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chronic lung allograft dysfunction

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https://www.readbyqxmd.com/read/28090432/update-on-chronic-lung-allograft-dysfunction
#1
Jason M Gauthier, Ramsey R Hachem, Daniel Kreisel
Chronic lung allograft dysfunction (CLAD) encompasses a range of pathologies that cause a transplanted lung to not achieve or maintain normal function. CLAD manifests as airflow restriction and/or obstruction and is predominantly a result of chronic rejection. Three distinct phenotypes of chronic rejection are now recognized: bronchiolitis obliterans, neutrophilic reversible allograft dysfunction, and restrictive allograft syndrome. Recent investigations have revealed that each phenotype has a unique pathology and histopathological findings, suggesting that treatment regimens should be tailored to the underlying etiology...
September 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28078769/interleukin-1%C3%AE-induced-release-of-interleukin-8-by-human-bronchial-epithelial-cells-in-vitro-assessing-mechanisms-and-possible-treatment-options
#2
REVIEW
Hannelore Bellon, Elly Vandermeulen, Carolien Mathyssen, Annelore Sacreas, Stijn E Verleden, Tobias Heigl, Hanne Vriens, Elise Lammertyn, Charles Pilette, Peter Hoet, Robin Vos, Bart M Vanaudenaerde, Geert M Verleden
BACKGROUND: Survival after lung transplantation is hampered by chronic lung allograft dysfunction (CLAD). Persistently elevated BAL-neutrophilia is observed in some patients despite treatment with azithromycin, which may be induced by IL-1α. Our aim is to establish an in vitro model, assess mechanistic pathways and test different therapeutic strategies of IL-1α induced release of IL-8 by human bronchial epithelial cells. METHODS: Bronchial epithelial cells (16HBE) were stimulated with IL-1α with or without azithromycin or dexamethasone...
January 12, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28017335/two-decades-of-lung-retransplantation-a-single-center-experience
#3
David J Hall, Erol V Belli, Jon A Gregg, Juan C Salgado, Maher A Baz, E Denmark Staples, Thomas M Beaver, Tiago N Machuca
BACKGROUND: Lung retransplantation (ReTx) comprises an increasing share of lung transplants and recently has shown improved outcomes. The aim of this study was to identify risk factors affecting overall survival after pulmonary ReTx. METHODS: The United Network for Organ Sharing database was used to identify patients undergoing lung transplantation at our institution from 1995 to 2014. Of the total 542 lung transplants performed, 87 (16.1%) were ReTxs. The primary outcome was overall survival...
December 22, 2016: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28008659/balf-cytokines-in-different-phenotypes-of-chronic-lung-allograft-dysfunction-in-lung-transplant-patients
#4
C Berastegui, S Gómez-Ollés, S Sánchez-Vidaurre, M Culebras, V Monforte, M López-Meseguer, C Bravo, M A Ramon, L Romero, J Sole, M J Cruz, A Román
The long-term success of lung transplantation (LT) is limited by chronic lung allograft dysfunction (CLAD). Different phenotypes of CLAD have been described, such as bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The purpose of this study was to investigate levels of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) as markers of these CLAD phenotypes. BALF was collected from 51 recipients who underwent (bilateral and unilateral) LT. The study population was divided into three groups: stable (ST), BOS, and RAS...
December 23, 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/27982503/t-cells-promote-bronchial-epithelial-cells-secretion-of-matrix-metalloproteinase-9-via-a-c-c-chemokine-receptor-type-2-pathway-implications-for-chronic-lung-allograft-dysfunction
#5
M Pain, P-J Royer, J Loy, A Girardeau, A Tissot, P Lacoste, A Roux, M Reynaud-Gaubert, R Kessler, S Mussot, C Dromer, O Brugière, J-F Mornex, R Guillemain, M Dahan, C Knoop, K Botturi, C Pison, R Danger, S Brouard, A Magnan
Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation (LT). CLAD manifests as Bronchiolitis Obliterans Syndrome (BOS) or Restrictive Allograft Syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity on epithelial cell differentiation. Primary human bronchial epithelial cells (BEC) were treated with activated T cells in the presence or absence of TGF-β...
December 16, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27933655/immunological-diversity-in-phenotypes-of-chronic-lung-allograft-dysfunction-a-comprehensive-immunohistochemical-analysis
#6
Elly Vandermeulen, Elise Lammertyn, Stijn E Verleden, David Ruttens, Hannelore Bellon, Mario Ricciardi, Jana Somers, Ken R Bracke, Kathleen Van Den Eynde, Thomas Tousseyn, Guy G Brusselle, Erik K Verbeken, Johny Verschakelen, Marie-Paule Emonds, Dirk E Van Raemdonck, Geert M Verleden, Robin Vos, Bart M Vanaudenaerde
Chronic rejection after organ transplantation is defined as a humoral- and cell-mediated immune response directed against the allograft. In lung transplantation, chronic rejection is nowadays clinically defined as a cause of chronic lung allograft dysfunction (CLAD), consisting of different clinical phenotypes including restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS). However, the differential role of humoral and cellular immunity is not investigated up to now. Explant lungs of patients with end-stage BOS (n = 19) and RAS (n = 18) were assessed for the presence of lymphoid (B and T cells) and myeloid cells (dendritic cells, eosinophils, mast cells, neutrophils, and macrophages) and compared to nontransplant control lung biopsies (n = 21)...
November 7, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27931084/association-of-higher-cd4-cd25-high-cd127-low-foxp3-and-il-2-t-cell-frequencies-early-after-lung-transplantation-with-less-chronic-lung-allograft-dysfunction-at-two-years
#7
J Salman, F Ius, A-K Knoefel, W Sommer, Th Siemeni, C Kuehn, I Tudorache, M Avsar, T Nakagiri, G Preissler, R Hatz, M Greer, T Welte, A Haverich, G Warnecke
Regulatory T cells (Treg) can regulate alloantigens and may counteract chronic lung allograft dysfunction (CLAD) in lung transplantation. We analyzed Treg in peripheral blood prospectively and correlated percentages of subpopulations with the incidence of CLAD at two years. Among lung-transplanted patients between 01/2009 and 07/2011, only patients with sufficient Treg measurements were included into the study. Tregs were measured immediately before lung transplantation, at 3 weeks and 3, 6, 12 and 24 months after transplantation and were defined as CD4(+) CD25(high) T cells and further analyzed for CTLA4, CD127, FoxP3 and IL-2 expressions...
December 8, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27893614/the-presence-of-pretransplant-hla-antibodies-does-not-impact-the-development-of-chronic-lung-allograft-dysfunction-or-clad-related-death
#8
Oscar E Zazueta, Sara E Preston, Anna Moniodis, Sabrina Fried, Miae Kim, Keri Townsend, Isabelle Wood, Steve Boukedes, Indira Guleria, Phillip Camp, Souheil El-Chemaly, Ivan O Rosas, Anil Chandraker, Edgar Milford, Hilary J Goldberg
BACKGROUND: Development of Donor-specific Antibodies (DSA) after lung transplantation is associated with antibody mediated rejection (AMR), acute cellular rejection, and bronchiolitis obliterans syndrome (BOS); however, the significance of circulating antibodies before transplant remains unclear. METHODS: We performed a retrospective cohort study including recipients of primary lung transplants between 2008 and 2012.We assessed the impact of circulating human leukocyte (HLA) and noncytotoxic Donor Specific antibodies (DSA) detected before transplant on development of Chronic Lung Allograft Dysfunction (CLAD) or CLAD related death...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27878373/restrictive-allograft-syndrome-after-lung-transplantation-new-radiological-insights
#9
Adriana Dubbeldam, Caroline Barthels, Johan Coolen, Johny A Verschakelen, Stijn E Verleden, Robin Vos, Geert M Verleden, Walter De Wever
OBJECTIVES: To describe the CT changes in patients with restrictive allograft syndrome (RAS) after lung transplantation, before and after clinical diagnosis. METHODS: This retrospective study included 22 patients with clinical diagnosis of RAS. Diagnosis was based on a combination of forced expiratory volume (FEV1) decline (≥20 %) and total lung capacity (TLC) decline (≥10 %). All available CT scans after transplantation were analyzed for the appearance and evolution of lung abnormalities...
November 22, 2016: European Radiology
https://www.readbyqxmd.com/read/27873483/successful-lung-transplantation-from-hepatitis-c-positive-donor-to-seronegative-recipient
#10
Basha Khan, Lianne G Singer, Cecilia Chaparro, Tereza Martinu, Stephen Juvet, Mauricio Pipkin, Thomas K Waddell, Shaf Keshavjee, Atul Humar, Marcelo Cypel
Lung Transplantation using RNA+ hepatitis C (HCV+) donors to seronegative recipients is not currently performed due to the very high risk of transmission. Previous reports have shown poor survival when this practice was applied. The emergence of new direct-acting antiviral drugs (DAA) suggests a high chance of sustained virologic response (SVR) in immunocompetent patients. We report here successful transplantation of lungs from HCV+ donor to HCV- recipient. The recipient was an HCV- patient with chronic lung allograft dysfunction (CLAD)...
November 22, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27863518/safety-and-efficacy-of-bridging-to-lung-transplantation-with-antifibrotic-drugs-in-idiopathic-pulmonary-fibrosis-a-case-series
#11
Isabelle Delanote, Wim A Wuyts, Jonas Yserbyt, Eric K Verbeken, Geert M Verleden, Robin Vos
BACKGROUND: Following recent approval of pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF), questions arise about the use of these antifibrotics in patients awaiting lung transplantation (LTx). METHODS: Safety and efficacy of antifibrotic drugs in IPF patients undergoing LTx were investigated in a single-centre retrospective cohort analysis. RESULTS: A total of nine patients, receiving antifibrotic therapy for 419 ± 315 days until subsequent LTx, were included...
November 18, 2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27837271/airway-remodelling-in-the-transplanted-lung
#12
REVIEW
Mark Kuehnel, Lavinia Maegel, Jens Vogel-Claussen, Jan Lukas Robertus, Danny Jonigk
Following lung transplantation, fibrotic remodelling of the small airways has been recognized for almost 5 decades as the main correlate of chronic graft failure and a major obstacle to long-term survival. Mainly due to airway fibrosis, pulmonary allografts currently show the highest attrition rate of all solid organ transplants, with a 5-year survival rate of 58 % on a worldwide scale. The observation that these morphological changes are not just the hallmark of chronic rejection but rather represent a manifestation of a multitude of alloimmune-dependent and -independent injuries was made more recently, as was the discovery that chronic lung allograft dysfunction manifests in different clinical phenotypes of respiratory impairment and corresponding morphological subentities...
November 12, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27836956/an-association-of-particulate-air-pollution-and-traffic-exposure-with-mortality-after-lung-transplantation-in-europe
#13
David Ruttens, Stijn E Verleden, Esmée M Bijnens, Ellen Winckelmans, Jens Gottlieb, Gregor Warnecke, Federica Meloni, Monica Morosini, Wim Van Der Bij, Erik A Verschuuren, Urte Sommerwerck, Gerhard Weinreich, Markus Kamler, Antonio Roman, Susana Gomez-Olles, Cristina Berastegui, Christian Benden, Are Martin Holm, Martin Iversen, Hans Henrik Schultz, Bart Luijk, Erik-Jan Oudijk, Johanna M Kwakkel-van Erp, Peter Jaksch, Walter Klepetko, Nikolaus Kneidinger, Claus Neurohr, Paul Corris, Andrew J Fisher, James Lordan, Gerard Meachery, Davide Piloni, Elly Vandermeulen, Hannelore Bellon, Barbara Hoffmann, Danielle Vienneau, Gerard Hoek, Kees de Hoogh, Benoit Nemery, Geert M Verleden, Robin Vos, Tim S Nawrot, Bart M Vanaudenaerde
Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies.13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10 µm (PM10) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway...
November 11, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/27819763/diagnosis-of-acute-cellular-rejection-and-antibody-mediated-rejection-on-lung-transplant-biopsies-a-perspective-from-members-of-the-pulmonary-pathology-society
#14
Anja C Roden, Dara L Aisner, Timothy C Allen, Marie Christine Aubry, Roberto J Barrios, Mary B Beasley, Philip T Cagle, Vera L Capelozzi, Sanja Dacic, Yimin Ge, Lida P Hariri, Sylvie Lantuejoul, Ross A Miller, Mari Mino-Kenudson, Andre L Moreira, Kirtee Raparia, Natasha Rekhtman, Lynette Sholl, Maxwell L Smith, Ming S Tsao, Marina Vivero, Yasushi Yatabe, Eunhee S Yi
CONTEXT: - The diagnosis and grading of acute cellular and antibody-mediated rejection (AMR) in lung allograft biopsies is important because rejection can lead to acute graft dysfunction and/or failure and may contribute to chronic graft failure. While acute cellular rejection is well defined histologically, no reproducible specific features of AMR are currently identified. Therefore, a combination of clinical features, serology, histopathology, and immunologic findings is suggested for the diagnosis of AMR...
November 7, 2016: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/27816902/aspergillus-related-pulmonary-diseases-in-lung-transplantation
#15
S Pasupneti, O Manouvakhova, M R Nicolls, J L Hsu
While lung transplantation is an attractive treatment option for many end stage lung diseases, the relatively high 5-year mortality continues to be a significant limiting factor. Among the foremost reasons for this is the eventual development of obstructive chronic lung allograft dysfunction. Infections, which the lung allograft is especially prone to, are a major risk factor. Specifically, the Aspergillus species cause a higher burden of disease among lung transplant recipients, due to unique risk factors, such as relative hypoxemia...
January 1, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/27737799/the-role-of-recipient-derived-interleukin-17a-in-a-murine-orthotopic-lung-transplant-model-of-restrictive-chronic-lung-allograft-dysfunction
#16
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 CB57BL/6, IL-17 WT and IL-17 KO mice...
November 2016: Transplant Immunology
https://www.readbyqxmd.com/read/27713201/-fatal-respiratory-failure-developed-during-chemotherapy-for-diffuse-large-b-cell-lymphoma-that-occurred-late-after-lung-transplantation
#17
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
https://www.readbyqxmd.com/read/27713199/-development-of-personalized-and-targeted-preventive-therapies-for-chronic-lung-allograft-dysfunction-subtypes-a-novel-strategy
#18
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
https://www.readbyqxmd.com/read/27713198/-the-history-and-development-of-experimental-rodent-models-of-chronic-lung-allograft-dysfunction-after-lung-transplantation
#19
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
https://www.readbyqxmd.com/read/27713193/-prevention-and-treatment-strategy-for-infectious-complication-after-lung-transplantation
#20
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
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