chronic thromboembolic disease, backtable PTE may be performed safely and can improve graft function.

Purpose: Late onset non-infectious pulmonary complications (LONIPCs) of allogeneic hematopoietic stem cell transplantation (HSCT) are often fatal, and their primary pathogenesis appears to be graft-versus-host disease. The clinical and radiological features of LONIPCs are similar to those of chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). The objective of this study was to investigate whether CLAD occurs more frequently after lung transplantation for LONIPCs of HSCT. The impact of the donor source was also examined, comparing living-donor lobar lung transplantation (LDLLT) with deceased-donor lung transplantation (DDLT).

Purpose: Living-donor lobar lung transplantation (LDLLT) is a life-saving treatment option for critically ill patients unable to endure prolonged waiting times, especially in situations of severe brain-dead donor shortages. This study aims to compare perioperative and early post-transplant outcomes between LDLLT and deceased-donor lung transplantation (DDLT).

Purpose: Intercellular adhesion molecule-1(ICAM-1) and leukocyte function-associated antigen-1(LFA-1) regulate leukocyte recruitment from circulation to sites of inflammation. We hypothesized that ICAM-1 and LFA-1 were essential in lymphocyte homing in the process of lung allograft rejection. This study aimed to investigate the effect of inhibiting ICAM-1 and LFA-1 on acute cellular rejection and subsequent fibrosis.

Purpose: Generally, HLA matching between donors and recipients is not performed in lung transplantation (LT); therefore, whether HLA mismatch between donors and recipients (D/R mismatch) influences postoperative outcomes after LT remains uncertain. In this study, the influences of D/R mismatch on postoperative outcomes after cadaveric LT (CLT) were investigated.

Purpose: Living donor lobar lung transplantation (LDLLT) has become a life saving option for severe patients in Japan. Single-lobe lung transplant procedure was required when small pediatric patients received oversized grafts or only one donor was available. The aim of this study was to evaluate posttransplant outcomes of LDLLT using a single lobar graft.

Purpose: This study aimed to assess the effects of specialized pro-resolving lipid mediators (SPMs) and their precursors on ischemia-reperfusion injury (IRI) in a mouse model. We also measured the dynamics of SPMs and their precursors derived from Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) early after clinical lung transplantation.

Introduction: Dyskeratosis congenita (DKC) is a rare, multi-system disorder caused by telomere abnormality. Most patients with DKC develop inherited bone marrow failure syndrome that requires hematopoietic stem cell transplantation. DKC also causes interstitial pneumonia, and a few studies have reported cases of pulmonary arteriovenous malformations (AVMs) in patients with DKC.

Purpose: Delayed chest closure (DCC) is sometimes used as an alternative to primary chest closure (PCC) in lung transplantation when dealing with oversized grafts and hemodynamic instability. However, there is limited data available regarding the clinical impact of DCC in lung transplantation. The aim of this study was to compare DCC with PCC in terms of both early and late outcomes. The impact of the donor source was also examined, comparing deceased-donor lung transplantation (DDLT) with living-donor lobar lung transplant (LDLLT).

The pathological diagnosis of cancer is essential to determine the surgical approach for lung resection surgery; however, the diagnostic rates of a transbronchial lung biopsy for peripheral small-sized lung cancer range from 18% to 62%. Therefore, an intraoperative needle biopsy (INB) is often performed for preoperatively undiagnosed lung lesions, even though this aspiration technique carries a potential risk of dissemination or recurrence. However, the precise impact of an INB on recurrence remains controversial, as both the needle size and clinicopathological factors are associated with recurrence (tumor size, lymphovascular invasion, pleural invasion, and EGFR mutation status).

PurposeCytotoxic T-Lymphocyte Associated Protein-4-Ig (CTLA-4-Ig), a fusion-protein of the extracellular domain of CTLA-4 and IgG1, is a co-stimulatory blockade already used as an immunosuppressant in clinics. The objective of this study was to investigate the efficacy of CTLA-4-Ig in murine chronic lung allograft dysfunction (CLAD) model.MethodsLeft lung of donor BALB/c mouse was transplanted into recipient C57BL/6J mouse, followed by low-dose cyclosporine (CyA; 10 mg/kg, 3 times/week) and methylprednisolone (mPSL; 1.6 mg/kg, 3 times/week). In this model, allograft showed acute cellular rejection without fibrosis on 15 days after transplantation (D15) and severe fibrosis on D30. In the preventive CTLA-4-Ig group, administration of CTLA-4-Ig (7 mg/kg, every 4 days) was started immediately after transplantation. In the therapeutic CTLA-4-Ig group, administration of CTLA-4-Ig was started on D15 when cellular rejection without fibrosis was observed. In the control group, IgG1 Fc-isotype (7 mg/kg, every 4 days) was administered from D0. All recipient mice (n = 5, each group) were sacrificed at D30 to evaluate histology.ResultsCompared with the control group, allograft in the preventive CTLA-4-Ig group showed significantly lower A grade rejection (p = 0.032) and significantly less fibrosis (p < 0.01) evaluated by the percentage of collagen fiber area to total lung area. Allograft in the therapeutic CTLA-4-Ig group showed no significant difference in A grade rejection (p = 0.41) and fibrosis (p = 0.15) compared with the control group.ConclusionCTLA-4-Ig effectively prevented fibrotic progression with cellular rejection in a mouse model of CLAD induced by inadequate CyA and mPSL when the administration was started immediately after transplantation, but did not when it was started after the occurrence of acute cellular rejection. Further investigation is necessary to determine the optimal treatment regimen to prevent fibrosis. Cytotoxic T-Lymphocyte Associated Protein-4-Ig (CTLA-4-Ig), a fusion-protein of the extracellular domain of CTLA-4 and IgG1, is a co-stimulatory blockade already used as an immunosuppressant in clinics. The objective of this study was to investigate the efficacy of CTLA-4-Ig in murine chronic lung allograft dysfunction (CLAD) model. Left lung of donor BALB/c mouse was transplanted into recipient C57BL/6J mouse, followed by low-dose cyclosporine (CyA; 10 mg/kg, 3 times/week) and methylprednisolone (mPSL; 1.6 mg/kg, 3 times/week). In this model, allograft showed acute cellular rejection without fibrosis on 15 days after transplantation (D15) and severe fibrosis on D30. In the preventive CTLA-4-Ig group, administration of CTLA-4-Ig (7 mg/kg, every 4 days) was started immediately after transplantation. In the therapeutic CTLA-4-Ig group, administration of CTLA-4-Ig was started on D15 when cellular rejection without fibrosis was observed. In the control group, IgG1 Fc-isotype (7 mg/kg, every 4 days) was administered from D0. All recipient mice (n = 5, each group) were sacrificed at D30 to evaluate histology. Compared with the control group, allograft in the preventive CTLA-4-Ig group showed significantly lower A grade rejection (p = 0.032) and significantly less fibrosis (p < 0.01) evaluated by the percentage of collagen fiber area to total lung area. Allograft in the therapeutic CTLA-4-Ig group showed no significant difference in A grade rejection (p = 0.41) and fibrosis (p = 0.15) compared with the control group. CTLA-4-Ig effectively prevented fibrotic progression with cellular rejection in a mouse model of CLAD induced by inadequate CyA and mPSL when the administration was started immediately after transplantation, but did not when it was started after the occurrence of acute cellular rejection. Further investigation is necessary to determine the optimal treatment regimen to prevent fibrosis.

Purpose Prevention of chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx) is a significant challenge. Recently, we showed diabetes mellitus as a risk for CLAD (EJCTS 2022, ISHLT 2022). We also presented the relevance between CD26 and CLAD development, and the efficacy of CD26/dipeptidyl peptidase 4 (DPP-4) inhibitor, an anti-diabetic agent, in post-LTx graft protection. This study aims to elucidate if DPP-4 inhibitors can effectively prevent CLAD after LTx. Methods We retrospectively reviewed the records of patients who had an initial LTx between 2010-2021 and extracted those with perioperative DM. We established 6 months post-LTx as the landmark point to predict CLAD development. Cox regression analysis was used for the landmark analysis. We selected the variables, such as DPP-4 inhibitor usage, primary graft dysfunction, donor type (cadaveric/ living), and respiratory infection up to discharge. We also performed pathological evaluation, including immunohistochemistry on LTx grafts. Results Of 102 LTx patients with DM, 29 were treated with DPP-4 inhibitors. Twenty-six patients developed CLAD, and 33 died. The patients treated with DPP-4 inhibitors were likely associated with high age, collagen diseases, and preoperative DM. The five-year CLAD-free survival was 57.5%. At 6 months post-LTx, the adjusted hazard ratio of DPP-4 inhibitor usage for CLAD-free survival was 0.44 (95% confidence interval, 0.19-1.00). CLAD pathology was available in four patients. All of them did not receive DPP-4 inhibitors. In three of them, CD26+ cells in CLAD lesions were detected (Figure). Conclusion According to the multivariate landmark analysis of LTx patients with DM, DPP-4 inhibitor was a favorable factor in preventing CLAD development. The pathology detected CD26+ cells in CLAD lesions, which can be a target of the therapy. Then, we need to validate DPP-4 inhibitors in non-DM LTx patients as prophylaxis of CLAD.

Purpose: Level of evidence is low regarding the choice of calcineurin inhibitor (CNI) for immunosuppression after lung transplantation (LTx).A randomized clinical trial (RCT) was therefore designed and compared tacrolimus with cyclosporine after LTx.The ScanCLAD study is an investigator-initiated, open-label, multi-center RCT evaluating if an immunosuppressive protocol based on ATG-induction, once daily tacrolimus-dose, mycophenolate mofetil and corticosteroid reduces the incidence of chronic lung allograft dysfunction (CLAD) after LTx, compared to a cyclosporine-based protocol with all other immunosuppressive and prophylactic drugs being identical between groups.Methods: Patients were recruited from all institutions performing LTx within the Scandia transplant area and were followed for three years, to determine the primary endpoint CLAD, using the most updated definition, as well as more than ten other sub-studies.Recruitment was performed between 2016 and 2019, and 249 patients were correctly randomized, transplanted, received first dose of the study drug and constituted the intention-to-treat population.Endpoints: Groups were well balanced, and all patients were followed with the registration of AE/SAE and lung function tests according to protocol.Last patient was followed for three years in October 2022.The primary outcome will be disclosed as well as survival and some secondary outcomes.The ScanCLAD study investigates which CNI is to be preferred from a CLAD perspective after LTx, and will be revealed at the ISHLT annual meeting in Denver in 2023.

Purpose The standard immunosuppressive therapy after lung transplantation is a combination of calcineurin inhibitors (CNIs), antimetabolites, and corticosteroids. In the cases where CNIs need to be reduced or discontinued early after transplantation due to renal dysfunction or other side effects, basiliximab is used as an alternative at our hospital. In this study, we investigated the efficacy and safety of basiliximab administered early after transplantation as an alternative of CNIs. Methods All lung transplant recipients between April 2002 and April 2021 at our hospital were retrospectively reviewed. Among 272 lung transplant recipients (108 living-donor, 163 deceased-donor, and 1 hybrid), 18 recipients were treated with basiliximab due to the need for CNI reduction or discontinuation. We reviewed indications of basiliximab and the outcome. Acute rejection was diagnosed based on radiologic and clinical parameters without transbronchial biopsy. The incidence of clinically diagnosed acute rejection and that of chronic lung allograft dysfunction (CLAD) were compared between the basiliximab group (n = 18) and the non-basiliximab group (n = 254). Results The indications of basiliximab were preoperatively existing poor renal function (n = 11) postoperative acute kidney disease (eGFR < 50, n = 4), and posterior reversible encephalopathy syndrome (PRES, n = 3) due to CNIs. The first dose of basiliximab (20 mg for adults, 10 mg for children) was administered postoperatively (median 0, range 0-7 days) and the second dose was administered 4 days later. No apparent adverse effects were encountered. None of the recipients with poor renal function required dialysis in the perioperative period, and all the recipients with PRES showed complete recovery. The incidence of clinically diagnosed acute rejection before discharge was 44.4% in the basiliximab group and 41.3% in the non-basiliximab group (p = 0.81). Five-year CLAD-free survival was 50% in the basiliximab group and 60.6% in the non-basiliximab group (p = 0.41). Conclusion The use of basiliximab as an alternative of CNIs early after lung transplantation was safe and increased neither the risk of acute rejection nor CLAD.

Purpose Living-donor lobar lung transplantation (LDLLT) is a valuable life-saving option for pediatric patients due to the scarcity of pediatric donor. The purpose of this study was to evaluate the long-term outcome and the lung growth of the transplanted adult lobe in growing pediatric recipients. Methods The clinical data of 30 pediatric LDLLTs (age<17) performed between June 2008 and December 2020 were reviewed. The annual pulmonary function test and CT scan data of the 12 recipients who were followed up for more than 5 years without significant complications were used for evaluating growth in height, graft function and radiological evidence of lung growth. Radiologic graft weight and air volume were calculated with CT value using 3D volume analyzer. Results Median age and height were 10 (3-15) and 125.3 cm (95-165), respectively. The procedures were unilateral transplantation of right lower lobe (n=12), bilateral transplantation of 2 lower lobes (n=13), and others including segmental and middle lobe transplantation (n=5). Ten-year overall survival and CLAD-free survival were 76.8% (Fig A) and 64.4%, respectively. In 12 recipients followed up for more than 5 years (median 6.5 years), the mean increase in height, vital capacity, and graft volume were 15.9%, 14.0%, and 55.4% (Fig B), respectively. Mean CT volumetric size matching (donor/recipient) at transplantation was 154% (53-367). The transplanted graft volume exceeded the original volume within the donor chest in 11 of 12 recipients (92%). During the median follow-up period of 3.0 years after the transplanted graft volume exceeded original one, the mean increase in radiologic graft weight was 6.6% and the radiologic graft weight was positively correlated with its air volume (r2=0.580, p<0.01, Fig C). Conclusion Pediatric LDLLT provided satisfactory long-term outcome with the radiological suggestion that the lung growth of transplanted mature lobe occurred in growing chest cavity.