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chronic lung allograft dysfunction

Y Yamada, E Vandermeulen, T Heigl, J Somers, A Vaneylen, S E Verleden, H Bellon, S De Vleeschauwer, E K Verbeken, D E Van Raemdonck, R Vos, G M Verleden, W Jungraithmayr, B M Vanaudenaerde
The single most important cause of late mortality after lung transplantation is chronic lung allograft dysfunction (CLAD). However, the pathological development of CLAD was not as simple as previously presumed and subclassification phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD), have been introduced. We want to re-investigate how CLAD manifests in the murine orthotopic lung transplant model and investigate the role of interleukin 17A (IL-17A) within this model. Orthotopic LTx was performed in CB57Bl6, IL-17 WT and IL-17 KO mice...
October 10, 2016: Transplant Immunology
Akihiko Kitahara, Seijiro Sato, Terumoto Koike, Masanori Tsuchida
We report here a case of fatal respiratory failure developed during chemotherapy for diffuse large B cell lymphoma that occurred late after lung transplantation. 25-year- old man underwent lung transplantation from brain death donor for respiratory failure due to interstitial pneumonia at the age of 16 years old. Two years after transplantation, his respiratory function decreased gradually. Chronic lung allograft dysfunction including bronchiolitis obliterans( BOS) and restrictive allograft syndrome was suspected and immunosuppression was enhanced...
October 2016: Kyobu Geka. the Japanese Journal of Thoracic Surgery
Tomohito Saito, Masaaki Sato, Yohei Taniguchi, Tomohiro Murakawa, Shaf Keshavjee
Chronic lung allograft dysfunction (CLAD) is a major limitation to long-term success of lung transplantation. Restrictive allograft syndrome (RAS) is a recently discovered subtype of CLAD, showing distinct clinical, pathological and radiological features compared with the major CLAD subtype, bronchiolitis obliterans syndrome (BOS). Introduction of the novel CLAD classification system that differentiates CLAD into BOS and RAS has stimulated research activities aiming delineation of the underlying pathological mechanism in the 2 CLAD subtypes...
October 2016: Kyobu Geka. the Japanese Journal of Thoracic Surgery
Hidemi Suzuki, Atsushi Hata, Yuki Shina, Takamasa Yun, Kazuhisa Tanaka, Yuichi Sakairi, Hironobu Wada, Taiki Fujiwara, Takahiro Nakajima, Takekazu Iwata, Masako Chiyo, Shigetoshi Yoshida, Ichiro Yoshino
Chronic lung allograft dysfunction (CLAD) is a critical impediment to the long-term survival after lung transplantation. A rat orthotopic lung transplantation model was developed in the early 1970s, and using this model, our laboratory has shown that the immunopathogenesis of CLAD involves both allogeneic immunity and autoimmunity. However, further investigation of CLAD is limited by the scarcity of transgenic and knockout strains. The model most widely used to study CLAD, the mouse model of heterotopic tracheal transplantation, has some incomplete pathophysiologic features of CLAD, which limits the utility of this model...
October 2016: Kyobu Geka. the Japanese Journal of Thoracic Surgery
Takeshi Shiraishi, Akinori Iwasaki
The most frequent cause of death within a year after lung transplantation is infectious complications, which shifts to chronic allograft rejection or chronic lung allograft dysfunction(CLAD) thereafter. It is no doubt that minimization of the dose of immunosuppression within the acceptable therapeutic range is a best strategy to avoid infectious complications however, adequate dose of immunosuppressant is mandatory to protect lung allografts from acute or chronic rejection. Carefully balanced therapy of immunosuppression and infection control is extremely important for patient's long term survival after lung transplantation...
October 2016: Kyobu Geka. the Japanese Journal of Thoracic Surgery
M Y Shino, S S Weigt, N Li, A Derhovanessian, D M Sayah, R H Huynh, R Saggar, A L Gregson, A Ardehali, D J Ross, J P Lynch, R M Elashoff, J A Belperio
The impact of allograft injury time-of-onset on the risk of chronic lung allograft dysfunction (CLAD) remains unknown. We hypothesized that episodes of late-onset (≥6 months) allograft injury would produce an augmented CXCR3/ligand immune response, leading to increased CLAD. In a retrospective single-center study, 1894 transbronchial biopsies from 441 lung transplant recipients were reviewed for the presence of acute rejection (AR), lymphocytic bronchiolitis (LB), diffuse alveolar damage (DAD) and organizing pneumonia (OP)...
September 27, 2016: American Journal of Transplantation
Julien Guihaire, Ryo Itagaki, Mandy Stubbendorff, Xiaoqin Hua, Tobias Deuse, Sebastian Ullrich, Elie Fadel, Peter Dorfmüller, Robert C Robbins, Hermann Reichenspurner, Udo Schumacher, Sonja Schrepfer
Bronchiolitis obliterans syndrome (BOS) is a main cause of allograft dysfunction and mortality after lung transplantation (LTx). A better understanding of BOS pathogenesis is needed to overcome this treatment-refractory complication. Orthotopic tracheal transplantation using human bronchus was performed in Brown Norway (BN) and nude (RNU) rats. Allografts were recovered in both strains at Day 7 (BN7 , n = 6; RNU7 , n = 7) or Day 28 (BN28 , n = 6; RNU28 , n = 6). Immune response of the host against the bronchial graft was assessed...
September 10, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Kartik V Shenoy
No abstract text is available yet for this article.
September 1, 2016: American Journal of Respiratory and Critical Care Medicine
S Izhakian, W G Wasser, B D Fox, B Vainshelboim, J E Reznik, M R Kramer
BACKGROUND: Rabbit antithymocyte globulin (rATG) therapy has been shown to be beneficial in lung transplant recipients as induction therapy for treating acute lung rejection; however, its role in chronic lung rejection has been reported only rarely. We evaluated the effectiveness of rATG therapy in slowing the progression of chronic lung allograft dysfunction (CLAD) syndrome. METHODS: We conducted a retrospective review of 25 lung transplant patients with CLAD who received rATG therapy in the Pulmonary Institute of Rabin Medical Center, Israel, between May 2005 and February 2016...
July 2016: Transplantation Proceedings
Stefano Di Carlo, Elena Rossi, Gianfranco Politano, Simona Inghilleri, Patrizia Morbini, Fiorella Calabrese, Alfredo Benso, Alessandro Savino, Emanuela Cova, Davide Zampieri, Federica Meloni
The pathogenesis of Bronchiolitis Obliterans Syndrome (BOS), the main clinical phenotype of chronic lung allograft dysfunction, is poorly understood. Recent studies suggest that epigenetic regulation of microRNAs might play a role in its development. In this paper we present the application of a complex computational pipeline to perform enrichment analysis of miRNAs in pathways applied to the study of BOS. The analysis considered the full set of miRNAs annotated in miRBase (version 21), and applied a sequence of filtering approaches and statistical analyses to reduce this set and to score the candidate miRNAs according to their potential involvement in BOS development...
2016: PloS One
Elly Vandermeulen, Stijn E Verleden, Hannelore Bellon, David Ruttens, Elise Lammertyn, Sandra Claes, Jennifer Vandooren, Estafania Ugarte-Berzal, Dominique Schols, Marie-Paule Emonds, Dirk E Van Raemdonck, Ghislain Opdenakker, Geert M Verleden, Robin Vos, Bart M Vanaudenaerde
BACKGROUND: Recently, antibody mediated rejection (AMR) has been associated with a higher incidence of chronic lung allograft dysfunction (CLAD) and mortality after lung transplantation (LTx). We investigated markers related to AMR and matrix remodeling in CLAD, with special attention for its two phenotypes being bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD). METHODS: Immunoglobulins (IgA, IgE, IgG1-IgG4, total IgG and IgM) and complement (C4d and C1q) were quantified in lung lavage samples at the moment of BOS (n=15) or RAS (n=16) diagnosis; and were compared to stable transplant patients who served as control (n=14)...
September 2016: Transplant Immunology
Ning Cao, Xiaofang Ma, Zhenzhen Guo, Yaqiu Zheng, Shengnan Geng, Mingjing Meng, Zhenhua Du, Haihong Lin, Yongjian Duan, Gangjun Du
Obesity is a risk factor for cancer and cancer-related mortality, however, its role in lung cancer progression remains controversial. This study aimed to assess whether high-fat diet (HFD)-induced obesity promotes lung cancer progression and whether the promotion can be decreased by Kanglaite injection (KLTI). In vivo, HFD-induced overweight or obesity increases the lung carcinoma incidence and multiplicity in a urethane-induced lung carcinogenic model and cancer-related mortality in a LLC allograft model by increasing oxidative stress and cellular signaling molecules including JAK, STAT3, Akt, mTOR, NF-κB and cyclin D1...
August 11, 2016: Oncotarget
Julie Di Cristofaro, Mathieu Pelardy, Anderson Loundou, Agnès Basire, Carine Gomez, Jacques Chiaroni, Pascal Thomas, Martine Reynaud-Gaubert, Christophe Picard
Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E(⁎)01:01 and HLA-E(⁎)01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD)...
2016: Journal of Immunology Research
Paul R Allyn, Erin L Duffy, Romney M Humphries, Patil Injean, S Samuel Weigt, Rajan Saggar, Michael Y Shino, Joseph P Lynch, Abbas Ardehali, Bernard Kubak, Chi-Hong Tseng, John A Belperio, David J Ross, Aric L Gregson
BACKGROUND: Community acquired respiratory virus (CARV) infections occur frequently after lung transplantation and may adversely impact outcomes. We hypothesized that while asymptomatic carriage would not increase the risk of chronic lung allograft dysfunction (CLAD) and graft loss, severe infection would. METHODS: All lung transplant cases between January 2000 and July 2013 performed at our center were reviewed for respiratory viral samples. Each isolation of virus was classified according to clinical level of severity: asymptomatic, symptomatic without pneumonia, and viral pneumonia...
July 27, 2016: Transplantation
Andreas Wallinder, Gerdt C Riise, Sven-Erik Ricksten, Martin Silverborn, Göran Dellgren
BACKGROUND: A large proportion of donor lungs are discarded due to known or presumed organ dysfunction. Ex vivo lung perfusion (EVLP) has proven its value as a tool for discrimination between reversible and irreversible donor lung pathology. However, the long-term outcome after transplantation of lungs after EVLP is essentially unknown. We report short-term and midterm outcomes of recipients who received transplants of EVLP-evaluated lungs. METHODS: Single-center results of recipients of lungs with prior EVLP were compared with consecutive recipients of non-EVLP lungs (controls) during the same period...
May 31, 2016: Journal of Heart and Lung Transplantation
Jérôme Le Pavec, Caroline Suberbielle, Lilia Lamrani, Séverine Feuillet, Laurent Savale, Peter Dorfmüller, François Stephan, Sacha Mussot, Olaf Mercier, Elie Fadel
BACKGROUND: The impact of de-novo donor-specific anti-HLA antibodies (DSA) on patient and graft survival after lung transplantation remains controversial. We analyzed DSA that developed at Day 7 and Month (M) 1, M3, M6 and M12 after lung transplantation and evaluated their impact on chronic lung allograft dysfunction (CLAD) development and survival. METHODS: One hundred thirty-four patients who underwent lung transplantation at our institution between November 2007 and August 2013 were included in this study...
September 2016: Journal of Heart and Lung Transplantation
Sina A Gharib, Jeffery D Edelman, Lingyin Ge, Peter Chen
Acute cellular rejection (ACR) is a common complication in lung transplantation and associated with increased risk of chronic allograft dysfunction. MicroRNAs are critical controllers of cellular transcription whose expression can be altered in disease states. The purpose of this pilot study was to evaluate whether microRNA profiling of epithelial cells obtained from airway brushings can distinguish lung transplant patients with ACR from those without rejection. We studied 21 subjects (10 with ACR, 11 without ACR) and assessed the expression of over 700 microRNAs in their airway epithelium...
November 2015: Transplantation Direct
Stijn E Verleden, Bart M Vanaudenaerde, Robin Vos, Geert M Verleden
Being involved in clinical practice and research concerning chronic lung allograft dysfunction (CLAD) nowadays is an extremely complicated matter. It used to be more simple: When a lung transplant recipient presented with a persistent decline in pulmonary function for which no other cause could be identified, the diagnosis of bronchiolitis obliterans syndrome (BOS) was made. BOS patients were typically obstructive and non-responsive to therapies. Spirometric and pathological findings not consistent with this typical presentation were mostly discarded (1)...
June 15, 2016: American Journal of Transplantation
Pierre-Joseph Royer, Gustavo Olivera-Botello, Angela Koutsokera, John-David Aubert, Eric Bernasconi, Adrien Tissot, Christophe Pison, Laurent Nicod, Jean-Pierre Boissel, Antoine Magnan
Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction...
September 2016: Transplantation
Claudia Del Fante, Luigia Scudeller, Alberto Martinasso, Gianluca Viarengo, Cesare Perotti
BACKGROUND: Extracorporeal photopheresis (ECP) is an effective cell therapy employed in several diseases, including graft versus host disease (GVHD) and organ rejection. When ECP is performed using an off-line technique, mononuclear cell (MNC) collection by leukapheresis is necessary for further manipulation (addition of 8-methoxypsoralen and ultraviolet A irradiation before reinfusion to the patient). We report the results of the first crossover equivalence study on yield and purity of MNCs collected from patients undergoing ECP with two different automated systems: MNC and CMNC (working with intermittent and continuous-flow collection, respectively), released by Terumo BCT...
August 2016: Transfusion
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