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Sample records for lung transplantation incidence

  1. Lung Transplant

    MedlinePlus

    ... the NHLBI on Twitter. What Is a Lung Transplant? A lung transplant is surgery to remove a person's diseased lung ... a healthy lung from a deceased donor. Lung transplants are used for people who are likely to ...

  2. Lung transplantation

    PubMed Central

    2013-01-01

    Lung transplantation may be the only intervention that can prolong survival and improve quality of life for those individuals with advanced lung disease who are acceptable candidates for the procedure. However, these candidates may be extremely ill and require ventilator and/or circulatory support as a bridge to transplantation, and lung transplantation recipients are at risk of numerous post-transplant complications that include surgical complications, primary graft dysfunction, acute rejection, opportunistic infection, and chronic lung allograft dysfunction (CLAD), which may be caused by chronic rejection. Many advances in pre- and post-transplant management have led to improved outcomes over the past decade. These include the creation of sound guidelines for candidate selection, improved surgical techniques, advances in donor lung preservation, an improving ability to suppress and treat allograft rejection, the development of prophylaxis protocols to decrease the incidence of opportunistic infection, more effective therapies for treating infectious complications, and the development of novel therapies to treat and manage CLAD. A major obstacle to prolonged survival beyond the early post-operative time period is the development of bronchiolitis obliterans syndrome (BOS), which is the most common form of CLAD. This manuscript discusses recent and evolving advances in the field of lung transplantation. PMID:23710330

  3. Lung transplant

    MedlinePlus

    ... nih.gov/pubmed/20675678 . Kotloff RM, Keshavjee S. Lung transplantation. In: Broaddus VC, Mason RJ, Ernst MD, et ... 58. Solomon M, Grasemann H, Keshavjee S. Pediatric lung transplantation. Pediatr Clin North Am . 2010; 57(2):375- ...

  4. Lung transplantation

    PubMed Central

    Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

  5. Lung transplant

    MedlinePlus

    ... diseases that may require a lung transplant are: Cystic fibrosis Damage to the arteries of the lung because ... BC; Clinical Practice Guidelines for Pulmonary Therapies Committee; ... Therapies Committee. Cystic fibrosis pulmonary guidelines: ...

  6. Lung Transplantation

    MedlinePlus

    ... years. Their conditions are so severe that other treatments, such as medicines or breathing devices, no longer work. Lung transplants most often are used to treat people who have severe COPD Cystic fibrosis Idiopathic pulmonary fibrosis Alpha-1 antitrypsin deficiency Pulmonary ...

  7. Who Needs a Lung Transplant?

    MedlinePlus

    ... from the NHLBI on Twitter. Who Needs a Lung Transplant? Your doctor may recommend a lung transplant ... lungs to pick up oxygen. Applying to a Lung Transplant Program Lung transplants are done in medical ...

  8. Lung transplantation at Duke

    PubMed Central

    Gray, Alice L.; Hartwig, Matthew G.

    2016-01-01

    Lung transplantation represents the gold-standard therapy for patients with end-stage lung disease. Utilization of this therapy continues to rise. The Lung Transplant Program at Duke University Medical Center was established in 1992, and since that time has grown to one of the highest volume centers in the world. The program to date has performed over 1,600 lung transplants. This report represents an up-to-date review of the practice and management strategies employed for safe and effective lung transplantation at our center. Specific attention is paid to the evaluation of candidacy for lung transplantation, donor selection, surgical approach, and postoperative management. These evidence-based strategies form the foundation of the clinical transplantation program at Duke. PMID:27076968

  9. Immunosuppression for lung transplantation

    PubMed Central

    Ng, Choo Y.; Madsen, Joren C.; Rosengard, Bruce R.; Allan, James S.

    2010-01-01

    1. ABSTRACT As a result of advances in surgical techniques, immunosuppressive therapy, and postoperative management, lung transplantation has become an established therapeutic option for individuals with a variety of end-stage lung diseases. The current 1-year actuarial survival rate following lung transplantation is approaching 80%. However, the 5- year actuarial survival rate has remained virtually unchanged at approximately 50% over the last 15 years due to the processes of acute and chronic lung allograft rejection (1). Clinicians still rely on a vast array of immunosuppressive agents to suppress the process of graft rejection, but find themselves limited by an inescapable therapeutic paradox. Insufficient immunosuppression results in graft loss due to rejection, while excess immunosuppression results in increased morbidity and mortality from opportunistic infections and malignancies. Indeed, graft rejection, infection, and malignancy are the three principal causes of mortality for the lung transplant recipient. One should also keep in mind that graft loss in a lung transplant recipient is usually a fatal event, since there is no practical means of long-term mechanical support, and since the prospects of re-transplantation are low, given the shortage of acceptable donor grafts. This chapter reviews the current state of immunosuppressive therapy for lung transplantation and suggests alternative paradigms for the management of future lung transplant recipients. PMID:19273152

  10. Xenogeneic lung transplantation models

    PubMed Central

    Burdorf, Lars; Azimzadeh, Agnes M.; Pierson, Richard N.

    2014-01-01

    Summary Study of lung xenografts has proven useful to understand the remaining barriers to successful transplantation of other organ xenografts. In this chapter, the history and current status of lung xenotransplantation will be briefly reviewed and two different experimental models, the ex vivo porcine-to-human lung perfusion and the in vivo xenogeneic lung transplantation, will be presented. We will focus on the technical details of these lung xenograft models in sufficient detail, list the needed materials and mention analysis techniques to allow others to adopt them with minimal learning curve. PMID:22565996

  11. Overview of Clinical Lung Transplantation

    PubMed Central

    Yeung, Jonathan C.; Keshavjee, Shaf

    2014-01-01

    Since the first successful lung transplant 30 years ago, lung transplantation has rapidly become an established standard of care to treat end-stage lung disease in selected patients. Advances in lung preservation, surgical technique, and immunosuppression regimens have resulted in the routine performance of lung transplantation around the world for an increasing number of patients, with wider indications. Despite this, donor shortages and chronic lung allograft dysfunction continue to prevent lung transplantation from reaching its full potential. With research into the underlying mechanisms of acute and chronic lung graft dysfunction and advances in personalized diagnostic and therapeutic approaches to both the donor lung and the lung transplant recipient, there is increasing confidence that we will improve short- and long-term outcomes in the near future. PMID:24384816

  12. What Are the Risks of Lung Transplant?

    MedlinePlus

    ... NHLBI on Twitter. What Are the Risks of Lung Transplant? A lung transplant can improve your quality of life and ... highest. In recent years, short-term survival after lung transplant has improved. Recent data on single-lung ...

  13. Heart-lung transplant - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100147.htm Heart-lung transplant - series To use the sharing features on this ... A.M. Editorial team. Related MedlinePlus Health Topics Heart Transplantation Lung Transplantation A.D.A.M., Inc. is ...

  14. Lung Transplantation for Cystic Fibrosis

    PubMed Central

    Adler, Frederick R.; Aurora, Paul; Barker, David H.; Barr, Mark L.; Blackwell, Laura S.; Bosma, Otto H.; Brown, Samuel; Cox, D. R.; Jensen, Judy L.; Kurland, Geoffrey; Nossent, George D.; Quittner, Alexandra L.; Robinson, Walter M.; Romero, Sandy L.; Spencer, Helen; Sweet, Stuart C.; van der Bij, Wim; Vermeulen, J.; Verschuuren, Erik A. M.; Vrijlandt, Elianne J. L. E.; Walsh, William; Woo, Marlyn S.; Liou, Theodore G.

    2009-01-01

    Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing and transplantation on the patient's quality of life. Although recent population-based analyses of the US lung allocation system for the CF population have raised controversies about the survival benefits of transplantation, studies from the United Kingdom and Canada have suggested a definite survival advantage for those receiving transplants. In response to these and other controversies, leaders in transplantation and CF met together in Lansdowne, Virginia, to consider the state of the art in lung transplantation for CF in an international context, focusing on advances in surgical technique, measurement of outcomes, use of prognostic criteria, variations in local control over listing, and prioritization among the United States, Canada, the United Kingdom, and The Netherlands, patient adherence before and after transplantation and other issues in the broader context of lung transplantation. Finally, the conference members carefully considered how efforts to improve outcomes for lung transplantation for CF lung disease might best be studied. This Roundtable seeks to communicate the substance of our discussions. PMID:20008865

  15. What to Expect During a Lung Transplant

    MedlinePlus

    ... NHLBI on Twitter. What To Expect During a Lung Transplant Just before lung transplant surgery, you will ... airway and its blood vessels to your heart. Lung Transplant The illustration shows the process of a ...

  16. Heart-lung transplant - series (image)

    MedlinePlus

    A combined heart-lung transplant may be recommended for patients who have both cardiac and lung disease. The most common reasons for a combined heart-lung transplant are pulmonary hypertension, cystic fibrosis, ...

  17. Physical therapy in lung transplantation.

    PubMed

    Downs, A M

    1996-06-01

    Lung transplantation requires the skillful attention of a health care team to provide optimal results. The physical therapist is an integral part of this team, providing expertise in exercise testing and prescription in all phases, from initial evaluation through postoperative rehabilitation and beyond. In addition, the physical therapist promotes effective ventilation, offers techniques for enhanced coughing and mucociliary clearance, and provides treatment of the musculoskeletal system. Lung transplantation is reserved for patients in whom all other treatments have been exhausted. It is important for the physical therapist to stay abreast of the evolving field of lung transplantation, including medications and complications. The physical therapist has a critical role in helping lung transplant recipients achieve optimal function, increased survival, and improved quality of life. PMID:8650277

  18. Evolving practice: X-linked agammaglobulinemia and lung transplantation.

    PubMed

    Barnes, S; Kotecha, S; Douglass, J A; Paul, E; Hore-Lacey, F; Stirling, R; Snell, G I; Westall, G P

    2015-04-01

    X-linked agammaglobulinemia (XLA) is a rare primary humoral immunodeficiency syndrome characterized by agammaglobulinemia, recurrent infections and bronchiectasis. Despite the association with end-stage bronchiectasis, the literature on XLA and lung transplantation is extremely limited. We report a series of 6 XLA patients with bronchiectasis who underwent lung transplantation. Short-term outcomes were excellent however long-term outcomes were disappointing with a high incidence of pulmonary sepsis and chronic lung allograft dysfunction (CLAD). PMID:25736826

  19. What To Expect Before a Lung Transplant

    MedlinePlus

    ... NHLBI on Twitter. What To Expect Before a Lung Transplant If you get into a medical center's ... friends also can offer support. When a Donor Lung Becomes Available OPTN matches donor lungs to recipients ...

  20. Bioengineering Lungs for Transplantation.

    PubMed

    Gilpin, Sarah E; Charest, Jonathan M; Ren, Xi; Ott, Harald C

    2016-05-01

    Whole lung extracellular matrix scaffolds can be created by perfusion of cadaveric organs with decellularizing detergents, providing a platform for organ regeneration. Lung epithelial engineering must address both the proximal airway cells that function to metabolize toxins and aid mucociliary clearance and the distal pneumocytes that facilitate gas exchange. Engineered pulmonary vasculature must support in vivo blood perfusion with low resistance and intact barrier function and be antithrombotic. Repopulating the native lung matrix with sufficient cell numbers in appropriate anatomic locations is required to enable organ function. PMID:27112255

  1. Pediatric lung transplantation: 10 years of experience

    PubMed Central

    Camargo, Priscila C. L. B.; Pato, Eduardo Z. S.; Campos, Silvia V.; Afonso, José E.; Carraro, Rafael M.; Costa, André N.; Teixeira, Ricardo H. O. B.; Samano, Marcos N.; Pêgo-Fernandes, Paulo M.

    2014-01-01

    Lung transplantation is a well-established treatment for advanced lung diseases. In children, the diseases that most commonly lead to the need for a transplantation are cystic fibrosis, pulmonary hypertension, and bronchiolitis. However, the number of pediatric lung transplantations being performed is low compared with the number of transplants performed in the adult age group. The objective of this study was to demonstrate our experience with pediatric lung transplants over a 10-year period in a program initially designed for adults. PMID:24860860

  2. Antibody-Mediated Lung Transplant Rejection

    PubMed Central

    Hachem, Ramsey

    2012-01-01

    Antibody-mediated rejection after lung transplantation remains enigmatic. However, emerging evidence over the past several years suggests that humoral immunity plays an important role in allograft rejection. Indeed, the development of donor-specific antibodies after transplantation has been identified as an independent risk factor for acute cellular rejection and bronchiolitis obliterans syndrome. Furthermore, cases of acute antibody-mediated rejection resulting in severe allograft dysfunction have been reported, and these demonstrate that antibodies can directly injure the allograft. However, the incidence and toll of antibody-mediated rejection are unknown because there is no widely accepted definition and some cases may be unrecognized. Clearly, humoral immunity has become an important area for research and clinical investigation. PMID:23002428

  3. Paraquat Poisoning—Lung Transplantation

    PubMed Central

    Matthew, Henry; Logan, Andrew; Woodruff, M. F. A.; Heard, Brian

    1968-01-01

    A 15-year-old boy ingested a mouthful of paraquat and developed severe respiratory distress. Treatment included the transplantation of one lung, but subsequently changes developed in the graft which are thought to have been due to paraquat, and the patient died two weeks after the operation The dangers of keeping poisonous substances in incorrectly labelled bottles has once again been demonstrated, while the pattern of paraquat poisoning, especially the development of proliferative alveolitis and terminal bronchiolitis, is confirmed. Immediate forced diuresis followed by haemodialysis is necessary to remove paraquat, thereby perhaps avoiding initiation of the changes in the lungs. The technical feasibility of human lung transplantation has again been demonstrated. It has also been shown that infection does not necessarily pose an insuperable problem, at any rate if, as in the case described, there was no preoperative pulmonary infection in either recipient or donor. ImagesFig. 1Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5-8Fig. 9-12Fig. 13Fig. 14Fig. 15-16Fig. 16 PMID:4877735

  4. Translational Insights on Lung Transplantation: Learning from Immunology.

    PubMed

    Mohamed, Mohamed Shehata Ali

    2015-09-01

    The introduction of ex vivo lung perfusion (EVLP) in the practice of lung transplantation has allowed the reconditioning of the marginal grafts and their conversion into transplantable grafts. In addition, EVLP can provide a platform for the application of various preventive measures to decrease the incidence of post-transplant complications. While the Toronto team targets the attenuation of the cytokine production within the graft through gene therapy to up-regulate IL-10, other measures could be applied to achieve significant attenuation of the cytokine load of the graft. This manuscript provides a short overview on the importance of the attenuation of the cytokine production within the transplanted lung grafts and some possible strategies to achieve this goal. PMID:26412634

  5. Longitudinal Analysis of the Lung Microbiome in Lung Transplantation

    PubMed Central

    Borewicz, Klaudyna; Pragman, Alexa A.; Kim, Hyeun Bum; Hertz, Marshall; Wendt, Christine; Isaacson, Richard E.

    2012-01-01

    Lung transplant recipients experience poor long-term survival, largely due to chronic rejection. The pathogenesis of chronic rejection is incompletely understood, but bacterial colonization of the lung is associated with chronic rejection, while antibiotic use slows its progression. The lung harbors a bacterial community, termed the microbiome, which is present both in health and disease. We hypothesize that the lung microbiome will change following transplantation, and these changes may correspond to the development of rejection. Twelve bronchoalveolar lavage fluid (BALF) samples were obtained from four patients at three time points after transplantation and two BALF samples were obtained from healthy, non-transplant controls. The microbiome of each sample was determined by pyrosequencing the 16S rDNA hypervariable 3 region. The data were analyzed using mothur, Ribosomal Database Project Classifier, Fast UniFrac, and Metastats. Transplanted lungs contained more bacterial sequences and demonstrated more microbial diversity than did control lungs. Bacteria in the phyla Proteobacteria (class Betaproteobacteria) predominated in the transplant samples. In contrast, the microbiome of the healthy lung consisted of the phyla Proteobacteria (class Gammaproteobacteria) and Firmicutes. The microbiome of the transplanted lung is vastly different from that of healthy lungs, mainly due to the presence of the family Burkholderiaceae in transplant samples. PMID:23173619

  6. Surgical treatment of pulmonary hypertension: Lung transplantation

    PubMed Central

    Long, Jason; Russo, Mark J.; Muller, Charlie; Vigneswaran, Wickii T.

    2011-01-01

    Pulmonary hypertension (PH) is a serious and progressive disorder that results in right ventricular dysfunction that lead to subsequent right heart failure and death. When untreated the median survival for these patients is 2.8 years. Over the past decade advances in disease specific medical therapy considerably changed the natural history. This is reflected in a threefold decrease in the number of patients undergoing lung transplantation for PH which used to be main stay of treatment. Despite the successful development of medical therapy lung transplant still remains the gold standard for patients who fail medical therapy. Referral for lung transplant is recommended when patients have a less than 2-3 years of predicted survival or in NYHA class III or IV. Both single and bilateral lung transplants have been successfully performed for PH but outcome analyses and survival comparisons generally favor a bilateral lung transplant. PMID:22140622

  7. Lung Transplantation for Lymphangioleiomyomatosis in Japan

    PubMed Central

    Ando, Katsutoshi; Okada, Yoshinori; Akiba, Miki; Kondo, Takashi; Kawamura, Tomohiro; Okumura, Meinoshin; Chen, Fengshi; Date, Hiroshi; Shiraishi, Takeshi; Iwasaki, Akinori; Yamasaki, Naoya; Nagayasu, Takeshi; Chida, Masayuki; Inoue, Yoshikazu; Hirai, Toyohiro; Seyama, Kuniaki; Mishima, Michiaki

    2016-01-01

    Background Lung transplantation has been established as the definitive treatment option for patients with advanced lymphangioleiomyomatosis (LAM). However, the prognosis after registration and the circumstances of lung transplantation with sirolimus therapy have never been reported. Methods In this national survey, we analyzed data from 98 LAM patients registered for lung transplantation in the Japan Organ Transplantation Network. Results Transplantation was performed in 57 patients as of March 2014. Survival rate was 86.7% at 1 year, 82.5% at 3 years, 73.7% at 5 years, and 73.7% at 10 years. Of the 98 patients, 21 had an inactive status and received sirolimus more frequently than those with an active history (67% vs. 5%, p<0.001). Nine of twelve patients who remained inactive as of March 2014 initiated sirolimus before or while on a waiting list, and remained on sirolimus thereafter. Although the statistical analysis showed no statistically significant difference, the survival rate after registration tended to be better for lung transplant recipients than for those who awaited transplantation (p = 0.053). Conclusions Lung transplantation is a satisfactory therapeutic option for advanced LAM, but the circumstances for pre-transplantation LAM patients are likely to alter with the use of sirolimus. PMID:26771878

  8. Lung cancer treatment outcomes in recipients of lung transplant

    PubMed Central

    Du, Lingling; Pennell, Nathan A.; Elson, Paul

    2015-01-01

    Background Lung transplant recipients develop lung cancer more commonly than the general population. The best treatment approach for these patients is unclear. The goal of this study is to evaluate treatment outcomes in this population. Methods We used the Cleveland Clinic lung transplant database to identify patients diagnosed with lung cancer at the time of or after lung transplant. Transplant and lung cancer-related data were retrospectively reviewed. Results Among 847 patients underwent lung transplant between 2005 and 2013, 17 (2%) were diagnosed with lung cancer and included. Median age was 61 (range, 48–70) years. Majority were stage I/II (n=11), one had stage IIIA, five had stage IV. Non-small cell lung cancer (NSCLC) were more common than small cell lung cancer (SCLC) (n=15 vs. 2). Curative treatment was performed as lobectomy in native lung (n=1), and radiation in transplanted lung (n=2). Chemotherapy was given in 10 patients, primarily carboplatin-based doublets with docetaxel, pemetrexed, or etoposide. Six of these received palliative chemotherapy for either metastases at diagnosis (n=3) or recurrence after early stage disease (n=3). Except for one patient with complete response, all others had progressive disease following palliative chemotherapy. Overall, patients who received chemotherapy had a median survival of 7.5 months from the initiation of chemotherapy, but 30% developed grade 5 sepsis. Median survival for stage I–IIIA and stage IV were 23.2 and 2.5 months respectively. Conclusions Lung cancer in lung transplant recipients carries various clinical courses. Patients with metastatic disease have substantial toxicities from chemotherapy and poor survival. Early stage patients should be offered treatment with modified dosages to decrease the risk of severe toxicities. PMID:26798588

  9. Airway anastomosis for lung transplantation

    PubMed Central

    Diso, Daniele; Rendina, Erino Angelo; Venuta, Federico

    2016-01-01

    Lung transplantation (LT) is the only viable option for a selected group of patients with end stage pulmonary diseases. During the recent years satisfactory results in terms of long-term survival and quality of life have been achieved with improvements in surgical technique, immunosuppression and perioperative management. Since the beginning, the airway anastomosis has been considered crucial and significant efforts have been made to understand the healing process. A number of experimental studies allowed improving the surgical technique by modifying the technique of suturing, the anastomotic protection and type and dose of immunosuppression, reducing the risk of airway complications. Furthermore, a huge progress has been made in the management of such complications. Early diagnosis of bronchial complications and their prompt and correct management are crucial to achieve long-term survival. PMID:26981271

  10. Comorbidities impacting on prognosis after lung transplant.

    PubMed

    Vaquero Barrios, José Manuel; Redel Montero, Javier; Santos Luna, Francisco

    2014-01-01

    The aim of this review is to give an overview of the clinical circumstances presenting before lung transplant that may have negative repercussions on the long and short-term prognosis of the transplant. Methods for screening and diagnosis of common comorbidities with negative impact on the prognosis of the transplant are proposed, both for pulmonary and extrapulmonary diseases, and measures aimed at correcting these factors are discussed. Coordination and information exchange between referral centers and transplant centers would allow these comorbidities to be detected and corrected, with the aim of minimizing the risks and improving the life expectancy of transplant receivers. PMID:24355755

  11. Leukocyte filtration in lung transplantation.

    PubMed

    Kurusz, Mark; Roach, John D; Vertrees, Roger A; Girouard, Mark K; Lick, Scott D

    2002-05-01

    Controlled reperfusion of the transplanted lung has been used in nine consecutive patients to decrease manifestations of lung reperfusion injury. An extracorporeal circuit containing a roller pump, heat exchanger and leukodepleting filter is primed with substrate-enhanced reperfusion solution mixed with approximately 2000 ml of the patient's blood. This solution is slowly recirculated to remove leukocytes prior to reperfusion. When the pulmonary anastomoses are completed, the pulmonary artery is cannulated through the untied anastomosis using a catheter containing a pressure lumen for measurement of infusion pressure. An atrial clamp is left in place on the patient's native atrial cuff to decrease the risk of systemic air embolism during the brief period of reperfusion from the extracorporeal reservoir. During reperfusion, the water bath to the heat exchanger is kept at 35 degrees C and the flow rate for reperfusion solution is between 150 and 200 m/min, keeping the pulmonary artery pressure <14 mmHg. Eight of nine patients were ventilated on 40% inspired oxygen within a few hours of operation and 7/9 were extubated on or before postoperative day 1. Six of nine patients are long-term survivors. PMID:12009087

  12. Obliterative airway remodelling in transplanted and non-transplanted lungs.

    PubMed

    Jonigk, Danny; Theophile, Katharina; Hussein, Kais; Bock, Oliver; Lehmann, Ulrich; Bockmeyer, Clemens L; Gottlieb, Jens; Fischer, Stefan; Simon, Andre; Welte, Tobias; Maegel, Lavinia; Kreipe, Hans; Laenger, Florian

    2010-09-01

    Obliterative airway remodelling is a morphological sequence in a variety of pulmonary diseases. Notably, bronchiolitis obliterans represents one of the key complications of lung transplantation, induced by (immigrating) myofibroblasts. A comparative expression analysis of obliterative airway remodelling in transplanted and non-transplanted patients has not been reported so far. Obliterated and unremodelled airways from explanted lungs (n = 19) from patients suffering from chronic allograft dysfunction, infection, graft-versus-host disease and toxic exposure were isolated by laser-assisted microdissection. Airways from lung allografts harvested shortly before and after transplantation (n = 4) as well as fibroblastic foci from lungs with interstitial pulmonary fibrosis (n = 4) served as references. Pre-amplified cDNA was analysed by quantitative real-time RT-PCR for expression of fibrosis, inflammation and apoptosis-associated genes. Composition of infiltrating cells and protein expression were assessed by conventional histology and immunohistochemistry. Bronchiolitis obliterans in transplanted patients showed a significant increase of BMP-7 expression (p = 0.0141 compared with controls), while TGF-beta1 and FGF-2 as well as BMP-4 and BMP-7 were up-regulated in fibroblastic foci in interstitial pulmonary fibrosis (p < 0.0424 compared with controls). Regarding other fibrosis-associated genes (BMP-6, SMAD-3, CASP-3 and CASP-9, FASLG, NF-KB1, IL-1 and IL-2) as well as cellularity and cellular composition, no significant differences between obliterative airway remodelling in transplanted and non-transplanted patients could be shown. Obliterative airway remodelling in lung allografts and in non-transplanted patients share many morphological and genetic traits. BMPs, especially BMP-7, warrant further investigation as possible markers for the aggravation of airway remodelling. PMID:20632031

  13. Simkania negevensis and acute cellular rejection in lung transplant recipients.

    PubMed

    Jamal, Alainna J; Resende, Mariangela R; Prochnow, Taisa; McGilvray, Ian; Pilewski, Joseph M; Crespo, Maria M; Singer, Lianne G; McCurry, Kenneth R; Kolls, Jay K; Keshavjee, Shaf; Liles, W Conrad; Husain, Shahid

    2015-08-01

    Simkania negevensis infection has been hypothesized to play a role in lung transplant rejection. The incidence of S. negevensis infection and its association with acute cellular rejection (ACR) were determined in a prospective cohort study of 78 lung transplant recipients (LTRs) in Toronto, Canada, and Pittsburgh, USA, from July 2007 to January 2010. Simkania negevensis testing was detected by quantitative polymerase chain reaction (PCR) on bronchoalveolar lavage fluid. The relationship between S. negevensis and ACR was examined using Cox proportional hazards models and generalized linear and latent mixed models. Cumulative incidence estimates for time-to-ACR in S. negevensis PCR-positive vs. PCR-negative LTRs were 52.7% vs. 31.1% at six months and 68.9% vs. 44.6% at one yr, respectively. Although not statistically significant, there was a trend toward a higher risk of ACR among S. negevensis PCR-positive vs. PCR-negative LTRs in all statistical models. PMID:26009941

  14. Lung transplant immunosuppression – time for a new approach?

    PubMed Central

    Witt, CA; Puri, V; Gelman, AE; Krupnick, AS; Kreisel, D

    2015-01-01

    Summary Outcomes after lung transplantation remain worse compared to other solid organ transplants, which is in large part due to high rates of graft rejection. Despite emerging data that immune responses to lungs differ from other organs, immunosuppression for lung transplant recipients is still based on strategies established for recipients of other grafts. There exists an urgent need to develop immunosuppressive strategies for lung transplant recipients that take the unique immunological features of this organ into account. PMID:25220652

  15. Lung Transplant Recipient with Pulmonary Alveolar Proteinosis

    PubMed Central

    Hahn, M. Frances; Abdelrazek, Hesham; Patel, Vipul J.; Walia, Rajat

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF), and tacrolimus who ultimately developed PAP, which worsened when MMF was replaced with everolimus. PMID:27213073

  16. Lung Transplant Recipient with Pulmonary Alveolar Proteinosis.

    PubMed

    Tokman, Sofya; Hahn, M Frances; Abdelrazek, Hesham; Panchabhai, Tanmay S; Patel, Vipul J; Walia, Rajat; Omar, Ashraf

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF), and tacrolimus who ultimately developed PAP, which worsened when MMF was replaced with everolimus. PMID:27213073

  17. Bronchoscopic procedures and lung biopsies in pediatric lung transplant recipients.

    PubMed

    Wong, Jackson Y; Westall, Glen P; Snell, Gregory I

    2015-12-01

    Bronchoscopy remains a pivotal diagnostic and therapeutic intervention in pediatric patients undergoing lung transplantation (LTx). Whether performed as part of a surveillance protocol or if clinically indicated, fibre-optic bronchoscopy allows direct visualization of the transplanted allograft, and in particular, an assessment of the patency of the bronchial anastomosis (or tracheal anastomosis following heart-lung transplantation). Additionally, bronchoscopy facilitates differentiation of infective processes from rejection episodes through collection and subsequent assessment of bronchoalveolar lavage (BAL) and transbronchial biopsy (TBBx) samples. Indeed, the diagnostic criteria for the grading of acute cellular rejection is dependent upon the histopathological assessment of biopsy samples collected at the time of bronchoscopy. Typically, performed in an out-patient setting, bronchoscopy is generally a safe procedure, although complications related to hemorrhage and pneumothorax are occasionally seen. Airway complications, including stenosis, malacia, and dehiscence are diagnosed at bronchoscopy, and subsequent management including balloon dilatation, laser therapy and stent insertion can also be performed bronchoscopically. Finally, bronchoscopy has been and continues to be an important research tool allowing a better understanding of the immuno-biology of the lung allograft through the collection and analysis of collected BAL and TBBx samples. Whilst new investigational tools continue to evolve, the simple visualization and collection of samples within the lung allograft by bronchoscopy remains the gold standard in the evaluation of the lung allograft. This review describes the use and experience of bronchoscopy following lung transplantation in the pediatric setting. PMID:25940429

  18. Lung Transplantation: The State of the Airways.

    PubMed

    Husain, Aliya N; Garrity, Edward R

    2016-03-01

    Context .- Lung transplantation has become a viable option for definitive treatment of several end-stage lung diseases for which there are no other options available. However, long-term survival continues to be limited by chronic lung allograft dysfunction, which primarily affects the airways. Objective . -To highlight the complications occurring mainly in the airways of the lung transplant recipient from the early to late posttransplant periods. Data Sources .- Review literature focusing on the airways in patients with lung transplants and clinical experience of the authors. Conclusions .- Postsurgical complications and infections of the airways have decreased because of better techniques and management. Acute cellular rejection of the airways can be distinguished from infection pathologically and on cultures. Separating small from large airways need not be an issue because both are risk factors for bronchiolitis obliterans. Grading of airway rejection needs to be standardized. Chronic lung allograft dysfunction consists of both bronchiolitis obliterans and restrictive allograft syndrome, neither of which can be treated very effectively at present. PMID:26927718

  19. The incidence of cancer in a population-based cohort of Canadian heart transplant recipients.

    PubMed

    Jiang, Y; Villeneuve, P J; Wielgosz, A; Schaubel, D E; Fenton, S S A; Mao, Y

    2010-03-01

    To assess the long-term risk of developing cancer among heart transplant recipients compared to the Canadian general population, we carried out a retrospective cohort study of 1703 patients who received a heart transplant between 1981 and 1998, identified from the Canadian Organ Replacement Register database. Vital status and cancer incidence were determined through record linkage to the Canadian Mortality Database and Canadian Cancer Registry. Cancer incidence rates among heart transplant patients were compared to those of the general population. The observed number of incident cancers was 160 with 58.9 expected in the general population (SIR = 2.7, 95% CI = 2.3, 3.2). The highest ratios were for non-Hodgkin's lymphoma (NHL) (SIR = 22.7, 95% CI = 17.3, 29.3), oral cancer (SIR = 4.3, 95% CI = 2.1, 8.0) and lung cancer (SIR = 2.0, 95% CI = 1.2, 3.0). Compared to the general population, SIRs for NHL were particularly elevated in the first year posttransplant during more recent calendar periods, and among younger patients. Within the heart transplant cohort, overall cancer risks increased with age, and the 15-year cumulative incidence of all cancers was estimated to be 17%. There is an excess of incident cases of cancer among heart transplant recipients. The relative excesses are most marked for NHL, oral and lung cancer. PMID:20121725

  20. Lung transplantation: overall approach regarding its major aspects

    PubMed Central

    de Camargo, Priscila Cilene León Bueno; Teixeira, Ricardo Henrique de Oliveira Braga; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Afonso, José Eduardo; Costa, André Nathan; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a well-established treatment for patients with advanced lung disease. The evaluation of a candidate for transplantation is a complex task and involves a multidisciplinary team that follows the patient beyond the postoperative period. Currently, the mean time on the waiting list for lung transplantation in the state of São Paulo, Brazil, is approximately 18 months. For Brazil as a whole, data from the Brazilian Organ Transplant Association show that, in 2014, there were 67 lung transplants and 204 patients on the waiting list for lung transplantation. Lung transplantation is most often indicated in cases of COPD, cystic fibrosis, interstitial lung disease, non-cystic fibrosis bronchiectasis, and pulmonary hypertension. This comprehensive review aimed to address the major aspects of lung transplantation: indications, contraindications, evaluation of transplant candidates, evaluation of donor candidates, management of transplant recipients, and major complications. To that end, we based our research on the International Society for Heart and Lung Transplantation guidelines and on the protocols used by our Lung Transplant Group in the city of São Paulo, Brazil. PMID:26785965

  1. Lung transplantation: overall approach regarding its major aspects.

    PubMed

    de Camargo, Priscila Cilene León Bueno; Teixeira, Ricardo Henrique de Oliveira Braga; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Afonso Junior, José Eduardo; Costa, André Nathan; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    Lung transplantation is a well-established treatment for patients with advanced lung disease. The evaluation of a candidate for transplantation is a complex task and involves a multidisciplinary team that follows the patient beyond the postoperative period. Currently, the mean time on the waiting list for lung transplantation in the state of São Paulo, Brazil, is approximately 18 months. For Brazil as a whole, data from the Brazilian Organ Transplant Association show that, in 2014, there were 67 lung transplants and 204 patients on the waiting list for lung transplantation. Lung transplantation is most often indicated in cases of COPD, cystic fibrosis, interstitial lung disease, non-cystic fibrosis bronchiectasis, and pulmonary hypertension. This comprehensive review aimed to address the major aspects of lung transplantation: indications, contraindications, evaluation of transplant candidates, evaluation of donor candidates, management of transplant recipients, and major complications. To that end, we based our research on the International Society for Heart and Lung Transplantation guidelines and on the protocols used by our Lung Transplant Group in the city of São Paulo, Brazil. PMID:26785965

  2. Probable Phaeoacremonium parasiticum as a cause of cavitary native lung nodules after single lung transplantation.

    PubMed

    Shah, S K; Parto, P; Lombard, G A; James, M A; Beckles, D L; Lick, S; Valentine, V G

    2013-02-01

    Lung nodules after lung transplantation most often represent infection or post-transplant lymphoproliferative disorder in the allograft. Conversely, native lung nodules in single lung transplant recipients are more likely to be bronchogenic carcinoma. We present a patient who developed native lung cavitary nodules. Although malignancy was anticipated, evaluation revealed probable Phaeoacremonium parasiticum infection. Phaeoacremonium parasiticum is a dematiaceous fungus first described as a cause of soft tissue infection in a renal transplant patient. Lung nodules have not been previously described and this is the first case, to our knowledge, of P. parasiticum identified after lung transplantation. PMID:23279754

  3. [Ischemia-reperfusion injury after lung transplantation].

    PubMed

    Gennai, Stéphane; Pison, Christophe; Briot, Raphaël

    2014-09-01

    Lung ischemia-reperfusion is characterized by diffuse alveolar damage arising from the first hours after transplantation. The first etiology of the primary graft dysfunction in lung is ischemia-reperfusion. It is burdened by an important morbi-mortality. Lung ischemia-reperfusion increases the oxidative stress, inactivates the sodium pump, increases the intracellular calcium, leads to cellular death and the liberation of pro-inflammatory mediators. Researches relative to the reduction of the lung ischemia-reperfusion injuries are numerous but few of them found a place in common clinical practice, because of an insufficient level of proofs. Ex vivolung evaluation is a suitable technique in order to evaluate therapeutics supposed to limit lung ischemia-reperfusion injuries. PMID:24935680

  4. Lung and heart-lung transplantation. Evolution and new applications.

    PubMed Central

    Bolman, R M; Shumway, S J; Estrin, J A; Hertz, M I

    1991-01-01

    Heart-lung transplantation (HLT) and lung transplantation (LT) are effective treatment modalities for patients with advanced pulmonary parenchymal or vascular disease. Lung transplantation offers potential advantages over HLT, including reduced pretransplant waiting time and improved efficiency of organ utilization, and is currently being offered to patients formerly treated by HLT. To explore the relative merits of these procedures, the authors examined the results in 44 procedures (23 HLT and 21 LT) in 42 patients transplanted at their institution. Heart-lung transplant recipients included 20 adults and three children (ages 5,5 and 3). Most HLT patients had primary pulmonary hypertension (PPH) (n = 9) or Eisenmenger's syndrome (ES) (n = 8). Twenty-two of twenty-three patients have been long-term survivors (mean follow-up = 17.8 months, Kapaln-Meier survival at 12 months = 85%). Obliterative bronchiolitis (OB) has occurred in five patients (22%), and all have died. Of 21 LTs in 19 patients, nine had obstructive and eight had restrictive lung diseases. Three single-LT (SLT) patients had PPH, and one had ES secondary to a ventricular septal defect. Mean pulmonary artery pressures fell from 55 +/- 6 mm Hg before SLT to 21 +/- 3 mm Hg after SLT; p less than 0.001. Three pediatric patients (ages 4, 10, 17, and 17[re-transplant]) have undergone four SLTs. With mean follow-up of 6.4 months, LT patients have survival at 12 months of 80% (Kaplan-Meier). Lung transplant patients wait a far shorter time for their transplant than do HLT patients (166 vs. 384 days, p less than 0.03). Three patients (19%) have evidence of OB after SLT, with one death. By virtue of equal intermediate-term outcomes, shorter waiting times, and better use of donor organs in comparison with HLT, LT should be offered whenever possible to patients with end-stage pulmonary parenchymal or vascular disease. The authors' pediatric LT and HLT experience (7 treatments in 6 patients) is the largest reported

  5. [Lung transplantation in patients with interstitial lung disease/idiopathic pulmonary fibrosis].

    PubMed

    Murer, Christian; Benden, Christian

    2016-01-01

    Lung transplantation is an established therapy for advanced lung disease. Among the common disease indications for lung transplantation, patients with interstitial lung disease, in particular, idiopathic pulmonary fibrosis (IPF), have the worst prognosis. Thus referral to a transplant center should ideally be realised at the time of diagnosis of usual interstitial pneumonitis (UIP), regardless of lung function, in order to carry out a through initial assessment and evaluation. PMID:26884220

  6. Lung Transplantation in Cystic Fibrosis: Trends and Controversies

    PubMed Central

    Sweet, Stuart

    2015-01-01

    This article is not an overview of all facets of lung transplantation in cystic fibrosis (CF), but rather it is intended as a review of current allocation controversies, as well as of trends in diagnostics and management in lung transplant recipients and in patients with end-stage lung disease. Despite changes in donor and recipient selection, long-term survival in pediatric lung transplant has continued to be limited by chronic lung allograft dysfunction (CLAD). Due to, in part, this short survival benefit, transplant continues to be an appropriate option for only a subset of pediatric patients with CF. The feasibility of transplant as a therapeutic option is also affected by the limited pediatric organ supply, which has moreover contributed to controversy over lung allocation. Debates over the allocation of this scarce resource, however, may also help to drive innovation in the field of lung transplant. Longer pretransplant survival—as aided by new lung bypass technologies, for example—could help to alleviate organ shortages, as well as facilitate the transport of organs to suitable pediatric recipients. Improved diagnosis and treatment for CLAD and for antibody-mediated rejection have the potential to extend survival in pediatric lung transplant. Regardless, the relative rarity of transplant could pose future challenges for pediatric lung transplant programs, which require adequate numbers of patients to maintain proper expertise. PMID:26697265

  7. Lung procurement for transplantation: new criteria for lung donor selection.

    PubMed

    Moretti, M P; Betto, C; Gambacorta, M; Vesconi, S; Scalamogna, M; Benazzi, E; Ravini, M

    2010-05-01

    In Italy, like everywhere in the world, the organ shortage for transplantation is a real problem. It is well known that lung donors (LD) are particularly difficult to procure and that management of the organ do not care during the diagnosis of cerebral death represents a difficult challenge. In this context, the salvage of the so-called "marginal donors" may increase the pool of donors, favoring organ retrieval. To increase lung procurement, the intensivist must recognize "marginal donors," optimizing organ selection and function. The aim of our study was to review LD procured in 2008, as identified by the unrestricted criteria, of the Nord Italian Transplant program Center (NITp). Particularly, the age and habits of donors and the presence of a parenchyma contusion were not sufficient per se to exclude donation. We revisited lung ventilation and monitoring modalities during cerebral death before retrieval. In 2008, the application of enlarged criteria for LD enabled us to collect 21 LD, namely 33% of all cerebral deaths, versus 13% in 2007. Seeking to maintain good gas exchange and lung function, we implemented a safe ventilation program avoided high peak pressures, and fluid therapy properly guided by the cardiac index and extravascular lung water index monitoring. Specific actions to improve LD procurement may help cope with the organ-donor shortage. Although our series was small, our results were encouraging; they underline the necessity to continuously review donor criteria and care, allowing good donor/recipient matching. PMID:20534222

  8. Zurich University Hospital lung transplantation programme: update 2012.

    PubMed

    Inci, Ilhan; Schuurmans, Macé M; Boehler, Annette; Weder, Walter

    2013-01-01

    Lung transplantation is an established therapeutic option for end-stage lung disease in selected patients. During the last 30 years more than 34,000 transplantations have been performed worldwide. Emphysema, pulmonary fibrosis, cystic fibrosis and primary pulmonary hypertension are the most common indications. This type of surgical treatment is increasingly successful, with better early and late survival rates. However, lung transplantation is still hampered by persisting problems such as donor organ shortage, primary graft dysfunction, late graft dysfunction and morbidity related to long-term immunosuppression. The first lung transplantation in Switzerland was performed the 10th November 1992 at Zurich University Hospital. Since then the lung transplant programme has progressively increased its yearly transplant volume. Since the beginning of our lung transplantation programme, overall patient survival has increased steadily and has been at benchmark levels since the year 2000. The most important factors influencing this result are presumably good teamwork among all involved specialists, improved surgical techniques, and close and long-term patient follow-up by the transplant pulmonologists. In this paper we present our programme structure, managing strategies for some specific problems and outcome after lung transplantation. The results presented here are from recipients who underwent lung transplantation up to the end of 2011. PMID:23986418

  9. Successful lung transplantation after donor lung reconditioning with urokinase in ex vivo lung perfusion system.

    PubMed

    Inci, Ilhan; Yamada, Yoshito; Hillinger, Sven; Jungraithmayr, Wolfgang; Trinkwitz, Michael; Weder, Walter

    2014-11-01

    Acute pulmonary embolism is considered a contraindication to lung donation for transplantation as it might result in graft dysfunction. Ex vivo lung perfusion (EVLP) is a novel method to assess and recondition a questionable donor graft before transplantation. In this report we present a case of successful bilateral lung transplant after donor lung assessment and treatment with a fibrinolytic agent, urokinase, during EVLP. PMID:25441801

  10. Sirolimus use and incidence of venous thromboembolism in cardiac transplant recipients.

    PubMed

    Thibodeau, Jennifer T; Mishkin, Joseph D; Patel, Parag C; Kaiser, Patricia A; Ayers, Colby R; Mammen, Pradeep P A; Markham, David W; Ring, W Steves; Peltz, Matthias; Drazner, Mark H

    2012-01-01

    Sirolimus is an immunosuppressive agent increasingly used in cardiac transplant recipients in the setting of allograft vasculopathy or worsening renal function. Recently, sirolimus has been associated with increased risk of venous thromboembolism (VTE) in lung transplant recipients. To investigate whether this association is also present in cardiac transplant recipients, we retrospectively reviewed the charts of 67 cardiac transplant recipients whose immunosuppressive regimen included sirolimus and 134 matched cardiac transplant recipients whose regimen did not include sirolimus. Rates of VTE were compared. Multivariable Cox proportional hazards models tested the association of sirolimus use with VTE. A higher incidence of VTE was seen in patients treated with vs. without sirolimus (8/67 [12%] vs. 9/134 [7%], log-rank statistic: 4.66, p=0.03). Lower body mass index (BMI) and total cholesterol levels were also associated with VTE (p<0.05). The association of sirolimus with VTE persisted when adjusting for BMI (hazard ratio [95% confidence interval]: 2.96 [1.13, 7.75], p=0.03) but not when adjusting for total cholesterol (p=0.08). These data suggest that sirolimus is associated with an increased risk of VTE in cardiac transplant recipients, a risk possibly mediated through comorbid conditions. Larger, more conclusive studies are needed. Until such studies are completed, a heightened level of awareness for VTE in cardiac transplant recipients treated with sirolimus appears warranted. PMID:22775970

  11. Bridge to lung transplantation and rescue post-transplant: the expanding role of extracorporeal membrane oxygenation

    PubMed Central

    Gulack, Brian C.; Hirji, Sameer A.

    2014-01-01

    Over the last several decades, the growth of lung transplantation has been hindered by a much higher demand for donor lungs than can be supplied, leading to considerable waiting time and mortality among patients waiting for transplant. This has led to the search for an alternative bridging strategy in patients with end-stage lung disease. The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation as well as a rescue strategy post-transplant for primary graft dysfunction (PGD) has been studied previously, however due to initially poor outcomes, its use was not heavily instituted. In recent years, with significant improvement in technologies, several single and multi-center studies have shown promising outcomes related to the use of ECMO as a bridging strategy as well as a therapy for patients suffering from PGD post-transplant. These results have challenged our current notion on ECMO use and hence forced us to reexamine the utility, efficacy and safety of ECMO in conjunction with lung transplantation. Through this review, we will address the various aspects related to ECMO use as a bridge to lung transplantation as well as a rescue post-transplant in the treatment of PGD. We will emphasize newer technologies related to ECMO use, examine recent observational studies and randomized trials of ECMO use before and after lung transplantation, and reflect upon our own institutional experience with the use of ECMO in these difficult clinical situations. PMID:25132974

  12. Long term complications following 54 consecutive lung transplants

    PubMed Central

    Tabarelli, Walther; Bonatti, Hugo; Tabarelli, Dominique; Eller, Miriam; Müller, Ludwig; Ruttmann, Elfriede; Lass-Flörl, Cornelia; Larcher, Clara

    2016-01-01

    Background Due to the complex therapy and the required high level of immunosuppression, lung recipients are at high risk to develop many different long term complications. Methods From 1993–2000, a total of 54 lung transplantation (LuTx) were performed at our center. Complications, graft and patient survival of this cohort was retrospectively analyzed. Results One/five and ten-year patient survival was 71.4%, 41.2% and 25.4%; at last follow up (4/2010), twelve patients were alive. Of the 39 deceased patients, 26 died from infectious complications. Other causes of death were myocardial infarction (n=1), progressive graft failure (n=1), intracerebral bleeding (n=2), basilary vein thrombosis (n=1), pulmonary emboli (n=1), others (n=7). Surgical complication rate was 27.7% during the first year and 25% for the 12 long term survivors. Perioperative rejection rate was 35%, and 91.6% for the 12 patients currently alive. Infection incidence during first hospitalization was 79.6% (1.3 episodes per transplant) and 100% for long term survivors. Commonly isolated pathogens were cytomegalovirus (56.8%), Aspergillus (29.4%), RSV (13.7%). Other common complications were renal failure (56.8%), osteoporosis (54.9%), hypertension (45%), diabetes mellitus (19.6%). Conclusions Infection and rejection remain the most common complications following LuTx with many other events to be considered. PMID:27293842

  13. Imaging in lung transplants: Checklist for the radiologist

    PubMed Central

    Madan, Rachna; Chansakul, Thanissara; Goldberg, Hilary J

    2014-01-01

    Post lung transplant complications can have overlapping clinical and imaging features, and hence, the time point at which they occur is a key distinguisher. Complications of lung transplantation may occur along a continuum in the immediate or longer postoperative period, including surgical and mechanical problems due to size mismatch and vascular as well as airway anastomotic complication, injuries from ischemia and reperfusion, acute and chronic rejection, pulmonary infections, and post-transplantation lymphoproliferative disorder. Life expectancy after lung transplantation has been limited primarily by chronic rejection and infection. Multiple detector computed tomography (MDCT) is critical for evaluation and early diagnosis of complications to enable selection of effective therapy and decrease morbidity and mortality among lung transplant recipients. PMID:25489125

  14. Incidence of Carbapenem-Resistant Gram Negatives in Italian Transplant Recipients: A Nationwide Surveillance Study

    PubMed Central

    Lanini, Simone; Costa, Alessandro Nanni; Puro, Vincenzo; Procaccio, Francesco; Grossi, Paolo Antonio; Vespasiano, Francesca; Ricci, Andrea; Vesconi, Sergio; Ison, Michael G.; Carmeli, Yehuda; Ippolito, Giuseppe

    2015-01-01

    Background Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients. Methods and Findings Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients’ mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not. Conclusion The isolation of gram-negative bacteria is most frequent among recipient with hospital stays

  15. Transfer of peanut allergy following lung transplantation: a case report.

    PubMed

    Schuller, A; Barnig, C; Matau, C; Geny, S; Gosselin, M; Moal, M C; Champion, G; Atal, L; de Blay, F; Massard, G; Kessler, R

    2011-12-01

    This case study describes a patient who developed peanut allergy following lung transplantation. A 54-year-old woman underwent bilateral lung transplantation on June 2009 owing to severe chronic obstructive pulmonary disease. She had no history of food allergy before transplantation. The donor, however, was a 20-year-old man who was fatally injured during an automobile accident; he was allergic to peanuts. At 3 months after transplantation, the lung recipient presented with acute dyspnea and urticaria 15 minutes after consuming food containing peanut derivatives. Pre- and posttransplantation recipient blood samples analyzed for the presence of IgE antibodies specific for peanut allergens confirmed that the allergy had been passively transfered as a consequence of transplantation. Food allergy following solid organ transplantation is thought to be rare, mostly occurring in children. Two mechanisms may explain the observations described for the patient reported in this study: de novo development of peanut allergies after transplantation, or passive transfer of peanut allergies from a peanut-sensitized organ donor. This case report documenting pre- and posttransplantation IgE status in a lung transplantation case suggested that the allergic status of organ donors should be thoroughly assessed before transplantation, and potential allergy transfer risks must be discussed with the transplant team and the patient. PMID:22172896

  16. Obesity and Primary Graft Dysfunction after Lung Transplantation

    PubMed Central

    Kawut, Steven M.; Wickersham, Nancy; Winterbottom, Christopher; Bhorade, Sangeeta; Palmer, Scott M.; Lee, James; Diamond, Joshua M.; Wille, Keith M.; Weinacker, Ann; Lama, Vibha N.; Crespo, Maria; Orens, Jonathan B.; Sonett, Joshua R.; Arcasoy, Selim M.; Ware, Lorraine B.; Christie, Jason D.

    2011-01-01

    Rationale: Obesity has been linked to acute lung injury and is a risk factor for early mortality after lung transplantation. Objectives: To examine the associations of obesity and plasma adipokines with the risk of primary graft dysfunction after lung transplantation. Methods: We performed a prospective cohort study of 512 adult lung transplant recipients with chronic obstructive pulmonary disease or interstitial lung disease enrolled in the Lung Transplant Outcomes Group Study. In a nested case-control study, we measured plasma leptin, adiponectin, and resistin before lung transplantation and 6 and 24 hours after lung transplantation in 40 cases of primary graft dysfunction and 80 control subjects. Generalized linear mixed models and logistic regression were used to estimate risk ratios and odds ratios. Measurements and Main Results: Grade 3 primary graft dysfunction developed within 72 hours of transplantation in 29% participants. Obesity was associated with a twofold increased risk of primary graft dysfunction (adjusted risk ratio 2.1; 95% confidence interval, 1.7–2.6). The risk of primary graft dysfunction increased by 40% (confidence interval, 30–50%) for each 5 kg/m2 increase in body mass index after accounting for center, diagnosis, cardiopulmonary bypass, and transplant procedure. Higher plasma leptin levels were associated with a greater risk of primary graft dysfunction (sex-adjusted P = 0.02). The associations of both obesity and leptin with primary graft dysfunction tended to be stronger among those who did not undergo cardiopulmonary bypass. Conclusions: Obesity is an independent risk factor for primary graft dysfunction after lung transplantation. PMID:21799077

  17. Lung Transplantation and Survival in Children with Cystic Fibrosis

    PubMed Central

    Liou, Theodore G.; Adler, Frederick R.; Cox, David R.; Cahill, Barbara C.

    2016-01-01

    BACKGROUND The effects of lung transplantation on the survival and quality of life in children with cystic fibrosis are uncertain. METHODS We used data from the U.S. Cystic Fibrosis Foundation Patient Registry and from the Organ Procurement and Transplantation Network to identify children with cystic fibrosis who were on the waiting list for lung transplantation during the period from 1992 through 2002. We performed proportional-hazards survival modeling, using multiple clinically relevant covariates that were available before the children were on the waiting list and the interactions of these covariates with lung transplantation as a time-dependent covariate. The data were insufficient in quality and quantity for a retrospective quality-of-life analysis. RESULTS A total of 248 of the 514 children on the waiting list underwent lung transplantation in the United States during the period from 1992 through 2002. Proportional-hazards modeling identified four variables besides transplantation that were associated with changes in survival. Burkholderia cepacia infection was associated with a trend toward decreased survival, regardless of whether the patient underwent transplantation. A diagnosis of diabetes before the patient was placed on the waiting list decreased survival while the patient was on the waiting list but did not decrease survival after transplantation, whereas older age did not affect waiting-list survival but decreased post-transplantation survival. Staphylococcus aureus infection increased waiting-list survival but decreased post-transplantation survival. Using age, diabetes status, and S. aureus infection status as covariates, we estimated the effect of transplantation on survival for each patient group, expressed as a hazard factor of less than 1 for a benefit and more than 1 for a risk of harm. Five patients had a significant estimated benefit, 283 patients had a significant risk of harm, 102 patients had an insignificant benefit, and 124 patients

  18. Risk of Post-Lung Transplant Renal Dysfunction in Adults With Cystic Fibrosis

    PubMed Central

    Mayer-Hamblett, Nicole; Aitken, Moira L.; Goss, Christopher H.

    2012-01-01

    Background: Cystic fibrosis (CF) is one of the leading indications for lung transplantation. The incidence and pre-lung transplant risk factors for posttransplant renal dysfunction in the CF population remain undefined. Methods: We conducted a cohort study using adults (≥ 18 years old) in the CF Foundation Patient Registry from 2000 to 2008 to determine the incidence of post-lung transplant renal dysfunction, defined by an estimated glomerular filtration rate of < 60 mL/min/1.73 m2. Multivariable Cox proportional hazards modeling was used to identify independent pretransplant risk factors for post-lung transplant renal dysfunction. Results: The study cohort included 993 adult lung transplant recipients with CF, with a median follow-up of 2 years. During the study period, 311 individuals developed renal dysfunction, with a 2-year risk of 35% (95% CI, 32%-39%). Risk of posttransplant renal dysfunction increased substantially with increasing age (25 to < 35 years vs 18 to < 25 years: hazard ratio [HR], 1.60; 95% CI, 1.15-2.23; vs ≥ 35 years: HR, 2.45; 95% CI, 1.73-3.47) and female sex (HR, 1.56; 95% CI, 1.22-1.99). CF-related diabetes requiring insulin therapy (HR, 1.30; 95% CI, 1.02-1.67) and pretransplant renal function impairment (estimated glomerular filtration rate, 60-90 mL/min/m2 vs > 90 mL/min/m2: HR, 1.58; 95% CI, 1.19-2.12) also increased the risk of posttransplant renal dysfunction. Conclusions: Renal dysfunction is common following lung transplant in the adult CF population. Increased age, female sex, CF-related diabetes requiring insulin, and pretransplant renal impairment are significant risk factors. PMID:22222189

  19. Experience of the Reina Sofia hospital in lobar lung transplantation.

    PubMed

    Espinosa, D; Algar, F J; Moreno, P; Illana, J; Alvarez, A; Cerezo, F; Baamonde, C; Santos, F; Vaquero, J M; Redel, J; Salvatierra, A

    2010-10-01

    The number of patients awaiting lung transplantation has steadily increased over the past decade, but the number of donors has remained relatively stable. Owing to the increasing scarcity of donor lungs, especially for pediatric and small adult recipients, advanced operative strategies for the use of larger grafts for smaller recipients have been developed. Size matching between donors and recipients represents one of the organ distribution criteria widely accepted by lung transplantation teams. However, in some cases it is not possible to allocate a donor to the corresponding size-compatible recipient. To avoid possible complications derived from the implantation of oversized lungs into smaller recipients, various methods of downsizing are applied for cadaveric donor lungs, such as lobar transplantation. We review our experience in 6 patients undergoing volume reduction of the lung graft by lobar resection at the time of transplantation. Graft volume reduction by anatomic resection (lobar transplantation) is a reliable and safe procedure to overcome size disparities between the donor and the recipient of a lung transplant, and thus to maximize the number of donors. PMID:20970656

  20. MECHANICAL VENTILATION FOR THE LUNG TRANSPLANT RECIPIENT

    PubMed Central

    Barnes, Lindsey; Reed, Robert M.; Parekh, Kalpaj R.; Bhama, Jay K.; Pena, Tahuanty; Rajagopal, Srinivasan; Schmidt, Gregory A.; Klesney-Tait, Julia A.; Eberlein, Michael

    2015-01-01

    Mechanical ventilation (MV) is an important aspect in the intraoperative and early postoperative management of lung transplant (LTx)-recipients. There are no randomized-controlled trials of LTx-recipient MV strategies; however there are LTx center experiences and international survey studies reported. The main early complication of LTx is primary graft dysfunction (PGD), which is similar to the adult respiratory distress syndrome (ARDS). We aim to summarize information pertinent to LTx-MV, as well as PGD, ARDS, and intraoperative MV and to synthesize these available data into recommendations. Based on the available evidence, we recommend lung-protective MV with low-tidal-volumes (≤6 mL/kg predicted body weight [PBW]) and positive end-expiratory pressure for the LTx-recipient. In our opinion, the MV strategy should be based on donor characteristics (donor PBW as a parameter of actual allograft size), rather than based on recipient characteristics; however this donor-characteristics-based protective MV is based on indirect evidence and requires validation in prospective clinical studies. PMID:26495241

  1. Special considerations for the use of lung transplantation in pediatrics.

    PubMed

    Schmid, Florian A; Benden, Christian

    2016-06-01

    Lung transplantation has become an accepted therapy in infants, children and adolescents suffering from end-stage lung diseases, an impaired quality of life as well as a reduced life expectancy. Within Europe, pediatric lung transplantation is largely performed in predominantly adult centers due to a relatively low overall case volume. Children do represent a specific and challenging cohort facing a transplant procedure, where the selection of potential candidates becomes a crucial step to maximize net survival benefit. Therefore, interdisciplinary evaluation and early listing in view of current indications and contraindications, adequate preoperative education of the child and family members, discussion of possibly required bridging procedures in case of deterioration, appropriate technical planning of the operation, adherence to postoperative medical treatment and follow-up are all crucial steps in this demanding puzzle. In this article, the authors review recent advances in the field of pediatric lung transplantation and outline challenges in the future. PMID:26998955

  2. Imaging in Lung Transplantation: Surgical Considerations of Donor and Recipient.

    PubMed

    Backhus, Leah M; Mulligan, Michael S; Ha, Richard; Shriki, Jabi E; Mohammed, Tan-Lucien H

    2016-03-01

    Modifications in recipient and donor criteria and innovations in donor management hold promise for increasing rates of lung transplantation, yet availability of donors remains a limiting resource. Imaging is critical in the work-up of donor and recipient including identification of conditions that may portend to poor posttransplant outcomes or necessitate modifications in surgical technique. This article describes the radiologic principles that guide selection of patients and surgical procedures in lung transplantation. PMID:26896228

  3. The surgical technique of bilateral sequential lung transplantation

    PubMed Central

    Hayanga, J. W. Awori

    2014-01-01

    Since the first successful lung transplant performed three decades ago, the technique of lung transplantation has evolved with acceptable short- and long-term outcomes such that it has become the standard for those with end stage pulmonary disease. Herein, we describe our current favored approach and discuss some of the current areas in need of further investigation as they relate to the technical aspects of the operation. PMID:25132973

  4. Airway stenoses after lung transplantation: management with expanding metal stents.

    PubMed

    Higgins, R; McNeil, K; Dennis, C; Parry, A; Large, S; Nashef, S A; Wells, F C; Flower, C; Wallwork, J

    1994-01-01

    Success in lung transplantation has been hindered by airway complications, usually as a result of anastomotic ischemia and stenosis. We report our experience with expanding metal stents in managing airway stenoses after lung transplantation. From April 1984 through November 1993, 46 single lung, 5 double lung, and 154 heart-lung transplantations were performed at Papworth Hospital. All patients received immunosuppression with azathioprine, cyclosporine, methylprednisolone, and induction antithymocyte globulin. Fourteen patients (nine single lung, two double lung, and three heart-lung) had an airway stenosis requiring a stent. The most common features were shortness of breath, wheezing or stridor, and a fall in pulmonary function tests (11 patients). Three patients had pneumonia. Airway stenosis was diagnosed on bronchoscopy an average of 61 days after transplantation (range 3 to 245 days). Stent placement occurred an average of 18 days after the diagnosis (range 2 to 84 days). One heart-lung transplant recipient received a silicone rubber stent. All other patients received expanding metal stents. Six patients required multiple stent placements. After stent placement the average increase in the forced expiratory volume in 1 second was 117%. Infection complicated the stenoses in 12 patients. Pseudomonas aeruginosa and Aspergillus fumigatus were the most common pathogens, each occurring in six cases. Multiple pathogens were isolated in seven cases. Three patients died as a direct consequence of their airway problems. Two died of pneumonia despite stenting, and a third died of acute occlusion of the silicone rubber stent. Expanding metal stents are an effective treatment of airway stenoses in lung transplant recipients. Patients with suspected airway problems should be referred for early bronchoscopy with the potential for stent placement. PMID:7803417

  5. To transplant or not? The importance of psychosocial and behavioural factors before lung transplantation.

    PubMed

    Dobbels, F; Verleden, G; Dupont, L; Vanhaecke, J; De Geest, S

    2006-01-01

    The gratifying results of lung transplantation in terms of survival and quality of life stimulate the referral of an ever-increasing number of patients with end-stage lung disease. This in turn compounds the organ shortage, which is the limiting factor in the transplantation rate. In the absence of good alternative treatment modalities, an evidence-based pretransplant screening process is a prerequisite to determine which patients will benefit most from transplantation. Within this evidence-based screening process, medical selection criteria are well established. There is a growing awareness that psychosocial and behavioural factors may determine outcome after transplantation as well. This paper reviews the available evidence for psychosocial and behavioural factors in the screening process for lung transplantation. The relation of various factors with post-transplant outcome was explored. Psychosocial characteristics before transplantation consist of 1) anxiety and depression, 2) personality disorders, 3) neurocognitive problems, and 4) lack of social support. Pretransplant behavioural factors include 1) noncompliance with medication, 2) alcohol abuse or dependence, 3) smoking, 4) noncompliance with dietary guidelines, and 5) noncompliance with monitoring of vital parameters and infections. It appears that the lack of rigorous studies limit the feasibility of an evidence-based screening process. Prospective studies are crucial to this further investigation of the relationship between psychosocial and behavioural determinants before transplantation and outcomes after transplantation, in terms of compliance, morbidity, and mortality. Identification of modifiable risk factors for poor outcome before transplantation is a first step in developing interventions. PMID:16509176

  6. Long-Term Lung Transplantation in Nonhuman Primates

    PubMed Central

    Aoyama, A.; Tonsho, M.; Ng, C. Y.; Lee, S.; Millington, T.; Nadazdin, O.; Wain, J. C.; Cosimi, A. B.; Sachs, D. H.; Smith, R. N.; Colvin, R. B.; Kawai, T.; Madsen, J. C.; Benichou, G.; Allan, J. S.

    2015-01-01

    Despite advances in surgical technique and clinical care, lung transplantation still remains a short-term solution for the treatment of end-stage lung disease. To date, there has been limited experience in experimental lung transplantation using nonhuman primate models. Therefore, we have endeavored to develop a long-term, nonhuman primate model of orthotopic lung transplantation for the ultimate purpose of designing protocols to induce tolerance of lung grafts. Here, we report our initial results in developing this model and our observation that the nonhuman primate lung is particularly prone to rejection. This propensity toward rejection may be a consequence of 1) upregulated nonspecific inflammation, and 2) a larger number of pre-existing alloreactive memory T cells, leading to augmented deleterious immune responses. Our data show that triple-drug immunosuppression mimicking clinical practice is not sufficient to prevent acute rejection in nonhuman primate lung transplantation. The addition of horse-derived anti-thymocyte globulin and a monoclonal antibody to the IL-6 receptor allowed six out of six lung recipients to be free of rejection for over 120 days. PMID:25772308

  7. Guidelines for the selection of lung transplantation candidates.

    PubMed

    Román, Antonio; Ussetti, Pietat; Solé, Amparo; Zurbano, Felipe; Borro, José M; Vaquero, José M; de Pablo, Alicia; Morales, Pilar; Blanco, Marina; Bravo, Carlos; Cifrian, José; de la Torre, Mercedes; Gámez, Pablo; Laporta, Rosalía; Monforte, Víctor; Mons, Roberto; Salvatierra, Angel; Santos, Francisco; Solé, Joan; Varela, Andrés

    2011-06-01

    The present guidelines have been prepared with the consensus of at least one representative of each of the hospitals with lung transplantation programs in Spain. In addition, prior to their publication, these guidelines have been reviewed by a group of prominent reviewers who are recognized for their professional experience in the field of lung transplantation. Within the following pages, the reader will find the selection criteria for lung transplantation candidates, when and how to remit a patient to a transplantation center and, lastly, when to add the patient to the waiting list. A level of evidence has been identified for the most relevant questions. Our intention is for this document to be a practical guide for pulmonologists who do not directly participate in lung transplantations but who should consider this treatment for their patients. Finally, these guidelines also propose an information form in order to compile in an organized manner the patient data of the potential candidate for lung transplantation, which are relevant in order to be able to make the best decisions possible. PMID:21536362

  8. Challenging immunosuppression treatment in lung transplant recipients with kidney failure.

    PubMed

    Högerle, Benjamin A; Kohli, Neeraj; Habibi-Parker, Kirsty; Lyster, Haifa; Reed, Anna; Carby, Martin; Zeriouh, Mohamed; Weymann, Alexander; Simon, André R; Sabashnikov, Anton; Popov, Aron-Frederik; Soresi, Simona

    2016-03-01

    Kidney failure after lung transplantation is a risk factor for chronic kidney disease. Calcineurin inhibitors are immunosuppressants which play a major role in terms of postoperative kidney failure after lung transplantation. We report our preliminary experience with the anti-interleukin-2 monoclonal antibody Basiliximab utilized as a "calcineurin inhibitor-free window" in the setting of early postoperative kidney failure after lung transplantation. Between 2012 and 2015 nine lung transplant patients who developed kidney failure for more than 14 days were included. Basiliximab was administrated in three doses (Day 0, 4, and 20) whilst Tacrolimus was discontinued or reduced to maintain a serum level between 2 and 4 ng/mL. Baseline glomerular filtration rate pre transplant was normal for all patients. Seven patients completely recovered from kidney failure (67%, mean eGFR pre and post Basiliximab: 42.3 mL/min/1.73 m(2) and 69 mL/min/1.73 m(2)) and were switched back on Tacrolimus. Only one of these patients still needs ongoing renal replacement therapy. Two patients showed no recovery from kidney failure and did not survive. Basiliximab might be a safe and feasible therapeutical option in patients which are affected by calcineurin inhibitor-related kidney failure in the early post lung transplant period. Further studies are necessary to confirm our preliminary results. PMID:26892232

  9. Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience.

    PubMed

    Sivam, S; Al-Hindawi, Y; Di Michiel, J; Moriarty, C; Spratt, P; Jansz, P; Malouf, M; Plit, M; Pleass, H; Havryk, A; Bowen, D; Haber, P; Glanville, A R; Bye, P T P

    2016-07-01

    Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation. PMID:27405894

  10. Penicillium marneffei infection in a lung transplant recipient.

    PubMed

    Stathakis, A; Lim, K P; Boan, P; Lavender, M; Wrobel, J; Musk, M; Heath, C H

    2015-06-01

    Penicillium marneffei is a thermally dimorphic fungus that can cause severe opportunistic infections in endemic regions of Southeast Asia, particularly in individuals infected with human immunodeficiency virus-1, but has rarely been reported in solid organ transplant recipients. Herein, we report the first case, to our knowledge, of P. marneffei infection in a lung transplant recipient, occurring in a 41-year-old woman 28 months post lung transplantation, after recent travel to Vietnam. We have reviewed the literature to derive some management principles for this rare infection in this clinical context. The number of P. marneffei infections in transplant recipients may increase, as a result of increasing rates of transplantation and travel to endemic areas. PMID:25809145

  11. A rare occurrence of pulmonary alveolar proteinosis after lung transplantation.

    PubMed

    Albores, Jeffrey; Seki, Atsuko; Fishbein, Michael C; Abtin, Fereidoun; Lynch, Joseph P; Wang, Tisha; Weigt, S Samuel

    2013-06-01

    We present a case of pulmonary alveolar proteinosis (PAP) initially diagnosed 28 months after left single-lung transplantation for idiopathic pulmonary fibrosis. The diagnosis was based upon the presence of periodic acid-Schiff (PAS)-positive and surfactant immunostain-positive acellular lipoproteinaceous material within alveoli seen on transbronchial biopsy as well as in bronchoalveolar lavage fluid. The patient eventually also displayed a characteristic "crazy paving" pattern on radiographic imaging. Granulocyte macrophage-colony stimulating factor antibodies were negative, consistent with secondary PAP. PAP is a rare interstitial lung disease with only a few reported cases occurring after lung transplantation. The etiology is thought to be related to a defect in macrophage function caused by immunosuppression. Reduced immunosuppression has been associated with stabilization, but not reversal, of the condition in the case reported here. PAP is an exceptionally rare cause of dyspnea and radiographic infiltrates after lung transplantation and may be related to toxicity of immune-suppressive medications. PMID:23821516

  12. Ex vivo lung perfusion in clinical lung transplantation--state of the art.

    PubMed

    Andreasson, Anders S I; Dark, John H; Fisher, Andrew J

    2014-11-01

    Ex vivo lung perfusion (EVLP) has emerged as a new technique for assessing and potentially reconditioning human donor lungs previously unacceptable for clinical transplantation with the potential to dramatically push the limits of organ acceptability. With the recent introduction of portable EVLP, a new era in lung preservation may be upon us with the opportunity to also limit organ ischaemic times and potentially improve the outcome of donor lungs already deemed acceptable for transplantation. It took over half a century for the technique to evolve from basic theory to semi-automated circuits fit for clinical use that are now rapidly being adopted in transplant centres across the globe. With this field in constant evolution and many unanswered questions remaining, our review serves as an update on the state of the art of EVLP in clinical lung transplantation. PMID:25061215

  13. Successful emergent lung transplantation after remote ex vivo perfusion optimization and transportation of donor lungs.

    PubMed

    Wigfield, C H; Cypel, M; Yeung, J; Waddell, T; Alex, C; Johnson, C; Keshavjee, S; Love, R B

    2012-10-01

    A recent clinical trial provided evidence that ex vivo lung perfusion (EVLP) results in optimized human donor lungs for transplantation. Excellent recipient outcomes were documented after 4 h of normothermic perfusion. We report a clinical case utilizing remote EVLP to assess and improve function of initially otherwise unacceptable injured donor lungs followed by transportation and subsequent bilateral lung transplantation in a patient with virally induced refractory respiratory failure supported with extracorporeal membrane oxygenation. This is the first lung transplantation with the application of remote EVLP, wherein the donor lungs were transported from the donor hospital to a center for EVLP and then transported to another hospital for transplantation. It is also the first case of lung transplantation in the United States utilizing EVLP for functional optimization leading to successful transplantation. Organ procurement data, EVLP assessment, and the pre- and postoperative course of the recipient are presented. The available evidence supporting EVLP, the humanitarian and cooperative utilization of lungs otherwise discarded, are discussed. PMID:23009140

  14. Recurrence of lymphangioleiomyomatosis: Nine years after a bilateral lung transplantation

    PubMed Central

    Zaki, Khawaja S; Aryan, Zahra; Mehta, Atul C; Akindipe, Olufemi; Budev, Marie

    2016-01-01

    Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive lethal lung disease primary afflicting young women. LAM is characterized by proliferation of abnormal smooth muscle cells that target the lungs, causing cystic destruction and eventual respiratory failure leading to death. Recent ten year mortality due to end stage LAM has been reported to be approximately 10%-20%, but may vary. The decline in lung function in LAM is gradual, occurring at a rate of about 3% to 15% per year but can vary from patient to patient. But recently therapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus has shown promising results in the stabilization of lung function and reduction of chylous effusions in LAM. Lung transplantation is a viable option for patients who continue to have decline in lung function despite mTOR therapy. Unique issues that may occur post-transplant in a recipient with LAM include development of chylous effusion and a risk of recurrence. We describe a case of LAM recurrence in a bilateral lung transplant recipient who developed histological findings of LAM nine years after transplantation. PMID:27011924

  15. Atelectasis--an unusual and late complication of lung transplant.

    PubMed

    Zhao, Y; Al-Kaade, S; Keller, C A; deMello, D E

    2002-06-01

    We report a previously unrecognized late complication of allograft lung transplantation - persistent recurrent atelectasis of the transplanted lung. The patient developed sudden, severe respiratory distress about 2 yr after a right lung transplant, because of acute atelectasis of her transplanted lung. Multiple transbronchial biopsies at the time revealed minimal inflammation and no evidence of rejection. She was treated with surfactant replacement therapy, and her collapsed lung fully expanded following surfactant installation. To eliminate the possibility of acquired deficiency of surfactant lipids or proteins, ultrastructural examination and immunostains for surfactant proteins were performed in a transbronchial lung biopsy. No deficiency of surfactant lipids or proteins was found. On ultrastructural examination of the lung biopsy, the number of Type II cells per alveolus and the number of lamellar bodies per square micron of Type II cell cross-sectional area was increased compared with an age-matched control. We conclude that synthesis of surfactant lipids and proteins was unimpaired and because of the patient's response to surfactant replacement therapy, that the increase in number of lamellar bodies could reflect a compensatory mechanism for a surfactant functional defect. The patient later developed breast carcinoma to which she succumbed. We raise the possibility that the functional surfactant defect is a hitherto unrecognized non-metastatic manifestation of malignancy. PMID:12010150

  16. [Therapeutic Drug Management for Transplanted Women with a Planned Pregnancy: About Two Cases of Lung and Heart-lung Transplantation].

    PubMed

    Zecchini, Céline; Chanoine, Sébastien; Chapuis, Claire; Claustre, Johanna; Schir, Edith; Allenet, Benoît; Saint Raymond, Christel; Bedouch, Pierrick

    2015-01-01

    Advances in lung transplantation allow the women of childbearing age to consider becoming mothers. When planning to become pregnant, a therapeutic drug management of immunosuppressive drugs and associated therapies is required. It must take into account teratogenic and fetotoxic drugs, as well as pharmacokinetic changes encountered during pregnancy. Increasingly data are currently available on the management of immunosuppressive drugs and associated therapies during pregnancy. We report the case management of drug therapy before and during pregnancy in two patients after a lung or heart-lung transplantation. To prevent the emergence of complications for mother and child, a literature review has been necessary to manage drug therapies of each patient. PMID:26223163

  17. Gastroesophageal Reflux and Altered Motility in Lung Transplant Rejection

    PubMed Central

    Castor, John M; Wood, Richard K.; Muir, Andrew J.; Palmer, Scott M.; Shimpi, Rahul A.

    2010-01-01

    Background Lung transplantation has become an effective therapeutic option for selected patients with end stage lung disease. Long-term survival is limited by chronic rejection manifest as bronchiolitis obliterans syndrome (BOS). The aspiration of gastric contents has been implicated as a causative or additive factor leading to BOS. Gastroesophageal reflux (GER) and altered foregut motility are common both before and after lung transplantation. Further, the normal defense mechanisms against reflux are impaired in the allograft. Recent studies using biomarkers of aspiration have added to previous association studies to provide a growing body of evidence supporting the link between rejection and GER. Further, the addition of high-resolution manometry (HRM) and impedance technology to characterize bolus transit and the presence and extent of reflux regardless of pH might better identify at-risk patients. Although additional prospective studies are needed, fundoplication appears useful in the prevention or treatment of post-transplant BOS. Purpose This review will highlight the existing literature on the relationship of gastroesophageal reflux and altered motility to lung transplant rejection, particularly BOS. The article will conclude with a discussion of the evaluation and management of patients undergoing lung transplantation at our center. PMID:20507544

  18. Fractal circuit sensors enable rapid quantification of biomarkers for donor lung assessment for transplantation

    PubMed Central

    Sage, Andrew T.; Besant, Justin D.; Mahmoudian, Laili; Poudineh, Mahla; Bai, Xiaohui; Zamel, Ricardo; Hsin, Michael; Sargent, Edward H.; Cypel, Marcelo; Liu, Mingyao; Keshavjee, Shaf; Kelley, Shana O.

    2015-01-01

    Biomarker profiling is being rapidly incorporated in many areas of modern medical practice to improve the precision of clinical decision-making. This potential improvement, however, has not been transferred to the practice of organ assessment and transplantation because previously developed gene-profiling techniques require an extended period of time to perform, making them unsuitable in the time-sensitive organ assessment process. We sought to develop a novel class of chip-based sensors that would enable rapid analysis of tissue levels of preimplantation mRNA markers that correlate with the development of primary graft dysfunction (PGD) in recipients after transplant. Using fractal circuit sensors (FraCS), three-dimensional metal structures with large surface areas, we were able to rapidly (<20 min) and reproducibly quantify small differences in the expression of interleukin-6 (IL-6), IL-10, and ATP11B mRNA in donor lung biopsies. A proof-of-concept study using 52 human donor lungs was performed to develop a model that was used to predict, with excellent sensitivity (74%) and specificity (91%), the incidence of PGD for a donor lung. Thus, the FraCS-based approach delivers a key predictive value test that could be applied to enhance transplant patient outcomes. This work provides an important step toward bringing rapid diagnostic mRNA profiling to clinical application in lung transplantation. PMID:26601233

  19. Refractory Pulmonary Edema Caused by Late Pulmonary Vein Thrombosis After Lung Transplantation: A Rare Adverse Event.

    PubMed

    Denton, Eve J; Rischin, Adam; McGiffin, David; Williams, Trevor J; Paraskeva, Miranda A; Westall, Glen P; Snell, Greg

    2016-09-01

    After lung transplantation, pulmonary vein thrombosis is a rare, potentially life-threatening adverse event arising at the pulmonary venous anastomosis that typically occurs early and presents as graft failure and hemodynamic compromise with an associated mortality of up to 40%. The incidence, presentation, outcomes, and treatment of late pulmonary vein thrombosis remain poorly defined. Management options include anticoagulant agents for asymptomatic clots, and thrombolytic agents or surgical thrombectomy for hemodynamically significant clots. We present a rare case highlighting a delayed presentation of pulmonary vein thrombosis occurring longer than 2 weeks after lung transplantation and manifesting clinically as graft failure secondary to refractory pulmonary edema. The patient was treated successfully with surgical thrombectomy and remains well. We recommend a high index of suspicion of pulmonary vein thrombosis when graft failure after lung transplantation occurs and is not responsive to conventional therapy, and consideration of investigation with transesophageal echocardiography or computed tomography with venous phase contrast in such patients even more than 2 weeks after lung transplantation. PMID:27549541

  20. A consensus document for the selection of lung transplant candidates: 2014--an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation.

    PubMed

    Weill, David; Benden, Christian; Corris, Paul A; Dark, John H; Davis, R Duane; Keshavjee, Shaf; Lederer, David J; Mulligan, Michael J; Patterson, G Alexander; Singer, Lianne G; Snell, Greg I; Verleden, Geert M; Zamora, Martin R; Glanville, Allan R

    2015-01-01

    The appropriate selection of lung transplant recipients is an important determinant of outcomes. This consensus document is an update of the recipient selection guidelines published in 2006. The Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) organized a Writing Committee of international experts to provide consensus opinion regarding the appropriate timing of referral and listing of candidates for lung transplantation. A comprehensive search of the medical literature was conducted with the assistance of a medical librarian. Writing Committee members were assigned specific topics to research and discuss. The Chairs of the Writing Committee were responsible for evaluating the completeness of the literature search, providing editorial support for the manuscript, and organizing group discussions regarding its content. The consensus document makes specific recommendations regarding the timing of referral and of listing for lung transplantation. These recommendations include discussions not present in previous ISHLT guidelines, including lung allocation scores, bridging to transplant with mechanical circulatory and ventilator support, and expanded indications for lung transplantation. In the absence of high-grade evidence to support decision making, these consensus guidelines remain part of a continuum of expert opinion based on available studies and personal experience. Some positions are immutable. Although transplant is rightly a treatment of last resort for end-stage lung disease, early referral allows proper evaluation and thorough patient education. Subsequent waiting list activation implies a tacit agreement that transplant offers a significant individual survival advantage. It is both the challenge and the responsibility of the transplant community globally to ensure organ allocation maximizes the potential benefits of a scarce resource, thereby achieving that advantage. PMID:25085497

  1. Successful extended hypothermic cardiopulmonary preservation for heart-lung transplantation.

    PubMed

    Bando, K; Teramoto, S; Tago, M; Teraoka, H; Seno, S; Senoo, Y

    1989-07-01

    The inability to obtain sufficiently extended hypothermic organ preservation is a major restriction on clinical heart-lung transplantation. We used core cooling, nonrecirculating retrograde heart perfusion, and lung immersion with liposomal recombinant human superoxide dismutase in an attempt to provide effective 12-hour cardiopulmonary preservation. Donor dogs supported by cardiopulmonary bypass were rapidly cooled to 15 degrees C with cardioplegic arrest, and heterotopic heart and unilateral left lung transplantations were performed. In control dogs (n = 7), hearts and lungs, harvested after core cooling and cardioplegic arrest, were transplanted with a total mean ischemic time of 88 +/- 5 minutes. In group II (n = 7), heart-lung blocks were similarly excised but preserved at 4 degrees C for 12 hours (756 +/- 30 minutes) and then transplanted. During preservation, the lungs were immersed in hyperosmolar extracellular solution. For the heart, retrograde coronary sinus perfusion was performed with intracellular solution containing perfluorochemicals at a temperature of 4 degrees C and a rate of 30 ml/hr for 12 hours. In group III (n = 7), donor organs were similarly excised and preserved for 12 hours (726 +/- 39 minutes), except that liposomal recombinant human superoxide dismutase was administered during harvest, preservation, and reperfusion. Myocardial function, assessed by the ratio of end-systolic pressure to end-systolic dimension, after the 12-hour preservation period in both experimental groups was similar to that of the control group 4 and 6 hours after transplantation. The mean arterial oxygen capacity of the transplanted left lung during ventilation with an inspired oxygen concentration of 40% was also similar in each group. In contrast, the 12-hour preservation of pulmonary function assessed by pulmonary vascular resistance, the accumulation of extravascular lung water, and histologic evidence of alveolar wall injury, interstitial edema, and

  2. Leaky lysosomes in lung transplant macrophages: azithromycin prevents oxidative damage

    PubMed Central

    2012-01-01

    Background Lung allografts contain large amounts of iron (Fe), which inside lung macrophages may promote oxidative lysosomal membrane permeabilization (LMP), cell death and inflammation. The macrolide antibiotic azithromycin (AZM) accumulates 1000-fold inside the acidic lysosomes and may interfere with the lysosomal pool of Fe. Objective Oxidative lysosomal leakage was assessed in lung macrophages from lung transplant recipients without or with AZM treatment and from healthy subjects. The efficiency of AZM to protect lysosomes and cells against oxidants was further assessed employing murine J774 macrophages. Methods Macrophages harvested from 8 transplant recipients (5 without and 3 with ongoing AZM treatment) and 7 healthy subjects, and J774 cells pre-treated with AZM, a high-molecular-weight derivative of the Fe chelator desferrioxamine or ammonium chloride were oxidatively stressed. LMP, cell death, Fe, reduced glutathione (GSH) and H-ferritin were assessed. Results Oxidant challenged macrophages from transplants recipients without AZM exhibited significantly more LMP and cell death than macrophages from healthy subjects. Those macrophages contained significantly more Fe, while GSH and H-ferritin did not differ significantly. Although macrophages from transplant recipients treated with AZM contained both significantly more Fe and less GSH, which would sensitize cells to oxidants, these macrophages resisted oxidant challenge well. The preventive effect of AZM on oxidative LMP and J774 cell death was 60 to 300 times greater than the other drugs tested. Conclusions AZM makes lung transplant macrophages and their lysososomes more resistant to oxidant challenge. Possibly, prevention of obliterative bronchiolitis in lung transplants by AZM is partly due to this action. PMID:23006592

  3. Practical Guidelines: Lung Transplantation in Patients with Cystic Fibrosis

    PubMed Central

    Hirche, T. O.; Knoop, C.; Hebestreit, H.; Shimmin, D.; Solé, A.; Elborn, J. S.; Ellemunter, H.; Aurora, P.; Hogardt, M.; Wagner, T. O. F.; ECORN-CF Study Group

    2014-01-01

    There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation. PMID:24800072

  4. Lung transplantation and extracorporeal photopheresis: The answer to bronchiolitis obliterans?

    PubMed

    Yung, Gordon L; Craig, Vanessa

    2015-04-01

    Bronchiolitis obliterans (BO) is a rare condition characterized by narrowing of small airways. Although it can be caused by variety of conditions, most cases occur after lung and bone marrow transplantation in the form of graft-versus-host-disease and chronic rejection, respectively. Extracorporeal photopheresis (ECP) has emerged as a promising treatment for the condition, especially for BO after lung transplantation. Available data suggest that around two-thirds of patients may demonstrate either slowing or cessation of disease progression after treatment with ECP. Recent researches also provide interesting insights into possible mechanism of action of ECP in BO. PMID:25881738

  5. Cavitary lung lesion 6 years after renal transplantation.

    PubMed

    Subbiah, Arun Kumar; Arava, Sudheer; Bagchi, Soumita; Madan, Karan; Das, Chandan J; Agarwal, Sanjay Kumar

    2016-06-24

    The differential diagnoses of a cavitary lung lesion in renal transplant recipients would include infection, malignancy and less commonly inflammatory diseases. Bacterial infection, Tuberculosis, Nocardiosis, fungal infections like Aspergillosis and Cryptococcosis need to be considered in these patients. Pulmonary cryptococcosis usually presents 16-21 mo after transplantation, more frequently in patients who have a high level of cumulative immunosuppression. Here we discuss an interesting patient who never received any induction/anti-rejection therapy but developed both BK virus nephropathy as well as severe pulmonary Cryptococcal infection after remaining stable for 6 years after transplantation. This case highlights the risk of serious opportunistic infections even in apparently low immunologic risk transplant recipients many years after transplantation. PMID:27358792

  6. Cavitary lung lesion 6 years after renal transplantation

    PubMed Central

    Subbiah, Arun Kumar; Arava, Sudheer; Bagchi, Soumita; Madan, Karan; Das, Chandan J; Agarwal, Sanjay Kumar

    2016-01-01

    The differential diagnoses of a cavitary lung lesion in renal transplant recipients would include infection, malignancy and less commonly inflammatory diseases. Bacterial infection, Tuberculosis, Nocardiosis, fungal infections like Aspergillosis and Cryptococcosis need to be considered in these patients. Pulmonary cryptococcosis usually presents 16-21 mo after transplantation, more frequently in patients who have a high level of cumulative immunosuppression. Here we discuss an interesting patient who never received any induction/anti-rejection therapy but developed both BK virus nephropathy as well as severe pulmonary Cryptococcal infection after remaining stable for 6 years after transplantation. This case highlights the risk of serious opportunistic infections even in apparently low immunologic risk transplant recipients many years after transplantation. PMID:27358792

  7. Lung transplantation from donors after circulatory death using portable ex vivo lung perfusion

    PubMed Central

    Bozso, Sabin; Vasanthan, Vishnu; Luc, Jessica GY; Kinaschuk, Katie; Freed, Darren; Nagendran, Jayan

    2015-01-01

    BACKGROUND: Donation after circulatory death is a novel method of increasing the number of donor lungs available for transplantation. Using organs from donors after circulatory death has the potential to increase the number of transplants performed. METHODS: Three bilateral lung transplants from donors after circulatory death were performed over a six-month period. Following organ retrieval, all sets of lungs were placed on a portable ex vivo lung perfusion device for evaluation and preservation. RESULTS: Lung function remained stable during portable ex vivo perfusion, with improvement in partial pressure of oxygen/fraction of inspired oxygen ratios. Mechanical ventilation was discontinued within 48 h for each recipient and no patient stayed in the intensive care unit longer than eight days. There was no postgraft dysfunction at 72 h in two of the three recipients. Ninety-day mortality for all recipients was 0% and all maintain excellent forced expiratory volume in 1 s and forced vital capacity values post-transplantation. CONCLUSION: The authors report excellent results with their initial experience using donors after circulatory death after portable ex vivo lung perfusion. It is hoped this will allow for the most efficient use of available donor lungs, leading to more transplants and fewer deaths for potential recipients on wait lists. PMID:25379654

  8. Answers about Lung Transplantation for Pulmonary Hypertension

    MedlinePlus

    ... East PH Medical Resources Worldwide Resources in Other Languages Recursos en Español Connect with a Global Community ... essence, when undergoing transplant, a recipient trades their current medical disease for another medical condition that has ...

  9. Lobar lung transplantation--is it comparable with standard lung transplantation?

    PubMed

    Slama, Alexis; Ghanim, Bahil; Klikovits, Thomas; Scheed, Axel; Hoda, Mir A; Hoetzenecker, Konrad; Jaksch, Peter; Matilla, Jose; Taghavi, Sharokh; Klepetko, Walter; Aigner, Clemens

    2014-09-01

    Lobar lung transplantation is used mainly for urgent small recipients who are less likely to obtain size matched lungs in due time. Only limited numbers have been published, and we herewith report the largest series of lobar-LuTX. We analyzed our LuTX database from 1/2001 to 12/2012 and compared the outcome of lobar-LuTX recipients with those receiving standard LuTX. Seven hundred and seventy-eighty LuTX (group 1) were performed either in standard technique by implanting the whole lungs (n = 539) or with downsizing by wedge resection of the right middle lobe and/or the left lingula (n = 239). One hundred and thirty-eight LuTX were performed in lobar technique (group 2) to overcome more pronounced size discrepancies. Patients in group 1 had a different spectrum of diagnoses and were less frequently bridged to LuTX (P < 0.001). Intubation time, ICU stay, and hospital stay were shorter in group 1 (P < 0.001). One-year survival was 84.8% vs. 65.1%, and 5-years survival 69.9% vs. 54.9% (P < 0.001). In multivariate analyzes, procedure, diagnosis, and pre-operative bridging were shown to be significant prognostic factors in survival. Early postoperative outcome in Lobar LuTX was significantly inferior to standard LuTX recipients. However, survival rates of successfully dismissed patients were comparable with standard LuTX (P = 0.168); thereby, Lobar-LuTX remains an important option in the management of urgent small recipients. PMID:24810771

  10. Regeneration and orthotopic transplantation of a bioartificial lung.

    PubMed

    Ott, Harald C; Clippinger, Ben; Conrad, Claudius; Schuetz, Christian; Pomerantseva, Irina; Ikonomou, Laertis; Kotton, Darrell; Vacanti, Joseph P

    2010-08-01

    About 2,000 patients now await a donor lung in the United States. Worldwide, 50 million individuals are living with end-stage lung disease. Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange. We decellularized lungs by detergent perfusion and yielded scaffolds with acellular vasculature, airways and alveoli. To regenerate gas exchange tissue, we seeded scaffolds with epithelial and endothelial cells. To establish function, we perfused and ventilated cell-seeded constructs in a bioreactor simulating the physiologic environment of developing lung. By day 5, constructs could be perfused with blood and ventilated using physiologic pressures, and they generated gas exchange comparable to that of isolated native lungs. To show in vivo function, we transplanted regenerated lungs into orthotopic position. After transplantation, constructs were perfused by the recipient's circulation and ventilated by means of the recipient's airway and respiratory muscles, and they provided gas exchange in vivo for up to 6 h after extubation. PMID:20628374

  11. State of the Art of Combined Heart-Lung Transplantation for Advanced Cardiac and Pulmonary Dysfunction.

    PubMed

    Idrees, Jay J; Pettersson, Gösta B

    2016-04-01

    Over the last several decades, significant advances and improvements in care of transplant patients have resulted in markedly improved outcomes. A number of options are available for patients with advanced cardiopulmonary dysfunction requiring transplantation. There is a debate about when isolated heart or isolated lung transplantation is no longer possible or advisable and combined heart-lung transplantation is justified. Organ availability and allocation severely limit the latter option to very few well-selected patients. We review practice patterns, trends, and outcomes after triple-organ heart-lung transplant (HLTx) worldwide, as well as our own experience with heart-lung transplant in the modern era. PMID:26922590

  12. Risk factors for lung diseases after renal transplantation

    PubMed Central

    Pencheva, Ventsislava P.; Petrova, Daniela S.; Genov, Diyan K.; Georgiev, Ognian B.

    2015-01-01

    Background: Lung diseases are one of the major causes of morbidity and mortality after renal transplantation. The aim of the study is to define the risk factors for infectious and noninfectious pulmonary complications in kidney transplant patients. Materials and Methods: We prospectively studied 267 patients after renal transplantation. The kidney recipients were followed-up for the development of pulmonary complications for a period of 7 years. Different noninvasive and invasive diagnostic tests were used in cases suspected of lung disease. Results: The risk factors associated with the development of pulmonary complications were diabetes mellitus (odds ratio [OR] = 4.60; P = 0.001), arterial hypertension (OR = 1.95; P = 0.015), living related donor (OR = 2.69; P = 0.004), therapy for acute graft rejection (OR = 2.06; P = 0.038), immunosuppressive regimens that includes mycophenolate (OR = 2.40; P = 0.011), azathioprine (OR = 2.25; P = 0.023), and tacrolimus (OR = 1.83; P = 0.041). The only factor associated with the lower risk of complications was a positive serology test for Cytomegalovirus of the recipient before transplantation (OR = 0.1412; P = 0.001). Conclusion: The risk factors can be used to identify patients at increased risk for posttransplant lung diseases. Monitoring of higher-risk patients allow timely diagnosis and early adequate treatment and can reduce the morbidity and mortality after renal transplantation. PMID:26958045

  13. Persistent Human Cosavirus Infection in Lung Transplant Recipient, Italy

    PubMed Central

    Campanini, Giulia; Rovida, Francesca; Meloni, Federica; Cascina, Alessandro; Ciccocioppo, Rachele; Piralla, Antonio

    2013-01-01

    Human cosavirus is a novel picornavirus recently identified in feces from children in southern Asia. We report infection with human cosavirus in a patient in the Mediterranean area. The patient was an adult double lung transplant recipient who had chronic diarrhea associated with persistent infection with human cosavirus. PMID:24047954

  14. Mycobacterium bovis hip bursitis in a lung transplant recipient.

    PubMed

    Dan, J M; Crespo, M; Silveira, F P; Kaplan, R; Aslam, S

    2016-02-01

    We present a report of extrapulmonary Mycobacterium bovis infection in a lung transplant recipient. M. bovis is acquired predominantly by zoonotic transmission, particularly from consumption of unpasteurized foods. We discuss epidemiologic exposure, especially as relates to the Mexico-US border, clinical characteristics, resistance profile, and treatment. PMID:26671334

  15. Moving Back to the Future: Use of Organ Care System Lung for Lobectomy Before Lobar Lung Transplantation.

    PubMed

    Sabashnikov, Anton; Zeriouh, Mohamed; Mohite, Prashant N; Patil, Nikhil P; García-Sáez, Diana; Schmack, Bastian; Soresi, Simona; Dohmen, Pascal M; Popov, Aron-Frederik; Weymann, Alexander; Simon, André R; De Robertis, Fabio

    2016-01-01

    BACKGROUND Lung transplantation remains the gold standard treatment for patients with end-stage lung disease. Lobar lung transplantation allows for transplantation of size-mismatch donor lungs in small recipients; however, donor lung volume reduction represents a challenging surgical technique. In this paper we present our initial experience with bilateral lobectomy in donor lungs before lobar lung transplantation using normothermic perfusion on the Organ Care System (OCS) Lung. MATERIAL AND METHODS Specifics of the surgical technique for donor lung instrumentation on the OCS, lobar dissection on the OCS, and right and left donor lobectomies are presented in detail. RESULTS Potential advantages of the use of the OCS for lobectomy for lobar lung transplantation are described in this section. Donor lung volume reduction utilizing OCS appeared to be easier and safer compared to the conventional cold storage technique, due to continuous perfusion of the lungs with blood and well-distended vessels that offer the feel of live lobectomy. Moreover, the OCS represents a platform for donor organ assessment and optimization of its function before transplantation. CONCLUSIONS Donor lung volume reduction was safe and feasible utilizing the OCS, which could be a useful tool for volume reduction in cases of size mismatch. Further research is needed to evaluate early and long-term results after lobar lung transplantation using the OCS in clinical studies. PMID:27425199

  16. Moving Back to the Future: Use of Organ Care System Lung for Lobectomy Before Lobar Lung Transplantation

    PubMed Central

    Sabashnikov, Anton; Zeriouh, Mohamed; Mohite, Prashant N.; Patil, Nikhil P.; García-Sáez, Diana; Schmack, Bastian; Soresi, Simona; Dohmen, Pascal M.; Popov, Aron-Frederik; Weymann, Alexander; Simon, André R.; De Robertis, Fabio

    2016-01-01

    Background Lung transplantation remains the gold standard treatment for patients with end-stage lung disease. Lobar lung transplantation allows for transplantation of size-mismatch donor lungs in small recipients; however, donor lung volume reduction represents a challenging surgical technique. In this paper we present our initial experience with bilateral lobectomy in donor lungs before lobar lung transplantation using normothermic perfusion on the Organ Care System (OCS) Lung. Material/Methods Specifics of the surgical technique for donor lung instrumentation on the OCS, lobar dissection on the OCS, and right and left donor lobectomies are presented in detail. Results Potential advantages of the use of the OCS for lobectomy for lobar lung transplantation are described in this section. Donor lung volume reduction utilizing OCS appeared to be easier and safer compared to the conventional cold storage technique, due to continuous perfusion of the lungs with blood and well-distended vessels that offer the feel of live lobectomy. Moreover, the OCS represents a platform for donor organ assessment and optimization of its function before transplantation. Conclusions Donor lung volume reduction was safe and feasible utilizing the OCS, which could be a useful tool for volume reduction in cases of size mismatch. Further research is needed to evaluate early and long-term results after lobar lung transplantation using the OCS in clinical studies. PMID:27425199

  17. The putative role of mast cells in lung transplantation.

    PubMed

    Jungraithmayr, W

    2015-03-01

    Mast cells (MCs) were primarily recognized as effector cells of allergy. These cells are acting predominantly at the interface between the host and the external environment, such as skin, gastrointestinal and the respiratory tract. Only recently, MCs have gained increased recognition as cells of functional plasticity with immune-regulatory properties that influence both the innate and the adaptive immune response in inflammatory disorders, cancer and transplantation. Through the secretion of both proinflammatory and antiinflammatory mediators, MCs can either ameliorate or deteriorate the course and outcome in lung transplantation. Recent research from other models recognized the immune-protective activity of MCs including its role as an important source of IL-10 and TGF-β for the modulation of alloreactive T cell responses or assistance in Treg activity. This paper summarizes the current understanding of MCs in lung transplantation and discusses MC-mediated immune-mechanisms by which the outcome of the engrafted organ is modulated. PMID:25693471

  18. Beneficial effects of synthetic KL₄ surfactant in experimental lung transplantation.

    PubMed

    Sáenz, A; Alvarez, L; Santos, M; López-Sánchez, A; Castillo-Olivares, J L; Varela, A; Segal, R; Casals, C

    2011-04-01

    The aim of this study was to investigate whether intratracheal administration of a new synthetic surfactant that includes the cationic, hydrophobic 21-residue peptide KLLLLKLLLLKLLLLKLLLLK (KL₄), might be effective in reducing ischaemia-reperfusion injury after lung transplantation. Single left lung transplantation was performed in Landrace pigs 22 h post-harvest. KL₄ surfactant at a dose of 25 mg total phospholipid·kg body weight⁻¹ (2.5 mL·kg body weight⁻¹) was instilled at 37°C to the donor left lung (n = 8) prior to explantation. Saline (2.5 mL·kg body weight⁻¹; 37°C) was instilled into the donor left lung of the untreated group (n = 6). Lung function in recipients was measured during 2 h of reperfusion. Recipient left lung bronchoalveolar lavage (BAL) provided native cytometric, inflammatory marker and surfactant data. KL(4) surfactant treatment recovered oxygen levels in the recipient blood (mean ± sd arterial oxygen tension/inspiratory oxygen fraction 424 ± 60 versus 263 ± 101 mmHg in untreated group; p=0.01) and normalised alveolar-arterial oxygen tension difference. Surfactant biophysical function was also recovered in KL₄ surfactant-treated lungs. This was associated with decreased C-reactive protein levels in BAL, and recovery of surfactant protein A content, normalised protein/phospholipid ratios, and lower levels of both lipid peroxides and protein carbonyls in large surfactant aggregates. These findings suggest an important protective role for KL₄ surfactant treatment in lung transplantation. PMID:20650990

  19. Lung-enriched Organisms and Aberrant Bacterial and Fungal Respiratory Microbiota after Lung Transplant

    PubMed Central

    Charlson, Emily S.; Diamond, Joshua M.; Bittinger, Kyle; Fitzgerald, Ayannah S.; Yadav, Anjana; Haas, Andrew R.; Bushman, Frederic D.

    2012-01-01

    Rationale: Long-term survival after lung transplantation is limited by infectious complications and by bronchiolitis obliterans syndrome (BOS), a form of chronic rejection linked in part to microbial triggers. Objectives: To define microbial populations in the respiratory tract of transplant patients comprehensively using unbiased high-density sequencing. Methods: Lung was sampled by bronchoalveolar lavage (BAL) and upper respiratory tract by oropharyngeal wash (OW). Bacterial 16S rDNA and fungal internal transcribed spacer sequencing was used to profile organisms present. Outlier analysis plots defining taxa enriched in lung relative to OW were used to identify bacteria enriched in lung against a background of oropharyngeal carryover. Measurements and Main Results: Lung transplant recipients had higher bacterial burden in BAL than control subjects, frequent appearance of dominant organisms, greater distance between communities in BAL and OW indicating more distinct populations, and decreased respiratory tract microbial richness and diversity. Fungal populations were typically dominated by Candida in both sites or by Aspergillus in BAL but not OW. 16S outlier analysis identified lung-enriched taxa indicating bacteria replicating in the lower respiratory tract. In some cases this confirmed respiratory cultures but in others revealed enrichment by anaerobic organisms or mixed outgrowth of upper respiratory flora and provided quantitative data on relative abundances of bacteria found by culture. Conclusions: Respiratory tract microbial communities in lung transplant recipients differ in structure and composition from healthy subjects. Outlier analysis can identify specific bacteria replicating in lung. These findings provide novel approaches to address the relationship between microbial communities and transplant outcome and aid in assessing lung infections. PMID:22798321

  20. Impairment of bronchial mucociliary clearance in long-term survivors of heart/lung and double-lung transplantation. The Paris-Sud Lung Transplant Group.

    PubMed

    Herve, P; Silbert, D; Cerrina, J; Simonneau, G; Dartevelle, P

    1993-01-01

    The study objective was to investigate bronchial mucociliary clearance after heart/lung and double lung transplantation. Bronchial mucociliary clearance was measured using a noninvasive radioaerosol technique: 99mTc-labeled albumin was aerosolized using a spinning-top generator (mass median aerodynamic diameter, 7.5 mu; geometric standard deviation, 1.5 mu). Radioactivity counts were acquired during 60 min with a gamma camera. A region of interest was drawn over the right lung delineated by a 133Xe lung ventilation image. Bronchial mucociliary clearance was assessed as the percentage of decrease in radioactivity per hour calculated on time-activity curves fitted by a monoexponential model. To exclude patients with acute lung rejection, opportunistic lung infection, and obliterative bronchiolitis, all patients with transplants underwent pulmonary function tests and bronchoscopic examination before clearance measurement. Eight heart/lung and five double-lung nonsmoking transplant patients with normal lung histology were studied 19.3 +/- 4.0 mo after surgery and compared to nine normal nonsmokers. A similar proximal deposition of the aerosol was obtained in patients with transplants and normal subjects; skew values of distribution histograms of aerosol radioactivity counts were 2.1 +/- 0.2 and 1.8 +/- 0.1, respectively, and the ratios between central and peripheral 99mTc radioactivity counts were 2.4 +/- 0.1 and 2.3 +/- 0.2, respectively. No significant difference was observed in bronchial clearance values between patients with heart/lung and double-lung transplants (26.4 +/- 3.0 percent/h vs 35.9 +/- 3.5 percent/h). Conversely, bronchial clearance was significantly lower in transplant recipients (30.0 +/- 2.5 percent/h) than in normal controls (58.7 +/- 6.2 percent/h; p < 0.001). This decreased bronchial clearance can be expected to increase the risk of lung infection in long-term survivors of heart/lung and double-lung transplantation. PMID:8380268

  1. What to Expect After a Lung Transplant

    MedlinePlus

    ... recovery. You'll be taught how to do deep breathing exercises with an incentive spirometer (spi-ROM- ... This hand-held device helps you take slow, deep breaths. You also may have lung function tests ...

  2. A staged approach for a lung-liver transplant patient using ex vivo reconditioned lungs first followed by an urgent liver transplantation.

    PubMed

    Van De Wauwer, Caroline; Verschuuren, Erik A M; Nossent, George D; van der Bij, Wim; den Hamer, Inez J; Klinkenberg, Theo J; van den Berg, Aad P; de Boer, Marieke T; Mariani, Massimo A; Erasmus, Michiel E

    2015-01-01

    Combined lung-liver transplantation is a logistically challenging procedure hampered by shortage of organ donors. We describe the case of a young patient with end-stage lung disease due to of cystic fibrosis and liver cirrhosis who needed combined lung-liver transplantation. The long waiting for this caused an interesting clinical dilemma. We decided to change our policy in this situation by listing him only for the lung transplantation and to apply for a high urgent liver transplantation if the liver failed after the lung transplantation. This strategy enabled us to use lungs treated with ex vivo lung perfusion (EVLP) from an unsuitable donor after circulatory death. After conditioning for 4 h via EVLP, the pO2 was 59.7 kPa. The lungs were transplanted successfully. He developed an acute-on-chronic liver failure for which he received a successful liver transplantation 19 days after the lung transplantation. PMID:25070399

  3. Systematic review of melanoma incidence and prognosis in solid organ transplant recipients

    PubMed Central

    2014-01-01

    Cutaneous melanoma carries the potential for substantial morbidity and mortality in the solid organ transplant population. We systematically reviewed the literature published from January 1995 to January 2012 to determine the overall relative risk and prognosis of melanoma in transplant recipients. Our search identified 7,512 citations. Twelve unique non-overlapping studies reported the population-based incidence of melanoma in an inception cohort of solid organ transplant recipients. Compared to the general population, there is a 2.4-fold (95% confidence interval, 2.0 to 2.9) increased incidence of melanoma after transplantation. No population-based outcome data were identified for melanoma arising post-transplant. Data from non-population based cohort studies suggest a worse prognosis for late-stage melanoma developing after transplantation compared with the general population. For patients with a history of pre-transplant melanoma, one population-based study reported a local recurrence rate of 11% (2/19) after transplantation, although staging and survival information was lacking. There is a need for population-based data on the prognosis of melanoma arising pre- and post-transplantation. Increased incidence and potentially worse melanoma outcomes in this high-risk population have implications for clinical care in terms of prevention, screening and reduction of immunosuppression after melanoma development post-transplant, as well as transplantation decisions in patients with a history of pre-transplant melanoma. PMID:24834346

  4. Effect of lung transplantation on diaphragmatic function in patients with chronic obstructive pulmonary disease.

    PubMed Central

    Wanke, T.; Merkle, M.; Formanek, D.; Zifko, U.; Wieselthaler, G.; Zwick, H.; Klepetko, W.; Burghuber, O. C.

    1994-01-01

    BACKGROUND--To date there are no data on the effects of lung transplantation on diaphragmatic function in patients with end stage chronic obstructive pulmonary disease (COPD). It is not known whether the relation between the transdiaphragmatic pressure (PDI) and lung volume is altered in recipients after transplantation as a result of changes in diaphragmatic structure caused by chronic hyperinflation. The effect of lung transplantation on diaphragmatic strength was determined in patients with COPD and the relation between postoperative PDI and lung volume analysed. METHODS--Diaphragmatic strength was assessed in eight double lung transplant recipients, six single lung transplant recipients, and in 14 patients with COPD whose lung function was similar to those of the transplant recipients preoperatively. PDI obtained during unilateral and bilateral phrenic nerve stimulation at 1 Hz (twitch PDI) at functional residual capacity (FRC) and during maximal sniff manoeuvres (sniff PDI) at various levels of inspiratory vital capacity (VCin) served as parameters for diaphragmatic strength. Sniff PDI assessed at the various VCin levels were used to analyse the PDI/lung volume relation. RESULTS--Lung transplantation caused a reduction in lung volume, especially in the double lung transplant recipients. As a consequence sniff PDI was higher in the double lung transplant recipients than in the patients with COPD at all levels of VCin analysed. However, sniff PDI values analysed at comparable intrathoracic gas volumes were not reduced in the patients with COPD when compared with those who underwent lung transplantation. Bilateral twitch PDI values were similar in the patients with COPD and in the lung transplant recipients. In the single lung transplant recipients unilateral twitch PDI values were similar on the transplanted and the non-transplanted side. The relation between PDI and lung volume was similar in the patients with COPD and in the lung transplant recipients

  5. Fatal obstructive lung disease after haploidentical sibling cord blood transplantation.

    PubMed

    Ohnuma, K; Toyoda, Y; Ishida, Y; Honda, K; Nagao, T; Ijiri, R; Tanaka, Y; Goto, K; Hiroki, K; Kigasawa, H; Nishihira, H

    1998-05-01

    We report the case of a patient with fatal obstructive lung disease after an HLA-haploidentical sibling cord blood transplant (CBT), with severe acute GVHD. A 2-year-old girl developed expiratory air trapping gradually with acute and chronic GVHD after CBT for the treatment of ALL. Anti-CMV and immunosuppressive therapy were ineffective, and the patient died of progressive respiratory acidosis. Necropsy of the lung revealed severe bronchiolitis obliterans with cytomegalic inclusion cells in the granulation tissues of the bronchiolitis. Thus, immunologic and GVHD problems can occur even in CBT. PMID:9613788

  6. Rhodococcal lung abscess in a renal transplant recipient

    PubMed Central

    Wong, Koh-Wei; Thevarajah, Bharathan

    2012-01-01

    Summary Background: Rhodococcus species are relatively rare human pathogens, but are being increasingly recognized as causes of infection especially in immunosuppressed patients. Case Report: We present a case of Rhodococcus lung abscess in a patient 10 months post-cadaveric renal transplant, successfully treated with a combination of antibiotics. She required a prolonged course of oral antibiotics for 6 months. She did not require surgical intervention. Chest X-rays and CT thorax showed complete resolution of the initial lesion. We also review the medical literature related to Rhodococcus infection in patients with renal transplantation. Rhodococcus infection should be considered as in the differential diagnosis of immunosuppressed patients who present with lung abscess/mass. Conclusions: A literature review indicates this is a potentially fatal condition with disseminated sepsis/abscesses. PMID:23569526

  7. Thrombotic microangiopathy associated with tacrolimus in lung transplantation.

    PubMed

    Reig Mezquida, Juan Pablo; Jover, Amparo Solé; Ansótegui Barrera, Emilio; Escrivá Peiró, Juan; Pastor Colom, Maria Desamparados; Pastor Guillem, Juan

    2015-05-01

    Thrombotic microangiopathy (TMA) is a rare complication associated with the use of calcineurin inhibitors in lung transplantation, irrespective of the underlying disease of the graft recipient. It usually occurs in incomplete forms, complicating and delaying diagnosis until damage is already irreversible. It is unrelated to time from transplantation and often presents with concomitant infection, which tends to confound diagnosis. The cases discussed here have a common causative agent and all present with concomitant infection. Treatment recommendations have changed in recent years with the introduction of plasmapheresis or, more recently, the availability of the antibody eculizumab. Notwithstanding, the most cost-effective measure is withdrawal or switching of the calcineurin inhibitor. TMA is an underdiagnosed clinical entity that should be considered in the management of transplantation patients. PMID:25138798

  8. Incidence and etiology of lung cancer in the Pacific Basin.

    PubMed

    Hirohata, T; Fukuda, K

    1979-11-01

    Incidence of lung cancer in the Pacific Basin was either compiled from published reports or computed by the authors. The results showed a great variation in age-standardized annual incidence rates of lung cancer among 10 countries and 17 areas in the Pacific Basin where tumor registry statistics are available. For males the incidence rates ranged from 10 to over 70 and for females from less than 5 to over 30/100,000 population. The reason(s) for the great variation is unclear. Ionizing radiation, carcinogenic chemical substances (e.g., chromium, arsenic compounds, asbestos, etc.), or air pollution are unlikely to be responsible. Because cigarette smoking is known to be a major cause of lung cancer, the authors have suggested that surveys on cigarette smoking be conducted among various populations in the Pacific Basin so that etiologic significance of cigarette smoking for the noted variation can be assessed. In Hawaii such a survey is underway, and a preliminary analysis was made to examine the association between lung cancer and cigarette smoking among five races. PMID:537621

  9. Anesthetic experience in patient for single lung transplantation with previous contralateral pneumonectomy -A case report-.

    PubMed

    Chung, Ji-Hyun; Cha, Seung-Cheol; Hwang, Jin-Hwan; Woo, Seong Chang

    2012-05-01

    A 48-year-old woman with cystic fibrosis and a previous left pneumonectomy had surgery planned for single lung transplantation under general anesthesia. Due to progressive dyspnea and recurrent respiratory infection, she could not maintain her normal daily life without lung transplantation. The anesthetic management and surgical procedure was expected to be difficult because of the left mediastinal shift and an asymmetric thorax after the left pneumonectomy, but the single lung transplantation was successfully done under cardiopulmonary bypass. PMID:22679547

  10. When the Battle is Lost and Won: Delayed Chest Closure After Bilateral Lung Transplantation

    PubMed Central

    Soresi, Simona; Sabashnikov, Anton; Weymann, Alexander; Zeriouh, Mohamed; Simon, André R.; Popov, Aron-Frederik

    2015-01-01

    In this article we summarize benefits of delayed chest closure strategy in lung transplantation, addressing indications, different surgical techniques, and additional perioperative treatment. Delayed chest closure seems to be a valuable and safe strategy in managing patients with various conditions after lung transplantation, such as instable hemodynamics, need for high respiratory pressures, coagulopathy, and size mismatch. Therefore, this approach should be considered in lung transplant centers to give patients time to recover before the chest is closed. PMID:26456363

  11. When the Battle is Lost and Won: Delayed Chest Closure After Bilateral Lung Transplantation.

    PubMed

    Soresi, Simona; Sabashnikov, Anton; Weymann, Alexander; Zeriouh, Mohamed; Simon, André R; Popov, Aron-Frederik

    2015-01-01

    In this article we summarize benefits of delayed chest closure strategy in lung transplantation, addressing indications, different surgical techniques, and additional perioperative treatment. Delayed chest closure seems to be a valuable and safe strategy in managing patients with various conditions after lung transplantation, such as instable hemodynamics, need for high respiratory pressures, coagulopathy, and size mismatch. Therefore, this approach should be considered in lung transplant centers to give patients time to recover before the chest is closed. PMID:26456363

  12. ST-Elevation Myocardial Infarction 33 Days after Lung Transplant in a Patient with Non-Significant CAD before Transplantation: A Case Report

    PubMed Central

    Parsa, Saeed Alipour; Dousti, Amir; Naghashzadeh, Farah; Ataeinia, Bahar

    2016-01-01

    Acute myocardial infarction after lung transplantation is not well illustrated in the literature. We present a patient with documented non significant Coronary Artery Disease (CAD) in coronary angiography before lung transplant who was referred to our hospital with acute Myocardial Infarction (MI) 33 days following lung transplantation.

  13. Viral metagenomics reveal blooms of anelloviruses in the respiratory tract of lung transplant recipients

    PubMed Central

    Young, Jacque C.; Chehoud, Christel; Bittinger, Kyle; Bailey, Aubrey; Diamond, Joshua M.; Cantu, Edward; Haas, Andrew R.; Abbas, Arwa; Frye, Laura; Christie, Jason D.; Bushman, Frederic D.; Collman, Ronald G.

    2014-01-01

    Few studies have examined the lung virome in health and disease. Outcomes of lung transplantation are known to be influenced by several recognized respiratory viruses, but global understanding of the virome of the transplanted lung is incomplete. To define the DNA virome within the respiratory tract following lung transplantation we carried out metagenomic analysis of allograft bronchoalveolar lavage (BAL), and compared to healthy and HIV+ subjects. Viral concentrates were purified from BAL and analyzed by shotgun DNA sequencing. All of the BAL samples contained reads mapping to anelloviruses, with high proportions in lung transplant samples. Anellovirus populations in transplant recipients were complex, with multiple concurrent variants. Q-PCR quantification revealed that anellovirus sequences were 56-fold more abundant in BAL from lung transplant recipients compared with healthy controls or HIV+ subjects (p<0.0001). Anellovirus sequences were also more abundant in upper respiratory tract specimens from lung transplant recipients than controls (p=0.006). Comparison to metagenomic data on bacterial populations showed that high anellovirus loads correlated with dysbiotic bacterial communities in allograft BAL (p=0.00816). Thus the respiratory tracts of lung transplant recipients contain high levels and complex populations of anelloviruses, warranting studies of anellovirus lung infection and transplant outcome. PMID:25403800

  14. Invasive Microascus trigonosporus Species Complex Pulmonary Infection in a Lung Transplant Recipient

    PubMed Central

    Schoeppler, Kelly E.; Zamora, Martin R.; Northcutt, Noelle M.; Barber, Gerard R.; O'Malley-Schroeder, Gayle; Lyu, Dennis M.

    2015-01-01

    Because of the high incidence of morbidity and mortality associated with invasive fungal infections, antifungal prophylaxis is often used in solid organ transplant recipients. However, this prophylaxis is not universally effective and may contribute to the selection of emerging, resistant pathogens. Here we present a rare case of invasive infection caused by Microascus trigonosporus species complex in a human, which developed during voriconazole prophylaxis in a lung transplant recipient. Nebulized liposomal amphotericin B was used in addition to systemic therapy in order to optimize antifungal drug exposure; this regimen appeared to reduce the patient's fungal burden. Despite this apparent improvement, the patient's pulmonary status progressively declined in the setting of multiple comorbidities, ultimately leading to respiratory failure and death. PMID:26075134

  15. Invasive Microascus trigonosporus Species Complex Pulmonary Infection in a Lung Transplant Recipient.

    PubMed

    Schoeppler, Kelly E; Zamora, Martin R; Northcutt, Noelle M; Barber, Gerard R; O'Malley-Schroeder, Gayle; Lyu, Dennis M

    2015-01-01

    Because of the high incidence of morbidity and mortality associated with invasive fungal infections, antifungal prophylaxis is often used in solid organ transplant recipients. However, this prophylaxis is not universally effective and may contribute to the selection of emerging, resistant pathogens. Here we present a rare case of invasive infection caused by Microascus trigonosporus species complex in a human, which developed during voriconazole prophylaxis in a lung transplant recipient. Nebulized liposomal amphotericin B was used in addition to systemic therapy in order to optimize antifungal drug exposure; this regimen appeared to reduce the patient's fungal burden. Despite this apparent improvement, the patient's pulmonary status progressively declined in the setting of multiple comorbidities, ultimately leading to respiratory failure and death. PMID:26075134

  16. Trends in Lung Cancer Incidence in a Healthcare Area.

    PubMed

    Molina, Antonio J; García-Martínez, Lidia; Zapata-Alvarado, Julio; Alonso-Orcajo, Nieves; Fernández-Villa, Tania; Martín, Vicente

    2015-11-01

    The aim of this study was to identify trends in the incidence of lung cancer in the Leon Healthcare Area. All cases of cancer among residents of the Leon healthcare catchment area listed in the hospital-based tumor registry of the Centro Asistencial Universitario de Leon (CAULE) between 1996 and 2010 were included. Gross incidence rates over 3-year intervals were calculated and adjusted for the worldwide and European populations. A total of 2,491 cases were included. In men, incidence adjusted for the European population rose from 40.1 new cases per 100,000 population (1996-1998) to 61.8 (2005-2007), and then fell to 54.6 (2008-2010). In women, incidence tripled from 3.0 (1996-1998) to 9.2 new cases per 100,000 (2008-2010). Although lung cancer is an avoidable disease, it is a serious problem in the Leon Healthcare Area. Of particular concern is the rising incidence among women. PMID:26153559

  17. Invasive pulmonary Aspergillosis in organ transplants--Focus on lung transplants.

    PubMed

    Geltner, Christian; Lass-Flörl, Cornelia

    2016-03-01

    Infections with filamentous fungi are common in transplant recipients. The risk for aspergillosis and other invasive pulmonary mycosis (IPM) is high in patients undergoing stem cell and lung transplantations. The mortality rates range from 20% to 60% and depend on a number of risk factors. The typical manifestations of IPM are lung infiltrates, consolidations, and fungal tracheobronchitis. The most common infectious agent is Aspergillus fumigatus. Infections caused by non-Aspergillus molds are more frequent for various reasons. The species distribution of non-Aspergillus molds varies in different locations. Furthermore, infections caused by Mucor and Penicillium are increasing, as are infections caused by species resistant to azoles and amphotericin B. Most centers use antifungal prophylaxis with inhaled amphotericin B or oral azoles. Early diagnosis and therapy is crucial. Reliable information on the local microbiological spectrum is a prerequisite for the effective treatment of molds with primary or secondary resistance to antimycotic drugs. PMID:26879476

  18. Incidence of Malignancy after Living Kidney Transplantation: A Multicenter Study from Iran

    PubMed Central

    Einollahi, Behzad; Rostami, Zohreh; Nourbala, Mohammad Hossein; Lessan-Pezeshki, Mahboob; Simforoosh, Naser; Nemati, Eghlim; Pourfarziani, Vahid; Beiraghdar, Fatemeh; Nafar, Mohsen; Pour-Reza-Gholi, Fatemeh; Mazdeh, Mitra Mahdavi; Amini, Manochehr; Ahmadpour, Pedram; Makhdoomi, Khadijeh; Ghafari, Ali; Ardalan, Mohammad Reza; Khosroshahi, Hamid Taebi; Oliaei, Farshid; Shahidi, Shahrzad; Abbaszadeh, Shahin; Fatahi, Mohammad Reza; Hiedari, Fatemeh; Makhlogh, Atehieh; Azmandian, Jalal; Samimagham, Hamid Reza; Shahbazian, Heshmatollah; Nazemian, Fatemeh; Naghibi, Massih; Khosravi, Masoud; Monfared, Ali; Mosavi, Seyed Majid; Ahmadi, Javad; Jalalzadeh, Mojgan

    2012-01-01

    Malignancy is a common complication after renal transplantation. However, limited data are available on post-transplant malignancy in living kidney transplantation. Therefore, we made a plan to evaluate the incidence and types of malignancies, association with the main risk factors and patient survival in a large population of living kidney transplantation. We conducted a large retrospective multicenter study on 12525 renal recipients, accounting for up to 59% of all kidney transplantation in Iran during 22 years follow up period. All information was collected from observation of individual notes or computerized records for transplant patients. Two hundred and sixty-six biopsy-proven malignancies were collected from 16 Transplant Centers in Iran; 26 different type of malignancy categorized in 5 groups were detected. The mean age of patients was 46.2±12.9 years, mean age at tumor diagnosis was 50.8±13.2 years and average time between transplantation and detection of malignancy was 50.0±48.4 months. Overall tumor incidence in recipients was 2%. Kaposis' sarcoma was the most common type of tumor. The overall mean survival time was 117.1 months (95% CI: 104.9-129.3). In multivariate analysis, the only independent risk factor associated with mortality was type of malignancy. This study revealed the lowest malignancy incidence in living unrelated kidney transplantation. PMID:22712025

  19. Effect of Irradiation on Incidence of Post-Transplant Lymphoproliferative Disorder after Hematopoietic Cell Transplantation in Miniature Swine.

    PubMed

    Matar, Abraham J; Patil, Aarti R; Al-Musa, Ahmad; Hanekamp, Isabel; Sachs, David H; Huang, Christene A; Duran-Struuck, Raimon

    2015-10-01

    Post-transplant lymphoproliferative disease (PTLD) is a major complication of clinical organ and cell transplantation. Conditioning and immunosuppressive regimens that significantly impair T cell immunity, including depleting antibodies and calcineurin inhibitors, increase the risk of PTLD after transplantation. Swine PTLD has been shown to closely resemble human PTLD in morphology, histology, and viral-driven reactivation of B cells. Previously, we reported high incidences of PTLD after hematopoietic cell transplantation (HCT) in miniature swine recipients conditioned with thymic irradiation (TI) in addition to T cell depletion and cyclosporine A monotherapy after transplantation. Replacement of TI with 100 cGy of total body irradiation resulted in similar numbers of B cells early post-transplantation, greater numbers of T cells at day 0, and markedly decreased incidence of PTLD, suggesting that a threshold number of T cells may be necessary to prevent subsequent B cell proliferation and development of overt PTLD. Results from this large cohort of animals provide insight into the important effect of irradiation and T cell immunity on the incidence of PTLD after HCT and reinforce the pig model as a valuable tool for the study of PTLD and HCT. PMID:26210443

  20. The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation.

    PubMed

    Weber, Daniel J; Gracon, Adam S A; Ripsch, Matthew S; Fisher, Amanda J; Cheon, Bo M; Pandya, Pankita H; Vittal, Ragini; Capitano, Maegan L; Kim, Youngsong; Allette, Yohance M; Riley, Amanda A; McCarthy, Brian P; Territo, Paul R; Hutchins, Gary D; Broxmeyer, Hal E; Sandusky, George E; White, Fletcher A; Wilkes, David S

    2014-09-01

    Traumatic brain injury (TBI) results in systemic inflammatory responses that affect the lung. This is especially critical in the setting of lung transplantation, where more than half of donor allografts are obtained postmortem from individuals with TBI. The mechanism by which TBI causes pulmonary dysfunction remains unclear but may involve the interaction of high-mobility group box-1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). To investigate the role of HMGB1 and RAGE in TBI-induced lung dysfunction, RAGE-sufficient (wild-type) or RAGE-deficient (RAGE(-/-)) C57BL/6 mice were subjected to TBI through controlled cortical impact and studied for cardiopulmonary injury. Compared to control animals, TBI induced systemic hypoxia, acute lung injury, pulmonary neutrophilia, and decreased compliance (a measure of the lungs' ability to expand), all of which were attenuated in RAGE(-/-) mice. Neutralizing systemic HMGB1 induced by TBI reversed hypoxia and improved lung compliance. Compared to wild-type donors, lungs from RAGE(-/-) TBI donors did not develop acute lung injury after transplantation. In a study of clinical transplantation, elevated systemic HMGB1 in donors correlated with impaired systemic oxygenation of the donor lung before transplantation and predicted impaired oxygenation after transplantation. These data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway before transplant may improve recipient outcomes after lung transplantation. PMID:25186179

  1. Noninvasive monitoring of infection and rejection after lung transplantation

    PubMed Central

    De Vlaminck, Iwijn; Martin, Lance; Kertesz, Michael; Patel, Kapil; Kowarsky, Mark; Strehl, Calvin; Cohen, Garrett; Luikart, Helen; Neff, Norma F.; Okamoto, Jennifer; Nicolls, Mark R.; Cornfield, David; Weill, David; Valantine, Hannah; Khush, Kiran K.; Quake, Stephen R.

    2015-01-01

    The survival rate following lung transplantation is among the lowest of all solid-organ transplants, and current diagnostic tests often fail to distinguish between infection and rejection, the two primary posttransplant clinical complications. We describe a diagnostic assay that simultaneously monitors for rejection and infection in lung transplant recipients by sequencing of cell-free DNA (cfDNA) in plasma. We determined that the levels of donor-derived cfDNA directly correlate with the results of invasive tests of rejection (area under the curve 0.9). We also analyzed the nonhuman cfDNA as a hypothesis-free approach to test for infections. Cytomegalovirus is most frequently assayed clinically, and the levels of CMV-derived sequences in cfDNA are consistent with clinical results. We furthermore show that hypothesis-free monitoring for pathogens using cfDNA reveals undiagnosed cases of infection, and that certain infectious pathogens such as human herpesvirus (HHV) 6, HHV-7, and adenovirus, which are not often tested clinically, occur with high frequency in this cohort. PMID:26460048

  2. Noninvasive monitoring of infection and rejection after lung transplantation.

    PubMed

    De Vlaminck, Iwijn; Martin, Lance; Kertesz, Michael; Patel, Kapil; Kowarsky, Mark; Strehl, Calvin; Cohen, Garrett; Luikart, Helen; Neff, Norma F; Okamoto, Jennifer; Nicolls, Mark R; Cornfield, David; Weill, David; Valantine, Hannah; Khush, Kiran K; Quake, Stephen R

    2015-10-27

    The survival rate following lung transplantation is among the lowest of all solid-organ transplants, and current diagnostic tests often fail to distinguish between infection and rejection, the two primary posttransplant clinical complications. We describe a diagnostic assay that simultaneously monitors for rejection and infection in lung transplant recipients by sequencing of cell-free DNA (cfDNA) in plasma. We determined that the levels of donor-derived cfDNA directly correlate with the results of invasive tests of rejection (area under the curve 0.9). We also analyzed the nonhuman cfDNA as a hypothesis-free approach to test for infections. Cytomegalovirus is most frequently assayed clinically, and the levels of CMV-derived sequences in cfDNA are consistent with clinical results. We furthermore show that hypothesis-free monitoring for pathogens using cfDNA reveals undiagnosed cases of infection, and that certain infectious pathogens such as human herpesvirus (HHV) 6, HHV-7, and adenovirus, which are not often tested clinically, occur with high frequency in this cohort. PMID:26460048

  3. A Violaceous Nodule in a Lung-transplant Patient.

    PubMed

    Milford, Emily; Winslow, Caroline; Danhof, Rebecca

    2016-01-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a rare complication of solid organ or allogenic bone marrow transplantation. Cases localized to the skin are even rarer, with only around 100 cases recorded in the literature [2]. We present a case of 60 year-old-woman, a lung transplant recipient, who presented with an asymptomatic violaceous nodule on her left medial calf. Histopathology was consistent with PTLD of the B-cell subtype, EBV negative. This case is unique in that it was of the B cell subtype of cutaneous PTLD, which has been less commonly observed than the T cell subtype. In addition, the case was EBV negative, which is rare in B cell cutaneous PTLD. The patient was treated with rituximab 600 mg IV weekly for four weeks and cytomegalovirus immune globulin (Cytogam) 100 mg/kg once, with resolution of the nodule. PMID:27617611

  4. Objective estimates improve risk stratification for primary graft dysfunction after lung transplantation

    PubMed Central

    Shah, Rupal J.; Diamond, Joshua M.; Cantu, Edward; Flesch, Judd; Lee, James C.; Lederer, David J.; Lama, Vibha N.; Orens, Jonathon; Weinacker, Ann; Wilkes, David S.; Roe, David; Bhorade, Sangeeta; Wille, Keith M.; Ware, Lorraine B.; Palmer, Scott M.; Crespo, Maria; Demissie, Ejigayehu; Sonnet, Joshua; Shah, Ashish; Kawut, Steven M.; Bellamy, Scarlett L.; Localio, A. Russell; Christie, Jason D.

    2016-01-01

    Primary graft dysfunction (PGD) is a major cause of early mortality after lung transplant. We aimed to define objective estimates of PGD risk based on readily available clinical variables, using a prospective study of 11 centers in Lung Transplant Outcomes Group (LTOG). Derivation included 1255 subjects from 2002–2010; with separate validation in 382 subjects accrued from 2011–2012. We used logistic regression to identify predictors of grade 3 PGD at 48/72 hours, and decision curve methods to assess impact on clinical decisions. 211/1255 subjects in the derivation and 56/382 subjects in the validation developed PGD. We developed 3 prediction models, where low-risk recipients had a normal BMI (18.5–25 kg/m2), COPD/CF, and absent or mild PH (mPAP< 40mmHg). All others were considered higher-risk. Low-risk recipients had a predicted PGD risk of 4–7%, and high-risk a predicted PGD risk of 15–18%. Adding a donor-smoking lung to a higher-risk recipient significantly increased PGD risk, although risk did not change in low-risk recipients. Validation demonstrated that probability estimates were generally accurate and that models worked best at baseline PGD incidences between 5–25%. We conclude that valid estimates of PGD risk can be produced using readily-available clinical variables. PMID:25877792

  5. Cancer Incidence among Heart, Kidney, and Liver Transplant Recipients in Taiwan

    PubMed Central

    Lee, Kwai-Fong; Tsai, Yi-Ting; Lin, Chih-Yuan; Hsieh, Chung-Bao; Wu, Sheng-Tang; Ke, Hung-Yen; Lin, Yi-Chang; Lin, Feng-Yen; Lee, Wei-Hwa; Tsai, Chien-Sung

    2016-01-01

    Population-based evidence of the relative risk of cancer among heart, kidney, and liver transplant recipients from Asia is lacking. The Taiwan National Health Insurance Research Database was used to conduct a population-based cohort study of transplant recipients (n = 5396), comprising 801 heart, 2847 kidney, and 1748 liver transplant recipients between 2001 and 2012. Standardized incidence ratios and Cox regression models were used. Compared with the general population, the risk of cancer increased 3.8-fold after heart transplantation, 4.1-fold after kidney transplantation and 4.6-fold after liver transplantation. Cancer occurrence showed considerable variation according to transplanted organs. The most common cancers in all transplant patients were cancers of the head and neck, liver, bladder, and kidney and non-Hodgkin lymphoma. Male recipients had an increased risk of cancers of the head and neck and liver, and female kidney recipients had a significant risk of bladder and kidney cancer. The adjusted hazard ratio for any cancer in all recipients was higher in liver transplant recipients compared with that in heart transplant recipients (hazard ratio = 1.5, P = .04). Cancer occurrence varied considerably and posttransplant cancer screening should be performed routinely according to transplanted organ and sex. PMID:27196400

  6. Transplantation.

    PubMed

    Faro, Albert; Weymann, Alexander

    2016-08-01

    Despite improvement in median life expectancy and overall health, some children with cystic fibrosis (CF) progress to end-stage lung or liver disease and become candidates for transplant. Transplants for children with CF hold the promise to extend and improve the quality of life, but barriers to successful long-term outcomes include shortage of suitable donor organs; potential complications from the surgical procedure and immunosuppressants; risk of rejection and infection; and the need for lifelong, strict adherence to a complex medical regimen. This article reviews the indications and complications of lung and liver transplantation in children with CF. PMID:27469184

  7. Physiology of sleep and breathing before and after lung transplantation.

    PubMed

    Pierucci, Paola; Malouf, Monique

    2014-09-01

    During the past 20 years, lung transplantation (LTX) has evolved and it is now accepted as a mainstream modality for care of patients with severe life-threatening respiratory diseases that are refractory to maximal conventional therapies. Improvements in surgical techniques and in antirejection medications have resulted in prolonged survival in these patients. Several studies have explored quality of life after LTX and its improvement has been noted especially in the early period between 3 and 6 months. This article discusses the salient features of the physiology of breathing and sleep disturbances before and after LTX and its alterations during sleep. PMID:25156767

  8. Broader Geographic Sharing of Pediatric Donor Lungs Improves Pediatric Access to Transplant.

    PubMed

    Tsuang, W M; Chan, K M; Skeans, M A; Pyke, J; Hertz, M I; Israni, A J; Robbins-Callahan, L; Visner, G; Wang, X; Wozniak, T C; Valapour, M

    2016-03-01

    US pediatric transplant candidates have limited access to lung transplant due to the small number of donors within current geographic boundaries, leading to assertions that the current lung allocation system does not adequately serve pediatric patients. We hypothesized that broader geographic sharing of pediatric (adolescent, 12-17 years; child, <12 years) donor lungs would increase pediatric candidate access to transplant. We used the thoracic simulated allocation model to simulate broader geographic sharing. Simulation 1 used current allocation rules. Simulation 2 offered adolescent donor lungs across a wider geographic area to adolescents. Simulation 3 offered child donor lungs across a wider geographic area to adolescents. Simulation 4 combined simulations 2 and 3. Simulation 5 prioritized adolescent donor lungs to children across a wider geographic area. Simulation 4 resulted in 461 adolescent transplants per 100 patient-years on the waiting list (range 417-542), compared with 206 (range 180-228) under current rules. Simulation 5 resulted in 388 adolescent transplants per 100 patient-years on the waiting list (range 348-418) and likely increased transplant rates for children. Adult transplant rates, waitlist mortality, and 1-year posttransplant mortality were not adversely affected. Broader geographic sharing of pediatric donor lungs may increase pediatric candidate access to lung transplant. PMID:26523747

  9. Venovenous Extracorporeal Membrane Oxygenation With Atrial Septostomy as a Bridge to Lung Transplantation.

    PubMed

    Kon, Zachary N; Pasrija, Chetan; Shah, Aakash; Griffith, Bartley P; Garcia, Jose P

    2016-03-01

    We report the first successful bridge to lung transplantation using venovenous extracorporeal membrane oxygenation (ECMO) with an atrial septostomy for both pulmonary and right ventricular support. This strategy may provide an alternative to other forms of ECMO support as a bridge to lung transplantation, and potentially allow for ambulation and rehabilitation. PMID:26897198

  10. Residential radon and lung cancer incidence in a Danish cohort

    SciTech Connect

    Braeuner, Elvira V.; Andersen, Claus E.; Sorensen, Mette; Jovanovic Andersen, Zorana; Gravesen, Peter; Ulbak, Kaare; Hertel, Ole; Pedersen, Camilla; Overvad, Kim; Tjonneland, Anne; Raaschou-Nielsen, Ole

    2012-10-15

    High-level occupational radon exposure is an established risk factor for lung cancer. We assessed the long-term association between residential radon and lung cancer risk using a prospective Danish cohort using 57,053 persons recruited during 1993-1997. We followed each cohort member for cancer occurrence until 27 June 2006, identifying 589 lung cancer cases. We traced residential addresses from 1 January 1971 until 27 June 2006 and calculated radon at each of these addresses using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for lung cancer risk associated with residential radon exposure with and without adjustment for sex, smoking variables, education, socio-economic status, occupation, body mass index, air pollution and consumption of fruit and alcohol. Potential effect modification by sex, traffic-related air pollution and environmental tobacco smoke was assessed. Median estimated radon was 35.8 Bq/m{sup 3}. The adjusted IRR for lung cancer was 1.04 (95% CI: 0.69-1.56) in association with a 100 Bq/m{sup 3} higher radon concentration and 1.67 (95% CI: 0.69-4.04) among non-smokers. We found no evidence of effect modification. We find a positive association between radon and lung cancer risk consistent with previous studies but the role of chance cannot be excluded as these associations were not statistically significant. Our results provide valuable information at the low-level radon dose range.

  11. Shear stress-related mechanosignaling with lung ischemia: lessons from basic research can inform lung transplantation

    PubMed Central

    Nieman, Gary F.; Christie, Jason D.; Fisher, Aron B.

    2014-01-01

    Cessation of blood flow represents a physical event that is sensed by the pulmonary endothelium leading to a signaling cascade that has been termed “mechanotransduction.” This paradigm has clinical relevance for conditions such as pulmonary embolism, lung bypass surgery, and organ procurement and storage during lung transplantation. On the basis of our findings with stop of flow, we postulate that normal blood flow is “sensed” by the endothelium by virtue of its location at the interface of the blood and vessel wall and that this signal is necessary to maintain the endothelial cell membrane potential. Stop of flow is sensed by a “mechanosome” consisting of PECAM-VEGF receptor-VE cadherin that is located in the endothelial cell caveolae. Activation of the mechanosome results in endothelial cell membrane depolarization that in turn leads to activation of NADPH oxidase (NOX2) to generate reactive oxygen species (ROS). Endothelial depolarization additionally results in opening of T-type voltage-gated Ca2+ channels, increased intracellular Ca2+, and activation of nitric oxide (NO) synthase with resultant generation of NO. Increased NO causes vasodilatation whereas ROS provide a signal for neovascularization; however, with lung transplantation overproduction of ROS and NO can cause oxidative injury and/or activation of proteins that drive inflammation and cell death. Understanding the key events in the mechanosignaling cascade has important lessons for the design of strategies or interventions that may reduce injury during storage of donor lungs with the goal to increase the availability of lungs suitable for donation and thus improving access to lung transplantation. PMID:25239915

  12. Shear stress-related mechanosignaling with lung ischemia: lessons from basic research can inform lung transplantation.

    PubMed

    Chatterjee, Shampa; Nieman, Gary F; Christie, Jason D; Fisher, Aron B

    2014-11-01

    Cessation of blood flow represents a physical event that is sensed by the pulmonary endothelium leading to a signaling cascade that has been termed "mechanotransduction." This paradigm has clinical relevance for conditions such as pulmonary embolism, lung bypass surgery, and organ procurement and storage during lung transplantation. On the basis of our findings with stop of flow, we postulate that normal blood flow is "sensed" by the endothelium by virtue of its location at the interface of the blood and vessel wall and that this signal is necessary to maintain the endothelial cell membrane potential. Stop of flow is sensed by a "mechanosome" consisting of PECAM-VEGF receptor-VE cadherin that is located in the endothelial cell caveolae. Activation of the mechanosome results in endothelial cell membrane depolarization that in turn leads to activation of NADPH oxidase (NOX2) to generate reactive oxygen species (ROS). Endothelial depolarization additionally results in opening of T-type voltage-gated Ca(2+) channels, increased intracellular Ca(2+), and activation of nitric oxide (NO) synthase with resultant generation of NO. Increased NO causes vasodilatation whereas ROS provide a signal for neovascularization; however, with lung transplantation overproduction of ROS and NO can cause oxidative injury and/or activation of proteins that drive inflammation and cell death. Understanding the key events in the mechanosignaling cascade has important lessons for the design of strategies or interventions that may reduce injury during storage of donor lungs with the goal to increase the availability of lungs suitable for donation and thus improving access to lung transplantation. PMID:25239915

  13. Low Incidence of Hyperfibrinolysis and Thromboembolism in 195 Primary Liver Transplantations Transfused with Solvent/Detergent-Treated Plasma

    PubMed Central

    Haugaa, Håkon; Taraldsrud, Eli; Nyrerød, Hans Christian; Tønnessen, Tor Inge; Foss, Aksel; Solheim, Bjarte G.

    2014-01-01

    Background Liver transplantation regularly requires transfusion of red blood cells (RBCs), plasma, and platelets. Compared to fresh frozen plasma (FFP) from single blood donors, solvent/detergent-treated plasma (SD-plasma) pooled from several hundred blood donors has advantages with respect to pathogen reduction, standardized content of plasma proteins, and significantly reduced risk of transfusion related lung injury and allergic/immunologic adverse reactions. However, SD-plasma has been suspected to increase the incidence of hyperfibrinolysis and thromboembolic events. Study Design and Methods We investigated the transfusion practices, hyperfibrinolysis parameters, and thrombosis outcomes in 195 consecutive adult primary liver transplants in our center using SD-plasma (Octaplas) as the exclusive source of plasma. Results Perioperatively, median (interquartile range) 4 (1 to 9) RBC-units, 10 (4 to 18) plasma-bags, and 0 (0 to 2) platelet-units were transfused. Hyperfibrinolysis defined as LY30 ≤ 7.5% was detected in 12/138 thrombelastography-monitored patients (9%). These patients received significantly more RBCs, plasma, and platelets than did patients without hyperfibrinolysis. Thrombotic graft complications were observed in three patients (2%). Pulmonary embolism was not observed in any patient. Conclusion SD-plasma is a safe plasma product for liver transplant recipients, and the incidences of hyperfibrinolysis and thromboembolic events are not significantly different from those seen in centers using FFP. PMID:24415744

  14. Lung transplantation in the rat. III. Functional studies in iso- and allografts

    SciTech Connect

    Marck, K.W.; Prop, J.; Wildevuur, C.R.

    1983-08-01

    Recently a microsurgical technique for orthotopic left lung transplantation in the rat was developed. The aim of this study was to investigate the influence of the operation itself and of an unmodified rejection reaction on the function of the transplanted rat lung. Orthotopic left lung transplantation was performed in 59 rats (34 isografts and 25 allografts). Isografts demonstrated a mean left lung perfusion of 23.1% in the first two postoperative weeks. Seven out of the 10 animals, subjected to a repeated scintigraphy 5-10 weeks later, had an increased graft perfusion, resulting in an almost normal mean left lung perfusion of 34.8%. At that time chest roentgenography revealed a good aeration of the grafts, that at autopsy had a normal aspect. Allografts showed an initial mean left lung perfusion (24.6%) similar to the isografts, which, however, declined sharply a few days later (4.3%). At that time chest roentgenography revealed totally opalescent grafts that at autopsy had the hepatized aspect characteristic of lung allograft rejection. These results of isogeneic and allogeneic lung transplantation in the rat were comparable with those of canine auto- and allotransplantation. For immunogenetic and economical reasons lung transplantation in the rat is a good alternative animal model in lung transplantation research.

  15. Disruption of the aortic anastomosis after heart-lung transplantation.

    PubMed

    Dowling, R D; Baladi, N; Zenati, M; Dummer, J S; Kormos, R L; Armitage, J M; Yousem, S A; Hardesty, R L; Griffith, B P

    1990-01-01

    Disruption of the aorta at the anastomotic site occurred in 4 of 66 consecutive heart-lung transplant recipients and was associated with a 100% mortality. In 3 of these patients, Candida either was cultured from the suture line or was seen in the wall of the aorta at postmortem examination. In 2 of these 3 patients, cultures of material from the donor trachea taken at the time of explanation grew Candida species. Two patients were seen with sudden massive hemorrhage on postoperative day 26 and postoperative day 28. One patient experienced acute decompensation due to right ventricular outflow tract obstruction on postoperative day 30, and the remaining patient was seen 7 months postoperatively with obstruction of both the left main bronchus and the right pulmonary artery caused by extrinsic compression by an aortic pseudoaneurysm. A high index of suspicion should be maintained when transplanting lungs containing Candida species, as we believe there is substantial evidence of donor transmission of the fungal agents. We now include amphotericin B in our antibiotic prophylactic regimen in an attempt to prevent fungal infection because previous treatment has been uniformly unsuccessful. Furthermore, we wrap both the trachea and the aorta with omentum to lessen the likelihood of mediastinal spread of infection to the aortic suture line. PMID:2297258

  16. Lung Transplantation for Cystic Fibrosis: Results, Indications, Complications, and Controversies

    PubMed Central

    Lynch, Joseph P.; Sayah, David M.; Belperio, John A.; Weigt, S. Sam

    2016-01-01

    Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (~50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. PMID:25826595

  17. Standardised incidence ratios (SIRs) for cancer after renal transplant in systemic lupus erythematosus (SLE) and non-SLE recipients

    PubMed Central

    Ramsey-Goldman, Rosalind; Brar, Amarpali; Richardson, Carrie; Salifu, Moro O; Clarke, Ann; Bernatsky, Sasha; Stefanov, Dimitre G; Jindal, Rahul M

    2016-01-01

    Objective We investigated malignancy risk after renal transplantation in patients with and without systemic lupus erythematosus (SLE). Methods Using the United States Renal Data System from 2001 to 2009, 143 652 renal transplant recipients with and without SLE contributed 585 420 patient-years of follow-up to determine incident cancers using Medicare claims codes. We calculated standardised incidence ratios (SIRs) of cancer by group using age, sex, race/ethnicity-specific and calendar year-specific cancer rates compared with the US population. Results 10 160 cancers occurred at least 3 months after renal transplant. Overall cancer risk was increased in both SLE and non-SLE groups compared with the US general population, SIR 3.5 (95% CI 2.1 to 5.7) and SIR 3.7 (95% CI 2.4 to 5.7), respectively. Lip/oropharyngeal, Kaposi, neuroendocrine, thyroid, renal, cervical, lymphoma, liver, colorectal and breast cancers were increased in both groups, whereas only melanoma was increased in SLE and lung cancer was increased in non-SLE. In Cox regression analysis, SLE status (HR 1.1, 95% CI 0.9 to 1.3) was not associated with increased risk of developing cancer, adjusted for other independent risk factors for developing cancer in renal transplant recipients. We found that smoking (HR 2.2, 95% CI 1.2 to 4.0), cytomegalovirus positivity at time of transplant (HR 1.3, 95% CI 1.2 to 1.4), white race (HR 1.2, 95% CI 1.2 to 1.3) and older recipient age at time of transplantation (HR 1.0 95% CI 1.0 to 1.2) were associated with an increased risk for development of cancer, whereas shorter time on dialysis, Epstein-Barr virus or HIV were associated with a lower risk for development of cancer. Conclusions Cancer risk in renal transplant recipients appeared similar in SLE and non-SLE subjects, aside from melanoma. Renal transplant recipients may need targeted counselling regarding surveillance and modifiable risk factors. PMID:27335659

  18. Proteome Profiling in Lung Injury after Hematopoietic Stem Cell Transplantation.

    PubMed

    Bhargava, Maneesh; Viken, Kevin J; Dey, Sanjoy; Steinbach, Michael S; Wu, Baolin; Jagtap, Pratik D; Higgins, LeeAnn; Panoskaltsis-Mortari, Angela; Weisdorf, Daniel J; Kumar, Vipin; Arora, Mukta; Bitterman, Peter B; Ingbar, David H; Wendt, Chris H

    2016-08-01

    Pulmonary complications due to infection and idiopathic pneumonia syndrome (IPS), a noninfectious lung injury in hematopoietic stem cell transplant (HSCT) recipients, are frequent causes of transplantation-related mortality and morbidity. Our objective was to characterize the global bronchoalveolar lavage fluid (BALF) protein expression of IPS to identify proteins and pathways that differentiate IPS from infectious lung injury after HSCT. We studied 30 BALF samples from patients who developed lung injury within 180 days of HSCT or cellular therapy transfusion (natural killer cell transfusion). Adult subjects were classified as having IPS or infectious lung injury by the criteria outlined in the 2011 American Thoracic Society statement. BALF was depleted of hemoglobin and 14 high-abundance proteins, treated with trypsin, and labeled with isobaric tagging for relative and absolute quantification (iTRAQ) 8-plex reagent for two-dimensional capillary liquid chromatography (LC) and data dependent peptide tandem mass spectrometry (MS) on an Orbitrap Velos system in higher-energy collision-induced dissociation activation mode. Protein identification employed a target-decoy strategy using ProteinPilot within Galaxy P. The relative protein abundance was determined with reference to a global internal standard consisting of pooled BALF from patients with respiratory failure and no history of HSCT. A variance weighted t-test controlling for a false discovery rate of ≤5% was used to identify proteins that showed differential expression between IPS and infectious lung injury. The biological relevance of these proteins was determined by using gene ontology enrichment analysis and Ingenuity Pathway Analysis. We characterized 12 IPS and 18 infectious lung injury BALF samples. In the 5 iTRAQ LC-MS/MS experiments 845, 735, 532, 615, and 594 proteins were identified for a total of 1125 unique proteins and 368 common proteins across all 5 LC-MS/MS experiments. When comparing IPS to

  19. Lung Transplantation in Gaucher Disease: A Learning Lesson in Trying to Avoid Both Scylla and Charybdis.

    PubMed

    de Boer, Geertje M; van Dussen, Laura; van den Toorn, Leon M; den Bakker, Michael A; Hoek, Rogier A S; Hesselink, Dennis A; Hollak, Carla E M; van Hal, Peter Th W

    2016-01-01

    Gaucher disease (GD), a lysosomal storage disorder, may result in end-stage lung disease. We report successful bilateral lung transplantation in a 49-year-old woman with GD complicated by severe pulmonary hypertension and fibrotic changes in the lungs. Before receiving the lung transplant, the patient was undergoing both enzyme replacement therapy (imiglucerase) and triple pulmonary hypertension treatment (epoprostenol, bosentan, and sildenafil). She had a history of splenectomy, severe bone disease, and renal involvement, all of which were related to GD and considered as relative contraindications for a lung transplantation. In the literature, lung transplantation has been suggested for severe pulmonary involvement in GD but has been reported only once in a child. To our knowledge, until now, no successful procedure has been reported in adults, and no reports deal with the severe potential posttransplantation complications specifically related to GD. PMID:26757299

  20. [Nocardia farcinica lung infection in a patient with cystic fibrosis and a lung transplant].

    PubMed

    Chacón, C F; Vicente, R; Ramos, F; Porta, J; Lopez Maldonado, A; Ansotegui, E

    2015-03-01

    Patients with cystic fibrosis have a higher risk of developing chronic respiratory infectious diseases. The Nocardia farcinica lung infection is rare in this group of patients, and there are limited publications about this topic. Its diagnosis is complex, due to the clinical and the radiology signs being non-specific. Identification of the agent responsible in the sputum culture is occasionally negative. It is a slow growing organism and for this reason treatment is delayed, which can lead to an increase in complications, hospitable stays, and mortality. A case is reported on a 26 year-old woman with cystic fibrosis and chronic lung colonization by Nocardia farcinica and Aspergillus fumigatus, on long-term treatment with ciprofloxacin, trimethoprim-sulfamethoxazole, and posaconazole, who was admitted to ICU after bilateral lung transplantation. The initial post-operative progress was satisfactory. After discharge, the patient showed a gradual respiratory insufficiency with new chest X-ray showing diffuse infiltrates. Initially, the agent was not seen in the sputum culture. Prompt and aggressive measures were taken, due to the high clinical suspicion of a Nocardia farcinica lung infection. Treatment with a combination of amikacin and meropenem, and later combined with linezolid, led to the disappearance of the lung infiltrates and a clinical improvement. In our case, we confirm the rapid introduction of Nocardia farcinica in the new lungs. The complex identification and the delay in treatment increased the morbimortality. There is a special need for its eradication in patients with lung transplant, due to the strong immunosuppressive treatment. PMID:25443661

  1. Lung size mismatch and primary graft dysfunction after bilateral lung transplantation *

    PubMed Central

    Eberlein, Michael; Reed, Robert M.; Bolukbas, Servet; Wille, Keith M.; Orens, Jonathan B.; Brower, Roy G.; Christie, Jason D.

    2014-01-01

    BACKGROUND Donor to recipient lung size matching at lung transplantation (LTx) can be estimated by the predicted total lung capacity (pTLC)ratio (donor pTLC/recipient pTLC). We aimed to determine whether the pTLC-ratio is associated with the risk of primary graft dysfunction (PGD) after bilateral LTx (BLT). METHODS We calculated the pTLC-ratio for 812 adult BLTs from the Lung Transplant Outcomes Group between 3/2002-12/2010. Patients were stratified by pTLC-ratio>1.0 (“oversized”) and pTLC-ratio≤1.0 (“undersized”). PGD was defined as any ISHLT grade 3 PGD within 72 hours of reperfusion (PGD 3). We analyzed the association between risk factors and PGD using multivariable conditional logistic regression. As transplant diagnoses can influence the size matching decisions and also modulate the risk for PGD, we performed pre-specified analyses by assessing the impact of lung size mismatch within diagnostic categories. RESULTS In univariate analyses oversizing was associated with a 39% lower odds of PGD3 (OR 0.61, 95% CI, p=0.003). In a multivariate model accounting for center effects and known PGD risks, oversizing remained independently associated with a decreased odds of PGD3 (OR 0.58, 95% CI 0.38-0.88, p=0.01). The risk adjusted point estimate was similar for the non-COPD diagnoses groups (OR 0.52, 95%CI 0.32-0.86, p=0.01); however there was no detected association within the COPD group (OR 0.72, 95% CI 0.29-1.78, p=0.5). CONCLUSION Oversized allografts are associated with a decreased risk of PGD3 after BLT; this effect appears most apparent in non-COPD patients. PMID:25447586

  2. Use of endobronchial valves for native lung hyperinflation associated with respiratory failure in a single-lung transplant recipient for emphysema.

    PubMed

    Crespo, Maria M; Johnson, Bruce A; McCurry, Kenneth R; Landreneau, Rodney J; Sciurba, Frank C

    2007-01-01

    Emphysema is a common indication for adult pulmonary transplantation. Double-lung transplantation is increasingly the preferred approach because severe posttransplant native lung hyperinflation (NLH) following single-lung transplantation may compromise allograft lung function. We describe successful emergency use of bronchoscopic lung volume reduction using endobronchial valves (EBVs) [Zephyr; Emphasys Medical; Redwood, CA] in a single-lung transplant recipient who was critically ill with ventilator dependence from complications of NLH and at excessive risk for lung volume reduction surgery or pneumonectomy. Following placement of 17 valves in all segments of the native lung, atelectasis of the native lung was accompanied by volume expansion of the allograft. Immediately following valve placement, peak airway pressure decreased and alveolar ventilation increased. The patient was subsequently weaned from mechanical ventilation. This report suggests the need for clinical trials to evaluate the effectiveness of EBVs in single-lung transplant recipients with less critical functional impairment associated with NLH. PMID:17218578

  3. Management of Scedosporium apiospermum in a pre- and post-lung transplant patient with cystic fibrosis.

    PubMed

    Rolfe, Nancy E; Haddad, Tarik J; Wills, Todd S

    2013-01-24

    Although the predominant type of infection seen in the cystic fibrosis lung remains bacterial, fungal organisms are being isolated more frequently and are associated with a high mortality rate in lung transplant recipients. We present a case of a patient with CF with sputum cultures positive for Scedosporium apiospermum prior to a successful lung transplant. She remains without evidence of infection 18 months later following treatment with a combination of triazoles and terbinafine. PMID:24432212

  4. Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

    PubMed Central

    Meyer, Keith C; Nathanson, Ian; Angel, Luis; Bhorade, Sangeeta M; Chan, Kevin M; Culver, Daniel; Harrod, Christopher G; Hayney, Mary S; Highland, Kristen B; Limper, Andrew H; Patrick, Herbert; Strange, Charlie; Whelan, Timothy

    2012-01-01

    Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. PMID:23131960

  5. Psychological criteria for contraindication in lung transplant candidates: a five-year study*

    PubMed Central

    Hojaij, Elaine Marques; Romano, Bellkiss Wilma; Costa, André Nathan; Afonso, Jose Eduardo; de Camargo, Priscila Cilene Leon Bueno; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Samano, Marcos Naoyuki; Teixeira, Ricardo Henrique de Oliveira Braga

    2015-01-01

    Lung transplantation presents a wide range of challenges for multidisciplinary teams that manage the care of the recipients. Transplant teams should perform a thorough evaluation of transplant candidates, in order to ensure the best possible post-transplant outcomes. That is especially true for the psychologist, because psychological issues can arise at any point during the perioperative period. The objective of our study was to evaluate the psychological causes of contraindication to waiting list inclusion in a referral program for lung transplantation. We retrospectively analyzed data on psychological issues presented by lung transplant candidates, in order to understand these matters in our population and to reflect upon ways to improve the selection process. PMID:26176522

  6. Role of Complement Activation in Obliterative Bronchiolitis Post Lung Transplantation

    PubMed Central

    Suzuki, Hidemi; Lasbury, Mark E.; Fan, Lin; Vittal, Ragini; Mickler, Elizabeth A.; Benson, Heather L.; Shilling, Rebecca; Wu, Qiang; Weber, Daniel J.; Wagner, Sarah R.; Lasaro, Melissa; Devore, Denise; Wang, Yi; Sandusky, George E.; Lipking, Kelsey; Pandya, Pankita; Reynolds, John; Love, Robert; Wozniak, Thomas; Gu, Hongmei; Brown, Krista M.; Wilkes, David S.

    2013-01-01

    Obliterative bronchiolitis (OB) post lung transplantation involves IL-17 regulated autoimmunity to type V collagen and alloimmunity, which could be enhanced by complement activation. However, the specific role of complement activation in lung allograft pathology, IL-17 production, and OB are unknown. The current study examines the role of complement activation in OB. Complement regulatory protein (CRP) (CD55, CD46, Crry/CD46) expression was down regulated in human and murine OB; and C3a, a marker of complement activation, was up regulated locally. IL-17 differentially suppressed Crry expression in airway epithelial cells in vitro. Neutralizing IL-17 recovered CRP expression in murine lung allografts and decreased local C3a production. Exogenous C3a enhanced IL-17 production from alloantigen or autoantigen (type V collagen) reactive lymphocytes. Systemically neutralizing C5 abrogated the development of OB, reduced acute rejection severity, lowered systemic and local levels of C3a and C5a, recovered CRP expression, and diminished systemic IL-17 and IL-6 levels. These data indicated that OB induction is in part complement dependent due to IL-17 mediated down regulation of CRPs on airway epithelium. C3a and IL-17 are part of a feed forward loop that may enhance CRP down regulation, suggesting that complement blockade could be a therapeutic strategy for OB. PMID:24043901

  7. Telephone-Based Coping Skills Training for Patients Awaiting Lung Transplantation

    ERIC Educational Resources Information Center

    Blumenthal, James A.; Babyak, Michael A.; Keefe, Francis J.; Davis, R. Duane; LaCaille, Rick A.; Carney, Robert M.; Freedland, Kenneth E.; Trulock, Elbert; Palmer, Scott M.

    2006-01-01

    Impaired quality of life is associated with increased mortality in patients with advanced lung disease. Using a randomized controlled trial with allocation concealment and blinded outcome assessment at 2 tertiary care teaching hospitals, the authors randomly assigned 328 patients with end-stage lung disease awaiting lung transplantation to 12…

  8. Iatrogenic “buffalo chest” bilateral pneumothoraces following unilateral transbronchial lung biopsies in a bilateral lung transplant recipient

    PubMed Central

    Sawalha, Leith; Gibbons, William J.

    2015-01-01

    We present a 54 year old male patient who had a bilateral lung transplant sixteen years ago for Alpha-1 Antitrypsin Deficiency-related emphysema. He was referred for flexible bronchoscopy with transbronchial biopsies to evaluate new mild exertional dyspnea and worsening of his FEV1. Eight transbronchial biopsies were done from the right middle lobe and the right lower lobe. Post procedure he developed bilateral pneumothoces that required emergent bilateral pleural ‘pigtail’ catheters. To our knowledge, this is the first reported case of bilateral pneumothoraces that developed after a unilateral procedure in a bilateral lung transplant recipient relatively late after the transplant. PMID:26236604

  9. Lung transplantation: does oxidative stress contribute to the development of bronchiolitis obliterans syndrome?

    PubMed

    Madill, Janet; Aghdassi, Ellie; Arendt, Bianca; Hartman-Craven, Brenda; Gutierrez, Carlos; Chow, Chung-Wai; Allard, Johane

    2009-04-01

    Lung transplantation is the ultimate treatment of end-stage lung disease. After transplantation, the 1-year survival rate is 80%. However, 5-year survival rates drop to 50% due to bronchiolitis obliterans syndrome (BOS). Ischemia/reperfusion injury, infections, and acute rejection are major risk factors contributing to the development of BOS. These risk factors are also associated with increased oxidative stress. Oxidative stress is a condition whereby prooxidants overwhelm the antioxidant defense system and may contribute to the pathogenesis of BOS by inducing more tissue injury and inflammation. This article reviews the current state of knowledge on oxidative stress in lung transplantation and BOS. PMID:19298941

  10. Regional pulmonary perfusion following human heart-lung transplantation

    SciTech Connect

    Lisbona, R.; Hakim, T.S.; Dean, G.W.; Langleben, D.; Guerraty, A.; Levy, R.D. )

    1989-08-01

    Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

  11. Cognitive Function, Mental Health, and Health-related Quality of Life after Lung Transplantation

    PubMed Central

    Cohen, David G.; Christie, Jason D.; Anderson, Brian J.; Diamond, Joshua M.; Judy, Ryan P.; Shah, Rupal J.; Cantu, Edward; Bellamy, Scarlett L.; Blumenthal, Nancy P.; Demissie, Ejigayehu; Hopkins, Ramona O.

    2014-01-01

    Rationale: Cognitive and psychiatric impairments are threats to functional independence, general health, and quality of life. Evidence regarding these outcomes after lung transplantation is limited. Objectives: Determine the frequency of cognitive and psychiatric impairment after lung transplantation and identify potential factors associated with cognitive impairment after lung transplantation. Methods: In a retrospective cohort study, we assessed cognitive function, mental health, and health-related quality of life using a validated battery of standardized tests in 42 subjects post-transplantation. The battery assessed cognition, depression, anxiety, resilience, and post-traumatic stress disorder (PTSD). Cognitive function was assessed using the Montreal Cognitive Assessment, a validated screening test with a range of 0 to 30. We hypothesized that cognitive function post-transplantation would be associated with type of transplant, cardiopulmonary bypass, primary graft dysfunction, allograft ischemic time, and physical therapy post-transplantation. We used multivariable linear regression to examine the relationship between candidate risk factors and cognitive function post-transplantation. Measurements and Main Results: Mild cognitive impairment (score, 18–25) was observed in 67% of post-transplant subjects (95% confidence interval [CI]: 50–80%) and moderate cognitive impairment (score, 10–17) was observed in 5% (95% CI, 1–16%) of post-transplant subjects. Symptoms of moderate to severe anxiety and depression were observed in 21 and 3% of post-transplant subjects, respectively. No transplant recipients reported symptoms of PTSD. Higher resilience correlated with less psychological distress in the domains of depression (P < 0.001) and PTSD (P = 0.02). Prolonged graft ischemic time was independently associated with worse cognitive performance after lung transplantation (P = 0.001). The functional gain in 6-minute-walk distance achieved at the end of post-transplant

  12. Gastroesophageal Reflux Disease Is Associated With an Increased Rate of Acute Rejection in Lung Transplant Allografts

    PubMed Central

    Shah, N.S.; Force, S.D.; Mitchell, P.O.; Lin, E.; Lawrence, E.C.; Easley, K.; Qian, J.; Ramirez, A.; Neujahr, D.C.; Gal, A.; Leeper, K.; Pelaez, A.

    2012-01-01

    Purpose Gastric fundoplication (GF) for gastroesophageal reflux disease (GERD) may protect against the progression of chronic rejection in lung transplant (LT) recipients. However, the association of GERD with acute rejection episodes (ARE) is uncertain. This study sought to identify if ARE were linked to GERD in LT patients. Methods This single-center retrospective observational study, of patients transplanted from January 1, 2000, to January 31, 2009, correlated results of pH probe testing for GERD with ARE (≥International Society for Heart and Lung Transplantation A1 or B1). We compared the rates of ARE among patients with GERD (DeMeester Score > 14.7) versus without GERD as number of ARE per 1,000 patient-days after LT. Patients undergoing GF prior to LT were excluded. Results The analysis included 60 LT subjects and 9,249 patient-days: 33 with GERD versus 27 without GERD. We observed 51 ARE among 60 LT recipients. The rate of ARE was highest among patients with GERD: 8.49 versus 2.58, an incidence density ratio (IDR) of 3.29 (P = .00016). Upon multivariate negative binomial regression modeling, only GERD was associated with ARE (IDR 2.15; P = .009). Furthermore, GERD was associated with multiple ARE (36.4% vs 0%; P < .0001) and earlier onset compared with patients without GERD: ARE proportion at 2 months was 0.55 versus 0.26 P = .004). Conclusion In LT recipients, GERD was associated with a higher rate, multiple events, and earlier onset of ARE. The efficacy of GF to reduce ARE among patients with GERD needs further evaluation. PMID:20832573

  13. The First Successful Heart-Lung Transplant in a Korean Child with Humidifier Disinfectant-Associated Interstitial Lung Disease

    PubMed Central

    Kim, Yong-Hee; Hong, Sang-Bum

    2016-01-01

    From 2006 to 2011, an outbreak of a particular type of childhood interstitial lung disease occurred in Korea. The condition was intractable and progressed to severe respiratory failure, with a high mortality rate. Moreover, in several familial cases, the disease affected young women and children simultaneously. Epidemiologic, animal, and post-interventional studies identified the cause as inhalation of humidifier disinfectants. Here, we report a 4-year-old girl who suffered from severe progressive respiratory failure. She could survive by 100 days of extracorporeal membrane oxygenation support and finally, underwent heart-lung transplantation. This is the first successful pediatric heart-lung transplantation carried out in Korea. PMID:27134508

  14. The First Successful Heart-Lung Transplant in a Korean Child with Humidifier Disinfectant-Associated Interstitial Lung Disease.

    PubMed

    Jhang, Won Kyoung; Park, Seong Jong; Lee, Eun; Yang, Song I; Hong, Soo Jong; Seo, Ju-Hee; Kim, Hyung-Young; Park, Jeong-Jun; Yun, Tae-Jin; Kim, Hyeong Ryul; Kim, Yong-Hee; Kim, Dong Kwan; Park, Seung-Il; Lee, Sang-Oh; Hong, Sang-Bum; Shim, Tae-Sun; Choi, In-Cheol; Yu, Jinho

    2016-05-01

    From 2006 to 2011, an outbreak of a particular type of childhood interstitial lung disease occurred in Korea. The condition was intractable and progressed to severe respiratory failure, with a high mortality rate. Moreover, in several familial cases, the disease affected young women and children simultaneously. Epidemiologic, animal, and post-interventional studies identified the cause as inhalation of humidifier disinfectants. Here, we report a 4-year-old girl who suffered from severe progressive respiratory failure. She could survive by 100 days of extracorporeal membrane oxygenation support and finally, underwent heart-lung transplantation. This is the first successful pediatric heart-lung transplantation carried out in Korea. PMID:27134508

  15. Lung transplantation in chronic obstructive pulmonary disease: patient selection and special considerations.

    PubMed

    Lane, C Randall; Tonelli, Adriano R

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity. Lung transplantation is one of the few treatments available for end-stage COPD with the potential to improve survival and quality of life. The selection of candidates and timing of listing present challenges, as COPD tends to progress fairly slowly, and survival after lung transplantation remains limited. Though the natural course of COPD is difficult to predict, the use of assessments of functional status and multivariable indices such as the BODE index can help identify which patients with COPD are at increased risk for mortality, and hence which are more likely to benefit from lung transplantation. Patients with COPD can undergo either single or bilateral lung transplantation. Although many studies suggest better long-term survival with bilateral lung transplant, especially in younger patients, this continues to be debated, and definitive recommendations about this cannot be made. Patients may be more susceptible to particular complications of transplant for COPD, including native lung hyperinflation, and development of lung cancer. PMID:26491282

  16. Outcomes of Lung Transplantation in Recipients With Hepatitis C Virus Infection.

    PubMed

    Doucette, K E; Halloran, K; Kapasi, A; Lien, D; Weinkauf, J G

    2016-08-01

    Hepatitis C virus (HCV) infection negatively impacts patient and graft survival following nonhepatic solid organ transplantation. Most data, however, are in kidney transplant, where despite modest impact on outcomes, transplantation is recommended for those with mild to moderate hepatic fibrosis given overall benefit compared to remaining on dialysis. In lung transplantation (LuTx), there is little data on outcomes and international guidelines are vague on the criteria under which transplant should be considered. The University of Alberta Lung Transplant Program routinely considers patients with HCV for lung transplant based on criteria extrapolated from the kidney transplant literature. Here we describe the outcomes of 27 HCV-positive, compared to 443 HCV-negative LuTx recipients. Prior to transplant, five patients were treated for HCV and cured. At the time of transplant, 14 patients remained HCV RNA positive. The 1-, 3-, and 5-year survival were similar in HCV RNA-positive versus -negative recipients at 93%, 77%, and 77% versus 86%, 75%, and 66% (p = 0.93), respectively. Long-term follow-up in eight patients demonstrated no significant progression of fibrosis. In our cohort, HCV did not impact LuTx outcomes and in the era of interferon-free HCV therapies this should not be a barrier to LuTx. PMID:26998739

  17. Incidence, characteristics, and treatment outcomes of mycobacterial diseases in transplant recipients.

    PubMed

    Yoo, Jung-Wan; Jo, Kyung-Wook; Kim, Sung-Han; Lee, Sang-Oh; Kim, Jae Joong; Park, Su-Kil; Lee, Je-Hwan; Han, Duck Jong; Hwang, Shin; Lee, SeungGyu; Shim, Tae Sun

    2016-05-01

    The incidence, clinical characteristics, and treatment outcomes of tuberculosis (TB) and nontuberculous mycobacterial (NTM) disease developed after transplantation (TPL) in transplant recipients were investigated retrospectively. Between 1996 and 2013, 7342 solid-organ transplantation and 1266 hematopoietic stem cell transplantation were performed at a tertiary referral center in South Korea. Among them, TB and NTM disease developed in 130 and 22 patients, respectively. The overall incidence of TB was 257.4 cases/100 000 patient-years (95% confidence interval [CI], 215.1-305.7) and that of NTM disease was 42.7 cases/100 000 patient-years (95% CI, 26.8-64.7). The median interval from organ TPL to the development of mycobacterial disease was 8.5 months (95% CI, 6.3-11.4) in recipients with TB patients and 24.2 months (95% CI, 13.5-55.7) in those with NTM, respectively. Among NTM patients, Mycobacterium avium-intracellulare complex was the most common causative organism, and nodular bronchiectatic type (77.8%) was the most frequent radiologic feature. Favorable treatment outcome was achieved in 83.7% (95% CI, 76.4-89.1) and 68.8% (95% CI, 44.4-85.8) of TB and NTM patients, respectively (P = 0.166). In conclusion, the overall incidence of TB was higher than that of NTM disease in transplant recipients and treatment outcomes were favorable in both drug-susceptible TB and NTM patients. PMID:26840221

  18. A novel dual ex vivo lung perfusion technique improves immediate outcomes in an experimental model of lung transplantation.

    PubMed

    Tanaka, Y; Noda, K; Isse, K; Tobita, K; Maniwa, Y; Bhama, J K; D'Cunha, J; Bermudez, C A; Luketich, J D; Shigemura, N

    2015-05-01

    The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation. PMID:25777770

  19. Umbilical cord blood transplantation in adults with advanced hodgkin's disease: high incidence of post-transplant lymphoproliferative disease.

    PubMed

    Piñana, José Luis; Sanz, Jaime; Esquirol, Albert; Martino, Rodrigo; Picardi, Alessandra; Barba, Pere; Parody, Rocio; Gayoso, Jorge; Montesinos, Pau; Guidi, Stefano; Terol, Maria José; Moscardó, Federico; Solano, Carlos; Arcese, William; Sanz, Miguel A; Sierra, Jorge; Sanz, Guillermo

    2016-02-01

    We report the outcome of 30 consecutive patients with Hodgkin disease (HD) who underwent single-unit UCBT. Most (90%) patients had failed previous autologous hematopoietic stem cell transplantation. The conditioning regimens were based on combinations of thiotepa, busulfan, cyclophosphamide or fludarabine, and antithymocyte globulin. The cumulative incidence (CI) of myeloid engraftment was 90% [95% confidence interval (C.I.), 74-98%] with a median of 18 d (range, 10-48). CI of acute graft-versus-host disease (GvHD) grades II-IV was 30% (95% C.I., 17-44%), while the incidence of chronic GVHD was 42% (95% C.I., 23-77%). The non-relapse mortality (NRM) at 100 d and 4 yr was 30% (95% C.I., 13-46%) and 47% (95% C.I., 29-65%), respectively. EBV-related post-transplant lymphoproliferative disease (EBV-PTLD) accounted for more than one-third of transplant-related death, with an estimate incidence of 26% (95% C.I., 9-44). The incidence of relapse at 4 yr was 25% (95% C.I., 9-42%). Four-year event-free survival (EFS) and overall survival (OS) were 28% and 30%, respectively. Despite a high NRM and an unexpected high incidence of EBV-PTLD, UCBT in heavily pretreated HD patients is an option for patients lacking a suitable adult donor, provided the disease is not in refractory relapse. PMID:25845981

  20. Scintigraphy at 3 months after single lung transplantation and observations of primary graft dysfunction and lung function.

    PubMed

    Belmaati, Esther Okeke; Iversen, Martin; Kofoed, Klaus F; Nielsen, Michael B; Mortensen, Jann

    2012-06-01

    Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation-perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation, and to investigate whether scintigraphic findings at 3 months were predictive for the outcome at 12 months in relation to primary graft dysfunction (PGD) and lung function. A retrospective study was carried out on all patients who prospectively and consecutively were referred for a routine lung scintigraphy procedure 3 months after single lung transplantation (SLTX). A total of 41 patients were included in the study: 20 women and 21 men with the age span of patients at transplantation being 38-66 years (mean ± SD: 54.2 ± 6.0). Patient records also included lung function tests and chest X-ray images. We found no significant correlation between lung function distribution at 3 months and PGD at 72 h. There was also no significant correlation between PGD scores at 72 h and lung function at 6 and 12 months. The same applied to scintigraphic scores for heterogeneity at 3 months compared with lung function at 6 and 12 months. Fifty-five percent of all patients had decreased ventilation function measured in the period from 6 to 12 months. Forty-nine percent of the patients had normal perfusion evaluations, and 51% had abnormal perfusion evaluations at 3 months. For ventilation evaluations, 72% were normal and 28% were abnormal. There was a significant difference in the normal versus abnormal perfusion and ventilation scintigraphic images evaluated from the same patients. Ventilation was distributed more homogenously in the transplanted lung than perfusion in the same lung. The relative distribution of perfusion and ventilation to the transplanted lung of patients with and without a primary diagnosis of fibrosis did not differ significantly from each other. We conclude that PGD

  1. Lung transplantation in patients with cystic fibrosis: special focus to infection and comorbidities.

    PubMed

    Dorgan, Daniel J; Hadjiliadis, Denis

    2014-06-01

    Despite advances in medical care, patients with cystic fibrosis still face limited life expectancy. The most common cause of death remains respiratory failure. End-stage cystic fibrosis can be treated with lung transplantation and is the third most common reason for which the procedure is performed. Outcomes for cystic fibrosis are better than most other lung diseases, but remain limited (5-year survival 60%). For patients with advanced disease lung transplantation appears to improve survival. Outcomes for patients with Burkholderia cepacia remain poor, although they are better for patients with certain genomovars. Controversy exists about Mycobacterium abscessus infection and appropriateness for transplant. More information is also becoming available for comorbidities, including diabetes and pulmonary hypertension among others. Extra-corporeal membrane oxygenation is used more frequently for end-stage disease as a bridge to lung transplantation and will likely be used more in the future. PMID:24655065

  2. Single lung transplantation in a patient with retrospective positive cross-match

    PubMed Central

    Piotrowska, Maria; Dec, Paweł; Wasilewski, Piotr; Kubisa, Anna; Pieróg, Jarosław; Wójcik, Norbert; Czarnecka, Michalina; Kubisa, Bartosz; Grodzki, Tomasz

    2015-01-01

    Lung transplantation is a method useful in such non-malignant end-stage parenchymal and vascular diseases as: chronic obstructive pulmonary disease (COPD), idiopathic interstitial pulmonary fibrosis, cystic fibrosis, or primary pulmonary hypertension. The main aim of this procedure is to extend the patient's lifespan and quality of life. However, the availability of the operation is limited by organ access. In this paper we present the case of a 58-year-old female in the fourth stage of COPD, who was classified to have a single lung transplantation. Because of some technical problems it was decided to transplant a left donor lung in the right recipient lung locus. Positive cross match was demonstrated retrospectively, and we applied five courses of plasmapheresis. Human immunoglobulin and rituximab treatment were performed to decrease the impact of lymphocytotoxic antibodies. The patient survived 498 days after transplantation, 271 in the hospital. PMID:26855654

  3. Non-melanoma skin cancer in Portuguese kidney transplant recipients - incidence and risk factors*

    PubMed Central

    Pinho, André; Gouveia, Miguel; Cardoso, José Carlos; Xavier, Maria Manuel; Vieira, Ricardo; Alves, Rui

    2016-01-01

    Background Cancer is currently among the three leading causes of death after solid organ transplantation and its incidence is increasing. Non-melanoma skin cancer - squamous cell carcinoma and basal cell carcinoma - is the most common malignancy found in kidney transplant recipients (KTRs). The incidence of non-melanoma skin cancer in KTRs has not been extensively studied in Portugal. Objectives To determine the incidence of non-melanoma skin cancer in KTRs from the largest Portuguese kidney transplant unit; and to study risk factors for non-melanoma skin cancer. Methods Retrospective analysis of clinical records of KTRs referred for the first time for a dermatology consultation between 2004 and 2013. A case-control study was performed on KTRs with and without non-melanoma skin cancer. Results We included 288 KTRs with a median age at transplantation of 47 years, a male gender predominance (66%) and a median transplant duration of 3.67 years. One fourth (n=71) of KTRs developed 131 non-melanoma skin cancers, including 69 (53%) squamous cell carcinomas and 62 (47%) basal cell carcinomas (ratio squamous cell carcinoma: basal cell carcinoma 1.11), with a mean of 1.85 neoplasms per patient. Forty percent of invasive squamous cell carcinomas involved at least two clinical or histological high-risk features. The following factors were associated with a higher risk of non-melanoma skin cancer: an older age at transplantation and at the first consultation, a longer transplant duration and the presence of actinic keratosis. KTRs treated with azathioprine were 2.85 times more likely to develop non-melanoma skin cancer (p=0.01). Conclusion Non-melanoma skin cancer was a common reason for dermatology consultation in Portuguese KTRs. It is imperative for KTRs to have access to specialized dermatology consultation for early referral and treatment of skin malignancies. PMID:27579740

  4. Single-Lung Transplant Results in Position Dependent Changes in Regional Ventilation: An Observational Case Series Using Electrical Impedance Tomography

    PubMed Central

    Ramanathan, Kollengode; Mohammed, Hend; Hopkins, Peter; Corley, Amanda; Caruana, Lawrence; Dunster, Kimble; Barnett, Adrian G.; Fraser, John F.

    2016-01-01

    Background. Lung transplantation is the optimal treatment for end stage lung disease. Donor shortage necessitates single-lung transplants (SLT), yet minimal data exists regarding regional ventilation in diseased versus transplanted lung measured by Electrical Impedance Tomography (EIT). Method. We aimed to determine regional ventilation in six SLT outpatients using EIT. We assessed end expiratory volume and tidal volumes. End expiratory lung impedance (EELI) and Global Tidal Variation of Impedance were assessed in supine, right lateral, left lateral, sitting, and standing positions in transplanted and diseased lungs. A mixed model with random intercept per subject was used for statistical analysis. Results. EELI was significantly altered between diseased and transplanted lungs whilst lying on right and left side. One patient demonstrated pendelluft between lungs and was therefore excluded for further comparison of tidal variation. Tidal variation was significantly higher in the transplanted lung for the remaining five patients in all positions, except when lying on the right side. Conclusion. Ventilation to transplanted lung is better than diseased lung, especially in lateral positions. Positioning in patients with active unilateral lung pathologies will be implicated. This is the first study demonstrating changes in regional ventilation, associated with changes of position between transplanted and diseased lung. PMID:27445522

  5. Single lung transplantation and fatal fat embolism acquired from the donor: management and literature review.

    PubMed

    López-Sánchez, Marta; Alvarez-Antoñán, Carlos; Arce-Mateos, Félix P; Gómez-Román, José; Quesada-Suescun, Antonio; Zurbano-Goñi, Felipe

    2010-01-01

    Fat embolism (FE) is a consequence of skeletal trauma that occurs in more than 90% of cases of severe trauma. However, most of these emboli are clinically insignificant. We report the case of a 59-yr-old man with massive progressive fibrosis who died from widespread FE after a single-lung transplantation (SLT). The lung donor was a 22-yr-old woman who died from traumatic cerebral injury. She had sustained a closed fracture of the tibia, fibula and pelvis. The PaO(2)/FiO(2) before procurement was 452 mmHg. A left SLT using cardiopulmonary bypass was performed. In the immediate postoperative period, profound pulmonary edema in the transplanted lung developed, with overinflation of the native lung and systemic hypotension. Severe Primary Graft Dysfunction (PGD) was suspected and nitric oxide (NO) and independent lung ventilation (ILV) initiated. Over the next 24 h the patient's condition deteriorated and extracorporeal membrane oxygenation (ECMO) was initiated. The patient died 45 h after transplantation as cardiovascular and respiratory function continued to decline and massive thoracic bleeding secondary to coagulopathy appeared. Post-mortem examination revealed both massive FE in the non-transplanted donor lung and in the allograft lung. Only two previous cases of donor-acquired FE and PGD after lung transplantation (LT) have been reported. Occult pulmonary FE in a traumatized donor should be considered a cause of PGD. PMID:19888997

  6. A Review of Organ Transplantation: Heart, Lung, Kidney, Liver, and Simultaneous Liver-Kidney.

    PubMed

    Scheuher, Cynthia

    2016-01-01

    Heart, lung, kidney, liver, and simultaneous liver-kidney transplants share many features. They all follow the same 7-step process, the same 3 immunosuppressant medications, and the same reason for organ transplantation. Organs are transplanted because of organ failure. The similarities end there. Each organ has its unique causes for failure. Each organ also has its own set of criteria that must be met prior to transplantation. Simultaneous liver-kidney transplant criteria vary per transplant center but are similar in nature. Both the criteria required and the 7-step process are described by the United Network of Organ Sharing, which is a private, nonprofit organization, under contract with the US Department of Health and Human Services. Its function is to increase the number of transplants, improve survival rates after transplantation, promote safe transplant practices, and endorse efficiency. The purpose of this article is to review the reasons transplant is needed, specifically heart, lung, kidney, liver, and simultaneous liver-kidney, and a brief overview of the transplant process including criteria used, contraindications, and medications prescribed. PMID:27254636

  7. A Promoter Polymorphism in the CD59 Complement Regulatory Protein Gene in Donor Lungs Correlates With a Higher Risk for Chronic Rejection After Lung Transplantation.

    PubMed

    Budding, K; van de Graaf, E A; Kardol-Hoefnagel, T; Broen, J C A; Kwakkel-van Erp, J M; Oudijk, E-J D; van Kessel, D A; Hack, C E; Otten, H G

    2016-03-01

    Complement activation leads primarily to membrane attack complex formation and subsequent target cell lysis. Protection against self-damage is regulated by complement regulatory proteins, including CD46, CD55, and CD59. Within their promoter regions, single-nucleotide polymorphisms (SNPs) are present that could influence transcription. We analyzed these SNPs and investigated their influence on protein expression levels. A single SNP configuration in the promoter region of CD59 was found correlating with lower CD59 expression on lung endothelial cells (p = 0.016) and monocytes (p = 0.013). Lung endothelial cells with this SNP configuration secreted more profibrotic cytokine IL-6 (p = 0.047) and fibroblast growth factor β (p = 0.036) on exposure to sublytic complement activation than cells with the opposing configuration, whereas monocytes were more susceptible to antibody-mediated complement lysis (p < 0.0001). Analysis of 137 lung transplant donors indicated that this CD59 SNP configuration correlates with impaired long-term survival (p = 0.094) and a significantly higher incidence of bronchiolitis obliterans syndrome (p = 0.046) in the recipient. These findings support a role for complement in the pathogenesis of this posttransplant complication and are the first to show a deleterious association of a donor CD59 promoter polymorphism in lung transplantation. PMID:26517734

  8. Postinfectious bronchiolitis obliterans in children: lessons from bronchiolitis obliterans after lung transplantation and hematopoietic stem cell transplantation

    PubMed Central

    2015-01-01

    Postinfectious bronchiolitis obliterans (PIBO) is an irreversible obstructive lung disease characterized by subepithelial inflammation and fibrotic narrowing of the bronchioles after lower respiratory tract infection during childhood, especially early childhood. Although diagnosis of PIBO should be confirmed by histopathology, it is generally based on history and clinical findings. Irreversible airway obstruction is demonstrated by decreased forced expiratory volume in 1 second with an absent bronchodilator response, and by mosaic perfusion, air trapping, and/or bronchiectasis on computed tomography images. However, lung function tests using spirometry are not feasible in young children, and most cases of PIBO develop during early childhood. Further studies focused on obtaining serial measurements of lung function in infants and toddlers with a risk of bronchiolitis obliterans (BO) after lower respiratory tract infection are therefore needed. Although an optimal treatment for PIBO has not been established, corticosteroids have been used to target the inflammatory component. Other treatment modalities for BO after lung transplantation or hematopoietic stem cell transplantation have been studied in clinical trials, and the results can be extrapolated for the treatment of PIBO. Lung transplantation remains the final option for children with PIBO who have progressed to end-stage lung disease. PMID:26770220

  9. Postinfectious bronchiolitis obliterans in children: lessons from bronchiolitis obliterans after lung transplantation and hematopoietic stem cell transplantation.

    PubMed

    Yu, Jinho

    2015-12-01

    Postinfectious bronchiolitis obliterans (PIBO) is an irreversible obstructive lung disease characterized by subepithelial inflammation and fibrotic narrowing of the bronchioles after lower respiratory tract infection during childhood, especially early childhood. Although diagnosis of PIBO should be confirmed by histopathology, it is generally based on history and clinical findings. Irreversible airway obstruction is demonstrated by decreased forced expiratory volume in 1 second with an absent bronchodilator response, and by mosaic perfusion, air trapping, and/or bronchiectasis on computed tomography images. However, lung function tests using spirometry are not feasible in young children, and most cases of PIBO develop during early childhood. Further studies focused on obtaining serial measurements of lung function in infants and toddlers with a risk of bronchiolitis obliterans (BO) after lower respiratory tract infection are therefore needed. Although an optimal treatment for PIBO has not been established, corticosteroids have been used to target the inflammatory component. Other treatment modalities for BO after lung transplantation or hematopoietic stem cell transplantation have been studied in clinical trials, and the results can be extrapolated for the treatment of PIBO. Lung transplantation remains the final option for children with PIBO who have progressed to end-stage lung disease. PMID:26770220

  10. Invasive candidiasis in liver transplant patients: Incidence and risk factors in a pediatric cohort.

    PubMed

    De Luca, M; Green, M; Symmonds, J; Klieger, S B; Soltys, K; Fisher, B T

    2016-03-01

    Prolonged OR, re-transplantation, and high-volume intraoperative transfusion have been associated with increased risk for IC in adult LT recipients. Antifungal prophylaxis is recommended for adult patients with these risk factors. There are limited data on the incidence of and risk factors for IC in pediatric LT recipients. A retrospective cohort study of all pediatric LT patients at the CHOP between 2000 and 2012 and the CHP between 2004 and 2012 was performed to define the incidence of IC within 30 days of LT. A 3:1 matched case-control study with incidence density sampling was performed. Conditional logistic regression analyses were used to explore risk factors associated with IC. Among 397 recipients, the incidence of IC was 2.5%. Bivariate analyses showed that ICU admission prior to transplant, OR > 10 h, intraoperative volume infusion of >300 mL/kg, and broad-spectrum antibiotics were significantly associated with IC. In a multivariate model, only ICU admission remained significantly associated with IC. Antifungal prophylaxis was not significantly protective against IC. The low incidence of IC and lack of an identified protective effect from antifungal prophylaxis suggest that prophylaxis in pediatric LT recipients should not be routinely recommended to prevent IC events in the first 30 days post-transplant. PMID:26748472

  11. Can lungs be taken for transplantation from donors with a significant smoking history?

    PubMed

    Attaran, Saina; Chukwuemeka, Andrew; Anderson, Jon R

    2013-07-01

    A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was 'Can lungs be taken for transplantation from donors with a significant smoking history?’. Five papers were found using the reported search that represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. These studies compared the outcome and survival between patients who receive lungs from smokers with those receiving non-smoker lungs. None of these studies were randomized controlled trials. They retrospectively analysed a cohort of patients undergoing lung transplantation for the past 10 years. These studies showed worse outcomes in the early postoperative period, such as longer intensive care unit stay, longer ventilation time and higher early postoperative mortality, with lungs harvested from smokers. Two studies also demonstrated a worse long-term outcome in recipients of lungs from smokers, whereas the other two showed worse results during the early postoperative period only. These latter two studies reported similar survival rates after 3 months and up to 3 years in recipients receiving smoker vs non-smoker lungs. One study, however, showed a better 5-year survival with smoker lungs compared with non-smokers, although in this study, lungs from heavy smokers showed the worse outcome. Despite the difference in long-term results and outcome reported by these authors, all of these studies unanimously indicate that lungs from smokers should not be rejected, as survival in these patients receiving smoker lungs is still significantly higher in 3 and 5 years compared with that in those who remain on the transplant waiting list. In conclusion, the current evidence in the literature suggests that lungs from smokers can be used for transplantation. Patients should, however, be fully informed of

  12. Neutrophil Extracellular Traps Are Pathogenic in Primary Graft Dysfunction after Lung Transplantation

    PubMed Central

    Mallavia, Beñat; Liu, Fengchun; Ortiz-Muñoz, Guadalupe; Caudrillier, Axelle; DerHovanessian, Ariss; Ross, David J.; Lynch III, Joseph P.; Saggar, Rajan; Ardehali, Abbas; Ware, Lorraine B.; Christie, Jason D.; Belperio, John A.; Looney, Mark R.

    2015-01-01

    Rationale: Primary graft dysfunction (PGD) causes early mortality after lung transplantation and may contribute to late graft failure. No effective treatments exist. The pathogenesis of PGD is unclear, although both neutrophils and activated platelets have been implicated. We hypothesized that neutrophil extracellular traps (NETs) contribute to lung injury in PGD in a platelet-dependent manner. Objectives: To study NETs in experimental models of PGD and in lung transplant patients. Methods: Two experimental murine PGD models were studied: hilar clamp and orthotopic lung transplantation after prolonged cold ischemia (OLT-PCI). NETs were assessed by immunofluorescence microscopy and ELISA. Platelet activation was inhibited with aspirin, and NETs were disrupted with DNaseI. NETs were also measured in bronchoalveolar lavage fluid and plasma from lung transplant patients with and without PGD. Measurements and Main Results: NETs were increased after either hilar clamp or OLT-PCI compared with surgical control subjects. Activation and intrapulmonary accumulation of platelets were increased in OLT-PCI, and platelet inhibition reduced NETs and lung injury, and improved oxygenation. Disruption of NETs by intrabronchial administration of DNaseI also reduced lung injury and improved oxygenation. In bronchoalveolar lavage fluid from human lung transplant recipients, NETs were more abundant in patients with PGD. Conclusions: NETs accumulate in the lung in both experimental and clinical PGD. In experimental PGD, NET formation is platelet-dependent, and disruption of NETs with DNaseI reduces lung injury. These data are the first description of a pathogenic role for NETs in solid organ transplantation and suggest that NETs are a promising therapeutic target in PGD. PMID:25485813

  13. Increased Numbers of Circulating CD8 Effector Memory T Cells before Transplantation Enhance the Risk of Acute Rejection in Lung Transplant Recipients

    PubMed Central

    San Segundo, David; Ballesteros, María Ángeles; Naranjo, Sara; Zurbano, Felipe; Miñambres, Eduardo; López-Hoyos, Marcos

    2013-01-01

    The effector and regulatory T cell subpopulations involved in the development of acute rejection episodes in lung transplantation remain to be elucidated. Twenty-seven lung transplant candidates were prospectively monitored before transplantation and within the first year post-transplantation. Regulatory, Th17, memory and naïve T cells were measured in peripheral blood of lung transplant recipients by flow cytometry. No association of acute rejection with number of peripheral regulatory T cells and Th17 cells was found. However, effector memory subsets in acute rejection patients were increased during the first two months post-transplant. Interestingly, patients waiting for lung transplant with levels of CD8+ effector memory T cells over 185 cells/mm3 had a significant increased risk of rejection [OR: 5.62 (95% CI: 1.08-29.37), p=0.04]. In multivariate analysis adjusted for age and gender the odds ratio for rejection was: OR: 5.89 (95% CI: 1.08-32.24), p=0.04. These data suggest a correlation between acute rejection and effector memory T cells in lung transplant recipients. The measurement of peripheral blood CD8+ effector memory T cells prior to lung transplant may define patients at high risk of acute lung rejection. PMID:24236187

  14. Comparison of Predicted Total Lung Capacity and Total Lung Capacity by Computed Tomography in Lung Transplantation Candidates

    PubMed Central

    Hwang, Sung Ho; Lee, Jin Gu; Kim, Tae Hoon; Paik, Hyo Chae; Park, Chul Hwan

    2016-01-01

    Purpose Lung size mismatch is a major cause of poor lung function and worse survival after lung transplantation (LTx). We compared predicted total lung capacity (pTLC) and TLC measured by chest computed tomography (TLCCT) in LTx candidates. Materials and Methods We reviewed the medical records of patients on waiting lists for LTx. According to the results of pulmonary function tests, patients were divided into an obstructive disease group and restrictive disease group. The differences between pTLC calculated using the equation of the European Respiratory Society and TLCCT were analyzed in each group. Results Ninety two patients met the criteria. Thirty five patients were included in the obstructive disease group, and 57 patients were included in the restrictive disease group. pTLC in the obstructive disease group (5.50±1.07 L) and restrictive disease group (5.57±1.03 L) had no statistical significance (p=0.747), while TLCCT in the restrictive disease group (3.17±1.15 L) was smaller than that I the obstructive disease group (4.21±1.38 L) (p<0.0001). TLCCT/pTLC was 0.770 in the obstructive disease group and 0.571 in the restrictive disease group. Conclusion Regardless of pulmonary disease pattern, TLCCT was smaller than pTLC, and it was more apparent in restrictive lung disease. Therefore, we should consider the difference between TLCCT and pTLC, as well as lung disease patterns of candidates, in lung size matching for LTx. PMID:27189292

  15. The incidence of autoimmune hemolytic anemia in pediatric hematopoietic stem cell recipients post first and second hematopoietic stem cell transplant

    PubMed Central

    Ahmed, Ibrahim; Teruya, Jun; Murray-Krezan, Cristina; Krance, Robert

    2015-01-01

    The reported incidence of post allogeneic hematopoietic stem cell transplant (HSCT) auto-immune hemolytic anemia (AIHA) was between 4.4% and 6% following a single transplant. Cord blood transplantation, T-cell depletion and chronic GvHD are significantly associated with post-transplant AIHA. During an 11 year period, data for 500 pediatric HSCT recipients were eligible for evaluation of the incidence of AIHA post first and second transplants. Demographic, transplant, and post-transplant related variables were analyzed. Twelve/500 (2.4%) recipients at a median of 273 days and 7/72 (9.7%) recipients at a median of 157 days developed AIHA post first and second HSCT respectively. Post first HSCT, none of the matched related donor recipients developed AIHA (0/175 MRD vs. 12/325 other donors, p=0.04). Four/12 required a second HSCT to control the AIHA. Post the second HSCT, matched unrelated donor was significantly associated with the development of AIHA. No other variables were associated with the post-second transplant AIHA. The incidence of AIHA post first and second HSCT was less than reported. The increased incidence of AIHA among recipients of second HSCT is most likely due to the profound immune dysregulation. A much larger, prospective study would be needed to evaluate the incidence, complications and management of post-transplant AIHA. PMID:25809012

  16. Donor age and early graft failure after lung transplantation: a cohort study

    PubMed Central

    Baldwin, Matthew R; Peterson, Eric R; Easthausen, Imaani; Quintanilla, Isaac; Colago, Eric; Sonett, Joshua R.; D’Ovidio, Frank; Costa, Joseph; Diamond, Joshua M; Christie, Jason D; Arcasoy, Selim M; Lederer, David J

    2014-01-01

    Lungs from older adult organ donors are often unused because of concerns for increased mortality. We examined associations between donor age and transplant outcomes among 8,860 adult lung transplant recipients using Organ Procurement and Transplantation Network and Lung Transplant Outcomes Group data. We used stratified Cox proportional hazard models and generalized linear mixed models to examine associations between donor age and both 1-year graft failure and primary graft dysfunction. The rate of 1-year graft failure was similar among recipients of lungs from donors age 18–64 years, but severely ill recipients (LAS > 47.7 or use of mechanical ventilation) of lungs from donors age 56–64 years had increased rates of 1-year graft failure (p-values for interaction = 0.04 and 0.02, respectively). Recipients of lungs from donors <18 and ≥65 years had increased rates of 1-year graft failure (adjusted hazard ratio 1.23, 95% CI 1.01–1.50 and adjusted hazard ratio 2.15, 95% CI 1.47–3.15, respectively). Donor age was not associated with the risk of primary graft dysfunction. In summary, the use of lungs from donors age 56–64 years may be safe for adult candidates without a high LAS, and the use of lungs from pediatric donors is associated with a small increase in early graft failure. PMID:24034167

  17. Substantial Increases Occur in Serum Activins and Follistatin during Lung Transplantation

    PubMed Central

    de Kretser, David M.; Bensley, Jonathan G.; Phillips, David J.; Levvey, Bronwyn J.; Snell, Greg I.; Lin, Enjarn; Hedger, Mark P.; O’Hehir, Robyn E.

    2016-01-01

    Background Lung transplantation exposes the donated lung to a period of anoxia. Re-establishing the circulation after ischemia stimulates inflammation causing organ damage. Since our published data established that activin A is a key pro-inflammatory cytokine, we assessed the roles of activin A and B, and their binding protein, follistatin, in patients undergoing lung transplantation. Methods Sera from 46 patients participating in a published study of remote ischemia conditioning in lung transplantation were used. Serum activin A and B, follistatin and 11 other cytokines were measured in samples taken immediately after anaesthesia induction, after remote ischemia conditioning or sham treatment undertaken just prior to allograft reperfusion and during the subsequent 24 hours. Results Substantial increases in serum activin A, B and follistatin occurred after the baseline sample, taken before anaesthesia induction and peaked immediately after the remote ischemia conditioning/sham treatment. The levels remained elevated 15 minutes after lung transplantation declining thereafter reaching baseline 2 hours post-transplant. Activin B and follistatin concentrations were lower in patients receiving remote ischemia conditioning compared to sham treated patients but the magnitude of the decrease did not correlate with early transplant outcomes. Conclusions We propose that the increases in the serum activin A, B and follistatin result from a combination of factors; the acute phase response, the reperfusion response and the use of heparin-based anti-coagulants. PMID:26820896

  18. Lung transplantation in an intensive care patient with pulmonary alveolar microlithiasis - a case report

    PubMed Central

    Güçyetmez, Bülent; Ogan, Aylin; Çimet Ayyıldız, Aylin; Yalçın Güder, Berrin; Klepetko, Walter

    2014-01-01

    Introduction: Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disease characterized by the deposition of phosphate and calcium in the alveoli. The disease progresses asymptomatically until later stages. When it becomes symptomatic, lung transplantations performed before the onset of right heart failure may improve life expectancy and quality. Here we present a case report concerning the very first Turkish PAM patient to have undergone lung transplantation surgery. Patient information: A 52 year-old female, Caucasian patient, already diagnosed with PAM in infancy, was admitted to the intensive care unit, diagnosed with pneumonia and hospitalized for 20 days. We decided to refer the patient to a specialized center for lung transplantation. Bilateral lung transplantation was performed in Vienna 14 months later and no recurrence was observed during the first postoperative year. Conclusion: Bilateral lung transplantation may improve both the life expectancy and the quality of life of PAM diagnosed patients with severe respiratory failure who do not suffer from right heart failure. The risk of recurrence should not be considered as a justifying reason to avoid transplantation as a treatment method. PMID:25165536

  19. A case of acute fibrinous and organizing pneumonia during early postoperative period after lung transplantation.

    PubMed

    Alici, I O; Yekeler, E; Yazicioglu, A; Turan, S; Tezer-Tekce, Y; Demirag, F; Karaoglanoglu, N

    2015-04-01

    Acute fibrinous and organizing pneumonia (AFOP) is a distinct histologic pattern usually classified under the term chronic lung allograft dysfunction. We present a 48-year-old female patient who experienced AFOP during the 2nd week of double lung transplantation for pulmonary Langerhans cell histiocytosis and secondary pulmonary hypertension. During the 8th day after transplantation, fever and neutrophilia developed together with bilateral consolidation. Infection markers were elevated. Despite coverage of a full antimicrobial spectrum, the situation progressed. The patient was diagnosed with AFOP with transbronchial biopsy. The infiltration resolved and the patient improved dramatically with the initiation of pulse corticosteroid treatment. AFOP should be suspected when there is a pulmonary consolidation after lung transplantation, even in the very early post-transplantation period. Several causes, such as alveolar damage and drug reactions, should be considered in the differential diagnosis. PMID:25891742

  20. Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient

    PubMed Central

    Bahr, Nathan C.; Janssen, Katherine; Billings, Joanne; Loor, Gabriel; Green, Jaime S.

    2015-01-01

    Background. De novo and donor-derived invasive fungal infections (IFIs) contribute to morbidity and mortality in solid organ transplant (SOT) recipients. Reporting of donor-derived IFIs (DDIFIs) to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes. PMID:26697244

  1. Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient.

    PubMed

    Bahr, Nathan C; Janssen, Katherine; Billings, Joanne; Loor, Gabriel; Green, Jaime S

    2015-01-01

    Background. De novo and donor-derived invasive fungal infections (IFIs) contribute to morbidity and mortality in solid organ transplant (SOT) recipients. Reporting of donor-derived IFIs (DDIFIs) to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes. PMID:26697244

  2. Advances in Understanding Bronchiolitis Obliterans After Lung Transplantation.

    PubMed

    Verleden, Stijn E; Sacreas, Annelore; Vos, Robin; Vanaudenaerde, Bart M; Verleden, Geert M

    2016-07-01

    Bronchiolitis obliterans syndrome (BOS) remains a major complication after lung transplantation, causing significant morbidity and mortality in a majority of recipients. BOS is believed to be the clinical correlate of chronic allograft dysfunction, and is defined as an obstructive pulmonary function defect in the absence of other identifiable causes, mostly not amenable to treatment. Recently, it has become clear that BOS is not the only form of chronic allograft dysfunction and that other clinical phenotypes exist; however, we focus exclusively on BOS. Radiologic findings typically demonstrate air trapping, mosaic attenuation, and hyperinflation. Pathologic examination reveals obliterative bronchiolitis lesions and a pure obliteration of the small airways (< 2 mm), with a relatively normal surrounding parenchyma. In this review, we highlight recent advances in diagnosis, pathologic examination, and risk factors, such as microbes, viruses, and antibodies. Although the pathophysiological mechanisms remain largely unknown, we review the role of the airway epithelium and inflammation and the various experimental animal models. We also clarify the clinical and therapeutic implications of these findings. Although significant progress has been made, the exact pathophysiological mechanisms and adequate therapy for posttransplantation BOS remain unknown, highlighting the need for further research to improve long-term posttransplantation BOS-free and overall survival. PMID:27212132

  3. Immunomodulatory Effects of Mixed Hematopoietic Chimerism: Immune Tolerance in Canine Model of Lung Transplantation

    PubMed Central

    Nash;, Richard A.; Yunosov;, Murad; Abrams;, Kraig; Hwang;, Billanna; Castilla-Llorente;, Cristina; Chen;, Peter; Farivar;, Alexander S.; Georges;, George E.; Hackman;, Robert C.; Lamm;, Wayne J.E.; Lesnikova;, Marina; Ochs;, Hans D.; Randolph-Habecker;, Julie; Ziegler;, Stephen F.; Storb;, Rainer; Storer;, Barry; Madtes;, David K.; Glenny;, Robb; Mulligan, Michael S.

    2010-01-01

    Long-term survival after lung transplantation is limited by acute and chronic graft rejection. Induction of immune tolerance by first establishing mixed hematopoietic chimerism (MC) is a promising strategy to improve outcomes. In a preclinical canine model, stable MC was established in recipients after reduced-intensity conditioning and hematopoietic cell transplantation from a DLA-identical donor. Delayed lung transplantation was performed from the stem cell donor without pharmacological immunosuppression. Lung graft survival without loss of function was prolonged in chimeric (n=5) vs. nonchimeric (n=7) recipients (p≤0.05, Fisher’s test). There were histological changes consistent with low grade rejection in 3/5 of the lung grafts in chimeric recipients at ≥1 year. Chimeric recipients after lung transplantation had a normal immune response to a T-dependent antigen. Compared to normal dogs, there were significant increases of CD4+INFγ+, CD4+IL-4+ and CD8+ INFγ+ T-cell subsets in the blood (p <0.0001 for each of the 3 T-cell subsets). Markers for regulatory T-cell subsets including foxP3, IL10 and TGFβ were also increased in CD3+ T cells from the blood and peripheral tissues of chimeric recipients after lung transplantation. Establishing MC is immunomodulatory and observed changes were consistent with activation of both the effector and regulatory immune response. PMID:19422333

  4. Higher Risk of Acute Cellular Rejection in Lung Transplant Recipients with Cystic Fibrosis.

    PubMed

    Calabrese, Fiorella; Lunardi, Francesca; Nannini, Nazarena; Balestro, Elisabetta; Loy, Monica; Marulli, Giuseppe; Calabrese, Francesca; Vuljan, Stefania Edith; Schiavon, Marco; Perissinotto, Egle; Rea, Federico

    2015-01-01

    BACKGROUND Acute cellular rejection (ACR) affects up to 40% of recipients within the first year after lung transplant (LTx). The aim of this study was to determine the frequency of ACR and associated major risk factors in cystic fibrosis (CF) recipients. Bronchiolitis obliterans syndrome (BOS) and 1-year/long-term survival were also evaluated. MATERIAL AND METHODS ACR was reviewed in 643 scheduled biopsies from 44 CF (Group 1) versus 89 other recipients (Group 2). We performed univariate/multivariate analyses of risk factors for ACR and BOS, and survival analysis. RESULTS Group 1 showed higher ACR frequency, especially for ACR ≥ A2. Multivariable generalized linear models considering both native lung disease and age showed that higher values of ACR index were significantly related to the pretransplant diagnosis of CF. BOS and long-term survival were not influenced by the increased incidence of ACR. Poorer long-term survival was observed in Group 2. CONCLUSIONS CF recipients have a higher ACR risk, which may be due to enhanced immune activation related to a genetic disorder, and younger age. PMID:26718747

  5. Body Composition and Mortality after Adult Lung Transplantation in the United States

    PubMed Central

    Singer, Jonathan P.; Peterson, Eric R.; Snyder, Mark E.; Katz, Patricia P.; Golden, Jeffrey A.; D’Ovidio, Frank; Bacchetta, Matthew; Sonett, Joshua R.; Kukreja, Jasleen; Shah, Lori; Robbins, Hilary; Van Horn, Kristin; Shah, Rupal J.; Diamond, Joshua M.; Wickersham, Nancy; Sun, Li; Hays, Steven; Arcasoy, Selim M.; Palmer, Scott M.; Ware, Lorraine B.; Christie, Jason D.

    2014-01-01

    Rationale: Obesity and underweight are contraindications to lung transplantation based on their associations with mortality in studies performed before implementation of the lung allocation score (LAS)–based organ allocation system in the United States Objectives: To determine the associations of body mass index (BMI) and plasma leptin levels with survival after lung transplantation. Methods: We used multivariable-adjusted regression models to examine associations between BMI and 1-year mortality in 9,073 adults who underwent lung transplantation in the United States between May 2005 and June 2011, and plasma leptin and mortality in 599 Lung Transplant Outcomes Group study participants. We measured body fat and skeletal muscle mass using whole-body dual X-ray absorptiometry in 142 adult lung transplant candidates. Measurements and Main Results: Adjusted mortality rates were similar among normal weight (BMI 18.5–24.9 kg/m2), overweight (BMI 25.0–29.9), and class I obese (BMI 30–34.9) transplant recipients. Underweight (BMI < 18.5) was associated with a 35% increased rate of death (95% confidence interval, 10–66%). Class II–III obesity (BMI ≥ 35 kg/m2) was associated with a nearly twofold increase in mortality (hazard ratio, 1.9; 95% confidence interval, 1.3–2.8). Higher leptin levels were associated with increased mortality after transplant surgery performed without cardiopulmonary bypass (P for interaction = 0.03). A BMI greater than or equal to 30 kg/m2 was 26% sensitive and 97% specific for total body fat–defined obesity. Conclusions: A BMI of 30.0–34.9 kg/m2 is not associated with 1-year mortality after lung transplantation in the LAS era, perhaps because of its low sensitivity for obesity. The association between leptin and mortality suggests the need to validate alternative methods to measure obesity in candidates for lung transplantation. A BMI greater than or equal to 30 kg/m2 may no longer contraindicate lung transplantation. PMID

  6. Development and characterization of a lung-protective method of bone marrow transplantation in the mouse.

    PubMed

    Janssen, William J; Muldrow, Alaina; Kearns, Mark T; Barthel, Lea; Henson, Peter M

    2010-05-31

    Allogeneic bone marrow transplantation is a common method used to study the contribution of myeloid and lymphoid cell populations in murine models of disease. The method requires lethal doses of radiation to ablate the bone marrow. Unintended consequences of radiation include organ injury and inflammatory cell activation. The goal of our study was to determine the degree to which bone marrow transplantation alters lungs and to develop a system to protect the lungs during radiation. C57BL/6 mice were subjected to total body irradiation with 900cGy and then transplanted with bone marrow from green fluorescent protein (GFP) expressing mice. Resultant chimeras exhibited a significant decline in alveolar macrophage numbers within 72h, modest influx of neutrophils in the lungs at 14days, and repopulation of the lungs by alveolar macrophages of bone marrow origin by 28days. Neutrophil influx and alveolar macrophage turnover were prevented when 1cm thick lead shields were used to protect the lungs during radiation, such that 8weeks after transplantation less than 30% of alveolar macrophages were of donor origin. Lung-shielded mice achieved a high level of bone marrow engraftment with greater than 95% of circulating leukocytes expressing GFP. In addition, their response to intratracheal lipopolysaccharide was similar to non-transplanted mice. We describe a model whereby lead shields protect resident cell populations in the lungs from radiation during bone marrow transplantation but permit full bone marrow engraftment. This system may be applicable to other organ systems in which protection from radiation during bone marrow transplantation is desired. PMID:20347833

  7. Functional improvement in patients with idiopathic pulmonary fibrosis undergoing single lung transplantation *

    PubMed Central

    Rubin, Adalberto Sperb; Nascimento, Douglas Zaione; Sanchez, Letícia; Watte, Guilherme; Holand, Arthur Rodrigo Ronconi; Fassbind, Derrick Alexandre; Camargo, José Jesus

    2015-01-01

    Abstract Objective: To evaluate the changes in lung function in the first year after single lung transplantation in patients with idiopathic pulmonary fibrosis (IPF). Methods: We retrospectively evaluated patients with IPF who underwent single lung transplantation between January of 2006 and December of 2012, reviewing the changes in the lung function occurring during the first year after the procedure. Results: Of the 218 patients undergoing lung transplantation during the study period, 79 (36.2%) had IPF. Of those 79 patients, 24 (30%) died, and 11 (14%) did not undergo spirometry at the end of the first year. Of the 44 patients included in the study, 29 (66%) were men. The mean age of the patients was 57 years. Before transplantation, mean FVC, FEV1, and FEV1/FVC ratio were 1.78 L (50% of predicted), 1.48 L (52% of predicted), and 83%, respectively. In the first month after transplantation, there was a mean increase of 12% in FVC (400 mL) and FEV1 (350 mL). In the third month after transplantation, there were additional increases, of 5% (170 mL) in FVC and 1% (50 mL) in FEV1. At the end of the first year, the functional improvement persisted, with a mean gain of 19% (620 mL) in FVC and 16% (430 mL) in FEV1. Conclusions: Single lung transplantation in IPF patients who survive for at least one year provides significant and progressive benefits in lung function during the first year. This procedure is an important therapeutic alternative in the management of IPF. PMID:26398749

  8. Autologous endothelial progenitor cells improve allograft survival in porcine lung transplantation with prolonged ischemia

    PubMed Central

    Yen, Yi-Ting; Roan, Jun-Neng; Fang, Shih-Yuan; Chang, Shi-Wei; Tseng, Yau-Lin

    2016-01-01

    Background As endothelial progenitor cells (EPCs) attenuated acute lung injury (ALI) in rabbit model, we hypothesized that autologous EPCs preserved lung graft function during the acute reperfusion period of lung transplantation and tested the therapeutic potential of EPCs in a porcine model of lung transplantation with prolonged graft ischemia. Methods Day-7 EPCs isolated from the recipient subjects or plain culture media were administered into the left pulmonary artery immediately before restoration of pulmonary blood flow in a porcine lung allotransplantation model, with the transplantation surgeons blinded to the content of injection. Hemodynamics and arterial blood gas were recorded, and the right pulmonary artery was occluded 30 min after reperfusion to evaluate the lung graft function. The lung grafts were sectioned for histological examination at the end of experiments. The total ischemic time for lung graft was approximately 14 h. Results All animals receiving plain medium died within 40 min after reperfusion, but 3 out of 5 (60%) piglets receiving EPCs survived up to 4 h after diversion of the entire cardiac output into the lung graft (P<0.01). The donor body weight, recipient body weight, cold ischemic time, and time for anastomosis were comparable between the EPC and control group (P=0.989, 0.822, 0.843, and 0.452, respectively). The mean aortic pressure decreased, and the cardiac output and mean pulmonary artery pressure elevated after right pulmonary artery occlusion. All these parameters were gradually compensated in the EPC group but decompensated in the control group. Better preservation of gas exchange function, reduced thrombi formation in the terminal pulmonary arterioles, and attenuated interstitial hemorrhage of the lung graft were observed in the EPC group. Conclusions We concluded autologous EPCs significantly enhanced the function of lung allograft and improved survival in a porcine model of lung transplantation with prolonged ischemia

  9. Perioperative management of pulmonary hypertension during lung transplantation (a lesson for other anaesthesia settings).

    PubMed

    Rabanal, J M; Real, M I; Williams, M

    2014-10-01

    Patients with pulmonary hypertension are some of the most challenging for an anaesthesiologist to manage. Pulmonary hypertension in patients undergoing surgical procedures is associated with high morbidity and mortality due to right ventricular failure, arrhythmias and ischaemia leading to haemodynamic instability. Lung transplantation is the only therapeutic option for end-stage lung disease. Patients undergoing lung transplantation present a variety of challenges for anaesthesia team, but pulmonary hypertension remains the most important. The purpose of this article is to review the anaesthetic management of pulmonary hypertension during lung transplantation, with particular emphasis on the choice of anaesthesia, pulmonary vasodilator therapy, inotropic and vasopressor therapy, and the most recent intraoperative monitoring recommendations to optimize patient care. PMID:25156939

  10. The Etiology, Incidence, and Impact of Preservation Fluid Contamination during Liver Transplantation

    PubMed Central

    Lladó, Laura; Vila, Marina; Baliellas, Carme; Tubau, Fe; Sabé, Núria; Fabregat, Joan; Carratalà, Jordi

    2016-01-01

    The role of contaminated preservation fluid in the development of infection after liver transplantation has not been fully elucidated. To assess the incidence and etiology of contaminated preservation fluid and determine its impact on the subsequent development of infection after liver transplantation, we prospectively studied 50 consecutive liver transplants, and cultured the following samples in each instance: preservation fluid (immediately before and at the end of the back-table procedure, and just before implantation), blood, and bile from the donor, and ascitic fluid from the recipient. When any culture was positive, blood cultures were obtained and targeted antimicrobial therapy was started. We found that the incidence of contaminated preservation fluid was 92% (46 of 50 cases of liver transplantation per year), but only 28% (14/50) were contaminated by recognized pathogens. Blood and bile cultures from the donor were positive in 28% and 6% respectively, whereas ascitic fluid was positive in 22%. The most frequently isolated microorganisms were coagulase-negative staphylococci. In nine cases, the microorganisms isolated from the preservation fluid concurred with those grown from the donor blood cultures, and in one case, the isolate matched with the one obtained from bile culture. No liver transplant recipient developed an infection due to the transmission of an organism isolated from the preservation fluid. Our findings indicate that contamination of the preservation fluid is frequent in liver transplantation, and it is mainly caused by saprophytic skin flora. Transmission of infection is low, particularly among those recipients given targeted antimicrobial treatment for organisms isolated in the preservation fluid. PMID:27513941

  11. Avascular necrosis of bone after allogeneic bone marrow transplantation: clinical findings, incidence and risk factors.

    PubMed

    Socié, G; Sélimi, F; Sedel, L; Frija, J; Devergie, A; Esperou Bourdeau, H; Ribaud, P; Gluckman, E

    1994-03-01

    In the present study we describe the incidence, clinical course, and management of avascular necrosis of bone following allogeneic bone marrow transplantation, and identify risk factors related to its development. All patients developing avascular necrosis of bone after allogeneic bone marrow transplantation between January 1974 and September 1992 were included in the analysis and were studied using the Hôpital Saint Louis Bone Marrow Transplant Database and hospital records. 27/727 allogeneic transplant recipients developed avascular necrosis leading to an 8.1% incidence at 5 years, by product limit estimate, ranging from 5% to 11.2%. Symptoms developed 119-1747 d (median 398 d) after transplantation. In these 27 patients a total of 52 joints were affected (mean 1.92 per patient, range 1-7). The hip joint was most often affected (69% of patients). All patients had joint pain that led to diagnosis by means of standard radiographs with or without the help of technetium-99 scans and/or magnetic resonance imaging. All but three patients received steroid therapy for acute graft-versus-host disease. Among 10 factors tested, three were shown to be significantly linked to an increased risk for developing avascular necrosis by multivariate analysis: male gender (relative risk (RR) 4.72, P = 0.002), age older than 16 (RR = 3.87, P = 0.004), and acute graft-versus-host disease requiring steroid therapy (RR = 6.30, P = 0.0002). 10 patients (37%) required joint replacement within 19 months (range 2-42) following diagnosis of avascular necrosis. In conclusion, avascular necrosis of bone is a frequent late complication of allogeneic bone marrow transplantation causing significant morbidity and requiring replacement surgery in one-third of affected patients. In this 18-year single-centre survey, older age, male gender and steroid therapy given for acute graft-versus-host disease were shown to independently increase the risk of avascular necrosis of bone. PMID:8043445

  12. Engraftment syndrome after nonmyeloablative allogeneic hematopoietic stem cell transplantation: incidence and effects on survival.

    PubMed

    Gorak, Edward; Geller, Nancy; Srinivasan, Ramaprasad; Espinoza-Delgado, Igor; Donohue, Teresa; Barrett, A John; Suffredini, Anthony; Childs, Richard

    2005-07-01

    Engraftment syndrome (ES) encompasses a constellation of symptoms that occur during neutrophil recovery after both autologous and allogeneic hematopoietic stem cell transplantation (HCT). Although it is well characterized after conventional myeloablative procedures, limited data exist on this complication after nonmyeloablative allogeneic HCT. The clinical manifestations, incidence, and risk factors associated with ES were investigated in a consecutive series of patients undergoing cyclophosphamide/fludarabine-based nonmyeloablative allogeneic HCT from a related HLA-compatible donor. Fifteen (10%) of 149 patients (median age, 53 years; range, 27-66 years) developed ES; the onset of symptoms occurred at a median of 10 days (range, 3-14 days), and they consisted of fever (100%), cough (53%), diffuse pulmonary infiltrates (100%), rash (13%), and room air hypoxia (87%). ES was more likely to develop in patients who received empiric amphotericin formulations after transplant conditioning (Fisher exact test; P=.007). In a multivariate analysis, older patient age, female sex, and treatment with amphotericin were predictors for the development of ES. Intravenous methylprednisolone led to the rapid resolution of ES; however, transplant-related mortality was significantly higher (cumulative incidence, 49% versus 16%; P=.0005), and median survival was significantly shorter (168 versus 418 days; P=.005) in patients with ES compared with non-ES patients. In conclusion, ES occurs commonly after cyclophosphamide/fludarabine-based nonmyeloablative transplantation and responds rapidly to corticosteroid treatment, but it is associated with a higher risk of nonrelapse mortality and with shorter overall survival. PMID:15983554

  13. Effects of exogenous surfactant on the non-heart-beating donor lung graft in experimental lung transplantation - a stereological study.

    PubMed

    Herrmann, Gudrun; Knudsen, Lars; Madershahian, Navid; Mühlfeld, Christian; Frank, Konrad; Rahmanian, Parwis; Wahlers, Thorsten; Wittwer, Thorsten; Ochs, Matthias

    2014-05-01

    The use of non-heart-beating donor (NHBD) lungs may help to overcome the shortage of lung grafts in clinical lung transplantation, but warm ischaemia and ischaemia/reperfusion injury (I/R injury) resulting in primary graft dysfunction represent a considerable threat. Thus, better strategies for optimized preservation of lung grafts are urgently needed. Surfactant dysfunction has been shown to contribute to I/R injury, and surfactant replacement therapy is effective in enhancing lung function and structural integrity in related rat models. In the present study we hypothesize that surfactant replacement therapy reduces oedema formation in a pig model of NHBD lung transplantation. Oedema formation was quantified with (SF) and without (non-SF) surfactant replacement therapy in interstitial and alveolar compartments by means of design-based stereology in NHBD lungs 7 h after cardiac arrest, reperfusion and transplantation. A sham-operated group served as control. In both NHBD groups, nearly all animals died within the first hours after transplantation due to right heart failure. Both SF and non-SF developed an interstitial oedema of similar degree, as shown by an increase in septal wall volume and arithmetic mean thickness as well as an increase in the volume of peribron-chovascular connective tissue. Regarding intra-alveolar oedema, no statistically significant difference could be found between SF and non-SF. In conclusion, surfactant replacement therapy cannot prevent poor outcome after prolonged warm ischaemia of 7 h in this model. While the beneficial effects of surfactant replacement therapy have been observed in several experimental and clinical studies related to heart-beating donor lungs and cold ischaemia, it is unlikely that surfactant replacement therapy will overcome the shortage of organs in the context of prolonged warm ischaemia, for example, 7 h. Moreover, our data demonstrate that right heart function and dysfunctions of the pulmonary vascular bed are

  14. Anti-reflux surgery in lung transplant recipients: outcomes and effects on quality of life.

    PubMed

    Robertson, A G N; Krishnan, A; Ward, C; Pearson, J P; Small, T; Corris, P A; Dark, J H; Karat, D; Shenfine, J; Griffin, S M

    2012-03-01

    Fundoplication may improve survival after lung transplantation. Little is known about the effects of fundoplication on quality of life in these patients. The aim of this study was to assess the safety of fundoplication in lung transplant recipients and its effects on quality of life. Between June 1, 2008 and December 31, 2010, a prospective study of lung transplant recipients undergoing fundoplication was undertaken. Quality of life was assessed before and after surgery. Body mass index (BMI) and pulmonary function were followed up. 16 patients, mean ± sd age 38 ± 11.9 yrs, underwent laparoscopic Nissen fundoplication. There was no peri-operative mortality or major complications. Mean ± SD hospital stay was 2.6 ± 0.9 days. 15 out of 16 patients were satisfied with the results of surgery post fundoplication. There was a significant improvement in reflux symptom index and DeMeester questionnaires and gastrointestinal quality of life index scores at 6 months. Mean BMI decreased significantly after fundoplication (p = 0.01). Patients operated on for deteriorating lung function had a statistically significant decrease in the rate of lung function decline after fundoplication (p = 0.008). Laparoscopic fundoplication is safe in selected lung transplant recipients. Patient benefit is suggested by improved symptoms and satisfaction. This procedure is acceptable, improves quality of life and may reduce deterioration of lung function. PMID:21778169

  15. The cough response to ultrasonically nebulized distilled water in heart-lung transplantation patients

    SciTech Connect

    Higenbottam, T.; Jackson, M.; Woolman, P.; Lowry, R.; Wallwork, J.

    1989-07-01

    As a result of clinical heart-lung transplantation, the lungs are denervated below the level of the tracheal anastomosis. It has been questioned whether afferent vagal reinnervation occurs after surgery. Here we report the cough frequency, during inhalation of ultrasonically nebulized distilled water, of 15 heart-lung transplant patients studied 6 wk to 36 months after surgery. They were compared with 15 normal subjects of a similar age and sex. The distribution of the aerosol was studied in five normal subjects using /sup 99m/technetium diethylene triamine pentaacetate (/sup 99m/Tc-DTPA) in saline. In seven patients, the sensitivity of the laryngeal mucosa to instilled distilled water (0.2 ml) was tested at the time of fiberoptic bronchoscopy by recording the cough response. Ten percent of the aerosol was deposited onto the larynx and trachea, 56% on the central airways, and 34% in the periphery of the lung. The cough response to the aerosol was strikingly diminished in the patients compared with normal subjects (p less than 0.001), but all seven patients coughed when distilled water was instilled onto the larynx. As expected, the laryngeal mucosa of heart-lung transplant patients remains sensitive to distilled water. However, the diminished coughing when the distilled water is distributed by aerosol to the central airways supports the view that vagal afferent nerves do not reinnervate the lungs after heart-lung transplantation, up to 36 months after surgery.

  16. Autoperfused working heart-lung preparation versus hypothermic cardiopulmonary preservation for transplantation.

    PubMed

    Adachi, H; Fraser, C D; Kontos, G J; Borkon, A M; Hutchins, G M; Galloway, E; Brawn, J; Reitz, B A; Baumgartner, W A

    1987-01-01

    The effects of preserving the heart and lungs with an autoperfused working heart-lung preparation or simple hypothermia via cardiopulmonary bypass were studied in 18 dairy calves that had combined heart-lung transplantation. Group 1 (n = 6) served as the control group in which animals were cooled with cardiopulmonary bypass and immediately had allotransplantations. In group 2 (n = 6), cardiopulmonary function was maintained in the autoperfusion circuit for 4 hours, followed by transplantation. In group 3 (n = 6), the organs were harvested after cooling by cardiopulmonary bypass, stored in cold (4 degrees C) saline solution for 4 hours, and then transplanted. Cardiopulmonary function was compared between the three groups for 6 hours after implantation. Cardiac function was determined by the ratio of the end-systolic pressure to end-systolic dimension. Pulmonary function was evaluated by the measurement of extravascular lung water, arterial oxygenation on 100% inspired oxygen static lung compliance, and histologic lung injury score. All measurements in groups 2 and 3 were similar to those of the control group at 6 hours after implantation. One may use either the hypothermic cardiopulmonary preservation method after cardiopulmonary bypass or the autoperfused working heart-lung preparation for distant organ procurement and expect adequate cardiopulmonary function after transplantation. PMID:3119800

  17. Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation.

    PubMed

    Bacigalupo, Andrea; Lamparelli, Teresa; Barisione, Giovanni; Bruzzi, Paolo; Guidi, Stefano; Alessandrino, Paolo Emilio; di Bartolomeo, Paolo; Oneto, Rosi; Bruno, Barbara; Sacchi, Nicoletta; van Lint, Maria Teresa; Bosi, Alberto

    2006-05-01

    This is an update of a randomized study on antithymocyte globulin (ATG; Thymoglobulin) before transplantation in patients undergoing unmanipulated marrow transplantation from unrelated donors. The median follow-up for surviving patients is 5.7 years. At last follow-up, chronic graft-versus-host disease (GVHD) was scored in 60% of non-ATG and in 37% of ATG patients (P=.05), and extensive chronic GVHD was present in 41% and 15%, respectively (P=.01). Chronic lung dysfunction was diagnosed in 51% versus 19% of patients (P=.005). Forced vital capacity decreased significantly with time in non-ATG patients (P=.005), but not in patients who received ATG (P=.30). The proportion of patients with Karnofsky scores of >or=90% at 4 years was 57% versus 89% in non-ATG versus ATG patients (P=.03). The actuarial 6-year survival for all patients randomized was 31% versus 44% (non-ATG versus ATG; P=.80). The cumulative incidence of transplant-related mortality was 51% versus 41% (P=.70) and of relapse was 32% versus 40% (P=.90). For patients who survived 1 year, transplant-related mortality was 25% versus 3% (P=.03), and actuarial survival was 58% versus 85% (P=.09). In conclusion, the addition of ATG to cyclosporine/methotrexate provides significant protection against extensive chronic GVHD and chronic lung dysfunction, reduces late transplant mortality, and improves quality of life in patients undergoing unrelated donor transplantation. PMID:16635791

  18. Birth cohort effects on incidence of lung cancers: a population-based study in Nagasaki, Japan.

    PubMed

    Soda, H; Oka, M; Soda, M; Nakatomi, K; Kawabata, S; Suenaga, M; Kasai, T; Yamada, Y; Kamihira, S; Kohno, S

    2000-10-01

    Smoking prevalence remains high (around 60%) among Japanese males, but smoking initiation among males born in the 1930s decreased by approximately 10% due to economic difficulties following World War II. The present study was designed to examine whether this temporary decline in smoking initiation influenced the subsequent incidence of lung cancers, especially adenocarcinoma. Trends of lung cancer incidence by histological type in both sexes were investigated using data from the population-based cancer registry in Nagasaki, Japan, from 1986 through 1995. During this period, 5668 males and 2309 females were diagnosed as having lung cancer, and the overall incidence of lung cancers among both sexes remained stable. However, males aged 55 - 59 years showed a decrease in the age-specific incidence of adenocarcinoma and squamous-cell carcinoma (P < 0.05 and P < 0.01, respectively). In birth cohort analyses, the incidence of adenocarcinoma and squamous-cell carcinoma was lower in the 1935 - 1939 birth male cohort than in the successive cohorts. The incidence of lung cancers among females with low smoking prevalence did not change with birth cohort. The low smoking initiation among the 1935 - 1939 birth male cohort appeared to have resulted in a decreased incidence of adenocarcinoma and squamous cell carcinoma among middle-aged Japanese males. The present study suggests that smoking prevention has an effect in reducing the incidence of lung adenocarcinoma, as well as squamous-cell carcinoma, among smokers. PMID:11050464

  19. Advanced therapies for COPD-What's on the horizon? Progress in lung volume reduction and lung transplantation.

    PubMed

    Trotter, Michael A; Hopkins, Peter M

    2014-11-01

    Advanced chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity. Treatment options beyond conventional medical therapies are limited to a minority of patients. Lung volume reduction surgery (LVRS) although effective in selected subgroups of patients is not commonly undertaken. Morbidity associated with the procedure has contributed to this low utilisation. In response to this, less invasive bronchoscopic lung volume techniques are being developed to attempt to mitigate some of the risks and costs associated with surgery. Of these, endobronchial valve therapy is the most comprehensively studied although the presence of collateral ventilation in a significant proportion of patients has compromised its widespread utility. Bronchial thermal vapour ablation and lung volume reduction (LVR) coils are not dependent on collateral ventilation. These techniques have shown promise in early clinical trials; ongoing work will establish whether they have a role in the management of advanced COPD. Lung transplantation, although effective in selected patients for palliation of symptoms and improving survival, is limited by donor organ availability and economic constraint. Reconditioning marginal organs previously declined for transplantation with ex vivo lung perfusion (EVLP) is one potential strategy in improving the utilisation of donor organs. By increasing the donor pool, it is hoped lung transplantation might be more accessible for patients with advanced COPD into the future. PMID:25478204

  20. Advanced therapies for COPD—What’s on the horizon? Progress in lung volume reduction and lung transplantation

    PubMed Central

    Hopkins, Peter M.

    2014-01-01

    Advanced chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity. Treatment options beyond conventional medical therapies are limited to a minority of patients. Lung volume reduction surgery (LVRS) although effective in selected subgroups of patients is not commonly undertaken. Morbidity associated with the procedure has contributed to this low utilisation. In response to this, less invasive bronchoscopic lung volume techniques are being developed to attempt to mitigate some of the risks and costs associated with surgery. Of these, endobronchial valve therapy is the most comprehensively studied although the presence of collateral ventilation in a significant proportion of patients has compromised its widespread utility. Bronchial thermal vapour ablation and lung volume reduction (LVR) coils are not dependent on collateral ventilation. These techniques have shown promise in early clinical trials; ongoing work will establish whether they have a role in the management of advanced COPD. Lung transplantation, although effective in selected patients for palliation of symptoms and improving survival, is limited by donor organ availability and economic constraint. Reconditioning marginal organs previously declined for transplantation with ex vivo lung perfusion (EVLP) is one potential strategy in improving the utilisation of donor organs. By increasing the donor pool, it is hoped lung transplantation might be more accessible for patients with advanced COPD into the future. PMID:25478204

  1. Post-transplant lymphoproliferative disorders and Epstein-Barr virus DNAemia in a cohort of lung transplant recipients

    PubMed Central

    2011-01-01

    Background Post-transplant lymphoproliferative disorders (PTLD) are serious complications in lung transplant recipients. No consensus on EBV DNAemia levels predictive of PTLD has been reached. In addition, in many instances EBV DNAemia is determined in patients with suggestive symptoms only. Methods The characteristics of five patients with PTLD as well as the prevalence of EBV DNAmia in a cohort of 137 consecutive patients receiving lung transplantation are described. Results Twenty-six out of 137 patients (18.9%) were excluded from the analysis because lost at follow-up or dead from PTLD-independent reasons within three months of transplantation. EBV DNA in peripheral blood mononuclear cells (PBMC) was determined in 83/111 patients (74.8%) because of potential PTLD-related symptoms, while 28 patients (25.2%) showed no symptoms and were not examined. EBV DNAemia was positive in 53/83 patients (63.8%), and negative in 30/83 patients (36.2%). PTLD was diagnosed in five (4.5%) patients at a median time of 270 (range 120-870) days following transplantation. All five PTLD (three large B-cell lymphomas, one Hodgkin lymphoma and one possible pre-neoplastic lesion) were potentially associated with EBV infection. However, only 3/5 patients with PTLD had detectable EBV DNAemia: < 1,000 copies EBV DNA/1 × 105 PBMC in one patient and > 1,000 copies EBV DNA/1 × 105 PBMC in two patients. Conclusion A systematic multidisciplinary (clinical, radiologic, virologic and histologic) approach is mandatory for the diagnosis and management of PTLD in lung transplant recipients, while monitoring of symptomatic patients only may provide an incomplete or late picture of the clinical problem. In addition, staining for EBV antigens and quantification of EBV DNA in biopsy specimens should always be performed to understand the role of EBV infection in the pathogenesis of PTLD. PMID:21892950

  2. Incidence and outcome of transplant renal artery stenosis: single center experience.

    PubMed

    Polak, W G; Jezior, D; Garcarek, J; Chudoba, P; Patrzałek, D; Boratyńska, M; Szyber, P; Klinger, M

    2006-01-01

    Since the incidence of transplant renal artery stenosis (TRAS) in renal allografts varies from 1% to 23%, we sought to examine its incidence, to analyze treatment options, and to ascertain its outcomes. Retrospective analysis of 793 kidney allograft recipients transplanted between 1996 and 2004 revealed an incidence of 0.9% (n = 7). Time from kidney transplantation to the first symptoms varied from 1 week to 3 years (median, 4 months). Three patients experiences refractory hypertension and six patients developed allograft dysfunction. Screening color Doppler ultrasonography showed hemodynamic changes in six patients with the definitive diagnosis confirmed by angiography in all patients. One patient with an anastomotic stenosis was treated with a surgical operation and six patients, percutaneous transluminal angioplasty (PTA), with stenting in three cases. Both surgical as well as PTA treatment were successful in all but one patient, who underwent PTA alone, developed chronic renal insufficiency necessitating hemodialysis and finally lost his allograft. In the other patients all symptoms resolved after treatment and the patients are doing well with functioning allografts. Although TRAS was an uncommon complication, if recognized promptly it could be treated by surgery or PTA with a high success rate. PMID:16504683

  3. Factors related to health locus of control among lung transplant candidates.

    PubMed

    Burker, Eileen J; Phillips, Kristin M; Giza, Mallory

    2012-01-01

    As the number of individuals pursuing lung transplantation to treat lung disease increases, transplant team members have an opportunity to maximize patients' chances for post-transplant success through identifying and addressing psychosocial factors that have been previously associated with patients' post-transplant survival, such as health locus of control (HLC). The purpose of this cross-sectional study was to understand the factors associated with HLC in lung transplant candidates. The aims were to (i) identify the demographic factors associated with internal (IHLC), chance (CHLC), and powerful others (PHLC) HLC; (ii) examine the associations between HLC and anxiety, depression, and optimism; and (iii) determine whether these factors explain a significant proportion of variance in HLC. Hierarchical regression analyses indicated that age, education, trait anxiety, and optimism explained 20% of the variance in CHLC; gender, trait anxiety, and depression accounted for 9% of the variance in IHLC; and lower education accounted for 5% of the variance in PHLC. Helping transplant team members understand the factors that influence patients' perceptions that their own behaviors impact their health status is important for maximizing post-transplant success. PMID:22515175

  4. Lung transplant in end-staged chronic obstructive pulmonary disease (COPD) patients: a concise review

    PubMed Central

    Aziz, Fahad; Penupolu, Sudheer; Xu, Xin; He, Jianxing

    2010-01-01

    Lung transplantation is commonly used for patients with end-stage lung disease. However, there is continuing debate on the optimal operation for patients with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Single-lung transplantation (SLT) provides equivalent short- and medium-term results compared with bilateral lung transplantation (BLT), but long-term survival appears slightly better in BLT recipients (especially in patients with COPD). The number of available organs for lung transplantation also influences the choice of operation. Recent developments suggest that the organ donor shortage is not as severe as previously thought, making BLT a possible alternative for more patients. Among the different complications, re-implantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict. PMID:22263028

  5. Donor core-cooling provides improved static preservation for heart-lung transplantation.

    PubMed

    Fraser, C D; Tamura, F; Adachi, H; Kontos, G J; Brawn, J; Hutchins, G M; Borkon, A M; Reitz, B A; Baumgartner, W A

    1988-03-01

    Twenty-three dairy calves underwent heart-lung allotransplantation after donor organs were procured using either donor core-cooling through cardiopulmonary bypass (CPB) or pulmonary artery flush (PAF) to assess which method provides optimal graft preservation. In Groups 1 (control) and 2, donors were cooled to 15 degrees C on CPB and organs were either immediately transplanted (Group 1) or stored in saline solution (4 degrees C) for 4 hours (Group 2) prior to transplantation. In Group 3, donors were pretreated with prostaglandin E1 prior to PAF with modified Euro-Collins solution. Organs were stored in saline solution (4 degrees C) for 4 hours and were then transplanted. Acute cardiopulmonary function following transplantation was assessed by the ratio of end-systolic pressure to end-systolic dimension, extravascular lung water (EVLW), lung compliance, arterial oxygenation, and lung biopsy. Cardiac function after the transplantation procedure was similar in all groups, but EVLW values and lung biopsy scores were worse after PAF. Arterial O2 tension appeared lower after PAF, but not significantly so. Core-cooling provides superior static preservation and thus improved graft function in the acute bovine model. PMID:3126721

  6. Starting a lung transplant program: a roadmap for long-term excellence.

    PubMed

    Klesney-Tait, Julia; Eberlein, Michael; Geist, Lois; Keech, John; Zabner, Joseph; Gruber, Peter J; Iannettoni, Mark D; Parekh, Kalpaj

    2015-05-01

    Lung transplantation is an effective therapy for many patients with end-stage lung disease. Few centers across the United States offer this therapy, as a successful lung transplant program requires significant institutional resources and specialized personnel. Analysis of the United Network of Organ Sharing database reveals that the failure rate of new programs exceeds 40%. These data suggest that an accurate assessment of program viability as well as a strategy to continuously assess defined quality measures is needed. As part of strategic planning, regional availability of recipient and donors should be assessed. Additionally, analysis of institutional expertise at the physician, support staff, financial, and administrative levels is necessary. In May of 2007, we started a new lung transplant program at the University of Iowa Hospitals and Clinics and have performed 101 transplants with an average recipient 1-year survival of 91%, placing our program among the top in the country for the past 5 years. Herein, we review internal and external factors that impact the viability of a new lung transplant program. We discuss the use of four prospectively identified quality measures: volume, recipient outcomes, financial solvency, and academic contribution as one approach to achieve programmatic excellence. PMID:25940255

  7. Clinico-pathological Analysis of the Lungs from Patients with Lung Transplantation in a Single Institute in Korea.

    PubMed

    Kim, Hyojin; Jeon, Yoon Kyung; Lee, Hyun Joo; Kim, Young Tae; Chung, Doo Hyun

    2015-10-01

    Recently, the numbers of lung transplantation (LT) has been increased in Korea. However, post-LT outcome has not been successful in all patients, which may be partially affected by the primary lung disease. Therefore comprehensive understanding in original pathological diagnosis of patients with LT would be needed for achieving better clinical outcome. To address this issue, we performed clinico-pathological analysis of the explanted lungs from 29 patients who underwent LT over a 9-yr period in Seoul National University Hospital. Among them, 26 patients received single (1/26) or double (25/26) LT, while heart-lung transplantation was performed in 3 patients. The final clinico-pathological diagnoses were idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP) (n = 6), acute interstitial pneumonia (AIP)/diffuse alveolar damage (DAD) (n = 4), AIP/non-specific interstitial pneumonia with DAD (n = 1), collagen vascular disease-related interstitial lung disease (CVD-ILD)/DAD (n = 3), CVD-ILD/UIP (n = 1), lymphangioleiomyomatosis (n = 1), bronchiectasis (n = 4), pulmonary arterial hypertension (n = 2), tuberculosis (n = 1), bronchiolitis obliterans (BO) (n = 1), and lung cancer (n = 1). Moreover, 4 patients who had chemotherapy and hematopoietic stem cell transplantation due to hematologic malignancy showed unclassifiable interstitial pneumonia with extensive fibrosis in the lungs. Our study demonstrates that pathology of the explanted lungs from Korean patients with LT is different from that of other countries except for interstitial lung disease and bronchiectasis, which may be helpful for optimization of selecting LT candidates for Korean patients. PMID:26425040

  8. High Incidence of Herpes Zoster in Nonmyeloablative Hematopoietic Stem Cell Transplantation

    PubMed Central

    Su, Shih Hann; Martel-Laferrière, Valérie; Labbé, Annie-Claude; Snydman, David R.; Kent, David; Laverdière, Michel; Béliveau, Claire; Logvinenko, Tanya; Cohen, Sandra; Lachance, Silvy; Kiss, Thomas; Roy, Jean

    2016-01-01

    Background Nonmyeloablative (NMA) stem cell transplant (HSCT) regimens have expanded in the past decade, but little data exists to support antiviral prophylaxis to prevent zoster in recipients seropositive for varicella-zoster virus in this population. The objectives of this study were to describe the clinical features, incidence and risk factors for herpes zoster (HZ) in a homogeneous cohort of NMA allogeneic HSCT recipients. Methods Retrospective cohort study assessing all patients undergoing sibling NMA HSCT at Hôpital Maisonneuve-Rosemont (Montréal, Canada) between 7/2000-12/2008. All patients transplanted received the same conditioning regimen, immunoprophylaxis and graft-versus-host therapy. Herpes zoster diagnosis was defined clinically. Factors associated with HZ occurrence were identified using a Cox proportional hazards model. Results A total of 179 patients were followed for 33 months (median, IQR: 21-59). Zoster developed in 66 patients (37%) at a median of 8.3 months post-HSCT; the incidence rate was 175 cases/1,000 person-years. Estimated cumulative HZ incidence was 27, 36, and 44% at 1, 2, and 3 years respectively. Thoracic dermatomes were most frequently involved (30%); dissemination occurred in 5 patients. No death resulted from HZ, but 23% developed post-herpetic neuralgia. In multivariate analysis, CMV and HSV reactivations were associated with a reduced likelihood of HZ (hazard ratios=0.54 and 0.33, respectively). Conclusion The incidence of HZ in our cohort of NMA allogeneic transplant recipients is similar to the incidence reported following myeloablative regimens. Antiviral prophylaxis or treatment for CMV and HSV reactivations were protective against HZ. Given the observed high risk, we conclude that recommendations for antiviral prophylaxis should also apply, at least for the first year, to the NMA HSCT population. PMID:20977944

  9. Uncontrolled Donation After Circulatory Determination of Death Donors (uDCDDs) as a Source of Lungs for Transplant.

    PubMed

    Egan, T M; Requard, J J

    2015-08-01

    In April 2014, the American Journal of Transplantation published a report on the first lung transplant in the United States recovered from an uncontrolled donation after circulatory determination of death donor (uDCDD), assessed by ex vivo lung perfusion (EVLP). The article identified logistical and ethical issues related to introduction of lung transplant from uDCDDs. In an open clinical trial, we have Food and Drug Administration and Institutional Review Board approval to transplant lungs recovered from uDCDDs judged suitable after EVLP. Through this project and other experiences with lung recovery from uDCDDs, we have identified solutions to many logistical challenges and have addressed ethical issues surrounding lung transplant from uDCDDs that were mentioned in this case report. Here, we discuss those challenges, including issues related to recovery of other solid organs from uDCDDs. Despite logistical challenges, uDCDDs could solve the critical shortage of lungs for transplant. Furthermore, by avoiding the deleterious impact of brain death and days of positive pressure ventilation, and by using opportunities to treat lungs in the decedent or during EVLP, lungs recovered from uDCDDs may ultimately prove to be better than lungs currently being transplanted from conventional brain-dead organ donors. PMID:25873272

  10. Impact of cyclosporine versus tacrolimus on the incidence of de novo malignancy following liver transplantation: a single center experience with 609 patients.

    PubMed

    Wimmer, Cosmas D; Angele, Martin K; Schwarz, Bettina; Pratschke, Sebastian; Rentsch, Markus; Khandoga, Andrej; Guba, Markus; Jauch, Karl-Walter; Bruns, Christiane; Graeb, Christian

    2013-10-01

    De novo malignancies are a major cause of late death after liver transplantation. Aim of the present study was to determine whether use of cyclosporine versus tacrolimus affects long-term tumor incidence considering potential confounders. De novo malignancies in 609 liver transplant recipients at Munich Transplant Centre between 1985 and 2007 were registered. In 1996, the standard immunosuppressive regimen was changed from cyclosporine to tacrolimus. Different effects of those drugs on long-term tumor incidence were analyzed in multivariate analysis. During 3765 patient years of follow-up (median 4.78 years), 87 de novo malignancies occurred in 71 patients (mean age 47.5 ± 13.3 years, mean time after liver transplantation 5.7 ± 3.7 years). The cumulative incidence of de novo malignancies was 34.7% for all tumor entities after 15 years as compared to 8.9% for a nontransplanted population. The most frequent tumors observed were nonmelanoma skin cancers (44.83%). Moreover, post-transplant lymphoid disease, oropharyngeal cancer (n = 6, 6.9%), upper gastrointestinal tract cancer (n = 4, 4.6%), lung cancer (n = 4, 4.6%), gynecological malignancies (n = 4, 4.6%), and kidney cancer (n = 3, 3.45%) were detected. Multivariate analysis revealed recipient age [hazards ratio (HR) 1.06], male gender (HR 1.73), and tacrolimus-based immunosuppression (HR 2.06) as significant risk factors. Based on those results, a tacrolimus-based immunosuppression should be discussed especially in older male patients. Whether reducing tacrolimus target levels may reduce the risk for de novo malignancies has yet to be determined in prospective trials. PMID:23952102

  11. Heart transplant

    MedlinePlus

    ... 10 years. Alternative Names Cardiac transplant; Transplant - heart; Transplantation - heart Images Heart, section through the middle Heart, ... 28. Bernstein D. Pediatric heart and heart-lung transplantation. In: Kliegman RM, Behrman RE, Jenson HB, Stanton ...

  12. T cell immunohistochemistry refines lung transplant acute rejection diagnosis and grading

    PubMed Central

    2013-01-01

    Objective Lung transplant volume has been increasing. However, inaccurate and uncertain diagnosis for lung transplant rejection hurdles long-term outcome due to, in part, interobserver variability in rejection grading. Therefore, a more reliable method to facilitate diagnosing and grading rejection is warranted. Method Rat lung grafts were harvested on day 3, 7, 14 and 28 post transplant for histological and immunohistochemical assessment. No immunosuppressive treatment was administered. We explored the value of interstitial T lymphocytes quantification by immunohistochemistry and compared the role of T cell immunohistochemistry with H&E staining in diagnosing and grading lung transplant rejection. Results Typical acute rejection from grade A1 to A4 was found. Rejection severity was heterogeneously distributed in one-third transplanted lungs (14/40): lesions in apex and center were more augmented than in the base and periphery of the grafts, respectively. Immunohistochemistry showed profound difference in T lymphocyte infiltration among grade A1 to A4 rejections. The coincidence rate of H&E and immunohistochemistry was 77.5%. The amount of interstitial T lymphocyte infiltration increased gradually with the upgrading of rejection. The statistical analysis demonstrated that the difference in the amount of interstitial T lymphocytes between grade A2 and A3 was not obvious. However, T lymphocytes in lung tissue of grade A4 were significantly more abundant than in other grades. Conclusions Rejection severity was heterogeneously distributed within lung grafts. Immunohistochemistry improves the sensitivity and specificity of rejection diagnosis, and interstitial T lymphocyte quantitation has potential value in diagnosing and monitoring lung allograft rejection. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1536075282108217. PMID:24330571

  13. Lung transplantation with donation after circulatory determination of death donors and the impact of ex vivo lung perfusion.

    PubMed

    Machuca, T N; Mercier, O; Collaud, S; Tikkanen, J; Krueger, T; Yeung, J C; Chen, M; Azad, S; Singer, L; Yasufuku, K; de Perrot, M; Pierre, A; Waddell, T K; Keshavjee, S; Cypel, M

    2015-04-01

    The growing demand for suitable lungs for transplantation drives the quest for alternative strategies to expand the donor pool. The aim of this study is to evaluate the outcomes of lung transplantation (LTx) with donation after circulatory determination of death (DCDD) and the impact of selective ex vivo lung perfusion (EVLP). From 2007 to 2013, 673 LTx were performed, with 62 (9.2%) of them using DCDDs (seven bridged cases). Cases bridged with mechanical ventilation/extracorporeal life support were excluded. From 55 DCDDs, 28 (51%) underwent EVLP. Outcomes for LTx using DCDDs and donation after neurological determination of death (DNDD) donors were similar, with 1 and 5-year survivals of 85% and 54% versus 86% and 62%, respectively (p = 0.43). Although comparison of survival curves between DCDD + EVLP versus DCDD-no EVLP showed no significant difference, DCDD + EVLP cases presented shorter hospital stay (median 18 vs. 23 days, p = 0.047) and a trend toward shorter length of mechanical ventilation (2 vs. 3 days, p = 0.059). DCDDs represent a valuable source of lungs for transplantation, providing similar results to DNDDs. EVLP seems an important technique in the armamentarium to safely increase lung utilization from DCDDs; however, further studies are necessary to better define the role of EVLP in this context. PMID:25772069

  14. Role of Th17 cells and IL-17 in lung transplant rejection

    PubMed Central

    Wilkes, David S.

    2013-01-01

    In the past decade, advances in immunology have led to the recognition that T cell differentiation is not simply Th1 or Th2 but involves differentiation to other subsets, such as T regulatory cells, T follicular helper cells, and Th17 cells. Th17 cells, characterized by production of IL-17, IL-22, and IL-21, have been implicated in the pathogenesis of autoimmune diseases, like rheumatoid arthritis and multiple sclerosis, but also play an important role in host defense and mucosal immunity. IL-17, with its pleiotropic effects on stromal cells, as well as hematopoietic cells, has long been recognized as a possible mediator of rejection after lung transplantation. Recent data have implicated IL-17 and Th17 cells in the development of autoimmunity and chronic rejection after lung transplantation in both animal models and humans. In this review, we will discuss the current data on Th17 and the prospects for the future for lung transplantation. PMID:21279808

  15. Resident Rounds Part III: Case Report: Fatal Cryptococcal Panniculitis in a Lung Transplant Recipient.

    PubMed

    Reddy, Bobby Y; Shaigany, Sheila; Schulman, Lawrence; Grossman, Marc E

    2015-05-01

    Cryptococcal panniculitis is a rare entity previously reported in only 13 solid organ transplant (SOT) recipients. Cutaneous cryptococcosis in SOT recipients warrants extensive systemic workup and treatment as if central nervous system (CNS) disease is present. It should be included in the differential diagnosis of panniculitis in the immunocompromised host, as early diagnosis and treatment are critical. We report a fatal case of cryptococcal panniculitis in a 44-year-old lung transplant recipient. PMID:25942673

  16. Anastomotic Airway Complications After Lung Transplant: Clinical, Bronchoscopic and CT Correlation.

    PubMed

    Luecke, Kyle; Trujillo, Camilo; Ford, Jonathan; Decker, Summer; Pelaez, Andres; Hazelton, Todd R; Rojas, Carlos A

    2016-09-01

    The purpose of this article is to review the normal appearance and common complications of the airway anastomosis in lung transplant patients with emphasis on computed tomography images with bronchoscopic correlation. The spectrum of complications will be presented as early (<1 mo after transplant) or late (>1 mo). Variations in surgical technique as well as presentation and management options for airway complications will also be discussed. PMID:27428022

  17. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation

    PubMed Central

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-01-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca’ Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2/FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2/FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40–84] vs. 39 [36–46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). PMID:24628890

  18. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation.

    PubMed

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-06-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2 /FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40-84] vs. 39 [36-46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). PMID:24628890

  19. Clinical Outcomes of Heart-Lung Transplantation: Review of 10 Single-Center Consecutive Patients

    PubMed Central

    Yun, Jae Kwang; Choi, Se Hoon; Park, Seung-Il

    2016-01-01

    Background Heart-lung transplantation (HLT) has provided hope to patients with end-stage lung disease and irreversible heart dysfunction. We reviewed the clinical outcomes of 10 patients who underwent heart-lung transplantation at Asan Medical Center. Methods Between July 2010 and August 2014, a total of 11 patients underwent HLT at Asan Medical Center. After excluding one patient who underwent concomitant liver transplantation, 10 patients were enrolled in our study. We reviewed the demographics of the donors and the recipients’ baseline information, survival rate, cause of death, and postoperative complications. All patients underwent follow-up, with a mean duration of 26.1±16.7 months. Results Early death occurred in two patients (20%) due to septic shock. Late death occurred in three patients (38%) due to bronchiolitis obliterans (n=2) and septic shock (n=1), although these patients survived for 22, 28, and 42 months, respectively. The actuarial survival rates at one year, two years, and three years after HLT were 80%, 67%, and 53%, respectively. Conclusion HLT is a procedure that is rarely performed in Korea, even in medical centers with large heart and lung transplant programs. In order to achieve acceptable clinical outcomes, it is critical to carefully choose the donor and the recipient and to be certain that all aspects of the transplant procedure are planned in advance with the greatest care. PMID:27298792

  20. Hepatic Veno-Occlusive Disease following Stem Cell Transplantation: Incidence, Clinical Course, and Outcome

    PubMed Central

    Coppell, Jason A.; Richardson, Paul G.; Soiffer, Robert; Martin, Paul L.; Kernan, Nancy A.; Chen, Allen; Guinan, Eva; Vogelsang, Georgia; Krishnan, Amrita; Giralt, Sergio; Revta, Carolyn; Carreau, Nicole A.; Iacobelli, Massimo; Carreras, Enric; Ruutu, Tapani; Barbui, Tiziano; Antin, Joseph H.; Niederwieser, Dietger

    2011-01-01

    The occurrence of hepatic veno-occlusive disease (VOD) has been reported in up to 60% of patients following stem cell transplantation (SCT), with incidence varying widely between studies depending on the type of transplant, conditioning regimen, and criteria used to make the diagnosis. Severe VOD is characterized by high mortality and progression to multiorgan failure (MOF); however, there is no consensus on how to evaluate severity. This review and analysis of published reports attempts to clarify these issues by calculating the overall mean incidence of VOD and mortality from severe VOD, examining the effect of changes in SCT practice on the incidence of VOD over time, and discussing the methods used to evaluate severity. Across 135 studies performed between 1979 and October 2007, the overall mean incidence of VOD was 13.7% (95% confidence interval [CI] = 13.3%–14.1%). The mean incidence of VOD was significantly lower between 1979–1994 than between 1994–2007 (11.5% [95% CI, 10.9%–12.1%] vs 14.6% [95% CI, 14.0%–15.2%]; P < .05). The mortality rate from severe VOD was 84.3% (95% CI, 79.6%–88.9%); most of these patients had MOF, which also was the most frequent cause of death. Thus, VOD is less common than early reports suggested, but the current incidence appears to be relatively stable despite recent advances in SCT, including the advent of reduced-intensity conditioning. The evolution of MOF in the setting of VOD after SCT can be considered a reliable indication of severity and a predictor of poor outcome. PMID:19766729

  1. A simple technique can reduce cardiopulmonary bypass use during lung transplantation

    PubMed Central

    Samano, Marcos N; Iuamoto, Leandro R; Fonseca, Hugo V S; Fernandes, Lucas M; Abdalla, Luis G; Jatene, Fabio B; Pêgo-Fernandes, Paulo M

    2016-01-01

    Cardiopulmonary bypass causes an inflammatory response and consumption of coagulation factors, increasing the risk of bleeding and neurological and renal complications. Its use during lung transplantation may be due to pulmonary hypertension or associated cardiac defects or just for better exposure of the pulmonary hilum. We describe a simple technique, or open pericardium retraction, to improve hilar exposure by lifting the heart by upward retraction of the pericardial sac. This technique permits lung transplantation without cardiopulmonary bypass when bypass use is recommended only for better exposure. PMID:27166775

  2. Relationship between trough plasma and epithelial lining fluid concentrations of voriconazole in lung transplant recipients.

    PubMed

    Heng, Siow-Chin; Snell, Gregory I; Levvey, Bronwyn; Keating, Dominic; Westall, Glen P; Williams, Trevor J; Whitford, Helen; Nation, Roger L; Slavin, Monica A; Morrissey, Orla; Kong, David C M

    2013-09-01

    Trough (predose) voriconazole concentrations in plasma and pulmonary epithelial lining fluid (ELF) of lung transplant recipients receiving oral voriconazole preemptive treatment were determined. The mean (± standard deviation [SD]) ELF/plasma ratio was 12.5 ± 6.3. A strong positive linear relationship was noted between trough plasma and ELF voriconazole concentrations (r(2) = 0.87), suggesting the feasibility of using trough plasma voriconazole concentration as a surrogate to estimate the corresponding concentration in ELF of lung transplant recipients. PMID:23817382

  3. A simple technique can reduce cardiopulmonary bypass use during lung transplantation.

    PubMed

    Samano, Marcos N; Iuamoto, Leandro R; Fonseca, Hugo V S; Fernandes, Lucas M; Abdalla, Luis G; Jatene, Fabio B; Pêgo-Fernandes, Paulo M

    2016-04-01

    Cardiopulmonary bypass causes an inflammatory response and consumption of coagulation factors, increasing the risk of bleeding and neurological and renal complications. Its use during lung transplantation may be due to pulmonary hypertension or associated cardiac defects or just for better exposure of the pulmonary hilum. We describe a simple technique, or open pericardium retraction, to improve hilar exposure by lifting the heart by upward retraction of the pericardial sac. This technique permits lung transplantation without cardiopulmonary bypass when bypass use is recommended only for better exposure. PMID:27166775

  4. Influence on ICU course, outcome and costs for lung transplantation after implementation of the new Swiss transplantation law

    PubMed Central

    2014-01-01

    Background The Swiss organ allocation system for donor lungs was implemented on 1 July 2007. The effects of this implementation on patient selection, intensive care unit course, outcomes and intensive care costs are unknown. Methods The first 37 consecutive lung transplant recipients following the implementation of the new act were compared with the previous 42 lung transplant recipients. Results Following implementation of the new law, baseline characteristics and cumulative one-year patient survival were comparable in both groups (88.1% vs 83.8%, P = 0.58). The costs for each case increased by 35,000 euros after adoption of the new law. Stratifying patients after implementation of the law according to urgency status shows that urgent patients required longer mechanical ventilation (P = 0.04), a longer ICU stay (P = 0.045) and a longer hospital stay (P = 0.04) and ICU costs (median 64,050 euros) were higher compared to regular patients. Conclusion The new transplantation law has increased ICU costs with the implementation of the Swiss organ allocation system. Patients listed as ‘urgent’ contribute significantly to the increase in ICU costs. PMID:24690254

  5. The incidence and mortality of lung cancer and their relationship to development in Asia

    PubMed Central

    Pakzad, Reza; Mohammadian-Hafshejani, Abdollah; Ghoncheh, Mahshid; Pakzad, Iraj

    2015-01-01

    Background Lung cancer is the deadliest cancer worldwide and the most common cancer in Asia. It is necessary to get information on epidemiology and inequalities related to incidence and mortality of the cancer to use for planning and further research. This study aimed to investigate epidemiology and inequality of incidence and mortality from lung cancer in Asia. Methods The study was conducted based on data from the world data of cancer and the World Bank [including the Human Development Index (HDI) and its components]. The incidence and mortality rates, and cancer distribution maps were drawn for Asian countries. To analyze data, correlation test between incidence and death rates, and HDI and its components at significant was used in the significant level of 0.05 using SPSS software. Results A total of 1,033,881 incidence (71.13% were males and 28.87% were females. Sex ratio was 2.46) and 936,051 death (71.45% in men and 28.55% in women. The sex ratio was 2.50) recorded in Asian countries in 2012. Five countries with the highest standardized incidence and mortality rates of lung cancer were Democratic Republic of Korea, China, Armenia, Turkey, and Timor-Leste, respectively. Correlation between HDI and standardized incidence rate was 0.345 (P=0.019), in men 0.301 (P=0.042) and in women 0.3 (P=0.043); also between HDI and standardized mortality rate 0.289 (P=0.052), in men 0.265 (P=0.075) and in women 0.200 (P=0.182). Conclusions The incidence of lung cancer has been increasing in Asia. It is high in men. Along with development, the incidence and mortality from lung cancer increases. It seems necessary to study reasons and factors of increasing the incidence and mortality of lung cancer in Asian countries. PMID:26798586

  6. Multifocal periostitis as a complication of chronic use of voriconazole in a lung transplant recipient.

    PubMed

    Tedja, R; El-Sherief, A; Olbrych, T; Gordon, S

    2013-08-01

    Fungal infections are common in solid organ transplantation. An increasing number of transplant recipients receive antifungal therapy for prolonged duration owing to invasive fungal infections. Herein, we describe a diagnosis of periostitis as a complication of chronic use of voriconazole in a lung transplant recipient. The patient was diagnosed with probable pulmonary aspergillosis and was treated with oral voriconazole for a total of 9 months. Evidence of multifocal periostitis was observed in the axial and appendicular skeleton. Early recognition of this phenomenon is important to prevent unnecessary tests and procedures. Prompt discontinuation of voriconazole should result in improvement of symptoms. PMID:23663268

  7. Use of CT densitometry to predict lung toxicity in bone marrow transplant patients

    SciTech Connect

    el-Khatib, E.E.; Freeman, C.R.; Rybka, W.B.; Lehnert, S.; Podgorsak, E.B.

    1989-01-01

    Total body irradiation (TBI) is considered an integral part of the preparation of patients with hematological malignancies for marrow transplantation. One of the major causes of death following bone marrow transplantation is interstitial pneumonia. Its pathogenesis is complex but radiation may play a major role in its development. Computed tomography (CT) has been used in animal and human studies as a sensitive non-invasive method for detecting changes in the lung following radiotherapy. In the present study CT scans are studied before and up to 1 year after TBI. Average lung densities measured before TBI showed large variations among the individual patients. On follow-up scans, lung density decreases were measured for patients who did not develop lung complications. Significant lung density increases were measured in patients who subsequently had lung complications. These lung density increases were observed prior to the onset of respiratory complications and could be correlated with the clinical course of the patients, suggesting the possibility for the usage of CT lung densitometry to predict lung complications before the onset of clinical symptoms.

  8. Obliterative airway remodeling: molecular evidence for shared pathways in transplanted and native lungs.

    PubMed

    Jonigk, Danny; Merk, Marlene; Hussein, Kais; Maegel, Lavinia; Theophile, Katharina; Muth, Michaela; Lehmann, Ulrich; Bockmeyer, Clemens L; Mengel, Michael; Gottlieb, Jens; Welte, Tobias; Haverich, Axel; Golpon, Heiko; Kreipe, Hans; Laenger, Florian

    2011-02-01

    Obliteration of the small airways is a largely unresolved challenge in pulmonary medicine. It represents either the irreversible cause of functional impairment or a morphologic disorder of limited importance in a multitude of diseases. Bronchiolitis obliterans is a key complication of lung transplantation. No predictive markers for the onset of obliterative remodeling are currently available. To further elucidate the molecular mechanisms of airway remodeling, compartment-specific expression patterns were analyzed in patients. For this purpose, remodeled and nonremodeled bronchioli were isolated from transplanted and nontransplanted lung explants using laser-assisted microdissection (n = 24). mRNA expression of 45 fibrosis-associated genes was measured using quantitative real-time RT-PCR. For 20 genes, protein expression was also analyzed by immunohistochemistry. Infiltrating cells were characterized at conventional histology and immunohistochemistry. Obliterative remodeling of the small airways in transplanted and nontransplanted lungs shared similar grades of chronic inflammation and pivotal fibrotic pathways such as transforming growth factor β signaling and increased collagen expression. Bone morphogenetic protein and thrombospondin signaling, and also matrix metalloproteinases and tissue inhibitor of metalloproteinases, were primarily up-regulated in obliterative airway remodeling in nontransplanted lungs. In transplanted lungs, clinical remodeled bone morphogenetic protein but nonremodeled bronchioli were characterized by a concordant up-regulation of matrix metalloproteinase-9, RANTES, and tissue inhibitor of metalloproteinase-1. These distinct expression patterns warrant further investigation as potential markers of impending airway remodeling, especially for prospective longitudinal molecular profiling. PMID:21281792

  9. Basal segmental auto-transplantation after pneumonectomy for advanced central lung cancer.

    PubMed

    Oto, Takahiro; Kiura, Katsuyuki; Toyooka, Shinichi; Miyoshi, Shinichiro

    2012-09-01

    In patients with central lung cancer that extensively involves the bronchus/pulmonary artery, a double-sleeve lobectomy is often difficult to perform. We describe a case of post-pneumonectomy basal segmental auto-transplantation using a lung preservation technique that uses cold low-potassium dextran glucose solution to protect the lung graft from ischaemia-reperfusion injury during the ex situ division of the segmental graft and the pathological investigations for the clearance of the surgical margins. A right basal segmental auto-transplantation procedure was performed in a patient with stage-IIIA squamous cell lung cancer. This technique could allow extensive pulmonary resection while minimizing the loss of pulmonary reserve. PMID:22544868

  10. Trends in lung cancer incidence and mortality in Croatia, 1988 to 2008

    PubMed Central

    Janković, Mateja; Samaržija, Miroslav; Jakopović, Marko; Kuliš, Tomislav; Znaor, Ariana

    2012-01-01

    Aim To describe and interpret lung cancer incidence and mortality trends in Croatia between 1988 and 2008. Methods Incidence data on lung cancer for the period 1988-2008 were obtained from the Croatian National Cancer Registry, while mortality data were obtained from the World Health Organization mortality database. Population estimates for Croatia were obtained from the Population Division of the Department of Economic and Social Affairs of the United Nations. We also calculated and analyzed age-standardized incidence and mortality rates. To describe time incidence and mortality trends, we used joinpoint regression analysis. Results Lung cancer incidence and mortality rates in men decreased significantly in all age groups younger than 70 years. Age-standardized incidence rates in men decreased significantly by -1.3% annually. Joinpoint analysis of mortality in men identified three trends, and average annual percent change (AAPC) decreased significantly by -1.1%. Lung cancer incidence and mortality rates in women increased significantly in all age groups older than 40 years and decreased in younger women (30-39- years). Age-standardized incidence rates increased significantly by 1.7% annually. Joinpoint analysis of age-standardized mortality rates in women identified two trends, and AAPC increased significantly by 1.9%. Conclusion Despite the overall decreasing trend, Croatia is still among the European countries with the highest male lung cancer incidence and mortality. Although the incidence trend in women is increasing, their age standardized incidence rates are still 5-fold lower than in men. These trends follow the observed decrease and increase in the prevalence of male and female smokers, respectively. These findings indicate the need for further introduction of smoking prevention and cessation policies targeting younger population, particularly women. PMID:22522986

  11. Three-dimensional x-ray imaging of the anatomy and function of the lungs and pulmonary arteries in dogs following single lung transplant

    NASA Astrophysics Data System (ADS)

    Wu, Qing-Hua; McGregor, Christopher G. A.; Wu, Xue-Si; Rinaldi, Mauro; Nilsson, Folke N.; Tazelaar, Henry D.; Ritman, Erik L.

    1996-04-01

    It was the goal of this study to see if relatively noninvasive CT studies could provide a quantitative index of acute lung rejection in single lung transplantation. Using volume scanning fast CT, the change in cross-sectional area of the major pulmonary arteries from systole to diastole, regional lung perfusion and ventilation was measured in 12 dogs with left lung allotransplantation before and during rejection and four dogs with left lung autotransplantation. All dogs were anesthetized and scanned in a fast computed tomography scanner (dynamic spatial reconstructor--DSR) during several ventilatory cycles and again during injection of contrast medium into the right atrium. There was significant reduction of regional air content, ventilation, perfusion and pulmonary artery compliance during rejection of the transplanted lung. The severity of these changes related linearly with the histological indices of rejection. It is concluded that minimally invasive dynamic CT imaging of transplanted lung can be used to detect acute rejection and its severity.

  12. Early Lung Computed Tomography Scan after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Cornetto, Marie Alice; Chevret, Sylvie; Abbes, Sarah; de Margerie-Mellon, Constance; Hussenet, Claire; Sicre de Fontbrune, Flore; Tazi, Abdellatif; Ribaud, Patricia; Bergeron, Anne

    2016-08-01

    A lung computed tomography (CT) scan is essential for diagnosing lung diseases in hematopoietic stem cell transplantation (HSCT) recipients. As a result, lung CT scans are increasingly prescribed in the early phase after allogeneic HSCT, with no assessment of the added value for global patient management. Among 250 patients who underwent allogeneic HSCT in our center over a 2-year period, we evaluated 68 patients who had at least 1 lung CT scan within the first 30 days post-transplantation. The median interval between allogeneic HSCT and lung CT scan was 8.5 days. Patients who underwent an early lung CT scan were more immunocompromised and had a more severe course. Fever was the main indication for the CT scan (78%). The lung CT scan was abnormal in 52 patients, including 17 patients who had an abnormal pre-HSCT CT scan. A therapeutic change was noted in 37 patients (54%) within 24 hours after the lung CT scan. The main changes included the introduction of corticosteroids (n = 23; 62%), especially in patients with a normal CT scan (89%). In univariate models, we found that a normal pretransplantation CT scan (P = .002), the absence of either dyspnea (P = .029) or hypoxemia (P = .015), and a serum C-reactive protein level <10 mg/L (P = .004) were associated with a normal post-HSCT lung CT scan. We found that the association of these variables could predict the normality of early post-HSCT lung CT scans. Pretransplantation lung CT scans are useful for the interpretation of subsequent lung CT scans following allogeneic HSCT, which are frequently abnormal. Early post-HSCT lung CT scans are helpful in patient management, but prescriptions could be more targeted. PMID:27189110

  13. Single-lung transplantation in emphysema: Retrospective study analyzing survival and waiting list mortality

    PubMed Central

    Borro, José M; Delgado, María; Coll, Elisabeth; Pita, Salvador

    2016-01-01

    AIM: To performed remains a subject of debate and is the principal aim of the study. METHODS: This retrospective analysis included 73 patients with emphysema (2000-2012). The outcomes of patients undergoing single-lung transplantation (SL) (n = 40) or double-lung transplant (DL) (n = 33) were compared in a Cox multivariate analysis to study the impact of the technique, postoperative complications and acute and chronic rejection on survival rates. Patients were selected for inclusion in the waiting list according to the International Society of Heart Lung Transplantation criteria. Pre and postoperative rehabilitation and prophylaxis, surgical technique and immunosuppressive treatment were similar in every patients. Lung transplantation waiting list information on a national level and retrospective data on emphysema patient survival transplanted in Spain during the study period, was obtained from the lung transplantation registry managed by the National Transplant Organization (ONT). RESULTS: Both groups were comparable in terms of gender and clinical characteristics. We found significant differences in the mean age between the groups, the DL patients being younger as expected from the inclusion criteria. Perioperative complications occurred in 27.6% SL vs 54% DL (P = 0.032). Excluding perioperative mortality, median survival was 65.3 mo for SL and 59.4 mo for DL (P = 0.96). Bronchiolitis obliterans and overall 5-year survival were similar in both groups. Bacterial respiratory infection, cytomegalovirus and fungal infection rates were higher but not significant in SL. No differences were found between type of transplant and survival (P = 0.48). To support our results, national data on all patients with emphysema in waiting list were obtained (n = 1001). Mortality on the waiting list was 2.4% for SL vs 6.2% for DL. There was no difference in 5 year survival between 235 SL and 430 DL patients transplanted (P = 0.875). CONCLUSION: Our results suggest that SL

  14. Deguelin Attenuates Reperfusion Injury and Improves Outcome after Orthotopic Lung Transplantation in the Rat

    PubMed Central

    Paulus, Patrick; Ockelmann, Pia; Tacke, Sabine; Karnowski, Nora; Ellinghaus, Peter; Scheller, Bertram; Holfeld, Johannes; Urbschat, Anja; Zacharowski, Kai

    2012-01-01

    The main goal of adequate organ preservation is to avoid further cellular metabolism during the phase of ischemia. However, modern preservation solutions do rarely achieve this target. In donor organs hypoxia and ischemia induce a broad spectrum of pathologic molecular mechanisms favoring primary graft dysfunction (PGD) after transplantation. Increased hypoxia-induced transcriptional activity leads to increased vascular permeability which in turn is the soil of a reperfusion edema and the enhancement of a pro-inflammatory response in the graft after reperfusion. We hypothesize that inhibition of the respiration chain in mitochondria and thus inhibition of the hypoxia induced mechanisms might reduce reperfusion edema and consecutively improve survival in vivo. In this study we demonstrate that the rotenoid Deguelin reduces the expression of hypoxia induced target genes, and especially VEGF-A, dose-dependently in hypoxic human lung derived cells. Furthermore, Deguelin significantly suppresses the mRNA expression of the HIF target genes VEGF-A, the pro-inflammatory CXCR4 and ICAM-1 in ischemic lungs vs. control lungs. After lung transplantation, the VEGF-A induced reperfusion-edema is significantly lower in Deguelin-treated animals than in controls. Deguelin-treated rats exhibit a significantly increased survival-rate after transplantation. Additionally, a downregulation of the pro-inflammatory molecules ICAM-1 and CXCR4 and an increase in the recruitment of immunomodulatory monocytes (CD163+ and CD68+) to the transplanted organ involving the IL4 pathway was observed. Therefore, we conclude that ischemic periods preceding reperfusion are mainly responsible for the increased vascular permeability via upregulation of VEGF. Together with this, the resulting endothelial dysfunction also enhances inflammation and consequently lung dysfunction. Deguelin significantly decreases a VEGF-A induced reperfusion edema, induces the recruitment of immunomodulatory monocytes and thus

  15. EBNA1 expression in a lung transplant recipient with hypocomplementemic urticarial vasculitis syndrome.

    PubMed

    Berggren, Malin A M; Heinlen, Latisha; Isaksson, Asa; Nyström, Ulla; Ricksten, Anne

    2007-07-01

    This article describes a transplant recipient with underlying hypocomplementemic urticarial vasculitis syndrome who expressed persistently Epstein-Barr virus nuclear antigen 1 (EBNA1) in peripheral blood. The patient received a bilateral lung transplant and was subsequently followed with monitoring of EBV expression in peripheral blood. Evaluation of viral expression in peripheral blood, serum, and graft tissue was performed with RT-PCR, Q-PCR, indirect immunofluorescence, anti-peptide assays, and in situ hybridization; samples were collected at various time-points up to 91 days post-transplantation. The patient expressed EBNA1 in 8/10 (80%) of the peripheral blood samples tested during the post-transplantation period, and interestingly, even including the day of transplantation. After analyses of indicative EBV mRNA, EBNA1 expression was found mainly to be Qp-initiated EBNA1, known to be important for EBV maintenance. Anti-EBNA1 epitope mapping showed significantly higher and broader antibody responses to EBNA1 epitopes pre-transplantation when compared to normal controls and a matched lung transplant control. Post-transplantation this response was largely diminished but there were still epitopes significantly higher than controls. Our results show the presence of EBV-positive proliferating cells before onset of intensive immunosuppressive treatment. Although no previous connection between EBV and hypocomplementemic urticarial vasculitis syndrome has been reported, it is tempting to speculate that the continuous EBNA1 expression is not caused by immunosuppression or post-transplant lymphoproliferative disease, but may be a factor involved in the etiology of the autoimmune disease. PMID:17516536

  16. Induction Therapy for Lung Transplantation in COPD: Analysis of the UNOS Registry.

    PubMed

    Duffy, Joseph S; Tumin, Dmitry; Pope-Harman, Amy; Whitson, Bryan A; Higgins, Robert S D; Hayes, Don

    2016-10-01

    Although studies demonstrate that induction therapy improves outcomes after lung transplantation, its influence on survival in patients with chronic obstructive pulmonary disease (COPD) is not clear. The United Network for Organ Sharing database was queried to obtain data regarding adult patients with COPD receiving lung transplant between May 2005 and June 2014. Therapies evaluated include anti-thymocyte globulin, anti-lymphocyte globulin, thymoglobulin, basiliximab, and alemtuzumab. Data were categorized based on receiving induction (INDUCED) and no induction (NONE). Kaplan-Meier plots, Cox proportional hazards models of patient survival, and competing-risks regression models for secondary endpoints were utilized. A total of 3,405 patients who underwent lung transplantation for COPD were enrolled with 1,761 (52%) receiving induction therapy. Of INDUCED, 1,146 (65%) received basiliximab, 380 (22%) received alemtuzumab, and 235 (13%) received a polyclonal preparation. The hazard ratio for INDUCED vs. NONE was 0.793 (95% CI = 0.693, 0.909; p = 0.001) in the fully adjusted Cox model. A multivariable competing-risks model also found a protective influence of induction therapy with respect to delayed onset of bronchiolitis obliterans syndrome after transplantation (SHR = 0.801; 95% CI = 0.694, 0.925; p = 0.003). In a cohort of recently transplanted patients with COPD, there appears to be a benefit from contemporary induction agents with no concurrent increase in the risk of death due to infection. PMID:26829054

  17. The immediate post-operative period following lung transplantation: mapping of nursing interventions

    PubMed Central

    Duarte, Rayssa Thompson; Linch, Graciele Fernanda da Costa; Caregnato, Rita Catalina Aquino

    2014-01-01

    OBJECTIVES: to investigate the principle nursing interventions/actions, prescribed in the immediate post-operative period for patients who receive lung transplantation, recorded in the medical records, and to map these using the Nursing Interventions Classification (NIC) taxonomy. METHOD: retrospective documental research using 183 medical records of patients who received lung transplantation (2007/2012). The data of the patients' profile were grouped in accordance with the variables investigated, and submitted to descriptive analysis. The nursing interventions prescribed were analyzed using the method of cross-mapping with the related interventions in the NIC. Medical records which did not contain nursing prescriptions were excluded. RESULTS: the majority of the patients were male, with medical diagnoses of pulmonary fibrosis, and underwent lung transplantation from a deceased donor. A total of 26 most frequently-cited interventions/actions were found. The majority (91.6%) were in the complex and basic physiological domains of the NIC. It was not possible to map two actions prescribed by the nurses. CONCLUSIONS: it was identified that the main prescriptions contained general care for the postoperative period of major surgery, rather than prescriptions individualized to the patient in the postoperative period following lung transplantation. Care measures related to pain were underestimated in the prescriptions. The mapping with the taxonomy can contribute to the elaboration of the care plan and to the use of computerized systems in this complex mode of therapy. PMID:25493673

  18. Epstein-Barr virus associated graft failure following heart/lung transplantation.

    PubMed Central

    Egan, J J; Stewart, J P; Hasleton, P S; Yonan, N; Bishop, P; Arrand, J R; Rahman, A N; Carroll, K B; Woodcock, A A

    1996-01-01

    A case is described of late pulmonary graft failure in a heart/lung transplant recipient. The major characteristics were alveolar fibrosis and a restrictive physiological deficit. Epstein-Barr virus was implicated as an aetiological agent using immunohistochemical analysis and by a response to treatment with ganciclovir. Images PMID:8958903

  19. Invasive Fungal Sinusitis Caused by Scytalidium dimidiatum in a Lung Transplant Recipient

    PubMed Central

    Dunn, James J.; Wolfe, Michael J.; Trachtenberg, Joel; Kriesel, John D.; Orlandi, Richard R.; Carroll, Karen C.

    2003-01-01

    We describe a case of invasive fungal sinusitis caused by Scytalidium dimidiatum in a lung transplant recipient. Treatment was complicated by renal failure with amphotericin B therapies. Following 6 months of voriconazole treatment, the patient remained radiographically and clinically stable for a short time before dying of respiratory failure precipitated by graft rejection. PMID:14662991

  20. The Nitric Oxide/Cyclic GMP Pathway in Organ Transplantation: Critical Role in Successful Lung Preservation

    NASA Astrophysics Data System (ADS)

    Pinsky, David J.; Naka, Yoshifumi; Chowdhury, Nepal C.; Liao, Hui; Oz, Mehmet C.; Michler, Robert E.; Kubaszewski, Eugeniusz; Malinski, Tadeusz; Stern, David M.

    1994-12-01

    Reestablishment of vascular homeostasis following ex vivo preservation is a critical determinant of successful organ transplantation. Because the nitric oxide (NO) pathway modulates pulmonary vascular tone and leukocyte/endothelial interactions, we hypothesized that reactive oxygen intermediates would lead to decreased NO (and hence cGMP) levels following pulmonary reperfusion, leading to increased pulmonary vascular resistance and leukostasis. Using an orthotopic rat model of lung transplantation, a porphyrinic microsensor was used to make direct in vivo measurements of pulmonary NO. NO levels measured at the surface of the transplanted lung plummeted immediately upon reperfusion, with levels moderately increased by topical application of superoxide dismutase. Because cGMP levels declined in preserved lungs after reperfusion, this led us to buttress the NO pathway by adding a membrane-permeant cGMP analog to the preservation solution. Compared with grafts stored in its absence, grafts stored with supplemental 8-Br-cGMP and evaluated 30 min after reperfusion demonstrated lower pulmonary vascular resistances with increased graft blood flow, improved arterial oxygenation, decreased neutrophil infiltration, and improved recipient survival. These beneficial effects were dose dependent, mimicked by the type V phosphodiesterase inhibitor 2-o-propoxyphenyl-8-azapurin-6-one, and inhibited by a cGMP-dependent protein kinase antagonist, the R isomer of 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate. Augmenting the NO pathway at the level of cGMP improves graft function and recipient survival following lung transplantation.

  1. Extended cardiopulmonary preservation for heart-lung transplantation: a comparative study of superoxide dismutase.

    PubMed

    Bando, K; Tago, M; Teraoka, H; Seno, S; Senoo, Y; Teramoto, S

    1989-01-01

    We examined an 8-hour cardiopulmonary preservation technique and the role of free radical-induced injury during cardiopulmonary preservation and transplantation. Hence, donor dogs were placed on cardiopulmonary bypass, rapidly cooled to 15 degrees C, and heterotopic heart-unilateral left lung transplantations were performed. In group 1 (n = 5), hearts and lungs were transplanted immediately after core-cooling and cardioplegic arrest. In groups 2 to 5 (n = 5 in each group), heart-lung blocks were excised and stored at 4 degrees C for 8 hours before transplantation. During preservation hearts were perfused (20 mm Hg) with oxygenated extracellular solution (pH 7.4, 410 m0sm/L) and the lungs immersed in the same solution. In groups 3 through 5 recombinant human superoxide distumase (r,h-SOD, total 40 mg/kg) was administered during either donor cooling, donor preservation, or just before and during reperfusion, respectively. Load independent analysis of myocardial function was assessed by determining the ratio of the end-systolic pressure to end-systolic dimension. Pulmonary preservation was evaluated by determination of extravascular lung water of the implanted left lung, arterial oxygenation on 40% inspired oxygen, and pulmonary vascular resistance. Although arterial oxygenation was similar in each group, pulmonary vascular resistance was increased in groups 2 through 4 after implantation. Furthermore, in groups 2 and 4 impaired myocardial function and increased extravascular lung water were observed. Administration of r,h-SOD, however, just before and during reperfusion significantly enhanced cardiopulmonary preservation. These results indicate that free radical-induced injury is primarily the result of reperfusion. Thus the best time for administration of r,h-SOD is before and during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2494311

  2. Incidence, etiology, and significance of acute kidney injury in the early post-kidney transplant period.

    PubMed

    Panek, Romuald; Tennankore, Karthik K; Kiberd, Bryce A

    2016-01-01

    Little is known about the incidence, causes, and significance of acute kidney injury (AKI) in the early transplant period. This study used a definition as >26 μmol/L increase in creatinine within 48 h or >50% increase over a period >48 h. In 326 adult consecutive recipients of a solitary kidney transplant from 2006 to 2014 followed at this center, 21% developed AKI within the first six months. Most etiologies were CNI toxicity (33%) or unknown (26%), whereas acute rejection accounted for 17% and urinary tract obstruction for 10%. Those with AKI had a significantly lower glomerular filtration rate (GFR) at one-yr post-transplant (adjusted beta coefficient -5.5 mL/min/1.73 m(2) , 95% CI: -10.4, -0.7, p = 0.025) in a multivariable linear regression model. However, the AKI definition missed 6 of 19 episodes of acute rejection and 4 of 10 episodes of urinary tract obstruction. When acute rejection (including those that did not satisfy AKI criteria) was included in the model, other causes of AKI were not significantly associated with GFR at year 1. Although AKI, using current criteria, is likely to be a significant predictor of later outcomes, important causes are missed and the criteria are not sensitive for clinical decision-making. PMID:26497636

  3. Lung cancer incidence decreases with elevation: evidence for oxygen as an inhaled carcinogen.

    PubMed

    Simeonov, Kamen P; Himmelstein, Daniel S

    2015-01-01

    The level of atmospheric oxygen, a driver of free radical damage and tumorigenesis, decreases sharply with rising elevation. To understand whether ambient oxygen plays a role in human carcinogenesis, we characterized age-adjusted cancer incidence (compiled by the National Cancer Institute from 2005 to 2009) across counties of the elevation-varying Western United States and compared trends displayed by respiratory cancer (lung) and non-respiratory cancers (breast, colorectal, and prostate). To adjust for important demographic and cancer-risk factors, 8-12 covariates were considered for each cancer. We produced regression models that captured known risks. Models demonstrated that elevation is strongly, negatively associated with lung cancer incidence (p < 10(-16)), but not with the incidence of non-respiratory cancers. For every 1,000 m rise in elevation, lung cancer incidence decreased by 7.23 99% CI [5.18-9.29] cases per 100,000 individuals, equivalent to 12.7% of the mean incidence, 56.8. As a predictor of lung cancer incidence, elevation was second only to smoking prevalence in terms of significance and effect size. Furthermore, no evidence of ecological fallacy or of confounding arising from evaluated factors was detected: the lung cancer association was robust to varying regression models, county stratification, and population subgrouping; additionally seven environmental correlates of elevation, such as exposure to sunlight and fine particulate matter, could not capture the association. Overall, our findings suggest the presence of an inhaled carcinogen inherently and inversely tied to elevation, offering epidemiological support for oxygen-driven tumorigenesis. Finally, highlighting the need to consider elevation in studies of lung cancer, we demonstrated that previously reported inverse lung cancer associations with radon and UVB became insignificant after accounting for elevation. PMID:25648772

  4. HLA-E(⁎)01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence.

    PubMed

    Di Cristofaro, Julie; Pelardy, Mathieu; Loundou, Anderson; Basire, Agnès; Gomez, Carine; Chiaroni, Jacques; Thomas, Pascal; Reynaud-Gaubert, Martine; Picard, Christophe

    2016-01-01

    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). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, HLA-E(⁎)01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E(⁎)01:01 status (HR: 3.563 (CI 95%, 1.016-12), p = 0.047). HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort. PMID:27493971

  5. HLA-E⁎01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence

    PubMed Central

    Di Cristofaro, Julie; Basire, Agnès; Gomez, Carine; Chiaroni, Jacques; Thomas, Pascal; Reynaud-Gaubert, Martine

    2016-01-01

    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). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, HLA-E⁎01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E⁎01:01 status (HR: 3.563 (CI 95%, 1.016–12), p = 0.047). HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort. PMID:27493971

  6. Onset of Inflammation With Ischemia: Implications for Donor Lung Preservation and Transplant Survival.

    PubMed

    Tao, J-Q; Sorokina, E M; Vazquez Medina, J P; Mishra, M K; Yamada, Y; Satalin, J; Nieman, G F; Nellen, J R; Beduhn, B; Cantu, E; Habashi, N M; Jungraithmayr, W; Christie, J D; Chatterjee, S

    2016-09-01

    Lungs stored ahead of transplant surgery experience ischemia. Pulmonary ischemia differs from ischemia in the systemic organs in that stop of blood flow in the lung leads to loss of shear alone because the lung parenchyma does not rely on blood flow for its cellular oxygen requirements. Our earlier studies on the ischemia-induced mechanosignaling cascade showed that the pulmonary endothelium responds to stop of flow by production of reactive oxygen species (ROS). We hypothesized that ROS produced in this way led to induction of proinflammatory mediators. In this study, we used lungs or cells subjected to various periods of storage and evaluated the induction of several proinflammatory mediators. Isolated murine, porcine and human lungs in situ showed increased expression of cellular adhesion molecules; the damage-associated molecular pattern protein high-mobility group box 1 and the corresponding pattern recognition receptor, called the receptor for advanced glycation end products; and induction stabilization and translocation of hypoxia-inducible factor 1α and its downstream effector VEGFA, all of which are participants in inflammation. We concluded that signaling with lung preservation drives expression of inflammatory mediators that potentially predispose the donor lung to an inflammatory response after transplant. PMID:26998598

  7. Lung Transplantation Is Increasingly Common Among Patients With Coal Workers’ Pneumoconiosis

    PubMed Central

    Blackley, David J.; Halldin, Cara N.; Cummings, Kristin J.; Laney, A. Scott

    2016-01-01

    Background The prevalence of coal workers’ pneumoconiosis (CWP) in U.S. coal miners has increased, and severe presentations are increasingly common. Methods We describe trends in lung transplantation during 1996–2014 for recipients with a primary diagnosis of CWP or pneumoconiosis unspecified, and we summarize recipient characteristics and estimate survival. Results A total of 47 transplants were included; nearly three-quarters were performed during 2008–2014. All recipients were male, 96% were white, and the mean age was 56 years. Mean FEV1% was 35%; mean FVC% was 53%. Mean time on a waitlist was 155 days, and 60% of transplants were bilateral. Median survival was 3.7 years. Conclusions These transplants reflect the use of a scarce resource for an entirely preventable disease, and highlight the need for enhanced efforts to reduce coal mine dust exposures. PMID:26725917

  8. Incidence of post-transplant glomerulonephritis and its impact on graft outcome

    PubMed Central

    An, Jung Nam; Lee, Jung Pyo; Oh, Yun Jung; Oh, Yun Kyu; Ha, Jong-won; Chae, Dong-Wan; Kim, Yon Su; Lim, Chun Soo

    2012-01-01

    Background Herein, the significance of post-transplant glomerulonephritis (PTGN) has been revisited to investigate whether PTGN induces allograft failure. The aim of this study was to identify the incidence of PTGN and its association with allograft failure, as well as to analyze the risk factors for PTGN. Methods Among the 996 Korean patients who underwent kidney transplantation in a multicenter cohort from 1995 to 2010, 764 patients were enrolled in this study. Results The incidence rate of PTGN was 9.7% and 17.0% at 5 and 10 years of follow-up, respectively. PTGN was diagnosed in 17.8% of the recipients with results of biopsy tests or clinical diagnosis identifying glomerular diseases as the underlying cause, compared with 0.0%, 4.4%, 4.9%, 5.5%, and 5.7% of the recipients with renal vascular diseases, renal interstitial diseases/pyelonephritis/uropathy, diabetic renal disease, hereditary renal diseases, and diseases with unknown etiologies, respectively. Allograft survival was significantly decreased in patients with PTGN. PTGN was associated with a fourfold increase in graft failure with a hazard ratio of 7.11 for both acute rejection and PTGN. Results of the risk factor analysis for PTGN revealed that the underlying glomerular renal diseases and treatment methods using drugs such as tacrolimus and basiliximab significantly increased PTGN development, after adjusting for other risk factors. Conclusion We conclude that PTGN is strongly associated with poor kidney allograft survival. Therefore, optimal management of recurrent or de novo GN should be the critical focus of post-transplant care. PMID:26889425

  9. Sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: Incidence, risk factors and outcomes.

    PubMed

    Yakushijin, K; Atsuta, Y; Doki, N; Yokota, A; Kanamori, H; Miyamoto, T; Ohwada, C; Miyamura, K; Nawa, Y; Kurokawa, M; Mizuno, I; Mori, T; Onizuka, M; Taguchi, J; Ichinohe, T; Yabe, H; Morishima, Y; Kato, K; Suzuki, R; Fukuda, T

    2016-03-01

    This retrospective study was conducted in Japan to determine the incidence, risk factors and outcomes of sinusoidal obstruction syndrome (SOS) after allogeneic hematopoietic stem cell transplantation (HSCT). Among 4290 patients undergoing allogeneic HSCT between 1999 and 2010, 462 were diagnosed with SOS according to the Seattle criteria (cumulative incidence, 10.8%). The cumulative incidence of SOS diagnosed by the modified Seattle criteria was 9.3%. Of 462 patients, 107 met the Baltimore criteria and 168 had severe SOS with renal and/or respiratory failure. The median onset for SOS was 12 days after HSCT (range, -2-30). Overall survival at day 100 was 32% for SOS and 15% for severe SOS. Multivariate analyses showed that significant independent risk factors for SOS were the number of HSCTs, age, performance status, hepatitis C virus-seropositivity, advanced disease status and myeloablative regimen. SOS was highly associated with overall mortality (hazard ratio, 2.09; P<0.001). Our retrospective survey showed that the cumulative incidence of SOS in Japan was 10.8%, similar to that previously reported in Western countries, and that the overall survival of patients who developed SOS was low. Furthermore, several risk factors were identified. Preventive and therapeutic strategies for high-risk SOS patients must be established to improve overall survival. PMID:26595082

  10. Ex Vivo Lung Perfusion and Transplant: State of the Art and View to the Future.

    PubMed

    Mohamed, Mohamed S A

    2015-12-01

    After the first clinical application of ex vivo lung perfusion in 2001, the technique has been used in many lung transplant centers worldwide. In addition, many modifications have been tested, leading to the development of various ex vivo lung perfusion systems and application protocols. Currently, the Lund protocol, the Toronto protocol, and Organ Care System Lung protocol are the clinically applied ex vivo lung perfusion protocols, based on the favorable results of the safety studies. Accordingly, the comparison among these EVLP systems and protocols should be an important research target, in order to provide the evidence based medical data that would recommend one protocol over the others. In this manuscript, the current experience with EVLP is reviewed and some molecular and clinical targets, that could be used to compare the various protocols of the technique, are introduced. PMID:26643670

  11. Role of interleukin-17A in early graft rejection after orthotopic lung transplantation in mice

    PubMed Central

    Chen, Qi-Rui; Wang, Li-Feng; Xia, Si-Si; Zhang, Ya-Mei; Xu, Jiang-Nan

    2016-01-01

    Background The cellular and molecular mechanisms underlying lung allograft rejection remain poorly understood. We investigated the potential role of interleukin (IL)-17A in lung transplant rejection in a mouse model, because previous studies in clinical and rodent models have implicated IL-17A in both acute and chronic rejection. Methods To generate an orthotopic lung transplantation model, lungs from C57BL/6 or BALB/c mice were transplanted into C57BL/6 mice (isograft and allograft models, respectively). The effects of anti-IL-17A treatment in allograft recipients were investigated. The histological features and rejection status of isografts and allografts were assessed at 3, 7, and 28 days after transplantation, and differences in graft infiltrating cells and mRNA expression of relevant cytokines were quantified at 3 and 7 days after transplantation. Results As expected, isografts showed no obvious signs of rejection, whereas allografts exhibited minimal-to-mild rejection (grade A1–A2) by day 3 and moderate-to-severe rejection (grade A3–A4) by day 7, without evidence of obliterative bronchiolitis (OB). However, by 28 days, evidence of OB was observed in 67% (2/3) of allografts and severe rejection (grade A4) was observed in all. IL-17 mRNA expression in allografts was increased with rejection, and interferon (IFN)-γ and IL-6 mRNA expression levels followed a similar pattern. In contrast, IL-22 expression in allografts was only slightly increased. Antibody (Ab) neutralization of IL-17A diminished the signs of acute rejection at 7 days after transplantation in allografts, and this early protection was accompanied by a decrease in cellular stress according to histological evaluation, suggesting the involvement of IL-17A in the development of early post-transplantation lesions. Conclusions Our data indicate that IL-17A is important in the pathophysiology of allograft rejection, and neutralization of IL-17A is a potential therapeutic strategy to preventing lung

  12. Dendritic Cell Depletion and Repopulation in the Lung after Irradiation and Bone Marrow Transplantation in Mice

    PubMed Central

    Hahn, Ines; Klaus, Anna; Maus, Regina; Christman, John W.; Welte, Tobias

    2011-01-01

    Dendritic cells (DCs) are essential for innate and adaptive immunity, but are purported to exhibit variable radiosensitivity in response to irradiation in various bone marrow transplantation (BMT) protocols. To address this controversy, we analyzed the magnitude of depletion and repopulation of both lung CD11bpos DC and CD103pos DC subsets in response to irradiation and BMT in a murine model. In our study, CD45.2pos donor bone marrow cells were transplanted into irradiated CD45.1pos recipient mice to examine the depletion of recipient DC subsets and the repopulation of donor DC subsets. We observed an apoptosis-mediated and necrosis-mediated depletion (> 90%) of the recipient CD103pos DC subset, and only a 50–60% depletion of recipient CD11bpos DCs from lung parenchymal tissue on Days 3 and 5, whereas recipient alveolar and lung macrophages were much less radiosensitive, showing an approximately 50% depletion by Days 14–21 after treatment. A repopulation of lung tissue with donor DC subsets had occurred by Days 10 and 28 for CD11bpos DCs and CD103pos DCs, whereas alveolar and lung macrophages were repopulated by 6 and 10 weeks after treatment. Furthermore, the infection of mice with Streptococcus pneumoniae further accelerated the turnover of lung DCs and lung macrophage subsets. Our data illustrate the vulnerability of lung CD103pos DCs and CD11bpos DCs to irradiation, and indicate that an accelerated turnover of lung DC subsets occurs, relative to pulmonary and lung macrophages. Our findings may have important implications in the development of adjuvant immune-stimulatory protocols that could reduce the risk of opportunistic infections in patients undergoing BMT. PMID:21177980

  13. A pharmacokinetic analysis of posaconazole oral suspension in the serum and alveolar compartment of lung transplant recipients.

    PubMed

    Thakuria, L; Packwood, K; Firouzi, A; Rogers, P; Soresi, S; Habibi-Parker, K; Lyster, H; Zych, B; Garcia-Saez, D; Mohite, P; Patil, N; Sabashnikov, A; Capoccia, M; Chibvuri, M; Lamba, H; Tate, H; Carby, M; Simon, A; Leaver, N; Reed, A

    2016-01-01

    Invasive fungal infections cause significant morbidity and mortality after lung transplantation. Fungal prophylaxis following lung transplantation is not standardised, with transplant centres utilising a variety of regimens. Posaconazole is a broad-spectrum antifungal triazole that requires further investigation within the setting of lung transplantation. This prospective, single-centre, observational study explored the pharmacokinetics of posaconazole oral suspension (POS) in the early perioperative period following lung transplantation in 26 patients. Organ recipients were scheduled to receive 400mg POS twice daily for 6 weeks as primary antifungal prophylaxis. Therapeutic drug monitoring (TDM) of serum posaconazole levels was performed in accordance with local clinical protocols. Bronchoalveolar lavage fluid (BALF) was sampled during routine bronchoscopies. Posaconazole levels were measured both in serum and BALF using mass spectrometry. Posaconazole levels were highly variable within lung transplant recipients during the perioperative period and did not achieve 'steady-state'. Serum posaconazole concentrations positively correlated with levels within the BALF (r=0.5527; P=0.0105). Of the 26 patients, 10 failed to complete the study for multiple reasons and so the trial was terminated early. Unlike study findings in stable recipients, serum posaconazole levels rarely achieved steady-state in the perioperative period; however, they do reflect the concentrations within the airways of newly transplanted lungs. The role of POS as primary prophylaxis in the perioperative period is uncertain, but if used TDM may be helpful for determining attainment of therapeutic levels. PMID:26607341

  14. Pharmacokinetics and Toxicity of Tacrolimus Early After Heart and Lung Transplantation.

    PubMed

    Sikma, M A; van Maarseveen, E M; van de Graaf, E A; Kirkels, J H; Verhaar, M C; Donker, D W; Kesecioglu, J; Meulenbelt, J

    2015-09-01

    Annually, about 8000 heart and lung transplantations are successfully performed worldwide. However, morbidity and mortality still pose a major concern. Renal failure in heart and lung transplant recipients is an essential adverse cause of morbidity and mortality, often originating in the early postoperative phase. At this time of clinical instability, the kidneys are exposed to numerous nephrotoxic stimuli. Among these, tacrolimus toxicity plays an important role, and its pharmacokinetics may be significantly altered in this critical phase by fluctuating drug absorption, changed protein metabolism, anemia and (multi-) organ failure. Limited understanding of tacrolimus pharmacokinetics in these circumstances is hampering daily practice. Tacrolimus dose adjustments are generally based on whole blood trough levels, which widely vary early after transplantation. Moreover, whole blood trough levels are difficult to predict and are poorly related to the area under the concentration-time curve. Even within the therapeutic range, toxicity may occur. These shortcomings of tacrolimus monitoring may not hold for the unbound tacrolimus plasma concentrations, which may better reflect tacrolimus toxicity. This review focuses on posttransplant tacrolimus pharmacokinetics, discusses relevant factors influencing the unbound tacrolimus concentrations and tacrolimus (nephro-) toxicity in heart and lung transplantation patients. PMID:26053114

  15. Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation

    PubMed Central

    Cantu, Edward; Meyer, Nuala J.; Shah, Rupal J.; Lederer, David J.; Kawut, Steven M.; Lee, James; Bellamy, Scarlett L.; Palmer, Scott M.; Lama, Vibha N.; Bhorade, Sangeeta M.; Crespo, Maria; Demissie, Ejigayehu; Wille, Keith; Orens, Jonathan; Shah, Pali D.; Weinacker, Ann; Weill, David; Arcasoy, Selim; Wilkes, David S.; Ware, Lorraine B.; Christie, Jason D.

    2012-01-01

    Introduction Primary graft dysfunction (PGD) is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD. Methods We performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE). Results There were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40%) and 47 non-PGD subjects (59%) received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF). Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03). The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02); there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD) (p = 0.9). Conclusions Angiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated. PMID:23284823

  16. Removal of metallic tracheobronchial stents in lung transplantation with flexible bronchoscopy

    PubMed Central

    2010-01-01

    Background Airway complications are among the most challenging problems after lung transplantation, and Self-Expandable Metallic Stents (SEMS) are used to treat airway complications such as stenosis or malacia at the bronchial anastomosis sites. Several transplantation centers are reluctant to use SEMS since their removal is sometimes needed and usually requires the use of rigid bronchoscopy under general anesthesia. The objective of the current report is to describe our experience in SEMS retrieval by flexible bronchoscopy under conscious sedation. Methods A retrospective review was done of patients requiring tracheobronchial stent placement after lung transplantation in which the SEMS had to be removed. The retrieval procedure was done by flexible bronchoscopy on a day-care ambulatory basis. Results Between January 2004 and January 2010, out of 305 lung transplantation patients, 24 (7.8%) underwent SEMS placement. Indications included bronchial stenosis in 20 and bronchomalacia in 4. In six patients (25%) the SEMS had to be removed due to excessive granulation tissue formation and stent obstruction. The average time from SEMS placement to retrieval was 30 months (range 16-48 months). The stent was completely removed in five patients and partially removed in one patient; no major complications were encountered, and all patients were discharged within 3 hours of the procedure. In all procedures, new SEMS was successfully re-inserted thereafter. Conclusions The retrieval of SEMS in patients that underwent lung transplantation can be effectively and safely done under conscious sedation using flexible bronchoscopy on a day-care basis, this observation should encourage increasing usage of SEMS in highly selected patients. PMID:20831830

  17. Abnormal skeletal muscle oxidative capacity after lung transplantation by 31P-MRS.

    PubMed

    Evans, A B; Al-Himyary, A J; Hrovat, M I; Pappagianopoulos, P; Wain, J C; Ginns, L C; Systrom, D M

    1997-02-01

    Although lung transplantation improves exercise capacity by removal of a ventilatory limitation, recipients' postoperative maximum oxygen uptake (VO2max) remains markedly abnormal. To determine if abnormal skeletal muscle oxidative capacity contributes to this impaired aerobic capacity, nine lung transplant recipients and eight healthy volunteers performed incremental quadriceps exercise to exhaustion with simultaneous measurements of pulmonary gas exchange, minute ventilation, blood lactate, and quadriceps muscle pH and phosphorylation potential by 31P-magnetic resonance spectroscopy (31P-MRS). Five to 38 mo after lung transplantation, peak VO2 was decreased compared with that of normal control subjects (6.7 +/- 0.4 versus 12.3 +/- 1.0 ml/min/kg, p < 0.001), even after accounting for differences in age and lean body weight. Neither ventilation, arterial O2 saturation nor mild anemia could account for the decrease in aerobic capacity. Quadriceps muscle intracellular pH (pH(i)) was more acidic at rest (7.07 +/- 0.01 versus 7.12 +/- 0.01 units, p < 0.05) and fell during exercise from baseline values at a lower metabolic rate (282 +/- 21 versus 577 +/- 52 ml/min, p < 0.001). Regressions for pH(i) versus VO2, phosphocreatine/inorganic phosphate ratio (PCr/Pi) versus VO2, and blood lactate versus pH(i) were not different. Among transplant recipients, the metabolic rate at which pH(i) fell correlated closely with VO2max (r = 0.87, p < 0.01). The persistent decrease in VO2max after lung transplantation may be related to abnormalities of skeletal muscle oxidative capacity. PMID:9032203

  18. Incidence and causes of hospital readmission in pediatric patients after hematopoietic cell transplantation.

    PubMed

    Shulman, David Stephen; London, Wendy B; Guo, Dongjing; Duncan, Christine N; Lehmann, Leslie E

    2015-05-01

    Allogeneic (allo) and autologous (auto) hematopoietic cell transplantation (HCT) provide the potential to cure otherwise fatal diseases but they are resource-intense therapies. There is scant literature describing the burden of hospital readmission in the critical 6-month period of immunosuppression after HCT. We report the incidence, causes, and outcomes of readmission in the 6 months after day 0 of HCT and in the 30 days after hospital discharge. This study is an institutional review board-approved retrospective medical record review of children who underwent HCT at a single institution. Between January 1, 2008 and December 31, 2011, 291 children underwent HCT at our institute. Of these, 140 patients were excluded because they were not followed primarily at our institute for the first 6 months after transplantation, 14 patients were excluded because they died during their initial hospitalization, and 1 patient was excluded because the initial hospitalization was longer than 6 months. Of the remaining 136 patients, 63% had at least 1 readmission. Of the patients who underwent allo-HCT, 78% were readmitted, in contrast to 38% of auto-HCT patients (P < .001). For the 206 readmissions, the mean length of hospital stay was 10.7 days (range, 1 to 129). Seventy-two percent of auto-HCT patients were initially readmitted for fever, and 46% ultimately had a source identified. No risk factors for readmission were found in the auto-HCT group. Fifty-two percent of allo-HCT patients were readmitted for fever and 28% of these patients ultimately had an identified source. Gastrointestinal-related problems accounted for 30% of primary readmissions among allo-HCT patients. Patients with an unrelated donor had a trend towards increased rates of 30-day readmission (P = .06) and were more likely to have a second readmission (P = .002). Patients who were cytomegalovirus (CMV) positive before transplantation were more likely to be readmitted (P = .02). The majority of children who

  19. Interstitial Pneumonitis and the Risk of Chronic Allograft Rejection in Lung Transplant Recipients

    PubMed Central

    Mihalek, Andrew D.; Rosas, Ivan O.; Padera, Robert F.; Fuhlbrigge, Anne L.; Hunninghake, Gary M.; DeMeo, Dawn L.; Camp, Phillip C.

    2013-01-01

    Background: The presence of interstitial pneumonitis (IP) on surveillance lung biopsy specimens in lung transplant recipients is poorly described, and its impact on posttransplant outcomes is not established. The following study assessed the association of posttransplant IP with the development of bronchiolitis obliterans syndrome (BOS). Methods: We examined all recipients of primary cadaveric lung transplants at our institution between January 1, 2000, and December 31, 2007 (N = 145). Patients had bronchoscopies with BAL, and transbronchial biopsies performed for surveillance during posttransplant months 1, 3, 6, and 12 as well as when clinically indicated. Patients were given a diagnosis of IP if, in the absence of active infection and organizing pneumonia, they showed evidence of interstitial inflammation and fibrosis on two or more biopsy specimens. Results: IP was a significant predictor of BOS (OR, 7.84; 95% CI, 2.84-21.67; P < .0001) and was significantly associated with time to development of BOS (hazard ratio, 3.8; 95% CI, 1.93-7.39; P = .0001) within the first 6 years posttransplant. The presence of IP did not correlate with a significantly higher risk of mortality or time to death. There was no association between the presence of IP and the development of or time to acute rejection. Conclusions: The presence of IP on lung transplant biopsy specimens suggests an increased risk for BOS, which is independent of the presence of acute cellular rejection. PMID:23715594

  20. Successful management of bilateral refractory chylothorax after double lung transplantation for lymphangioleiomyomatosis

    PubMed Central

    Hussein, Mohammed; Aljehani, Yasser M.; Nizami, Imran; Saleh, Waleed

    2014-01-01

    Lymphangioleiomyomatosis (LAM) is a rare disease that leads to airways and lymphatic channels obstruction due to abnormal smooth muscle proliferation. It presents with dyspnea, pneumothorax or chylothorax. Lung transplantation (LT) has emerged as a valuable therapeutic option with limited reports. We report a case of LAM that underwent double LT and complicated by refractory bilateral chylothorax which was managed successfully by povidone-iodine pleurodesis and the addition of sirolimus to the post-transplantation immunosuppressive therapy. The patient has no recurrence with 24 months follow-up. PMID:24791177

  1. Subcutaneous IgG replacement therapy is safe and well tolerated in lung transplant recipients.

    PubMed

    Shankar, T; Gribowicz, J; Crespo, M; Silveira, F P; Pilewski, J; Petrov, A A

    2013-04-01

    Intravenous immunoglobulin (IVIG) replacement has been shown to decrease the risk of post-transplant infections secondary to hypogammaglobulinemia, however the use of subcutaneous immunoglobulin (SCIG) in this population has not been reported. A retrospective analysis of the efficacy and tolerability of subcutaneous immunoglobulin replacement on 10 lung-transplant recipients was performed. All 10 patients demonstrated an increase in IgG levels at three months that was sustained at 6-12 months with SCIG replacement therapy, with the majority (70%) tolerating infusion without complications. The results of this study suggest that subcutaneous IgG replacement therapy is a well tolerated alternative to IVIG. PMID:23499641

  2. Acute liver failure due to Varicella zoster virus infection after lung transplantation: a case report.

    PubMed

    Verleden, G M; Vos, R; Van Raemdonck, D E; Laleman, W; Vanaudenaerde, B M

    2012-06-01

    Most adults are Varicella zoster virus (VZV)-positive at the age of 20 years. Some, however, remain antibody-negative and may develop primary chicken pox during adulthood. We report a patient with Williams-Campbell syndrome who underwent double-lung transplantation while being VZV-negative. One year after the successful procedure, he was admitted with fulminant hepatic failure and some cutaneous vesicles in his face. Despite a rapid diagnosis of VZV infection and treatment with acyclovir, his situation deteriorated within 24 hours and while awaiting an urgent liver transplantation, he developed multiple organ failure and died. PMID:22664036

  3. Clinical grade allogeneic human mesenchymal stem cells restore alveolar fluid clearance in human lungs rejected for transplantation

    PubMed Central

    Curley, G. F.; Hamid, U. I.; Laffey, J. G.; Abbott, J.; McKenna, D. H.; Fang, X.; Matthay, M. A.; Lee, J. W.

    2014-01-01

    The lack of suitable donors for all solid-organ transplant programs is exacerbated in lung transplantation by the low utilization of potential donor lungs, due primarily to donor lung injury and dysfunction, including pulmonary edema. The current studies were designed to determine if intravenous clinical-grade human mesenchymal stem (stromal) cells (hMSCs) would be effective in restoring alveolar fluid clearance (AFC) in the human ex vivo lung perfusion model, using lungs that had been deemed unsuitable for transplantation and had been subjected to prolonged ischemic time. The human lungs were perfused with 5% albumin in a balanced electrolyte solution and oxygenated with continuous positive airway pressure. Baseline AFC was measured in the control lobe and if AFC was impaired (defined as <10%/h), the lungs received either hMSC (5 × 106 cells) added to the perfusate or perfusion only as a control. AFC was measured in a different lung lobe at 4 h. Intravenous hMSC restored AFC in the injured lungs to a normal level. In contrast, perfusion only did not increase AFC. This positive effect on AFC was reduced by intrabronchial administration of a neutralizing antibody to keratinocyte growth factor (KGF). Thus, intravenous allogeneic hMSCs are effective in restoring the capacity of the alveolar epithelium to remove alveolar fluid at a normal rate, suggesting that this therapy may be effective in enhancing the resolution of pulmonary edema in human lungs deemed clinically unsuitable for transplantation. PMID:24532289

  4. Stem cells--potential for repairing damaged lungs and growing human lungs for transplant.

    PubMed

    Bishop, Anne E; Rippon, Helen J

    2006-08-01

    Repair or regeneration of defective lung epithelium would be of great therapeutic potential. It is estimated by the British Lung Foundation that 1 in 7 people in the UK is affected by a lung disease and that 1 in 4 admissions to children's wards are as a result of respiratory problems. Potential cellular sources for the regeneration of lung tissue in vivo or lung tissue engineering in vitro include endogenous pulmonary epithelial stem cells, extrapulmonary circulating stem cells and embryonic stem cells. This article discusses the potential role of each of these stem cell types in future approaches to the treatment of lung injury and disease. PMID:16856797

  5. The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis.

    PubMed

    Williams, K M; Ahn, K W; Chen, M; Aljurf, M D; Agwu, A L; Chen, A R; Walsh, T J; Szabolcs, P; Boeckh, M J; Auletta, J J; Lindemans, C A; Zanis-Neto, J; Malvezzi, M; Lister, J; de Toledo Codina, J S; Sackey, K; Chakrabarty, J L H; Ljungman, P; Wingard, J R; Seftel, M D; Seo, S; Hale, G A; Wirk, B; Smith, M S; Savani, B N; Lazarus, H M; Marks, D I; Ustun, C; Abdel-Azim, H; Dvorak, C C; Szer, J; Storek, J; Yong, A; Riches, M R

    2016-04-01

    Pneumocystis jiroveci pneumonia (PJP) is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Little is known about PJP infections after HSCT because of the rarity of disease given routine prophylaxis. We report the results of a Center for International Blood and Marrow Transplant Research study evaluating the incidence, timing, prophylaxis agents, risk factors and mortality of PJP after autologous (auto) and allogeneic (allo) HSCT. Between 1995 and 2005, 0.63% allo recipients and 0.28% auto recipients of first HSCT developed PJP. Cases occurred as early as 30 days to beyond a year after allo HSCT. A nested case cohort analysis with supplemental data (n=68 allo cases, n=111 allo controls) revealed that risk factors for PJP infection included lymphopenia and mismatch after HSCT. After allo or auto HSCT, overall survival was significantly poorer among cases vs controls (P=0.0004). After controlling for significant variables, the proportional hazards model revealed that PJP cases were 6.87 times more likely to die vs matched controls (P<0.0001). We conclude PJP infection is rare after HSCT but is associated with high mortality. Factors associated with GVHD and with poor immune reconstitution are among the risk factors for PJP and suggest that protracted prophylaxis for PJP in high-risk HSCT recipients may improve outcomes. PMID:26726945

  6. Incidence and clinical features of extramedullary multiple myeloma in patients who underwent stem cell transplantation.

    PubMed

    Weinstock, Mathew; Aljawai, Yosra; Morgan, Elizabeth A; Laubach, Jacob; Gannon, Muriel; Roccaro, Aldo M; Varga, Cindy; Mitsiades, Constantine S; Paba-Prada, Claudia; Schlossman, Robert; Munshi, Nikhil; Anderson, Kenneth C; Richardson, Paul P; Weller, Edie; Ghobrial, Irene M

    2015-06-01

    Extramedullary disease (EMD), defined as an infiltrate of clonal plasma cells at an anatomic site distant from the bone marrow, is an uncommon manifestation of multiple myeloma. Six hundred and sixty-three consecutive patients with multiple myeloma who underwent stem cell transplantation between January 2005 and December 2011 were assessed for the presence of EMD. A cohort of 55 patients with biopsy-proven EMD was identified, comprising 8·3% of the total study population. EMD was present at the time of diagnosis in 14·5% of cases and at the time of relapse in 76% of patients. The most common EMD presentations at relapse were liver involvement and pleural effusions. EMD specimens had high expression of CD44 (92%) and moderate expression of CXCR4. The median overall survival from time of myeloma diagnosis was 4·1 years (95% CI: 3·1, 5·1) and the median overall survival from time of EMD diagnosis was 1·3 years (95% CI: 0·8, 2·3). This report demonstrates that the incidence of EMD has not increased with the introduction of novel agents and stem cell transplantation. The most common EMD presentations in the relapsed setting were liver and pleural fluid. The presence of CD44 and CXCR4 expression may represent new markers of EMD that warrant further investigation. PMID:25833301

  7. Incidence and risk factors for early renal dysfunction after liver transplantation

    PubMed Central

    Wiesen, Patricia; Massion, Paul B; Joris, Jean; Detry, Olivier; Damas, Pierre

    2016-01-01

    AIM: To determine renal dysfunction post liver transplantation, its incidence and risk factors in patients from a Belgian University Hospital. METHODS: Orthotopic liver transplantations performed from January 2006 until September 2012 were retrospectively reviewed (n = 187). Patients with no renal replacement therapy (RRT) before transplantation were classified into four groups according to their highest creatinine plasma level during the first postoperative week. The first group had a peak creatinine level below 12 mg/L, the second group between 12 and 20 mg/L, the third group between 20 and 35 mg/L, and the fourth above 35 mg/L. In addition, patients who needed RRT during the first week after transplantation were also classified into the fourth group. Perioperative parameters were recorded as risk factors, namely age, sex, body mass index (BMI), length of preoperative hospital stay, prior bacterial infection within one month, preoperative ascites, preoperative treatment with β-blocker, angiotensin-converting enzyme inhibitor or non steroidal anti-inflammatory drugs, preoperative creatinine and bilirubin levels, donor status (cardiac death or brain death), postoperative lactate level, need for intraoperative vasopressive drugs, surgical revision, mechanical ventilation for more than 24 h, postoperative bilirubin and transaminase peak levels, postoperative hemoglobin level, amount of perioperative blood transfusions and type of immunosuppression. Univariate and multivariate analysis were performed using logistic ordinal regression method. Post hoc analysis of the hemostatic agent used was also done. RESULTS: There were 78 patients in group 1 (41.7%), 46 in group 2 (24.6%), 38 in group 3 (20.3%) and 25 in group 4 (13.4%). Twenty patients required RRT: 13 (7%) during the first week after transplantation. Using univariate analysis, the severity of renal dysfunction was correlated with presence of ascites and prior bacterial infection, preoperative bilirubin, urea and

  8. Video fluoroscopy swallow study and nutritional support during ambulatory venovenous extracorporeal membrane oxygenation as a bridge to lung transplantation.

    PubMed

    Hayes, Don; Tobias, Joseph D; Galantowicz, Mark; Preston, Thomas J; Tzemos, Kallirroe K; McConnell, Patrick I

    2014-01-01

    We present the successful completion of a video fluoroscopy swallow study and subsequent nutritional plan of a child bridged to lung transplantation with ambulatory venovenous (VV) extracorporeal membrane oxygenation (ECMO). With a limited number of programs bridging pediatric patients to lung transplantation with VV ECMO, a better understanding of nutritional support is needed to provide optimal care to this patient population awaiting organ donation. PMID:24403362

  9. Incidence, risk factors and outcomes of de novo malignancies post liver transplantation

    PubMed Central

    Mukthinuthalapati, Pavan Kedar; Gotur, Raghavender; Ghabril, Marwan

    2016-01-01

    Liver transplantation (LT) is associated with a 2 to 7 fold higher, age and gender adjusted, risk of de novo malignancy. The overall incidence of de novo malignancy post LT ranges from 2.2% to 26%, and 5 and 10 years incidence rates are estimated at 10% to 14.6% and 20% to 32%, respectively. The main risk factors for de novo malignancy include immunosuppression with impaired immunosurveillance, and a number of patient factors which include; age, latent oncogenic viral infections, tobacco and alcohol use history, and underlying liver disease. The most common cancers after LT are non-melanoma skin cancers, accounting for approximately 37% of de novo malignancies, with a noted increase in the ratio of squamous to basal cell cancers. While these types of skin cancer do not impact patient survival, post-transplant lymphoproliferative disorders and solid organ cancer, accounting for 25% and 48% of malignancies, are associated with increased mortality. Patients developing these types of cancer are diagnosed at more advanced stages, and their cancers behave more aggressively compared with the general population. Patients undergoing LT for primary sclerosing cholangitis (particularly with inflammatory bowel disease) and alcoholic liver disease have high rates of malignancies compared with patients undergoing LT for other indications. These populations are at particular risk for gastrointestinal and aerodigestive cancers respectively. Counseling smoking cessation, skin protection from sun exposure and routine clinical follow-up are the current approach in practice. There are no standardized surveillance protocol, but available data suggests that regimented surveillance strategies are needed and capable of yielding cancer diagnosis at earlier stages with better resulting survival. Evidence-based strategies are needed to guide optimal surveillance and safe minimization of immunosuppression. PMID:27134701

  10. Lung transplantation from the non-heart beating donor.

    PubMed

    Dark, John H

    2008-07-27

    The inflated lung, with its unique tolerance of the absence of a circulation, is particularly suited to retrieval from the non-heart beating donor. Absence of some of the squeal of brain death may be a further potential advantage. This concept has been embraced by several centers around the world, with promising early results. PMID:18645477

  11. Should We Reconsider Lung Transplantation Through Uncontrolled Donation After Circulatory Death?

    PubMed Central

    Suzuki, Y.; Tiwari, J. L.; Lee, J.; Diamond, J.M.; Blumenthal, N. P.; Carney, K.; Borders, C.; Strain, J.; Alburger, G.W.; Jackson, D.; Timar, J.; Berg, J.; Hasz, R.D.; Cantu, E.

    2014-01-01

    Lung transplantation through controlled donation after circulatory death (cDCD) has slowly gained universal acceptance with reports of equivalent outcomes to those through donation after brain death. In contrast, uncontrolled DCD (uDCD) lung use is controversial and requires ethical, legal and medical complexities to be addressed in a limited time. Consequently, uDCD lung use has not previously been reported in the United States. Despite these potential barriers, we present a case of a patient with multiple gunshot wounds to the head and the body who was unsuccessfully resuscitated and ultimately became an uDCD donor. A cytomegalovirus positive recipient who had previously consented for CDC high-risk, DCD and participation in the NOVEL trial was transplanted from this uDCD donor, following 3 hours of ex vivo lung perfusion. The postoperative course was uneventful and the recipient was discharged home on day 9. While this case represents a “best-case scenario,” it illustrates a method for potential expansion of the lung allograft pool through uDCD after unsuccessful resuscitation in hospitalized patients. PMID:24712333

  12. Recurrence of Liver Transplantation Combined With Lung and Diaphragm Resection for Alveolar Echinococcosis: A Case Report.

    PubMed

    Pang, C; Chu, Y K

    2015-09-01

    Liver transplantation (LT) for alveolar echinococcosis (AE) with multiple-organ involvement is controversial. We report on a 31-year-old female patient suffering from AE with liver, lung, and diaphragm involvement. After an "extended" resection (liver, lung, and diaphragm were performed) combined with LT, recurrence still occurred after 6 years and the patient presented with hemoptysis. Puncture, aspiration, injection, reaspiration, and drainage (PAIRD) were performed and the effect was instantaneous. To our knowledge, no such surgical strategy for AE has previously been reported. In spite of the high risk of recurrence, choosing this surgical method is acceptable for a fatal AE and the recurrence could be controlled. PMID:26361699

  13. Unemployment and lung cancer incidence in the Province of Opole. Brief report.

    PubMed

    Chawińska, Ewa; Tukiendorf, Andrzej; Miszczyk, Leszek

    2013-06-01

    In this geostatistical analysis we present the results of interrelation between unemployment rate and lung cancer incidence ratios in the Province of Opole, Poland. In the study, unemployment statistics and population data were analyzed together with the registered (histopathologically confirmed) lung cancer cases (C34, ICD10) in sex-stratified working age population (18-65 years). The data were collected in the years 2006-2008 in the Statistical Office in Opole and Opole Cancer Registry, Poland. The statistically significant positive correlation/interrelation between unemployment rate and lung cancer incidence ratios in male population was established; in females, this effect was statistically insignificant. The obtained results are consistent with the most up-to-date reports supporting the thesis that a higher burden of disease is observed in more deprived areas. The statistics may have practical relevance in terms of improving health status of the local population following economic reforms. PMID:24053069

  14. Interdisciplinary collaboration applied to clinical research: an example of remote monitoring in lung transplantation.

    PubMed

    VanWormer, Arin; Lindquist, Ruth; Robiner, William; Finkelstein, Stanley

    2012-01-01

    Collaboration across disciplines is vital in clinical practice. It is also needed to generate high-quality actionable research, yet few frameworks for interdisciplinary collaboration exit to promote effective communications among researchers with common goals, but varied backgrounds. A review of what has been learned about collaboration was undertaken to determine attributes of effective interdisciplinary collaboration and barriers to its realization in patients undergoing lung transplantation. PMID:22475710

  15. Interdisciplinary collaboration applied to clinical research: an example of remote monitoring in lung transplantation

    PubMed Central

    VanWormer, Arin; Robiner, William; Finkelstein, Stanley

    2012-01-01

    Collaboration across disciplines is vital in clinical practice. It is also needed to generate high-quality actionable research, yet few frameworks for interdisciplinary collaboration exit to promote effective communications among researchers with common boals, but varied backgrounds. A review of that has been learned about collaboration was undertaken to determine attributes of effective interdisciplinary collaboration and barriers to its realization in patients undergoing lung transplantation. PMID:22475710

  16. Early cardiac tamponade due to tension pneumopericardium after bilateral lung transplantation.

    PubMed

    Lasocki, Sigismond; Castier, Yves; Geffroy, Arnaud; Mal, Hervé; Brugière, Olivier; Lesèche, Guy; Montravers, Philippe

    2007-10-01

    We report the case of a 42-year-old woman who developed severe hemodynamic instability with marked arterial pulsed pressure variation in the early course of bilateral lung transplantation. The diagnosis of tension pneumopericardium was made on Day 2 post-operatively based on chest X-ray and echocardiography. Transoesophageal echocardiography revealed both a cardiac tamponade and a right-to-left shunt via a patent foramen ovale. The treatment and mechanisms of these two rare complications are discussed. PMID:17919630

  17. Predictors of Posttraumatic Psychological Growth in the Late Years After Lung Transplantation

    PubMed Central

    Fox, Kristen R.; Posluszny, Donna M.; DiMartini, Andrea F.; DeVito Dabbs, Annette J.; Rosenberger, Emily M.; Zomak, Rachelle A.; Bermudez, Christian; Dew, Mary Amanda

    2014-01-01

    Background Although lung transplantation improves quality of life, most psychosocial research focuses on adverse psychological and social functioning outcomes. Positive effects, particularly in the late-term years as physical morbidities increase, have received little attention. We provide the first data on a psychological benefit—posttraumatic growth (PTG)—and we focused on long-term (>5 year) survivors. Methods Among 178 patients from a prospective study of mental health during the first two years posttransplant, we re-contacted survivors 6–11 years posttransplant. We assessed PTG (i.e., positive psychological change resulting from the transplant) and examined its relationship to other patient characteristics with multivariable regression analyses. Results 64 patients (86% of survivors) were assessed (M=8.1 years posttransplant, SD=1.2). Mean PTG exceeded the scale’s midpoint (M=38.6, SD=10.0; scale midpoint=25). Recipients experiencing greater PTG were female (p=.022), less educated (p=.014), and had a history of posttransplant panic disorder (p=.005), greater friend support (p=.048), and better perceived health (p=.032). Neither other pre- or posttransplant mood and anxiety disorders nor transplant-related morbidities (acute rejection, bronchiolitis obliterans syndrome) predicted PTG. Conclusions PTG exceeded levels observed in other chronic disease populations, suggesting that lung transplantation may uniquely foster positive psychological change in long-term survivors. PTG occurs despite physical and psychiatric morbidities. Whether PTG promotes other positive posttransplant psychosocial outcomes deserves attention. PMID:24750288

  18. Changes in the Lung Microbiome following Lung Transplantation Include the Emergence of Two Distinct Pseudomonas Species with Distinct Clinical Associations

    PubMed Central

    Dickson, Robert P.; Erb-Downward, John R.; Freeman, Christine M.; Walker, Natalie; Scales, Brittan S.; Beck, James M.; Martinez, Fernando J.; Curtis, Jeffrey L.; Lama, Vibha N.; Huffnagle, Gary B.

    2014-01-01

    Background Multiple independent culture-based studies have identified the presence of Pseudomonas aeruginosa in respiratory samples as a positive risk factor for bronchiolitis obliterans syndrome (BOS). Yet, culture-independent microbiological techniques have identified a negative association between Pseudomonas species and BOS. Our objective was to investigate whether there may be a unifying explanation for these apparently dichotomous results. Methods We performed bronchoscopies with bronchoalveolar lavage (BAL) on lung transplant recipients (46 procedures in 33 patients) and 26 non-transplant control subjects. We analyzed bacterial communities in the BAL fluid using qPCR and pyrosequencing of 16S rRNA gene amplicons and compared the culture-independent data with the clinical metadata and culture results from these subjects. Findings Route of bronchoscopy (via nose or via mouth) was not associated with changes in BAL microbiota (p = 0.90). Among the subjects with positive Pseudomonas bacterial culture, P. aeruginosa was also identified by culture-independent methods. In contrast, a distinct Pseudomonas species, P. fluorescens, was often identified in asymptomatic transplant subjects by pyrosequencing but not detected via standard bacterial culture. The subject populations harboring these two distinct pseudomonads differed significantly with respect to associated symptoms, BAL neutrophilia, bacterial DNA burden and microbial diversity. Despite notable differences in culturability, a global database search of UM Hospital Clinical Microbiology Laboratory records indicated that P. fluorescens is commonly isolated from respiratory specimens. Interpretation We have reported for the first time that two prominent and distinct Pseudomonas species (P. fluorescens and P. aeruginosa) exist within the post-transplant lung microbiome, each with unique genomic and microbiologic features and widely divergent clinical associations, including presence during acute infection

  19. Lung transplantation from donors outside standard acceptability criteria--are they really marginal?

    PubMed

    Zych, Bartlomiej; García Sáez, Diana; Sabashnikov, Anton; De Robertis, Fabio; Amrani, Mohamed; Bahrami, Toufan; Mohite, Prashant N; Patil, Nikhil P; Weymann, Alexander; Popov, Aron F; Reed, Anna; Carby, Martin; Simon, André R

    2014-11-01

    Lung transplantation (LTx) from "extended donor criteria" donors may reduce significantly organ shortage. However, its influence on results remains unclear. In this study, we evaluate retrospectively the results of LTx from donors outside standard criteria: PaO2/FiO2 ratio < 300 mmHg, age over 55 years, and history of smoking > 20 pack-years. Two hundred and forty-eight patients underwent first time LTx in our institution between January 2007 and January 2013. Seventy-nine patients (Group I) received organs from "extended donor criteria" and 169 patients (Group II) from "standard donor criteria." Recipients' and donors' demographics, perioperative variables, and outcome were compared. Donors from Group I were significantly older [median (interquartile range)]: 52.5 (44;58) vs. 42 (28.5;48.5) years (P < 0.001) with lower PaO2/FiO2 ratio: 366 ± 116.1 455 ± 80.5 mmHg (P < 0.001), higher incidence of smoking history: 57.7% vs. 41.8% (P = 0.013), and more extensive smoking history: 24(15;30) vs. 10(3.75;14) pack-years (P < 0.001). Other parameters were comparable. Recipients' gender, diagnosis, percentage of patients operated on pump and receiving double LTx were also comparable. Recipients from Group I were significantly older: 50 (42;57) vs. 44 (29.5;53.5) years (P = 001). There were no differences observed in recipients' prevalence of primary graft dysfunction (PGD) grade 3 over first three postoperative days, duration of mechanical ventilation, intensive care and hospital length of stay, prevalence of rejection, and bronchiolitis obliterans syndrome (BOS). 90-day, 1-year, and 5-year survival (Group I vs. II) were also similar: 88.6% vs. 91.7%, 83.2% vs. 84.6%, and 59% vs. 68.2% (log rank P = 0.367). Carefully selected donor lungs from outside the standard acceptability criteria may expand existing donor pool with no detrimental effect on LTx outcome. PMID:25070600

  20. Cognitive and behavioral functioning of children listed for heart and/or lung transplantation.

    PubMed

    Wray, J; Radley-Smith, R

    2010-11-01

    The objective of the study was to assess cognitive function and behavior in a group of children listed for heart and/or lung transplantation. Ninety-nine children (3.7-16.8 years) listed for heart and/or lung transplant for congenital heart disease (CHD), cardiomyopathy (CM), cystic fibrosis (CF) or primary pulmonary hypertension (PPH) were evaluated with standardized measures of cognitive function, academic ability and behavior. Results were compared with a historical cohort of healthy children and comparisons were made between the four diagnostic subgroups. Mean subtest scores, overall IQ and achievement scores were within the normal range for the total group but were significantly lower than those of the healthy group. Although there were few significant differences between the diagnostic subgroups children with CHD or CF tended to perform at a lower level than those with CM or PPH. There were some significant issues with behavior for all diagnostic subgroups, particularly in the domain of social competence. Patients with end-stage heart or lung disease are at increased risk for cognitive and/or behavioral problems, particularly those with CHD. Follow-up of these patients after transplant is important to determine the role that psychological functioning prior to surgery has in the longer term after surgery. PMID:20977644

  1. Lung-Derived Mesenchymal Stromal Cell Post-Transplantation Survival, Persistence, Paracrine Expression, and Repair of Elastase-Injured Lung

    PubMed Central

    Paxson, Julia A.; Mazan, Melissa R.; Davis, Airiel M.; Tyagi, Shivraj; Murthy, Shankar; Ingenito, Edward P.

    2011-01-01

    While multipotent mesenchymal stromal cells have been recently isolated from adult lung (L-MSCs), there is very limited data on their biological properties and therapeutic potential in vivo. How L-MSCs compare with bone marrow-derived MSCs (BM-MSCs) is also unclear. In this study, we characterized L-MSC phenotype, clonogenicity, and differentiation potential, and compared L-MSCs to BM-MSCs in vivo survival, retention, paracrine gene expression, and repair or elastase injury after transplantation. L-MSCs were highly clonogenic, frequently expressed aldehyde dehydrogenase activity, and differentiated into osteocytes, chondrocytes, adipocytes, myofibroblasts, and smooth muscle cells. After intravenous injection (2 h), L-MSCs showed greater survival than BM-MSCs; similarly, L-MSCs were significantly more resistant than BM-MSCs to anchorage independent culture (4 h) in vitro. Long after transplantation (4 or 32 days), a significantly higher number of CD45neg L-MSCs were retained than BM-MSCs. By flow cytometry, L-MSCs expressed more intercellular adhesion molecule-1 (ICAM-1), platelet derived growth factor receptor alpha (PDGFRα), and integrin α2 than BM-MSCs; these proteins were found to modulate endothelial adherence, directional migration, and migration across Matrigel in L-MSCs. Further, L-MSCs with low ICAM-1 showed poorer lung retention and higher phagocytosis in vivo. Compared with BM-MSCs, L-MSCs expressed higher levels of several transcripts (e.g., Ccl2, Cxcl2, Cxcl10, IL-6, IL-11, Hgf, and Igf2) in vitro, although gene expression in vivo was increased by L-MSCs and BM-MSCs equivalently. Accordingly, both L-MSCs and BM-MSCs reduced elastase injury to the same extent. This study demonstrates that tissue-specific L-MSCs possess mechanisms that enhance their lung retention after intravenous transplantation, and produce substantial healing of elastase injury comparable to BM-MSCs. PMID:21585237

  2. The incidence of infectious diseases after renal transplantation: a single-centre experience.

    PubMed

    Lyerová, L; Viklický, O; Nemcová, D; Teplan, V

    2008-02-01

    This single-centre study was designed to investigate the incidence of infections and their causative pathogens during the first three months after renal transplantation (RTx) in patients who had undergone the procedure in 2005 (n=174). We compared this group of patients with a previous one (1998-2000, n=437). In 2005, infection was diagnosed in 82 patients (47%). Symptomatic lower urinary tract infection (UTI) was present in 43 patients (25%), pyelonephritis in 15 (8.6%), and urosepsis in 7 (4%). Wound infection developed in 21 patients (12%), cytomegalovirus (CMV) disease in 15 (8.6%), and pneumonia in 5 (3%). The most frequent pathogens in UTI were Klebsiella pneumoniae and Enterococcus faecalis. Pathogens of wound infection included Staphylococcus coagulase negative and K. pneumoniae. Pneumonia was frequently caused by Mycoplasma pneumophila. Compared with the previous group, we noted decreases in the total number of infections (77.7 vs. 47%, P<0.001), pneumonia (8.5 vs. 3%, P<0.02) and UTI (33.3 vs. 24.7%, P<0.05). We observed an increased incidence of multiresistant Klebsiella. Based on these results, we have changed our scheme of antibiotic prophylaxis and the algorithms of antibiotic treatment. We reduced the use of antibiotics with an adverse epidemiological effect (quinolones, third-generation cephalosporins) and increased the use of relatively safe antibiotics (penicillins, aminopenicillins, with and without beta-lactam inhibitors). PMID:18160263

  3. Incidence, etiology, and outcome of pleural effusions in allogeneic hematopoietic stem cell transplantation.

    PubMed

    Modi, Dipenkumar; Jang, Hyejeong; Kim, Seongho; Deol, Abhinav; Ayash, Lois; Bhutani, Divaya; Lum, Lawrence G; Ratanatharathorn, Voravit; Manasa, Richard; Mellert, Kendra; Uberti, Joseph P

    2016-09-01

    Pleural effusion is a known entity in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT); however, the incidence, risk factors, and morbidity-mortality outcomes associated with pleural effusions remain unknown. We retrospectively evaluated pleural effusions in 618 consecutive adult patients who underwent allogeneic HSCT from January 2008 to December 2013 at our institution. Seventy one patients developed pleural effusion at a median of 40 days (range, 1 - 869) post-HSCT with the cumulative incidence of 9.9% (95% CI, 7.7 - 12.5%) at 1 year. Infectious etiology was commonly associated with pleural effusions followed by volume overload and serositis type chronic GVHD. In multivariate analysis, higher comorbidity index (P = 0.03) and active GVHD (P = 0.018) were found to be significant independent predictors for pleural effusion development. Higher comorbidity index, very high disease risk index, ≤7/8 HLA matching, and unrelated donor were associated with inferior overall survival (OS) (P < 0.03). More importantly, patients with pleural effusion were noted to have poor OS in comparison to patients without pleural effusion (P < 0.001). Overall, pleural effusion is a frequently occurring complication after allogeneic HSCT, adding to morbidity and mortality and hence, early identification is required. Am. J. Hematol. 91:E341-E347, 2016. © 2016 Wiley Periodicals, Inc. PMID:27238902

  4. 10 years of prophylaxis with nebulized liposomal amphotericin B and the changing epidemiology of Aspergillus spp. infection in lung transplantation.

    PubMed

    Peghin, Maddalena; Monforte, Victor; Martin-Gomez, Maria-Teresa; Ruiz-Camps, Isabel; Berastegui, Cristina; Saez, Berta; Riera, Jordi; Ussetti, Piedad; Solé, Juan; Gavaldá, Joan; Roman, Antonio

    2016-01-01

    The aim of this study was to assess the outcome and tolerability of prophylactic nebulized liposomal amphotericin B (n-LAB) in lung transplant recipients (LTR) and the changing epidemiology of Aspergillus spp. infection and colonization. We performed an observational study including consecutive LTR recipients (2003-2013) undergoing n-LAB prophylaxis lifetime. A total of 412 patients were included (mean postoperative follow-up 2.56 years; IQR 1.01-4.65). Fifty-three (12.8%) patients developed 59 Aspergillus spp. infections, and 22 invasive aspergillosis (overall incidence 5.3%). Since 2009, person-time incidence rates of Aspergillus spp. colonization and infection decreased (2003-2008, 0.19; 2009-2014, 0.09; P = 0.0007), but species with reduced susceptibility or resistance to amphotericin significantly increased (2003-2008, 38.1% vs 2009-2014, 58.1%; P = 0.039). Chronic lung allograft dysfunction (CLAD) was associated with Aspergillus spp. colonization and infection (HR 24.4, 95% CI 14.28-41.97; P = 0.00). Only 2.9% of patients presented adverse effects, and 1.7% required discontinuation. Long-term administration of prophylaxis with n-LAB has proved to be tolerable and can be used for preventing Aspergillus spp. infection in LTR. Over the last years, the incidence of Aspergillus spp. colonization and infection has decreased, but species with reduced amphotericin susceptibility or resistance are emerging. CLAD is associated with Aspergillus spp. colonization and infection. PMID:26339864

  5. Altering Transplantation Time to Avoid Periods of High Temperature Can Efficiently Reduce Bacterial Wilt Disease Incidence with Tomato.

    PubMed

    Wei, Zhong; Huang, Jian-Feng; Hu, Jie; Gu, Yi-An; Yang, Chun-Lan; Mei, Xin-Lan; Shen, Qi-Rong; Xu, Yang-Chun; Friman, Ville-Petri

    2015-01-01

    Tomato bacterial wilt caused by Ralstonia solanacearum bacterium is a severe problem in Southern China, where relatively high environmental temperatures commonly prevails during the crop seasons. Previous research has indicated that bacterial wilt disease incidence generally increases during the warm months of summer leading to reduced tomato yield. Moreover, the efficacy of bio-organic fertilizers (BOFs)-organic compost fortified with pathogen-suppressive bacteria-is often lost during the periods of high environmental temperatures. Here we studied if the disease incidence could be reduced and the BOF performance enhanced by simply preponing and postponing the traditional seedling transplantation times to avoid tomato plant development during periods of high environmental temperature. To this end, a continuous, two-year field experiment was conducted to evaluate the performance of BOF in two traditional (late-spring [LS] and early-autumn [EA]) and two alternative (early-spring [ES] and late-autumn [LA]) crop seasons. We found that changing the transplantation times reduced the mean disease incidence from 33.9% (LS) and 54.7% (EA) to 11.1% (ES) and 7.1% (LA), respectively. Reduction in disease incidence correlated with the reduction in R. Solanacearum pathogen density in the tomato plant rhizosphere and stem base. Applying BOF during alternative transplantation treatments improved biocontrol efficiency from 43.4% (LS) and 3.1% (EA) to 67.4% (ES) and 64.8% (LA). On average, the mean maximum air temperatures were positively correlated with the disease incidence, and negatively correlated with the BOF biocontrol efficacy over the crop seasons. Crucially, even though preponing the transplantation time reduced the tomato yield in general, it was still economically more profitable compared to LS season due to reduced crop losses and relatively higher market prices. Preponing and postponing traditional tomato transplantation times to cooler periods could thus offer simple

  6. Altering Transplantation Time to Avoid Periods of High Temperature Can Efficiently Reduce Bacterial Wilt Disease Incidence with Tomato

    PubMed Central

    Wei, Zhong; Huang, Jian-Feng; Hu, Jie; Gu, Yi-An; Yang, Chun-Lan; Mei, Xin-Lan; Shen, Qi-Rong; Xu, Yang-Chun; Friman, Ville-Petri

    2015-01-01

    Tomato bacterial wilt caused by Ralstonia solanacearum bacterium is a severe problem in Southern China, where relatively high environmental temperatures commonly prevails during the crop seasons. Previous research has indicated that bacterial wilt disease incidence generally increases during the warm months of summer leading to reduced tomato yield. Moreover, the efficacy of bio-organic fertilizers (BOFs)–organic compost fortified with pathogen-suppressive bacteria—is often lost during the periods of high environmental temperatures. Here we studied if the disease incidence could be reduced and the BOF performance enhanced by simply preponing and postponing the traditional seedling transplantation times to avoid tomato plant development during periods of high environmental temperature. To this end, a continuous, two-year field experiment was conducted to evaluate the performance of BOF in two traditional (late-spring [LS] and early-autumn [EA]) and two alternative (early-spring [ES] and late-autumn [LA]) crop seasons. We found that changing the transplantation times reduced the mean disease incidence from 33.9% (LS) and 54.7% (EA) to 11.1% (ES) and 7.1% (LA), respectively. Reduction in disease incidence correlated with the reduction in R. Solanacearum pathogen density in the tomato plant rhizosphere and stem base. Applying BOF during alternative transplantation treatments improved biocontrol efficiency from 43.4% (LS) and 3.1% (EA) to 67.4% (ES) and 64.8% (LA). On average, the mean maximum air temperatures were positively correlated with the disease incidence, and negatively correlated with the BOF biocontrol efficacy over the crop seasons. Crucially, even though preponing the transplantation time reduced the tomato yield in general, it was still economically more profitable compared to LS season due to reduced crop losses and relatively higher market prices. Preponing and postponing traditional tomato transplantation times to cooler periods could thus offer

  7. Familial aggregation of lung cancer in a high incidence area in China

    PubMed Central

    Jin, Y T; Xu, Y C; Yang, R D; Huang, C F; Xu, C W; He, X Z

    2005-01-01

    To investigate whether lung cancer clusters in families in a high incidence county of China, an analysis was conducted using data on domestic fuel history and tobacco use for family members of 740 deceased lung cancer probands and 740 controls (probands' spouses). Lung cancer prevalence was compared among first-degree relatives of probands and of controls, taking into account various factors using logistic regression and generalised estimating equations. First-degree relatives of probands, compared with those of controls, showed an excess risk of lung cancer (odds ratio (OR)=2.05, 95% confidence interval (CI): 1.68–2.53). Overall, female relatives of probands had a greater risk than did their male counterparts, and the risk was 2.90-fold for parents of probands as compared with parents of spouses. Female relatives of probands had 2.67-fold greater risk than female controls. Lung cancer risk was particularly marked among mothers (OR=3.78, 95% CI: 2.03–7.12). Having two or more affected relatives was associated with a 2.69–5.40-fold risk increase. The risk elevation was also found for other cancers overall. Results confirm previous findings of a genetic predisposition to lung cancer, and also imply that lung cancer may share a genetic background with other cancers. PMID:15756270

  8. Combined Lung-Kidney Transplantation: An Analysis of the UNOS/OPTN Database.

    PubMed

    Reich, Heidi J; Chan, Joshua L; Czer, Lawrence S C; Mirocha, James; Annamalai, Alagappan A; Cheng, Wen; Jordan, Stanley C; Chaux, George; Ramzy, Danny

    2015-10-01

    Poor outcomes after thoracic transplantation with concurrent renal dysfunction are well described: without transplantation or with thoracic-only transplantation, patients face unacceptably high mortality. Outcomes after combined lung-kidney transplantation (LKT) remain largely uninvestigated. The United Network for Organ Sharing/Organ Procurement and Transplantation Network database was queried to identify all LKTs, lung transplantations (LTs), and kidney transplantations (KTs) performed in the United States from 1995 to 2013. Survival was calculated using the Kaplan-Meier method and compared using log-rank tests or Cox regression models. Thirty-one LKTs were performed. Mean recipient age was 45.4 ± 13.5 years; 48.3 per cent were male. Retransplantation for graft failure was the leading indication for LT (n = 13) and the most common renal indication was calcineurin inhibitor nephrotoxicity (n = 11). Mean lung allocation score was 46.6 ± 14.4, mean creatinine was 3.7 ± 2.8 g/dL, and glomerular filtration rate was 23.1 (interquartile range 11.9, 38.3) mL/min/1.7 m(2), and 11 (35.5%) were dialysis dependent. Patient survival after LKT was 92.9 per cent, 71.0 per cent, and 71.0 per cent at one month, six months, and one year, with a median survival of 95.2 months. One- and five-year survival after LKT, 71.0 per cent and 59.9 per cent, were similar to LT (n = 23,913), 81.7 per cent and 51.4 per cent (P = 0.061 and 0.55), and inferior to KT (n = 175,269), 94.9 per cent and 82.8 per cent (P < 0.0001), respectively. Patient survival after LKT was similar to isolated LT, and these results suggest that LKT is a feasible therapeutic option for LT candidates with significant renal dysfunction. PMID:26463306

  9. Improved quality of life after lung transplantation in individuals with cystic fibrosis.

    PubMed

    Vermeulen, Karin M; van der Bij, Wim; Erasmus, Michiel E; Duiverman, Eric J; Koëter, Gerard H; TenVergert, Elisabeth M

    2004-05-01

    The aim of the present study was to assess the effect of lung transplantation (LgTX) on health-related quality of life (HRQL) in a group of patients with cystic fibrosis (CF), compared to patients with other diagnoses (non-CF). HRQL was assessed before transplantation in a group of 32 CF patients and 183 non-CF patients. After LgTX, we conducted a prospective longitudinal study among 10 CF patients and 35 non-CF patients who survived at least 31 months after LgTX. Measures were the Nottingham Health Profile (NHP), the State-Trait Anxiety Inventory (STAI), the Self-Rating Depression Scale (ZUNG), the Index of Well-Being (IWB), and the Karnofsky Performance Index. Patients in the CF group were younger, spent more days on the waiting list, and were more likely to be working or going to school than patients with other indications. Before transplantation, CF patients and non-CF patients experienced restrictions on almost all HRQL measures, compared to the general population. On the NHP dimensions of mobility and energy, CF patients had significantly better scores than non-CF patients. Between 1-4 months after transplantation, scores on the NHP, ZUNG, and Karnofsky performance indices improved, and STAI and IWB scores even occurred within the reference value in both groups. Significantly better scores in the CF group compared to the non-CF group were found on the NHP dimension of mobility 4 months after transplantation, and on the dimension of sleep 7 and 13 months after transplantation. Scores remained more or less stable over time in both groups. It may be concluded that patients in both groups experience major restrictions in HRQL before transplantation. However, pretransplant non-CF patients experience more restrictions than CF patients. After LgTX, both groups of patients showed substantial improvement in HRQL, and this improvement was maintained until 31 months after LgTX. PMID:15095325

  10. An Ecologic Analysis of County-Level PM2.5 Concentrations and Lung Cancer Incidence and Mortality

    PubMed Central

    Vinikoor-Imler, Lisa C.; Davis, J. Allen; Luben, Thomas J.

    2011-01-01

    Few studies have explored the relationship between PM2.5 and lung cancer incidence. Although results are mixed, some studies have demonstrated a positive relationship between PM2.5 and lung cancer mortality. Using an ecologic study design, we examined the county-level associations between PM2.5 concentrations (2002–2005) and lung cancer incidence and mortality in North Carolina (2002–2006). Positive trends were observed between PM2.5 concentrations and lung cancer incidence and mortality; however, the R2 for both were <0.10. The slopes for the relationship between PM2.5 and lung cancer incidence and mortality were 1.26 (95% CI 0.31, 2.21, p-value 0.01) and 0.73 (95% CI 0.09, 1.36, p-value 0.03) per 1 μg/m3 PM2.5, respectively. These associations were slightly strengthened with the inclusion of variables representing socioeconomic status and smoking. Although variability is high, thus reflecting the importance of tobacco smoking and other etiologic agents that influence lung cancer incidence and mortality besides PM2.5, a positive trend is observed between PM2.5 and lung cancer incidence and mortality. This suggests the possibility of an association between PM2.5 concentrations and lung cancer incidence and mortality. PMID:21776206

  11. Smoking, exposure to crocidolite, and the incidence of lung cancer and asbestosis.

    PubMed Central

    de Klerk, N H; Musk, A W; Armstrong, B K; Hobbs, M S

    1991-01-01

    In 1979 all former workers from the Wittenoom asbestos industry who could be traced to an address were sent a questionnaire to determine smoking history. Occupational exposure to crocidolite was known from employment records. Of 2928 questionnaires sent, satisfactory replies were received from 2400 men and 149 women. Eighty per cent of these had smoked at some time and 50% were still smoking. Since that time 40 cases of lung cancer and 66 cases of compensatable asbestosis have occurred in this cohort. The incidence of both lung cancer and asbestosis was greatest in those subjects with the highest levels of exposure to crocidolite and in ex-smokers. Statistical modelling of the joint effects of these exposures on the incidence of each disease indicated that crocidolite exposure multiplied the rates of lung cancer due to smoking and that smoking has no measurable effect on the rates of asbestosis. There was also some evidence that the incidence rate of lung cancer is falling with time. PMID:1648376

  12. A Human-Mouse Chimeric Model of Obliterative Bronchiolitis after Lung Transplantation

    PubMed Central

    Xue, Jianmin; Zhu, Xuehai; George, M. Patricia; Myerburg, Michael M.; Stoner, Michael W.; Pilewski, Joseph W.; Duncan, Steven R.

    2011-01-01

    Obliterative bronchiolitis is a frequent, morbid, and usually refractory complication of lung transplantation. Mechanistic study of obliterative bronchiolitis would be aided by development of a relevant model that uses human immune effector cells and airway targets. Our objective was to develop a murine chimera model that mimics obliterative bronchiolitis of lung allograft recipients in human airways in vivo. Human peripheral blood mononuclear cells were adoptively transferred to immunodeficient mice lacking activity of T, B, and NK cells, with and without concurrent transplantations of human small airways dissected from allogeneic cadaveric lungs. Chimerism with human T cells occurred in the majority of recipient animals. The chimeric T cells became highly activated, rapidly infiltrated into the small human airway grafts, and caused obliterative bronchiolitis. In contrast, airways implanted into control mice that did not also receive human peripheral blood mononuclear cell transfers remained intact. In vitro proliferation assays indicated that the chimeric T cells had enhanced specific proliferative responses to donor airway alloantigens. This model confirms the critical role of T cells in development of obliterative bronchiolitis among human lung allograft recipients and provides a novel and easily implemented mechanism for detailed, reductionist in vivo studies of human T-cell responses to allogeneic human small airways. PMID:21801868

  13. Functional status and quality of life in patients surviving 10 years after lung transplantation.

    PubMed

    Rutherford, Robert M; Fisher, Andrew J; Hilton, Colin; Forty, Jonathan; Hasan, Asif; Gould, Francis K; Dark, John H; Corris, Paul A

    2005-05-01

    Although many lung allograft recipients achieve long-term survival, there is a lack of published data regarding these patients' functional status and quality of life (QoL). We evaluated all 10-year survivors at our institution and, utilizing the SF-36 questionnaire, compared their QoL to population normative and chronic illness data. Twenty-eight (29%) of 96 patients survived > or =10 years following 11 single, 6 bilateral and 11 heart-lung procedures. At the most recent evaluation, median FEV(1) in single and double lung recipients was predicted to be 54% and 74%, respectively. Five (18%) patients had BOS score 0, 13 (46%) BOS 1, 5 (18%) BOS 2 and 5 (18%) BOS 3 and median time to BOS was 7 years. Four (14%) patients required renal replacement therapy. Three patients (11%) developed symptomatic osteoporosis, 2 (7%) post-transplant lymphoma and 1 (4%) an ischaemic stroke. Scores for physical function, role-physical/emotional and general health, but not mental health and bodily pain, were significantly lower compared to normative and chronic illness data. Energy and social-function scores were significantly lower than normative data alone. Long-term survival after lung transplantation is characterized by an absence or delayed development of BOS, low iatrogenic morbidity and preserved mental, but reduced physical health status. PMID:15816892

  14. The need for a new animal model for chronic rejection after lung transplantation.

    PubMed

    De Vleeschauwer, S; Vanaudenaerde, B; Vos, R; Meers, C; Wauters, S; Dupont, L; Van Raemdonck, D; Verleden, G

    2011-11-01

    The single most important cause of late mortality after lung transplantation is obliterative bronchiolitis (OB), clinically characterized by a decrease in lung function and morphologically by characteristic changes. Recently, new insights into its pathogenesis have been acquired: risk factors have been identified and the use of azithromycin showed a dichotomy with at least 2 different phenotypes of bronchiolitis obliterans syndrome (BOS). It is clear that a good animal model is indispensable to further dissect and unravel the pathogenesis of BOS. Many animal models have been developed to study BOS but, so far, none of these models truly mimics the human situation. Looking at the definition of BOS, a good animal model implies histological OB lesions, possibility to measure lung function, and airway inflammation. This review sought to discuss, including pros and cons, all potential animal models that have been developed to study OB/BOS. It has become clear that a new animal model is needed; recent developments using an orthotopic mouse lung transplantation model may offer the answer because it mimics the human situation. The genetic variants among this species may open new perspectives for research into the pathogenesis of OB/BOS. PMID:22099823

  15. Effect of a single injection of high-dose FK506 on lung transplantation in rats.

    PubMed

    Sano, Y; Maruyama, S; Aoe, M; Date, H; Shimizu, N

    1996-01-01

    Orthotopic left lung grafts from Brown Norway (BN) donors were transplanted to Lewis (LEW) rat recipients which had been treated with a single dose of FK506 10mg/kg body weight intramuscularly on postoperative day 3. Although the lungs were rejected with a median survival time of 7 days, with a range of 6-8 days in the untreated controls, maximum survival was prolonged to 60 days. The major adverse effects of this therapy were reduction of feeding, loss of body weight, and diarrhea. One of the 7 rats died on the 21st postoperative day due to anorexia. The effects of this therapy were investigated by histopathological examination and flow cytometric analysis using monoclonal antibodies against rat lymphocytes: OX-39 (anti-interleukin 2 receptor (IL-2R)) and OX-6 (anti-class II MHC). Histopathologically, the lung allografts showed mild perivascular and peribronchiolar cuffs of mononuclear cells, while marked reduction of the thymic medulla with FK506 treatment was also observed. Flow cytometric analysis of the transplanted lung showed no significant changes. Regarding the thymus, the percentages of positive cells labeled with OX-39 and OX-6 were significantly suppressed after this treatment. In the spleen, the number of OX-6-positive cells significantly decreased. The results using this therapy thus suggest that the suppression of IL-2R and MHC class II expression was systemically maintained for a long time. PMID:9017963

  16. Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy

    PubMed Central

    Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

    2016-01-01

    Abstract Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three‐dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity‐modulated radiotherapy appears to be the appropriate treatment in heart‐transplanted oncologic patients. PMID:27148425

  17. Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy.

    PubMed

    Giugliano, Francesca M; Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

    2016-04-26

    Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three-dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity-modulated radiotherapy appears to be the appropriate treatment in heart-transplanted oncologic patients. PMID:27148425

  18. Impact of Early Blood Transfusion After Kidney Transplantation on the Incidence of Donor-Specific Anti-HLA Antibodies.

    PubMed

    Ferrandiz, I; Congy-Jolivet, N; Del Bello, A; Debiol, B; Trébern-Launay, K; Esposito, L; Milongo, D; Dörr, G; Rostaing, L; Kamar, N

    2016-09-01

    Little is known about the impact of posttransplant blood transfusion on the sensitization of anti-HLA antibodies and the formation of donor-specific antibodies (DSAs). The aims of our study were to determine the 1-year incidence of DSAs (assessed using a solid-phase assay) and antibody-mediated rejection (AMR) in kidney transplant patients who had or had not received a blood transfusion during the first year after transplantation. Included were 390 non-HLA-sensitized patients who had received an ABO-compatible kidney transplant and had not previously or simultaneously received a nonkidney transplant. Overall, 64% of patients received a red blood cell transfusion within the first year after transplantation, most within the first month. The overall 1-year incidence of DSAs was significantly higher in patients that had undergone transfusion (7.2% vs. 0.7% in patients with no transfusion, p < 0.0001). AMR occurred more often in the transfusion group (n = 15, 6%) compared with the nontransfusion group (n = 2, 1.4%; p = 0.04). Blood transfusion was an independent predictive factor for de novo DSA formation but not for AMR. Patients who had a transfusion and developed DSAs were more often treated with cyclosporin A (n = 10, 55.5%) rather than tacrolimus (n = 45, 19.4%; p = 0.0001). In conclusion, early posttransplant blood transfusion may increase immunological risk, especially in underimmunosuppressed patients. PMID:26998676

  19. Animal models of ex vivo lung perfusion as a platform for transplantation research

    PubMed Central

    Nelson, Kevin; Bobba, Christopher; Ghadiali, Samir; Jr, Don Hayes; Black, Sylvester M; Whitson, Bryan A

    2014-01-01

    Ex vivo lung perfusion (EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time, EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result, this technique provides unique advantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript, we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine. PMID:24977117

  20. Animal models of ex vivo lung perfusion as a platform for transplantation research.

    PubMed

    Nelson, Kevin; Bobba, Christopher; Ghadiali, Samir; Hayes, Don; Black, Sylvester M; Whitson, Bryan A

    2014-05-20

    Ex vivo lung perfusion (EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time, EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result, this technique provides unique advantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript, we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine. PMID:24977117

  1. Incidence of A-V Fistulas after Renal Biopsy of Native and Transplanted Kidney - Two Centers Experience

    PubMed Central

    Lubomirova, Mila; Krasteva, Rumiana; Bogov, Boris; Paskalev, Emil

    2015-01-01

    AIM: The aim of the study is to make a retrospective analysis of the incidence of AV fistulas after renal biopsy (RB) of native and transplanted kidney. MATERIALS AND METHODS: Five hundred and sixteen (516) RB were analyzed. One hundred twenty nine (129) were native kidneys RB performed in Clinic of Nephrology (CN), 190 were performed in Clinic of Nephrology and transplantation (CNT) and 197 were transplanted kidney biopsies from the same clinic. Biopsy technique type Gun with needle 14G, 16 and 18 G was used in CN, CNT used the same technique with needles 16G. Doppler ultrasound was made for A-V fistulas diagnosis. RESULTS: The A-V fistulas incidence was 0.8%. The frequency of A-V fistulas registered in CN was significantly higher than that registered in CNT (2.3% vs. 0.5%, p < 0.01). Biopsies performed by 14 G needles provide a higher percentage of A-V fistulas compared to those done by 16 G. (3.3% vs. 2.4%, p < 0.5). The frequency of the A-V fistulas in native and transplanted kidneys in CNT was similar (0.5% vs. 0.5%, p > 0.05). CONCLUSION: The A-V fistulas incidence is very low. The needle thickness is an important factor relevant to the risk of occurrence of A-V fistulas.

  2. Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans

    PubMed Central

    David, Sean P.; Wang, Ange; Kapphahn, Kristopher; Hedlin, Haley; Desai, Manisha; Henderson, Michael; Yang, Lingyao; Walsh, Kyle M.; Schwartz, Ann G.; Wiencke, John K.; Spitz, Margaret R.; Wenzlaff, Angela S.; Wrensch, Margaret R.; Eaton, Charles B.; Furberg, Helena; Mark Brown, W.; Goldstein, Benjamin A.; Assimes, Themistocles; Tang, Hua; Kooperberg, Charles L.; Quesenberry, Charles P.; Tindle, Hilary; Patel, Manali I.; Amos, Christopher I.; Bergen, Andrew W.; Swan, Gary E.; Stefanick, Marcia L.

    2016-01-01

    Background Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene–environment interactions is not well understood. Methods We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case–control study of African-American females and males (1078 lung cancer cases and 822 controls). Findings Nine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09 × 10− 5). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD = − 0.017, p = 0.0061, corrected p = 0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans. Interpretation These results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers. PMID:26981579

  3. Laparoscopic Fundoplication with or Without Pyloroplasty in Patients with Gastroesophageal Reflux Disease After Lung Transplantation: How I Do It

    PubMed Central

    Davis, Christopher S.; Jellish, W. Scott

    2011-01-01

    Introduction Several studies have confirmed that gastroesophageal reflux disease (GERD) in lung transplant patients is a risk factor for the development and progression of bronchiolitis obliterans syndrome (BOS), a form of rejection after lung transplantation. Moreover, numerous reports indicate that surgical correction of GERD may control the decline in lung function characteristic of BOS. Although laparoscopic fundoplication is an accepted treatment option for these patients with GERD, the surgical technique, which often includes a laparoscopic pyloroplasty, has not been standardized. Methods The purpose of this article is to describe a step-by-step approach to the laparoscopic treatment of GERD in lung transplant patients. We also address specific technical concerns encountered in the surgical management of this high-risk patient population; we provide data on the safety of this operation; and we illustrate the evidence-based rationale for each technical step of the procedure. PMID:20499201

  4. Bias From Using Occupational Smoking Prevalence to Adjust Occupational Incidence Cohort Lung Cancer Mortality Rates

    PubMed Central

    Roth, H. Daniel

    2015-01-01

    Objective: To describe how smoking correction factors based on comparing worker smoking prevalence with population smoking prevalence are biased if applied to an occupational incidence cohort. Methods: Relative rates of smoking for shorter-tenure workers derived from occupational cohort lung cancer studies were applied to incidence and prevalence population tenure distributions to calculate relative smoking estimates. Results: High smoking rates in short-tenure workers have little effect on prevalent worker rates (relative smoking estimates, 1.04 and 1.02) and much larger effect in occupational incidence populations (relative smoking estimates, 1.58 and 1.21), which have a much higher proportion of short tenure-workers. Conclusions: Smoking correction estimates derived from surveys of smoking habits in prevalent workers may introduce bias when applied to incidence workers because of very different proportions of short-tenure workers (length-time biased sampling). PMID:25427172

  5. A computer simulation model of the cost-effectiveness of routine Staphylococcus aureus screening and decolonization among lung and heart-lung transplant recipients.

    PubMed

    Clancy, C J; Bartsch, S M; Nguyen, M H; Stuckey, D R; Shields, R K; Lee, B Y

    2014-06-01

    Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations. PMID:24500598

  6. Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic Transplantation – A Report from CIBMTR

    PubMed Central

    Arai, Sally; Arora, Mukta; Wang, Tao; Spellman, Stephen R.; He, Wensheng; Couriel, Daniel R.; Urbano-Ispizua, Alvaro; Cutler, Corey S.; Bacigalupo, Andrea A.; Battiwalla, Minoo; Flowers, Mary E.; Juckett, Mark B.; Lee, Stephanie J.; Loren, Alison W.; Klumpp, Thomas R.; Prockup, Susan E.; Ringdén, Olle T.H.; Savani, Bipin N.; Socié, Gérard; Schultz, Kirk R.; Spitzer, Thomas; Teshima, Takanori; Bredeson, Christopher N.; Jacobsohn, David A.; Hayashi, Robert J.; Drobyski, William R.; Frangoul, Haydar A.; Akpek, Görgün; Ho, Vincent T.; Lewis, Victor A.; Gale, Robert Peter; DSc(hon); Koreth, John; Chao, Nelson J.; Aljurf, Mahmoud D.; Cooper, Brenda W.; Laughlin, Mary J.; Hsu, Jack W.; Hematti, Peiman; Verdonck, Leo F.; Solh, Melhelm M.; Norkin, Maxim; Reddy, Vijay; Martino, Rodrigo; Gadalla, Shahinaz; Goldberg, Jenna D.; McCarthy, Philip L.; Pérez-Simón, José A.; Khera, Nandita; Lewis, Ian D.; Atsuta, Yoshiko; Olsson, Richard F.; Saber, Wael; Waller, Edmund K.; Blaise, Didier; Pidala, Joseph A.; Martin, Paul J.; Satwani, Prakash; Bornhäuser, Martin; Inamoto, Yoshihiro; Weisdorf, Daniel J.; Horowitz, Mary M.; Pavletic, Steven Z.

    2015-01-01

    Although transplant practices have changed over the last decades there is no information on trends in incidence and outcome of cGVHD over time. This study utilized the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe the time trends for cGVHD incidence, non-relapse mortality, and the risk factors for cGVHD. The 12-year period was divided into three intervals: 1995-1999, 2000-2003, 2004-2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndrome. In the multivariate analysis, the incidence of cGVHD was shown to be increased in more recent years (odds ratio= 1.19, p<0.0001) and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, non-relapse mortality has decreased over time, but at 5-years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. PMID:25445023

  7. Ochroconis gallopavum infection in a lung transplant recipient: report of a case.

    PubMed

    Brokalaki, E I; Sommerwerck, U; von Heinegg, E H; Hillen, U

    2012-11-01

    Disseminated phaeohyphomycoses are rare infections caused by dematiaceous fungi. Ochroconis gallopavum is a neurotropic dematiaceous mold responsible for life-threatening respiratory and central nervous system infections in domestic poultry and in immunologically compromised humans. The world literature describes only 13 previous O gallopavum infections in solid organ transplant recipients. We report herein an O gallopavum phaeohyphomycosis with involvement of skin in a transplant recipient. A 69-year-old white man with a history of bilateral lung transplantation 6 years ago presented with acute onset of severe respiratory distress. Chest X-ray showed no evidence of pneumonia. Lung function showed bronchiolitis obliterans syndrome. Excision biopsy was performed because of a suspected pigmented basal cell carcinoma. Histopathology revealed dermal granulomatous dermatitis, focally suppurative, dominated by epitheloid cells with brownish round fungi. Further microbiological work-up of the biopsy specimen subsequently revealed O gallopavum as the causative organism. No brain involvement was observed. Antimycotic therapy with voriconazole 200 mg twice a day was immediately initiated and the patient was treated for 3 months. Additional intravenous therapy with tobramycin and imipenem was started upon detection of Enterobacter clocae and Enterococci in the sputum. The patient recovered during the next few weeks and was discharged on day 26. PMID:23146522

  8. Recurrence of pulmonary alveolar proteinosis after bilateral lung transplantation in a patient with a nonsense mutation in CSF2RB.

    PubMed

    Takaki, Masahiro; Tanaka, Takeshi; Komohara, Yoshihiro; Tsuchihashi, Yoshiko; Mori, Daisuke; Hayashi, Kentaro; Fukuoka, Junya; Yamasaki, Naoya; Nagayasu, Takeshi; Ariyoshi, Koya; Morimoto, Konosuke; Nakata, Koh

    2016-01-01

    Hereditary pulmonary alveolar proteinosis (PAP) caused by mutations in CSF2RA or CSF2RB, which encode GM-CSF receptor α and β respectively, is a rare disease. Although some experimental therapeutic strategies have been proposed, no clinical evidence has yet been reported. We herein describe the clinical course and recurrence of hereditary PAP after lung transplantation. A 36-year-old woman developed PAP of unknown etiology. She underwent bilateral lung transplantation from living donors at the age of 42 years because of severe respiratory failure complicated by pulmonary fibrosis. However, PAP recurred after 9 months, and we found that donor-origin alveolar macrophages had been almost completely replaced with recipient-origin macrophages. We performed a genetic analysis and identified a point deletion in the CSF2RB gene that caused a GM-CSF receptor-mediated signaling defect. PAP progressed with fibrosis in both transplanted lungs, and the patient died of respiratory failure 5 years after the lung transplantation. Distinct from recent reports on pulmonary macrophage transplantation in mice, this case suggests that human alveolar macrophages might not maintain their population only by self-renewal but may depend on a supply of precursor cells from the circulation. Bone marrow transplantation should be considered for treatment of severe PAP with GM-CSF receptor gene deficiency. PMID:27595063

  9. Lung cancer: is the increasing incidence due to radioactive polonium in cigarettes

    SciTech Connect

    Marmorstein, J.

    1986-02-01

    This paper presents clinical, experimental, and epidemiologic evidence to help explain the rapidly increasing incidence of primary lung cancer, with recently observed reversal in leading cell type from squamous cell to adenocarcinoma. It postulates that this may be due to changes in modern cigarettes, with or without filters, which allow inhalation of increased amounts of radioactive lead and polonium and decreased amounts of benzopyrene. This hypothesis is based upon measurements of increased concentrations of radioactive polonium in the lungs of cigarette smokers, in modern tobaccos grown since 1950, and in high-phosphate fertilizers used for tobacco farming in industrialized countries. Critical support for this thesis is based upon experimental animal studies in which lung cancers that resemble adenocarcinomas are induced with as little as 15 rads of radioactive polonium, equal to one fifth the dosage inhaled by cigarette smokers who average two packs a day during a 25-year period.

  10. Radiation and smoking effects on lung cancer incidence among atomic bomb survivors.

    PubMed

    Furukawa, Kyoji; Preston, Dale L; Lönn, Stefan; Funamoto, Sachiyo; Yonehara, Shuji; Matsuo, Takeshi; Egawa, Hiromi; Tokuoka, Shoji; Ozasa, Kotaro; Kasagi, Fumiyoshi; Kodama, Kazunori; Mabuchi, Kiyohiko

    2010-07-01

    While radiation increases the risk of lung cancer among members of the Life Span Study (LSS) cohort of atomic bomb survivors, there are still important questions about the nature of its interaction with smoking, the predominant cause of lung cancer. Among 105,404 LSS subjects, 1,803 primary lung cancer incident cases were identified for the period 1958-1999. Individual smoking history information and the latest radiation dose estimates were used to investigate the joint effects of radiation and smoking on lung cancer rates using Poisson grouped survival regression methods. Relative to never-smokers, lung cancer risks increased with the amount and duration of smoking and decreased with time since quitting smoking at any level of radiation exposure. Models assuming generalized interactions of smoking and radiation fit markedly better than simple additive or multiplicative interaction models. The joint effect appeared to be super-multiplicative for light/moderate smokers, with a rapid increase in excess risk with smoking intensity up to about 10 cigarettes per day, but additive or sub-additive for heavy smokers smoking a pack or more per day, with little indication of any radiation-associated excess risk. The gender-averaged excess relative risk per Gy of lung cancer (at age 70 after radiation exposure at 30) was estimated as 0.59 (95% confidence interval: 0.31-1.00) for nonsmokers with a female : male ratio of 3.1. About one-third of the lung cancer cases in this cohort were estimated to be attributable to smoking while about 7% were associated with radiation. The joint effect of smoking and radiation on lung cancer in the LSS is dependent on smoking intensity and is best described by the generalized interaction model rather than a simple additive or multiplicative model. PMID:20681801

  11. The 'euthyroid sick syndrome': incidence, risk factors and prognostic value soon after allogeneic bone marrow transplantation.

    PubMed

    Vexiau, P; Perez-Castiglioni, P; Socié, G; Devergie, A; Toubert, M E; Aractingi, S; Gluckman, E

    1993-12-01

    We studied the incidence of thyroid function abnormalities observed soon after allogeneic bone marrow transplantations (BMT) and their predictive value on the overall prognosis. Free serum thyroxine, free serum triiodothyronine, total serum reverse triiodothyronine and serum thyrotropin levels were systematically measured in 78 patients before and 3 months after BMT. 41 (52%) had normal hormone levels and 37 (48%) had abnormal ones, among whom four (5%) had peripheral compensated hypothyroidism and 33 (43%) were described as having 'euthyroid sick syndrome' (low thyroxine state, or low T3 syndrome). Two factors strongly influenced the appearance of thyroid abnormalities: steroid dose at the time of thyroid function testing, and age (< or = 16 years/ > 16 years). Among the younger patients, 21 had no thyroid abnormalities, while five did. Among the older patients, 20 had no thyroid abnormalities, while 32 did (P < 0.001). The occurrence of thyroid abnormalities seemed to influence survival strongly, since the 30-month projected survival time was 83% for patients without abnormalities whereas it was 49% for patients with an abnormal profile (P < 0.001). In conclusion, evidence obtained among our population reveals that euthyroid sick syndrome indicates a poor prognosis and that it is very important to monitor thyroid hormone levels (particularly free hormones) soon after allogeneic BMT and regularly thereafter. PMID:7918043

  12. The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR® analysis

    PubMed Central

    Williams, Kirsten M.; Ahn, Kwang Woo; Chen, Min; Aljurf, Mahmoud D.; Agwu, Allison L.; Chen, Allen R.; Walsh, Thomas J.; Szabolcs, Paul; Boeckh, Michael J.; Auletta, Jeffrey J.; Lindemans, Caroline A.; Zanis-Neto, Jose; Malvezzi, Mariester; Lister, John; de Toledo Codina, Jose Sanchez; Sackey, Kwesi; Holter Chakrabarty, Jennifer L.; Ljungman, Per; Wingard, John R.; Seftel, Matthew D.; Seo, Sachiko; Hale, Gregory A.; Wirk, Baldeep; Smith, Marilyn S.; Savani, Bipin N.; Lazarus, Hillard M.; Marks, David I.; Ustun, Celalettin; Abdel-Azim, Hisham; Dvorak, Christopher C.; Szer, Jeffrey; Storek, Jan; Yong, Agnes; Riches, Marcie R.

    2015-01-01

    Pneumocystis jiroveci pneumonia (PJP) is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Little is known about PJP infections after HSCT because of the rarity of disease given routine prophylaxis. We report the results of a CIBMTR study evaluating the incidence, timing, prophylaxis agents, risk factors, and mortality of PJP after autologous (auto) and allogeneic (allo) HSCT. Between 1995 and 2005, 0.63% allo recipients and 0.28% auto recipients of first HSCT developed PJP. Cases occurred as early as 30 days to beyond a year after allo HSCT. A nested case cohort analysis with supplemental data (n=68 allo cases, n=111 allo controls) revealed that risk factors for PJP infection included lymphopenia and mismatch after HSCT. After allo or auto HSCT, overall survival was significantly poorer among cases vs. controls (p=0.0004). After controlling for significant variables, proportional hazards model revealed that PJP cases were 6.87 times more likely to die vs. matched controls (p<0.0001). We conclude PJP infection is rare after HSCT but is associated with high mortality. Factors associated with GVHD and with poor immune reconstitution are among the risk factors for PJP and suggest that protracted prophylaxis for PJP in high-risk HSCT recipients may improve outcomes. PMID:26726945

  13. Fatal Scopulariopsis infection in a lung transplant recipient: lessons of organ procurement.

    PubMed

    Shaver, C M; Castilho, J L; Cohen, D N; Grogan, E L; Miller, G G; Dummer, J S; Gray, J N; Lambright, E S; Loyd, J E; Robbins, I M

    2014-12-01

    Seventeen days after double lung transplantation, a 56-year-old patient with idiopathic pulmonary fibrosis developed respiratory distress. Imaging revealed bilateral pulmonary infiltrates with pleural effusions and physical examination demonstrated sternal instability. Broad-spectrum antibacterial and antifungal therapy was initiated and bilateral thoracotomy tubes were placed. Both right and left pleural cultures grew a mold subsequently identified as Scopulariopsis brumptii. The patient underwent pleural irrigation and sternal debridement three times but pleural and wound cultures continued to grow S. brumptii. Despite treatment with five antifungal agents, the patient succumbed to his illness 67 days after transplantation. Autopsy confirmed the presence of markedly invasive fungal disease and pleural rind formation. The patient's organ donor had received bilateral thoracostomy tubes during resuscitation in a wilderness location. There were no visible pleural abnormalities at the time of transplantation. However, the patient's clinical course and the location of the infection, in addition to the lack of similar infection in other organ recipients, strongly suggest that Scopulariopsis was introduced into the pleural space during prehospital placement of thoracostomy tubes. This case of lethal infection transmitted through transplantation highlights the unique risk of using organs from donors who are resuscitated in an outdoor location. PMID:25376207

  14. Lung metastasis of fatty hepatocellular carcinoma after liver transplant: a case report.

    PubMed

    Tepeoğlu, Merih; Özdemir, B Handan; Ok Atılgan, Alev; Akdur, Aydıncan; Haberal, Mehmet

    2014-03-01

    Hepatocellular carcinoma with prominent fatty change is rare, and to date only a few cases have been reported. In this article, we present a 57-yearold woman who underwent a liver transplant for hepatocellular carcinoma. Ten months after liver transplant, she presented with a persistent cough. Computed tomography of the chest was performed, revealing a solid lung mass that measured 1 × 0.9 cm in the right inferior lobe. Right inferior lobectomy was performed, and the final diagnosis was noted as hepatocellular carcinoma with prominent fatty change. Fatty change was extensive in the tumor; therefore, lipoid pneumonia was the first condition that was considered in the differential diagnosis during examination of the lobectomy material. For the differential diagnosis, the immunohistochemistry panel was studied to show the hepatocellular nature of the tumor. Although metastasis of hepatocellular carcinoma to the lungs is expected, hepatocellular carcinoma with prominent fatty change can cause diagnostic difficulties, such as lipoid pneumonia, especially in small lung biopsies. PMID:24635803

  15. Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation.

    PubMed

    Porteous, Mary K; Rivera-Lebron, Belinda N; Kreider, Maryl; Lee, James; Kawut, Steven M

    2016-03-01

    Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4-93.3) in 6-minute walk distance ([Formula: see text]). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0-21.1; [Formula: see text]). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1-29.5; [Formula: see text]). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis. PMID:27076905

  16. Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation

    PubMed Central

    Rivera-Lebron, Belinda N.; Kreider, Maryl; Lee, James; Kawut, Steven M.

    2016-01-01

    Abstract Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4–93.3) in 6-minute walk distance (P=0.02). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0–21.1; P<0.001). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1–29.5; P=0.006). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis. PMID:27076905

  17. Ex Vivo Adenoviral Vector Gene Delivery Results in Decreased Vector-associated Inflammation Pre- and Post–lung Transplantation in the Pig

    PubMed Central

    Yeung, Jonathan C; Wagnetz, Dirk; Cypel, Marcelo; Rubacha, Matthew; Koike, Terumoto; Chun, Yi-Min; Hu, Jim; Waddell, Thomas K; Hwang, David M; Liu, Mingyao; Keshavjee, Shaf

    2012-01-01

    Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function. PMID:22453765

  18. The incidence of autoimmune hemolytic anemia in pediatric hematopoietic stem cell recipients post-first and post-second hematopoietic stem cell transplant.

    PubMed

    Ahmed, Ibrahim; Teruya, Jun; Murray-Krezan, Cristina; Krance, Robert

    2015-06-01

    The reported incidence of post-allogeneic HSCT AIHA was between 4.4% and 6% following a single transplant. Cord blood transplantation, T-cell depletion, and chronic GvHD are significantly associated with post-transplant AIHA. During an 11-yr period, data for 500 pediatric HSCT recipients were eligible for evaluation of the incidence of AIHA post-first and post-second transplants. Demographic, transplant, and post-transplant-related variables were analyzed. Twelve of 500 (2.4%) recipients at a median of 273 days and seven of 72 (9.7%) recipients at a median of 157 days developed AIHA post-first and post-second HSCT, respectively. Post-first HSCT, none of the MRD recipients developed AIHA (0/175 MRD vs. 12/325 other donors, p = 0.04). Four of 12 required a second HSCT to control the AIHA. After the second HSCT, MUD was significantly associated with the development of AIHA. No other variables were associated with the post-second transplant AIHA. The incidence of AIHA post-first and post-second HSCT was less than the reported. The increased incidence of AIHA among recipients of second HSCT is most likely due to the profound immune dysregulation. A much larger, prospective study would be needed to evaluate the incidence, complications, and management of post-transplant AIHA. PMID:25809012

  19. Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts.

    PubMed

    Lama, Vibha N; Smith, Lisa; Badri, Linda; Flint, Andrew; Andrei, Adin-Cristian; Murray, Susan; Wang, Zhuo; Liao, Hui; Toews, Galen B; Krebsbach, Paul H; Peters-Golden, Marc; Pinsky, David J; Martinez, Fernando J; Thannickal, Victor J

    2007-04-01

    The origin and turnover of connective tissue cells in adult human organs, including the lung, are not well understood. Here, studies of cells derived from human lung allografts demonstrate the presence of a multipotent mesenchymal cell population, which is locally resident in the human adult lung and has extended life span in vivo. Examination of plastic-adherent cell populations in bronchoalveolar lavage samples obtained from 76 human lung transplant recipients revealed clonal proliferation of fibroblast-like cells in 62% (106 of 172) of samples. Immunophenotyping of these isolated cells demonstrated expression of vimentin and prolyl-4-hydroxylase, indicating a mesenchymal phenotype. Multiparametric flow cytometric analyses revealed expression of cell-surface proteins, CD73, CD90, and CD105, commonly found on mesenchymal stem cells (MSCs). Hematopoietic lineage markers CD14, CD34, and CD45 were absent. Multipotency of these cells was demonstrated by their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. Cytogenetic analysis of cells from 7 sex-mismatched lung transplant recipients harvested up to 11 years after transplant revealed that 97.2% +/- 2.1% expressed the sex genotype of the donor. The presence of MSCs of donor sex identity in lung allografts even years after transplantation provides what we believe to be the first evidence for connective tissue cell progenitors that reside locally within a postnatal, nonhematopoietic organ. PMID:17347686

  20. Factors related to the incidence and severity of cyclosporin-induced gingival overgrowth in transplant patients. A longitudinal study.

    PubMed

    Somacarrera, M L; Hernández, G; Acero, J; Moskow, B S

    1994-07-01

    A longitudinal study was conducted during the first 6 months following transplant surgery in 100 heart, liver, or kidney transplant patients to assess the incidence and severity of cyclosporin-induced gingival overgrowth, as well as the most important associated factors. Gingival overgrowth, plaque, and gingivitis indices, in addition to cyclosporin blood concentration, were assessed monthly. Statistical analysis was applied to evaluate the relationship between gingival overgrowth and other study variables and to test the influence of age, sex, time, and transplant type. Forty-three percent (43%) of the patients developed gingival overgrowth. Gingival overgrowth increased significantly during the study, while plaque and gingivitis, subject to an oral hygiene training and motivation program, decreased significantly. The findings from this study would suggest that the basic factor influencing gingival overgrowth is cyclosporin blood concentration, followed by plaque/gingivitis level. The significant differences observed among transplant types, as well as among age groups, might be attributed to the differences in cyclosporin concentrations. An oral hygiene program prior to the transplant surgery is recommended. PMID:7608843

  1. Candida albicans pancreatitis in a child with cystic fibrosis post lung transplantation.

    PubMed

    Hammer, Mark M; Zhang, Lingxin; Stoll, Janis M; Sheybani, Elizabeth F

    2016-04-01

    We present a case of Candida albicans infection of a previously intact pancreas in a child with cystic fibrosis status post lung transplantation. Although Candida superinfection in necrotizing pancreatitis is not uncommon, this is a unique case of Candida infection of non-necrotic pancreatic parenchyma. This case presented a diagnostic dilemma for radiologists because it appeared virtually identical to acute interstitial edematous pancreatitis on imaging. Ultimately, endoscopic US-based biopsy was pursued for diagnosis. Although difficult to treat and compounded by the immunocompromised status of the child, the pancreatic infection improved with antifungal therapy. PMID:26546567

  2. [Effect of acetylsalicylic acid on immunologically induced morphologic changes after experimental lung transplantation (light and electron microscopic study)].

    PubMed

    Hoyer, J; Garbe, L; Sicardi, F; Noirclerc, M

    1976-01-01

    In 3 comparing series the behavior of platelets after experimental lung transplantation was examined in 33 dogs. After allogenic transplantations (21 animals) the ultrastructural findings were pathologic changes of the platelets, such as hyperaggregability with irreversible aggregation prevailing, as well as capillary wall alterations. X-rays showed considerable reduction of functioning parenchyma. Since these findings were absent in animals which underwent merely pulmonary re-implantation (4 animals) and can be considered a controll group, the authors conclude that these alterations are caused by mainly immunologic reactions. Acetylsalicylic acid given to animals with grafted lungs significantly inhibited is specific and certainly immuneinduced pathologic development. Absolutely necessary, therefore, appears the application of such aggregation inhibitor as additional treatment in lung transplantations. PMID:793217

  3. Incidence of lung cancer by histological type among asbestos cement workers in Denmark.

    PubMed Central

    Raffn, E; Lynge, E; Korsgaard, B

    1993-01-01

    OBJECTIVE--A significant twofold increased risk of lung cancer was found among 8000 men employed in the Danish asbestos cement industry between 1928 and 1984. The histological pattern of 104 lung cancer cases was studied with the aim of evaluating a relation between specific morphological types, duration of employment, and time since first employment. METHODS--Age, sex, and calendar time specific incidence of morphological subtypes of lung cancer (adenocarcinoma, squamous cell carcinoma, anaplastic carcinoma, and unspecified malignant tumour) for all Danish men were computed from 1943 to 1984, from data routinely collected by the Danish Cancer Registry. Person-years of observation were counted from 15 years after the date of first employment until date of diagnosis of cancer, death, emigration, or the end of follow up on 31 December 1984. Expected numbers of cases were computed by applying person-years at risk to the appropriate incidence rates. Observed numbers were distributed accordingly and the relative risk calculated. RESULTS--The relative risk for adenocarcinoma was 3.31 (observed (O) 24, expected (E) 7.26), for squamous cell carcinoma 1.67 (O, 37, E, 22.12), for anaplastic carcinoma 1.58 (O, 23, E, 14.53), and for unspecified malignant tumour 1.57 (O, 18, E, 11.46). An increased risk by duration of employment and time since first employment was most pronounced for adenocarcinoma. CONCLUSION--The link between adenocarcinoma and asbestos was confirmed in this, the first study of risk of lung cancer by histological category based on incident cancer cases for a whole population during a 50 year period. PMID:8431397

  4. Use of Dieselized Farm Equipment and Incident Lung Cancer: Findings from the Agricultural Health Study Cohort

    PubMed Central

    Tual, Séverine; Silverman, Debra T.; Koutros, Stella; Blair, Aaron; Sandler, Dale P.; Lebailly, Pierre; Andreotti, Gabriella; Hoppin, Jane A.; Freeman, Laura E. Beane

    2015-01-01

    Background: Diesel exhaust is a known lung carcinogen. Farmers use a variety of dieselized equipment and thus may be at increased risk of lung cancer, but farm exposures such as endotoxins may also be protective for lung cancer. Objectives: We evaluated the relative risk of incident lung cancer, including histological subtype, from enrollment (1993–1997) to 2010–2011 in relation to farm equipment use in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators and spouses in Iowa and North Carolina, USA. Methods: Farm equipment use was reported by 21,273 farmers and 29,840 spouses. Rate ratios (RRs) were estimated separately for farmers and spouses with Poisson regression models adjusted for smoking and other confounders. We conducted stratified analyses by exposure to animals or stored grain, a surrogate for endotoxin exposure. Results: Daily diesel tractor use (vs. no use) was positively associated with lung cancer in farmers (RR = 1.48; 95% CI: 0.87, 2.50; 35 exposed, 32 unexposed cases), particularly adenocarcinoma (RR = 3.39; 95% CI: 1.23, 9.33; 12 exposed, 7 unexposed cases). The association of adenocarcinoma with daily (vs. low/no) use of diesel tractors was stronger for farmers with no animal or stored grain exposures (RR = 6.23; 95% CI: 2.25, 17.25; 5 exposed, 18 unexposed cases) than among farmers with these exposures (RR = 1.19; 95% CI: 0.51, 2.79; 7 exposed, 27 unexposed cases) (p-interaction = 0.05). Conclusions: This study provides preliminary evidence of an increased risk of lung adenocarcinoma among daily drivers of diesel tractors and suggests that exposure to endotoxins may modify the impact of diesel exposure on lung cancer risk. Confirmation of these findings with more exposed cases and more detailed exposure information is warranted. Citation: Tual S, Silverman DT, Koutros S, Blair A, Sandler DP, Lebailly P, Andreotti G, Hoppin JA, Beane Freeman LE. 2016. Use of dieselized farm equipment and incident lung

  5. The feasibility of CT lung volume as a surrogate marker of donor-recipient size matching in lung transplantation.

    PubMed

    Jung, Woo Sang; Haam, Seokjin; Shin, Jae Min; Han, Kyunghwa; Park, Chul Hwan; Byun, Min Kwang; Chang, Yoon Soo; Kim, Hyung Jung; Kim, Tae Hoon

    2016-07-01

    Donor-recipient size matching in lung transplantation (LTx) by computed tomography lung volume (CTvol) may be a reasonable approach because size matching is an anatomical issue. The purpose of this study is to evaluate the feasibility of CTvol as a surrogate marker of size matching in LTx by comparing CTvol and predicted total lung capacity (pTLC) to reference total lung capacity (TLC) values.From January to December 2014, data from 400 patients who underwent plethysmography, pulmonary function testing (PFT), and chest computed tomography scans were reviewed retrospectively. Enrolled 264 patients were divided into 3 groups according to PFT results: Group I, obstructive pattern; Group II, restrictive pattern; Group III, normal range. The correlations between pTLC and TLC and between CTvol and TLC were analyzed, and the linear correlation coefficients were compared. The percentage error rates of pTLC and CTvol were calculated and absolute error rates were compared.The correlation coefficient between CTvol and TLC in Group I was larger than that of pTLC and TLC (0.701 vs 0.432, P = 0.002). The absolute percentage error rate between CTvol and pTLC was lower than that of pTLC in Group II (15.3% ± 11.9% vs 42.2% ± 28.1%, P < 0.001).CTvol showed similar or better correlation with TLC compared to the pTLC in normal participants and patients with obstructive or restrictive pulmonary diseases. CTvol showed a smaller error rate in patients with restrictive disease. The results suggest that CTvol may be a feasible method for size matching in LTx. PMID:27399069

  6. Development and psychometric properties of the Pulmonary-specific Quality-of-Life Scale in lung transplant patients

    PubMed Central

    Hoffman, Benson M.; Stonerock, Gregory L.; Smith, Patrick J.; O’Hayer, C. Virginia F.; Palmer, Scott; Davis, Robert D.; Kurita, Keiko; Carney, Robert M.; Freeland, Kenneth; Blumenthal, James A.

    2016-01-01

    BACKGROUND The Pulmonary-specific Quality-of-Life Scale (PQLS) was developed to measure quality of life (QoL) among patients awaiting lung transplant. The objective of this study was to determine the psychometric properties of the PQLS, identify empirically derived sub-scales, and examine ability to detect changes in pulmonary-specific QoL scores after lung transplantation. METHODS Data were derived from the INSPIRE trial, a dual-site randomized controlled trial of coping skills training in 389 lung transplant candidates (obstructive [48.3%], restrictive [24.2%], cystic fibrosis [13.6%], and other [13.9%]). Cronbach alpha was calculated to assess the internal reliability of the PQLS (n = 388). Test-retest reliability was assessed with correlation coefficients between baseline and 12-week post-baseline scores for the usual care control condition (n = 140). Convergent validity was assessed with correlation coefficients between the PQLS and established measures of QoL and emotional distress, 6-minute walk test distance, forced expiratory volume in 1 second, and use of supplemental oxygen at rest (n = 388). Change from baseline to 6 months post-transplantation was assessed with repeated measures analysis of variance (n = 133). RESULTS The PQLS was internally reliable and stable across 12 weeks. The PQLS correlated strongly with QoL measures (e.g., Shortness of Breath Questionnaire, r = 0.78, p < 0.0001), moderately with mood and anxiety (e.g., Beck Depression Inventory-II, r = 0.59, p < 0.0001), and modestly with lung disease severity (e.g., 6-minute walk test, r = −0.41, p < 0.0001). PQLS scores improved by nearly 2 SDs after transplant. CONCLUSIONS These results demonstrated the reliability, validity, and sensitivity to change of the PQLS for measuring pulmonary QoL among patients with advanced lung disease and the responsiveness of the PQLS to changes in QoL after lung transplantation. PMID:25980570

  7. Neisseria lactamica Causing a Lung Cavity and Skin Rash in a Renal Transplant Patient: First Report from India

    PubMed Central

    Raina, Adnan; Altaf, Sheikh Shoaib

    2016-01-01

    Neisseria lactamica, a commensal, has been very rarely reported to cause diseases in immunocompromised hosts. In medical literature, there is only one report of a cavitatory lung lesion caused by it. The patient was a kidney transplant recipient. Neisseria lactamica was found to be the cause of his pulmonary cavity and a desquamating rash on feet. With the rapidly spreading medical advance, more and more patients are getting organ transplants, so the population of immunocompromised people is on the rise. We expect more sinister and less expected organisms to cause diseases in patients who have organ transplants. PMID:27006840

  8. Variation in incidence of breast, lung and cervical cancer and malignant melanoma of skin by socioeconomic group in England

    PubMed Central

    Shack, Lorraine; Jordan, Catrina; Thomson, Catherine S; Mak, Vivian; Møller, Henrik

    2008-01-01

    Background Cancer incidence varies by socioeconomic group and these variations have been linked with environmental and lifestyle factors, differences in access to health care and health seeking behaviour. Socioeconomic variations in cancer incidence by region and age are less clearly understood but they are crucial for targeting prevention measures and health care commissioning. Methods Data were obtained from all eight English cancer registries for patients diagnosed between 1998 and 2003, for all invasive cases of female breast cancer (ICD-10 code C50), lung cancer (ICD-10 codes C33-C34), cervical cancer (ICD-10 code C53), and malignant melanoma of the skin (ICD-10 code C43). Socioeconomic status was assigned to each patient based on their postcode of residence at diagnosis, using the income domain of the Index of Multiple Deprivation 2004. We analysed the socioeconomic variations in the incidence of breast, lung and cervical cancer and malignant melanoma of the skin for England, and regionally and by age. Results Incidence was highest for the most deprived patients for lung cancer and cervical cancer, whilst the opposite was observed for malignant melanoma and breast cancer. The difference in incidence between the most and the least deprived groups was higher for lung cancer patients aged under 65 at diagnosis than those over 65 at diagnosis, which may indicate a cohort effect. There were regional differences in the socioeconomic gradients with the gap being widest for lung and cervical cancer in the North (North East, North West and Yorkshire and Humberside) and for malignant melanoma in the East and South West. There were only modest variations in breast cancer incidence by region. If the incidence of lung and cervical cancer were decreased to that of the least deprived group it would prevent 36% of lung cancer cases in men, 38% of lung cancer cases in women and 28% of cervical cancer cases. Incidence of breast cancer and melanoma was highest in the least

  9. Radiation and Smoking Effects on Lung Cancer Incidence by Histological Types Among Atomic Bomb Survivors

    PubMed Central

    Egawa, Hiromi; Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Matsuo, Takeshi; Tokuoka, Shoji; Suyama, Akihiko; Ozasa, Kotaro; Kodama, Kazunori; Mabuchi, Kiyohiko

    2014-01-01

    While the risk of lung cancer associated separately with smoking and radiation exposure has been widely reported, it is not clear how smoking and radiation together contribute to the risk of specific lung cancer histological types. With individual smoking histories and radiation dose estimates, we characterized the joint effects of radiation and smoking on type-specific lung cancer rates among the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404 cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer incident cases were diagnosed and classified by histological type. Poisson regression methods were used to estimate excess relative risks under several interaction models. Adenocarcinoma (636 cases), squamous-cell carcinoma (330) and small-cell carcinoma (194) made up 90% of the cases with known histology. Both smoking and radiation exposure significantly increased the risk of each major lung cancer histological type. Smoking-associated excess relative risks were significantly larger for small-cell and squamous-cell carcinomas than for adenocarcinoma. The gender-averaged excess relative risks per 1 Gy of radiation (for never-smokers at age 70 after radiation exposure at age 30) were estimated as 1.49 (95% confidence interval 0.1–4.6) for small-cell carcinoma, 0.75 (0.3–1.3) for adenocarcinoma, and 0.27 (0–1.5) for squamous-cell carcinoma. Under a model allowing radiation effects to vary with levels of smoking, the nature of the joint effect of smoking and radiation showed a similar pattern for different histological types in which the radiation-associated excess relative risk tended to be larger for moderate smokers than for heavy smokers. However, in contrast to analyses of all lung cancers as a group, such complicated interactions did not describe the data significantly better than either simple additive or multiplicative interaction models for any of the type-specific analyses. PMID:22862780

  10. Lung Cancer Incidence and Long-Term Exposure to Air Pollution from Traffic

    PubMed Central

    Raaschou-Nielsen, Ole; Andersen, Zorana Jovanovic; Hvidberg, Martin; Jensen, Steen Solvang; Ketzel, Matthias; Sørensen, Mette; Loft, Steffen; Overvad, Kim; Tjønneland, Anne

    2011-01-01

    Background Previous studies have shown associations between air pollution and risk for lung cancer. Objective We investigated whether traffic and the concentration of nitrogen oxides (NOx) at the residence are associated with risk for lung cancer. Methods We identified 592 lung cancer cases in the Danish Cancer Registry among 52,970 members of the Diet, Cancer and Health cohort and traced residential addresses from 1 January 1971 in the Central Population Registry. We calculated the NOx concentration at each address by dispersion models and calculated the time-weighted average concentration for all addresses for each person. We used Cox models to estimate incidence rate ratios (IRRs) after adjustment for smoking (status, duration, and intensity), environmental tobacco smoke, length of school attendance, occupation, and dietary intake of fruit. Results For the highest compared with the lowest quartile of NOx concentration at the residence, we found an IRR for lung cancer of 1.30 [95% confidence interval (CI), 1.05–1.61], and the IRR for lung cancer in association with living within 50 m of a major road (> 10,000 vehicles/day) was 1.21 (95% CI, 0.95–1.55). The results showed tendencies of stronger associations among nonsmokers, among those with a relatively low fruit intake, and among those with a longer school attendance; only length of school attendance modified the effect significantly. Conclusions This study supports that risk for lung cancer is associated with different markers of air pollution from traffic near the residence. PMID:21227886

  11. Radiation and smoking effects on lung cancer incidence by histological types among atomic bomb survivors.

    PubMed

    Egawa, Hiromi; Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Matsuo, Takeshi; Tokuoka, Shoji; Suyama, Akihiko; Ozasa, Kotaro; Kodama, Kazunori; Mabuchi, Kiyohiko

    2012-09-01

    While the risk of lung cancer associated separately with smoking and radiation exposure has been widely reported, it is not clear how smoking and radiation together contribute to the risk of specific lung cancer histological types. With individual smoking histories and radiation dose estimates, we characterized the joint effects of radiation and smoking on type-specific lung cancer rates among the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404 cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer incident cases were diagnosed and classified by histological type. Poisson regression methods were used to estimate excess relative risks under several interaction models. Adenocarcinoma (636 cases), squamous-cell carcinoma (330) and small-cell carcinoma (194) made up 90% of the cases with known histology. Both smoking and radiation exposure significantly increased the risk of each major lung cancer histological type. Smoking-associated excess relative risks were significantly larger for small-cell and squamous-cell carcinomas than for adenocarcinoma. The gender-averaged excess relative risks per 1 Gy of radiation (for never-smokers at age 70 after radiation exposure at age 30) were estimated as 1.49 (95% confidence interval 0.1-4.6) for small-cell carcinoma, 0.75 (0.3-1.3) for adenocarcinoma, and 0.27 (0-1.5) for squamous-cell carcinoma. Under a model allowing radiation effects to vary with levels of smoking, the nature of the joint effect of smoking and radiation showed a similar pattern for different histological types in which the radiation-associated excess relative risk tended to be larger for moderate smokers than for heavy smokers. However, in contrast to analyses of all lung cancers as a group, such complicated interactions did not describe the data significantly better than either simple additive or multiplicative interaction models for any of the type-specific analyses. PMID:22862780

  12. Utilization of the Organ Care System Lung for the assessment of lungs from a donor after cardiac death (DCD) before bilateral transplantation.

    PubMed

    Mohite, P N; Sabashnikov, A; García Sáez, D; Pates, B; Zeriouh, M; De Robertis, F; Simon, A R

    2015-07-01

    In this manuscript, we present the first experience of evaluating donation after circulatory death (DCD) lungs, using the normothermic preservation Organ Care System (OCS) and subsequent successful transplantation. The OCS could be a useful tool for the evaluation of marginal lungs from DCD donors as it allows a proper recruitment and bronchoscopy in such donations in addition to continuous ex-vivo perfusion and assessment and treatment during transport. The OCS could potentially be a standard of care in the evaluation of marginal lungs from DCD. PMID:25332197

  13. Reduction in Airway Complications After Lung Transplantation With Novel Anastomotic Technique

    PubMed Central

    FitzSullivan, Elizabeth; Gries, Cynthia J.; Phelan, Patrick; Farjah, Farhood; Gilbert, Erin; Keech, John C.; Wood, Douglas E.; Raghu, Ganesh; Mulligan, Michael S.

    2013-01-01

    Background Bronchial anastomotic complications develop in 31% of lung transplant recipients, leading to additional operative procedures and increased morbidity. Advances in surgical technique have thus far resulted in only modestly improved outcomes. We hypothesized that creating the bronchial anastomosis at the secondary carina using a combination of running and figure-of-eight sutures would minimize donor bronchial ischemia and airway complications. Methods This retrospective review of a single surgeon’s operative experience from 2000 to 2007 compares a new bronchial anastomotic technique with the conventional technique. The primary outcome was the occurrence of bronchial anastomotic complications requiring invasive intervention. The secondary outcome was distal airway complications. Patients were monitored for 1 year after transplant. Recipient and donor demographic data as well as relevant variables from their preoperative, perioperative, and postoperative courses were collected for analysis. These data were compared using t tests for normally distributed continuous variables, Mann-Whitney tests for nonnormally distributed continuous variables, and χ2 tests or Fisher exact test for categoric variables. Logistic regression was used to control for covariates while comparing the primary outcome between the new and conventional bronchial anastomotic techniques. Results The analysis included 230 patients, representing 407 anastomoses. The occurrence of anastomotic complications requiring intervention and distal airway complications decreased from 18.1% to 2.3% of anastomoses and 12.2% to 4.4% of patients, respectively. After controlling for available risk factors, the new technique significantly reduced both anastomotic (p < 0.001) and distal (p = 0.03) airway complications. Conclusions This new anastomotic technique dramatically reduces anastomotic and distal airway complications after lung transplantation. PMID:21511248

  14. Long-Term Persistence of Donor Alveolar Macrophages in Human Lung Transplant Recipients That Influences Donor-Specific Immune Responses.

    PubMed

    Nayak, D K; Zhou, F; Xu, M; Huang, J; Tsuji, M; Hachem, R; Mohanakumar, T

    2016-08-01

    Steady-state alveolar macrophages (AMs) are long-lived lung-resident macrophages with sentinel function. Evidence suggests that AM precursors originate during embryogenesis and populate lungs without replenishment by circulating leukocytes. However, their presence and persistence are unclear following human lung transplantation (LTx). Our goal was to examine donor AM longevity and evaluate whether AMs of recipient origin seed the transplanted lungs. Origin of AMs was accessed using donor-recipient HLA mismatches. We demonstrate that 94-100% of AMs present in bronchoalveolar lavage (BAL) were donor derived and, importantly, AMs of recipient origin were not detected. Further, analysis of BAL cells up to 3.5 years post-LTx revealed that the majority of AMs (>87%) was donor derived. Elicitation of de novo donor-specific antibody (DSA) is a major post-LTx complication and a risk factor for development of chronic rejection. The donor AMs responded to anti-HLA framework antibody (Ab) with secretion of inflammatory cytokines. Further, in an experimental murine model, we demonstrate that adoptive transfer of allogeneic AMs stimulated humoral and cellular immune responses to alloantigen and lung-associated self-antigens and led to bronchiolar obstruction. Therefore, donor-derived AMs play an essential role in the DSA-induced inflammatory cascade leading to obliterative airway disease of the transplanted lungs. PMID:27062199

  15. Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation.

    PubMed

    Budding, Kevin; van de Graaf, Eduard A; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M; Luijk, Bart D; Oudijk, Erik-Jan D; van Kessel, Diana A; Grutters, Jan C; Hack, C Erik; Otten, Henderikus G

    2016-01-01

    CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx. PMID:27215188

  16. Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation

    PubMed Central

    Budding, Kevin; van de Graaf, Eduard. A.; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M.; Luijk, Bart D.; Oudijk, Erik-Jan D.; van Kessel, Diana A.; Grutters, Jan C.; Hack, C. Erik; Otten, Henderikus G.

    2016-01-01

    CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx. PMID:27215188

  17. A no-flush, core-cooling technique for successful cardiopulmonary preservation in heart-lung transplantation.

    PubMed

    Kontos, G J; Adachi, H; Borkon, M A; Cameron, D E; Baumgartner, W A; Hutchins, G M; Brawn, J; Reitz, B A

    1987-12-01

    In order to determine whether a no-flush, core-cooling technique could provide extended heart-lung preservation, we placed donor calves on cardiopulmonary bypass and instituted rapid cooling to 15 degrees C during the continuous infusion of isoproterenol. The heart and lungs were harvested after the administration of a cardioplegic solution through the aortic root. In the control group (N = 5), heart and lungs were orthotopically allotransplanted immediately. In the preserved group (N = 5), heart and lungs were similarly excised but were stored in a normal saline bath at 4 degrees C for approximately 4 hours and then transplanted. Both groups received isoproterenol during reperfusion and were studied for 6 hours after implantation. A load independent analysis of myocardial function was done by determining with a sonomicrometer the ratio of the end-systolic pressure to the end-systolic dimension. Pulmonary preservation was evaluated by measurement of extravascular lung water with a double-indicator dilution method, arterial oxygenation on 100% inspired oxygen, and serial lung biopsies. Myocardial and pulmonary function after 4 hours of static preservation was found to be similar to controls. No-flush, core-cooling with cardiopulmonary bypass provides adequate cardiorespiratory function after acute bovine heart-lung allotransplantation. With the use of this technique, successful extended cold ischemic cardiopulmonary preservation for heart-lung transplantation may be achieved. PMID:3119946

  18. Infections after lung transplantation: time of occurrence, sites, and microbiologic etiologies

    PubMed Central

    Yun, Ji Hyun; Jo, Kyung-Wook; Choi, Se Hoon; Lee, Jina; Chae, Eun Jin; Do, Kyung-Hyun; Choi, Dae-Kee; Choi, In-Cheol; Hong, Sang-Bum; Shim, Tae Sun; Kim, Hyeong Ryul; Kim, Dong Kwan; Park, Seung-Il

    2015-01-01

    Background/Aims Infections are major causes of both early and late death after lung transplantation (LT). The development of prophylaxis strategies has altered the epidemiology of post-LT infections; however, recent epidemiological data are limited. We evaluated infections after LT at our institution by time of occurrence, site of infections, and microbiologic etiologies. Methods All consecutive patients undergoing lung or heart-lung transplantation between October 2008 and August 2014 at our institution were enrolled. Cases of infections after LT were initially identified from the prospective registry database, which was followed by a detailed review of the patients' medical records. Results A total of 108 episodes of post-LT infections (56 bacterial, 43 viral, and nine fungal infections) were observed in 34 LT recipients. Within 1 month after LT, the most common bacterial infections were catheter-related bloodstream infections (42%). Pneumonia was the most common site of bacterial infection in the 2- to 6-month period (28%) and after 6 months (47%). Cytomegalovirus was the most common viral infection within 1 month (75%) and in the 2- to 6-month period (80%). Respiratory viruses were the most common viruses after 6 months (48%). Catheter-related candidemia was the most common fungal infection. Invasive pulmonary aspergillosis developed after 6 months. Survival rates at the first and third years were 79% and 73%, respectively. Conclusions Although this study was performed in a single center, we provide valuable and recent detailed epidemiology data for post-LT infections. A further multicenter study is required to properly evaluate the epidemiology of post-LT infections in Korea. PMID:26161017

  19. Elevated ST2 Distinguishes Incidences of Pediatric Heart and Small Bowel Transplant Rejection.

    PubMed

    Mathews, L R; Lott, J M; Isse, K; Lesniak, A; Landsittel, D; Demetris, A J; Sun, Y; Mercer, D F; Webber, S A; Zeevi, A; Fischer, R T; Feingold, B; Turnquist, H R

    2016-03-01

    Elevated serum soluble (s) suppressor of tumorigenicity-2 is observed during cardiovascular and inflammatory bowel diseases. To ascertain whether modulated ST2 levels signify heart (HTx) or small bowel transplant (SBTx) rejection, we quantified sST2 in serially obtained pediatric HTx (n = 41) and SBTx recipient (n = 18) sera. At times of biopsy-diagnosed HTx rejection (cellular and/or antibody-mediated), serum sST2 was elevated compared to rejection-free time points (1714 ± 329 vs. 546.5 ± 141.6 pg/mL; p = 0.0002). SBTx recipients also displayed increased serum sST2 during incidences of rejection (7536 ± 1561 vs. 2662 ± 543.8 pg/mL; p = 0.0347). Receiver operator characteristic (ROC) analysis showed that serum sST2 > 600 pg/mL could discriminate time points of HTx rejection and nonrejection (area under the curve [AUC] = 0.724 ± 0.053; p = 0.0003). ROC analysis of SBTx measures revealed a similar discriminative capacity (AUC = 0.6921 ± 0.0820; p = 0.0349). Quantitative evaluation of both HTx and SBTx biopsies revealed that rejection significantly increased allograft ST2 expression. Pathway and Network Analysis of biopsy data pinpointed ST2 in the dominant pathway modulated by rejection and predicted tumor necrosis factor-α and IL-1β as upstream activators. In total, our data indicate that alloimmune-associated pro-inflammatory cytokines increase ST2 during rejection. They also demonstrate that routine serum sST2 quantification, potentially combined with other biomarkers, should be investigated further to aid in the noninvasive diagnosis of rejection. PMID:26663613

  20. Comparative proteomic analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF) and lung transplant donor lungs.

    PubMed

    Korfei, Martina; Schmitt, Sigrid; Ruppert, Clemens; Henneke, Ingrid; Markart, Philipp; Loeh, Benjamin; Mahavadi, Poornima; Wygrecka, Malgorzata; Klepetko, Walter; Fink, Ludger; Bonniaud, Philippe; Preissner, Klaus T; Lochnit, Günter; Schaefer, Liliana; Seeger, Werner; Guenther, Andreas

    2011-05-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease for which no effective therapy exists to date. To identify the molecular mechanisms underlying IPF, we performed comparative proteome analysis of lung tissue from patients with sporadic IPF (n = 14) and human donor lungs (controls, n = 10) using two-dimensional gel electrophoresis and MALDI-TOF-MS. Eighty-nine differentially expressed proteins were identified, from which 51 were up-regulated and 38 down-regulated in IPF. Increased expression of markers for the unfolded protein response (UPR), heat-shock proteins, and DNA damage stress markers indicated a chronic cell stress-response in IPF lungs. By means of immunohistochemistry, induction of UPR markers was encountered in type-II alveolar epithelial cells of IPF but not of control lungs. In contrast, up-regulation of heat-shock protein 27 (Hsp27) was exclusively observed in proliferating bronchiolar basal cells and associated with aberrant re-epithelialization at the bronchiolo-alveolar junctions. Among the down-regulated proteins in IPF were antioxidants, members of the annexin family, and structural epithelial proteins. In summary, our results indicate that IPF is characterized by epithelial cell injury, apoptosis, and aberrant epithelial proliferation. PMID:21319792

  1. First Annual IMACS Report: A global International Society for Heart and Lung Transplantation Registry for Mechanical Circulatory Support.

    PubMed

    Kirklin, James K; Cantor, Ryan; Mohacsi, Paul; Gummert, Jan; De By, Theo; Hannan, Margaret M; Kormos, Robert L; Schueler, Stephan; Lund, Lars H; Nakatani, Takeshi; Taylor, Rhiannon; Lannon, Jenny

    2016-04-01

    The first annual report of the International Society for Heart and Lung Transplantation (ISHLT) Mechanically Assisted Circulatory Support (IMACS) registry provides global data on 5,942 patients from 31 countries. This initial report focuses on patient demographics, survival, device types, adverse events, competing outcomes, and a risk factor analysis. PMID:26922275

  2. Disseminated Trichosporon mycotoxinivorans, Aspergillus fumigatus, and Scedosporium apiospermum Coinfection after Lung and Liver Transplantation in a Cystic Fibrosis Patient

    PubMed Central

    Letscher-Bru, Valérie; Pottecher, Julien; Lannes, Béatrice; Jeung, Mi Young; Degot, Tristan; Santelmo, Nicola; Sabou, Alina Marcela; Herbrecht, Raoul; Kessler, Romain

    2012-01-01

    Trichosporon mycotoxinivorans is a novel pathogen recently found in cystic fibrosis patients. We report the first case of a disseminated fatal infection with T. mycotoxinivorans associated with invasive Aspergillus fumigatus and Scedosporium apiospermum infection after lung and liver transplantation in a cystic fibrosis patient. PMID:23035187

  3. The Interplay of "Big Five" Personality Factors and Metaphorical Schemas: A Pilot Study with 20 Lung Transplant Recipients

    ERIC Educational Resources Information Center

    Goetzmann, Lutz; Moser, Karin S.; Vetsch, Esther; Grieder, Erhard; Klaghofer, Richard; Naef, Rahel; Russi, Erich W.; Boehler, Annette; Buddeberg, Claus

    2007-01-01

    The aim of the present study was to investigate the interplay between personality factors and metaphorical schemas. The "Big Five" personality factors of 20 patients after lung transplantation were examined with the NEO-FFI. Patients were questioned about their social network, and self- and body-image. The interviews were assessed with metaphor…

  4. Successful prevention of scedosporiosis after lung transplantation in a cystic fibrosis patient by combined local and systemic triazole therapy.

    PubMed

    Hartmann, Carolin; Müller, Carsten; Weißbrodt, Hartmut; Suerbaum, Sebastian; Tintelnot, Kathrin; Stolle, Stefan; Hansen, Gesine; Sedlacek, Ludwig

    2013-05-23

    A persistent colonization with Scedosporium apiospermum (S. apiospermum) often results in disseminated infection with a high mortality rate in immunosuppressed patients. We present the first case of successful prevention of scedosporiosis in an adolescent female cystic fibrosis patient post double lung transplant, with a combination of local and systemic voriconazole therapy and surgical intervention. PMID:24432232

  5. Isolation of Stenotrophomonas maltophilia in asymptomatic lung transplant recipients: effects of treatment on eradication and outcome.

    PubMed

    Hofmann, Patrick; Hombach, Michael; Seifert, Burkhardt; Schuurmans, Macé M; Bürgi, Urs; Isenring, Bruno; Mueller, Nicolas J; Kohler, Malcolm; Benden, Christian; Huber, Lars C

    2016-08-01

    In this retrospective, single-center data analysis, we audited our clinical practice to treat Stenotrophomonas maltophilia in asymptomatic lung transplant recipients (LTRs). Eighteen LTRs with confirmed isolation of S. maltophilia were identified. Twelve of these LTRs have been treated with antibiotics, while 6 were managed without treatment. Treatment was based on antibiograms (trimethoprim/sulfamethoxazole [TMP/SMX] (8/12), levofloxacin (1/12), or both (3/12). Clearance (12/12 vs 6/6), eradication (10/12 vs 3/6, P=.27), and freedom from S. maltophilia recurrence (83%±11% vs 40%±22% after one year, log-rank P=.09) were not found to differ significantly between treated and untreated patients. None of the patient groups showed significant changes in lung function or biochemical variables. Creatinine levels at the end of the study period were found to be higher in treated patients compared to the untreated group (P=.049). De novo acquired TMP/SMX resistance in S. maltophilia strains was not observed. These results indicate no evidence that antibiotic treatment for S. maltophilia in asymptomatic LTRs alters lung function or the clinical outcome. PMID:27219076

  6. Successful treatment of bronchial anastomotic stenosis with modified Dumon Y-stent insertion in lung transplantation: report of a case.

    PubMed

    Higuchi, Takao; Shiraishi, Takeshi; Hiratsuka, Masafumi; Yanagisawa, Jun; Iwasaki, Akinori

    2011-09-01

    Bronchial complications owing to airway anastomosis still remain a cause of morbidity and mortality following lung transplantation, and bronchial stenosis is the most common manifestation. Current treatment strategies include endoscopic balloon dilation, laser ablation, and stent insertion. Although a variety of stent types are currently available, it is unclear as to which type of prosthesis is most suitable for post-transplant bronchial complications with regard to the primary effects and long-term outcomes. We herein discuss a case of stenosis of the right bronchial anastomosis in a patient who underwent right single lung transplantation for idiopathic pulmonary fibrosis. This complication was successfully treated with the placement of a modified Dumon Y-stent. The stent was removed 2 months after insertion, and the patient has subsequently maintained an adequate airway caliber. Computed tomography, especially the sagittal section through the chest, is useful for detecting bronchial stenosis and monitoring the healing of this condition. PMID:21874436

  7. [Incidence and management of anemia in renal transplantation: an observational-French study].

    PubMed

    Choukroun, Gabriel; Deray, Gilbert; Glotz, Denis; Lebranchu, Yvon; Dussol, Bertrand; Bourbigot, Bernard; Lefrançois, Nicole; Cassuto-Viguier, Elisabeth; Toupance, Olivier; Hacen, Chafik; Lang, Philippe; Mazouz, Hakim; Martinez, Franck

    2008-12-01

    The management of anemia after kidney transplantation remains poorly explored. The Management of Anemia in French Kidney Transplant Patients (MATRIX) study is an observational study conducted in 10 academic hospitals among kidney-transplant patients designed to evaluate the prevalence, associated factors and management of post-transplant anemia. Over two consecutive weeks, 418 recipients (males: 248; age: 50.8+/-12.7 years) were included, all were transplanted for more than six months. Mean serum creatinine (Scr) was 152+/-67 micromol/l and mean hemoglobin (Hb) was 12.4+/-1.8 g/dl (males: 12.8+/-1.9 g/dl; females 11.9+/-1.6 g/dl). Irrespective of the delay following transplantation, 23% of patients (n=95) were severely anemic (Hb < or = 11 g/dl). Eighteen percent of the patients received an antianemic treatment (10% oral iron, 7% erythropoiesis stimulating agents (ESA), 4% folic acid) and only 35% of the severely anemic patients were actually treated (n=33). A significantly-negative correlation was observed between eGFR and Hb levels (R= -0.347, p<0.02). Ninety-six percent of the 193 patients transplanted for more than six months and a Scr greater than 150 micromol/l (n=185) suffered at least one comorbidity (89% hypertension, 32% hypercholesterolemia, 13% diabetes); this group represent the second cohort. Seventy-four percent of them were treated with mycophenolate mofetil, 16% with azathioprine, and 62% with an ACEI or angiotensin II receptor antagonists. Since the transplantation, 127 patients (66%) have been anemic (Hb < or = 11 g/dl) and 58% (n=112) were treated (iron and/or ESA, respectively 81 and 55%). Among the patients not treated for anemia, 74% had an Hb level below 12g/dl. ESA-treated patients received a mean dose of 8500 UI+/-2800 per week. Anemia is under-diagnosed and under-treated in renal-transplant recipients, despite its high prevalence. As expected, a correlation between renal function and Hb levels was observed, as in CKD patients. Prospective

  8. Incidence, Characteristics, and Prognosis of Incidentally Discovered Hepatocellular Carcinoma after Liver Transplantation

    PubMed Central

    El Moghazy, Walid; Kashkoush, Samy; Meeberg, Glenda; Kneteman, Norman

    2016-01-01

    Background. We aimed to assess incidentally discovered hepatocellular carcinoma (iHCC) over time and to compare outcome to preoperatively diagnosed hepatocellular carcinoma (pdHCC) and nontumor liver transplants. Methods. We studied adults transplanted with a follow-up of at least one year. Patients were divided into 3 groups according to diagnosis of hepatocellular carcinoma. Results. Between 1990 and 2010, 887 adults were transplanted. Among them, 121 patients (13.6%) had pdHCC and 32 patients (3.6%) had iHCC; frequency of iHCC decreased markedly over years, in parallel with significant increase in pdHCC. Between 1990 and 1995, 120 patients had liver transplants, 4 (3.3%) of them had iHCC, and only 3 (2.5%) had pdHCC, while in the last 5 years, 263 patients were transplanted, 7 (0.03%) of them had iHCC, and 66 (25.1%) had pdHCC (P < 0.001). There was no significant difference between groups regarding patient survival; 5-year survival was 74%, 75.5%, and 77.3% in iHCC, pdHCC, and non-HCC groups, respectively (P = 0.702). Patients with iHCC had no recurrences after transplant, while pdHCC patients experienced 17 recurrences (15.3%) (P = 0.016). Conclusions. iHCC has significantly decreased despite steady increase in number of transplants for hepatocellular carcinoma. Patients with iHCC had excellent outcomes with no tumor recurrence and survival comparable to pdHCC. PMID:27403337

  9. Incidence of non-lung solid cancers in Czech uranium miners: A case-cohort study

    SciTech Connect

    Kulich, M.; Rericha, V.; Rericha, R.; Shore, D.L.; Sandler, D.P.

    2011-04-15

    Objectives: Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Pribram region, Czech Republic. Methods: A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. Results: Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. Conclusions: Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out. - Research highlights: {yields} Uranium miners are chronically exposed to radon. {yields} We evaluate risk of non-lung solid cancers among uranium miners. {yields} No cancer type was significantly associated with radon exposure. {yields} Malignant melanoma and gallbladder cancer showed non-significant elevated risk.

  10. Relationship between Fungal Colonisation of the Respiratory Tract in Lung Transplant Recipients and Fungal Contamination of the Hospital Environment

    PubMed Central

    Brugière, Olivier; Chochillon, Christian; Porcher, Raphael; Boelle, Pierre-Yves; Menotti, Jean; Houze, Sandrine; Lucet, Jean-Christophe

    2015-01-01

    Background Aspergillus colonisation is frequently reported after lung transplantation. The question of whether aspergillus colonisation is related to the hospital environment is crucial to prevention. Method To elucidate this question, a prospective study of aspergillus colonisation after lung transplantation, along with a mycological survey of the patient environment, was performed. Results Forty-four consecutive patients were included from the day of lung transplantation and then examined weekly for aspergillus colonisation until hospital discharge. Environmental fungal contamination of each patient was followed weekly via air and surface sampling. Twelve patients (27%) had transient aspergillus colonisation, occurring 1–13 weeks after lung transplantation, without associated manifestation of aspergillosis. Responsible Aspergillus species were A. fumigatus (6), A. niger (3), A. sydowii (1), A. calidoustus (1) and Aspergillus sp. (1). In the environment, contamination by Penicillium and Aspergillus was predominant. Multivariate analysis showed a significant association between occurrence of aspergillus colonisation and fungal contamination of the patient’s room, either by Aspergillus spp. in the air or by A.fumigatus on the floor. Related clinical and environmental isolates were genotyped in 9 cases of aspergillus colonisation. For A. fumigatus (4 cases), two identical microsatellite profiles were found between clinical and environmental isolates collected on distant dates or locations. For other Aspergillus species, isolates were different in 2 cases; in 3 cases of aspergillus colonisation by A. sydowii, A. niger and A. calidoustus, similarity between clinical and environmental internal transcribed spacer and tubulin sequences was >99%. Conclusion Taken together, these results support the hypothesis of environmental risk of hospital acquisition of aspergillus colonisation in lung transplant recipients. PMID:26629994

  11. Microvesicles Derived From Human Mesenchymal Stem Cells Restore Alveolar Fluid Clearance in Human Lungs Rejected for Transplantation

    PubMed Central

    Gennai, S.; Monsel, A.; Hao, Q.; Park, J.; Matthay, M. A.; Lee, J. W.

    2016-01-01

    The need to increase the donor pool for lung transplantation is a major public health issue. We previously found that administration of mesenchymal stem cells “rehabilitated” marginal donor lungs rejected for transplantation using ex vivo lung perfusion. However, the use of stem cells has some inherent limitation such as the potential for tumor formation. In the current study, we hypothesized that microvesicles, small anuclear membrane fragments constitutively released from mesenchymal stem cells, may be a good alternative to using stem cells. Using our well established ex vivo lung perfusion model, microvesicles derived from human mesenchymal stem cells increased alveolar fluid clearance (i.e. ability to absorb pulmonary edema fluid) in a dose-dependent manner, decreased lung weight gain following perfusion and ventilation, and improved airway and hemodynamic parameters compared to perfusion alone. Microvesicles derived from normal human lung fibroblasts as a control had no effect. Co-administration of microvesicles with anti-CD44 antibody attenuated these effects, suggesting a key role of the CD44 receptor in the internalization of the microvesicles into the injured host cell and its effect. In summary, microvesicles derived from human mesenchymal stem cells were as effective as the parent mesenchymal stem cells in rehabilitating marginal donor human lungs. PMID:25847030

  12. Hierarchical Bayesian modeling of spatio-temporal patterns of lung cancer incidence risk in Georgia, USA: 2000-2007

    NASA Astrophysics Data System (ADS)

    Yin, Ping; Mu, Lan; Madden, Marguerite; Vena, John E.

    2014-10-01

    Lung cancer is the second most commonly diagnosed cancer in both men and women in Georgia, USA. However, the spatio-temporal patterns of lung cancer risk in Georgia have not been fully studied. Hierarchical Bayesian models are used here to explore the spatio-temporal patterns of lung cancer incidence risk by race and gender in Georgia for the period of 2000-2007. With the census tract level as the spatial scale and the 2-year period aggregation as the temporal scale, we compare a total of seven Bayesian spatio-temporal models including two under a separate modeling framework and five under a joint modeling framework. One joint model outperforms others based on the deviance information criterion. Results show that the northwest region of Georgia has consistently high lung cancer incidence risk for all population groups during the study period. In addition, there are inverse relationships between the socioeconomic status and the lung cancer incidence risk among all Georgian population groups, and the relationships in males are stronger than those in females. By mapping more reliable variations in lung cancer incidence risk at a relatively fine spatio-temporal scale for different Georgian population groups, our study aims to better support healthcare performance assessment, etiological hypothesis generation, and health policy making.

  13. Epidemiology, incidence and mortality of lung cancer and their relationship with the development index in the world

    PubMed Central

    Rafiemanesh, Hosein; Mehtarpour, Mojtaba; Khani, Farah; Hesami, Sayed Mohammadali; Shamlou, Reza; Towhidi, Farhad; Makhsosi, Behnam Reza; Moini, Ali

    2016-01-01

    Background The highest incidence of lung cancer is seen in North America and the lowest incidence in central Africa. Socioeconomic factors of inequality reflect regional disparities in human development. Due to the importance of awareness about incidence and mortality of lung cancer in health programming and the possible role of the human development index (HDI), this study was done with the aim to investigate the epidemiology of lung cancer in the world and its relationship with HDI. Methods The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Data about the age-specific incidence and mortality rate (ASR) for every country in 2012 were getting from the global cancer project. To analyze data, correlation tests between incidence and death rates, and HDI and its components were employed with a significance level of 0.05 using SPSS software. Results Lung cancer with standardized incidence rate (ASIR) and standardized mortality rate (ASMR), equal to 23.1 and 19.7 (in 100,000 people), respectively. The highest and lowest values of mortality incidence ratio (MIR) for lung cancer due to continents division were 0.93 and 0.71 for Eastern Africa and Australia/New Zealand, respectively. Univariate analysis showed significant relationship (P<0.0001) between ASIR and ASMR with life expectancy at birth and mean years of schooling. Conclusions The highest MIR for lung cancer was for medium human development countries. Linear regression analysis showed a reverse significant relationship between MIR and HDI. PMID:27293825

  14. Pulmonary transplantation.

    PubMed Central

    Davis, R D; Pasque, M K

    1995-01-01

    OBJECTIVE: More than 2700 lung transplants have been performed since the initial clinical success in 1983. The evolution in the techniques of lung transplantation and patient management and the effects on results are reviewed. SUMMARY BACKGROUND DATA: Improvements in donor management, lung preservation, operative techniques, immunosuppression management, infection prophylaxis and treatment, rejection surveillance, and long-term follow-up have occurred in the decade following the first clinically successful lung transplant. A wider spectrum of diseases and patients treated with lung transplant have accentuated the shortage of suitable lung donors. The organ shortage has led to the use of marginal donors and a limited experience using living, related donors. METHODS: Changes in techniques and patient selection and management are reviewed and controversial issues and problems are highlighted. RESULTS: One-year survival of greater than 90% for single-lung transplant recipients and greater than 85% for bilateral lung transplant recipients have been achieved. Complications caused by airway complications has been reduced greatly. Obliterative bronchiolitis develops in 20% to 50% of long-term survivors and is the leading cause of morbidity and mortality after the first year after transplant. CONCLUSIONS: Lung transplantation has evolved into an effective therapy for a wide variety of causes of end-stage lung disease. Wider applicability requires solutions to the problems of donor shortage and development of obliterative bronchiolitis. Images Figure 1. PMID:7826157

  15. [Video-assisted thoracic surgery, lung transplantation and mediastinitis: major issues in thoracic surgery in 2010].

    PubMed

    Borro, José M; Moreno, Ramón; Gómez, Ana; Duque, José Luis

    2011-01-01

    We reviewed the major issues in thoracic surgery relating to the advances made in our specialty in 2010. To do this, the 43(rd) Congress of the Spanish Society of Pneumology and Thoracic Surgery held in La Coruña and the articles published in the Society's journal, Archivos de Bronconeumología, were reviewed. The main areas of interest were related to the development of video-assisted thoracic surgery, lung transplantation and descending mediastinitis. The new tumor-node-metastasis (TNM) classification (7(th) edition), presented last year, was still a topical issue this year. The First Forum of Thoracic Surgeons and the Update in Thoracic Surgery together with the Nurses' Area have constituted an excellent teaching program. PMID:21300211

  16. [The educational website Dermaguard to prevent the incidence of skin cancer after transplantation].

    PubMed

    Bühler, Meret N; Feldmeyer, Laurence; Wüthrich, Rudolf P; French, Lars E; Djamei, Vahid; Serra, Andreas L; Hofbauer, Günther F L

    2013-11-13

    Solid organ transplant recipients are highly susceptible to skin cancer. The major driving factors are immunosuppressive medication and ultraviolet light. Appropriate sun protection markedly reduces the development of skin cancer. Skin cancer recognized at an early stage can reliably be cured, and fatal outcomes can be prevented. The aim of this work is to educate organ transplant recipients and health care professionals involved in their care, to increase awareness of skin cancer in this high-risk population and thus to optimize the long-term outcome of patients with skin cancer. Our newly developed website provides free access to various educational materials, including leaflets, presentations and interactive elements using edutainment. PMID:24220062

  17. Conventional vs. Tablet Computer-Based Patient Education following Lung Transplantation – A Randomized Controlled Trial

    PubMed Central

    Suhling, Hendrik; Rademacher, Jessica; Zinowsky, Imke; Fuge, Jan; Greer, Mark; Warnecke, Gregor; Smits, Jacqueline M.; Bertram, Anna; Haverich, Axel; Welte, Tobias; Gottlieb, Jens

    2014-01-01

    Background Accurate immunosuppression is of critical importance in preventing rejection, while avoiding toxicity following lung transplantation. The mainstay immunosuppressants are calcineurin inhibitors, which require regular monitoring due to interactions with other medications and diet. Adherence to immunosuppression and patient knowledge is vital and can be improved through patient education. Education using tablet-computers was investigated. Objective To compare tablet-PC education and conventional education in improving immunosuppression trough levels in target range 6 months after a single education. Secondary parameters were ratio of immunosuppression level measurements divided by per protocol recommended measurements, time and patient satisfaction regarding education. Design Single-centre, open labelled randomised controlled trial. Participants Patients >6 months after lung-transplantation with <50% of calcineurin inhibitor trough levels in target range. Intervention Tablet-pc education versus personal, nurse-led education. Measurements Calcineurin inhibitor levels in target range 6 months after education, level variability, interval adherence, knowledge and adherence was studied. As outcome parameter, renal function was measured and adverse events registered. Results Sixty-four patients were 1:1 randomised for either intervention. Levels of immunosuppression 6 months after education were equal (tablet-PC 58% vs. conventional 48%, p = 0.27), both groups improved in achieving a CNI trough level within target range by either education method (delta tablet-PC 29% vs. conventional 20%). In all patients, level variability decreased (−20.4%), whereas interval adherence remained unchanged. Knowledge about immunosuppression improved by 7% and compliance tests demonstrated universal improvements with no significant difference between groups. Conclusion Education is a simple, effective tool in improving adherence to immunosuppression. Tablet-PC education was

  18. Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics.

    PubMed

    Roux, A; Bendib Le Lan, I; Holifanjaniaina, S; Thomas, K A; Hamid, A M; Picard, C; Grenet, D; De Miranda, S; Douvry, B; Beaumont-Azuar, L; Sage, E; Devaquet, J; Cuquemelle, E; Le Guen, M; Spreafico, R; Suberbielle-Boissel, C; Stern, M; Parquin, F

    2016-04-01

    In the context of lung transplant (LT), because of diagnostic difficulties, antibody-mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor-specific antibodies (DSAs), and C4d(+) staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSA(pos) AMR(pos) ); (ii) DSA positive, AMR negative (DSA(pos) AMR(neg) ); (iii) DSA limited, AMR negative (DSA(Lim) ; equal to one specificity, with mean fluorescence intensity of 500-1000 once); and (iv) DSA negative, AMR negative (DSA(neg) ). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSA(pos) AMR(pos) (n = 22), 40.3% were DSA(pos) AMR(neg) (n = 84), 6% were DSA(Lim) (n = 13) and 43% were DSA(neg) (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSA(pos) AMR(pos) group (2.1 ± 1.7) compared with DSA(pos) AMR(neg) (1 ± 1.2), DSA(Lim) (0.75 ± 1), and DSA(neg) (0.7 ± 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSA(pos) AMR(pos) patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis. PMID:26845386

  19. Propionibacterium acnes as a cause of lung abscess in a cardiac transplant recipient.

    PubMed

    Veitch, David; Abioye, Abu; Morris-Jones, Stephen; McGregor, Alastair

    2015-01-01

    A 29-year-old man was admitted with fevers, cough, left-sided chest pain and lethargy for 1 week. He had a cardiac transplant 10 years prior and was on immunosuppressive drugs. He was found to have a pulmonary lesion and went on to develop a lung abscess. Propionibacterium acnes was identified on matrix-assisted laser desorption ionisation mass spectrometry-time of flight and 16s rRNA gene sequencing after drainage. He was curatively treated with co-trimoxazole and co-amoxiclav. He divulged a longstanding history of seborrhoeic dermatitis with frequent flares leading to large volumes of squames collecting on his bed sheets. We hypothesise this was a possible route of entry: inhalation of the Propionibacterium. This case highlights how a common commensal bacterium, P. acnes, was able to cause pathology in an immunosuppressed patient. This is the only case of a patient with transplantation developing a P. acnes pulmonary infection and the only case of P. acnes causing these clinical features to be reported in the literature. PMID:26677153

  20. Myelosuppression associated with azathioprine-allopurinol interaction after heart and lung transplantation.

    PubMed

    Cummins, D; Sekar, M; Halil, O; Banner, N

    1996-06-15

    It is widely recommended that, during concurrent therapy with allopurinol, the azathioprine dosage should be decreased by at least two thirds. We retrospectively studied compliance with this guideline in 24 patients who had commenced allopurinol at a median of 33 months (range, 2-145 months) after heart and/or lung transplantation. The median reduction in azathioprine dose at initiation of allopurinol was 73.3% but ranged from 0% to 90% (>67% in 14 patients). Within 3 months, 11 (46%) of the patients became leukopenic (white blood cell count <4 x 10(9)/L), 7/23 (30%) became moderately anemic (hemoglobin <10 g/dl), and 5/23 (22%) became thrombocytopenic (platelets <150 X 10(9)/L). Decreasing the dose of azathioprine by two thirds or greater reduced but did not abolish the risk of myelotoxicity. These data highlight the need for close hematological monitoring of patients treated with this drug combination. Agents other than allopurinol should be considered for treating hyperuricemia after thoracic organ transplantation. PMID:8669118

  1. Incidence and Clinical Significance of De Novo Donor Specific Antibodies after Kidney Transplantation

    PubMed Central

    Panagiotellis, Konstantinos; Iniotaki, Aliki; Boletis, John N.

    2013-01-01

    Kidney transplantation has evolved over more than half a century and remarkable progress has been made in patient and graft outcomes. Despite these advances, chronic allograft dysfunction remains a major problem. Among other reasons, de novo formation of antibodies against donor human leukocyte antigens has been recognized as one of the major risk factors for reduced allograft survival. The type of treatment in the presence of donor specific antibodies (DSA) posttransplantation is largely related to the clinical syndrome the patient presents with at the time of detection. There is no consensus regarding the treatment of stable renal transplant recipients with circulating de novo DSA. On the contrast, in acute or chronic allograft dysfunction transplant centers use various protocols in order to reduce the amount of circulating DSA and achieve long-term graft survival. These protocols include removal of the antibodies by plasmapheresis, intravenous administration of immunoglobulin, or depletion of B cells with anti-CD20 monoclonal antibodies along with tacrolimus and mycophenolate mofetil. This review aims at the comprehension of the clinical correlations of de novo DSA in kidney transplant recipients, assessment of their prognostic value, and providing insights into the management of these patients. PMID:24348683

  2. Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine.

    PubMed

    Avsar, M; Jansson, K; Sommer, W; Kruse, B; Thissen, S; Dreckmann, K; Knoefel, A-K; Salman, J; Hafer, C; Hecker, J; Buechler, G; Karstens, J H; Jonigk, D; Länger, F; Kaever, V; Falk, C S; Hewicker-Trautwein, M; Ungefroren, H; Haverich, A; Strüber, M; Warnecke, G

    2016-05-01

    Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells. PMID:26602894

  3. Hepatitis B Vaccination in End-Stage Pulmonary Disease Patients Evaluated for Lung Transplantation: A Retrospective Single-Center Evaluation.

    PubMed

    Wald, Alexandra; Deterding, Lea; Maier, Melanie; Liebert, Uwe G; Berg, Thomas; Wirtz, Hubert; Wiegand, Johannes

    2016-01-01

    BACKGROUND In times of limited organs for transplantation, anti-HBc-positive organs can be accepted for lung transplantation to increase the number of donors. Transplant recipients should be vaccinated against hepatitis B to prevent HBV infection. However, response after HBV vaccination has only been poorly evaluated in patients with end-stage pulmonary disease. MATERIAL AND METHODS Anti-HBs titers of 40 anti-HBc negative patients with end-stage pulmonary disease evaluated for lung transplantation were analyzed with the Architect® system (Abbott, Germany). Responders, partial responders, or non-responders after HBV vaccination were defined by anti-HBs titers >100 IU/L, 10-100 IU/L, and <10 IU/L, respectively. RESULTS There were 34/40 individuals (85%) vaccinated against hepatitis B, and 6 were not vaccinated. Response, partial response, and non-response after vaccination were observed in 10/34 (29.4%), 11/34 (32.4%), and 13/34 (38.2%) of patients, respectively. Response to vaccination did not correlate with sex, pulmonary disease, comorbidities, immunosuppressive therapy, or smoking status. CONCLUSIONS Although 85% of patients evaluated for lung transplantation were vaccinated against hepatitis B, 38.2% did not show an anti-HBs titer >10 IU/L. Thus, anti-HBs titers should be regularly monitored. Nonresponders should be considered for booster vaccinations, alternative vaccination schedules, or prophylactic treatment with a nucleos(t)ide analogue in case of transplantation of an anti-HBc-positive organ. PMID:27297788

  4. Preoperative Mild-to-Moderate Coronary Artery Disease Does Not Affect Long-Term Outcomes of Lung Transplantation

    PubMed Central

    Zanotti, Giorgio; Hartwig, Matthew G.; Castleberry, Anthony W.; Martin, Jeremiah T.; Shaw, Linda K.; Williams, Judson B.; Lin, Shu S.; Davis, Robert D.

    2015-01-01

    Background Coronary artery disease has a high prevalence among lung transplant recipients and has historically been a contraindication to transplant at many institutions. In patients with mild-to-moderate coronary artery disease (Mod-CAD) undergoing lung transplant, outcomes are not well defined. Methods All patients who underwent pulmonary transplantation from January 1996 through November 2010 with pretransplant coronary angiogram were included in our study. Recipients of multivisceral, redo, and lobar lung transplants and those who underwent pretransplant coronary revascularization were excluded. Patients were grouped into Mod-CAD or no-coronary artery disease group (No-CAD). Primary end point was overall survival. Secondary end points were 30-day events and the need for posttransplant coronary revascularization. Results Approximately 539 patients were included in the study: 362 in the No-CAD, 177 in the Mod-CAD group. Patients with Mod-CAD were predominantly male, older, and had a higher body mass index. No difference in either perioperative morbidity and mortality (Mod-CAD, 4.2% vs. No-CAD 3.3%, P=0.705) or late overall mortality was shown between groups. Mod-CAD patients had a shorter hospitalization (median: 12 days vs. 14 days, P=0.009) and required a higher rate of late coronary revascularization procedures (PCI: Mod-CAD vs. No-CAD, 0.3% vs. 4.0%, P=0.0035; CABG: Mod-CAD vs. No-CAD, 0.3% vs. 2.3%, P=0.0411). Conclusions Mod-CAD does not appear to be associated with increased perioperative morbidity or decreased survival after transplant. Coronary artery disease may worsen and require coronary revascularization in patients with risk factors for disease progression. In these patients, close follow-up and screening for progression of coronary artery disease may help prevent late cardiac morbidity. PMID:24646771

  5. Prophylactic Azithromycin Therapy After Lung Transplantation: Post hoc Analysis of a Randomized Controlled Trial.

    PubMed

    Ruttens, D; Verleden, S E; Vandermeulen, E; Bellon, H; Vanaudenaerde, B M; Somers, J; Schoonis, A; Schaevers, V; Van Raemdonck, D E; Neyrinck, A; Dupont, L J; Yserbyt, J; Verleden, G M; Vos, R

    2016-01-01

    Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re-evaluated the long-term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention-to-treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD-free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long-term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p < 0.05). Prophylactic azithromycin therapy reduces long-term CLAD prevalence and improves CLAD-free survival, pulmonary function, and functional exercise capacity after LTx. PMID:26372728

  6. Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies

    PubMed Central

    Hagedorn, Peter H; Burton, Christopher M; Carlsen, Jørn; Steinbrüchel, Daniel; Andersen, Claus B; Sahar, Eli; Domany, Eytan; Cohen, Irun R; Flyvbjerg, Henrik; Iversen, Martin

    2010-01-01

    Obliterative bronchiolitis (OB) continues to be the major limitation to long-term survival after lung transplantation. The specific aetiology and pathogenesis of OB are not well understood. To explore the role of autoreactivity in OB, we spotted 751 different self molecules onto glass slides, and used these antigen microarrays to profile 48 human serum samples for immunoglobulin G (IgG) and IgM autoantibodies; 27 patients showed no or mild bronchiolitis obliterans syndrome (BOS; a clinical correlate of OB) and 15 patients showed medium to severe BOS. We now report that these BOS grades could be differentiated by a profile of autoantibodies binding to 28 proteins or their peptides. The informative autoantibody profile included down-regulation as well as up-regulation of both IgM and IgG specific reactivities. This profile was evaluated for robustness using a panel of six independent test patients. Analysis of the functions of the 28 informative self antigens showed that eight of them are connected in an interaction network involved in apoptosis and protein metabolism. Thus, a profile of autoantibodies may reflect pathological processes in the lung allograft, suggesting a role for autoimmunity in chronic rejection leading to OB. PMID:20201985

  7. Incidence and Correlates of Radiation Pneumonitis in Pediatric Patients With Partial Lung Irradiation

    SciTech Connect

    Hua Chiaho; Hoth, Kelly A.; Wu Shengjie; Kun, Larry E.; Metzger, Monika L.; Spunt, Sheri L.; Xiong Xiaoping; Krasin, Mathew J.

    2010-09-01

    Purpose: To provide a radiation pneumonitis risk estimate and investigate the correlation of clinical and dosimetric factors in pediatric patients receiving chest irradiation. Methods and Materials: A total of 122 patients diagnosed with sarcoma or Hodgkin lymphoma who received radiotherapy to the chest were evaluated for symptomatic radiation pneumonitis (Common Toxicity Criteria Grade 1 with respiratory symptom or higher grade). Pneumonitis data were collected from either prospective toxicity screenings as part of a clinical trial or through chart review. Dosimetric parameters including V{sub 10}-V{sub 25}, mean lung dose, binned lung dose, and tissue complication probability models were used, as well as clinical features to correlate with the development of pneumonitis. Results: The 1- and 2-year cumulative incidence of symptomatic radiation pneumonitis for all patients was 8.2% and 9.1%, respectively. Nine patients experienced symptomatic Grade 1 toxicity, and 2 experienced Grade 2. From univariate analysis, chemotherapy containing bleomycin ({chi}{sup 2} test, p = 0.027) and V{sub 24} (logistic regression, p = 0.019) were the clinical and dosimetric factors that resulted in statistically significant differences in the occurrence of pneumonitis. The probability of pneumonitis increased more dramatically with increasing V{sub 24} in patients receiving bleomycin than in those who did not. Adult tissue complication models did not differentiate pediatric patients with radiation pneumonitis from those without. Conclusions: The incidence of symptomatic radiation pneumonitis in pediatric patients is low and its severity mild. Parameters frequently used in adult radiation oncology provide some guidance as to risk, but pediatric patients warrant their own specific models for risk assessment, incorporating dosimetry and clinical factors.

  8. Acute Lung Injury Complicating Blood Transfusion in Post-Partum Hemorrhage: Incidence and Risk Factors

    PubMed Central

    Teofili, Luciana; Bianchi, Maria; Zanfini, Bruno A.; Catarci, Stefano; Sicuranza, Rossella; Spartano, Serena; Zini, Gina; Draisci, Gaetano

    2014-01-01

    Background We retrospectively investigated the incidence and risk factors for transfusion-related acute lung injury (TRALI) among patients transfused for post-partum hemorrhage (PPH). Methods We identified a series of 71 consecutive patients with PPH requiring the urgent transfusion of three or more red blood cell (RBC) units, with or without transfusion of fresh frozen plasma (FFP) and/or platelets (PLT). Clinical records were then retrieved and examined for respiratory distress events. According to the 2004 consensus definition, cases of new-onset hypoxemia, within 6 hours after transfusion, with bilateral pulmonary changes, in the absence of cardiogenic pulmonary edema were identified as TRALI. If an alternative risk factor for acute lung injury was present, possible TRALI was diagnosed. Results Thirteen cases of TRALI and 1 case of possible TRALI were identified (overall incidence 19.7%). At univariate analysis, patients with TRALI received higher number of RBC, PLT and FFP units and had a longer postpartum hospitalization. Among the diseases occurring in pregnancy- and various pre-existing comorbidities, only gestational hypertension and pre-eclampsia, significantly increased the risk to develop TRALI (p = 0.006). At multivariate analysis including both transfusion- and patient-related risk factors, pregnancy-related, hypertensive disorders were confirmed to be the only predictors for TRALI, with an odds ratio of 27.7 ( 95% CI 1.27–604.3, p=0.034). Conclusions Patients suffering from PPH represent a high-risk population for TRALI. The patients with gestational hypertension and pre-eclampsia, not receiving anti-hypertensive therapy, have the highest risk. Therefore, a careful monitoring of these patients after transfusions is recommended. PMID:25408855

  9. CT analysis of lung density changes in patients undergoing total body irradiation prior to bone marrow transplantation

    SciTech Connect

    Lee, J.Y.; Shank, B.; Bonfiglio, P.; Reid, A.

    1984-10-01

    Sequential changes in lung density measured by CT are potentially sensitive and convenient monitors of lung abnormalities following total body irradiation (TBI). Methods have been developed to compare pre- and post-TBI CT of lung. The average local features of a cross-sectional lung slice are extracted from three peripheral regions of interest in the anterior, posterior, and lateral portions of the CT image. Also, density profiles across a specific region may be obtained. These may be compared first for verification of patient position and breathing status and then for changes between pre- and post-TBI. These may also be compared with radiation dose profiles through the lung. A preliminary study on 21 leukemia patients undergoing total body irradiation indicates the following: (a) Density gradients of patients' lungs in the antero-posterior direction show a marked heterogeneity before and after transplantation compared with normal lungs. The patients with departures from normal density gradients pre-TBI correlate with later pulmonary complications. (b) Measurements of average peripheral lung densities have demonstrated that the average lung density in the younger age group is substantially higher: pre-TBI, the average CT number (1,000 scale) is -638 +/- 39 Hounsfield unit (HU) for 0-10 years old and -739 +/- 53 HU for 21-40 years old. (c) Density profiles showed no post-TBI regional changes in lung density corresponding to the dose profile across the lung, so no differentiation of a radiation-specific effect has yet been possible. Computed tomographic density profiles in the antero-posterior direction are successfully used to verify positioning of the CT slice and the breathing level of the lung.

  10. Listeriosis in bone marrow transplant recipients: incidence, clinical features, and treatment.

    PubMed

    Chang, J; Powles, R; Mehta, J; Paton, N; Treleaven, J; Jameson, B

    1995-11-01

    Cultures of blood and/or cerebrospinal fluid from four of 1,013 bone marrow transplant recipients treated at our center between January 1972 and April 1994 were positive for Listeria monocytogenes. The overall occurrence of listeriosis was 0.39 case per 100 transplantations. Allograft recipients had received prior treatment with parenteral methylprednisolone, thus supporting an association between listeriosis and corticosteroids. Treatment with parenteral ampicillin (200 mg/[kg.d]) and gentamicin is recommended for a minimum of 3 weeks before oral therapy. Two patients with penicillin allergies in this study failed to respond to chloramphenicol-based therapeutic regimens. Recurrent meningitis occurred in two patients, and the therapeutic use of intrathecal gentamicin/vancomycin did not confer a survival advantage (i.e., the patients did not survive). PMID:8589157

  11. History of periodontal disease diagnosis and lung cancer incidence in the Women’s Health Initiative Observational Study

    PubMed Central

    Mai, Xiaodan; LaMonte, Michael J.; Hovey, Kathleen M.; Nwizu, Ngozi; Freudenheim, Jo L.; Tezal, Mine; Scannapieco, Frank; Hyland, Andrew; Andrews, Christopher A.; Genco, Robert J.

    2014-01-01

    Purpose While some evidence suggests that periodontal disease (PD) might be positively associated with lung cancer, prospective studies in women are limited. Previous findings may reflect residual confounding by smoking. The study aims to determine whether history of PD diagnosis is associated with incident lung cancer in a large cohort of postmenopausal women. Methods Prospective analyses were conducted in a cohort of 77,485 postmenopausal women enrolled in the Women’s Health Initiative Observational Study. History of PD (prevalence of 26.1%) was self-reported and 754 incident lung cancer cases occurred during an average 6.8 (SD ±2.6) years of follow-up. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Overall, PD was positively associated with lung cancer risk after adjusting for detailed smoking history including smoking status and pack-years of smoking (HR=1.24, 95% CI: 1.07–1.45). There was a positive additive interaction between PD with pack-years of smoking (P=0.02), suggesting a potential synergistic effect between PD and smoking intensity on lung cancer. The association between PD and lung cancer was stronger in former smokers. When restricted to never-smokers, PD was not associated with lung cancer (HR=1.02, 95% CI: 0.68–1.53). Conclusions PD was not independently associated with lung cancer in non-smoking postmenopausal women. However, smoking and PD jointly increased lung cancer risk beyond that expected from the sum of the each effect separately. The potential synergism between PD and smoking on lung cancer warrants further examination. PMID:24913780

  12. Cytomegalovirus infection: its incidence and management in cytomegalovirus-seropositive living related liver transplant recipients: a single-center experience.

    PubMed

    Wadhawan, Manav; Gupta, Subash; Goyal, Neerav; Vasudevan, Karisangal R; Makki, Kausar; Dawar, Reetika; Sardana, Raman; Lal, Nand; Kumar, Ajay

    2012-12-01

    It is believed that antiviral prophylaxis decreases the incidence of cytomegalovirus (CMV) reactivation and disease. There are few data regarding weekly assays for CMV DNA after transplantation and the subsequent management of CMV. Here we report a cohort of living related liver transplantation (LRLT) patients who were treated for invasive CMV disease or for CMV infections if they were receiving steroids for rejection. Patients who underwent liver transplantation at our center between September 2006 and August 2010 and were recipient-positive/donor-positive (R(+) /D(+) ) were prospectively included. Patients were tested for CMV DNA 3 weeks after transplantation. CMV DNA-positive patients underwent weekly DNA monitoring until there were 2 consecutive negative reports. Those who developed CMV disease or had rising DNA titers while they were on treatment for rejection were treated. A Cox regression analysis was performed for factors predicting survival. Two hundred sixty-six of the 306 R(+) /D(+) patients were CMV DNA-negative 3 weeks after transplantation, and 40 had detectable DNA. One of the DNA-negative patients developed CMV disease after treatment for rejection with methylprednisolone. Thirty patients had <500 copies/mL, and 10 had ≥500 copies/mL. Two of the 30 patients with DNA levels < 500 copies/mL developed CMV disease. Six of the 10 patients with DNA levels ≥500 copies/mL developed disease. CMV disease occurred in 9 of the 306 patients (2.9%). One patient received treatment for a rise in DNA titers while he was receiving steroids. There was a significant correlation between steroid administration for acute cellular rejection (ACR) and CMV reactivation (P = 0.003) and disease (P = 0.002). A multivariate analysis showed that CMV reactivation/disease did not predict survival. There was no difference in survival between CMV DNA-positive patients and CMV DNA-negative patients (P = 0.68). In conclusion, CMV reactivation is common after LRLT (13%), but the

  13. Occupational exposure and 25-year incidence rate of non-specific lung disease: the Zutphen Study.

    PubMed

    Heederik, D; Kromhout, H; Burema, J; Biersteker, K; Kromhout, D

    1990-12-01

    Information gathered in the Zutphen Study, the Dutch contribution to the Seven Countries Study that started in the 1960s, was used for the present study. In 1960 878 men participated in the physical examination and they were followed for 25 years until 1 July 1985. During this follow-up, their morbidity status was verified regularly. With this information the occurrence of chronic non-specific lung disease (CNSLD) at a specific time was coded by one physician, using strict criteria. The CNSLD diagnosis was based on the following criteria: episodes of respiratory symptoms such as regular cough and phlegm for longer than three months or episodes of wheezing and shortness of breath reported to the survey physician, or: diagnosis of CNSLD, including chronic bronchitis or emphysema by a clinical specialist. Occupation in 1960 was coded and used to generate specific occupational exposures with a Job Exposure Matrix. Because the exact time of diagnosis of CNSLD was known, incidence densities could be calculated. For 804 men a complete set of data was available. A Poisson regression analysis was used to analyse the relationships between the incidence density and independent variables like age, calendar period, occupation and specific occupational exposures. Blue collar workers had a significantly elevated incidence density ratio (IDR) compared to white collar workers (1.82, 95% confidence limits (CL): 1.35, 2.46). Subgroups of blue collar workers, wood and paper workers, textile workers, and tailors, construction workers and transport workers had significantly elevated IDRs also. Of the specific exposures heavy metals, mineral dust and adhesives had a significantly elevated IDR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2084026

  14. Solid cancer incidence other than lung, liver and bone in Mayak workers: 1948–2004

    PubMed Central

    Hunter, N; Kuznetsova, I S; Labutina, E V; Harrison, J D

    2013-01-01

    Background: Cancer incidence in the Mayak Production Association (PA) cohort was analysed to investigate for the first time whether external gamma-ray and internal plutonium exposure are associated with raised incidence of solid cancers other than lung, liver and bone (other solid cancers). Methods: The cohort includes 22 366 workers of both sexes who were first employed between 1948 and 1982. A total of 1447 cases of other solid cancers were registered in the follow-up period until 2004. The Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative exposure to plutonium and external gamma-ray. Results: A weak association was found between cumulative exposure to external gamma-ray and the incidence of other solid cancers (ERR/Gy=0.07; 95% confidence intervals (CIs): 0.01–0.15), but this association lost its significance after adjusting for internal plutonium exposure. There was no indication of any association with plutonium exposure for other solid cancers. Among 16 individual cancer sites, there was a statistically significant association with external exposure for lip cancer (ERR/Gy=1.74; 95% CI: 0.37; 6.71) and with plutonium exposure for pancreatic cancer (ERR/Gy=1.58; 95% CI; 0.17; 4.77). Conclusion: This study of Mayak workers does not provide evidence of an increased risk of other solid cancers. The observed increase in the risk of cancer of the lip and pancreas should be treated with caution because of the limited amount of relevant data and because the observations may be simply due to chance. PMID:24022197

  15. Acute fibrinous and organizing pneumonia associated with influenza A/H1N1 pneumonia after lung transplantation

    PubMed Central

    2013-01-01

    Background Immunocompromised patients, particularly after lung transplantation, are at high risk to develop atypical forms of pulmonary infections including influenza A/H1N1. Acute Fibrinous and Organizing Pneumonia (AFOP) is a special histological pattern in acute respiratory failure with high mortality. Case presentation We describe a 66-year-old woman with double lung transplantation in August 2009 due to end stage pulmonary fibrosis. After prolonged weaning and subsequent promising course, she developed atypical pneumonia with diffuse pulmonary infiltrates in both lungs in January 2010. Infection with influenza A/H1N1 virus was verified. The patient rapidly suffered from respiratory insufficiency and died eight days after this diagnosis. The post-mortem revealed especially in the lower parts of the lungs the classical histological pattern of pure AFOP. Molecular analyses of lung tissue were positive for influenza A/H1N1. Conclusion To our knowledge we present the first case of AFOP triggered by viral infection, here proven to be influenza virus A/H1N1. Thus, also in the setting of viral infection the highly deadly differential diagnosis of AFOP must be considered. PMID:23683442

  16. Long-Term Extracorporeal Membrane Oxygenation as Bridging Strategies to Lung Transplantation in Rapidly Devastating Isolated Langerhans Cell Histiocytosis.

    PubMed

    Sacco, Oliviero; Moscatelli, Andrea; Conte, Massimo; Grasso, Chiara; Magnano, Gian Michele; Sementa, Angela Rita; Martelli, Alberto; Rossi, Giovanni A

    2016-05-01

    Isolated pulmonary involvement in pediatric Langerhans cell histiocytosis (LCH) is extremely rare. While the multisystem-LCH course varies from spontaneous remission to rapid deterioration with lethal outcome, single system involvement is generally associated with favorable prognosis. A child with isolated pulmonary LCH had an extremely rapid progression leading to respiratory failure, despite treatment with prednisone and vinblastine. Since lung hyperinflation and cystic degeneration contraindicated conventional mechanical ventilation, extracorporeal membrane oxygenation (ECMO) was chosen for 50 days as a bridge to lung transplantation. The mechanisms involved in disease progression and the usefulness of long-term ECMO are discussed. PMID:26840616

  17. Long-term leukopenia in a lung transplanted patient with cystic fibrosis treated with zoledronic acid: a case report.

    PubMed

    Karahasanovic, A; Thorsteinsson, A-L; Bjarnason, N H; Eiken, P

    2016-08-01

    Cystic fibrosis (CF) is a serious autosomal recessive genetic disorder associated with chronic lung disease, malabsorption, malnutrition, pancreatic insufficiency and premature respiratory failure. Recent advances in medical science and technology have increased the lifespan of patients with CF, albeit with long-term consequences of the disease, such as osteoporosis, becoming of increasing significance. The medical treatment of osteoporosis in patients with CF or after organ transplantation is still being explored, and no clear guidelines regarding the best choice of bisphosphonate exist. We report a case of a young woman with CF, lung transplantation and low bone mass developing long-term leukopenia after treatment with zoledronic acid. The leukopenia, with a strong affection of the neutrocytes, lasted for 4 months and the condition only went into remission after granulocyte-colony stimulating factor (G-CSF) treatment. It is important to be aware of symptomatic leukopenia in immunosuppressive patients after treatment with zoledronic acid. PMID:27080707

  18. Beyond cancer treatment – a review of total lymphoid irradiation for heart and lung transplant recipients

    SciTech Connect

    McKay, Clare Knight, Kellie A; Wright, Caroline

    2014-09-15

    Immunosuppressive drugs used in the management of heart and lung transplants have a large monetary and quality of life cost due to their side effects. Total lymphoid irradiation (TLI) is one method of minimising the need for or replacing post-operative immunosuppressive drugs. A literature review was conducted on electronic databases using defined search terms. The aim was to establish the indications for the use of TLI, its advantages and disadvantages and the weaknesses associated with the methods used in related research. Eight articles were located that focused on TLI usage in combating organ rejection. These studies identified that the use of TLI resulted in a reduction in early rejection. One study reported a drop in rejection episodes from 0.46 to 0.14 episodes per patient per month once the TLI was complete. While the short-term prognosis is excellent, the long-term outlook is less positive with an increased risk of organ rejection and myelodysplasia 3.5 years post-TLI. This review reminds us that radiation therapy (RT) is not exclusively indicated for cancer treatment. While TLI cannot replace immunosuppressive drug therapy, it can offer a treatment option for people that cannot tolerate immunosuppressive drugs, or when conventional anti-rejection treatment is no longer viable. Reported long-term complications suggest that TLI should be used with caution. However, this modality should not be overlooked in cases of chronic rejection. Further research is required to establish the efficacy of RT in the treatment of transplant patients who are unsuitable for drug-based anti-rejection therapies.

  19. A 54-Year-Old Man Presenting With an Abnormal Abdominal CT Scan 8 Months After Double Lung Transplant.

    PubMed

    Mistrot, Daniel P; Gemma, Vincent A; Gagliano, Ronald A; Omar, Ashraf; Panchabhai, Tanmay S

    2016-05-01

    A 54-year-old man who had undergone bilateral sequential lung transplant for idiopathic pulmonary fibrosis was admitted to the hospital for further evaluation of an abnormal abdominal CT scan. Three months previously a gastrojejunostomy tube had been placed after he was found to have evidence of silent aspiration with oral intake. At a recent clinic visit, he denied abdominal pain or problems with the feeding tube. He described frequent diarrhea since placement of the feeding tube. PMID:27157231

  20. Proteomic Characterization Reveals That MMP-3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation.

    PubMed

    Liu, X; Yue, Z; Yu, J; Daguindau, E; Kushekhar, K; Zhang, Q; Ogata, Y; Gafken, P R; Inamoto, Y; Gracon, A; Wilkes, D S; Hansen, J A; Lee, S J; Chen, J Y; Paczesny, S

    2016-08-01

    Improved diagnostic methods are needed for bronchiolitis obliterans syndrome (BOS), a serious complication after allogeneic hematopoietic cell transplantation (HCT) and lung transplantation. For protein candidate discovery, we compared plasma pools from HCT transplantation recipients with BOS at onset (n = 12), pulmonary infection (n = 16), chronic graft-versus-host disease without pulmonary involvement (n = 15) and no chronic complications after HCT (n = 15). Pools were labeled with different tags (isobaric tags for relative and absolute quantification), and two software tools identified differentially expressed proteins (≥1.5-fold change). Candidate proteins were further selected using a six-step computational biology approach. The diagnostic value of the lead candidate, matrix metalloproteinase 3 (MMP3), was evaluated by enzyme-linked immunosorbent assay in plasma of a verification cohort (n = 112) with and without BOS following HCT (n = 76) or lung transplantation (n = 36). MMP3 plasma concentrations differed significantly between patients with and without BOS (area under the receiver operating characteristic curve 0.77). Consequently, MMP3 represents a potential noninvasive blood test for diagnosis of BOS. PMID:26887344

  1. External stimuli in the form of vibratory massage after heart or lung transplantation.

    PubMed

    Doering, T J; Fieguth, H G; Steuernagel, B; Brix, J; Konitzer, M; Schneider, B; Fischer, G C

    1999-01-01

    Manual vibratory massage is part of the preventive physiotherapeutic activities performed in intensive care units. The vibratory massage can be performed manually or as electrovibratory massage. The manual massage is a fast rhythmical vibration performed by the arm and shoulder muscles of the masseur and transferred to the patient's thorax by the hand. The hand of the masseur has to achieve a tremor with a frequency of 8 to 11 tremors/s. The aim of the pilot study was to examine the influence of manual vibratory massage on the pulmonary function of postoperative patients who were receiving mechanical ventilation, with special interest being focused on pulmonary ventilation and perfusion and cerebral blood flow velocity. Manual vibratory massage was performed postoperatively in the intensive care unit on eight patients: three patients had undergone heart transplantation, three had undergone lung transplantation, and two had undergone coronary artery bypass grafting (mean age, 53.6+/-8 yr). With the aid of continuous monitoring, we examined the changes of the respiration parameters and the cerebral blood flow velocity (measured by transcranial Doppler sonography). The vibratory massage was performed with a frequency of 8 to 10 vibrations/s for 15 min, 7.5 min on each side of the thorax, starting from the lower costal arch and progressing to the upper thoracic aperture. For 10 min before, during, and 10 min after the massage, the parameters of peripheral oxygen saturation, central venous pressure, mean arterial pressure, heart rate, lung resistance and compliance, tidal volume, respiration rate, and cerebral blood flow velocity were recorded at 2-min intervals. Moreover, before and after vibratory massage, arterial blood gases were determined. In four of the eight patients, it was possible to determine pulmonary arterial pressure, pulmonary capillary wedge pressure, as well as pulmonary vascular resistance. During the vibratory massage, we could prove a significant

  2. Looking Beyond Respiratory Cultures: Microbiome-Cytokine Signatures of Bacterial Pneumonia and Tracheobronchitis in Lung Transplant Recipients.

    PubMed

    Shankar, J; Nguyen, M H; Crespo, M M; Kwak, E J; Lucas, S K; McHugh, K J; Mounaud, S; Alcorn, J F; Pilewski, J M; Shigemura, N; Kolls, J K; Nierman, W C; Clancy, C J

    2016-06-01

    Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia-colonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases. PMID:26693965

  3. Genotyping of Pseudomonas aeruginosa isolates from lung transplant recipients and aquatic environment-detected in-hospital transmission.

    PubMed

    Johansson, Ewa; Welinder-Olsson, Christina; Gilljam, Marita

    2014-02-01

    Lung infection with Pseudomonas aeruginosa is common in lung transplant recipients and may lead to severe complications. Bacteriological surveillance aims to detect transmission of microbes between hospital environment and patients. We sought to determine whether genotyping of P. aeruginosa isolates could improve identifications of pathways of infection. From 2004 to 2009, we performed genotyping with multiple-locus variable number of tandem repeats analysis (MLVA) and pulsed-field gel electrophoresis (PFGE) of P. aeruginosa isolates cultured from lung transplant recipients at Sahlgrenska University Hospital, Gothenburg. During a small outbreak in 2008, cultivation and genotyping of isolates from sink and drains samples from the hospital ward were performed. Pseudomona aeruginosa from 11/18 patients were genotyped to unique strains. The remaining seven patients were carriers of a P. aeruginosa strain of cluster A genotype. Pseudomona aeruginosa was isolated in 4/8 water samples, typed by MLVA also as cluster A genotype and confirmed by PFGE to be similar or identical to the isolates from four transplanted patients. In conclusion, genotyping of isolates revealed a clonal relationship between patient and water isolates, indicating in-hospital transmission of P. aeruginosa. We suggest genotyping with MLVA for rapid routine surveillance, with the PFGE method used for extended, confirmatory analyses. PMID:24450429

  4. Late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation: incidence and risk factors. European Group or Blood and Marrow Transplantation (EBMT) Working Party on Late Effects.

    PubMed

    Tichelli, A; Duell, T; Weiss, M; Socié, G; Ljungman, P; Cohen, A; van Lint, M; Gratwohl, A; Kolb, H J

    1996-06-01

    The incidence, time course and risk factors associated with late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation (BMT) was evaluated in a multicenter retrospective cohort study conducted by the European Group for Blood and Marrow Transplantation (EBMT) Working Party on Late Effects. Data were requested from participating European centers on all patients transplanted up to December 1980 and on all patients treated during the year of 1984. Twenty-eight centers reported data on 258 patients and 248 could be evaluated for keratoconjunctivitis. Forty-eight of the 248 (19%) patients developed a keratoconjunctivitis sicca syndrome between 3 and 127 months (13.8 months) after BMT. The actuarial probability of developing dry eyes was 21 +/- 3% at 15 years. Thirty-three of the 48 (69%) patients with sicca syndrome had graft-versus-host disease (GVHD) compared to 60 of 200 (30%) patients without keratoconjunctivitis (P < 0.0001). The probability of developing keratoconjunctivitis sicca syndrome at 15 years was 38 +/- 6% for patients with and 10 +/- 3% (P < 0.0001) for those without chronic GVHD. Factors associated with an increased risk for late-onset of keratoconjunctivitis are chronic GVHD (relative risk 3.5; CI, 1.9-6.9), female patients (5.6; CI, 1.6-18.8), age older than 20 years (3.1; CI, 1.6-5.6), single dose irradiation for preparation to BMT (3.8; CI, 1.3-11.3) and methotrexate for prevention of GVHD (3.6, CI, 1.05-12.8). Late-onset kerato- conjunctivitis is a frequent ocular complication of BMT. With adequate treatment, severe corneal defects can be avoided. It occurs more frequently in patients with chronic GVHD, but, independent of chronic GVHD, more frequently in older patients and in females as it is observed in de novo Sjögren's syndrome. These data support the current concept that chronic GVHD is a reaction of both, allo- and autoimmunity. PMID:8807122

  5. Transition to routine use of venoarterial extracorporeal oxygenation during lung transplantation could improve early outcomes

    PubMed Central

    Yu, Woo Sik; Paik, Hyo Chae; Haam, Seok Jin; Lee, Chang Young; Nam, Kyung Sik; Jung, Hee Suk; Do, Young Woo; Shu, Jee Won

    2016-01-01

    Background The study objective was to compare the outcomes of intraoperative routine use of venoarterial (VA) extracorporeal membrane oxygenation (ECMO) versus selective use of cardiopulmonary bypass (CPB). Methods Between January 2010 and February 2013, 41 lung transplantations (LTx) were performed, and CPB was used as a primary cardiopulmonary support modality by selective basis (group A). Between March 2013 and December 2014, 41 LTx were performed, and ECMO was used routinely (group B). The two groups were compared retrospectively. Results The operative time was significantly longer in group A (group A, 458 min; group B, 420 min; P=0.041). Postoperatively, patients in group B had less fresh frozen plasma (FFP) transfusion (P=0.030). Complications were not different between the two groups. The 30- and 90-day survival rates were better in group B (30-day survival: group A, 75.6%; group B, 95.1%, P=0.012; 90-day survival: group A, 68.3%; group B, 87.8%, P=0.033). The 1-year survival showed better trends in group B, but it was not significant. Forced vital capacity (FVC) at 1, 3, and 6 months after LTx was better in group B than in group A (1 month: group A, 43.8%; group B, 52.9%, P=0.043; 3 months: group A, 45.5%; group B, 59.0%, P=0.005; 6 months: group A, 51.5%; group B, 65.2%, P=0.020). Forced expiratory volume in 1 second (FEV1) at 3 months after LTx was better in patients in group B than that in patient in group A (group A, 53.3%; group B, 67.5%, P=0.017). Conclusions Routine use of ECMO during LTx could improve early outcome and postoperative lung function without increased extracorporeal-related complication such as vascular and neurologic complications. PMID:27499961

  6. Pharmacokinetics of Posaconazole Suspension in Lung Transplant Patients with and without Cystic Fibrosis.

    PubMed

    Zhang, Hongfei; Nguyen, M Hong; Clancy, Cornelius J; Joshi, Rujuta; Zhao, Wenchen; Ensor, Chris; Venkataramanan, Raman; Shields, Ryan K

    2016-06-01

    Invasive fungal infections (IFIs) are common among lung transplant recipients (LTRs). Posaconazole is an important antifungal agent for both prophylaxis and treatment of IFIs; however, detailed pharmacokinetic data are limited among LTRs, particularly those with cystic fibrosis (CF). Our objective was to conduct a pharmacokinetic study of posaconazole oral suspension among LTRs, with particular attention to patients with CF. We enrolled 20 LTRs, 7 with CF and 13 with other underlying lung diseases. Average daily doses in CF and non-CF patients were 829 and 862 mg, respectively. After ≥5 days of treatment, only 4 patients had average plasma concentrations of >0.7 μg/ml. Average steady-state plasma concentrations were 61% lower in CF patients (0.233 μg/ml) than in non-CF LTRs (0.594 μg/ml; P = 0.03). The average dose-normalized plasma area-under-the-curve (AUC) values were also lower in CF (0.007 h·μg/ml) than in non-CF LTRs (0.02 h·μg/ml; P = 0.02). The weight-normalized apparent oral clearance values were 2.51 and 0.74 liters/h/kg among CF and non-CF LTRs, respectively (P = 0.005). Despite significant interpatient variability, plasma trough concentrations were strongly correlated with posaconazole AUC across all LTRs (r(2) = 0.95, P < 0.0001). Taken together, our study highlights a critical need to incorporate new formulations of posaconazole into prophylaxis and treatment strategies for LTRs, particularly those with CF. Future pharmacokinetic studies of both tablet and intravenous formulations must consider LTR-specific factors and incorporate a therapeutic drug monitoring plan in this patient population. PMID:27021324

  7. Analysis of incidence, risk factors and clinical outcome of thromboembolic and bleeding events in 431 allogeneic hematopoietic stem cell transplantation recipients

    PubMed Central

    Labrador, Jorge; Lopez-Anglada, Lucia; Perez-Lopez, Estefania; Lozano, Francisco S.; Lopez-Corral, Lucia; Sanchez-Guijo, Fermin M.; Vazquez, Lourdes; Perez Rivera, Jose Angel; Martin-Herrero, Francisco; Sanchez-Barba, Mercedes; Guerrero, Carmen; del Cañizo, Maria Consuelo; Caballero, Maria Dolores; San Miguel, Jesus Fernando; Alberca, Ignacio; Gonzalez-Porras, Jose Ramon

    2013-01-01

    Allogeneic hematopoietic stem cell transplantation recipients have an increasing risk of both hemorrhagic and thrombotic complications. However, the competing risks of two of these life-threatening complications in these complex patients have still not been well defined. We retrospectively analyzed data from 431 allogeneic transplantation recipients to identify the incidence, risk factors and mortality due to thrombosis and bleeding. Significant clinical bleeding was more frequent than symptomatic thrombosis. The cumulative incidence of a bleeding episode was 30.2% at 14 years. The cumulative incidence of a venous or arterial thrombosis at 14 years was 11.8% and 4.1%, respectively. The analysis of competing factors for venous thrombosis revealed extensive chronic graft-versus-host disease to be the only independent prognostic risk factor. By contrast, six factors were associated with an increased risk of bleeding; advanced disease, ablative conditioning regimen, umbilical cord blood transplantation, anticoagulation, acute III-IV graft-versus-host disease, and transplant-associated microangiopathy. The development of thrombosis did not significantly affect overall survival (P=0.856). However, significant clinical bleeding was associated with inferior survival (P<0.001). In allogeneic hematopoietic stem cell transplantation, significant clinical bleeding is more common than thrombotic complications and affects survival. PMID:22899581

  8. Occupation and three-year incidence of respiratory symptoms and lung function decline: the ARIC Study

    PubMed Central

    2012-01-01

    Background Specific occupations are associated with adverse respiratory health. Inhalation exposures encountered in these jobs may place workers at risk of new-onset respiratory disease. Methods We analyzed data from 8,967 participants from the Atherosclerosis Risk in Communities (ARIC) study, a longitudinal cohort study. Participants included in this analysis were free of chronic cough and phlegm, wheezing, asthma, chronic bronchitis, emphysema, and other chronic lung conditions at the baseline examination, when they were aged 45-64 years. Using data collected in the baseline and first follow-up examination, we evaluated associations between occupation and the three-year incidence of cough, phlegm, wheezing, and airway obstruction and changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured by spirometry. All associations were adjusted for age, cigarettes per day, race, smoking status, and study center. Results During the approximately three-year follow-up, the percentage of participants developing chronic cough was 3%; chronic phlegm, 3%; wheezing, 3%; and airway obstruction, defined as FEV1 < lower limit of normal (LLN) and FEV1/FVC < LLN, 2%. The average annual declines in FEV1 and FVC were 56 mL and 66 mL, respectively, among men and 40 mL and 52 mL, respectively, among women. Relative to a referent category of managerial and administrative support occupations, elevated risks of new-onset chronic cough and chronic phlegm were observed for mechanics and repairers (chronic cough: RR: 1.81, 95% CI: 1.02, 3.21; chronic phlegm: RR: 2.10, 95% CI: 1.23, 3.57) and cleaning and building service workers (chronic cough: RR: 1.85, 95% CI: 1.01, 3.37; chronic phlegm: RR: 2.28, 95% CI: 1.27, 4.08). Despite the elevated risk of new-onset symptoms, employment in cleaning and building services was associated with attenuated lung function decline, particularly among men, who averaged annual declines in FEV1 and FVC of 14 mL and 23 m

  9. Antifungal prophylaxis in lung transplantation--a world-wide survey.

    PubMed

    Neoh, C F; Snell, G I; Kotsimbos, T; Levvey, B; Morrissey, C O; Slavin, M A; Stewart, K; Kong, D C M

    2011-02-01

    While variations in antifungal prophylaxis have been previously reported in lung transplant (LTx) recipients, recent clinical practice is unknown. Our aim was to determine current antifungal prophylactic practice in LTx centers world-wide. One nominated LTx clinician from each active center was invited by e-mail to participate in a web-based survey between September 2009 and January 2010. Fifty-seven percent (58/102) responded. The majority of responses were from medical directors of LTx centers (72.4%), and from the United States (44.8%). Within the first 6 months post-LTx, most centers (58.6%) employed universal prophylaxis, with 97.1% targeting Aspergillus species. Voriconazole alone, and in combination with inhaled amphotericin B (AmB), were the preferred first-line agents. Intolerance to side effects of voriconazole (69.2%) was the main reason for switching to alternatives. Beyond 6 months post-LTx, most (51.8%) did not employ antifungal prophylaxis. Fifteen centers (26.0%) conducted routine antifungal therapeutic drug monitoring during prophylactic period. There are differences in strategies employed between U.S. and European centers. Most respondents indicated a need for antifungal prophylactic guidelines. In comparison to earlier findings, there was a major shift toward prophylaxis with voriconazole and an increased use of echinocandins, posaconazole and inhaled lipid formulation AmB. PMID:21272239

  10. Successful Kidney and Lung Transplantation From a Deceased Donor With Blunt Abdominal Trauma and Intestinal Perforation

    PubMed Central

    van Smaalen, Tim C.; Krikke, Christina; Haveman, Jan Willem; van Heurn, L.W. Ernest

    2016-01-01

    The number of organ donors is limited by many contraindications for donation and poor quality of potential organ donors. Abdominal infection is a generally accepted contraindication for donation of abdominal organs. We present a 43-year-old man with lethal brain injury, blunt abdominal trauma, and intestinal perforation. After withdrawal of life-sustaining treatment and circulatory arrest, a minilaparotomy confirmed abdominal contamination with intestinal content. After closure of the abdomen, organs were preserved with in situ preservation with an aortic cannula inserted via the femoral artery. Thereafter, the kidneys were procured via bilateral lumbotomy to reduce the risk of direct bacterial contamination; lungs were retrieved following a standard practice. There was no bacterial or fungal growth in the machine preservation fluid of both kidneys. All organs were successfully transplanted, without postoperative infection, and functioned well after 6 months. We hereby show that direct contamination of organs can be avoided with the use of in situ preservation and retroperitoneal procurement. Intestinal perforation is not an absolute contraindication for donation, although the risk of bacterial or fungal transmission has to be evaluated per case.

  11. Successful Kidney and Lung Transplantation From a Deceased Donor With Blunt Abdominal Trauma and Intestinal Perforation.

    PubMed

    van Smaalen, Tim C; Krikke, Christina; Haveman, Jan Willem; van Heurn, L W Ernest

    2016-01-01

    The number of organ donors is limited by many contraindications for donation and poor quality of potential organ donors. Abdominal infection is a generally accepted contraindication for donation of abdominal organs. We present a 43-year-old man with lethal brain injury, blunt abdominal trauma, and intestinal perforation. After withdrawal of life-sustaining treatment and circulatory arrest, a minilaparotomy confirmed abdominal contamination with intestinal content. After closure of the abdomen, organs were preserved with in situ preservation with an aortic cannula inserted via the femoral artery. Thereafter, the kidneys were procured via bilateral lumbotomy to reduce the risk of direct bacterial contamination; lungs were retrieved following a standard practice. There was no bacterial or fungal growth in the machine preservation fluid of both kidneys. All organs were successfully transplanted, without postoperative infection, and functioned well after 6 months. We hereby show that direct contamination of organs can be avoided with the use of in situ preservation and retroperitoneal procurement. Intestinal perforation is not an absolute contraindication for donation, although the risk of bacterial or fungal transmission has to be evaluated per case. PMID:27500248

  12. Low incidence of acute rejection in hepatitis B virus positive liver transplant recipients and the impact of hepatitis B immunoglobulin.

    PubMed

    Veerappan, Annapoorani; VanWagner, Lisa B; Mathew, James M; Huang, Xuemei; Miller, Joshua; Lapin, Brittany; Levitsky, Josh

    2016-04-01

    Historically, hepatitis B virus (HBV) liver transplantation (LT) recipients have less acute cellular rejection (ACR) than those without HBV. We questioned whether this has persisted in an era of decreased Hepatitis B immunoglobulin use (HBIG) given its in vitro immunoregulatory effects. We compared the incidence, risk factors and outcomes of ACR among 40,593 primary LT recipients with HBV, hepatitis C, steatohepatitis, and immune liver disease (OPTN 2000-2011). We also assessed the in vitro effect of HBIG on alloimmune lymphoproliferation and regulatory T cell generation using mixed lymphocyte reactions. In multivariate analysis, HBV status remained a strong independent predictor of freedom from ACR (OR 0.58, 95% CI: 1.5-2.1). Patient (67.7% vs 72.3%) and graft (60.8% vs 69.1%) survival were significantly lower in patients with ACR versus no ACR for all causes except HBV. HBIG use had no statistical association with ACR. In vitro, HBIG at concentrations equivalent to clinical dosing did not inhibit lymphoproliferation or promote regulatory T cell development. In summary, the incidence and impact of ACR is lower now for HBV LT and does not appear to be secondary to HBIG by our in vitro and in vivo analyses. Rather, it may be due to the innate immunosuppressive properties of chronic HBV infection. PMID:26924082

  13. Particulate Matter Air Pollution Exposure, Distance to Road, and Incident Lung Cancer in the Nurses’ Health Study Cohort

    PubMed Central

    Hart, Jaime E.; Yanosky, Jeff D.; Spiegelman, Donna; Wang, Molin; Fisher, Jared A.; Hong, Biling; Laden, Francine

    2014-01-01

    Background: A body of literature has suggested an elevated risk of lung cancer associated with particulate matter and traffic-related pollutants. Objective: We examined the relation of lung cancer incidence with long-term residential exposures to ambient particulate matter and residential distance to roadway, as a proxy for traffic-related exposures. Methods: For participants in the Nurses’ Health Study, a nationwide prospective cohort of women, we estimated 72-month average exposures to PM2.5, PM2.5–10, and PM10 and residential distance to road. Follow-up for incident cases of lung cancer occurred from 1994 through 2010. Cox proportional hazards models were adjusted for potential confounders. Effect modification by smoking status was examined. Results: During 1,510,027 person-years, 2,155 incident cases of lung cancer were observed among 103,650 participants. In fully adjusted models, a 10-μg/m3 increase in 72-month average PM10 [hazard ratio (HR) = 1.04; 95% CI: 0.95, 1.14], PM2.5 (HR = 1.06; 95% CI: 0.91, 1.25), or PM2.5–10 (HR = 1.05; 95% CI: 0.92, 1.20) was positively associated with lung cancer. When the cohort was restricted to never-smokers and to former smokers who had quit at least 10 years before, the associations appeared to increase and were strongest for PM2.5 (PM10: HR = 1.15; 95% CI: 1.00, 1.32; PM2.5: HR = 1.37; 95% CI: 1.06, 1.77; PM2.5–10: HR = 1.11; 95% CI: 0.90, 1.37). Results were most elevated when restricted to the most prevalent subtype, adenocarcinomas. Risks with roadway proximity were less consistent. Conclusions: Our findings support those from other studies indicating increased risk of incident lung cancer associated with ambient PM exposures, especially among never- and long-term former smokers. Citation: Puett RC, Hart JE, Yanosky JD, Spiegelman D, Wang M, Fisher JA, Hong B, Laden F. 2014. Particulate matter air pollution exposure, distance to road, and incident lung cancer in the Nurses’ Health Study Cohort. Environ

  14. Whole-genome sequencing of asian lung cancers: second-hand smoke unlikely to be responsible for higher incidence of lung cancer among Asian never-smokers.

    PubMed

    Krishnan, Vidhya G; Ebert, Philip J; Ting, Jason C; Lim, Elaine; Wong, Swee-Seong; Teo, Audrey S M; Yue, Yong G; Chua, Hui-Hoon; Ma, Xiwen; Loh, Gary S L; Lin, Yuhao; Tan, Joanna H J; Yu, Kun; Zhang, Shenli; Reinhard, Christoph; Tan, Daniel S W; Peters, Brock A; Lincoln, Stephen E; Ballinger, Dennis G; Laramie, Jason M; Nilsen, Geoffrey B; Barber, Thomas D; Tan, Patrick; Hillmer, Axel M; Ng, Pauline C

    2014-11-01

    Asian nonsmoking populations have a higher incidence of lung cancer compared with their European counterparts. There is a long-standing hypothesis that the increase of lung cancer in Asian never-smokers is due to environmental factors such as second-hand smoke. We analyzed whole-genome sequencing of 30 Asian lung cancers. Unsupervised clustering of mutational signatures separated the patients into two categories of either all the never-smokers or all the smokers or ex-smokers. In addition, nearly one third of the ex-smokers and smokers classified with the never-smoker-like cluster. The somatic variant profiles of Asian lung cancers were similar to that of European origin with G.C>T.A being predominant in smokers. We found EGFR and TP53 to be the most frequently mutated genes with mutations in 50% and 27% of individuals, respectively. Among the 16 never-smokers, 69% had an EGFR mutation compared with 29% of 14 smokers/ex-smokers. Asian never-smokers had lung cancer signatures distinct from the smoker signature and their mutation profiles were similar to European never-smokers. The profiles of Asian and European smokers are also similar. Taken together, these results suggested that the same mutational mechanisms underlie the etiology for both ethnic groups. Thus, the high incidence of lung cancer in Asian never-smokers seems unlikely to be due to second-hand smoke or other carcinogens that cause oxidative DNA damage, implying that routine EGFR testing is warranted in the Asian population regardless of smoking status. PMID:25189529

  15. Incidence of and risk factors for ischemic-type biliary lesions following orthotopic liver transplantation.

    PubMed

    Heidenhain, Christoph; Pratschke, Johann; Puhl, Gero; Neumann, Ulf; Pascher, Andreas; Veltzke-Schlieker, Winfried; Neuhaus, Peter

    2010-01-01

    Ischemic-type biliary lesions (ITBL) account for a major part of patients' morbidity and mortality after orthotopic liver transplantation (OLT). The exact origin of this type of biliary complication remains unknown. This study retrospectively evaluated 1843 patients. Patients with primary sclerosing cholangitis were excluded from this study. The diagnosis of ITBL was established only when all other causes of destruction of the biliary tree were ruled out. Donor age (P = 0.028) and cold ischemic time (CIT) (P = 0.002) were found to be significant risk factors for the development of ITBL. Organs that were perfused with University of Wisconsin (UW) solution developed ITBL significantly more often than Histidine-Tryptophan-Ketoglutarate (HTK)-perfused organs (P = 0.036). The same applied to organs harvested externally and shipped to our center versus those that were procured locally by our harvest teams (P < 0.001). Pressure perfusion via the hepatic artery significantly reduced the risk of ITBL (P = 0.001). The only recipient factor that showed a significant influence was Child-Pugh score status C (P = 0.021). Immunologic factors had no significant impact on ITBL. The clinical consequences of this study for our institution have been the strict limitation of CIT to <10 h and the exclusive use of HTK solution. We further advocate that all organ procurement teams perform pressure perfusion on harvested organs. PMID:19691661

  16. Incidence and predictors of post-reperfusion syndrome in living donor liver transplantation.

    PubMed

    Chung, In S; Kim, Ha Y; Shin, Young H; Ko, Justin S; Gwak, Mi S; Sim, Woo S; Kim, Gaab S; Lee, Suk-Koo

    2012-01-01

    A characteristic pattern of hemodynamic changes that may occur in reperfusion phase of liver transplantation (LT) is known as post-reperfusion syndrome (PRS). In this study, we determined the frequency of PRS and evaluated possible predictors of PRS. The medical records of 152 patients who underwent living donor LT were reviewed. PRS was defined as a decrease in mean arterial pressure of more than 30% from the baseline value for more than one min during the first five min after reperfusion. The frequency of PRS was determined, and patients were divided into two groups: PRS group and non-PRS group. Donor factors, preoperative and intraoperative recipient factors, and postoperative outcomes were compared between the two groups. PRS occurred in 58 recipients (34.2%). Preoperative model for end-stage liver disease scores of recipients and percentage of graft steatotic changes were higher in PRS group. PRS group showed higher heart rates and lower hemoglobin values preoperatively. Before reperfusion, PRS group received more transfusion and their urine output was less than that of non-PRS group. Postoperatively, peak bilirubin during the first five d after LT was higher in PRS group. In conclusion, both severity of liver disease and graft steatosis may increase risk for PRS in LT. Further prospective studies of PRS in its relationship to outcome are indicated. PMID:22168355

  17. Latin American Dialysis and Transplant Registry: 2008 prevalence and incidence of end-stage renal disease and correlation with socioeconomic indexes.

    PubMed

    Cusumano, Ana M; Garcia-Garcia, Guillermo; Gonzalez-Bedat, Maria C; Marinovich, Sergio; Lugon, Jocemir; Poblete-Badal, Hugo; Elgueta, Susana; Gomez, Rafael; Hernandez-Fonseca, Fabio; Almaguer, Miguel; Rodriguez-Manzano, Sandra; Freire, Nelly; Luna-Guerra, Jorge; Rodriguez, Gaspar; Bochicchio, Tommaso; Cuero, Cesar; Cuevas, Dario; Pereda, Carlos; Carlini, Raul

    2013-05-01

    In 2008, 563,294,000 people were living in Latin America (LA), of which 6.6% were older than 65. The region is going through a fast demographic and epidemiologic transition process, in the context of an improvement in socio-economic indices. The Latin American Dialysis and Renal Transplant Registry has collected data since 1991, through an annual survey completed by 20 affiliated National Societies. Renal replacement treatment (RRT) prevalence and incidence showed an increase year by year. The prevalence rate (in all modalities) correlated with the World Bank country classification by income and the epidemiologic transition stage the countries were experiencing. RRT prevalence and kidney transplantation rates correlated significantly with gross national income (GNI), health expenditure in constant dollars (HeExp), % older than 65, life expectancy at birth, and % of the population living in urban settings. Kidney transplantation increased also, year by year, with more than 50% of transplants performed using kidneys from deceased donors. Double transplants were performed in six countries. RRT prevalence and incidence increased in LA, and are associated with indexes reflecting higher and more evenly distributed national wealth (GNI and HeExp), and the stage of demographic and epidemiological transition. PMID:25018980

  18. Comprehensive Analysis of the Incidence and Survival Patterns of Lung Cancer by Histologies, Including Rare Subtypes, in the Era of Molecular Medicine and Targeted Therapy

    PubMed Central

    Chang, Jeffrey.S.; Chen, Li-Tzong; Shan, Yan-Shen; Lin, Sheng-Fung; Hsiao, Sheng-Yen; Tsai, Chia-Rung; Yu, Shu-Jung; Tsai, Hui-Jen

    2015-01-01

    Abstract Lung cancer is the third most common cancer in the world and has the highest cancer mortality rate. A worldwide increasing trend of lung adenocarcinoma has been noted. In addition, the identification of epidermal growth factor receptor (EGFR) mutations and the introduction of EGFR inhibitors to successfully treat EGFR mutated non–small cell lung cancers are breakthroughs for lung cancer treatment. The current study evaluated the incidence and survival of lung cancer using data collected by the Taiwan Cancer Registry between 1996 and 2008. The results showed that the most common histologic subtype of lung cancer was adenocarcinoma, followed by squamous cell carcinoma, small cell carcinoma, large cell carcinoma, neuroendocrine tumors, lymphoma, and sarcoma. Overall, the incidence of lung cancer in Taiwan increased significantly from 1996 to 2008. An increased incidence was observed for adenocarcinoma, particularly for women, with an annual percentage change of 5.9, whereas the incidence of squamous cell carcinoma decreased. Among the subtypes of lung cancer, the most rapid increase occurred in neuroendocrine tumors with an annual percentage change of 15.5. From 1996–1999 to 2005–2008, the 1-year survival of adenocarcinoma increased by 10% for men, whereas the 1-, 3-, and 5-year survivals of adenocarcinoma for women increased by 18%, 11%, and 5%, respectively. Overall, the incidence of lung cancer has been increasing in Taiwan, although the trends were variable by subtype. The introduction of targeted therapies was associated with a significantly improved survival for lung adenocarcinoma in Taiwan; however, more studies are needed to explain the rising incidence of lung adenocarcinoma. In addition, it is important to investigate the molecular pathogenesis of the various subtypes of lung cancer to develop novel therapeutic agents.

  19. Efficacy of Oral Ribavirin in Lung Transplant Patients With Respiratory Syncytial Virus Lower Respiratory Tract Infection

    PubMed Central

    Pelaez, Andres; Lyon, G. Marshall; Force, Seth D.; Ramirez, Allan M.; Neujahr, David C.; Foster, Marianne; Naik, Priyumvada M.; Gal, Anthony A.; Mitchell, Patrick O.; Lawrence, E. Clinton

    2012-01-01

    Background Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infection (LRI) and is a risk factor for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Currently, the most widely used therapy for RSV is inhaled ribavirin. However, this therapy is costly and cumbersome. We investigated the utility of using oral ribavirin for the treatment of RSV infection after LTx. Methods RSV was identified in nasopharyngeal swabs (NPS) or bronchoalveolar lavage (BAL) using direct fluorescent antibody (DFA) in 5 symptomatic LTx patients diagnosed with LRI. Data were collected from December 2005 and August 2007 and included: age; gender; type of LTx; underlying disease; date of RSV; pulmonary function prior to, during and up to 565 days post-RSV infection; need for mechanical ventilation; concurrent infections; and radiographic features. Patients received oral ribavirin for 10 days with solumedrol (10 to 15 mg/kg/day intravenously) for 3 days, until repeat NPS were negative. Results Five patients had their RSV–LRI diagnosis made at a median of 300 days post-LTx. Mean forced expiratory volume in 1 second (FEV1) fell 21% (p < 0.012) during infection. After treatment, FEV1 returned to baseline and was maintained at follow-up of 565 days. There were no complications and no deaths with oral therapy. A 10-day course of oral ribavirin cost $700 compared with $14,000 for nebulized ribavirin at 6 g/day. Conclusions Treatment of RSV after LTx with oral ribavirin and corticosteroids is well tolerated, effective and less costly than inhaled ribavirin. Further studies are needed to directly compare the long-term efficacy of oral vs nebulized therapy for RSV. PMID:19134533

  20. Meta-analysis of incidence of early lung toxicity in 3-dimensional conformal irradiation of breast carcinomas

    PubMed Central

    2013-01-01

    Background This meta-analysis aims to ascertain the significance of early lung toxicity with 3-Dimensional (3D) conformal irradiation for breast carcinomas and identify the sub-groups of patients with increased risk. Methods Electronic databases, reference sections of major oncological textbooks and identified studies were searched for synonyms of breast radiotherapy and radiation pneumonitis (RP). Major studies in thoracic irradiation were reviewed to identify factors frequently associated with RP. Meta-analysis for RP incidence estimation and odds ratio calculation were carried out. Results The overall incidence of Clinical and Radiological RP is 14% and 42% respectively. Ten studies were identified. Dose-volume Histogram (DVH) related dosimetric factors (Volume of lung receiving certain dose, Vdose and Mean lung Dose, MLD), supraclavicular fossa (SCF) irradiation and age are significantly associated with RP, but not sequential chemotherapy and concomitant use of Tamoxifen. A poorly powered study in IMN group contributed to the negative finding. Smoking has a trend towards protective effect against RP. Conclusion Use of other modalities may be considered when Ipsilateral lung V20Gy > 30% or MLD > 15 Gy. Extra caution is needed in SCF and IMN irradiation as they are likely to influence these dosimetric parameters. PMID:24229418

  1. An unusual cause of respiratory failure in a 25-year-old heart and lung transplant recipient.

    PubMed

    Narotzky, Sarah; Kennedy, Cassie Colleen; Maldonado, Fabien

    2015-05-01

    A 25-year-old woman, a never smoker with a history of heart-lung transplantation for World Health Organization group 1 pulmonary arterial hypertension performed 20 months prior to presentation, was evaluated for shortness of breath. Following transplantation, she was initiated on standard therapy of prednisone, tacrolimus, and azathioprine, along with routine antimicrobial prophylaxis. Her posttransplant course was complicated by persistent acute cellular rejection, as determined from a transbronchial biopsy specimen, without evidence of rejection in an endomyocardial biopsy specimen. The immunosuppressive medications were supplemented with pulse-dosed steroids, and the patient was transitioned from azathioprine to mycophenolate mofetil. Sirolimus was added 9 months prior to presentation. Three months prior to presentation, she was admitted for increasing oxygen requirements, shortness of breath, and bilateral infiltrates on the CT scans of the chest. PMID:25940262

  2. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.

    PubMed

    Mehra, Mandeep R; Crespo-Leiro, Maria G; Dipchand, Anne; Ensminger, Stephan M; Hiemann, Nicola E; Kobashigawa, Jon A; Madsen, Joren; Parameshwar, Jayan; Starling, Randall C; Uber, Patricia A

    2010-07-01

    The development of cardiac allograft vasculopathy remains the Achilles heel of cardiac transplantation. Unfortunately, the definitions of cardiac allograft vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, cardiac allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers. This document represents a working formulation for an international nomenclature of cardiac allograft vasculopathy, similar to the development of the system for adjudication of cardiac allograft rejection by histology. PMID:20620917

  3. Timing of Umbilical Cord Blood Derived Mesenchymal Stem Cells Transplantation Determines Therapeutic Efficacy in the Neonatal Hyperoxic Lung Injury

    PubMed Central

    Ahn, So Yoon; Sung, Dong Kyung; Sung, Se In; Yoo, Hye Soo; Oh, Won Il; Park, Won Soon

    2013-01-01

    Intratracheal transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) attenuates the hyperoxia-induced neonatal lung injury. The aim of this study was to optimize the timing of MSCs transplantation. Newborn Sprague-Dawley rats were randomly exposed to hyperoxia (90% for 2 weeks and 60% for 1 week) or normoxia after birth for 21 days. Human UCB-derived MSCs (5×105 cells) were delivered intratracheally early at postnatal day (P) 3 (HT3), late at P10 (HT10) or combined early+late at P3+10 (HT3+10). Hyperoxia-induced increase in mortality, TUNEL positive cells, ED1 positive alveolar macrophages, myeloperoxidase activity and collagen levels, retarded growth and reduced alveolarization as evidenced by increased mean linear intercept and mean alveolar volume were significantly better attenuated in both HT3 and HT3+10 than in HT10. Hyperoxia-induced up-regulation of both cytosolic and membrane p47phox indicative of oxidative stress, and increased inflammatory markers such as tumor necrosis factor-α, interleukin (IL) -1α, IL-1β, IL-6, and transforming growth factor-β measured by ELISA, and tissue inhibitor of metalloproteinase-1, CXCL7, RANTES, L-selectin and soluble intercellular adhesion molecule-1 measured by protein array were consistently more attenuated in both HT3 and HT3+10 than in HT10. Hyperoxia-induced decrease in hepatocyte growth factor and vascular endothelial growth factor was significantly up-regulated in both HT3 and HT3+10, but not in HT10. In summary, intratracheal transplantation of human UCB derived MSCs time-dependently attenuated hyperoxia-induced lung injury in neonatal rats, showing significant protection only in the early but not in the late phase of inflammation. There were no synergies with combined early+late MSCs transplantation. PMID:23349686

  4. Case report of vertebral osteomyelitis and mycotic abdominal aortic aneurysm caused by Scedosporium apiospermum in a lung transplant patient with cystic fibrosis.

    PubMed

    Thomson, S; Alibhai, K; Winkelaar, G; Lien, D; Halloran, K; Kapasi, A; Weinkauf, J

    2015-01-01

    Cystic fibrosis patients are frequently plagued by infections, often with unusual or hardy organisms. Their infections are only complicated by transplantation. In this report, we review the case of a young woman who had a double lung transplant secondary to cystic fibrosis who developed a lumbar osteomyelitis/discitis several years after transplantation. After treatment, she went on to develop a mycotic abdominal aortic aneurysm. The patient underwent thoracic and abdominal aortic replacement, and histopathology revealed Scedosporium apiospermum infection. The patient recovered well from surgery and was discharged home on long-term antifungal therapy. This represents the first reported case of S apiospermum mycotic aneurysm in a lung transplant patient, and possibly the largest number and longest duration of S apiospermum infections reported in a single patient. PMID:25645805

  5. Randomization to Screening for Prostate, Lung, Colorectal and Ovarian Cancers and Thyroid Cancer Incidence in Two Large Cancer Screening Trials

    PubMed Central

    O'Grady, Thomas J.; Kitahara, Cari M.; DiRienzo, A. Gregory; Boscoe, Francis P.; Gates, Margaret A.

    2014-01-01

    Background Thyroid cancer incidence has increased significantly over the past three decades due, in part, to incidental detection. We examined the association between randomization to screening for lung, prostate, colorectal and/or ovarian cancers and thyroid cancer incidence in two large prospective randomized screening trials. Methods We assessed the association between randomization to low-dose helical CT scan versus chest x-ray for lung cancer screening and risk of thyroid cancer in the National Lung Screening Trial (NLST). In the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO), we assessed the association between randomization to regular screening for said cancers versus usual medical care and thyroid cancer risk. Over a median 6 and 11 years of follow-up in NLST and PLCO, respectively, we identified 60 incident and 234 incident thyroid cancer cases. Cox proportional hazards regression was used to calculate the cause specific hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer. Results In NLST, randomization to lung CT scan was associated with a non-significant increase in thyroid cancer risk (HR  = 1.61; 95% CI: 0.96–2.71). This association was stronger during the first 3 years of follow-up, during which participants were actively screened (HR  = 2.19; 95% CI: 1.07–4.47), but not subsequently (HR  = 1.08; 95% CI: 0.49–2.37). In PLCO, randomization to cancer screening compared with usual care was associated with a significant decrease in thyroid cancer risk for men (HR  = 0.61; 95% CI: 0.49–0.95) but not women (HR  = 0.91; 95% CI: 0.66–1.26). Similar results were observed when restricting to papillary thyroid cancer in both NLST and PLCO. Conclusion Our study suggests that certain medical encounters, such as those using low-dose helical CT scan for lung cancer screening, may increase the detection of incidental thyroid cancer. PMID:25192282

  6. Use of bilevel positive airway pressure (BIPAP) in end-stage patients with cystic fibrosis awaiting lung transplantation.

    PubMed

    Caronia, C G; Silver, P; Nimkoff, L; Gorvoy, J; Quinn, C; Sagy, M

    1998-09-01

    Nine consecutive end-stage patients with cystic fibrosis (CF) awaiting lung transplantation were admitted to the pediatric intensive care unit (PICU) in respiratory decompensation. They all received noninvasive bilevel positive airway pressure (BIPAP) support and were evaluated to determine whether or not it improved their oxygenation and provided them with long-term respiratory stability. BIPAP was applied to all patients after a brief period of assessment of their respiratory status. Inspiratory and expiratory positive airway pressures (IPAP, EPAP) were initially set at 8 and 4 cm H2O respectively. IPAP was increased by increments of 2 cm H2O and EPAP was increased by 1 cm H2O increments until respiratory comfort was achieved and substantiated by noninvasive monitoring. Patients were observed in the PICU for 48 to 72 hours and then discharged to home with instructions to apply BIPAP during night sleep and whenever subjectively required. Regular follow-up visits were scheduled through the hospital-based CF clinic. The patients' final IPAP and EPAP settings ranged from 14 to 18 cm H2O and 4 to 8 cm H2O, respectively. All nine patients showed a marked improvement in their respiratory status with nocturnal use of BIPAP at the time of discharge from the PICU. Their oxygen requirement dropped from a mean of 4.6 +/- 1.1 L/min to 2.3 +/- 1.5 L/min (P < 0.05). Their mean respiratory rate decreased from 34 +/- 4 to 28 +/- 5 breaths per minute (P < 0.05). The oxygen saturation of hemoglobin measured by pulse oximetry, significantly increased from a mean of 80% +/- 15% to 91% +/- 5% (P < 0.05). The patients have been followed up for a period of 2 to 43 months and have all tolerated the use of home nocturnal BIPAP without any reported discomfort. Six patients underwent successful lung transplantation after having utilized nocturnal BIPAP for 2, 6, 14, 15, 26, and 43 months, respectively. Three patients have utilized home BIPAP support for 2, 3, and 19 months, respectively

  7. Topical amphotericin B application in severe bronchial aspergillosis after lung transplantation: report of experiences in 3 cases.

    PubMed

    Boettcher, H; Bewig, B; Hirt, S W; Möller, F; Cremer, J

    2000-12-01

    Ulcerative tracheobronchial aspergillosis after lung transplantation (ltx) may lead to bronchial-pulmonary artery fistula that results in fatal bleeding. We report our early experience with combined systemic, aerolized and topical application of amphotericin B in 3 cases of bronchial aspergillosis after ltx. Two patients are still alive, but 1 died of bleeding from a fistula between the left upper lobe bronchus and the pulmonary artery. Aspergillosis in the second patient resolved with minimal stenosis of the left main and the left upper lobe bronchus, and the third patient developed an anastomotic stenosis that was successfully dilated. PMID:11124494

  8. [Role of biomarkers in the differential diagnosis of acute respiratory failure in the immediate postoperative period of lung transplantation].

    PubMed

    Ruano, L; Sacanell, J; Roman, A; Rello, J

    2013-01-01

    Lung transplant recipients are at high risk of suffering many complications during the immediate postoperative period, such as primary graft dysfunction, acute graft rejection or infection. The most common symptom is the presence of acute respiratory failure, and the use of biomarkers could be useful for establishing an early diagnosis of these conditions. Different biomarkers have been studied, but none have proven to be the gold standard in the differential diagnosis of acute respiratory failure. This paper offers a review of the different biomarkers that have been studied in this field. PMID:23462428

  9. Infectious Triggers of Chronic Lung Allograft Dysfunction.

    PubMed

    Gregson, Aric L

    2016-07-01

    Survival after lung transplantation is limited in large part due to the high incidence of chronic rejection, known as chronic lung allograft dysfunction (CLAD). Pulmonary infections are a frequent complication in lung transplant recipients, due both to immunosuppressive medications and constant exposure of the lung allograft to the external environment via the airways. Infection is a recognized risk factor for the development of CLAD, and both acute infection and chronic lung allograft colonization with microorganisms increase the risk for CLAD. Acute infection by community acquired respiratory viruses, and the bacteria Pseudomonas aeruginosa and Staphylococcus aureus are increasingly recognized as important risk factors for CLAD. Colonization by the fungus Aspergillus may also augment the risk of CLAD. Fostering this transition from healthy lung to CLAD in each of these infectious episodes is the persistence of an inflammatory lung allograft environment. PMID:27221821

  10. The Incidence and Severity of Oral Mucositis among Allogeneic Hematopoietic Stem Cell Transplantation Patients: A Systematic Review.

    PubMed

    Chaudhry, Hafsa M; Bruce, Alison J; Wolf, Robert C; Litzow, Mark R; Hogan, William J; Patnaik, Mrinal S; Kremers, Walter K; Phillips, Gordon L; Hashmi, Shahrukh K

    2016-04-01

    Oral mucositis (OM) is a debilitating early adverse effect of allogeneic hematopoietic stem cell transplantation (HSCT). The intensity of the conditioning regimen correlates with the incidence and severity of OM, but no studies have analyzed this relationship among various conditioning regimens. We performed a systematic review on the incidence and outcomes of OM in allogeneic HSCT patients and analyzed this association. A comprehensive search of several databases (Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Cochrane CRCT, Cochrane DSR, Scopus) from 1990 to 2014 for studies of OM in allogeneic HSCT patients was conducted. Professional societies' meeting abstracts were also searched. Grade of OM was analyzed based on the World Health Organization (WHO) or National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events scales. Severe mucositis was defined as either grades 2 to 4 or grades 3 and 4, depending on the studies' definition of severity. Cohorts were analyzed based on regimen intensity; ie, reduced-intensity conditioning (RIC) (including nonmyeloablative) and myeloablative (MA). Random effect (RE) and standard logistic models weighted by the number of patients in each cohort were used for comparisons. A total of 624 studies were generated from the search. Of the 395 patients in 8 eligible MA regimen studies, 73.2% experienced any OM, whereas in 245 patients in the 6 eligible RIC regimen studies, 86.5% experienced any OM (chi-square P < .0001; RE, P = .05). Severe (grades 2 to 4) OM occurred among 79.7% of the WHO/NCI-graded MA patients and 71.5% of RIC patients (chi-square, P = .0421; RE, P < .01). In comparing graft-versus-host disease (GVHD) prophylaxis, only 55.4% of patients receiving nonmethotrexate regimens experienced OM; this was lower (chi-square, P < .0001; RE, P = .06) than that found among patients who received methotrexate (83.4%), either standard or reduced dose. Besides NCI and WHO

  11. Five-year update on the mouse model of orthotopic lung transplantation: Scientific uses, tricks of the trade, and tips for success

    PubMed Central

    Lin, Xue; Li, Wenjun; Lai, Jiaming; Okazaki, Mikio; Sugimoto, Seiichiro; Yamamoto, Sumiharu; Wang, Xingan; Gelman, Andrew E.; Kreisel, Daniel

    2012-01-01

    It has been 5 years since our team reported the first successful model of orthotopic single lung transplantation in the mouse. There has been great demand for this technique due to the obvious experimental advantages the mouse offers over other large and small animal models of lung transplantation. These include the availability of mouse-specific reagents as well as knockout and transgenic technology. Our laboratory has utilized this mouse model to study both immunological and non-immunological mechanisms of lung transplant physiology while others have focused on models of chronic rejection. It is surprising that despite our initial publication in 2007 only few other laboratories have published data using this model. This is likely due to the technical complexity of the surgical technique and perioperative complications, which can limit recipient survival. As two of the authors (XL and WL) have a combined experience of over 2500 left and right single lung transplants, this review will summarize their experience and delineate tips and tricks necessary for successful transplantation. We will also describe technical advances made since the original description of the model. PMID:22754663

  12. Late presentation of encapsulating peritoneal sclerosis following renal transplantation and the potential under-reporting of the incidence and prevalence of encapsulating peritoneal sclerosis.

    PubMed

    Davenport, Andrew

    2015-07-01

    Encapsulating peritoneal sclerosis is an infrequent but potentially devastating complication of peritoneal dialysis. The reported incidence and prevalence of encapsulating peritoneal sclerosis vary markedly between countries. Currently, peritoneal dialysis vintage remains the major risk factor for encapsulating peritoneal sclerosis, and dialysis vintage differs between countries due to the relative competing risks of transplantation, availability of haemodialysis and peritonitis. However, the diagnosis of encapsulating peritoneal sclerosis is often only established when patients have transferred modality to transplantation or haemodialysis. Switching treatment modality may potentially lead to an under-reporting of encapsulating peritoneal sclerosis, as many countries which collect data on dialysis patients in national registries often have separate registries for dialysis and transplant patients, and this may potentially lead to under-reporting of encapsulating peritoneal sclerosis in patients presenting after renal transplantation. Secondly, the question arises as to how long former peritoneal dialysis patients should be followed before a diagnosis of encapsulating peritoneal sclerosis can be confidently excluded. To highlight this point, we present four cases that developed symptomatic encapsulating peritoneal sclerosis more than 5 years, and in once case more than 10 years after the discontinuation of peritoneal dialysis. Delayed or late presentation may not only delay the diagnosis, but also risk surgical interventions by non-specialists. A more robust system is required to record cases of encapsulating peritoneal sclerosis to determine the incidence and prevalence, and so provide accurate information to both patients and clinicians as to the risks of long-term peritoneal dialysis therapy. PMID:26063486

  13. Autoimmune thrombocytopenia in a patient with small cell lung cancer developing after chemotherapy and resolving following autologous peripheral blood stem cell transplantation.

    PubMed

    Demirer, T; Celebi, H; Arat, M; Ustün, C; Demirer, S; Dilek, I; Ozcan, M; Ilhan, O; Akan, H; Gürman, G; Koç, H

    1999-08-01

    A 46-year-old white male with small cell lung cancer (SCLC) limited to the thorax developed autoimmune thrombocytopenic purpura (AITP), following a cyclophosphamide, paclitaxel and G-CSF-containing regimen for peripheral blood stem cell (PBSC) mobilization. AITP associated with small or non-small cell lung cancer has been reported. We considered that the AITP in this case may be a part of paraneoplastic syndrome, which is frequently seen in patients with SCLC. The patient received HDC and autologous PBSC transplantation (APBSCT) for SCLC and the AITP resolved following transplantation, thus supporting the concept of HDC + APBSCT for the treatment of autoimmune diseases. PMID:10455376

  14. A case of diffuse panbronchiolitis, associated with severe pulmonary hypertension, managed with bilateral lung transplantation from a brain-dead donor.

    PubMed

    Onishi, Yasutaka; Kawamura, Tetsuji; Morimoto, Akie; Nakahara, Yasuharu; Mochizuki, Yoshiro; Miyoshi, Kentaroh; Oto, Takahiro

    2015-09-01

    Diffuse panbronchiolitis (DPB) is a chronic respiratory disease that mainly involves the respiratory bronchioles, and has historically been associated with a very poor prognosis. The development of long-term low dose macrolide therapy in the 1980s has dramatically improved the prognosis of DPB. Nevertheless, some cases are resistant to macrolide therapy, and ultimately develop severe respiratory failure and pulmonary hypertension; in such cases lung transplantation is a viable treatment option. Here we report the case of a 40-year-old patient with a 20-year history of DPB, who underwent bilateral lung transplantation due to severe respiratory failure with pulmonary hypertension. PMID:26344614

  15. Long-Term (Postnatal Day 70) Outcome and Safety of Intratracheal Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Neonatal Hyperoxic Lung Injury

    PubMed Central

    Ahn, So Yoon; Chang, Yun Sil; Kim, Soo Yoon; Sung, Dong Kyung; Kim, Eun Sun; Rime, So Yub; Yu, Wook Joon; Choi, Soo Jin; Oh, Won Il

    2013-01-01

    Purpose This study was performed to evaluate the long-term effects and safety of intratracheal (IT) transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in neonatal hyperoxic lung injury at postnatal day (P)70 in a rat model. Materials and Methods Newborn Sprague Dawley rat pups were subjected to 14 days of hyperoxia (90% oxygen) within 10 hours after birth and allowed to recover at room air until sacrificed at P70. In the transplantation groups, hUCB-MSCs (5×105) were administered intratracheally at P5. At P70, various organs including the heart, lung, liver, and spleen were histologically examined, and the harvested lungs were assessed for morphometric analyses of alveolarization. ED-1, von Willebrand factor, and human-specific nuclear mitotic apparatus protein (NuMA) staining in the lungs and the hematologic profile of blood were evaluated. Results Impaired alveolar and vascular growth, which evidenced by an increased mean linear intercept and decreased amount of von Willebrand factor, respectively, and the hyperoxia-induced inflammatory responses, as evidenced by inflammatory foci and ED-1 positive alveolar macrophages, were attenuated in the P70 rat lungs by IT transplantation of hUCB-MSCs. Although rare, donor cells with human specific NuMA staining were persistently present in the P70 rat lungs. There were no gross or microscopic abnormal findings in the heart, liver, or spleen, related to the MSCs transplantation. Conclusion The protective and beneficial effects of IT transplantation of hUCB-MSCs in neonatal hyperoxic lung injuries were sustained for a prolonged recovery period without any long-term adverse effects up to P70. PMID:23364976

  16. [Annual review of Archivos de Neumología in interventional pneumology, interstitial diseases and lung transplantation].

    PubMed

    Disdier, Carlos; Bollo, Elena; Morales, Pilar; Montero, Carmen

    2009-01-01

    A review has been made of original articles on invasive pneumology techniques, interstitial diseases and lung transplantation, published in the Archivos de Bronconeumología during the year 2008. We have selected the publication by Martínez-Olondrins et al on the mediastinal staging of bronchogenic carcinoma by transbronchial needle aspiration to highlight the role of this simple, safe and cost-effective technique at a time when aspiration by ultrasound-guided bronchoscopy is profiled as an alternative to staging by mediastinoscopy. Besides its usefulness in the study of lymph nodes, transbronchial needle aspiration increases the overall performance of bronchoscopy by 20%, which means that it should be considered as a basic tool in the study of lung cancer. We also comment on the work by Galvis-Caravajal et al, who describe percutaneous radiofrequency as an alternative to radiotherapy in small lung or metastasic tumours. In diffuse interstitial disease, Morell et al analysed the diagnostic methods in 500 patients with this clinical-radiological presentation in which a definitive diagnosis was achieved in 85%, with 25% of them being obtained by non-invasively. Baloira et al analysed the characteristics of 19 patients with desquamative interstitial pneumonia and respiratory bronchiolitis associated-interstitial lung disease obtained from the National register of Interstitial Diseases. PMID:19303530

  17. Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

    PubMed

    Girmenia, Corrado; Raiola, Anna Maria; Piciocchi, Alfonso; Algarotti, Alessandra; Stanzani, Marta; Cudillo, Laura; Pecoraro, Clara; Guidi, Stefano; Iori, Anna Paola; Montante, Barbara; Chiusolo, Patrizia; Lanino, Edoardo; Carella, Angelo Michele; Zucchetti, Elisa; Bruno, Benedetto; Irrera, Giuseppe; Patriarca, Francesca; Baronciani, Donatella; Musso, Maurizio; Prete, Arcangelo; Risitano, Antonio Maria; Russo, Domenico; Mordini, Nicola; Pastore, Domenico; Vacca, Adriana; Onida, Francesco; Falcioni, Sadia; Pisapia, Giovanni; Milone, Giuseppe; Vallisa, Daniele; Olivieri, Attilio; Bonini, Alessandro; Castagnola, Elio; Sica, Simona; Majolino, Ignazio; Bosi, Alberto; Busca, Alessandro; Arcese, William; Bandini, Giuseppe; Bacigalupo, Andrea; Rambaldi, Alessandro; Locasciulli, Anna

    2014-06-01

    Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P < .0001). Our findings indicate that tailored prevention strategies may be useful in subpopulations at differing levels of risk for PP-IFDs. PMID:24631738

  18. Sarcopenia of thoracic muscle mass is not a risk factor for survival in lung transplant recipients

    PubMed Central

    Lee, Seokkee; Paik, Hyo Chae; Haam, Seok Jin; Lee, Chang Young; Nam, Kyung Sik; Jung, Hee Suk; Do, Young Woo; Shu, Jee Won

    2016-01-01

    Background In lung transplantation (LTx), patients with thoracic muscle sarcopenia may have to require longer to recovery. We measured thoracic muscle volume by using the cross sectional area (CSA) and assessed its effect on early outcomes after LTx. Methods A retrospective analysis was conducted to evaluate the effect of thoracic sarcopenia in patients undergoing LTx between January 2010 and July 2015. The lowest CSA quartile (Q1) was defined as sarcopenia. Results In total, 109 patients were enrolled. The mean CSA was 58.24±15.82 cm2. Patients in the highest CSA quartile were more likely to be male (92.6% vs. 17.9%, P<0.001), older (55.2±10.1 vs. 43.2±14.9 years, P=0.001), to have a higher body mass index (BMI) (22.3±4.0 vs. 19.4±3.7 kg/m2, P=0.007), and to have pulmonary fibrosis (85.2% vs. 35.7%, P=0.003) compared with the lowest CSA quartile. Early outcomes including ventilator support duration [32.9±49.2 vs. 24.5±39.9 days, P= not significant (ns)], intensive care unit (ICU) stay duration (28.4±43.7 vs. 24.4±35.9 days, P= ns) and hospital stay duration (61.4±48.2 vs. 50.8±37.2 days, P= ns) tended to be longer in Q1 than Q4, but the difference was not significant. However, the 1-year survival rate was better in Q1 compared with Q4 (66.6% vs. 46.0%, P=0.04). Conclusions Although patients with thoracic sarcopenia seem to require a longer post-operative recovery time after LTx, this does not compromise their early outcomes. By contrast, patients with larger thoracic muscle volume (Q4) showed poorer survival times.

  19. Bilateral Lung Transplantation in a Patient with Humoral Immune Deficiency: A Case Report with Review of the Literature

    PubMed Central

    Farmer, Jocelyn R.; Sokol, Caroline L.; Bonilla, Francisco A.; Murali, Mandakolathur R.; Kradin, Richard L.; Astor, Todd L.; Walter, Jolan E.

    2014-01-01

    Humoral immune deficiencies have been associated with noninfectious disease complications including autoimmune cytopenias and pulmonary disease. Herein we present a patient who underwent splenectomy for autoimmune cytopenias and subsequently was diagnosed with humoral immune deficiency in the context of recurrent infections. Immunoglobulin analysis prior to initiation of intravenous immunoglobulin (IVIG) therapy was notable for low age-matched serum levels of IgA (11 mg/dL), IgG2 (14 mg/L), and IgG4 (5 mg/L) with a preserved total level of IgG. Flow cytometry was remarkable for B cell maturation arrest at the IgM+/IgD+ stage. Selective screening for known primary immune deficiency-causing genetic defects was negative. The disease course was uniquely complicated by the development of pulmonary arteriovenous malformations (AVMs), ultimately requiring bilateral lung transplantation in 2012. This is a patient with humoral immune deficiency that became apparent only after splenectomy, which argues for routine immunologic evaluation prior to vaccination and splenectomy. Lung transplantation is a rare therapeutic endpoint and to our knowledge has never before been described in a patient with humoral immune deficiency for the indication of pulmonary AVMs. PMID:25379312

  20. A Randomized Controlled Trial of a Mobile Health Intervention to Promote Self-Management After Lung Transplantation.

    PubMed

    DeVito Dabbs, A; Song, M K; Myers, B A; Li, R; Hawkins, R P; Pilewski, J M; Bermudez, C A; Aubrecht, J; Begey, A; Connolly, M; Alrawashdeh, M; Dew, M A

    2016-07-01

    Lung transplant recipients are encouraged to perform self-management behaviors, including (i) monitoring health indicators, (ii) adhering to their regimen, and (iii) reporting abnormal health indicators to the transplant coordinator, yet performance is suboptimal. When hospital discharge was imminent, this two-group trial randomized 201 recipients to use either the mobile health (mHealth) intervention (n = 99) or usual care (n = 102), to compare efficacy for promoting self-management behaviors (primary outcomes) and self-care agency, rehospitalization, and mortality (secondary outcomes) at home during the first year after transplantation. The mHealth intervention group performed self-monitoring (odds ratio [OR] 5.11, 95% confidence interval [CI] 2.95-8.87, p < 0.001), adhered to medical regimen (OR 1.64, 95% CI 1.01-2.66, p = 0.046), and reported abnormal health indicators (OR 8.9, 95% CI 3.60-21.99, p < 0.001) more frequently than the usual care group. However, the two groups did not differ in rehospitalization (OR 0.78, 95% CI 0.36-1.66, p = 0.51) or mortality (hazard ratio 1.71, 0.68-4.28, p = 0.25). The positive impact of the mHealth intervention on self-management behaviors suggests that the intervention holds promise and warrants further testing. PMID:26729617

  1. Smoking and interstitial lung disease. The effect of cigarette smoking on the incidence of pulmonary histiocytosis X and sarcoidosis.

    PubMed

    Hance, A J; Basset, F; Saumon, G; Danel, C; Valeyre, D; Battesti, J P; Chrétien, J; Georges, R

    1986-01-01

    Cigarette smoking produces marked alterations in the lung parenchyma and in the population of immune and inflammatory cells present in the lower respiratory tract. These cigarette-induced changes appear to influence the incidence of two different interstitial lung diseases, histiocytosis X and sarcoidosis. Smoking is a strong risk factor for the development of pulmonary histiocytosis X, since the incidence of smoking is very high among patients with histiocytosis X: 90% of the patients with histiocytosis X were smokers; 46% of the controls were smokers (p less than .001). In contrast, smoking appears to reduce the incidence of sarcoidosis: 31% of the patients with sarcoidosis were smokers (p less than .05 compared to controls). In an effort to understand how cigarette smoking influences the incidence of these two disorders, we compared the numbers and types of immune and inflammatory cells recovered by bronchoalveolar lavage from nonsmoking and smoking controls and patients with histiocytosis X and sarcoidosis. Although nonsmoking patients with histiocytosis X did not have a significant increase in the number of alveolar macrophages recovered by lavage (p greater than .2 compared to normals), smoking patients had an increase in the number of alveolar macrophages similar to that observed in the control population. In contrast, the number of macrophages recovered from patients with sarcoidosis who smoked was considerably less than that observed in normal smokers (p less than .05 comparing patients with sarcoidosis and controls who smoked 1-20 cigarettes/day). This difference in the intensity of the cigarette-induced macrophage alveolitis observed in the two patient groups may be important in explaining the opposite effects of cigarette smoking on the incidence of histiocytosis X and sarcoidosis. PMID:3488004

  2. Ultrastructural changes of the intracellular surfactant pool in a rat model of lung transplantation-related events

    PubMed Central

    2011-01-01

    Background Ischemia/reperfusion (I/R) injury, involved in primary graft dysfunction following lung transplantation, leads to inactivation of intra-alveolar surfactant which facilitates injury of the blood-air barrier. The alveolar epithelial type II cells (AE2 cells) synthesize, store and secrete surfactant; thus, an intracellular surfactant pool stored in lamellar bodies (Lb) can be distinguished from the intra-alveolar surfactant pool. The aim of this study was to investigate ultrastructural alterations of the intracellular surfactant pool in a model, mimicking transplantation-related procedures including flush perfusion, cold ischemia and reperfusion combined with mechanical ventilation. Methods Using design-based stereology at the light and electron microscopic level, number, surface area and mean volume of AE2 cells as well as number, size and total volume of Lb were determined in a group subjected to transplantation-related procedures including both I/R injury and mechanical ventilation (I/R group) and a control group. Results After I/R injury, the mean number of Lb per AE2 cell was significantly reduced compared to the control group, accompanied by a significant increase in the luminal surface area per AE2 cell in the I/R group. This increase in the luminal surface area correlated with the decrease in surface area of Lb per AE2. The number-weighted mean volume of Lb in the I/R group showed a tendency to increase. Conclusion We suggest that in this animal model the reduction of the number of Lb per AE2 cell is most likely due to stimulated exocytosis of Lb into the alveolar space. The loss of Lb is partly compensated by an increased size of Lb thus maintaining total volume of Lb per AE2 cell and lung. This mechanism counteracts at least in part the inactivation of the intra-alveolar surfactant. PMID:21669009

  3. Does the use of extended criteria donors influence early and long-term results of lung transplantation?

    PubMed

    Schiavon, Marco; Falcoz, Pierre-Emmanuel; Santelmo, Nicola; Massard, Gilbert

    2012-02-01

    A best evidence topic was constructed according to a structured protocol. The question addressed was whether the presence of extended criteria donors influences the early and long-term results in patients referred for lung transplantation. Of the 30 papers found using a report search, 14 presented the best evidence to answer the clinical question. The authors, journal, date, country of publication, study type, group studied, relevant outcomes and results of these papers are given. In total, we recorded 10 retrospective studies that considered all the donor criteria for comparing marginal donors (MDs) and standard donors. On the one hand, six of them showed no difference between the two groups in terms of early and long-term results. On the other hand, four studies demonstrated a negative impact of MDs on various early outcomes (mortality, primary graft dysfunction, duration of mechanical ventilation, length of stay in intensive care unit), whereas no significant negative influence on survival has ever been described when screening MD results. More precisely, when analysing the role of individual factors of marginality, as done in two of the 14 studies, a significant negative impact was observed for a low level of PaO(2) at the time of harvesting, positive bronchoscopy and smoking history. More specifically, the first two criteria have been validated by several authors, both in multicentre and cohort studies. Finally, the importance of avoiding the donation of the lung from an MD to a high-risk recipient emerged, whereas the association with single or bilateral transplants remains more controversial. Hence, current evidence suggests that there are no contraindications-given the absence of negative impact on survival-for the use of MDs for the transplant of a proposed standard receiver. However, given the low level of evidence of published studies, caution is necessary in order to avoid organ shortage, despite these encouraging results. PMID:22159257

  4. Incidence and risk of postherpetic neuralgia after varicella zoster virus infection in hematopoietic cell transplantation recipients: Hokkaido Hematology Study Group.

    PubMed

    Onozawa, Masahiro; Hashino, Satoshi; Haseyama, Yoshifumi; Hirayama, Yasuo; Iizuka, Susumu; Ishida, Tadao; Kaneda, Makoto; Kobayashi, Hajime; Kobayashi, Ryoji; Koda, Kyuhei; Kurosawa, Mitsutoshi; Masauji, Nobuo; Matsunaga, Takuya; Mori, Akio; Mukai, Masaya; Nishio, Mitsufumi; Noto, Satoshi; Ota, Shuichi; Sakai, Hajime; Suzuki, Nobuhiro; Takahashi, Tohru; Tanaka, Junji; Torimoto, Yoshihiro; Yoshida, Makoto; Fukuhara, Takashi

    2009-06-01

    To assess the incidence of and risk factors associated with postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT) varicella zoster virus (VZV) infection, we conducted a retrospective chart review of 418 consecutive patients who underwent HCT between April 2005 and March 2007. The male/female ratio was 221/197, median age at HCT was 47 years (range: 0-69 years), and autologous/allogeneic/syngeneic HCT ratio was 154/263/1. Seventy-eight patients developed VZV infection after HCT. Sixty-two patients had localized zoster, 11 patients had disseminated zoster (rash like chicken pox), and 4 patients had visceral zoster. All cases were treated with acyclovir (ACV) or valacyclovir (VACV), and there was no VZV infection-related death. Twenty-seven (35%) of the 78 patients with VZV infection suffered PHN after resolution of VZV infection. Multivariate analysis showed that advanced age is the only risk factor in autologous HCT (P = .0075; odds ratio [OR] = 1.14; 95% confidence interval [CI], 0.97-1.33). On the other hand, advanced age (P = .0097; OR = 1.06; 95% CI, 1.01-1.12), male gender (P = .0055; OR = 12.7; 95% CI, 1.61-100.1), and graft-versus-host disease (GVHD) prophylaxis with a tacrolimus-based regimen (P = .0092; OR = 9.56; 95% CI, 1.44-63.3) were associated with increased risk of PHN in allogeneic HCT. This study for the first time clarified the risk of PHN in HCT recipients. PMID:19450757

  5. Management of pulmonary alveolar proteinosis with whole lung lavage using extracorporeal membrane oxygenation support in a postrenal transplant patient with graft failure.

    PubMed

    Chauhan, Sandeep; Sharma, Kamal P; Bisoi, Akshay K; Pangeni, Raju; Madan, Karan; Chauhan, Yogendra S

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of excessive lung surfactant in the alveoli leading to restrictive lung functions and impaired gas exchange. Whole lung lavage (WLL) is the treatment modality of choice, which is usually performed using double lumen endobronchial tube insertion under general anesthesia and alternating unilateral lung ventilation and washing with normal saline. It may be difficult to perform WLL in patients with severe hypoxemia wherein patients do not tolerate single lung ventilation. Extracorporeal membrane oxygenation support (ECMO) has been used in such patients. We report a patient with autoimmune PAP following renal transplant who presented with marked hypoxemia and was managed by WLL under ECMO support. PMID:27052091

  6. Management of pulmonary alveolar proteinosis with whole lung lavage using extracorporeal membrane oxygenation support in a postrenal transplant patient with graft failure

    PubMed Central

    Chauhan, Sandeep; Sharma, Kamal P.; Bisoi, Akshay K.; Pangeni, Raju; Madan, Karan; Chauhan, Yogendra S.

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of excessive lung surfactant in the alveoli leading to restrictive lung functions and impaired gas exchange. Whole lung lavage (WLL) is the treatment modality of choice, which is usually performed using double lumen endobronchial tube insertion under general anesthesia and alternating unilateral lung ventilation and washing with normal saline. It may be difficult to perform WLL in patients with severe hypoxemia wherein patients do not tolerate single lung ventilation. Extracorporeal membrane oxygenation support (ECMO) has been used in such patients. We report a patient with autoimmune PAP following renal transplant who presented with marked hypoxemia and was managed by WLL under ECMO support. PMID:27052091

  7. Intravenous Transplantation of Mesenchymal Progenitors Distribute Solely to the Lungs and Improve Outcomes in Cervical Spinal Cord Injury.

    PubMed

    White, Seok Voon; Czisch, Chris E; Han, May H; Plant, Christine D; Harvey, Alan R; Plant, Giles W

    2016-07-01

    Cellular transplantation strategies utilizing intraspinal injection of mesenchymal progenitor cells (MPCs) have been reported as beneficial for spinal cord injuries. However, intraspinal injection is not only technically challenging, but requires invasive surgical procedures for patients. Therefore, we investigated the feasibility and potential benefits of noninvasive intravenous injection of MPCs in two models of cervical spinal cord injury, unilateral C5 contusion and complete unilateral C5 hemisection. MPCs isolated from green fluorescence protein (GFP)-luciferase transgenic mice compact bone (1 × 10(6) cells), or vehicle Hank's Buffered Saline Solution (HBSS), were intravenously injected via the tail vein at D1, D3, D7, D10, or D14. Transplanted MPCs were tracked via bioluminescence imaging. Live in vivo imaging data showed that intravenously injected MPCs accumulate in the lungs, confirmed by postmortem bioluminescence signal-irrespective of the time of injection or injury model. The results showed a rapid, positive modulation of the inflammatory response providing protection to the injured spinal cord tissue. Histological processing of the lungs showed GFP(+) cells evenly distributed around the alveoli. We propose that injected cells can act as cellular target decoys to an immune system primed by injury, thereby lessening the inflammatory response at the injury site. We also propose that intravenous injected MPCs modulate the immune system via the lungs through secreted immune mediators or contact interaction with peripheral organs. In conclusion, the timing of intravenous injection of MPCs is key to the success for improving function and tissue preservation following cervical spinal cord injury. Stem Cells 2016;34:1812-1825. PMID:26989838

  8. Composition of tobaccos from countries with high and low incidences of lung cancer. I. Selenium, polonium-210, Alternaria, tar, and nicotine

    SciTech Connect

    Bogden, J.D.; Kemp, F.W.; Buse, M.; Thind, I.S.; Louria, D.B.; Forgacs, J.; Llanos, G.; Terrones, I.M.

    1981-01-01

    Tobaccos from countries with high and low incidences of lung cancer were analyzed. Tobacco concentrations of polonium-210 were similar in cigarettes from high- and low-incidence countries, as were levels of cigarette smoke tar and nicotine. Tobaccos from low-incidence countries had significantly lower Alternaria spore counts. Mean selenium concentrations of tobaccos from the high-incidence countries (0.16 +- 0.05 ..mu..g/g) were significantly lower than those of tobaccos from the low-incidence countries (0.49 +- 0.22 ..mu..g/g).

  9. An Official American Thoracic Society Research Statement: Noninfectious Lung Injury after Hematopoietic Stem Cell Transplantation: Idiopathic Pneumonia Syndrome

    PubMed Central

    Panoskaltsis-Mortari, Angela; Griese, Matthias; Madtes, David K.; Belperio, John A.; Haddad, Imad Y.; Folz, Rodney J.; Cooke, Kenneth R.

    2011-01-01

    Rationale: Acute lung dysfunction of noninfectious etiology, known as idiopathic pneumonia syndrome (IPS), is a severe complication following hematopoietic stem cell transplantation (HSCT). Several mouse models have been recently developed to determine the underlying causes of IPS. A cohesive interpretation of experimental data and their relationship to the findings of clinical research studies in humans is needed to better understand the basis for current and future clinical trials for the prevention/treatment of IPS. Objectives: Our goal was to perform a comprehensive review of the preclinical (i.e., murine models) and clinical research on IPS. Methods: An ATS committee performed PubMed and OVID searches for published, peer-reviewed articles using the keywords “idiopathic pneumonia syndrome” or “lung injury” or “pulmonary complications” AND “bone marrow transplant” or “hematopoietic stem cell transplant.” No specific inclusion or exclusion criteria were determined a priori for this review. Measurements and Main Results: Experimental models that reproduce the various patterns of lung injury observed after HSCT have identified that both soluble and cellular inflammatory mediators contribute to the inflammation engendered during the development of IPS. To date, 10 preclinical murine models of the IPS spectrum have been established using various donor and host strain combinations used to study graft-versus-host disease (GVHD). This, as well as the demonstrated T cell dependency of IPS development in these models, supports the concept that the lung is a target of immune-mediated attack after HSCT. The most developed therapeutic strategy for IPS involves blocking TNF signaling with etanercept, which is currently being evaluated in clinical trials. Conclusions: IPS remains a frequently fatal complication that limits the broader use of allogeneic HSCT as a successful treatment modality. Faced with the clinical syndrome of IPS, one can categorize the

  10. Radiologically guided fine needle lung biopsies in the evaluation of focal pulmonary lesions in allogeneic stem cell transplant recipients.

    PubMed

    Jantunen, E; Piilonen, A; Volin, L; Ruutu, P; Parkkali, T; Koukila-Kähkölä, P; Ruutu, T

    2002-02-01

    Lung problems are common in allogeneic stem cell transplant (SCT) recipients. To evaluate the feasibility and diagnostic yield of radiologically guided fine needle lung biopsy (FNLB) in allogeneic SCT recipients with focal pulmonary lesions, a retrospective analysis was carried out. Between 1989 and 1998, radiologists performed a total of 30 FNLBs in 21 allogeneic SCT recipients, guided either by ultrasound (n = 17) or computed tomography (n = 13). The median time from SCT to the first FNLB was 131 days (20-343 days). Prophylactic platelet transfusions were given in 19 procedures (66%). The complications of FNLB included clinically insignificant pneumothorax in four procedures (13%) and self-limiting haemoptysis in one case (3%). The first FNLB was suggestive of invasive pulmonary aspergillosis (IPA) in five patients (24%). Additional clinically useful findings of FNLB included Pseudomonas (two patients) and Nocardia (one patient). The final diagnosis of pulmonary lesions was IPA in 14 patients, immunological lung problems in four patients and other in three patients. Radiologically guided FNLB is feasible in allogeneic SCT recipients and has a low complication rate. The diagnostic yield is high especially for IPA. PMID:11896433

  11. Rare complications after lung percutaneous radiofrequency ablation: Incidence, risk factors, prevention and management.

    PubMed

    Alberti, Nicolas; Buy, Xavier; Frulio, Nora; Montaudon, Michel; Canella, Mathieu; Gangi, Afshin; Crombe, Amandine; Palussière, Jean

    2016-06-01

    Among image-guided thermo-ablative techniques, percutaneous radiofrequency ablation (PRFA) is the most widely used technique for the treatment of primary and secondary lung malignancies. Tolerance of PRFA in the lung is excellent. However, relatively little is known about potential rare complications. This article presents both the clinical and imaging features of lung PRFA complications as well as their prevention and management. Complications may be classified in four groups: pleuropulmonary (e.g., bronchopleural or bronchial fistula, delayed abscess or aspergilloma inside post-PRFA cavitations, pulmonary artery pseudo aneurysm, gas embolism and interstitial pneumonia); thoracic wall and vertebral (e.g., rib or vertebral fractures and intercostal artery injury); mediastinal and apical (e.g., neural damage); or diaphragmatic. Most complications can be managed with conservative treatment, percutaneous or endoscopic drainage, or surgical repair. PMID:27161069

  12. How Is Childhood Interstitial Lung Disease Treated?

    MedlinePlus

    ... the NHLBI on Twitter. How Is Childhood Interstitial Lung Disease Treated? Childhood interstitial lung disease (chILD) is ... prevent acid reflux, which can lead to aspiration. Lung Transplant A lung transplant may be an option ...

  13. A combined therapeutic approach in progressive idiopathic pulmonary fibrosis-pirfenidone as bridge therapy for ex vivo lung transplantation: a case report.

    PubMed

    Paone, G; Sebastiani, A; Ialleni, E; Diso, D; Rose, D; Quagliarini, F; Ialongo, P; Peruzzi, M; Venuta, F; Frati, G

    2015-04-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial pneumonia of unknown etiology, which is associated with the histopathologic pattern of usual interstitial pneumonia (UIP) and leads to a progressive decrease of respiratory function. The present article describes a case of a 62-year-old ex-smoker referred to our hospital because of IPF. After 2 years of follow-up, the subject experienced a significant worsening of pulmonary function and was enrolled in a lung transplantation program. Afterward, a pharmacological treatment with pirfenidone was started, achieving a stabilization of respiratory function. The patient underwent a single lung transplantation by means of a normothermic ex vivo lung perfusion (EVLP) approach according to the Toronto model. At 20-month evaluation the subject's respiratory function was significantly improved, and quality of life was considerably ameliorated. We believe that an integrated multidisciplinary approach should be considered a key option for the treatment of individuals with IPF. PMID:25891747

  14. Chronic Rejection Pathology after Orthotopic Lung Transplantation in Mice: The Development of a Murine BOS Model and Its Drawbacks

    PubMed Central

    De Vleeschauwer, Stéphanie; Jungraithmayr, Wolfgang; Wauters, Shana; Willems, Stijn; Rinaldi, Manuela; Vaneylen, Annemie; Verleden, Stijn; Willems-Widyastuti, Anna; Bracke, Ken; Brusselle, Guy; Verbeken, Erik; Van Raemdonck, Dirk; Verleden, Geert; Vanaudenaerde, Bart

    2012-01-01

    Almost all animal models for chronic rejection (CR) after lung transplantation (LTx) fail to resemble the human situation. It was our attempt to develop a representative model of CR in mice. Orthotopic LTx was performed in allografts receiving daily immunosuppression with steroids and cyclosporine. Controls included isografts and mice only undergoing thoracotomy (SHAM). Allografts were sacrificed 2, 4, 6, 8, 10 or 12 weeks after LTx. Pulmonary function was measured repeatedly in the 12w allografts, isografts and SHAM mice. Histologically, all allografts demonstrated acute rejection (AR) around the blood vessels and airways two weeks after LTx. This decreased to 50–75% up to 10 weeks and was absent after 12 weeks. Obliterative bronchiolitis (OB) lesions were observed in 25–50% of the mice from 4–12 weeks. Isografts and lungs of SHAM mice were normal after 12 weeks. Pulmonary function measurements showed a decline in FEV0.1, TLC and compliance in the allografts postoperatively (2 weeks) with a slow recovery over time. After this initial decline, lung function of allografts increased more than in isografts and SHAM mice indicating that pulmonary function measurement is not a good tool to diagnose CR in a mouse. We conclude that a true model for CR, with clear OB lesions in about one third of the animals, but without a decline in lung function, is possible. This model is an important step forward in the development of an ideal model for CR which will open new perspectives in unraveling CR pathogenesis and exploring new treatment options. PMID:22238655

  15. The Association of Inbreeding With Lung Fibrosis Incidence in Beagle Dogs That Inhaled 238PuO2 or 239PuO2.

    SciTech Connect

    Wilson, Dulaney A.; Brigantic, Andrea M.; Morgan, William F.

    2011-09-12

    Studies of health effects in animals after exposure to internally deposited radionuclides were intended to supplement observational studies in humans. Both nuclear workers and Beagle dogs have exhibited plutonium associated lung fibrosis; however, the dogs smaller gene pool may limit the applicability of findings to humans. Data on Beagles that inhaled either plutonium-238 dioxide (238PuO2) or plutonium-239 dioxide (239PuO2) were analyzed. Wright's Coefficient of Inbreeding was used to measure genetic or familial susceptibility and was assessed as an explanatory variable when modeling the association between lung fibrosis incidence and plutonium exposure. Lung fibrosis was diagnosed in approximately 80% of the exposed dogs compared with 23.7% of the control dogs. The maximum degree of inbreeding was 9.4%. Regardless of isotope, the addition of inbreeding significantly improved the model in female dogs but not in males. In female dogs an increased inbreeding coefficient predicted decreased hazard of a lung fibrosis diagnosis. Lung fibrosis was common in these dogs with inbreeding affecting models of lung fibrosis incidence in females but not in males. The apparent protective effect in females predicted by these models of lung fibrosis incidence is likely to be minimal given the small degree of inbreeding in these groups.

  16. Bortezomib therapy-related lung disease in Japanese patients with multiple myeloma: Incidence, mortality and clinical characterization

    PubMed Central

    Yoshizawa, Kazutake; Mukai, Harumi Y; Miyazawa, Michiko; Miyao, Makiko; Ogawa, Yoshimasa; Ohyashiki, Kazuma; Katoh, Takao; Kusumoto, Masahiko; Gemma, Akihiko; Sakai, Fumikazu; Sugiyama, Yukihiko; Hatake, Kiyohiko; Fukuda, Yuh; Kudoh, Shoji

    2014-01-01

    Because of the potentially high mortality rate (6.5%) associated with bortezomib-induced lung disease (BILD) in Japanese patients with relapsed or refractory multiple myeloma, we evaluated the incidence, mortality and clinical features of BILD in a Japanese population. This study was conducted under the Risk Minimization Action Plan (RMAP), which was collaboratively developed by the pharmaceutical industry and public health authority. The RMAP consisted of an intensive dissemination of risk information and a recommended countermeasure to health-care professionals. All patients treated with bortezomib were consecutively registered in the study within 1 year and monitored for emerging BILD. Of the 1010 patients registered, 45 (4.5%) developed BILD, 5 (0.50%) of whom had fatal cases. The median time to BILD onset from the first bortezomib dose was 14.5 days, and most of the patients responded well to corticosteroid therapy. A retrospective review by the Lung Injury Medical Expert Panel revealed that the types with capillary leak syndrome and hypoxia without infiltrative shadows were uniquely and frequently observed in patients with BILD compared with those with conditions associated with other molecular-targeted anticancer drugs. The incidence rate of BILD in Japan remains high compared with that reported in other countries, but the incidence and mortality rates are lower than expected before the introduction of bortezomib in Japan. This study describes the radiographic pattern and clinical characterization of BILD in the Japanese population. The RMAP seemed clinically effective in minimizing the BILD risk among our Japanese population. PMID:24329927

  17. High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene.

    PubMed Central

    Lavigueur, A; Maltby, V; Mock, D; Rossant, J; Pawson, T; Bernstein, A

    1989-01-01

    We have investigated the role of the p53 gene in oncogenesis in vivo by generating transgenic mice carrying murine p53 genomic fragments isolated from a mouse Friend erythroleukemia cell line or BALB/c mouse liver DNA. Elevated levels of p53 mRNA were detected in several tissues of two transgenic lines tested. Increased levels of p53 protein were also detected in most of the tissues analyzed by Western blotting (immunoblotting). Because both transgenes encoded p53 proteins that were antigenically distinct from wild-type p53, it was possible to demonstrate that overexpression of the p53 protein was mostly, if not entirely, due to the expression of the transgenes. Neoplasms developed in 20% of the transgenic mice, with a high incidence of lung adenocarcinomas, osteosarcomas, and lymphomas. Tissues such as ovaries that expressed the transgene at high levels were not at higher risk of malignant transformation than tissues expressing p53 protein at much lower levels. The long latent period and low penetrance suggest that overexpression of p53 alone is not sufficient to induce malignancies and that additional events are required. These observations provide direct evidence that mutant alleles of the p53 oncogene have oncogenic potential in vivo and that different cell types show intrinsic differences in susceptibility to malignant transformation by p53. Since recent data suggest that p53 may be a recessive oncogene, it is possible that the elevated tumor incidence results from functional inactivation of endogenous p53 by overexpression of the mutant transgene. The high incidence of lung and bone tumors suggests that p53 transgenic mice may provide a useful model to investigate the molecular events that underlie these malignancies in humans. Images PMID:2476668

  18. Oxidant stress regulatory genetic variation in recipients and donors contributes to risk of primary graft dysfunction after lung transplantation

    PubMed Central

    Cantu, Edward; Shah, Rupal J.; Lin, Wei; Daye, Zhongyin J.; Diamond, Joshua M.; Suzuki, Yoshikazu; Ellis, John H.; Borders, Catherine F.; Andah, Gerald A.; Beduhn, Ben; Meyer, Nuala J.; Ruschefski, Melanie; Aplenc, Richard; Feng, Rui; Christie, Jason D.

    2014-01-01

    Objective Oxidant stress pathway activation during ischemia reperfusion injury may contribute to the development of primary graft dysfunction (PGD) after lung transplantation. We hypothesized oxidant stress gene variation in recipients and donors is associated with PGD. Methods Donors and recipients from the Lung Transplant Outcomes Group (LTOG) cohort were genotyped using the Illumina IBC chip filtered for oxidant stress pathway genes. Single nucleotide polymorphisms (SNPs) grouped into SNP-sets based on haplotype blocks within 49 oxidant stress genes selected from gene ontology pathways and literature review were tested for PGD association using a sequencing kernel association test. Analyses were adjusted for clinical confounding variables and population stratification. Results 392 donors and 1038 recipients met genetic quality control standards. 30% of subjects developed grade 3 PGD within 72 hours. Donor NADPH Oxidase 3 (NOX3) was associated with PGD (p=0.01) with 5 individual significant loci (p-values between 0.006 and 0.03). In recipients, variation in glutathione peroxidase (GPX1) and NRF-2 (NFE2L2) was significantly associated with PGD (p=0.01 for both). The GPX1 association included 3 individual loci (p-values between 0.006 and 0.049) and the NFE2L2 association included 2 loci (p=0.03 and 0.05). Significant epistatic effects influencing PGD susceptibility were evident between three different donor blocks of NOX3 and recipient NFE2L2 (p=0.026, p=0.017 and p=0.031). Conclusions Our study prioritizes GPX1, NOX3, and NFE2L2 genes for future research in PGD pathogenesis, and highlights a donor-recipient interaction of NOX3 and NFE2L2 that increases PGD risk. PMID:25439478

  19. Lung-Derived Microscaffolds Facilitate Diabetes Reversal after Mouse and Human Intraperitoneal Islet Transplantation

    PubMed Central

    Pawlick, Rena L.; Kahana, Meygal; Pepper, Andrew R.; Bruni, Antonio; Gala-Lopez, Boris; Kin, Tatsuya; Mitrani, Eduardo; Shapiro, A. M. James

    2016-01-01

    There is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. Endocrine micro-pancreata (EMPs) made up of acellular organ-derived micro-scaffolds seeded with human islets have been shown to express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than three months in vitro. The aim of this study was to investigate the capacity of EMPs to restore euglycemia in vivo after transplantation of mouse or human islets in chemically diabetic mice. We proposed that the organ-derived EMPs would restore the extracellular components of the islet microenvironment, generating favorable conditions for islet function and survival. EMPs seeded with 500 mouse islets were implanted intraperitoneally into streptozotocin-induced diabetic mice and reverted diabetes in 67% of mice compared to 13% of controls (p = 0.018, n = 9 per group). Histological analysis of the explanted grafts 60 days post-transplantation stained positive for insulin and exhibited increased vascular density in a collagen-rich background. EMPs were also seeded with human islets and transplanted into the peritoneal cavity of immune-deficient diabetic mice at 250 islet equivalents (IEQ), 500 IEQ and 1000 IEQ. Escalating islet dose increased rates of normoglycemia (50% of the 500 IEQ group and 75% of the 1000 IEQ group, n = 3 per group). Human c-peptide levels were detected 90 days post-transplantation in a dose-response relationship. Herein, we report reversal of diabetes in mice by intraperitoneal transplantation of human islet seeded on EMPs with a human islet dose as low as 500 IEQ. PMID:27227978

  20. Lung-Derived Microscaffolds Facilitate Diabetes Reversal after Mouse and Human Intraperitoneal Islet Transplantation.

    PubMed

    Abualhassan, Nasser; Sapozhnikov, Lena; Pawlick, Rena L; Kahana, Meygal; Pepper, Andrew R; Bruni, Antonio; Gala-Lopez, Boris; Kin, Tatsuya; Mitrani, Eduardo; Shapiro, A M James

    2016-01-01

    There is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. Endocrine micro-pancreata (EMPs) made up of acellular organ-derived micro-scaffolds seeded with human islets have been shown to express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than three months in vitro. The aim of this study was to investigate the capacity of EMPs to restore euglycemia in vivo after transplantation of mouse or human islets in chemically diabetic mice. We proposed that the organ-derived EMPs would restore the extracellular components of the islet microenvironment, generating favorable conditions for islet function and survival. EMPs seeded with 500 mouse islets were implanted intraperitoneally into streptozotocin-induced diabetic mice and reverted diabetes in 67% of mice compared to 13% of controls (p = 0.018, n = 9 per group). Histological analysis of the explanted grafts 60 days post-transplantation stained positive for insulin and exhibited increased vascular density in a collagen-rich background. EMPs were also seeded with human islets and transplanted into the peritoneal cavity of immune-deficient diabetic mice at 250 islet equivalents (IEQ), 500 IEQ and 1000 IEQ. Escalating islet dose increased rates of normoglycemia (50% of the 500 IEQ group and 75% of the 1000 IEQ group, n = 3 per group). Human c-peptide levels were detected 90 days post-transplantation in a dose-response relationship. Herein, we report reversal of diabetes in mice by intraperitoneal transplantation of human islet seeded on EMPs with a human islet dose as low as 500 IEQ. PMID:27227978

  1. Increased Lung and Bladder Cancer Incidence In Adults After In Utero and Early-Life Arsenic Exposure

    PubMed Central

    Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Yuan, Yan; Liaw, Jane; Durán, Viviana; Cuevas, Susana; García, José; Meza, Rodrigo; Valdés, Rodrigo; Valdés, Gustavo; Benítez, Hugo; VanderLinde, Vania; Villagra, Vania; Cantor, Kenneth P; Moore, Lee E; Perez, Saida G; Steinmaus, Scott; Smith, Allan H

    2014-01-01

    Background From 1958–70, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes including lung and bladder cancer. Methods We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007–2010, and 508 age and gender-matched controls. Results Odds ratios (ORs) adjusted for age, sex, and smoking in those only exposed in early-life to arsenic water concentrations of ≤110, 110–800, and >800 μg/L were 1.00, 1.88 (95% confidence interval (CI), 0.96–3.71), and 5.24 (3.05–9.00) (p-trend<0.001) for lung cancer, and 1.00, 2.94 (1.29–6.70), and 8.11 (4.31–15.25) (p-trend<0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 μg/L) involved exposures which started 49–52 years before, and ended 37–40 years before the cancer cases were diagnosed. Conclusion Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early-life, even up to 40 years after high exposures ceased. Findings like these have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure. Impact Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. PMID:24859871

  2. Parainfluenza virus-3-induced cytopathic effects on lung tissue and bronchoalveolar lavage fluid in a bone marrow transplant recipient: a case report.

    PubMed

    Pokharel, Saraswati; Merickel, C Ryan; Alatassi, Houda

    2014-06-01

    Parainfluenza virus type 3(PIV-3) commonly causes respiratory tract infections in hematopoietic stem cell transplant (HSCT) patients. The majority of PIV-3 infections develop in patients who have undergone stem cell transplantation from unrelated donors. From these patients, bronchoalveolar lavage (BAL) fluid and/or lung biopsies are often collected and sent for evaluation of infectious processes. However, cytologic findings associated with a PIV-3 infection in BAL fluid have not been reported in the literature. We describe BAL cytology and lung biopsy findings in a patient who received an HSCT from a related donor and subsequently developed a PIV-3 infection. This patient was noted to have scattered reticular-nodular opacities in both lungs on computed tomogram scan and underwent transbronchial biopsy and BAL of the left lower lobe. Examination of the BAL fluid revealed scattered multinucleated giant cells intermixed with inflammatory cells. The lung biopsy showed organizing pneumonia associated with several multinucleated respiratory epithelial cells containing rare intracytoplasmic inclusions. Gram, periodic acid Schiff, Gomori methenamine silver, and acid fast stains on the biopsy specimen failed to reveal microorganisms. A sample of the BAL fluid sent for respiratory viral culture grew PIV-3. These findings suggest that the presence of giant cells in transplant patients with organizing pneumonia should raise suspicion of a PIV-3 infection. PMID:23554422

  3. Protective function of pirfenidone and everolimus on the development of chronic allograft rejection after experimental lung transplantation.

    PubMed

    von Suesskind-Schwendi, M; Heigel, E; Pfaehler, S; Haneya, A; Schmid, C; Hirt, S W; Lehle, K

    2016-07-01

    Long-term survival of lung allografts is limited by chronic rejection (CR). Oxidative stress (OxS) plays a central role in the development of CR. We investigated the influence of pirfenidone (alone or in combination with everolimus) on OxS and CR. A rat model of left lung allo-transplantation (F344-to-WKY) was used to evaluate the effects of pirfenidone alone [0,85% in chow from postoperative day (POD) -3 to 20/60] and in combination with everolimus [2,5 mg/kg bw daily from POD 7 to 20/60]. Allografts of non-treated animals, everolimus treated animals and right, non-transplanted lungs were used as references. Immunohistology of myeloperoxidase (MPO), haemoxygenase-1 (HO-1), iron and platelet-derived-growth-factor-receptor-alpha (PDGFR-a) were performed. On POD 20, all groups showed severe acute rejection (ISHLT A3-4/B1R-B2R). Groups treated with pirfenidone showed a lower interstitial inflammatory infiltration and a lower participation of highly fibrotic degenerated vessels (ISHLT-D2R). In the long term follow up (POD 60), pirfenidone alone significantly reduced chronic airway rejection (ISHLT-C; p≤0.05), interstitial fibrosis (IF; p≤0.05), content of collagen (p≤0.05), expression of PDGFR-a (p≤0.05) and the deposition of iron (p≤0.05). All groups treated with pirfenidone showed a high expression of the cytoprotective enzyme HO-1 (p≤0.05). The additional application of everolimus resulted in a significant decrease of chronic airway rejection (ISHLT-C; p≤0.05), vasculopathy (ISHLT; p≤0.05) and IF (p≤0.05). In conclusion, early application of pirfenidone inhibited the progression of CR by its anti-fibrotic and anti-oxidative properties. The additional application of an m-TOR-inhibitor increased the anti-fibrotic effects of pirfenidone which resulted in a reduction of CR after experimental LTx. PMID:26707547

  4. Reduction in incidence of invasive fungal infection in patients receiving allogeneic stem cell transplantation using combined diagnostic-driven approach and itraconazole oral solution.

    PubMed

    Tzadok, Roie; Shapira, Michael Y; Moses, Allon E; Or, Reuven; Block, Colin; Strahilevitz, Jacob

    2015-12-01

    Invasive fungal infections are an important cause of morbidity and mortality after allogeneic haematopoietic stem cell transplantation. We evaluated, in our allogeneic stem cell transplant patients, the effect on the incidence of invasive fungal infection during neutropenia of a strategy combining a diagnostic-driven approach with chemoprophylaxis during higher risk periods of graft vs. host disease and prolonged neutropenia, using itraconazole oral solution with parenteral voriconazole bridging. One hundred and thirty patients admitted for allogeneic stem cell transplantation within two predefined 20 month periods were included in the study. Data for all patients were collected prospectively. Implementation of the protocol resulted in the administration of more prophylactic antifungals to more patients. Following implementation, there was a non-significant decrease in the overall number of invasive fungal infections (IFI) [11 of 65 patients (17.2%) vs. 4 of 65 patients (6.2%, P = 0.051)], as well as in the occurrence of invasive mould infections [8 of 65 patients (12.5%) vs. 2 of 65 patients (3.1%, P = 0.054)]. Survival rates at three and 6 months were not significantly affected. A combined diagnostic-driven approach and antifungal prophylaxis with oral itraconazole and an intravenous voriconazole bridging protocol, was associated with a reduced, albeit non-statistically significant, number of IFI in our medical centre. PMID:26429354

  5. Invasive Fungal Infections after Renal Transplantation

    PubMed Central

    Ezzatzadegan, S.; Chen, S.; Chapman, J. R.

    2012-01-01

    Background: Invasive fungal infection (IFI) is a leading cause of infection-related mortality among kidney allograft recipients.  Objective: To estimate the incidence and etiology of systemic fungal infection in renal allograft recipients in Sydney transplant facility. Methods: 471 kidney recipients, transplanted between 2000 and 2010 at the Westmead Hospital renal transplantation center, Sydney, Australia, were retrospectively surveyed. Results: IFI developed in 10 (2.1%) of 471 patients. With a mean±SD new kidney transplants per year of 42.9±13, the mean±SD incidence of IFI was 0.9±0.6 for each year of transplantation. 4 patients had received kidneys from living donors and 7 from cadavers with a mean±SD age of 50.5±14 years. The mean time to IFI was 33 months after transplantation with majority within the first 2 years. Cryptococcus neoformans was responsible for 50% of episodes (n=5) followed by Aspergillus fumigatus (n=3), and Pseudallescheria boydii (n=3); there was a single case of mucurmycosis. Lungs (n=5) followed by meninges (n=4) and skin (n=3) were the most commonly involved sites. Conclusion: IFI remains a major concern in renal transplantation. A high index of suspicion is required for early diagnosis and treatment to reduce the mortality. In this regard, appropriate diagnostic tests are necessary, particularly for C. neoformans. PMID:25013619

  6. Comparison of the effects of inhaled {sup 239}PuO{sub 2} and {beta}- emitting radionuclides on the incidence of lung carcinomas in laboratory animals

    SciTech Connect

    Hahn, F.F.; Griffith, W.C.; Boecker, B.B.; Muggenburg, B.A.; Lundgren, D.L.

    1991-12-31

    The health effects of inhaling radioactive particles when the lung is the primary organ irradiated were studied in rats and Beagle dogs. The animals were exposed to aerosols of {sup 239}PuO{sub 2} or fission-product radionuclides in insoluble forms and observed for their life span. Lung carcinomas were the primary late-occuring effect. The incidence rate for lung carcinomas was modeled using a proportional hazard rate model. Linear functions predominated below 5 Gy to the lung. The life-time risk for lung carcinomas per 10{sup 4} Gy for beta emitters was 60 for rats and 65 for dogs, and for {sup 239}PuO{sub 2} it was 1500 for rats and 2300 for dogs.

  7. Transfusion-Related Acute Lung Injury: Incidence, Pathogenesis and the Role of Multicomponent Apheresis in Its Prevention.

    PubMed

    Popovsky, Mark A

    2008-01-01

    SUMMARY: Although transfusion-related acute lung injury (TRALI) is now appreciated as the most common cause of death from transfusion, its incidence remains unknown. The most frequently cited figure is 1:5,000 plasma-containing components. Certain patient groups may be at significantly higher risk. TRALI is both underdiagnosed and un-derreported. It is misdiagnosed as transfusion-associated circulatory overload. Several mechanisms have been proposed for its pathogenesis-leukocyte antibodies and the 2-hit model. These may overlap, and both involve transfusion of leukocyte antibodies. Passive transfusion of leukocyte antibodies is strongly associated with TRALI; these are identified in 60-85% of cases. Multiparous blood donors are the most frequent source of these antibody-containing components. The antibodies are HLA class I and II and/or granulocyte-specific. In 50% of cases the antibody corresponds to an epitope in the patient. HLA class I antibodies have been shown to prime and activate neutrophils. Clinical reports and animal models link HNA-3a antibodies with severe lung injury. A number of TRALI prevention and risk mitigation strategies have been proposed. In the UK and the USA, these strategies have centered upon excluding 'high risk' (HLA/HNA antibody containing) plasma from fresh frozen plasma and platelet products. Multicomponent apheresis collection of platelets, plasma and red blood cells is a means of accomplishing this objective. PMID:21512631

  8. Scedosporium apiospermum and S. prolificans mixed disseminated infection in a lung transplant recipient: An unusual case of long-term survival with combined systemic and local antifungal therapy in intensive care unit

    PubMed Central

    Balandin, Bárbara; Aguilar, Miriam; Sánchez, Isabel; Monzón, Araceli; Rivera, Isabel; Salas, Clara; Valdivia, Miguel; Alcántara, Sara; Pérez, Aris; Ussetti, Piedad

    2016-01-01

    Infections due Scedosporium spp. in lung transplant recipients are associated with disseminated disease with high mortality rates. The adjunctive local antifungal therapy may be a useful option when systemic treatment is insufficient and/or surgery is not feasible. We present a case of mixed disseminated infection due Scedosporium apiospermum and S. prolificans in a lung transplant recipient. Combined local and systemic antifungal therapy provided an unusual long-term survival in the intensive care unit. PMID:27222774

  9. Scedosporium apiospermum and S. prolificans mixed disseminated infection in a lung transplant recipient: An unusual case of long-term survival with combined systemic and local antifungal therapy in intensive care unit.

    PubMed

    Balandin, Bárbara; Aguilar, Miriam; Sánchez, Isabel; Monzón, Araceli; Rivera, Isabel; Salas, Clara; Valdivia, Miguel; Alcántara, Sara; Pérez, Aris; Ussetti, Piedad

    2016-03-01

    Infections due Scedosporium spp. in lung transplant recipients are associated with disseminated disease with high mortality rates. The adjunctive local antifungal therapy may be a useful option when systemic treatment is insufficient and/or surgery is not feasible. We present a case of mixed disseminated infection due Scedosporium apiospermum and S. prolificans in a lung transplant recipient. Combined local and systemic antifungal therapy provided an unusual long-term survival in the intensive care unit. PMID:27222774

  10. Increased incidence of murine graft-versus-host disease after allogeneic bone marrow transplantation by previous infusion of syngeneic bone marrow cells

    SciTech Connect

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

    1984-10-01

    Different groups of BALB/c mice received supralethal total-body irradiation (TBI; 8.5 Gy, day 0). When 30 x 10(6) allogeneic (C57B1) bone marrow (BM) cells were infused with or without 10 x 10(6) syngeneic (BALB/c) bM cells on day 1, many animals (60%) died from graft-versus-host disease (GVHD). Typing of peripheral blood leukocytes for donor antigens showed that, respectively, 22/22 and 17/21 of the mice in both groups became chimeric. When syngeneic bone marrow was given on day 1 and allogeneic bone marrow on day 2 after TBI, a similar number of animals (21/23) became chimeric, but GVHD occurred more frequently in this group (25/26 mice, P less than 0.01). When the syngeneic bone marrow cells were replaced by spleen cells, or when the transplantation of allogeneic bone marrow was delayed till days 3 or 6 after TBI, almost all mice rejected the allogeneic BM graft and became long-term survivors. BALB/c mice receiving 30 x 10(6) C57B1 BM cells after 17 daily fractions of 0.2 Gy of total lymphoid irradiation (TLI), showed a high incidence of chimerism (15/17) and in none of the latter animals was GVHD observed. Despite the high incidence of GVHD in the mice receiving allogeneic BM after TBI and syngeneic BM transplantation, as compared with mice prepared with TLI which do not develop GVHD, suppressor cells were as easily induced after TBI and syngeneic BM transplantation as after TLI.

  11. The Presence of HLA-E-Restricted, CMV-Specific CD8+ T Cells in the Blood of Lung Transplant Recipients Correlates with Chronic Allograft Rejection

    PubMed Central

    Sullivan, Lucy C.; Westall, Glen P.; Widjaja, Jacqueline M. L.; Mifsud, Nicole A.; Nguyen, Thi H. O.; Meehan, Aislin C.; Kotsimbos, Tom C.; Brooks, Andrew G.

    2015-01-01

    The human cytomegalovirus (CMV) immune evasion protein, UL40, shares an identical peptide sequence with that found in the leader sequence of many human leukocyte antigen (HLA)-C alleles and when complexed with HLA-E, can modulate NK cell functions via interactions with the CD94-NKG2 receptors. However the UL40-derived sequence can also be immunogenic, eliciting robust CD8+ T cell responses. In the setting of solid organ transplantation these T cells may not only be involved in antiviral immunity but also can potentially contribute to allograft rejection when the UL40 epitope is also present in allograft-encoded HLA. Here we assessed 15 bilateral lung transplant recipients for the presence of HLA-E-restricted UL40 specific T cells by tetramer staining of peripheral blood mononuclear cells (PBMC). UL40-specific T cells were observed in 7 patients post-transplant however the magnitude of the response varied significantly between patients. Moreover, unlike healthy CMV seropositive individuals, longitudinal analyses revealed that proportions of such T cells fluctuated markedly. Nine patients experienced low-grade acute cellular rejection, of which 6 also demonstrated UL40-specific T cells. Furthermore, the presence of UL40-specific CD8+ T cells in the blood was significantly associated with allograft dysfunction, which manifested as Bronchiolitis Obliterans Syndrome (BOS). Therefore, this study suggests that minor histocompatibility antigens presented by HLA-E can represent an additional risk factor following lung transplantation. PMID:26302084

  12. The Presence of HLA-E-Restricted, CMV-Specific CD8+ T Cells in the Blood of Lung Transplant Recipients Correlates with Chronic Allograft Rejection.

    PubMed

    Sullivan, Lucy C; Westall, Glen P; Widjaja, Jacqueline M L; Mifsud, Nicole A; Nguyen, Thi H O; Meehan, Aislin C; Kotsimbos, Tom C; Brooks, Andrew G

    2015-01-01

    The human cytomegalovirus (CMV) immune evasion protein, UL40, shares an identical peptide sequence with that found in the leader sequence of many human leukocyte antigen (HLA)-C alleles and when complexed with HLA-E, can modulate NK cell functions via interactions with the CD94-NKG2 receptors. However the UL40-derived sequence can also be immunogenic, eliciting robust CD8+ T cell responses. In the setting of solid organ transplantation these T cells may not only be involved in antiviral immunity but also can potentially contribute to allograft rejection when the UL40 epitope is also present in allograft-encoded HLA. Here we assessed 15 bilateral lung transplant recipients for the presence of HLA-E-restricted UL40 specific T cells by tetramer staining of peripheral blood mononuclear cells (PBMC). UL40-specific T cells were observed in 7 patients post-transplant however the magnitude of the response varied significantly between patients. Moreover, unlike healthy CMV seropositive individuals, longitudinal analyses revealed that proportions of such T cells fluctuated markedly. Nine patients experienced low-grade acute cellular rejection, of which 6 also demonstrated UL40-specific T cells. Furthermore, the presence of UL40-specific CD8+ T cells in the blood was significantly associated with allograft dysfunction, which manifested as Bronchiolitis Obliterans Syndrome (BOS). Therefore, this study suggests that minor histocompatibility antigens presented by HLA-E can represent an additional risk factor following lung transplantation. PMID:26302084

  13. ASSESSMENT OF ACUTE LUNG INJURY INDUCED BY PM 2.5 SAMPLES FROM TWO CITIES IN GERMANY WITH DIFFERING INCIDENCE OF ALLERGIES AND ASTHMA

    EPA Science Inventory

    ASSESSMENT OF ACUTE LUNG INJURY INDUCED BY PM 2.5 SAMPLES FROM TWO CITIES IN GERMANY WITH DIFFERING INCIDENCE OF ALLERGIES AND ASTHMA.

    LR Bishop, J Heinrich*, MK Selgrade & MI Gilmour.
    Experimental Toxicology Division, ORD/ NHEERL, U.S. EPA, RTP, NC. *GSF, Neuherberg,...

  14. EFFECT OF SUBSEQUENT TREATMENT OF CHLOROFORM OF PHENOBARBITAL ON THE INCIDENCE OF LIVER AND LUNG TUMORS INITIATED BY ETHYLNITROSOUREA IN 15 DAY OLD MICE

    EPA Science Inventory

    The effect of subsequent administration of chloroform or phenobarbital on the incidence of ethylnitrosourea (ENU) initiated liver and lung tumors was investigated. Fifteen day old Swiss mice were administered ENU, and at weaning they started to receive either 1800 ppm chloroform ...

  15. Development and Preclinical Application of an Immunocompetent Transplant Model of Basal Breast Cancer with Lung, Liver and Brain Metastases

    PubMed Central

    Hoenerhoff, Mark; Hixon, Julie A.; Durum, Scott K.; Qiu, Ting-hu; He, Siping; Burkett, Sandra; Liu, Zi-Yao; Swanson, Steven M.; Green, Jeffrey E.

    2016-01-01

    Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is associated with a poor prognosis and for which no targeted therapies currently exist. In order to improve preclinical testing for TNBC that relies primarily on using human xenografts in immunodeficient mice, we have developed a novel immunocompetent syngeneic murine tumor transplant model for basal-like triple-negative breast cancer. The C3(1)/SV40-T/t-antigen (C3(1)/Tag) mouse mammary tumor model in the FVB/N background shares important similarities with human basal-like TNBC. However, these tumors or derived cell lines are rejected when transplanted into wt FVB/N mice, likely due to the expression of SV40 T-antigen. We have developed a sub-line of mice (designated REAR mice) that carry only one copy of the C3(1)/Tag-antigen transgene resulting from a spontaneous transgene rearrangement in the original founder line. Unlike the original C3(1)/Tag mice, REAR mice do not develop mammary tumors or other phenotypes observed in the original C3(1)/Tag transgenic mice. REAR mice are more immunologically tolerant to SV40 T-antigen driven tumors and cell lines in an FVB/N background (including prostate tumors from TRAMP mice), but are otherwise immunologically intact. This transplant model system offers the ability to synchronously implant the C3(1)/Tag tumor-derived M6 cell line or individual C3(1)/Tag tumors from various stages of tumor development into the mammary fat pads or tail veins of REAR mice. C3(1)/Tag tumors or M6 cells implanted into the mammary fat pads spontaneously metastasize at a high frequency to the lung and liver. M6 cells injected by tail vein can form brain metastases. We demonstrate that irradiated M6 tumor cells or the same cells expressing GM-CSF can act as a vaccine to retard tumor growth of implanted tumor cells in the REAR model. Preclinical studies performed in animals with an intact immune system should more authentically replicate treatment responses in

  16. Development and Preclinical Application of an Immunocompetent Transplant Model of Basal Breast Cancer with Lung, Liver and Brain Metastases.

    PubMed

    Aprelikova, Olga; Tomlinson, Christine C; Hoenerhoff, Mark; Hixon, Julie A; Durum, Scott K; Qiu, Ting-Hu; He, Siping; Burkett, Sandra; Liu, Zi-Yao; Swanson, Steven M; Green, Jeffrey E

    2016-01-01

    Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is associated with a poor prognosis and for which no targeted therapies currently exist. In order to improve preclinical testing for TNBC that relies primarily on using human xenografts in immunodeficient mice, we have developed a novel immunocompetent syngeneic murine tumor transplant model for basal-like triple-negative breast cancer. The C3(1)/SV40-T/t-antigen (C3(1)/Tag) mouse mammary tumor model in the FVB/N background shares important similarities with human basal-like TNBC. However, these tumors or derived cell lines are rejected when transplanted into wt FVB/N mice, likely due to the expression of SV40 T-antigen. We have developed a sub-line of mice (designated REAR mice) that carry only one copy of the C3(1)/Tag-antigen transgene resulting from a spontaneous transgene rearrangement in the original founder line. Unlike the original C3(1)/Tag mice, REAR mice do not develop mammary tumors or other phenotypes observed in the original C3(1)/Tag transgenic mice. REAR mice are more immunologically tolerant to SV40 T-antigen driven tumors and cell lines in an FVB/N background (including prostate tumors from TRAMP mice), but are otherwise immunologically intact. This transplant model system offers the ability to synchronously implant the C3(1)/Tag tumor-derived M6 cell line or individual C3(1)/Tag tumors from various stages of tumor development into the mammary fat pads or tail veins of REAR mice. C3(1)/Tag tumors or M6 cells implanted into the mammary fat pads spontaneously metastasize at a high frequency to the lung and liver. M6 cells injected by tail vein can form brain metastases. We demonstrate that irradiated M6 tumor cells or the same cells expressing GM-CSF can act as a vaccine to retard tumor growth of implanted tumor cells in the REAR model. Preclinical studies performed in animals with an intact immune system should more authentically replicate treatment responses in

  17. Bone marrow transplantation alters lung antigen presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection

    PubMed Central

    Zhou, Xiaofeng; Loomis-King, Hillary; Gurczynski, Stephen J.; Wilke, Carol A.; Konopka, Kristine E.; Ptaschinski, Catherine; Coomes, Stephanie M; Iwakura, Yoichiro; van Dyk, Linda F.; Lukacs, Nicholas W.; Moore, Bethany B.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplant (BMT) followed by infection with murine gamma herpesvirus (γHV-68) that results in pneumonitis and fibrosis and mimics human “non-infectious” HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection (dpi). CD4 T cells in BMT mice are skewed towards IL-17A rather than IFN-γ production. Transplantation of bone marrow from Il-17a−/− donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more TGF-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest “non-infectious” HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

  18. Reduced incidence of acute graft versus host disease (GVHD) of the gut in Chinese carriers of Helicobacter pylori during allogeneic bone marrow transplantation.

    PubMed

    Au, W Y; Wong, R W M; Wong, B C Y; Lie, A K W; Liang, R; Leung, A Y H; Kwong, Y-L

    2004-01-01

    Helicobacter pylori ( H. Pylori) infection is associated with gastritis and peptic ulcer, but its relationship with gut graft versus host disease (GVHD) is unknown. We investigated the association between H.