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chronic lung allograft dysfunction

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https://www.readbyqxmd.com/read/28207638/association-of-local-intrapulmonary-production-of-antibodies-specific-to-donor-major-histocompatibility-complex-class-i-with-the-progression-of-chronic-rejection-of-lung-allografts
#1
Ei Miyamoto, Hideki Motoyama, Masaaki Sato, Akihiro Aoyama, Toshi Menju, Kei Shikuma, Terumasa Sowa, Akihiko Yoshizawa, Masao Saito, Akihiro Takahagi, Satona Tanaka, Mamoru Takahashi, Keiji Ohata, Takeshi Kondo, Kyoko Hijiya, Toyofumi F Chen-Yoshikawa, Hiroshi Date
BACKGROUND: Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. METHODS: Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28186707/mesenchymal-stromal-cell-therapy-for-chronic-lung-allograft-dysfunction-results-of-a-first-in-man-study
#2
Daniel C Chambers, Debra Enever, Sharon Lawrence, Marian J Sturm, Richard Herrmann, Stephanie Yerkovich, Michael Musk, Peter M A Hopkins
Chronic lung transplant rejection (termed chronic lung allograft dysfunction [CLAD]) is the main impediment to long-term survival after lung transplantation. Bone marrow-derived mesenchymal stromal cells (MSCs) represent an attractive cell therapy in inflammatory diseases, including organ rejection, given their relative immune privilege and immunosuppressive and tolerogenic properties. Preclinical studies in models of obliterative bronchiolitis and human trials in graft versus host disease and renal transplantation suggest potential efficacy in CLAD...
February 1, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28185711/impact-of-gastroesophageal-reflux-and-delayed-gastric-emptying-on-pediatric-lung-transplant-outcomes
#3
Fei Jamie Dy, Dawn Freiberger, Enju Liu, Debra Boyer, Gary Visner, Rachel Rosen
BACKGROUND: Gastroesophageal reflux disease is thought to predispose to adverse lung allograft outcomes. However, little is known about the burden of gastroesophageal reflux (GER) and gastroparesis in pediatric patients. In this study we describe the burden of reflux and gastroparesis in children undergoing lung transplant, and evaluates their impact on allograft survival and rejection incidence. METHODS: This study is a retrospective analysis of pediatric lung transplant recipients who had combined pH and multichannel intraluminal impedance testing (pH-MII) and gastric-emptying scans (GES)...
January 6, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28164137/immune-responses-to-tissue-restricted-nonmajor-histocompatibility-complex-antigens-in-allograft-rejection
#4
REVIEW
Ankit Bharat, T Mohanakumar
Chronic diseases that result in end-stage organ damage cause inflammation, which can reveal sequestered self-antigens (SAgs) in that organ and trigger autoimmunity. The thymus gland deletes self-reactive T-cells against ubiquitously expressed SAgs, while regulatory mechanisms in the periphery control immune responses to tissue-restricted SAgs. It is now established that T-cells reactive to SAgs present in certain organs (e.g., lungs, pancreas, and intestine) are incompletely eliminated, and the dysregulation of peripheral immuneregulation can generate immune responses to SAgs...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28138398/comparative-analysis-of-morphological-and-molecular-motifs-in-bronchiolitis-obliterans-and-alveolar-fibroelastosis-after-lung-and-stem-cell-transplantation
#5
Danny Jonigk, Berenice Rath, Paul Borchert, Peter Braubach, Lavinia Maegel, Nicole Izykowski, Gregor Warnecke, Wiebke Sommer, Hans Kreipe, Robert Blach, Adrian Anklamm, Axel Haverich, Matthias Eder, Michael Stadler, Tobias Welte, Jens Gottlieb, Mark Kuehnel, Florian Laenger
Chronic lung allograft dysfunction (CLAD) remains the major obstacle to long-term survival following lung transplantation (LuTx). Morphologically CLAD is defined by obliterative remodelling of the small airways (bronchiolitis obliterans, BO) as well as a more recently described collagenous obliteration of alveoli with elastosis summarised as alveolar fibroelastosis (AFE). Both patterns are not restricted to pulmonary allografts, but have also been reported following haematopoietic stem cell transplantation (HSCT) and radio chemotherapy (RC)...
January 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28120410/restrictive-allograft-syndrome-and-idiopathic-pleuroparenchymal-fibroelastosis-do-they-really-have-the-same-histology
#6
M Angeles Montero, Tina Osadolor, Reena Khiroya, M Teresa Salcedo, Jan Lukas Robertus, Alexandra Rice, Andrew G Nicholson, Antonio Roman, Victor Monforte
AIMS: Restrictive Allograft Syndrome (RAS) and idiopathic pleuroparenchymal fibroelastosis (IPPFE) are two different diseases reported to share the same histology. RAS relates to chronic allograft dysfunction in lung transplantation with IPPFE being a rare condition in native lungs. Our aim is to compare their histologies, alongside biopsies of usual interstitial pneumonia (UIP), to determine if there are differences that might help to elucidate the pathogenesis. METHODS AND RESULTS: We selected 4 post-mortem allograft lungs from patients who developed clear clinical RAS pattern, 5 biopsies diagnosed as IPPFE, 5 UIP biopsies and 5 sections of normal lung...
January 25, 2017: Histopathology
https://www.readbyqxmd.com/read/28103284/gene-expression-profiling-of-bronchoalveolar-lavage-cells-preceding-a-clinical-diagnosis-of-chronic-lung-allograft-dysfunction
#7
S Samuel Weigt, Xiaoyan Wang, Vyacheslav Palchevskiy, Aric L Gregson, Naman Patel, Ariss DerHovanessian, Michael Y Shino, David M Sayah, Shirin Birjandi, Joseph P Lynch, Rajan Saggar, Abbas Ardehali, David J Ross, Scott M Palmer, David Elashoff, John A Belperio
BACKGROUND: Chronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects. METHODS: In a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n = 9) and CLAD free (n = 8) lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy...
2017: PloS One
https://www.readbyqxmd.com/read/28101803/lung-retransplantation-in-an-adult-13%C3%A2-years-after-single-lobar-transplant-in-childhood
#8
Seiichiro Sugimoto, Shinji Otani, Takashi Ohki, Takeshi Kurosaki, Kentaroh Miyoshi, Masaomi Yamane, Shinichiro Miyoshi, Takahiro Oto
Single living-donor lobar lung transplantation provides acceptable results for critically ill children; however, an additional lung transplantation may be required in the future as the recipient grows. We describe a case of successful lung retransplantation in a grown-up patient after single lobar lung transplantation in childhood. A 23-year-old man underwent bilateral cadaveric lung retransplantation for chronic lung allograft dysfunction 13 years after right single living-donor lobar transplantation for idiopathic pulmonary arterial hypertension performed at the age of 10 years...
January 18, 2017: General Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28100545/chronic-effects-of-air-pollution-on-lung-function-after-lung-transplantation-in-the-systems-prediction-of-chronic-lung-allograft-dysfunction-sysclad-study
#9
Meriem Benmerad, Rémy Slama, Karine Botturi, Johanna Claustre, Antoine Roux, Edouard Sage, Martine Reynaud-Gaubert, Carine Gomez, Romain Kessler, Olivier Brugière, Jean-François Mornex, Sacha Mussot, Marcel Dahan, Véronique Boussaud, Isabelle Danner-Boucher, Claire Dromer, Christiane Knoop, Annick Auffray, Johanna Lepeule, Laure Malherbe, Frederik Meleux, Laurent Nicod, Antoine Magnan, Christophe Pison, Valérie Siroux
An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs).The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6 months. The levels of air pollutants (nitrogen dioxide (NO2), particulate matter with an aerodynamic cut-off diameter of x µm (PMx) and ozone (O3)) at the patients' home address were averaged in the 12 months before each spirometry test...
January 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28100499/gremlin1-plays-a-key-role-in-kidney-development-and-renal-fibrosis
#10
Rachel H Church, Imran Ali, Mitchel Tate, Deborah Lavin, Arjun Krishnakumar, Helena M Kok, Roel Goldschmeding, Finian Martin, Derek Brazil
Grem1, an antagonist of bone morphogenetic proteins, plays a key role in embryogenesis. A highly specific temporospatial gradient of Grem1 and BMP signalling is critical to normal lung, kidney and limb development. Grem1 levels are increased in renal fibrotic conditions including acute kidney injury, diabetic nephropathy, chronic allograft nephropathy and immune glomerulonephritis. A small number of grem1-/- whole body knockout mice on a mixed genetic background (8 %) are viable, with a single, enlarged left kidney and grossly normal histology...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28090432/update-on-chronic-lung-allograft-dysfunction
#11
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
#12
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
#13
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
#14
Cristina Berastegui, Susana Gómez-Ollés, Sara Sánchez-Vidaurre, Mario Culebras, Victor Monforte, Manuel López-Meseguer, Carlos Bravo, Maria-Antonia Ramon, Laura Romero, Joan Sole, Maria-Jesus Cruz, Antonio 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 the 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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