. Interstitial lung disease (ILD) (103/180, 57.2%) and chronic obstructive pulmonary disease (COPD) (56/180, 31.1%) were the most common diseases in our study population. The mean pulmonary artery pressure (mPAP) of patients in the died-waiting group was higher than that of the survivors (53.29±21.71 mmHg vs. 42.11±18.58 mmHg, P=0.002). The mortality of patients with ILD (34/103, 33.00%) was nearly twice that of patients with COPD (10/56, 17.86%) while awaiting LTx (P=0.041). In the died-waiting group, patients with ILD had a shorter median waiting time than patients with COPD after being listed (0.865 months vs. 4.720 months, P=0.030). ILD as primary disease and mPAP > 35 mmHg were two significant independent risk factors for waitlist mortality, with hazard ratios (HR) of 3.483 (95% CI 1.311-9.111; P=0.011) and 3.500 (95% CI 1.435-8.536; P=0.006). Hence, LTx is more urgently needed in patients with ILD and pulmonary hypertension.

A Mixed Methods Assessment of Home-Based Video Pretransplant Lung Education.

Introduction: Patients awaiting lung transplantation must learn new information to successfully navigate the transplant process. A supplemental video series was piloted to patients at home during the Covid-19 pandemic to improve pre-transplant education. Methods: A mixed methods study was undertaken to assess patient experiences with this method of education, confirm the ideal timing of the education, and identify gaps that require further attention. Semi-structured interviews were conducted with 17 one-on-one or dyadic (patients and caregivers) who viewed the video series at home. A third-party researcher (not involved in creation of the educational materials) conducted the interviews by phone, which were audio recorded and then transcribed verbatim. NVivo 12 Pro for Windows software was used to code the data and identify emerging themes. Results: Participants indicated that home-based videos were applicable, and informative and helpful (4.7 on 5-point Likert scale) and appreciated the advice and experiences of real patients. They were satisfied with their transplant education (4.2/5). While there were few aspects that the participants disliked about the videos, the interviews elicited outstanding questions about the transplant process (eg, logistical aspects of travel) and transplant concerns (eg, medications, expenses, and precautions in daily life). Conclusion: Patients being assessed or listed for lung transplant valued the novel electronic video education, and we will implement the home-based process into standard of care after the patient's initial visit with the transplant respirologist. Pre-transplant education will be tailored to help address the outstanding gaps identified in this program evaluation.

A Case Report of ECMO Patient with Cerebrovascular Complication Caused by a Broken Dual Lumen Cannula

<h3>Introduction</h3> Dual-lumen cannula is used for extracorporeal membrane perfusion (ECMO) to support patients with ARDS due to COVID-19 as a bridge to lung recovery. It tends to be a longer support and there are several factors that can degrade the physical structure of the ECMO cannula and put the cannula at risk for breakage. <h3>Case Report</h3> A 63-year-old woman was admitted to the hospital with COVID-19 pneumonia. Two days later, she was intubated and VV-ECMO was initiated due to treatment-resistant acute respiratory failure; a 28Fr Crescent^TM dual-lumen cannula (Medtronic, MN) was inserted through the left subclavian vein and connected to a centrifugal oxygen pump with a centrifugal oxygenator. Within six weeks after onset, the patient was unable to be weaned from the ventilator and was transferred to our center with ECMO connected for consideration of lung transplantation. Two days after transfer, the patient developed acute aphasia, altered mental status, disturbed consciousness, and left arm seizures. A suction sound was heard from the left subclavian cannula insertion site and the ECMO bubble detector alarmed, but local inspection, chest X-rays, and CT scans of the brain and chest showed no obvious abnormalities. The patient was reintubated for encephalopathy and subsequently underwent a tracheostomy. The patient regained normal neurological function over the next 7 days. However, the air bubble sensor alarmed and suction sound was heard at the cannulation site again, and air bubbles were seen in the oxygenator. Due to concerns about air entrapment and cannula failure, we changed to a dual-canal VV-ECMO configuration using a right internal cervical and a left femoral cannula. The removed cannula had a 2 cm fracture distal to the skin insertion site. After resumption of ECMO, no new neurological episodes occurred. While awaiting lung transplantation, the patient died due to sepsis and multiple organ failure. An autopsy revealed a possible cause of cerebrovascular disease patent foramen ovale and air embolism to the brain. <h3>Summary</h3> If a patient has been on ECMO for a long time and the bubble sensor warns of air detection, cannula breakage and impending air embolism should be suspected clinically, even if the defect is not found on examination and is not evident on imaging. If the COVID-19 epidemic continues, increased transport events may increase ECMO cannula breakage.

Evaluation of Pre-Transplant Antifibrotic Agents on Post-Transplant Outcomes

<h3>Purpose</h3> Antifibrotic therapy, i.e. pirfenidone or nintedanib, is commonly used for idiopathic pulmonary fibrosis (IPF) patients awaiting lung transplantation. However, they are inferred to cause increased wound healing complications post-transplant. This study compares post-transplant outcomes in IPF patients on the basis of pre-transplant antifibrotic treatment. <h3>Methods</h3> IPF patients transplanted after January 2015 were included in a cohort study with three groups: no antifibrotic, pirfenidone, and nintedanib. Pre-specified outcomes of interest included: PGD grades immediately after transplant (T0) and on post-operative day 3 (T72), duration of mechanical ventilation, wound dehiscence, anastomosis complications, time to CLAD development, and overall survival. <h3>Results</h3> Of the 85 eligible patients, 26 received no pre-transplant antifibrotic medication, 31 received pirfenidone, and 28 received nintedanib. Fewer female patients received antifibrotic therapy, but the groups were otherwise similar with regards demographics and clinical variables (Table). There were no differences between groups in PGD status at T0 or T72, but patients who received antifibrotics pre-transplant were more likely resolve PGD between T0 and T72 than patients who did not (mean change in PGD grade: nintedanib -0.3±0.9 vs. pirfenidone -0.5±1.3 vs. no antifibrotic +0.3±1.5, p=0.026). There was a trend toward decreased time on mechanical ventilation in the patients receiving antifibrotic treatment (no-antifibrotic vs. any antifibrotic medication p=0.025, between all group p=0.07). Anastomosis stenosis was less common in the antifibrotic groups (p=0.020). No differences were observed for wound dehiscence, incidence of CLAD, or mortality. <h3>Conclusion</h3> Receiving any pre-transplant antifibrotic therapy is associated with increased resolution of PGD, shorter duration of mechanical ventilation, and decreased incidence of anastomosis stenosis.

A survey of use of mTOR inhibitors in patients with lymphangioleiomyomatosis listed for lung transplant

BackgroundLymphangioleiomyomatosis (LAM) is an uncommon indication for lung transplantation. The use of mechanistic target of rapamycin (mTOR) inhibitors, which are the mainstay of treatment in progressive LAM, in patients awaiting lung transplant is controversial. We sought to examine worldwide practice patterns in use of mTOR inhibitors in LAM patients on the lung transplant waiting list. MethodsWe designed and disseminated an online survey about institution-specific practice patterns, particularly regarding listing LAM patients for lung transplant and use of mTOR inhibitors in those patients on the transplant waitlist. ResultsOf the 49 unique respondent programs, 83.6% had previously listed a LAM patient for lung transplant. Thirteen centers allowed patients to continue on mTOR inhibitor until time of lung transplant. None of those centers reported any complications or deaths attributable to mTOR inhibitor adverse effects. ConclusionThere exists significant variability in practice patterns concerning the use of mTOR inhibitors in LAM patients on the lung transplant waiting list. Our survey suggests favorable outcomes for those patients that did continue mTOR inhibitor up to time of transplant. Further data regarding the risk of anastomotic complication with use of mTOR inhibitors in the pre-transplant period would help provide clarity in this debate.