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chronic lung allograft dysfunction

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https://www.readbyqxmd.com/read/29327719/the-histomorphological-spectrum-of-restrictive-chronic-lung-allograft-dysfunction-and-implications-for-prognosis
#1
Jan H von der Thüsen, Elly Vandermeulen, Robin Vos, Birgit Weynand, Erik K Verbeken, Stijn E Verleden
Chronic lung allograft dysfunction continues to be the main contributor to poor long-term allograft survival after lung transplantation. The restrictive phenotype of chronic lung allograft dysfunction carries a particularly poor prognosis. Little is known about the pathogenetic mechanisms involved in restrictive chronic lung allograft dysfunction. In this study, we performed histomorphological and immunohistochemical analysis of restrictive chronic lung allograft dysfunction lungs. Explant lung tissue from 21 restrictive chronic lung allograft dysfunction patients was collected and histopathologic patterns of rejection, fibrosis and vascular changes were scored after routine histochemical stains and additional immunohistochemistry for endothelial markers and C4d...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29322685/feasibility-safety-and-tolerance-of-mesenchymal-stem-cell-therapy-for-obstructive-chronic-lung-allograft-dysfunction
#2
Cesar Ariel Keller, Thomas Arthur Gonwa, David Orel Hodge, Derek Joseph Hei, John Michael Centanni, Abba Chedi Zubair
Feasibility, tolerance, and safety of intravenous infusions of allogeneic mesenchymal stem cell (MSC) therapy in lung transplant recipients with bronchiolitis obliterans syndrome (BOS) are not well established. MSCs were manufactured, cryopreserved, transported to our facility, thawed, and infused into nine recipients with moderate BOS (average drop in forced expiratory volume in 1 second was 56.8% ± 3.2% from post-transplant peak) who were refractory to standard therapy and not candidates for retransplant...
January 11, 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29312756/history-of-lung-transplantation
#3
REVIEW
Federico Venuta, Dirk Van Raemdonck
Lung transplantation nowadays is a well-accepted and routine treatment for well selected patients with terminal respiratory disease. However, it took several decades of experimental studies and clinical attempts to reach this success. In this paper, we describe the early experimental activity from the mid-forties until the early sixties. The first clinical attempt in humans was reported by Hardy and Webb in 1963 followed by others with short survival only except for one case by Derom et al. who lived for 10 months...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29312755/acute-rejection
#4
REVIEW
Mark Benzimra, Greg L Calligaro, Allan R Glanville
Despite induction immunosuppression and the use of aggressive maintenance immunosuppressive regimens, acute allograft rejection following lung transplantation is still a problem with important diagnostic and therapeutic challenges. As well as causing early graft loss and mortality, acute rejection also initiates the chronic alloimmune responses and airway-centred inflammation that predispose to bronchiolitis obliterans syndrome (BOS), also known as chronic lung allograft dysfunction (CLAD), which is a major source of morbidity and mortality after lung transplantation...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29300898/impact-of-human-leukocyte-antigen-mismatch-on-lung-transplant-outcome
#5
Yoshito Yamada, Tim Langner, Ilhan Inci, Christian Benden, Macé Schuurmans, Walter Weder, Wolfgang Jungraithmayr
OBJECTIVES: Human leucocyte antigen (HLA) mismatch between donor and recipient has a differential impact on the outcome after transplant (Tx) among transplantable solid organs. Although the lung is considered a highly antigenic organ, the impact of HLA matching between the donor and the recipient has been shown to be heterogeneous on lung Tx outcome. To provide further evidence that HLA matching should be considered in the decision process prior to lung Tx, we evaluated the impact of donor/recipient HLA mismatch on the outcome after lung Tx at our institution...
January 2, 2018: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29198928/lung-autoantibodies-ready-for-prime-time
#6
EDITORIAL
Luke Milross, Ramsey Hachem, Deborah Levine, Allan R Glanville
Despite advances in our understanding of the immunology of lung allograft tolerance and a reduction in the rate of acute allograft rejection using contemporary immunosuppressive protocols, the rate of chronic lung allograft dysfunction (CLAD), both obstructive and restrictive, remains unacceptably high. CLAD, particularly the restrictive phenotype, is a harbinger of a foreshortened survival. The development of a consensus approach to the diagnosis of antibody-mediated rejection by the International Society for Heart and Lung Transplantation has highlighted the need for a uniform approach toward the investigation, diagnosis, implications and management of both human leukocyte antigen (HLA) and non-HLA-related antibody formation...
November 8, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29178607/detection-and-clinical-impact-of-human-leukocyte-antigen-antibodies-in-lung-transplantation-a-systematic-review-and-meta-analysis
#7
A Courtwright, J M Diamond, I Wood, I Guleria, E Milford, S El-Chemaly, H J Goldberg
There is significant variability in lung transplant centers' approach to HLA (human leukocyte antigen) antibodies, creating heterogeneity regarding their clinical significance. Some institutions use beads coated with multiple HLA to screen candidate sera and then use single antigen beads (SAB) to determine antibody identity if the pre-screen is positive. Other centers do not pre-screen, using SAB alone, which may detect low-level antibodies of unknown significance. The primary objective of this study was to review the current literature to identify sources of heterogeneity in the identification of pre- and post-lung transplant HLA antibodies, particularly regarding antibody detection methods...
November 25, 2017: HLA
https://www.readbyqxmd.com/read/29151274/effect-of-hmg-coa-reductase-inhibitors-on-the-development-of-chronic-lung-allograft-dysfunction
#8
Amanda Szczepanik, Amanda Hulbert, Hui-Jie Lee, Clark Benedetti, Laurie Snyder, Jennifer Byrns
Lung transplant recipients (LR) have a reduced median five-year survival of approximately 55% primarily due to chronic lung allograft dysfunction (CLAD). Statins have anti-inflammatory and immunomodulatory effects that may facilitate CLAD prevention. This study sought to evaluate statin effect on CLAD development. Adult bilateral LR from January 2004-October 2013 were included. Statin group included recipients with early statin use and continued for minimum 6 months. Propensity score matching was performed for age, gender and native lung disease to select matched non-statin group...
November 19, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29149977/donor-smoking-and-older-age-increases-morbidity-and-mortality-after-lung-transplantation
#9
H H Schultz, C H Møller, M Zemtsovski, J Ravn, M Perch, T Martinussen, J Carlsen, M Iversen
BACKGROUND: The lack of lung transplant donors has necessitated the use of donors with a smoking history and donors of older age. We have evaluated the effects of donor smoking history and age on recipient morbidity and mortality with baseline values of pulmonary function and survival free of chronic lung allograft dysfunction (CLAD) as morbidity variables. METHODS: This is a retrospective analysis of 588 consecutive lung transplant recipients and their corresponding 454 donors...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29146602/donor-specific-and-nonspecific-hla-antibodies-and-outcome-post-lung-transplantation
#10
Stijn E Verleden, Bart M Vanaudenaerde, Marie-Paul Emonds, Dirk E Van Raemdonck, Arne P Neyrinck, Geert M Verleden, Robin Vos
Donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) are associated with chronic lung allograft dysfunction (CLAD) and mortality post lung transplantation, but data concerning prevalence, time of onset, persistence and effects on long-term outcome remain scarce.We assessed the association between HLA antibodies and CLAD-free and graft survival in a cohort of 362 patients. We stratified our analysis according to DSA status, persistence of antibodies and timing of antibodies (pre-transplant, early or late post-transplant)...
November 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29128018/update-in-chronic-lung-allograft-dysfunction
#11
REVIEW
Rupal J Shah, Joshua M Diamond
Chronic lung allograft dysfunction (CLAD) is the major limitation to posttransplant survival. This review highlights the evolving definition of CLAD, risk factors, treatment, and expected outcomes after the development of CLAD.
December 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/29128017/acute-rejection-and-antibody-mediated-rejection-in-lung-transplantation
#12
REVIEW
Ramsey R Hachem
Despite advances in immunosuppression over the past 25 years, acute cellular rejection remains a common complication early after lung transplantation. Although acute cellular rejection has often not resulted in clinical signs or symptoms of allograft dysfunction, it has been widely recognized as a strong independent risk factor for the development of chronic rejection, emphasizing its clinical significance. In recent years, the role of humoral immunity in lung rejection has been increasingly appreciated, and antibody-mediated rejection is now recognized as a form of rejection that may result in allograft failure...
December 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/29110800/long-term-outcomes-and-management-of-lung-transplant-recipients
#13
REVIEW
Joseph Costa, Luke J Benvenuto, Joshua R Sonett
Lung transplantation is an established treatment for patients with end-stage lung disease. Improvements in immunosuppression and therapeutic management of infections have resulted in improved long-term survival and a decline in allograft rejection. Allograft rejection continues to be a serious complication following lung transplantation, thereby leading to acute graft failure and, subsequently, chronic lung allograft dysfunction (CLAD). Bronchiolitis obliterans syndrome (BOS), the most common phenotype of CLAD, is the leading cause of late mortality and morbidity in lung recipients, with 50% having developed BOS within 5 years of lung transplantation...
June 2017: Best Practice & Research. Clinical Anaesthesiology
https://www.readbyqxmd.com/read/29100649/lung-retransplantation-for-chronic-rejection-a-single-center-experience
#14
Sreeja Biswas Roy, Roshan Panchanathan, Rajat Walia, Katherine E Varsch, Paul Kang, Jasmine Huang, A Samad Hashimi, Thalachallour Mohanakumar, Ross M Bremner, Michael A Smith
BACKGROUND: Chronic lung allograft dysfunction (CLAD) is nonreversible and remains the biggest obstacle to long-term survival after lung transplantation (LTx). Retransplantation is the sole definitive therapeutic option for CLAD. We analyzed our single-center experience with retransplantation as a treatment option for CLAD. METHODS: From March 1, 2010, to May 31, 2016, 419 consecutive patients underwent LTx at our institution; 29 of these procedures were retransplantations for CLAD...
November 1, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29075627/characteristics-of-donor-specific-antibodies-associated-with-antibody-mediated-rejection-in-lung-transplantation
#15
Antoine Roux, Ines Bendib Le Lan, Sonia Holifanjaniaina, Kimberly A Thomas, Clément Picard, Dominique Grenet, Sandra De Miranda, Benoit Douvry, Laurence Beaumont-Azuar, Edouard Sage, Jérôme Devaquet, Elise Cuquemelle, Morgan Le Guen, Caroline Suberbielle, Chantal Gautreau, Marc Stern, Maura Rossetti, Abdul Monem Hamid, Francois Parquin
Although donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) are frequently found in recipients after lung transplantation (LT), the characteristics of DSA which influence antibody-mediated rejection (AMR) in LT are not fully defined. We retrospectively analyzed 206 consecutive LT patients of our center (2010-2013). DSAs were detected by using luminex single antigen beads assay and mean fluorescence intensity was assessed. Within the study population, 105 patients had positive DSA. Patients with and without AMR (AMR(Pos), n = 22, and AMR(Neg), n = 83, respectively) were compared...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29055604/treatment-of-primary-graft-dysfunction-after-lung-transplantation-with-orally-inhaled-ap301-a-prospective-randomized-pilot-study
#16
Clemens Aigner, Alexis Slama, Maximilian Barta, Andreas Mitterbauer, Gyoergy Lang, Shahrokh Taghavi, Jose Matilla, Roman Ullrich, Katharina Krenn, Peter Jaksch, Klaus Markstaller, Walter Klepetko
BACKGROUND: Primary graft dysfunction (PGD) after lung transplantation (LTx) carries significant morbidity and mortality in the early post-operative period and is associated with the development of chronic lung allograft dysfunction. AP301, an activator of epithelial sodium channel-mediated Na+ uptake represents a new concept for prevention and treatment of pulmonary edema and has shown promising results in the pre-clinical setting. This pilot study investigated the clinical effect of inhaled AP301 on patients with development of PGD > 1 according to International Society of Heart and Lung Transplantation criteria after primary LTx in a high-volume center and was conducted as a randomized, placebo-controlled, single-center pilot-study including 20 patients...
September 30, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29039137/three-dimensional-image-in-lung-transplantation
#17
Toyofumi F Chen-Yoshikawa, Hiroshi Date
Three-dimensional computed tomography (3D-CT) technologies have been developed and, recently, high-speed and high-quality 3D-CT technologies have been introduced to the field of thoracic surgery. The purpose of this manuscript is to demonstrate the clinical application of 3D-CT technologies in lung transplantation. In Japan, because of the severe donor shortage, living-donor lobar lung transplantation (LDLLT) is essential, in addition to cadaveric lung transplantation. In LDLLT, size matching is a grave issue, since ideal size matching between donor and recipient is usually difficult because of the limited population of potential donor...
October 16, 2017: General Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/29035589/the-activity-of-nintedanib-in-an-animal-model-of-allogenic-left-lung-transplantation-resembling-aspects-of-allograft-rejection
#18
Marietta von Suesskind-Schwendi, Elke Boxhammer, Stephan W Hirt, Stephan Schreml, Christof Schmid, Lutz Wollin, Karla Lehle
AIM OF THE STUDY: The prevention and treatment of chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx) remain unsatisfactory. Growth factors may play an important role in the development of CLAD. This study evaluated the effects of nintedanib, a receptor tyrosine kinase inhibitor, in the treatment of CLAD after experimental LTx. MATERIALS AND METHODS: A rat model of left lung allo-transplantation (Fisher 344 to Wistar Kyoto) was used to evaluate the effect of nintedanib (50 mg/kg per day) on the development of CLAD...
October 16, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28992372/the-role-of-c4d-deposition-in-the-diagnosis-of-antibody-mediated-rejection-after-lung-transplantation
#19
P R Aguilar, D Carpenter, J Ritter, R D Yusen, C A Witt, D E Byers, T Mohanakumar, D Kreisel, E P Trulock, R R Hachem
Antibody-mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single-center study to characterize cases of C4d-negative probable AMR and to compare these to cases of definite (C4d-positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d-positive and 45 (62%) were C4d-negative. The two groups had a similar clinical presentation, and although more patients in the C4d-positive group had neutrophilic capillaritis (54% vs...
October 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28964417/continued-successful-evolution-of-extended-criteria-donor-lungs-for-transplantation
#20
Sakhee Kotecha, Jamie Hobson, Jeremy Fuller, Eldho Paul, Bronwyn J Levvey, Helen Whitford, Miranda Paraskeva, David McGiffin, Gregory I Snell, Glen P Westall
BACKGROUND: In an era of increasing ex vivo lung perfusion (EVLP) use, it remains important to describe what outcomes can be achieved without EVLP, by taking an aggressive approach to donor use to maximize lung transplantation. METHODS: Data for all lung transplant donor referrals to the Alfred Hospital in Melbourne, Australia were collected for 2012 to 2013. Donor variables were analyzed and calculated into a previously validated lung donor score. Lung transplant recipient outcome data included the following: primary graft dysfunction; duration of mechanical ventilation; need for cardiopulmonary bypass extracorporeal membrane oxygenation; intensive care and hospital length of stay; 30-day, 1-year, and 3- to 4-year survival rates; rates of acute rejection and chronic lung allograft dysfunction; and peak and 12-month lung function (forced expiratory volume in 1 second)...
November 2017: Annals of Thoracic Surgery
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