The Outcomes of Single Lung Retransplantation After Double Lung Transplantation.

OBJECTIVE: The aim of this study is to compare outcomes of single lung retransplantation (SLRTx) to double lung retransplantation (DLRTx) after an initial double lung transplantation. METHODS: The Organ Procurement and Transplantation Network/United Network for Organ Sharing database between May 2005 and December 2022 was retrospectively analyzed. Multiorgan transplantation, repeated retransplantation, and lung retransplantation when the status of the initial transplantation was unknown were excluded. RESULTS: 891 patients were included in the analysis: 698 cases (78.3%) were DLRTx and 193 cases (21.7%) were SLRTx. Mean lung allocation score was higher among DLRTx (59.6±20.7 vs 55.1±19.3, p = 0.007). Extracorporeal membrane oxygenation (ECMO) bridge to lung transplantation use was similar between groups (p=0.125), as was waitlist time (p=0.610). Need for mechanical ventilation (54.6% vs 35.8%, p = 0.005) and ECMO (17.9% vs 9.0%, p = 0.069) at 72 hours after transplantation was more frequent in DLRTx group. However, median post-transplant hospital stay (21.5 [IQR 12-35] vs 20 days [IQR 12-35], p=0.119) and in-hospital mortality (10.9% [76/698] vs 12.4% [24/193], p=0.547) were comparable between groups. Long-term survival was significantly better among DLRTx (log-rank test p < 0.001). In the propensity-score weighted multivariable model, DLRTx had 28% lower risk of mortality at any point during follow-up compared to SLRTx (HR: 0.72, 95% confidence interval: 0.57-0.91, p=0.006). CONCLUSIONS: Less invasiveness of single lung transplantation in the retransplant 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.

OUTCOMES OF CONTROLLED DCDD LUNG TRANSPLANTATION AFTER THORACO-ABDOMINAL VS ABDOMINAL NORMOTHERMIC REGIONAL PERFUSION: THE SPANISH EXPERIENCE.

OBJECTIVE: Thoraco-abdominal normothermic regional perfusion (TA-NRP) has emerged as a strategy for evaluating and recovering the heart in controlled donation after the circulatory determination of death (cDCDD). However, its impact on lung grafts remains largely unknown. We aimed to assess the impact of TA-NRP on the outcomes of recipients of cDCDD lungs. METHODS: This is a retrospective, multicenter, nationwide study describing the outcomes of cDCDD lung transplants (LTs) performed in Spain from January 2021 to November 2023. Patients were divided in two groups based on the recovery technique: TA-NRP with the simultaneous recovery of the heart versus abdominal NRP (A-NRP) without simultaneous heart recovery. The primary endpoint was the incidence of Primary Graft Dysfunction (PGD) grade 3 at 72 hours. Secondary endpoints included the overall incidence of PGD, days on mechanical ventilation, ICU and hospital length of stay, early survival rates, and mid-term outcomes. RESULTS: 283 cDCDD LTs were performed during the study period, 28 (10%) using TA-NRP and 255 (90%) using A-NRP. No differences were observed in the incidence of PGD grade 3 at 72 hours between the TA-NRP and the A-NRP group (0% vs. 7.6%; p=0.231), though the overall incidence of PGD was significantly lower with TA-NRP (14.3%% vs. 41.5%; p=0.005). We found no significant differences between the groups regarding other post-transplant outcome variables. CONCLUSIONS: TA-NRP allows the simultaneous recovery of both the heart and the lungs in the cDCDD scenario with appropriate LT outcomes comparable to those observed with the A-NRP approach.

Continuous serratus anterior plane block for postoperative analgesia following lung transplantation via anterolateral incision: a pilot study.

Background: Unilateral or bilateral anterolateral thoracotomy May lead to severe acute pain in lung transplantation (LTx). Although serratus anterior plane block (SAPB) is apparently effective for pain control after open thoracic surgery, there remains a lack of evidence for the application of SAPB for postoperative analgesia after LTx. Objective: In this case series pilot study, we describe the feasibility of continuous SAPB after lung transplantation and provide a preliminary investigation of its safety and efficacy. Methods: After chest incisions closure was complete, all patients underwent ultrasound-guided SAPB with catheter insertion. Numerical rating scale (NRS), additional opioid consumption, time to endotracheal tube removal, ICU length of stay, and catheter-related adverse events were followed up and recorded for each patient within 1 week after the procedure. Results: A total of 14 patients who received LTx at this center from August 2023 to November 2023 were included. All patients received anterolateral approaches, and 10 (71.4%) of them underwent bilateral LTx. The duration of catheter placement was 2 (2-3) days, and the Resting NRS during catheter placement was equal to or less than 4. A total of 11 patients (78.6%) were supported by extracorporeal membrane oxygenation (ECMO) in LTx, whereas 8 patients (57.1%) removed the tracheal tube on the first day after LTx. Intensive care unit (ICU) stay was 5 (3-6) days, with tracheal intubation retained for 1 (1-2) days, and only one patient was reintubated. The morphine equivalent dose (MED) in the first week after LTx was 11.95 mg, and no catheter-related adverse events were detected. Limitations: We did not assess the sensory loss plane due to the retrospective design. In addition, differences in catheter placement time May lead to bias in pain assessment. Conclusion: Although continuous SAPB May be a safe and effective fascial block technique for relieving acute pain after LTx, it should be confirmed by high-quality clinical studies.

Correlation of FAPI PET Uptake with Immunohistochemistry in Explanted Lungs from Patients with Advanced Interstitial Lung Disease.

Recent studies have demonstrated promising results of fibroblast activation protein (FAP) inhibitor (FAPI) PET in prognosticating and monitoring interstitial lung diseases (ILDs). As a first step toward successful translation, our primary aim was to validate the FAPI PET uptake through immunohistochemistry in patients with advanced ILD who underwent lung transplantation after a FAPI PET scan. Methods: This is a preliminary analysis of a single-center, open-label, single-arm, prospective exploratory biodistribution study of 68Ga-FAPI-46 PET imaging in patients with ILD (NCT05365802). Patients with ILD confirmed by high-resolution CT and scheduled for lung transplant were included. Tissue samples of explanted lungs were obtained from both the central and peripheral lung parenchyma of each lobe. Additional samples were obtained from areas of the lung corresponding to regions of FAPI PET activity. Immunohistochemical staining was performed with an anti-FAP antibody. Percentages of FAP immunohistochemistry-positive area were measured semiautomatically using QuPath software. SUVs in the areas of pathologic samples were measured on FAPI PET/CT by referencing the gross photomap of the explanted lung. A Spearman correlation coefficient test was used to assess the relationship between FAPI PET uptake and FAP immunohistochemical expression in each specimen. Results: Four patients with advanced ILD who underwent FAPI PET/CT before lung transplantation were included. The types of ILD were idiopathic pulmonary fibrosis (n = 2), rheumatoid arthritis-associated ILD (n = 1), and nonspecific interstitial pneumonia (n = 1). FAPI uptake was visualized mainly in the fibrotic area on CT. Twenty-nine surgical pathology samples from 3 patients were analyzed. FAP staining was predominantly positive in fibroblastic foci. FAPI PET SUVmax and SUVmean showed a positive correlation with the immunohistochemical FAP expression score (SUVmax: r = 0.57, P = 0.001; SUVmean: r = 0.54, P = 0.002). Conclusion: In this analysis conducted in patients who underwent lung transplantation after a FAPI PET scan, FAPI PET uptake was positively correlated with FAP immunohistochemistry. These findings provide a rationale for further investigation of FAPI PET as a potential imaging biomarker for ILD.

High-Risk HLA-DQ Mismatches Are Associated With Adverse Outcomes After Lung Transplantation.

Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students' t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients (p = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR (p = 0.03) and CLAD (p = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.

Analysis of high-risk factors for early pulmonary bacterial infection after lung transplantation and their correlation with long-term mortality.

OBJECTIVE: To investigate the high-risk factors for early pulmonary bacterial infection following lung transplantation and their association with long-term mortality. METHODS: A retrospective analysis was conducted on 142 lung transplant recipients treated at Wuxi People's Hospital between January 2018 and July 2022. After applying predefined inclusion and exclusion criteria, 111 cases were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for early pulmonary infection post-transplantation. Additionally, univariate and multivariate Cox regression analyses were used to identify independent prognostic factors affecting one-year survival post-transplantation. RESULTS: Univariate analysis identified age, bacterial infection in donor lungs, and operation duration as risk factors for early pulmonary infection (all P < 0.05). Multivariate analysis was confirmatory for these as independent risk factors (all P < 0.05). Univariate analysis also showed that intraoperative blood loss and oxygenation index impacted one-year survival (P < 0.05). Multivariate analysis was confirmatory for these as independent risk factors (P < 0.05). CONCLUSION: Early pulmonary bacterial infection was not found to be an independent factor affecting 1-year survival. However, substantial intraoperative blood loss and a reduced oxygenation index were identified as independent risk factors associated with increased mortality within 1 year post-transplantation.

Key Associations Found in the Struggle With Sleep in Lung Transplant Recipients.

INTRODUCTION: Gaps exist in the understanding of the etiology of poor sleep quality after lung transplantation. Research Question: What factors are associated with poor sleep quality in lung transplant recipients? DESIGN: A quantitative, single-site, cross-sectional study used an anonymous survey based on 3 scales. The Pittsburgh Sleep Quality Index scale with scores dichotomized to poor versus good sleepers based on the cutoff score > 8. The Hospital Anxiety and Depression Scale evaluated symptoms of anxiety and depression, and the Short Form-12 measured health-related quality of life using the mental and physical component scores. Additional self-reported data included demographic and transplant-related variables. RESULTS: The response rate was 38.4% (61/158), and 52.5% of the sample (32/61) evidenced a Pittsburgh Sleep Quality Index score > 8, suggestive of poor sleep quality. Bivariate analyses demonstrated that poor sleep was significantly related to symptoms of depression (P < .01), anxiety (P < .01), stressors of hospitalization (P < .05), and treatment of acute rejection (P < .05). Multivariate analysis demonstrated that anxiety was significantly associated with poor sleep (odds ratio = 1.34, P < .05). CONCLUSION: Poor subjective sleep quality remains prevalent in lung transplant recipients. Individuals with anxiety symptoms were at a greater risk for poor sleep. Guidance for strategies to improve sleep quality requires further in-depth exploration before implementation of interventions.

Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor.

BACKGROUND: Ischemia-reperfusion injury (IRI) stands as a major trigger for primary graft dysfunction (PGD) in lung transplantation (LTx). Especially in LTx from donation after cardiac death (DCD), effective control of IRI following warm ischemia (WIRI) is crucial to prevent PGD. This study aimed to identify the key factors affecting WIRI in LTx from DCD. METHODS: Previously reported RNA-sequencing dataset of lung WIRI was reanalyzed to identify nuclear receptor subfamily 4 group A member 1 (NR4A1) as the immediate early gene for WIRI. Dynamics of NR4A1 expression were verified using a mouse hilar clamp model. To investigate the role of NR4A1 in WIRI, a mouse model of LTx from DCD was established using Nr4a1 knockout (Nr4a1-/-) mice. RESULTS: NR4A1 was located around vascular cells, and its protein levels in the lungs increased rapidly and transiently during WIRI. LTｘ from Nr4a1-/- donors significantly improved pulmonary graft function compared to wild-type donors (P < 0.001). Histological analysis showed decreased microvascular endothelial cell death (P = 0.007), neutrophil infiltration (P < 0.001), and albumin leakage (P < 0.001). Evans blue permeability assay demonstrated maintained pulmonary microvascular barrier integrity in grafts from Nr4a1-/- donors, correlating with diminished pulmonary edema (P < 0.001). However, NR4A1 did not significantly affect the inflammatory response during WIRI, and IRI was not suppressed when a wild-type donor lung was transplanted into the Nr4a1-/- recipient. CONCLUSIONS: Donor NR4A1 plays a specialized role in the positive regulation of endothelial cell injury and microvascular hyperpermeability. These findings demonstrate the potential of targeting NR4A1 interventions to alleviate PGD and improve outcomes in LTx from DCD.

Angiotensin-converting enzyme 2 activation attenuates inflammation and oxidative stress in brain death donor followed by rat lung transplantation.

Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx. 3 h after BD induction, rats were injected with saline (BD group) or an ACE2 activator (ACE2a group; 15 mg/kg-1) and kept on mechanical ventilation for additional 3 h. A third group included a control ventilation (Control group) prior to transplant. After BD protocol, left LTx were performed, followed by 2 h-reperfusion. ACE2 activation was associated with better oxygenation after BD management (p = 0.01), attenuating edema (p = 0.05) followed by the reduction in tissue resistance (p = 0.01) and increase of respiratory compliance (p = 0.02). Nrf2 expression was also upregulated in the ACE2a group (p = 0.03). After transplantation, ACE2a group showed lower levels of TNF-α (p = 0.02), IL-6 (p = 0.001), IL-1ß (p = 0.01), ROS (p = 0.004) and MDA (p = 0.002), in addition to higher CAT activity (p = 0.04). In conclusion, our study suggests that ACE2 activation improves anti-inflammatory and antioxidant activity in a model of LTx.

Donor age over 55 is associated with worse outcome in lung transplant recipients with idiopathic pulmonary fibrosis.

BACKGROUND: Lung transplantation (LTx) remains the only efficient treatment for selected patients with end-stage pulmonary disease. The age limit for the acceptance of donor organs in LTx is still a matter of debate. We here analyze the impact of donor organ age and the underlying pulmonary disease on short- and long-term outcome and survival after LTx. METHODS: Donor and recipient characteristics of LTx recipients at our institution between 03/2003 and 12/2021 were analyzed. Statistical analysis was performed using SPSS and GraphPad software. RESULTS: In 230 patients analyzed, donor age ≥ 55 years was associated with a higher incidence of severe primary graft dysfunction (PGD2/3) (46% vs. 31%, p = 0.03) and reduced long-term survival after LTx (1-, 5- and 10-year survival: 75%, 54%, 37% vs. 84%, 76%, 69%, p = 0.006). Notably, this was only significant in recipients with idiopathic pulmonary fibrosis (IPF) (PGD: 65%, vs. 37%, p = 0.016; 1-, 5-, and 10-year survival: 62%, 38%, 16% vs. 80%, 76%, 70%, p = 0.0002 respectively). In patients with chronic obstructive pulmonary disease (COPD), donor age had no impact on the incidence of PGD2/3 or survival (21% vs. 27%, p = 0.60 and 68% vs. 72%; p = 0.90 respectively). Moreover, we found higher Torque-teno virus (TTV)-DNA levels after LTx in patients with IPF compared to COPD (X2 = 4.57, p = 0.033). Donor age ≥ 55 is an independent risk factor for reduced survival in the whole cohort and patients with IPF specifically. CONCLUSIONS: In recipients with IPF, donor organ age ≥ 55 years was associated with a higher incidence of PGD2/3 and reduced survival after LTx. The underlying pulmonary disease may thus be a relevant factor for postoperative graft function and survival. TRIAL REGISTRATION NUMBER DKRS: DRKS00033312.

Diagnostic Alignment to Optimize Inter-rater Reliability Among Lung Transplant Pathologists.

BACKGROUND: Poor agreement among lung transplant pathologists has been reported in the assessment of rejection. In addition to acute rejection (AR) and lymphocytic bronchiolitis (LB), acute lung injury (ALI) and organizing pneumonia (OP) were recently identified as histopathologic risk factors for chronic lung allograft dysfunction (CLAD). Therefore, maximizing inter-rater reliability (IRR) for identifying these histopathologic risk factors is important to guide individual patient care and to support incorporating them in inclusion criteria for clinical trials in lung transplantation. METHODS: Nine pathologists across eight North American lung transplant centers were surveyed for practices in the assessment of lung transplant transbronchial biopsies. We conducted seven diagnostic alignment sessions with pathologists discussing histomorphologic features of CLAD high-risk histopathology. Then, each pathologist blindly scored 75 digitized slides. Fleiss' kappa, accounting for agreement across numerous observers, was used to determine IRR across all raters for presence of any high-risk finding and each individual entity. RESULTS: IRR (95% confidence intervals) and % agreement for any high-risk finding (AR, LB, ALI and/or OP) and each individual finding is as follows: Any Finding, k = 0.578 (0.487, 0.668), 78.9%; AR, k = 0.582 (0.481, 0.651), 79.1%; LB, k = 0.683 (0.585, 0.764), 83.5%; ALI, k = 0.418 (0.312, 0.494), 70.9%; OP, k = 0.621 (0.560, 0.714), 81.0%. CONCLUSIONS: After pre-study diagnostic alignment sessions, a multi-center group of lung transplant pathologists seeking to identify histopathology high-risk for CLAD achieved good IRR.

[Risk analysis applied to the monitoring of immunosuppressor concentrations in lung transplant recipients]. / Analyse de risques appliquée au suivi des concentrations des immunosuppresseurs chez les patients transplantés pulmonaire.

Mastering and monitoring immunosuppressant concentrations is central to the care of lung transplant patients and involves multiple stakeholders. The objective is to conduct a risk analysis to evaluate the impact of various actions taken. The lung transplantation team was convened to carry out a failure mode effect analysis. The process was divided into stages where different risks were identified. The risk priority number (RPN) (severity, frequency, detectability) and risk level of criticality (frequency, severity) were established before implementation of actions (before 2009) and then after (in 2022) to classify risks according to four levels of criticality. The implemented actions included the establishment of a quality assurance process, computerization of monitoring, and double analysis by a physician/pharmacist pair. Thirty-two risks were identified during the four stages of the process: biological sampling (n=13), reception (n=3), analysis and treatment of levels (n=5), transmission of information/prescriptions to the patient (n=11). The total raw RPN (before 2009) was 839, with 12 major risks. The current total RPN (in 2022) was 452 (a decrease of 46.1%), with 7 major risks identified. The analysis enabled the objective evaluation of the effectiveness of the actions taken. The most secure stage of the process is the reception of residual level results. Efforts should focus on empowering and involving patients, as well as engaging local stakeholders in collaboration with the specialized transplantation team.

Adoption of the Robotic Platform across Thoracic Surgeries.

With the paradigm shift in minimally invasive surgery from the video-assisted thoracoscopic platform to the robotic platform, thoracic surgeons are applying the new technology through various commonly practiced thoracic surgeries, striving to improve patient outcomes and reduce morbidity and mortality. This review will discuss the updates in lung resections, lung transplantation, mediastinal surgeries with a focus on thymic resection, rib resection, tracheal resection, tracheobronchoplasty, diaphragm plication, esophagectomy, and paraesophageal hernia repair. The transition from open surgery to video-assisted thoracoscopic surgery (VATS) to now robotic video-assisted thoracic surgery (RVATS) allows complex surgeries to be completed through smaller and smaller incisions with better visualization through high-definition images and finer mobilization, accomplishing what might be unresectable before, permitting shorter hospital stay, minimizing healing time, and encompassing broader surgical candidacy. Moreover, better patient outcomes are not only achieved through what the lead surgeon could carry out during surgeries but also through the training of the next generation via accessible live video feedback and recordings. Though larger volume randomized controlled studies are pending to compare the outcomes of VATS to RVATS surgeries, published studies show non-inferiority data from RVATS performances. With progressive enhancement, such as overcoming the lack of haptic feedback, and future incorporation of artificial intelligence (AI), the robotic platform will likely be a cost-effective route once surgeons overcome the initial learning curve.

Bloodless Lung Transplantation: Comparison Between Two Central Venoarterial ECMO Anticoagulation Strategies and Their Impact on Lung Transplant Outcomes.

OBJECTIVE: We report differences between two anticoagulation protocols during VA-ECMO intraoperative support and their effects on outcomes following lung transplantation. METHODS: We performed a retrospective analysis of patients undergoing double lung transplantation with intraoperative VA-ECMO from 1/1/2016 - 12/30/2023. Two distinct anticoagulation protocols were in place during this period. One included targeted ACT > 180s at all times with protamine reversal after decannulation. The second included 75 Ui of heparin at the time of cannulation with no redosing plus a TXA infusion after ECMO initiation. RESULTS: A total of 116 patients (46 low heparin, 70 standard) were included in the analysis. Cannulation strategies and ECMO circuit were equivalent between the groups. The low heparin protocol group had a shorter surgical time (7.28 vs 8.53 hours, p<0.001) and required significantly less intraoperative pRBC (median 4.37 vs. 0 units p<0.001), FFP (median 2 vs 0 units, p<0.001), platelets (median 1 vs 0 units, p<0.001), cryoprecipitate (median 0 vs 0 units, p<0.001), and total blood products (median 9 vs 0 units, p<0.001) compared to the standard group. There were no differences in rates of DVT (p=0.13), airway dehiscence (p>0.99), pneumonia (p=0.38), or acute kidney injury require renal replacement therapy (p=0.59). There was no difference in rates of severe grade 3 PGD at 72 hours post-transplant (p=0.42). CONCLUSION: Our low heparin VA-ECMO protocol for intraoperative support during lung transplantation led to a significant reduction of blood product utilization. While this did not translate to a reduced PGD 3 rates, the low heparin protocol was associated with similar post-operative outcomes.

An epigenetic human cytomegalovirus infection score predicts viremia risk in seropositive lung transplant recipients.

Cytomegalovirus (CMV) infection and reactivation in solid organ transplant (SOT) recipients increases the risk of viremia, graft failure and death. Clinical studies of CMV serostatus indicate that donor positive recipient negative (D+/R-) patients have greater viremia risk than D-/R-. The majority of patients are R+ having intermediate serologic risk. To characterize the long-term impact of CMV infection and assess viremia risk, we sought to measure the effects of CMV on the recipient immune epigenome. Specifically, we profiled DNA methylation in 156 individuals before lung or kidney transplant. We found that the methylome of CMV positive SOT recipients is hyper-methylated at loci associated with neural development and Polycomb group (PcG) protein binding, and hypo-methylated at regions critical for the maturation of lymphocytes. In addition, we developed a machine learning-based model to predict the recipient CMV serostatus after correcting for cell type composition and ancestry. This CMV episcore measured at baseline in R+ individual stratifies viremia risk accurately in the lung transplant cohort, and along with serostatus the CMV episcore could be a potential biomarker for identifying R+ patients at high viremia risk.

The combination of post-mortem sevoflurane ventilation and in situ topical cooling provides improved 6h lung preservation in an uncontrolled DCD porcine model.

BACKGROUND: Recent clinical series on donation after uncontrolled cardiovascular death (uDCD) reported successful transplantation of lungs preserved by pulmonary inflation up to 3h post-mortem. This study aims to investigate the additive effects of in situ lowering of intrathoracic temperature and sevoflurane preconditioning on lung grafts in a porcine uDCD model. METHODS: After uDCD induction, donor pigs were allocated to one of the following groups: Control - static lung inflation only (SLI); TC - SLI + continuous intrapleural topical cooling (TC); or TC+Sevo - SLI + TC + sevoflurane. Lungs were retrieved 6h post-asystole and evaluated via ex vivo lung perfusion (EVLP) for 6h. A left single lung transplant was performed using lungs from the best performing group, followed by 4h of graft evaluation. RESULTS: Animals that received topical cooling achieved intrathoracic temperature < 15°C within 1 hour after chest filling of coolant. Only lungs from donors that received TC and TC+Sevo completed the planned post-preservation 6h EVLP assessment. Despite similar early performance of the two groups on EVLP, the TC+Sevo group was superior - associated with overall lower airway pressures, higher pulmonary compliances, less edema development, and less release of inflammatory cytokines. Transplantation was performed using lungs from the TC+Sevo group, and excellent graft function was observed post-reperfusion. CONCLUSION: Preservation of uDCD lungs with a combination of static lung inflation, topical cooling and sevoflurane treatment maintains good pulmonary function up to 6h post-mortem with excellent early post-lung transplant function. These interventions may significantly expand the clinical utilization of uDCD donor lungs.

Detailed cellular and spatial characterization of chronic lung allograft dysfunction using imaging mass cytometry.

Long-term survival after lung transplantation remains limited by chronic lung allograft dysfunction (CLAD), with two main phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). We aimed to assess CLAD lung allografts using imaging mass cytometry (IMC), a high dimensional tissue imaging system allowing a multiparametric in situ exploration at a single cell level. 4 BOS, 4 RAS, and 4 control lung samples were stained with 35 heavy metal-tagged antibodies selected to assess structural and immune proteins of interest. We identified 50 immune and non-immune cell clusters. CLAD lungs had significantly reduced club cells. A Ki67-high basal cell population was mostly present in RAS and in proximity to memory T cells. Memory CD8+ T cells were more frequent in CLAD lungs, regulatory T cells more prominent in RAS. IMC is a powerful technology for detailed cellular analysis within intact organ structures that may shed further light on CLAD mechanisms.

Expanding horizons: lung transplantation for non-IPF interstitial lung diseases.

OBJECTIVE: Interstitial lung diseases (ILDs) are diverse pulmonary disorders marked by diffuse lung inflammation and fibrosis. The variability in characteristics and treatment approaches complicates diagnosis and management. In advanced cases requiring transplantation, determining indications and selecting suitable candidates presents additional challenges. METHODS: Of all patients with non-IPF ILD between December 2016 to December 2022 were analyzed retrospectively. Patients were categorized into two groups: transplanted patients and deceased patients on the waiting list. Clinical data and survival outcomes were compared between groups. RESULTS: Of the 43 patients, 20 underwent lung transplantation while 23 died awaiting transplantation. Waiting list mortality was 53.4%, with median waiting times similar between groups (3 months for transplant patients and 6 months for those on the waiting list). There were no significant differences between groups in age, gender, height, BMI, 6-minute walk test (6MWT), or forced vital capacity (FVC). The prevalence of pulmonary hypertension (PH) was 76.7% in right heart catheterizations, similar in both groups. One single and 19 bilateral lung transplants were performed. Overall, 13 of the 20 patients survived to discharge from the hospital. One-year mortality was 7/20 (35%). The median follow-up was 34 months, with a 1-year conditional survival of 90.9% at 3 years and 70.7% at 5 years. CONCLUSIONS: This study underscores the importance of further research into non-IPF ILDs. Lung transplantation remains a viable option that can significantly enhance both the quality and longevity of life for patients with advanced ILD.

Cardiac Comorbidity and Exercise Intolerance in Bilateral Lung Transplant Recipients Followed at a Pediatric Center.

Reduced exercise capacity is common in young bilateral lung transplantation (Bi-LTx) recipients, but longer-term data on cardiac comorbidities are limited. We evaluate potential cardiac contributions to long-term exercise intolerance in this population. All Bi-LTx recipients at a single pediatric center, who completed routine clinical post-transplant cardiac assessment, including echocardiogram, cardiac exam, and cardiopulmonary exercise testing (CPET), were included. Cardiac risk factors (CRFs) were assessed by history and laboratory tests. CPET-derived peak and percent-predicted peak myocardial oxygen consumption (VO2 peak, ppVO2 peak) were used to quantitate exercise capacity. Percent-predicted peak oxygen pulse (pp peak O2 pulse) assessed stroke volume. 15 patients (67% M; median age 21.6 years, median follow-up from Bi-LTx 7.0 years) were included. Almost all patients (14, 93%) had multiple CRFs; hypertension and hyperlipidemia/dyslipidemia were the most common. On CPET, 93% (n = 14) had abnormal (≤ 85%) ppVO2 peak (median 59%). 73% (n = 11) had abnormal pp peak O2 pulse (median 74%). Ten had blunted heart rate response to exercise. Nine had left ventricular diastolic dysfunction (LV-DD) on echocardiogram. Median percent-predicted forced expiratory volume in one second was 70%. One had severe chronic lung allograft dysfunction. Cardiac risk factors and exercise intolerance are common among young Bi-LTx recipients years post-transplant, even among those without significant pulmonary dysfunction. High prevalence of multiple CRFs, LV-DD, chronotropic dysfunction, and abnormal stroke volume suggest cardiac comorbidities may contribute to intolerance. Medical management of CRFs and tailored exercise may decrease cardiac risk and improve functional capacity for Bi-LTx survivors.