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chronic lung allograft dysfunction

Ramsey Hachem, Paul Corris
BACKGROUND: Lung transplantation is a therapeutic option for select patients with end-stage lung disease. However, successful lung transplantation is hampered by chronic lung allograft dysfunction (CLAD), in particular bronchiolitis obliterans syndrome (BOS). Although there is no approved or standard treatment for BOS, which may have several distinct phenotypes, extracorporeal photopheresis (ECP) has shown promising results in patients who develop BOS refractory to azithromycin treatment...
March 19, 2018: Transplantation
Norihisa Shigemura, Shinya Tane, Kentaro Noda
Chronic allograft dysfunction (CLAD) remains a major complication, causing the poor survival after lung transplantation. Although strenuous efforts have been made at preventing CLAD, surgical approaches for lung transplantation have not been updated over the last 2 decades. The bronchial artery, which supplies oxygenated blood to the airways and constitutes a functional microvasculature, has occasionally been revascularized during transplants, but this technique did not gain popularity and is not standard in current lung transplantation protocols, despite the fact that a small number of studies have shown beneficial effects of bronchial artery revascularization (BAR) on limiting CLAD...
March 20, 2018: Transplantation
Souheil El-Chemaly, Kevin J O'Brien, Steven D Nathan, Gerald L Weinhouse, Hilary J Goldberg, Jean M Connors, Ye Cui, Todd L Astor, Philip C Camp, Ivan O Rosas, Merte Lemma, Vladislav Speransky, Melissa A Merideth, William A Gahl, Bernadette R Gochuico
Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers...
2018: PloS One
Patrick J Smith, Rebecca Byrd, Megan Lusby, Emily Clausen, Laurie D Snyder
BACKGROUND: Depressive symptoms are common among lung transplant recipients and have been associated with worse clinical outcomes. However, few studies have examined the association between depressive symptoms assessed at multiple time points or behavioral mechanisms by which post-transplant depressive symptoms may confer greater clinical risk. We therefore examined the associations between depressive symptoms, exercise capacity, chronic lung allograft dysfunction (CLAD), and mortality prospectively in a large sample of lung transplant recipients...
March 12, 2018: Psychosomatic Medicine
Christopher R Ensor, Carlo J Iasella, Kate M Harrigan, Matthew R Morrell, Cody A Moore, Norihisa Shigemura, Adriana Zeevi, John F McDyer, Raman Venkataramanan
Calcineurin inhibitors (CNIs) are the backbone of traditional immunosuppressive regimens for lung transplant recipients (LTR). The CNIs are both narrow therapeutic index drugs with significant interpatient and intrapatient variability that require therapeutic drug monitoring to ensure safety and effectiveness. We hypothesized that tacrolimus time-in-therapeutic range (TTR) affects acute and chronic rejection rates in LTRs. This was a single-center, observational, cross-sectional study of 292 adult LTRs. Subjects who received tacrolimus post-transplant for the first year were included...
March 7, 2018: American Journal of Transplantation
Anupong Tangaroonsanti, Augustine S Lee, Marcelo F Vela, Michael D Crowell, David Erasmus, Cesar Keller, Jorge Mallea, Francisco Alvarez, Cristina Almansa, Kenneth R DeVault, Lesley A Houghton
GOALS: To assess the effect of unilateral versus bilateral lung transplantation (LTx) on esophageal motility and gastroesophageal reflux, and the association with the development of obstructive chronic lung allograft dysfunction (o-CLAD). BACKGROUND: We have shown that esophagogastric junction outflow obstruction, incomplete bolus transit, and proximal reflux are all independent risk factors for the development of chronic allograft failure. However, it remains unclear whether these factors are influenced by the type of surgery and how this relates to allograft failure...
March 2, 2018: Journal of Clinical Gastroenterology
Mitsuteru Yoshida, Hisashi Oishi, Tereza Martinu, David M Hwang, Hiromitsu Takizawa, Junichi Sugihara, Trevor D McKee, Xiaohui Bai, Zehong Guana, Christina Lua, Hae-Ra Cho, Stephen Juvet, Marcelo Cypel, Shaf Keshavjee, Mingyao Liu
Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation and thought to represent chronic rejection. Increased expression of Pentraxin 3 (PTX3), an acute phase protein, was associated with worse outcome in lung transplant patients. To determine the role of recipient PTX3 in development of chronic rejection, we used a minor alloantigen-mismatched murine orthotopic single lung transplant model. Male C57BL/10 mice were used as donors. Male PTX3 knockout (KO) mice and their wild type (WT) littermates on 129/SvEv/C57BL6/J background were used as recipients...
February 2, 2018: Oncotarget
Claudia Del Fante, Jerard Seghatchian, Cesare Perotti
Renal rejection clinically represents a major cause of graft dysfunction and sadly the loss of the renal transplant. This is despite the considerable progress in immunosuppressive therapy. It is strongly believed that the complex immunologic network underlying the response against major histocompatibility molecules (MHC) is responsible for rejection, an unresolved issue that is, in part, not inhibited by the current prophylactic and therapeutic strategies. Extracorporeal photopheresis (ECP) is an effective cell therapy approach that was successfully used in immunomodulating heart rejection, acute and chronic GvHD, lung rejection and some selected autoimmune diseases...
February 21, 2018: Transfusion and Apheresis Science
A Tangaroonsanti, M F Vela, M D Crowell, K R DeVault, L A Houghton
BACKGROUND: Proximal reflux and incomplete transit of boluses swallowed are risk factors for obstructive chronic lung allograft dysfunction (o-CLAD) post-lung transplantation (LTx). Likewise, so is esophagogastric junction outflow obstruction (EGJOO), but not hypo-contractility, when diagnosed using Chicago Classification (CC) v3.0. Given, peristaltic breaks as defined using CCv2.0 can prolong esophageal clearance, both swallowed and refluxed, but which are deemed within normality using CCv3...
February 7, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Jessica Rademacher, Jan Fuge, Tobias Welte, Jens Gottlieb, Hendrik Suhling
BACKGROUND: The risk of transmission of infections in partnerships between two transplant recipients is unknown. The aim of this study was to evaluate transmission in such couples. METHODS: In this single centre study, lung transplant (LTx) couples were identified among outpatients between 1988 and 2016. Infection rates per year and survival were compared to matched LTx-recipients not living in a transplant partnership. RESULTS: Twelve transplant couples were analysed with cumulative 65 years of relationship...
January 29, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
H A Ali, E N Pavlisko, L D Snyder, M Frank, S M Palmer
The complement system is a cascade of multiple proteins that have been known to mediate inflammatory response. This tightly regulated system has been recognized to play a role in adaptive immunity via humoral and cell mediated processes. There is evidence from animal and human studies that the complement system is involved in various outcomes of solid organ transplantation. Most of the studies have been done in the field of kidney transplantation. In this paper we review the studies looking at lung transplantation...
January 23, 2018: Clinical Transplantation
Lynn D Haynes, Walker Julliard, Joshua Mezrich, Glen Leverson, Keith C Meyer, William J Burlingham
BACKGROUND: The greatest challenge to long-term graft survival is the development of chronic lung allograft dysfunction (CLAD). Th17 responses to collagen type V (colV) predispose lung transplant patients to the severe obstructive form of CLAD, known as bronchiolitis obliterans syndrome (BOS). In a previous study cohort (n=54), pre-transplant colV responses were increased in recipients expressing HLA-DR15, consistent with the high binding avidity of colV(α1) peptides for HLA-DR15, while BOS incidence, which was known to be strongly associated with post-transplant autoimmunity to colV, was higher in patients who themselves lacked HLA-DR15, but whose lung donor expressed it...
January 23, 2018: Transplantation
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
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...
February 2018: Stem Cells Translational Medicine
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
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
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
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
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 antibodies, creating heterogeneity regarding their clinical significance. Some institutions use beads coated with multiple HLA to screen candidate sera and then use single antigen bead (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...
February 2018: HLA
Amanda Szczepanik, Amanda Hulbert, Hui-Jie Lee, Clark Benedetti, Laurie Snyder, Jennifer Byrns
Lung transplant recipients (LRs) have a reduced median 5-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 LRs from January 2004 to 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 nonstatin group...
January 2018: Clinical Transplantation
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