Paraskeva, Miranda A; Westall, Glen P; Pilcher, David; McGiffin, David; Levvey, Bronwyn J; Williams, Trevor J; Snell, Gregory I
The management of patients undergoing lung transplantation has continued to evolve, leading to improvements in 90-day and 1-year survival. The significant advancements in donor management and utilization at our center have led to significant increases in lung transplant activity without any compromise in recipient outcomes. Through the use of a patient-centered multidisciplinary model of care involved in all aspects of recipient management, from assessment and waitlisting to pre-, peri- and post-operative care, our lung transplant outcomes represent 2015 world's best lung transplant practice.
Lung transplant Overview By Mayo Clinic Staff A lung transplant is a surgical procedure to replace a diseased or ... lung, usually from a deceased donor. A lung transplant is reserved for people who have tried other ...
Prais, Dario; Raviv, Yael; Shitrit, David; Yellin, Alon; Sahar, Gideon; Bendayan, Danielle; Yahav, Yaacov; Efrati, Ori; Reichart, Nira; Blau, Hannah; Bakal, Ilana; Buchman, Gila; Saute, Milton; Vidne, Bernardo; Kramer, Mordechai R
Lung transplantation is a well-established therapeutic option for end-stage lung disease in cystic fibrosis. Although it confers a clear survival advantage, outcome differs among centers according to local experience, patient selection, transplantation procedure, and postoperative care. To evaluate the national Israeli experience with lung transplantation in patients with CF. We reviewed the medical charts of all CF patients who underwent lung transplantation between January 1996 and June 2005 at the two Israeli centers that perform this procedure. Eighteen transplantations were performed in 17 patients. Mean patient age at transplantation was 25.3 +/- 9.1 years, and mean duration of follow-up in survivors (n=14) was 37.2 months (range 1-113 months). The actuarial survival rate was 88% at 1 year and 74% at 5 years. Pulmonary function, expressed as percent of predicted normal forced expiratory volume in 1 sec, improved from 22.4 +/- 8.1% to 76 +/- 16.8% at one year after transplantation. Bronchiolitis obliterans syndrome was diagnosed in 5 patients (29%), of whom 2 died and 2 are currently candidates for retransplantation. Median time to onset of BOS was 34.2 months (range 17-64 months). In Israel, the early and intermediate-term results of lung transplantation for cystic fibrosis are encouraging. BOS remains a major complication that threatens long-term outcome.
... who have severe COPD Cystic fibrosis Idiopathic pulmonary fibrosis Alpha-1 antitrypsin deficiency Pulmonary hypertension Complications of lung transplantation include rejection of the transplanted lung and infection. NIH: National Heart, Lung, and Blood Institute
Thomsen, Doris; Jensen, Birte Østergaard
To investigate the experiences of everyday life after lung transplantation of patients with previous chronic obstructive pulmonary disease (COPD). Compared with patients being transplanted due to other indications, those with COPD prior to lung transplantation report more problems in the form of shortness of breath, fatigue, sexual problems, insomnia and increased appetite. In addition, they are often faced with problems returning to normal working life. How these problems influence the patient's everyday life is unknown. An exploratory qualitative study. Ten COPD patients (five females and five males) aged 51-69 and more than six months post transplantation, were interviewed using of a semi-structured interview guide. All interviews were taperecorded, transcribed verbatim and analysed using qualitative content analysis. The analysis revealed four themes of experience: a second chance; an ordinary life without chronic rejection; even minor daily activities take time with chronic rejection; and need for support and knowledge that were considered important by the participants for their situation and daily life. This is the first study describing the experiences of everyday life after lung transplantation of patients with COPD prior to surgery. The findings highlight the importance of addressing these patients' experiences of gratitude, positive life orientation and informational needs in relation to everyday life. Health professionals should be aware of the kind of problems both women and men may experience a long time after the lung transplantation. They constitute a basic knowledge of a patient's everyday life that is important when planning individual counselling and rehabilitation.
Reichenspurner, H; Odell, J A; Cooper, D K; Novitzky, D; Rose, A G; Klinner, W; Reichart, B
Between February 1983 and July 1987, twelve patients underwent heart-lung transplantation at the University of Cape Town and the University of Munich. The patients included eight men and four women, whose ages ranged from 15 to 49 years (mean, 27 years). The underlying pathologic condition was idiopathic primary pulmonary hypertension in five cases, Eisenmenger's syndrome in four cases, idiopathic pulmonary fibrosis in one case, diffuse fibrosing alveolitis in one case, and chronic emphysema in one case. The immunosuppressive regimen consisted of cyclosporine A, azathioprine, and rabbit antithymocyte globulin (RATG) during the first 2 postoperative weeks; RATG was subsequently replaced by methylprednisolone. Pulmonary rejection frequently occurred in the absence of cardiac rejection; in one case, however, this situation was reversed. Two patients required retransplantation, which was undertaken for caseating pulmonary tuberculosis with obliterative bronchiolitis after 1 year in one case and for early pulmonary insufficiency after 2 days in the other case. There were no operative deaths, but three early deaths occurred, owing to respiratory insufficiency of unknown origin (10 days postoperatively), multiorgan failure (10 days postoperatively), and acute liver dystrophy (11 days postoperatively). Five weeks after operation, a fourth patient died of multi-organ failure. There were five late deaths, all of which resulted from infectious complications. Three patients, including one who underwent retransplantation, remain alive and well, 10 to 36 months postoperatively.
Reichenspurner, Hermann; Odell, John A.; Cooper, David K.C.; Novitzky, Dimitri; Rose, Alan G.; Klinner, Werner; Reichart, Bruno
Between February 1983 and July 1987, twelve patients underwent heart-lung transplantation at the University of Cape Town and the University of Munich. The patients included eight men and four women, whose ages ranged from 15 to 49 years (mean, 27 years). The underlying pathologic condition was idiopathic primary pulmonary hypertension in five cases, Eisenmenger's syndrome in four cases, idiopathic pulmonary fibrosis in one case, diffuse fibrosing alveolitis in one case, and chronic emphysema in one case. The immunosuppressive regimen consisted of cyclosporine A, azathioprine, and rabbit antithymocyte globulin (RATG) during the first 2 postoperative weeks; RATG was subsequently replaced by methylprednisolone. Pulmonary rejection frequently occurred in the absence of cardiac rejection; in one case, however, this situation was reversed. Two patients required retransplantation, which was undertaken for caseating pulmonary tuberculosis with obliterative bronchiolitis after 1 year in one case and for early pulmonary insufficiency after 2 days in the other case. There were no operative deaths, but three early deaths occurred, owing to respiratory insufficiency of unknown origin (10 days postoperatively), multiorgan failure (10 days postoperatively), and acute liver dystrophy (11 days postoperatively). Five weeks after operation, a fourth patient died of multi-organ failure. There were five late deaths, all of which resulted from infectious complications. Three patients, including one who underwent retransplantation, remain alive and well, 10 to 36 months postoperatively. (Texas Heart Institute Journal 1988; 15:3-6) Images PMID:15227270
Kramer, Mordechai R; Saute, Milton; Eidelman, Leonid; Aravot, Dan; Fink, Gershon; Shitrit, David; Izbicky, Gabriel; Izvicky, Gavriel; Dayan, Daniel Ben; Bakal, Ilana; Kogan, Alex; Gendel, Boris; Vidne, Bernardo; Sahar, Gideon
Lung transplantation is a relatively new field in solid organ transplantation. We present our early experience with the first 70 cases at the Rabin Medical Center during the years 1997-2003. Forty seven patients underwent single lung, eight double lung and eight heart-lung transplantations. The patients treated included 49 men and 21 women aged 5-66 years. There were 26 cases with emphysema COPD. 30 patients with pulmonary fibrosis. 5 patients with pulmonary hypertension/Eisenmenger and 9 patients with cystic fibrosis and bronchiectasis. Although early results (1997-1999) showed 1 and 3 year survival of only 50%, in the last 3 years (2000-2003), survival reached 84% and 82% at 1 and 3 years respectively. Improvement in the success rate is due to better patient selection, new immunosuppressive regimen and, most importantly, excellent teamwork. We conclude that lung transplantation is a viable option for selected patients with end-stage lung disease.
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
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
... 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: ...
Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold; Zemtsovski, Mikhail; Nilsson, Jens Christian; Seidelin, Casper Tobias; Perch, Michael; Iversen, Martin; Steinbrüchel, Daniel
The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its introduction. The study was conducted by prospective registration of donor offers and lung transplantations in Denmark from 1 May 2012 to 30 April 2013. Donor lungs without any contraindications were transplanted in the traditional manner. Taken for EVLP were donor lungs that were otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died of non-EVLP-related causes, but all other recipients were alive with normal graft function at the end of our registration period. All lungs showed an improved PaO2/FiO2 ratio from a median 23.1 kPa (8.8-38.9) within the donor to 58.8 kPa (34.9-76.5) (FiO2 = 1.0) after EVLP, which corresponds to a 155% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted as a result of their improved function. EVLP seems to be a safe way to increase the use of marginal donor lungs. no funding was granted for the present paper. not relevant.
... will recover in the hospital’s intensive care unit (ICU) before moving to a hospital room for one to three weeks. Your doctor may recommend pulmonary rehabilitation after your lung transplant surgery to help you ...
Sage, Edouard; Mussot, Sacha; Trebbia, Grégoire; Puyo, Philippe; Stern, Marc; Dartevelle, Philippe; Chapelier, Alain; Fischler, Marc
Only 15% of brain death donors are considered suitable for lung transplantation (LTx). The normothermic ex vivo lung perfusion technique is used to potentially increase the availability of high-risk lung donors. We report our experience of LTx with initially rejected donors after ex vivo lung reconditioning (EVLR). From April 2011 to May 2013, we performed EVLR for 32 pairs of donor lungs deemed unsuitable for transplantation and rejected by the 11 French lung transplant teams. After EVLR, lungs with acceptable function were transplanted. During the same period, 81 double-lung transplantations (DLTx) were used as controls. During EVLR, 31 of 32 donor lungs recovered physiological function with a median PO2/FiO2 ratio increasing from 274 (range 162-404) mmHg to 511 (378-668) mmHg at the end of EVLR (P < 0.0001). Thirty-one DLTx were performed. The incidence of primary graft dysfunction 72 h after LTx was 9.5% in the EVLR group and 8.5% in the control group (P = 1). The median time of extubation, intensive care unit and hospital lengths of stay were 1, 9 and 37 days in the EVLR group and 1 (P = 0.17), 6 (P = 0.06) and 28 days (P = 0.09) in the control group, respectively. Thirty-day mortality rates were 3.3% (n = 1) in the EVLR group and 3.7% (n = 3) in the control group (P = 0.69). One-year survival rates were 93% in the EVLR group and 91% in the control group. EVLR is a reliable and repeatable technique that offers a significant increase of available donors. The results of LTx with EVLR lungs are similar to those obtained with conventional donors. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Ivarsson, Bodil; Ingemansson, Richard; Sjöberg, Trygve
Lung transplant patients and their next of kin share the experiences of illness but little is known in the face of a lung re-transplantation. To describe patients' and next of kin's experiences of supportive care while awaiting lung re-transplantation and the objective was to highlight a small group with special circumstances and needs. Using qualitative content analysis, seven adult patients and seven next of kin were consecutively selected from a regional lung transplantation centre and individually interviewed shortly after decision about lung re-transplantation. The experiences of supportive care were captured in one main category: 'once again haunted by death' and three sub-categories: 'when life turns and death once again snorts down your neck', 'the importance of information', and 'perceptions of support'. A complex interaction between the experience of waiting, and communication patterns, emotional states, and social support was shown. This study provides insights into the complex interaction between the experience of waiting for a second lung transplant and communication patterns, emotional states, social support and social roles between patients, next of kin, healthcare professionals, and the health and social welfare system. There is a need for developing supportive care programme to achieve the best possible care.
Ivarsson, Bodil; Ingemansson, Richard; Sjöberg, Trygve
Objectives: Lung transplant patients and their next of kin share the experiences of illness but little is known in the face of a lung re-transplantation. To describe patients’ and next of kin’s experiences of supportive care while awaiting lung re-transplantation and the objective was to highlight a small group with special circumstances and needs. Methods: Using qualitative content analysis, seven adult patients and seven next of kin were consecutively selected from a regional lung transplantation centre and individually interviewed shortly after decision about lung re-transplantation. Results: The experiences of supportive care were captured in one main category: ‘once again haunted by death’ and three sub-categories: ‘when life turns and death once again snorts down your neck’, ‘the importance of information’, and ‘perceptions of support’. A complex interaction between the experience of waiting, and communication patterns, emotional states, and social support was shown. Conclusion: This study provides insights into the complex interaction between the experience of waiting for a second lung transplant and communication patterns, emotional states, social support and social roles between patients, next of kin, healthcare professionals, and the health and social welfare system. There is a need for developing supportive care programme to achieve the best possible care. PMID:28540044
Watson, T J; Starnes, V A
The disparity between available donors and potential recipients of lung transplants has demanded a certain degree of flexibility on the part of transplantation surgeons. Marginal donors are now being used more frequently, and downsizing lungs from larger donors to fit into small recipients is quite common. In some instances, particularly in the circumstances of children, a single lobe from a much larger donor may serve very well as an entire lung in the recipient. Although either the upper or lower lobes from either side may be used, the lower lobes, especially the left, are better suited for this purpose because of the anatomy of the arterial, venous, and bronchial systems. As an extension of this concept, living-donor lung transplantation is now an accepted practice in carefully selected patients. Most children are best treated with bilateral lobar transplantation, particularly when cystic fibrosis is the indication. For living-donor transplantation, this obviously involves engaging two willing donors able to pass a rigorous physical and psychological evaluation. Although the recipients are generally sicker than the average cadaveric lung transplant recipient, early results to date have been similar to those receiving cadaveric lungs. In this article, we will describe our experience with this procedure, including the evaluation process, the technical aspects of the donor and recipient operations, and the results in the donors and recipients.
Biscotti, Mauer; Gannon, Whitney D; Agerstrand, Cara; Abrams, Darryl; Sonett, Joshua; Brodie, Daniel; Bacchetta, Matthew
Extracorporeal membrane oxygenation (ECMO) is used as a bridge to lung transplantation, but characteristics that influence its success are poorly understood. This large, single-center experience evaluated the implementation and outcomes of ECMO in this setting. Data were collected for patients at our institution (New York-Presbyterian Hospital/Columbia University Medical Center in New York) who received ECMO as a bridge to lung transplantation from January 1, 2007 through July 10, 2016. Data were analyzed for demographics, baseline characteristics, survival, and ECMO configuration. Seventy-two patients received ECMO as a bridge to lung transplantation. Of the 72 patients, 40 (55.6%) underwent the transplantation procedure, 37 (92.5%) survived to discharge, and 21 (84.0%) survived for 2 years. Inotropy or vasopressor support (70% vs 93.8%; p = 0.011), Simplified Acute Physiology Score (26.8 vs 30.5; p = 0.048), and ambulation (80% vs 56.2%; p = 0.030) were significantly different between the patients who underwent lung transplantation and those who did not. Patients with cystic fibrosis were more likely to have a bridge to transplantation than patients with other lung diseases (47.5% vs 25%; p = 0.050). Daily participation in physical therapy was achieved in 50 patients (69.4%). This study demonstrated favorable survival in patients receiving ECMO as a bridge to lung transplantation and achieved high rates of physical therapy and avoidance of mechanical ventilation while ECMO was used in patients awaiting lung transplantation. With more than half of these patients successfully bridged to lung transplantation, we gained insight into the factors influencing patients' outcomes, including patient selection, timing of ECMO, and patient management. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Ramalingam, P; Rybicki, L; Smith, M D; Abrahams, N A; Tubbs, R R; Pettay, J; Farver, C F; Hsi, E D
PTLD is a well-recognized complication of organ transplantation. Large series of heart, renal, and liver transplants have been examined for the incidence and behavior of PTLD. However, reports of the incidence and characteristics of PTLDs in lung transplant (LTx) patients are few. We report our experience with PTLDs in a large series of LTx recipients at a single institution and compare them to other solid organ transplant recipient PTLDs seen at our institution. Twenty-eight patients were found to have PTLD, of whom 8 were lung transplant recipients. We evaluated nine PTLD specimens from these 8 patients for their histology, immunophenotype (CD20, CD3, EBV-LMP1), EBER status by in situ hybridization, and clinical features. The incidence of PTLD was 3.3% (8/244 patients). The time to development of PTLD, after transplant, was short (median time, 7 mo). All were of B-cell lineage. Overall, EBV was demonstrated in 77.7% (7 of 9 specimens) of PTLDs. All specimens tested for clonality were found to be monoclonal. Five patients died, with a median time to death of only 4.6 months. PTLDs in LTx patients are EBV-associated B-cell, predominantly monoclonal lymphoid lesions similar to other solid organ transplant PTLDs. Compared with other solid organ transplant recipients with PTLD at our institution, PTLDs in LTx patients have a propensity to involve the transplanted organ (P =.001, Fisher's exact test), occur earlier after transplant (P =.003, Wilcoxon test), and have a shorter survival (P =.002, log rank test). Reasons for this may include the relatively higher level of immunosuppression required in these patients and limited options in decreasing it. Although the incidence is low, careful early monitoring of lung transplantation patients is warranted because of the poor prognosis of patients developing this complication.
Davis, Steven Q; Garrity, Edward R
Since the first successful single-lung transplant in 1983 and double-lung transplant in 1986, thousands of patients have benefited from the procedures. Until 1995, allocation of donor lungs was based purely on time on the waiting list. In 1995, a 90-day credit was given to patients with idiopathic pulmonary fibrosis, while still maintaining allocation based on waiting list time. In 2005, the lung allocation score (LAS) was implemented, dramatically changing the way lungs are allocated. This article will explore the reasons for the creation of the LAS, the design of the score, early experience with transplant results under the new system, and further changes that may be made to the system of lung allocation. As surgical techniques and medical management evolve, so to will the management of potential donors and the allocation of their organs, with the aim of benefiting patients needing lung transplantation in the United States.
Lindstedt, Sandra; Eyjolfsson, Atli; Koul, Bansi; Wierup, Per; Pierre, Leif; Gustafsson, Ronny; Ingemansson, Richard
A major problem in clinical lung transplantation is the shortage of donor lungs. Only about 20% of donor lungs are accepted for transplantation. We have recently reported the results of the first six double lung transplantations performed with donor lungs reconditioned ex vivo that had been deemed unsuitable for transplantation by the Scandiatransplant, Eurotransplant, and UK Transplant organizations because the arterial oxygen pressure was less than 40 kPa. The three-month survival of patients undergoing transplant with these lungs was 100%. One patient died due to sepsis after 95 days, and one due to rejection after 9 months. Four recipients are still alive and well 24 months after transplantation, with no signs of bronchiolitis obliterans syndrome. The donor lungs were reconditioned ex vivo in an extracorporeal membrane oxygenation circuit using STEEN solution mixed with erythrocytes, to dehydrate edematous lung tissue. Functional evaluation was performed with deoxygenated perfusate at different inspired fractions of oxygen. The arterial oxygen pressure was significantly improved in this model. This ex vivo evaluation model is thus a valuable addition to the armamentarium in increasing the number of acceptable lungs in a donor population with inferior arterial oxygen pressure values, thereby, increasing the lung donor pool for transplantation. In the following paper we present our clinical experience from the first six patients in the world. We also present the technique we used in detail with flowchart. PMID:21876780
Abi Jaoude, Wassim; Tiu, Brian; Strieter, Nicole; Maloney, James D
Single lung transplants (SLTs) leave in place a diseased lung, a potential source of complications. Native lung pneumonectomy is occasionally indicated. We present 2 cases of native lung complications (NLCs) managed with video-assisted thoracoscopic surgery (VATS) pneumonectomy at our institution, a procedure never reported in this context before. Case 1 involves a 59-year old gentleman with refractory, invasive pulmonary aspergillosis of the native lung, 5 years after SLT for idiopathic pulmonary fibrosis. Case 2 involves a 66-year old gentleman with α-1 antitrypsin deficiency who developed severe haemoptysis and intraparenchymal haemorrhage in the native lung 12 years after SLT. A VATS pneumonectomy was performed in both cases because we believed it would facilitate wound healing and hasten recovery in immunosuppressed patients. Our short-term results align with this hypothesis. We conclude that VATS pneumonectomy is a feasible, adequate and safe procedure in this patient population; larger series are needed to draw definitive conclusions. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Burguete, Sergio R; Maselli, Diego J; Fernandez, Juan F; Levine, Stephanie M
Lung transplantation has become an accepted therapeutic procedure for the treatment of end-stage pulmonary parenchymal and vascular disease. Despite improved survival rates over the decades, lung transplant recipients have lower survival rates than other solid organ transplant recipients. The morbidity and mortality following lung transplantation is largely due to infection- and rejection-related complications. This article will review the common infections that develop in the lung transplant recipient, including the general risk factors for infection in this population, and the most frequent bacterial, viral, fungal and other less frequent opportunistic infections. The epidemiology, diagnosis, prophylaxis, treatment and outcomes for the different microbial pathogens will be reviewed. The effects of infection on lung transplant rejection will also be discussed.
Vazquez, R; Vazquez-Guillamet, M C; Suarez, J; Mooney, J; Montoya, J G; Dhillon, G S
Recipients of lung transplantation (LT) and heart-lung transplantation (HLT) are at increased risk of infection, including invasive mold infections (IMIs). The clinical presentation, radiographic correlates, and outcomes of Aspergillus and non-AspergillusIMIs in this population have not been well documented. LT and HLT recipients diagnosed with IMIs between 1990 and 2012 were identified using the Stanford Translational Research Integrated Database Environment and Stanford LT and HLT clinical database. Recipient clinical and radiographic characteristics were obtained via retrospective review of medical records and compared between Aspergillus and non-Aspergillus mold recipients. Risk factors for mortality were identified using multivariate logistic regression analysis. During the study period, 87 (14%) transplant recipients were diagnosed with IMIs. Aspergillus species were isolated in 63 (72%) and non-Aspergillus molds in 24 (28%) recipients. No significant difference was seen in presenting symptoms or radiographic findings between Aspergillus and non-Aspergillus mold recipients. Median time to diagnosis was 363 days in the Aspergillus group and 419 days in the non-Aspergillus group, with dissemination occurring only within the non-Aspergillus group (12.5%). Overall 90-day and 1-year mortality following IMI was 24% and 44%. One-year mortality was increased in the non-Aspergillus group (39.5% vs. 60.5%, P = 0.03). There is significant overlap in risk factors, presentation, and radiographic patterns in IMI in LT or HLT recipients. Non-Aspergillus molds were more likely to present late, with disseminated disease, and portend increased 1-year mortality. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Sweet, Stuart C
Pediatric lung transplant is a viable option for treatment of end-stage lung disease in children, with > 100 pediatric lung transplants reported to the Registry of the International Society of Heart and Lung Transplantation each year. Long-term success is limited by availability of donor organs, debilitation as a result of chronic disease, impaired mucus clearance resulting from both surgical and pharmacologic interventions, increased risk for infection resulting from immunosuppression, and most importantly late complications, such as chronic lung allograft dysfunction. Opportunities for investigation and innovation remain in all of these domains: (1) Ex vivo lung perfusion is a promising technology with the potential for increasing the lung donor pool, (2) evolving extracorporeal support strategies coupled with effective rehabilitation will effectively bridge critically ill patients to transplant, and most importantly, (3) research efforts intended to increase our understanding of the underlying mechanisms of chronic lung allograft dysfunction will ultimately lead to the development of effective therapies to prevent or treat the variety of chronic lung allograft dysfunction presentations. Copyright © 2017 by Daedalus Enterprises.
Moreno Galdó, Antonio; Solé Montserrat, Juan; Roman Broto, Antonio
Lung transplantation has become in recent years a therapeutic option for infantswith terminal lung disease with similar results to transplantation in adults.In Spain, since 1996 114 children lung transplants have been performed; this corresponds to3.9% of the total transplant number.The most common indication in children is cystic fibrosis, which represents between 70-80% of the transplants performed in adolescents. In infants common indications areinterstitial lung disease and pulmonary hypertension.In most children a sequential double lung transplant is performed, generally with the help ofextracorporeal circulation. Lung transplantation in children presents special challenges in monitoring and follow-up, especially in infants, given the difficulty in assessing lung function and performing transbronchial biopsies.There are some more specific complications in children like postransplant lymphoproliferative syndrome or a greater severity of respiratory virus infections .After lung transplantation children usually experiment a very important improvement in their quality of life. Eighty eight per cent of children have no limitations in their activity after 3 years of transplantation.According to the registry of the International Society for Heart & Lung Transplantation (ISHLT) survival at 5 years of transplantation is 54% and at 10 years is around 35%.
Baldi, Bruno Guedes; Samano, Marcos Naoyuki; Campos, Silvia Vidal; de Oliveira, Martina Rodrigues; Junior, José Eduardo Afonso; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique Oliveira Braga; Minguini, Isabela Pasqualini; Burlina, Roni; Pato, Eduardo Zinoni Silva; Carvalho, Carlos Roberto Ribeiro; Costa, André Nathan
Lung transplantation (LT) is the standard of care for patients with advanced lung diseases, including lymphangioleiomyomatosis (LAM). LAM accounts for only 1% of all LTs performed in the international registry. As a result, the global experience, including the use of mechanistic target of rapamycin (mTOR) inhibitors before and after LT in LAM, is still limited. We conducted a retrospective review of all LAM patients who underwent LT at our centre between 2003 and 2016. Pre- and post-transplant data were assessed. Eleven women with LAM underwent LT, representing 3.3% of all procedures. Ten (91%) patients underwent double-LT. The mean age at diagnosis was 39 ± 6 years and the mean FEV1 before LT was 28 ± 14%. Only one patient underwent pleurodesis for recurrent pneumothorax. Pulmonary hypertension was confirmed in 3 (27%) patients. Four (36%) patients received sirolimus preoperatively; three of them received it until the day of LT, and there was no occurrence of bronchial anastomotic dehiscence after the procedure. Four patients (36%) received mTOR inhibitors post-transplant. The median follow-up from LT was 44 months. There were 3 deaths (27%) during the study and survival probabilities at 1, 3, and 5 years after LT were, 90, 90, and 77%, respectively. This data reinforces the role of LT for LAM patients with end-stage disease. The use of sirolimus seems to be safe before LT and the occurrence of complications after LT, including those LAM-related, should be continuously monitored.
Shafaghi, S.; Najafizadeh, K.; Sheikhy, K.; Ansari Aval, Z.; Farzanegan, B.; Mafhoomi, Y.; Faghih Abdollahi, Z.; Emami, H.; Mortaz, E.; Porabdollah, M.; Jahangiri Fard, A.; Nikobayan Safaei, M.; Slama, A.; Aigner, C.; Hosseini-Baharanchi, F. S.; Abbasi Dezfuli, A.
Background: Although lung transplantation is a well-accepted treatment for end-stage lung diseases patients, only 15%–20% of the brain-dead donors’ lungs are usable for transplantation. This results in high mortality of candidates on waiting lists. Ex-vivo lung perfusion (EVLP) is a novel method for better evaluation of a potential lung for transplantation. Objective: To report the first experience of EVLP in Iran. Methods: The study included a pig in Vienna Medical University, Vienna, Austria, and 4 humans in Masih Daneshvari Hospital, Tehran, Iran. All brain-dead donors from 2013 to 2015 in Tehran were evaluated for EVLP. Donors without signs of severe chest trauma or pneumonia, with poor oxygenation were included. Results: An increasing trend in difference between the pulmonary arterial pO2 and left atrial pO2, an increasing pattern in dynamic lung compliance, and a decreasing trend in the pulmonary vascular resistance, were observed. Conclusion: The initial experience of EVLP in Iran was successful in terms of important/critical parameters. The results emphasize on some important considerations such as precisely following standard lung harvesting and monitoring temperature and pressure. EVLP technique may not be a cost-effective option for low-income countries at first glance. However, because this is the only therapeutic treatment for end-stage lung disease, it is advisable to continue working on this method to find alternatives with lesser costs. PMID:28078061
Schmitt, Jürgen W; Benden, Christian; Dora, Claudio; Werner, Clément M L
In recent years, the number of lung transplants has increased rapidly, with higher quality of life and improved survival rates in transplant recipients, including patients with advanced age. This, in turn, means that more transplant recipients will seek musculoskeletal care to treat degenerative joint disease and also trauma incidents. Safety concerns regarding elective and posttraumatic hip arthroplasty in transplant patients include an increased risk of infection, wound healing problems, periprosthetic fractures and loosening of the implants. Clinical outcomes and safety aspects were retrospectively reviewed for five primary total hip arthroplasties (THA) in lung transplant recipients with minimal follow-up of two years at average of 2.6 (2-11) years. Patients were recruited from the Zurich Lung Transplant Center comprising of a cohort of 253 patients between January 1st, 2004 and December 31st, 2013. All five patients subjectively reported excellent outcomes after THA with a final average Harris Hip Score of 97 (86-100). One 71-year-old patient died 26 months after THA unrelated to arthroplasty. One superficial wound healing disturbance was documented. No periprosthetic fractures, no dislocations, no periprosthetic infections, no further revision surgery, no implant loosening was observed. In conclusion, THA can be safely and successfully performed even in lung transplant patients under long-term immunosuppressive therapy and polymedication, provided a multidisciplinary approach can be granted.
Boussaud, V; Amrein, C; Guillemain, R; Achouh, P; Fabiani, J-N; Le Pimpec Barthes, F
Pediatric lung transplantations (LTx) remains a small part of LTx performed worldwide. The majority of these Tx concerns young adolescents, transplantations in infants being anecdotic. We conducted a retrospective study of LTx in children and adolescents in one center in Paris from the beginning of the 90's to 2013. Data from Broussais then HEGP were collected retrospectively from 1990 to 2013: 380 LTx were reported in 368 patients including 111 LTx performed among children from 5 to 18 years of age (30%). One hundred and eleven patients received 121 LTx: 86 bilateral LTx, 13 combined lung-liver, 3 monopulmonary, 5 heart-lung and 4 combined heart-lung-liver Tx. Eighty-eight percent of the patients had cystic fibrosis. Median age was 14 years, weight 34 kg and height 144 cm. Median age of donors was 27 years, weight 60 kg and height 167 cm. Conditional survival for children was not different than adults: 72% at one year, 42% at 5 years, 37% at 10 years and 26% at 15 years. There was not overall early mortality after transplantation. Era graft survival was significantly higher after year 2000 (53% at 5 years vs 32% P=0.03). Lung transplantation among children under 18 years have similar outcome to those of adult patients. Copyright © 2014. Published by Elsevier Masson SAS.
Morales, P; Briones, A; Torres, J J; Solé, A; Pérez, D; Pastor, A
The increase in the number of solid organ transplants has resulted in an increased incidence of opportunistic infections, including infection by typical and atypical mycobacteria, with risk of developing tuberculosis. Pretransplant chemoprophylaxis with isoniazid has become increasingly common in an attempt to prevent the disease. The source of infection in tuberculosis (TB) may be difficult to identify. Infection may be caused by reactivation of a primary infection in the recipient, reactivation of a lesion from the donor lung, or primary infection. There are few reports on TB in lung transplantation. Incidence in the reported series ranges from 6.5% to 10%. Our series of 7 patients out of a total 271 patients (2.58%) represents a rate higher than reported for the general Spanish population, 26.7/10(5) inhabitants and for lung transplant candidates (0.18%). Our aim was to evaluate the incidence, clinical signs, and outcome of TB in our series of patients undergoing lung transplantation in the 15 years since inception of the program (February 1990 to December 2004). Morbidity and mortality was high (42.8%), but limited to patients in whom treatment was not administered or could not be successfully completed. However, early detection and treatment are essential.
Klikovits, Thomas; Slama, Alexis; Hoetzenecker, Konrad; Waseda, Ryuichi; Lambers, Christopher; Murakoezy, Gabriella; Jaksch, Peter; Aigner, Clemens; Taghavi, Shahrokh; Klepetko, Walter; Lang, Gyoergy; Hoda, Mir Alireza
Pulmonary alveolar microlithiasis (PAM) is a rare lung disease caused by calcifications within the alveolar space. The only known effective treatment for an end-stage PAM is lung transplantation (LuTX). We performed a retrospective chart review of all individuals that underwent lung transplantation at our center between 1989 and 2013. Five consecutive patients with PAM were identified. Four females and one male with a mean age of 46.3 yr were identified. Extracorporeal membrane oxygenation (ECMO) support was required intraoperatively in four cases and post-operatively in one case. Mean post-operative intubation time was 3.3 (range, 2-5) d and mean intensive care unit (ICU) stay was 8.3 (range, 4-12) d. No intraoperative complications were observed. One early patient (operated in 1995) underwent acute re-transplantation on the second post-operative day (POD) and died from sepsis on the 11 POD. In one patient reperfusion edema was observed requiring a prolonged weaning process. No other severe perioperative complications were observed. Four of five patients are currently still alive with normal follow-up parameters. No recurrence of PAM was observed. Lung transplantation is a feasible therapy option in patients with end-stage PAM showing good post-operative results comparable to other indications for LuTX. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Roughly 10% of lung transplant recipients experience airway complications. Although the incidence has decreased dramatically since the first lung transplants were performed in the 1960s, airway complications have continued to adversely affect outcomes. Bronchoscopic interventions such as balloon dilation, airway stenting, and endobronchial electrocautery play an important role in ameliorating the morbidity and mortality associated with these complications. This review describes the array of bronchoscopic interventions used to treat airway complications after lung transplant and how these techniques can be used in nontransplant settings as well. PMID:28298961
Caetano Mota, Patrícia; Vaz, Ana Paula; Castro Ferreira, Inês; Bustorff, Manuela; Damas, Carla
Renal transplantation is the most common type of solid organ transplantation and kidney transplant recipients are susceptible to pulmonary complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge. To evaluate patients admitted to the Renal Transplant Unit (RTU) of Hospital de S. João with respiratory disease. We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Thirty-six patients were included. Mean age 55.2 (+/-13.4) years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9%) or tacrolimus (22.2%) or rapamycin (13.9%). Thirty-one patients (86.1%) presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2%) pneumonias, 5 (16.1%) opportunistic infections, 2 (6.5%) tracheobronchitis, and 1 case (3.2%) of lung abscesses. Microbiological agent was identified in 7 cases (22.6%). Five patients (13.9%) presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%), diagnostic in 10 cases (66.7%). Mean hospital stay was 17.1 (+/-18.5) days and no related death was observed. Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy.
Davis, LaShara A; Ryszkiewicz, Eric; Schenk, Emily; Peipert, John; LaSee, Claire; Miller, Carol; Richardson, Greg; Ridolfi, Gene; Trulock, Elbert P; Patterson, G Alexander; Waterman, Amy
Effective lung transplant education helps ensure informed decision making by patients and better transplant outcomes. To understand the educational needs and experiences of lung transplant patients. Mixed-method study employing focus groups and patient surveys. Barnes-Jewish Hospital in St Louis, Missouri. 50 adult lung transplant patients: 23 pretransplant and 27 posttransplant. Patients' interest in receiving specific transplant information, the stage in the transplant process during which they wanted to receive the education, and the preferred format for presenting the information. Patients most wanted information about how to sustain their transplant (72%), when to contact their coordinator immediately (56%), transplant benefits (56%), immunosuppressants (54%), and possible out-of-pocket expenses (52%). Patients also wanted comprehensive information early in the transplant process and a review of a subset of topics immediately before transplant (time between getting the call that a potential donor has been found and getting the transplant). Patients reported that they would use Internet resources (74%) and converse with transplant professionals (68%) and recipients (62%) most often. Lung transplant patients are focused on learning how to get a transplant and ensuring its success afterwards. A comprehensive overview of the evaluation, surgery, and recovery process at evaluation onset with a review of content about medications, pain management, and transplant recovery repeated immediately before surgery is ideal.
Wang, Yeming; Wei, Dong; Wang, Zhenxing; Zheng, Mingfeng; Chen, Jingyu
Because of the potential risk of recurrence and dissemination, lung carcinoma is rarely considered an indication for lung transplant, but as the technique has improved, novel end-stage pulmonary diseases can be treated successfully. Experience in lung transplant for patients with lung carcinoma has shown that select patients may benefit from this therapy. In this report, we examine the case of a bilateral lung transplant in a young man with bilateral bronchioloalveolar carcinoma. This report suggests that bilateral lung transplant might be an efficient therapeutic option for select patients with lung carcinoma.
Lau, C L; Patterson, G A
Two decades have passed since the first successful clinical lung transplant was performed in 1983, and, in the interim, lung transplantation has become the preferred treatment option for a variety of end-stage pulmonary diseases. Remarkable progress has been made in the field through refinement of technique and improved understanding of transplant immunology and microbiology. Unfortunately, donor shortages continue to limit the more widespread application of lung transplantation. In order to address this issue, marginal donors, living lobar and split lung donor techniques, and nonheartbeating donors have been used clinically to increase the number of donor lungs available. Chronic rejection of the lung allograft is currently the major hurdle limiting longterm survival. To date, prevention of known risk factors and treatment strategies have not lessened the devastating toll this process has on lung transplant survival. Better understanding of the cause of chronic rejection is needed in order to develop novel strategies for its treatment. Promotion of immune tolerance is a promising area that could potentially eliminate chronic rejection. The present article discusses recent advances in lung transplantation. It also details the major issues facing the field today. Only through continued clinical and experimental investigation will lung transplantation eventually reach its full potential.
Singer, Jonathan P.; Koth, Laura; Mooney, Joshua; Golden, Jeff; Hays, Steven; Greenland, John; Wolters, Paul; Ghio, Emily; Jones, Kirk D.; Leard, Lorriana; Kukreja, Jasleen; Blanc, Paul D.
BACKGROUND: Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). METHODS: To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. RESULTS: We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts. CONCLUSIONS: Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft. PMID:25412059
Lung transplantation has been a widely accepted treatment modality for patients with end-stage chronic obstructive lung disease (COPD). COPD is the most frequent indication for lung transplantation according to the report from International Society for Lung and Heart Transplantation. However, it is a minor population in Japan. A total of 204 lung transplants have been performed in Japan to date. Among them, 10 patients were suffering from severe COPD. Nine of them received cadaveric lung transplantation and one received living-donor lobar lung transplantation. All are currently alive during follow-up period of 3-87 months.
Richardson, Claire B.; Singer, Jonathan P
Lung transplantation for scleroderma-related lung disease is controversial due to extra-pulmonary organ involvement that may threaten allograft and patient survival after transplant surgery. Despite concerns, several lung transplant programs do offer lung transplantation to patients with scleroderma-related lung disease. In this review, we evaluate the scleroderma-related extra-pulmonary organ involvement that may result in poorer outcomes after lung transplantation as well as the existing evidence on survival, freedom from bronchiolitis obliterans syndrome (BOS), and other important clinical outcomes after lung transplantation. Among the nine studies reviewed, comprising 226 subjects, survival and freedom from BOS appears to be similar for subjects undergoing lung transplantation for scleroderma compared to non-scleroderma lung diseases. Although scleroderma is a systemic disease with several unique potential threats to allograft and patient survival, lung transplantation appears to be a reasonable intervention for this patient population. PMID:27833787
Eberlein, Michael; Geist, Lois; Keech, John; Zabner, Joseph; Gruber, Peter J.; Iannettoni, Mark D.; Parekh, Kalpaj
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
For end-stage lung disease refractory to medical management, lung transplantation remains the definitive treatment. However, this procedure presents unique challenges for the anesthesiologist. This review summarizes the recent literature regarding this procedure and its anesthetic management. Changes in the lung allocation system have had an impact on the characteristics of patients presenting for lung transplantation, resulting in patients who are older, sicker, and possibly presenting for retransplantation. In addition, various donor and recipient characteristics, including BMI, race, sex, and comorbidities such as diabetes and atrial fibrillation, have been shown to influence outcomes. Perioperative management, particularly colloid administration, adequate pain control, and treatment of pulmonary hypertension, may also affect outcomes. Careful preoperative assessment of pulmonary and cardiac function and comorbidities are particularly important for this patient population. Lung protective strategies, intra-operative transesophageal echocardiogram, pulmonary artery catheterization, cardiopulmonary bypass, inhaled nitric oxide, and inhaled prostacyclin are all important tools for the anesthesiologist to optimize patient care.
Wong, Jackson Y; Westall, Glen P; Snell, Gregory I
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.
Yang, Shun-Mao; Huang, Shu-Chien; Kuo, Shuenn-Wen; Huang, Pei-Ming; Pan, Sung-Ching; Lee, Jang-Ming; Lai, Hong-Shiee; Hsu, Hsao-Hsun
The aim of this study is to review the long-term outcomes of bilateral lung transplantation (BLTx) in our institution and examine the potential issues that may influence outcomes in a low-volume center. A retrospective review of BLTx performed in our institution between July 2006 and December 2012 was conducted. Standardized donor selection, procurement, and preservation protocols for brain-dead donors were applied. Measured outcomes were in-hospital mortality and actuarial survival using the Kaplan-Meier method. Twenty-five consecutive patients (13 male, 12 female) underwent BLTx with a mean age of 41.8 ± 13.5 years. Before LTx, the mean body mass index was 18.3 ± 3.1 kg/m2. Seven of these patients (28%) required oxygen supplementation at rest before LTx, while the remaining patients (72%) required noninvasive mechanical ventilation (n = 6, 24%), invasive mechanical ventilation (n = 9, 36%) or extracorporeal membrane oxygenation (ECMO) (n = 3, 12%). The lung grafts were procured from brain-dead donors with the mean age of 26.8 ± 11.4 year and the best PaO2 / FiO2 ratio of 513 ± 77 before procurement. All cross match results between same-race donors and recipients were negative. The percentage of same-sex matching and CMV mismatching were 64% and 4%, respectively. The mean time listed on the transplant list was 308 ± 261 days. The mean ischemic time for the first and second grafts were 222 ± 62 and 361 ± 67 minutes. During transplantation, 22 (88%) patients depended on ECMO and one (4%) on cardiopulmonary bypass support. All but two patients (82%) were discharged home in good condition; two (8%) patients died within 3 months after BLTx. The cumulative survival rates at 1-, 2-, 3-, and 5-years were 88%, 83%, 72%, and 72%, respectively. Although the comparatively few annual LTx performed is consistent with the low donation rate, our single-center growing experience demonstrates that good post-lung transplant outcomes can
Wigfield, Christopher H; Love, Robert B
Lung transplantation is the only established therapeutic option for several end-stage respiratory diseases. Limited mostly by lack of suitable allografts, the results have measurably improved over the last decade. Numerous surgical and pharmaceutical improvements have had positive impact on outcomes. The potential for critical care issues and the need for interdisciplinary management remains paramount. Cardiac, renal, and metabolic complications are frequently encountered in the acute postoperative phase. Allograft rejection and infectious diseases as well as problems related to immunosuppressive regimen are seen later after lung transplantation. Neurologic manifestations with a range of etiologies are discussed here in this context.
Machuzak, Michael; Santacruz, Jose F; Gildea, Thomas; Murthy, Sudish C
Airway complications after lung transplantation present a formidable challenge to the lung transplant team, ranging from mere unusual images to fatal events. The exact incidence of complications is wide-ranging depending on the type of event, and there is still evolution of a universal characterization of the airway findings. Management is also wide-ranging. Simple observation or simple balloon bronchoplasty is sufficient in many cases, but vigilance following more severe necrosis is required for late development of both anastomotic and nonanastomotic airway strictures. Furthermore, the impact of coexisting infection, rejection, and medical disease associated with high-level immunosuppression further complicates care.
Bates, Michael; Factor, Matthew; Parrino, P. Eugene; Bansal, Aditya; Rampolla, Reinaldo; Seoane, Leonardo; Mena, Jose; Gaudet, Matthew; Smith, William; McFadden, P. Michael
Background: From 1990-2005 at Ochsner Medical Center in New Orleans, LA, cardiopulmonary bypass (CPB) was used only when necessary during lung transplantation surgeries. Ochsner's lung transplant program was closed for more than 4 years after Hurricane Katrina, and since the program's reestablishment in 2010, the majority of lung transplantation surgeries have been performed with the patient on CPB and with a median sternotomy incision. The purpose of this study was to compare the outcomes of the CPB and non-CPB groups. Methods: After institutional review board approval, we conducted a retrospective review of the entire program using the Ochsner lung transplant database to identify patients in the non-CPB group from 1990-2005 and in the CPB group from 2010-2014. We calculated 1- and 3-year survival rates for each patient and reviewed medical records for evidence of stroke, the need for operative reexploration, and venous stenosis. We also performed a subgroup analysis of the first 20 consecutive patients undergoing lung transplantation on CPB with median sternotomy from February 2010 through April 2011 to examine intraoperative blood product use, the quantity of blood products administered, CPB cannulation and pump complications, ischemic time, and primary graft dysfunction. Results: Of the 208 patients in the non-CPB group, 74% had 1-year graft survival and 55% had 3-year survival following transplantation. After February 2010, 79 patients underwent lung transplantation on CPB with median sternotomy, and 90% of those patients had 1-year graft survival. Of the 46 patients available for 3-year follow-up, 59% were alive with functional grafts. The difference in 1-year survival rates between the 2 cohorts was statistically significant. Two deaths, 3 strokes, and 5 reexplorations of the chest for bleeding occurred during the perioperative time period in the CPB group, but no mortality was associated with these perioperative events. One patient who had perioperative
Wallinder, Andreas; Ricksten, Sven-Erik; Hansson, Christoffer; Riise, Gerdt C; Silverborn, Martin; Liden, Hans; Olausson, Michael; Dellgren, Göran
Ex vivo lung perfusion has the potential to increase the number of patients treated with lung transplantation. Our initial clinical experience with ex vivo lung perfusion is reviewed as well as early clinical outcome in patients transplanted with reconditioned lungs. Six pairs of donor lungs deemed unsuitable for transplantation underwent ex vivo lung perfusion with Steen solution mixed with red blood cells to a hematocrit of 10% to 15%. After reconditioning, lung function was evaluated and acceptable lungs were transplanted. Technical experience with ex vivo lung perfusion as well as clinical outcome for patients transplanted with ex vivo lung perfusion-treated lungs were evaluated. Donor lungs initially rejected either as a result of an inferior partial pressure of arterial oxygen/ fraction of inspired oxygen (n = 5; mean, 20.5 kPa; range, 9.1-29.9 kPa) or infiltrate on chest radiograph (n = 1) improved their oxygenation capacity to a mean partial pressure of arterial oxygen/fraction of inspired oxygen of 57 ± 10 kPa during the ex vivo lung perfusion (mean improvement, 33.6 kPa; range, 21-51 kPa; P < .01). During evaluation, hemodynamic (flow, vascular resistance, pressure) and respiratory (peak airway pressure, compliance) parameters were stable. Two single lungs were not used for lung transplantation because of subpleural hematoma or edema. Six recipients from the regular waiting list underwent single (n = 2) or double (n = 4) lung transplantation. One patient had primary graft dysfunction grade 2 at 72 hours. Median time to extubation was 7 hours. All patients survived 30 days and were discharged in good condition from the hospital. The use of ex vivo lung perfusion seems safe and indicates that some lungs otherwise refused for lung transplantation can be recovered and transplanted with acceptable short-term results. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
Gilpin, Sarah E; Charest, Jonathan M; Ren, Xi; Ott, Harald C
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.
Griffith, Bartley P.
The survival rate (average, 50%) of patients undergoing cardiopulmonary transplantation falls well below that expected for cardiac transplantation alone. We give a broad overview of the various grounds upon which this difference is likely based and discuss recent advances in each area: 1) criteria for the selection of candidates and donors, 2) methods for ex-vivo preservation of donor organs, 3) technical execution of the operative procedure, and 4) prevention of postoperative infection. In connection with the prevention of postoperative infection, we discuss the potential for the development of a chronic obliterative disease that, once established, has proved inexorable. Current efforts are focused on detection when the process is in an early, reversible stage, and on research into causation. (Texas Heart Institute Journal 1987; 14:364-368) Images PMID:15227291
Thompson, Bruce Robert; Westall, Glen Philip; Paraskeva, Miranda; Snell, Gregory Ian
The number of lung transplants performed globally continues to increase year after year. Despite this growing experience, long-term outcomes following lung transplantation continue to fall far short of that described in other solid-organ transplant settings. Chronic lung allograft dysfunction (CLAD) remains common and is the end result of exposure to a multitude of potentially injurious insults that include alloreactivity and infection among others. Central to any description of the clinical performance of the transplanted lung is an assessment of its physiology by pulmonary function testing. Spirometry and the evaluation of forced expiratory volume in 1 s and forced vital capacity, remain core indices that are measured as part of routine clinical follow-up. Spirometry, while reproducible in detecting lung allograft dysfunction, lacks specificity in differentiating the different complications of lung transplantation such as rejection, infection and bronchiolitis obliterans. However, interpretation of spirometry is central to defining the different 'chronic rejection' phenotypes. It is becoming apparent that the maximal lung function achieved following transplantation, as measured by spirometry, is influenced by a number of donor and recipient factors as well as the type of surgery performed (single vs double vs lobar lung transplant). In this review, we discuss the wide range of variables that need to be considered when interpreting lung function testing in lung transplant recipients. Finally, we review a number of novel measurements of pulmonary function that may in the future serve as better biomarkers to detect and diagnose the cause of the failing lung allograft.
Launay, David; Savale, Laurent; Berezne, Alice; Le Pavec, Jérôme; Hachulla, Eric; Mouthon, Luc; Sitbon, Olivier; Lambert, Benoit; Gaudric, Marianne; Jais, Xavier; Stephan, Francois; Hatron, Pierre-Yves; Lamblin, Nicolas; Vignaux, Olivier; Cottin, Vincent; Farge, Dominique; Wallaert, Benoît; Guillevin, Loic; Simonneau, Gerald; Mercier, Olaf; Fadel, Elie; Dartevelle, Philippe; Humbert, Marc; Mussot, Sacha
Systemic sclerosis per se should not be considered as an a priori contraindication for a pre-transplantation assessment in patients with advanced interstitial lung disease and/or pulmonary hypertension. For lung or heart-lung transplantation, a multidisciplinary approach, adapting the pre-transplant assessment to systemic sclerosis and optimizing systemic sclerosis patient management before, during and after surgery should improved the short- and long-term prognosis. Indications and contraindications for transplantation have to be adapted to the specificities of systemic sclerosis. A special focus on the digestive tract involvement and its thorough evaluation are mandatory before transplantation in systemic sclerosis. As the esophagus is almost always involved, isolated gastro-oesophageal reflux disease, pH metry and/or manometry abnormalities should not be a systematic per se contraindication for pre-transplantation assessment. Corticosteroids may be harmful in systemic sclerosis as they are associated with acute renal crisis. A low dose corticosteroids protocol for immunosuppression is therefore advisable in systemic sclerosis.
Picard, C; Roux, A
In France, the higher frequency of pulmonary sample in organ donors and the enhancement of surgical and perioperative life support techniques, have increased the number procedures and the short term prognosis of lung transplantation (LT). In this setting, the classical contraindications of LT need to be reconsidered. In this article, some of the classical contraindication of LT are confronted to the experience acquired in other solid organ transplantations or from some LT centers. Specific situations such as LT in patients with previous cancer, HIV infection, viral hepatitis, nutritional disorders, acutely ill LT candidates and aging candidates are addressed. Surgical contraindications are not reviewed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Solé, Amparo; Ussetti, Piedad
Invasive infections by molds, mainly Aspergillus infections, account for more than 10% of infectious complications in lung transplant recipients. These infections have a bimodal presentation: an early one, mainly invading bronchial airways, and a late one, mostly focused on lung or disseminated. The Aspergillus colonization at any time in the post-transplant period is one of the major risk factors. Late colonization, together with chronic rejection, is one of the main causes of late invasive forms. A galactomannan value of 0.5 in bronchoalveolar lavage is currently considered a predictive factor of pulmonary invasive infection. There is no universal strategy in terms of prophylaxis. Targeted prophylaxis and preemptive treatment instead of universal prophylaxis, are gaining more followers. The therapeutic drug monitoring level of azoles is highly recommended in the treatment. Monotherapy with voriconazole is the treatment of choice in invasive aspergillosis; combined antifungal therapies are only recommended in severe, disseminated, and other infections due to non-Aspergillus molds.
Mathur, Sunita; Hornblower, Elizabeth; Levy, Robert D
The benefits of exercise training in individuals with chronic lung diseases such as chronic obstructive pulmonary disease, cystic fibrosis, and interstitial lung disease have been well documented. Although there is limited research available, it appears that exercise is safe and beneficial for people with severe end-stage chronic lung disease who are awaiting lung transplantation in addition to recipients of lung transplants. Evidence-based guidelines for exercise training in the pre- and post-lung transplantation phases have not yet been developed. However, by considering exercise guidelines for people with chronic lung disease and in older adults in light of the physiological changes that can occur either pre- or post-lung transplantation, a safe and appropriate exercise training program can be developed. Depending on the individual's exercise capacity and goals, the training program may include aerobic and resistance exercise, and flexibility and balance training. In the pre-transplant and acute post-transplant phases, the intensity of exercise is dictated primarily by symptom limitation and adequate rest, which is required between exercise bouts to allow for recovery. In the post-transplant phase, it is possible for lung transplant recipients to increase their exercise capacity and even participate in sports. Further research needs to be conducted to determine the optimal training guidelines and the long-term benefits of exercise, both in lung transplant candidates and recipients.
Bennett, David; Fossi, Antonella; Bargagli, Elena; Refini, Rosa Metella; Pieroni, Maria; Luzzi, Luca; Ghiribelli, Claudia; Paladini, Piero; Voltolini, Luca; Rottoli, Paola
Lung transplantation (LTX) is nowadays accepted as a treatment option for selected patients with end-stage pulmonary disease. Idiopathic pulmonary fibrosis (IPF) is characterized by the radiological and histologic appearance of usual interstitial pneumonia. It is associated with a poor prognosis, and LTX is considered an effective treatment to significantly modify the natural history of this disease. The aim of the present study was to analyse mortality during the waiting list in IPF patients at a single institution. A retrospective analysis on IPF patients (n = 90) referred to our Lung Transplant Program in the period 2001-2014 was performed focusing on patients' characteristics and associated risk factors. Diagnosis of IPF was associated with high mortality on the waiting list with respect to other diagnosis (p < 0.05). No differences in demographic, clinical, radiological data and time spent on the waiting list were observed between IPF patients who underwent to LTX or lost on the waiting list. Patients who died showed significant higher levels of pCO2 and needed higher flows of O2-therapy on effort (p < 0.05). Pulmonary function tests failed to predict mortality and no other medical conditions were associated with survival. Patients newly diagnosed with IPF, especially in small to medium lung transplant volume centres and in Countries where a long waiting list is expected, should be immediately referred to transplantation, delay results in increased mortality. Early identification of IPF patients with a rapid progressive phenotype is strongly needed.
Hayes, Don; Benden, Christian; Sweet, Stuart C; Conrad, Carol K
Cardiothoracic transplantation has significantly impacted the lives of pediatric patients with advanced cardiopulmonary failure. The current state of lung transplantation in children as well as its ongoing and future challenges are discussed.
Garver, R I; Zorn, G L; Wu, X; McGiffin, D C; Young, K R; Pinkard, N B
Bronchioloalveolar carcinoma is a distinctive subtype of typical adenocarcinoma of the lung that tends to metastasize widely throughout the lungs but less commonly elsewhere. Because conventional therapies for intrapulmonary metastatic bronchioloalveolar carcinoma are generally ineffective, we treated seven patients who had intrapulmonary metastatic bronchioloalveolar carcinoma with lung transplantation. Seven patients with biopsy-proved bronchioloalveolar carcinoma and no evidence of extrapulmonary disease received transplants of either one or two cadaveric lungs. At transplantation, all native lung tissue was removed and replaced with a donor lung or lungs. The patients received the usual post-transplantation care given at the institution. Four of the seven patients had recurrent bronchioloalveolar carcinoma within the donor lungs; the recurrences appeared from 10 to 48 months after transplantation. All recurrences were limited to the donor lungs. Histologic and molecular analyses showed that the recurrent tumors in three patients originated from the recipients of the transplants. Lung transplantation for bronchioloalveolar carcinoma is technically feasible, but recurrence of the original tumor within the donor lungs up to four years after transplantation was common.
Although lung transplantation is a well-accepted treatment for advanced lung diseases, donor shortage remains a significant limiting factor resulting in an increasing number of deaths of people on waiting lists. Recently, some transplant centers have begun to use lungs retrieved from donors after circulatory arrest. This review outlines the relevant published experimental data and clinical experiences with lung transplantation from donation after cardiac-death donors (DCDs) or non-heart-beating donors (NHBDs). Techniques for lung preservation and ex vivo lung assessment of DCD (NHBD) lungs are reviewed, and aspects of primary graft dysfunction after DCD (NHBD) lung transplantation are discussed.
García-Covarrubias, Lisardo; Salerno, Tomas A; Panos, Anthony L; Pham, Si M
Lung transplantation is currently considered an established treatment for some advanced lung diseases. The beginning of experimental lung transplantation dates back to the 1940's when the Soviet Vladimir P. Demikhov performed the first lung transplants in animals. Two decades later, James Hardy performed the first lung transplant in humans. Unfortunately, the beginning of clinical lung transplantation was hampered by technical complications and the excessive toxicity of immunosuppressive drugs. Improvement in the surgical technique along with the development of more effective and less toxic immunosuppressive drugs has led to a better outcome in lunt transplant recipients. Donor selection and management before organ procurement play a key role in the receptor's outcome. Due to the shortage of donors, some institutions are using more liberal selection criteria, reporting satisfactory outcomes. The approach of the lung and heart-lung transplant patient is multidisciplinary and includes the cardiothoracic transplant surgeon, pulmonologist, anesthesiologist, and intensivist, among others. Herein, we review some relevant historical aspects and recent advances in the management of lung transplant recipients, including indications and contraindications, evaluation of donors and recipients, surgical techniques and peripost-operative care.
Farivar, A S; Yunusov, M Y; Chen, P; Leone, R J; Madtes, D K; Kuhr, C S; Spector, M R; Abrams, K; Hwang, B; Nash, R A; Mulligan, M S
While acute models of orthotopic lung transplantation have been described in dogs, the technical considerations of developing a survival model in this species have not been elaborated. Herein, we describe optimization of a canine survival model of orthotopic lung transplantation. Protocols of orthotopic left lung transplantation and single lung ventilation were established in acute experiments (n=9). Four dogs, serving as controls, received autologous, orthotopic lung transplants. Allogeneic transplants were performed in 16 DLA-identical and 16 DLA-mismatched unrelated recipient dogs. Selective right lung ventilation was utilized in all animals. A Malecot tube was left in the pleural space connected to a Heimlich valve for up to 24 hours. To date, animals have been followed up to 24 months by chest radiography, pulmonary function tests, bronchoscopy with lavage, and open biopsies. Long-term survival was achieved in 34/36 animals. Two recipients died intraoperatively secondary to cardiac arrest. All animals were extubated on the operating table, and in all cases the chest tube was removed within 24 hours. Major complications included thrombosis of the pulmonary artery and subcritical stenosis of bronchial anastamosis. One recipient underwent successful treatment of a small bowel intussusception. We report our experience in developing a survival canine model of orthotopic single lung transplantation. While short-term survival following canine lung transplantation is achievable, we report particular considerations that facilitate animal comfort, early extubation, and lung reexpansion in the immediate postoperative period, further optimizing use of this species for experimental modeling of long-term complications after lung transplantation.
Lehmann, Sven; Uhlemann, Madlen; Leontyev, Sergey; Seeburger, Joerg; Garbade, Jens; Merk, Denis R; Bittner, Hartmuth B; Mohr, Friedrich W
It is unknown if uni- or bilateral lung transplant is best for treatment of usual idiopathic pulmonary fibrosis. We reviewed our single-center experience comparing both treatments. Between 2002 and 2011, one hundred thirty-eight patients at our institution underwent a lung transplant. Of these, 58 patients presented with idiopathic pulmonary fibrosis (56.9%) and were the focus of this study. Thirty-nine patients received a single lung transplant and 19 patients a bilateral sequential lung transplant. The mean patient age was 54 ± 10 years, and 69% were male. The intraoperative course was uneventful, save for 7 patients who needed extracorporeal membrane oxygenation support. Three patients had respiratory failure before the lung transplant that required mechanical ventilation and was supported by extracorporeal membrane oxygenation. Elevated pulmonary artery pressure > 40 mm Hg was identified as an independent predictor of early mortality by uni- and multivariate analysis (P = .01; OR 9.7). Using a Cox regression analysis, postoperative extracorporeal membrane oxyge-nation therapy (P = .01; OR 10.2) and the need for > 10 red blood cell concentrate during the first 72 hours after lung transplant (P = .01; OR 5.6) were independent predictors of long-term survival. Actuarial survival at 1 and 5 years was 65.6% and 55.3%, with no significant between-group differences (70.6% and 54.3%). Lung transplant is a safe and curative treatment for idiopathic pulmonary fibrosis. According to our results, unilateral lung transplant for idiopathic pulmonary fibrosis is an alternative to bilateral lung transplant and may affect the allocation process.
Bennett, Daine T; Reece, T Brett; Smith, Phillip D; Grandhi, Miral Sadaria; Rove, Jessica A Yu; Justison, George A; Mitchell, John D; Fullerton, David A; Zamora, Martin R; Weyant, Michael J
Donor lungs acquired from victims of asphyxiation by hanging are not routinely used for lung transplantation because of the associated lung injury. Ex vivo lung perfusion (EVLP) is a technique to evaluate marginal donor lungs before transplantation. We report here our experience with the use of EVLP in donor lungs procured from victims of asphyxia by hanging. Lungs from 5 donors who became brain dead secondary to hanging were evaluated by EVLP. Donor organs were perfused according to trial protocol. Donor lungs were accepted for transplantation if they maintained a PaO2 greater than or equal to 350 mm Hg, had a clear roentgenogram, and had no significant worsening of physiologic metrics. Perfused organs included single and double lung blocs, and all were perfused without technical incident. Three of the 5 donor organs evaluated met criteria for transplantation after 3 hours of EVLP and were transplanted. Donor organs rejected for transplantation showed either signs of worsening PaO2 or deterioration of physiologic metrics. There were no intraoperative complications in the patients who underwent transplantation, and all were alive at 30 days. We report here the successful use of EVLP to assess donor lungs acquired from victims of asphyxiation by hanging. The use of EVLP in this particular group of donors has the potential to expand the available donor pool. We demonstrate that EVLP is a viable option for evaluating the function of lung allografts before transplantation and would recommend that all donor lungs obtained from hanging victims undergo EVLP to assess their suitability for transplantation. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Living-donor lobar lung transplantation (LDLLT) has been performed as a life-saving procedure for critically ill patients who are unlikely to survive the long wait for cadaveric lungs. This article will review the current status of LDLLT. As of 2011, LDLLT has been performed in approximately 400 patients worldwide. The use of LDLLT has decreased in the USA because of the recent change by the Organ Procurement and Transplantation Network to an urgency/benefit allocation system for cadaveric donor lungs. During the past several years, reports on LDLLT have been most exclusively from Japan where the average waiting time for a cadaveric lung is more than 2 years. LDLLT has been performed various lung diseases including bronchiolitis obliterans following hematopoietic stem cell transplantation. Successful LDLLTs have been reported for patients receiving oversized as well as undersized grafts. The 5-year survival after LDLLT was 74.6% in the 2008 official report of the Japanese Society of Lung and Heart-Lung Transplantation, and it was 88.8% in the author's personal experience. LDLLT can be performed for various lung diseases and appears to provide similar or better survival than cadaveric lung transplantation. Size mismatching can be overcome to a certain extent using various surgical techniques.
McFadden, P M; Ochsner, J L; Emory, W B; Van Meter, C H; Pridjian, A K; Young, G S; Harmon, D E; Smart, F W; Ventura, H O; Scharfenberg, J C
Lung transplantation is a successful alternative treatment for a variety of end-stage lung diseases. The first 20 lung transplants performed in Louisiana between November 1990 and July 1994 are reported from Ochsner Foundation Hospital. Transplant procedures included 1 heart-lung, 11 bilateral sequential lung, and 8 single-lung transplants in 8 males and 11 females (1 retransplantation). The average age was 38 years (range 7-60), and the median waiting time was 34.5 days (range 1-329). Indications for transplant included emphysema, pulmonary fibrosis, pulmonary hypertension, cystic fibrosis, bronchiectasis, and bronchiolitis obliterans. Overall 1-year and 3-year survival were 65.0% and 58.5%, respectively. Infection was the major cause of morbidity and mortality. Rejection episodes were observed but treated successfully in all 20 patients. Lung transplantation has proved to be a successful treatment for a variety of severely limiting and terminal pulmonary conditions for patients in our state.
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
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
Shigemura, Norihisa; Horai, Tetsuya; Bhama, Jay K; D'Cunha, Jonathan; Zaldonis, Diana; Toyoda, Yoshiya; Pilewski, Joseph M; Luketich, James D; Bermudez, Christian A
A shortage of donors has compelled the use of extended-criteria donor organs in lung transplantation. The purpose of this study was to evaluate the impact of using older donors on outcomes after lung transplantation using current protocols. From January 2003 to August 2009, 593 lung transplants were performed at our institution. We compared 87 patients (14.7%) who received lungs from donors aged 55 years or older with 506 patients who received lungs from donors less than 55 years old. We also examined risk factors for mortality in recipients of lungs from older donors. The incidence of major complications including severe primary graft dysfunction and early mortality rates were similar between the groups. However, posttransplant peak FEV1 was lower in the patients who received lungs from older donors (71.7% vs. 80.7%, P<0.05). In multivariate analysis, recipient pulmonary hypertension (transpulmonary pressure gradient >20 mm Hg) and prolonged intraoperative cardiopulmonary bypass were significant risk factors for mortality in the recipients of lungs from older donors. This large, single-center experience demonstrated that transplanting lungs from donors older than 55 years did not yield worse short- or long-term outcomes as compared with transplanting lungs from younger donors. However, transplanting lungs from older donors into recipients with pulmonary hypertension or recipients who required prolonged cardiopulmonary bypass increased the risk for mortality. Although lungs from older donors should not be excluded because of donor age alone, surgeons should carefully consider their patient selection criteria and surgical plans when transplanting lungs from older donors.
De Vito Dabbs, Annette; Song, Mi-Kyung
Transplant recipients have an unfavorable cardiovascular risk profile and experience more cardiovascular morbidity and mortality compared with the general population, primarily because of immunosuppressant-induced diabetes, hypertension, and hyperlipidemia. These discouraging prospects are even more ominous for lung transplant recipients who are more likely than other organ recipients to require intense immunosuppression and develop these conditions early and concomitantly. The purposes of this article are to heighten awareness of the prevalence, risk factors, and management of diabetes, hypertension, and hyperlipidemia in lung transplant patients, and to assist nurses to be proactive in helping recipients to reduce the likelihood of developing cardiovascular complications.
Kurusz, Mark; Roach, John D; Vertrees, Roger A; Girouard, Mark K; Lick, Scott D
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.
Vaquero Barrios, José Manuel; Redel Montero, Javier; Santos Luna, Francisco
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. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.
Hirji, Sameer A; Gulack, Brian C; Englum, Brian R; Speicher, Paul J; Ganapathi, Asvin M; Osho, Asishana A; Shimpi, Rahul A; Perez, Alexander; Hartwig, Matthew G
To examine the impact of lung transplantation on gastric motility. Adult recipients at a large, single center, who were retrospectively evaluated with solid gastric emptying (SGE) study post lung transplantation, but had no history of gastrointestinal intervention (i.e. pyloroplasty or fundoplication), were selected between June 2005 and August 2013. Multivariable logistic regression was performed to determine risk factors associated with delayed gastric emptying (DGE) after transplantation. DGE was noted in 236 patients (57%) after transplantation. On multivariable logistic regression, an underlining diagnosis of cystic fibrosis (CF)/bronchiectasis (Adjusted Odds Ratio (AOR) 3.26, p < 0.01) was a significant risk factor in predicting DGE after lung transplantation. There was no survival difference between patients with postoperative DGE versus those without (Log-rank test p=0.53). Delayed gastric emptying is very common following lung transplantation, occurring in over half of all lung transplant recipients with increased prevalence in CF patients. The association with cystic fibrosis could be secondary to extra-pulmonary manifestations of the underlying disease, or indicative of increased intra-operative vagal nerve injury. We speculate that DGE may play a substantial role in the increased reflux induced allograft injury seen after lung transplantation. Further prospective studies are needed to validate this hypothesis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Oto, Takahiro; Okada, Yoshinori; Bando, Toru; Minami, Masato; Shiraishi, Takeshi; Nagayasu, Takeshi; Chida, Masayuki; Okumura, Meinoshin; Date, Hiroshi; Miyoshi, Shinichiro; Kondo, Takashi
The Japanese Organ Transplant Law was amended, and the revised law took effect in July 2010 to overcome extreme donor shortage and to increase the availability of donor organs from brain-dead donors. It is now possible to procure organs from children. The year 2011 was the first year that it was possible to examine the results of this first extensive revision of the Japanese Organ Transplant Law, which took effect in 1997. Currently, seven transplant centers, including Tohoku, Dokkyo, Kyoto, Osaka, Okayama, Fukuoka and Nagasaki Universities, are authorized to perform lung transplantation in Japan, and by the end of 2011, a total of 239 lung transplants had been performed. The number of transplants per year and the ratio of brain-dead donor transplants increased dramatically after the revision of the Japanese Organ Transplant Law. The survival rates for lung transplant recipients registered with the Japanese Society for Lung and Heart-lung Transplantation were 93.3 % at 1 month, 91.5 % at 3 months, 86.3 % at 1 year, 79.0 % at 3 years, and 73.1 % at 5 years. The survival curves for brain-dead donor and living-donor lung transplantation were similar. The survival outcomes for both brain-dead and living-donor lung transplants were better than those reported by the International Society for Heart and Lung Transplantation. However, donor shortage remains a limitation of lung transplantation in Japan. The lung transplant centers in Japan should continue to make a special effort to save critically ill patients waiting for lung transplantation.
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
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.
Radiotherapy for nasopharyngeal carcinoma and combined capecitabine and nimotuzumab treatment for lung metastases in a liver transplantation recipient: a case experience of sustained complete response.
Yan, Senxiang; Jiang, Xue; Yang, Jinsong; Yan, Danfang; Wang, Yi-Xiang J
The primary treatment for nasopharyngeal carcinoma (NPC) is external beam radiotherapy. However, until now, there is little experience with the management of NPC occurred after solid organ transplantation. In this report, a 60-year-old man was found to have NPC (T2N1M0; stage III) 3 years after orthotopic liver transplantation treatment for hepatocellular carcinoma. Intensity-modulated radiotherapy (IMRT) was performed for NPC. One month after IMRT, complete response of NPC was achieved. However, multiple lung metastases occurred 18 months after the IMRT with the largest lesion measuring 4.1×5.5 cm and confirmed to be originated from NPC. Combined chemo-/targeted therapy consisted of capecitabine, and nimotuzumab was administered for four cycles. One month after initiation of capecitabine plus nimotuzumab treatment, a near-complete response was achieved for lung metastases. A repeat CT scan 1 year later showed sustained resolution of the lung metastases. The patient is still alive 16 months after the combined chemo-/targeted therapy.
Bhaskaran, Archana; Hosseini-Moghaddam, S M; Rotstein, Coleman; Husain, Shahid
Fungal infections continue to produce morbidity and mortality in lung transplant recipients despite the widespread use of antifungal prophylaxis. There has been a decline in Candida infections but Aspergillus species predominate. Other mold pathogens including Fusarium, Scedosporium, and Zygomycetes also cause infections in lung transplant recipients. Furthermore, the widespread use of antifungal prophylaxis has prompted a delay in onset of Aspergillus infection in lung transplant recipients. Pulmonary parenchymal disease has become the most common manifestation of invasive aspergillosis. Among the risk factors pre- or posttransplant Aspergillus colonization is the most important risk factor reported in several retrospective studies. Recently posttransplant colonization has been implicated in the development of bronchiolitis obliterans syndrome. Other factors that have been reported include preceding cytomegalovirus infections, hypogammaglobulinemia, and single-lung transplantation. The risk factors for other mold infections such as Scedosporium, Fusarium, and Zygomycetes are not well studied. The best antimold prophylaxis strategy and choice of drug remains to be elucidated. Most lung transplant centers use either voriconazole or inhaled amphotericin preparations. However, data have emerged regarding the increased risk of squamous cell cancer in lung transplant recipients on voriconazole prophylaxis. Advances in the diagnosis and treatment of invasive aspergillosis have resulted in a significant decrease in mortality. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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
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. Copyright © 2011 SEPAR. Published by Elsevier Espana. All rights reserved.
Daly, R C; McGregor, C G
To present an overview of the surgical issues in lung transplantation, including the historical context and the rationale for choosing a particular procedure for a specific patient, we reviewed and summarized the current medical literature and our personal experience. Several surgical options are available, including single lung transplantation; double lung transplantation; heart-lung transplantation; bilateral, sequential single lung transplantation; and (recently) single lobe transplantation. Although single lung transplantation is preferred for maximal use of the available organs, bilateral lung transplantation is necessary for septic lung diseases and may be appropriate for pulmonary hypertension and bullous emphysema. Heart-lung transplantation is performed for Eisenmenger's syndrome and for primary pulmonary hypertension with severe right ventricular failure. General factors for consideration in assessment of compatibility of the donor and potential recipient include ABO blood group, height (the donor should be within +/- 20% of the recipient's height), and length of the lungs (determined on an anteroposterior chest roentgenogram). Graft preservation and minimal duration of ischemia are important. Complications associated with airway healing are related to ischemia of the donor bronchus. We have addressed the issue of donor bronchial ischemia by direct revascularization of the donor bronchial arteries with use of the recipient's internal thoracic artery. Currently, lung transplantation offers a realistic therapeutic option to patients with end-stage pulmonary parenchymal or vascular disease.
Eshraghi, M; Habibi, G; Rahim, M B; Mirkazemi, R; Ghaemi, M; Omidimorad, A; Alavi, A A; Banazadeh, M
In the last 30 years lung transplantation has proven to be a lifesaving therapeutic option for patients with end-stage lung disease. The objective of this study was to perform a bibliometric analysis of lung transplantation research articles. A bibliometric evaluation of the evolution of scientific production in the field of lung transplantations between 1989 and 2009 was conducted using the ISI Web of Science. The search terms selected were "lung transplant" OR "pulmonary transplant". Specific features including year of publication, language, geographical distribution, first author, main journal publishing these articles, journals publishing highly cited articles, and institutional affiliation were analyzed. The citation characteristics of articles were additionally analyzed. A total of 6409 (58.0 %) research articles were found. The time trend of the number of articles showed an increase of more than 6.81 between 1989 and 2009. North America contributed 50.4 % and Europe contributed 46.0 % of published articles. The greatest number of contributions came from the USA (43.6 %), followed by England (9.1 %) and Germany (8.6 %). There were 104 522 citations of these articles by 25 July 2010. The average citation per article was 16.31. The New England Journal of Medicine ranked first with regard to the number of articles and the number of highly cited articles. G. A. Patterson, Washington University, and the US National Institutes of Health (NIH) were the top author, institution and funding agency, respectively. The number of publications and the scientific interest in lung transplantation has increased rapidly in recent years. Citations of articles published in the field of lung transplantation are increasing and the numbers of uncited articles are fewer compared to the average citations of articles and uncited articles in the field of medicine. © Georg Thieme Verlag KG Stuttgart · New York.
Ganapathi, Asvin M; Mulvihill, Michael S; Englum, Brian R; Speicher, Paul J; Gulack, Brian C; Osho, Asishana A; Yerokun, Babatunde A; Snyder, Laurie R; Davis, Duane; Hartwig, Matthew G
To maximize the benefit of lung transplantation, the effect of size mismatch on survival in lung transplant recipients with restrictive lung disease (RLD) was examined. All single and bilateral RLD lung transplants from 1987 to 2011 in the United Network for Organ Sharing (UNOS) Database were identified. Donor predicted total lung capacity (pTLC):Recipient pTLC ratio (pTLCr) quantified mismatch. pTLCr was segregated into five strata. A Cox proportional hazards model evaluated the association of pTLCr with mortality hazard. To identify a critical pTLCr, a Cox model using a restricted cubic spline for pTLCr was used. A total of 6656 transplants for RLD were identified. Median pTLCr for single orthotopic lung transplant (SOLT) and bilateral orthotopic lung transplant (BOLT) was 1.0 (0.69-1.47) and 0.98 (0.66-1.45). Examination of pTLCr as a categorical variable revealed that undersizing (pTLCr <0.8) for SOLT and moderate oversizing (pTLCr = 1.1-1.2) for SOLT and BOLT had a harmful survival effect [for SOLT pTLC <0.8: HR 1.711 (95% CI 1.146-2.557), P = 0.01 and for BOLT pTLC 1.1-1.2: HR 1.717 (95% CI 1.112-2.651), P = 0.02]. Spline analysis revealed significant changes in SOLT mortality by variation of pTLCr between 0.8-0.9 and 1.1-1.2. RLD patients undergoing SOLT are susceptible to detriments of an undersized lung. RLD patients undergoing BOLT have higher risk of mortality when pTLCr falls between 1.1 and 1.2. © 2017 Steunstichting ESOT.
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
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.
Bozso, Sabin; Vasanthan, Vishnu; Luc, Jessica GY; Kinaschuk, Katie; Freed, Darren; Nagendran, Jayan
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
Baumann, Brooke; Byers, Sara; Wasserman-Wincko, Tamara; Smith, Libby; Hathaway, Bridget; Bhama, Jay; Shigemura, Norihisa; Hayanga, J W Awori; D'Cunha, Jonathan; Johnson, Jonas T
Dysphagia, aspiration, and potential pneumonia represent a major source of morbidity in patients undergoing lung transplantation. Conditions that potentiate dysphagia and aspiration include frailty and prolonged intubation. Our group of speech-language pathologists has been actively involved in performance of a bedside evaluation of swallowing, and instrumental evaluation of swallowing with modified barium swallow, and postoperative management in patients undergoing lung transplantation. All lung transplant patients from April 2009 to September 2012 were evaluated retrospectively. A clinical bedside examination was performed by the speech-language pathology team, followed by a modified barium swallow or fiberoptic endoscopic evaluation of swallowing. A total of 321 patients were referred for evaluation. Twenty-four patients were unable to complete the evaluation. Clinical signs of aspiration were apparent in 160 patients (54%). Deep laryngeal penetration or aspiration were identified in 198 (67%) patients during instrumental testing. A group of 81 patients (27%) had an entirely normal clinical examination, but were found to have either deep penetration or aspiration. The majority of patients aspirate after lung transplantation. Clinical bedside examination is not sensitive enough and will fail to identify patients with silent aspiration. A standard of practice following lung transplantation has been established that helps avoid postoperative aspiration associated with complications. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Fildes, James E; Archer, Louise D; Blaikley, John; Ball, Alexandra L; Stone, John P; Sjöberg, Trygve; Steen, Stig; Yonan, Nizar
Lung transplantation is limited by a scarcity of suitable donors resulting in high waiting list mortality. Ex vivo lung perfusion (EVLP) allows the evaluation and reconditioning of marginal donor lungs for use in transplantation. This study aimed to compare clinical outcome of patients transplanted with marginal organs by means of EVLP with a standard lung transplant cohort through a multicenter open trial. Group 1 (n = 9) included patients transplanted using EVLP reconditioned marginal lungs. Group 2 (n = 46) consisted of date-matched patients transplanted using standard transplantation of acceptable lungs. The primary composite endpoint included acute rejection and infection at 12 months after transplantation. There was no significant difference in the overall incidence of acute rejection (P = 0.754) and the number of treated infection episodes (proven/probable pneumonia; P = 0.857/0.368 and proven/probable tracheobronchitis; P = 0.226/0.529) up to 12 months after transplantation, between group 1 and group 2. Additionally, there was no significant difference in early clinical outcome, including intensive care unit stay, hospital stay, and 1 year mortality between the two groups (P = 0.338, P = 0.112 and P = 0.372, respectively). This multicenter study demonstrates that EVLP is associated with no adverse effect on clinical outcome, including the incidence of acute rejection and infection after lung transplantation.
Singer, Jonathan P.; Singer, Lianne G.
Improving health-related quality of life is an important goal of lung transplantation. In this review, we describe background concepts including definitions, measurement and interpretation of health-related quality of life (HRQL) and other patient-reported outcomes. Lung transplantation is associated with dramatic and sustained improvements in health-related quality of life, particularly in measures of physical health and functioning. Physical rehabilitation may augment the early improvements in HRQL, while bronchiolitis obliterans syndrome and psychological conditions have a negative impact. More research is needed, particularly longitudinal, multicenter studies, to better understand the trajectory and determinants of HRQL after lung transplantation, and the impact of targeted interventions to improve HRQL. PMID:23821515
Rosengarten, Dror; Fox, Benjamin D; Fireman, Elizabeth; Blanc, Paul D; Rusanov, Victoria; Fruchter, Oren; Raviv, Yael; Shtraichman, Osnat; Saute, Milton; Kramer, Mordechai R
Silicosis is a progressive lung disease resulting from the inhalation of respirable crystalline silica. Lung transplantation is the only treatment for end-stage silicosis. The aim of this study was to analyze the survival experience following lung transplantation among patients with silicosis. We reviewed data for all patients who underwent lung transplantation for silicosis and a matched group undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF) at a single medical center between March 2006 and the end of December 2013. Survival was followed through 2015. A total of 17 lung transplantations were performed for silicosis among 342 lung transplantations (4.9%) during the study period. We observed non-statistically significant survival advantage (hazard ratio 0.6; 95%CI 0.24-1.55) for those undergoing lung transplantation for silicosis relative to IPF patients undergoing lung transplantation during the same period. Within the limits of a small sample, survival in silicosis patients following lung transplantation was not reduced compared to IPF. Am. J. Ind. Med. 60:248-254, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Witt, CA; Puri, V; Gelman, AE; Krupnick, AS; Kreisel, D
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
Hosseini-Moghaddam, S M; Husain, Shahid
The landscape of fungal infections in lung transplant recipients has significantly changed over the course of time. The initial predominance of CANDIDA species has given way to the prominence of ASPERGILLUS species in the current era followed by other mold infections, namely, SCEDOSPORIUM and Zygomycetes, which are emerging as newer pathogens. CRYPTOCOCCUS NEOFORMANS is another important pathogen responsible for the morbidity in lung transplant recipients. The use of widespread antifungal prophylaxis directed against the mold infections has resulted in delayed onset of invasive aspergillosis in lung transplant recipients. In recent studies cumulative incidence rate of invasive aspergillosis was noted to be 2.4% at 12 months. Invasive mold infections in lung transplant may present as tracheobronchitis, invasive pulmonary infections, or disseminated disease. Invasive pulmonary infections are now the most common manifestations of mold infections, followed by tracheobronchitis. Pre- or posttransplant ASPERGILLUS colonization, along with preceding cytomegalovirus infections, hypogammaglobulinemia, and single-lung transplants are considered significant risk factors for invasive aspergillosis. Recently posttransplant colonization has been implicated in the development of bronchiolitis obliterans syndrome. The appropriate antimold prophylaxis strategy, by the use of either voriconazole or inhaled amphotericin, remains to be fully determined. Advances in the diagnosis and treatment of invasive aspergillosis have resulted in significant decreases in mortality. The risk factors for other mold infections such as SCEDOSPORIUM or Zygomycetes are being elucidated. Infections with these organisms, however, carry mortality up to 80%. The current article reviews the changes in the epidemiology of invasive molds and CRYPTOCOCCUS infections and other emerging fungal pathogens and highlights the controversies surrounding antifungal prophylaxis in lung transplant recipients.
Miyoshi, Kentaroh; Oto, Takahiro
Lung allograft encounters changeable issues over the pre-and postransplant period. It is important to realize individual problems in each specific peritransplant stage and share the awareness between transplant team and patients. Long-sighted management policy is encouraged throughout posttransplant care because morbidities in each stage trigger each other and graft condition and management in acute posttransplant period have a considerable impact on long-term recipient survival after lung transplantation. The specific issues at hand are reviewed by going through the current important literature.
Cordova, Francis C
Over the last decade, advances in bronchoscopic and surgical techniques have expanded our treatment armamentarium for patients with severe emphysema who previously would have received a pessimistic outlook from their physician. Advances in our understanding of the different COPD phenotypes and its natural history has refined our selection process as to which group of emphysema patients will derive maximum benefit from LVR, bullectomy, or lung transplantation. Because emphysema is a progressive disease, initial treatment with bronchoscopic or surgical LVR or bullectomy does not preclude lung transplantation in the future.
Hahn, M. Frances; Abdelrazek, Hesham; Patel, Vipul J.; Walia, Rajat
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
Maltzman, Jonathan S.; Reed, Hasina Outtz; Kahn, Mark L.
Lung allografts are prone to rejection, even though recipients undergo aggressive immunosuppressive therapy. Lymphatic vessels serve as conduits for immune cell trafficking and have been implicated in the mediation of allograft rejection. In this issue of the JCI, Cui et al. provide compelling evidence that lymphatic vessel formation improves lung allograft survival in a murine transplant model. Moreover, their data suggest a potential mechanism for the beneficial effects of lymphatics that does not involve immune cell or antigen transport. Together, the results of this study provide new insight into the role of lymphatic vessels in transplant tolerance. PMID:26524589
Carneiro, Herman A.; Coleman, Jeffrey J.; Restrepo, Alejandro; Mylonakis, Eleftherios
Fusarium is a fungal pathogen of immunosuppressed lung transplant patients associated with a high mortality in those with severe and persistent neutropenia. The principle portal of entry for Fusarium species is the airways, and lung involvement almost always occurs among lung transplant patients with disseminated infection. In these patients, the immunoprotective mechanisms of the transplanted lungs are impaired, and they are, therefore, more vulnerable to Fusarium infection. As a result, fusariosis occurs in up to 32% of lung transplant patients. We studied fusariosis in 6 patients following lung transplantation who were treated at Massachusetts General Hospital during an 8-year period and reviewed 3 published cases in the literature. Cases were identified by the microbiology laboratory and through discharge summaries. Patients presented with dyspnea, fever, nonproductive cough, hemoptysis, and headache. Blood tests showed elevated white blood cell counts with granulocytosis and elevated inflammatory markers. Cultures of Fusarium were isolated from bronchoalveolar lavage, blood, and sputum specimens. Treatments included amphotericin B, liposomal amphotericin B, caspofungin, voriconazole, and posaconazole, either alone or in combination. Lung involvement occurred in all patients with disseminated disease and it was associated with a poor outcome. The mortality rate in this group of patients was high (67%), and of those who survived, 1 patient was treated with a combination of amphotericin B and voriconazole, 1 patient with amphotericin B, and 1 patient with posaconazole. Recommended empirical treatment includes voriconazole, amphotericin B or liposomal amphotericin B first-line, and posaconazole for refractory disease. High-dose amphotericin B is recommended for treatment of most cases of fusariosis. The echinocandins (for example, caspofungin, micafungin, anidulafungin) are generally avoided because Fusarium species have intrinsic resistance to them. Treatment
Shlomi, Dekel; Shitrit, David; Bendayan, Daniele; Sahar, Gidon; Saute, Milton; Kramer, Mordechai R
The shortage of organs for lung transplantation has led to the growing use of "marginal" donors. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, recent data suggest that they may be suitable in selected cases. This article describes the successful transplantation of two lungs from a single donor who had been receiving long-term hemodialysis treatment. In the absence of other causes of pulmonary diseases, such as smoking or lung infection, lungs from dialysis-dependent patients may be acceptable for lung transplantation.
Flynn, Katy; Daiches, Anna; Malpus, Zoey; Yonan, Nizar; Sanchez, Melissa
Exploring patients' narratives can lead to new understandings about perceived illness states. Intensive Care Unit delirium is when people experience transitory hallucinations, delusions or paranoia in the Intensive Care Unit and little is known about how this experience affects individuals who have had a heart or lung transplant. A total of 11 participants were recruited from two heart and lung transplant services and were invited to tell their story of transplant and Intensive Care Unit delirium. A narrative analysis was conducted and the findings were presented as a shared story. This shared story begins with death becoming prominent before the transplant: 'you live all the time with Mr Death on your shoulder'. Following the operation, death permeates all aspects of dream worlds, as dreams in intensive care 'tunes into the subconscious of your fears'. The next part of the shared story offers hope of restitution; however, this does not last as reality creeps in: 'I thought it was going to be like a miracle cure'. Finally, the restitution narrative is found to be insufficient and individuals differ in the extent to which they can achieve resolution. The societal discourse of a transplant being a 'gift', which gives life, leads to internalised responsibility for the 'success' or 'failure' of the transplant. Participants describe how their experiences impact their sense of self: 'a post-transplant person'. The clinical implications of these findings are discussed.
Blumenthal, James A.; Carney, Robert M.; Freedland, Kenneth E.; O’Hayer, C. Virginia F.; Trulock, Elbert P.; Martinu, Tereza; Schwartz, Todd A.; Hoffman, Benson M.; Koch, Gary G.; Davis, R. Duane; Palmer, Scott M.
Background: Neurobehavioral functioning is widely recognized as being an important consideration in lung transplant candidates, but little is known about whether these factors are related to clinical outcomes. The present study examined the relationship of neurobehavioral functioning, including measures of executive function and memory, depression, and anxiety, to long-term survival among lung transplant recipients. Methods: The sample was drawn from 201 patients who underwent transplantation at Duke University and Washington University who participated in a dual-site clinical trial investigating medical and psychosocial outcomes in transplant candidates with end-stage lung disease. All patients completed the Beck Depression Inventory-II (BDI-II) and Spielberger State-Trait Anxiety Inventory at baseline and again after 12 weeks, while a subset of 86 patients from Duke University also completed neurocognitive testing. Patients were followed for survival up to 12 years after completing baseline assessments. Results: One hundred eleven patients died over a mean follow-up of 10.8 years (SD = 0.8). Baseline depression, anxiety, and neurocognitive function were examined as predictors of posttransplant survival, controlling for age, 6-min walk distance, FEV, and native disease; education and cardiovascular risk factors were also included in the model for neurocognition. Lower executive function (hazard ratio [HR] = 1.09, P = .012) and memory performance (HR = 1.11, P = .030) were independently associated with greater mortality following lung transplant. Although pretransplant depression and anxiety were not predictive of mortality, patients who scored > 13 on the BDI-II at baseline and after 3 months pretransplant had greater mortality (HR = 1.85 [95% CI, 1.04, 3.28], P = .036). Conclusions: Neurobehavioral functioning, including persistently elevated depressive symptoms and lower neurocognitive performance, was associated with reduced survival after lung transplantation
Fisher, Andrew; Andreasson, Anders; Chrysos, Alexandros; Lally, Joanne; Mamasoula, Chrysovalanto; Exley, Catherine; Wilkinson, Jennifer; Qian, Jessica; Watson, Gillian; Lewington, Oli; Chadwick, Thomas; McColl, Elaine; Pearce, Mark; Mann, Kay; McMeekin, Nicola; Vale, Luke; Tsui, Steven; Yonan, Nizar; Simon, Andre; Marczin, Nandor; Mascaro, Jorge; Dark, John
stay was similar in both groups. There was a higher rate of very early grade 3 primary graft dysfunction (PGD) in the EVLP arm, but rates of PGD did not differ between groups after 72 hours. The requirement for extracorporeal membrane oxygenation (ECMO) support was higher in the EVLP arm (7/18, 38.8%) than in the standard arm (6/184, 3.2%). There were no major differences in rates of chest radiograph abnormalities, infection, lung function or rejection by 12 months. The cost of EVLP transplants is approximately £35,000 higher than the cost of standard transplants, as a result of the cost of the EVLP procedure, and the increased ECMO use and ITU stay. Predictors of cost were quality of life on joining the waiting list, type of transplant and number of lungs transplanted. An exploratory model comparing a NHS lung transplant service that includes EVLP and standard lung transplants with one including only standard lung transplants resulted in an incremental cost-effectiveness ratio of £73,000. Interviews showed that patients had a good understanding of the need for, and the processes of, EVLP. If EVLP can increase the number of usable donor lungs and reduce waiting, it is likely to be acceptable to those waiting for lung transplantation. Study limitations include small numbers in the EVLP arm, limiting analysis to descriptive statistics and the EVLP protocol change during the study. CONCLUSIONS Overall, one-third of donor lungs subjected to EVLP were deemed suitable for transplant. Estimated survival over 12 months was lower than in the standard group, but the data were also consistent with no difference in survival between groups. Patients receiving these additional transplants experience a higher rate of early graft injury and need for unplanned ECMO support, at increased cost. The small number of participants in the EVLP arm because of early study termination limits the robustness of these conclusions. The reason for the increased PGD rates, high ECMO requirement and
Although the demand of organ re-transplantation has increased, the organ shortage from brain-dead donor raises an ethical controversy about the fairness of organ allocation for re-transplantation. Living donor lobar lung transplantation has become an alternative therapeutic option to brain-dead donor lung transplantation for not only pediatric but also adult patients. Lung re-transplantation using lobes from living donors have the potential to alleviate the ethical problems. This review focused on indications, surgical techniques, perioperative care and postoperative follow-up of living donor lobar lung re-transplantation.
Shah, S K; Parto, P; Lombard, G A; James, M A; Beckles, D L; Lick, S; Valentine, V G
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.
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
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
Knoop, C; Andrien, M; Defleur, V; Antoine, M; de Francquen, P; Goldman, M; Estenne, M
It has been postulated that chimerism after transplantation might promote graft acceptance. In the present study, we prospectively assessed blood chimerism in 10 lung transplant recipients during the first posttransplant year and investigated whether chimerism was associated with an immunologically stable situation of the graft. The recipients' peripheral blood mononuclear cells were obtained before transplantation and at various time points during the first postoperative year. Donor cells were detected using nested polymerase chain reaction amplification of a donor-specific HLA-DRB1 allele. Clinical graft acceptance was determined by the number of rejection episodes. The incidence of blood chimerism was high during the first 3 postoperative months and then decreased over time. All patients experienced at least one acute rejection episode, and three patients developed chronic rejection. We, thus, conclude that rejection of the lung allograft may occur in the presence of blood chimerism.
Gennai, Stéphane; Pison, Christophe; Briot, Raphaël
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.
Sugimoto, Seiichiro; Miyoshi, Kentaroh; Yamane, Masaomi; Oto, Takahiro
Diffuse panbronchiolitis is a rare complex genetic disease predominantly affecting East Asians, and is characterized by chronic inflammation of the respiratory bronchioles and sinobronchial infection. Although long-term macrolide therapy has been shown to significantly improve the survival in patients with diffuse panbronchiolitis, some patients continue to deteriorate, eventually requiring lung transplantation. However, lung transplantation for diffuse panbronchiolitis has rarely been reported and the outcome in these patients remains unknown. We describe our experience of lung transplantation for diffuse panbronchiolitis. A total of 5 patients received long-term macrolide therapy and had airway colonization by Pseudomonas aeruginosa preoperatively. Three patients had undergone sinus surgery for chronic rhinosinusitis before the transplantation. Bilateral cadaveric lung transplantation was performed in 4 patients, and living-donor lung transplantation in 1. After the lung transplantation, 1 patient developed an A3 acute rejection episode; however, none of the recipients developed severe pneumonia or any fatal infections. One recipient developed chronic lung allograft dysfunction 3 years after the transplantation; however, none developed recurrence of diffuse panbronchiolitis. All of the 5 patients were still surviving after a median follow-up period of 4.9 years (3.7-12.3 years). Lung transplantation is a viable option for the treatment of progressive diffuse panbronchiolitis resistant to long-term macrolide therapy. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Brosig, Cheryl L
Although lung transplants are performed in children, experience with the pediatric population remains limited. There is growing interest in studying the psychological functioning and quality of life in these patients following transplant. There is a body of literature about quality of life in adult lung transplant recipients, but little is known about how pediatric patients and their families function psychologically after transplant. The current article summarizes the pediatric literature with respect to psychological outcomes for transplant recipients and their parents and points to areas where additional research is needed.
Amital, Anat; Shitrit, David; Raviv, Yael; Saute, Milton; Medalion, Benjamin; Bakal, Llana; Kramer, Mordechai R
Lung transplantation impairs surfactant activity, which may contribute to primary graft dysfunction (PGD). Prompted by studies in animals and a few reports in humans, this study sought to determine if the administration of surfactant during transplantation serves as an effective preventive measure. An open, randomized, controlled prospective design was used. Forty-two patients scheduled for single (n=38) or double (n=4) lung transplantation at a major tertiary medical center were randomly assigned to receive, or not, intraoperative surfactant treatment. In the treated group, bovine surfactant was administered at a dose of 20 mg phospholipids/kg through bronchoscope after the establishment of bronchial anastomosis. The groups were compared for oxygenation (PaO2/FiO2), chest X-ray findings, PGD grade, and outcome. Compared with the untreated group, the patients who received surfactant were characterized by better postoperative oxygenation mean PaO2/FiO2 (418.8+/-123.8 vs. 277.9+/-165 mm Hg, P=0.004), better chest radiograph score, a lower PGD grade (0.66 vs. 1.86, P=0.005), fewer cases of severe PGD (1 patient vs. 12, P<0.05), earlier extubation (by 2.2 hr; 95% CI 1.1-4.3 hr, P=0.027), shorter intensive care unit stay (by 2.3 days; 95% CI 1.47-3.74 days, P=0.001), and better vital capacity at 1 month (61% vs. 50%, P=0.022). One treated and 2 untreated patients died during the first postoperative month. Surfactant instillation during lung transplantation improves oxygenation, prevents PGD, shortens intubation time, and enhances early posttransplantation recovery. Further, larger studies are needed to assess whether surfactant should be used routinely in lung transplantation.
McKellar, Stephen H; Durham, Lucian A; Scott, John P; Cassivi, Stephen D
Lung transplant is an effective treatment for patients with end-stage lung disease but is limited because of the shortage of acceptable donor organs. Organ donation after cardiac death is one possible solution to the organ shortage because it could expand the pool of potential donors beyond brain-dead and living donors. We report the preliminary experience of Mayo Clinic with donation after cardiac death, lung procurement, and transplant.
Basturk, Ahmet; Yılmaz, Aygen; Sayar, Ersin; Dinçhan, Ayhan; Aliosmanoğlu, İbrahim; Erbiş, Halil; Aydınlı, Bülent; Artan, Reha
The aim of our study was to evaluate our liver transplant pediatric patients and to report our experience in the complications and the long-term follow-up results. Patients between the ages of 0 and 18 years, who had liver transplantation in the organ transplantation center of our university hospital between 1997 and 2016, were included in the study. The age, sex, indications for the liver transplantation, complications after the transplantation, and long-term follow-up findings were retrospectively evaluated. The obtained results were analyzed with statistical methods. In our organ transplantation center, 62 pediatric liver transplantations were carried out since 1997. The mean age of our patients was 7.3 years (6.5 months-17 years). The 4 most common reasons for liver transplantation were: Wilson's disease (n=10; 16.3%), biliary atresia (n=9; 14.5%), progressive familial intrahepatic cholestasis (n=8; 12.9%), and cryptogenic cirrhosis (n=7; 11.3%). The mortality rate after transplantation was 19.6% (12 of the total 62 patients). The observed acute and chronic rejection rates were 34% and 4.9%, respectively. Thrombosis (9.6%) was observed in the hepatic artery (4.8%) and portal vein (4.8%). Bile leakage and biliary stricture rates were 31% and 11%, respectively. 1-year and 5-year survival rates of our patients were 87% and 84%, respectively. The morbidity and mortality rates in our organ transplantation center, regarding pediatric liver transplantations, are consistent with the literature.
Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio
Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.
Altun, Gülbin Töre; Arslantaş, Mustafa Kemal; Cinel, İsmail
Primary graft dysfunction (PGD) is a severe form of acute lung injury that is a major cause of early morbidity and mortality encountered after lung transplantation. PGD is diagnosed by pulmonary oedema with diffuse alveolar damage that manifests clinically as progressive hypoxemia with radiographic pulmonary infiltrates. Inflammatory and immunological response caused by ischaemia and reperfusion is important with regard to pathophysiology. PGD affects short- and long-term outcomes, the donor organ is the leading factor affecting these adverse ramifications. To minimize the risk of PGD, reduction of lung ischaemia time, reperfusion optimisation, prostaglandin level regulation, haemodynamic control, hormone replacement therapy, ventilator management are carried out; for research regarding donor lung preparation strategies, certain procedures are recommended. In this review, recent updates in epidemiology, pathophysiology, molecular and genetic biomarkers and technical developments affecting PGD are described. PMID:27366539
Mahajan, Amit K; Folch, Erik; Khandhar, Sandeep J; Channick, Colleen L; Santacruz, Jose F; Mehta, Atul C; Nathan, Steven D
Airway complications following lung transplantation result in considerable morbidity and are associated with a mortality of 2% to 4%. The incidence of lethal and nonlethal airway complications has decreased since the early experiences with double- and single-lung transplantation. The most common risk factor associated with post-lung transplantation airway complications is anastomotic ischemia. Airway complications include the development of exophytic granulation tissue, bronchial stenosis, bronchomalacia, airway fistula, endobronchial infection, and anastomotic dehiscence. The broadening array of bronchoscopic therapies has enhanced treatment options for lung transplant recipients with airway complications. This article reviews the risk factors, clinical manifestations, and treatments of airway complications following lung transplantation and provides our expert opinion when evidence is lacking. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
Otani, Shinji; Levvey, Bronwyn J; Westall, Glen P; Paraskeva, Miranda; Whitford, Helen; Williams, Trevor; McGiffin, David C; Walker, Rowan; Menahem, Solomon; Snell, Gregory I
Renal dysfunction is common after lung and heart-lung transplantation (Tx), and it limits the recipient's survival and quality of life. This study analyzed the outcomes of simultaneous and late kidney Tx following lung and heart-lung Tx. From a single-center retrospective chart review of 1031 lung and heart-lung Tx recipients, we identified 13 simultaneous or late kidney Tx cases in 12 patients. Three patients underwent simultaneous deceased donor lung and kidney Tx. Eight patients underwent lung and heart-lung Tx, followed by nine living donor kidney Tx (including one ABO-incompatible Tx). One additional patient underwent a late deceased donor kidney Tx following heart-lung Tx. The median time from lung and heart-lung Tx to later kidney Tx was 127 (interquartile range [IQR], 23 to 263) months. Three patients died, 1 of sepsis, 1 of multiple organ failure, and 1 of transplant coronary disease. At a median follow-up of 33 (IQR, 10 to 51) months, 9 patients are alive and well. Eight patients required dialysis before kidney Tx for a median time of 14 months (IQR, 5 to 49). Kidney graft loss occurred in 1 patient at 51 months. After kidney Tx, dialysis was necessary in association with acute allograft dysfunction in 2 patients. No acute kidney rejection has been detected in any patient. Treatable acute lung rejection was seen in 1 patient. Well-preserved pulmonary function was noted in recipients of late kidney Tx. Simultaneous kidney Tx and late deceased donor kidney Tx have challenges in the setting of lung Tx. By contrast, late living related kidney Tx after lung Tx is associated with excellent long-term survival and acceptable kidney and lung allograft function. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Today, a main focus of the transplant community is the long-term outcomes of lung and heart allograft recipients. However, even early post-transplant survival (within the first post-transplant year) needs improvement, as early graft failure still accounts for many allograft losses. In this chapter, we review the experience of heart and lung transplantation as reported to the Organ Procurement Transplant Network/United Network of Organ Sharing registry and investigate the factors responsible for causing failure in the first post-transplant year. Trends indicate that sicker patients are increasingly being transplanted, thereby limiting improvements in early post-transplant survival. More lung and heart transplant patients are coming to transplant on dialysis. In heart transplant, there is an increase in the number of heart retransplant patients and an increase in patients on extracorporeal membrane oxygenation. For lung transplant, more patients are on a ventilator prior to transplant than in the past 25 years. Given that sicker/riskier patients are now receiving more heart and lung transplants, future studies need to take place to better understand these patients so that they can have the same survival as patients entering transplant with less severe illnesses.
Wang, X A; Jiang, G N
Despite rapid progress, clinical lung transplantation in China still lags far behind. A great challenge remains in donor lung utilization and perioperative medicine. It's really abnormal that we are so backward in lung transplantation when we have come up with the advanced world levels in thoracic surgery, pulmonology and critical care medicine. Our shortcomings were analyzed by comparing lung transplantation in China and in the advanced countries. The first problem is multidisciplinary teamwork. In the United States, a lung transplant team includes physician specialized in lung transplantation, thoracic surgeons, nurses, respiratory therapists and other specialists possibly needed. In contrast, our lung transplant teams are derived from thoracic surgery teams. Other specialists are invited for consultation just when thoracic surgeons are unable to deal with the tough issues in perioperative medicine. The low utilization and quality of donor lung also result from poor teamwork. The second problem is that we failed to integrate such advances as extra corporeal lung support and ex vivo lung perfusion into our lung transplant programs. In conclusion, the development of lung transplantation in China is dependent upon an initiative, multidisciplinary team approach.
Longmore, D. B.; Cooper, D. K. C.; Hall, R. W.; Sekabunga, J.; Welch, W.
It is estimated that an unknown, yet possibly large, number of patients would benefit from transplantation of the heart and both lungs if technically, physiologically, and immunologically feasible. In this paper we attempt to explore the main non-immunological areas in which we feel that cardiopulmonary transplantation requires further evaluation. A technique is described by which the heart and lungs, as one unit, can be removed from a donor animal, and viability of these organs can be maintained for several hours by autoperfusion (circulation being through the coronary and pulmonary vessels) with positive pressure ventilation via the trachea. This simple heart-lung preparation preserves the organs concerned for sufficient time to allow preparation of the recipient, transport of the donor organs, and tissue typing to be carried out. Our technique of implanting these donor organs into the recipient is also described. We have carried out this operation on approximately 100 dogs and have been impressed by the good cardiac function obtained, but spontaneous respiratory function has been either absent or inadequate to sustain life for more than a few hours. It would appear that dogs cannot tolerate bilateral pulmonary denervation, and our findings are discussed in the light of other work on this subject. Work on primates suggests that man would be able to undergo this procedure successfully. The organizational and ethical problems involved in cardiac and cardiopulmonary transplantation are briefly discussed. Images PMID:4894051
Fuehner, Thomas; Kuehn, Christian; Welte, Tobias; Gottlieb, Jens
Lung transplantation (LTx) has become an accepted treatment for carefully selected patients with end-stage lung disease. Critical care issues have gained importance concerning bridging of candidates by mechanical respiratory support and are involved in the care after transplantation. The nature of respiratory support varies from oxygen supply and noninvasive ventilation, to mechanical respiratory support either by mechanical ventilation and/or extracorporeal life support. Recent innovations in extracorporeal life support technology have resulted in its more widespread use. Retrospective studies have demonstrated promising outcomes in candidates on mechanical respiratory support as a bridge to lung transplantation. The role of mechanical respiratory support has influenced the selection criteria for LTx, although bridging remains technically and ethically challenging. Critical care is integral to manage and prevent postoperative complications of LTx. Primary graft dysfunction and prolonged mechanical ventilation are major obstacles to hospital survival after LTx. Clear evidence is lacking on how to ventilate and optimally manage patients after LTx. Prolonged extracorporeal life support after LTx may improve outcome in selected patients with a primary graft dysfunction. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
Hayes, Don; Diaz-Guzman, Enrique; Berger, Rolando; Hoopes, Charles W
Lung transplantation is an evolving specialty with the number of transplants growing annually. A structured lung transplant curriculum was developed for Pulmonary/Critical Care (Pulm/CC) fellows. Scores on pulmonary in-training examinations (ITE) 2 years prior to and 3 years after implementation were reviewed as well as completion of satisfaction surveys. The mean pulmonary ITE score of 1st-year fellows increased from 54.2 ± 2.5 to 63.6 ± 1.2 (M ± SD), p = .002, whereas mean pulmonary ITE score for 2nd-year fellows increased from 63.0 ± 3.0 to 70.7 ± 1.2, p = .019. The combined mean pulmonary ITE score increased from 58.6 ± 2.3 to 67.1 ± 1.2, p = .001. Satisfaction surveys revealed that fellow perception of the curriculum was that the experience contributed to an overall improvement in their knowledge base and clinical skills while opportunity to perform transbronchial biopsies was available. A structured educational lung transplant curriculum was associated with improved performance on the pulmonary ITE and was perceived by fellows to be beneficial in their education and training while providing opportunities for fellows to perform transbronchial biopsies.
Shah, Pali; Orens, Jonathan B
Despite advances in perioperative and post-operative management, lung transplant recipients with select pre transplant risk factors have been shown to experience worse post-transplant outcomes in comparison to those without such risk factors. Among these variables, previous studies have shown that select markers of poor nutritional status prior to transplant, such as low body mass index (BMI) and hypoalbuminemia, have been associated with increased post-transplant mortality. In a past issue of the journal, Chamogeorgakis el al. examine a comprehensive battery markers previously associated with malnutrition to determine their impact on outcomes after lung transplantation. The authors find that hypoalbuminemia is associated with worse survival, but does not appear to affect the risk of post-transplant infections. This article reviews the study presented by Chamogeorgakis et al. to discuss how it furthers our understanding of the impact of nutritional status on transplant-related outcomes and consider areas for future investigation.
Lanuza, Dorothy M.; Lefaiver, Cheryl A.; Brown, Roger; Muehrer, Rebecca; Murray, Margaret; Yelle, Maria; Bhorade, Sangeeta
Background Lung transplantation provides a viable option for survival of end-stage respiratory disease. In addition to prolonging survival, there is considerable interest in improving patient-related outcomes such as transplant recipients’ symptom experiences. Methods A prospective, repeated measures design was used to describe the symptom experience of 85 lung transplant recipients between 2000–2005. The Transplant Symptom Inventory (TSI) was administered before and at 1, 3, 6, 9, and 12 months post-transplant. Ridit analysis provided a unique method for describing symptom experiences and changes. Results After lung transplantation, significant (p<.05) improvements were reported for the most frequently occurring and most distressing pre-transplant symptoms (e.g., shortness of breath with activity). Marked increases in the frequency and distress of new symptoms, such as tremors were also reported. Patterns of symptom frequency and distress varied with the time since transplant. Conclusion The findings provide data-based information that can be used to inform pre- and post-transplant patient education and also help caregivers anticipate a general time frame for symptom changes in order to prevent or minimize symptoms and their associated distress. In addition, symptoms are described, using an innovative method of illustration which shows “at-a-glance” changes or lack of changes in patients’ symptoms from pre- to post-lung transplant. PMID:22988999
Kuehnel, Mark; Maegel, Lavinia; Vogel-Claussen, Jens; Robertus, Jan Lukas; Jonigk, Danny
Following lung transplantation, fibrotic remodelling of the small airways has been recognized for almost 5 decades as the main correlate of chronic graft failure and a major obstacle to long-term survival. Mainly due to airway fibrosis, pulmonary allografts currently show the highest attrition rate of all solid organ transplants, with a 5-year survival rate of 58 % on a worldwide scale. The observation that these morphological changes are not just the hallmark of chronic rejection but rather represent a manifestation of a multitude of alloimmune-dependent and -independent injuries was made more recently, as was the discovery that chronic lung allograft dysfunction manifests in different clinical phenotypes of respiratory impairment and corresponding morphological subentities. Although recent years have seen considerable advances in identifying and categorizing these subgroups on the basis of clinical, functional and histomorphological changes, as well as susceptibility to medicinal treatment, this process is far from over. Since the actual pathophysiological mechanisms governing airway remodelling are still only poorly understood, diagnosis and therapy of chronic lung allograft dysfunction presents a major challenge to clinicians, radiologists and pathologists alike. Here, we review and discuss the current state of the literature on chronic lung allograft dysfunction and shed light on classification systems, corresponding clinical and morphological changes, key cellular players and underlying molecular pathways, as well as on emerging diagnostic and therapeutic approaches.
Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan
Background Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Methods Using the Surveillance, Epidemiology and End Results registry linked to Medicare claims we identified 597 patients age ≥65 with NSCLC who had received organ transplants (kidney, liver, heart or lung) prior to cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Results Transplant recipients presented with earlier stage lung cancer (p=0.002) and were more likely to have squamous cell carcinoma (p=0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (p<0.05) while lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and non-transplant patients. Conclusions Non-lung solid organ transplant recipients who developed NSCLC had worse OS than non-transplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these two groups. PMID:25839704
Cheng, Guang-Shing; Edelman, Jeffrey D; Madtes, David K; Martin, Paul J; Flowers, Mary E D
Other than lung transplantation (LT), no specific therapies exist for end-stage lung disease resulting from hematopoietic stem cell transplantation (HCT)-related complications, such as bronchiolitis obliterans syndrome (BOS). We report the indications and outcomes in patients who underwent LT after HCT for hematologic disease from a retrospective case series at our institution and a review of the medical literature. We identified a total of 70 cases of LT after HCT, including 9 allogeneic HCT recipients from our institution who underwent LT between 1990 and 2010. In our cohort, the median age was 16 years (range, 10 to 35 years) at the time of HCT and 34 years (range, 17 to 44 years) at the time of LT, with a median interval between HCT and LT of 10 years (range, 2.9 to 27 years). Indications for LT-included pulmonary fibrosis (n = 4), BOS (n = 3), interstitial pneumonitis related to graft-versus-host disease (GVHD) (n = 1), and primary pulmonary hypertension (n = 1). Median survival was 49 months (range, 2 weeks to 87 months), and 1 patient remains alive at more than 3 years after LT. Survival at 1 year and 5 years after LT was 89% and 37%, respectively. In the medical literature between 1992 and July 2013, we identified 20 articles describing 61 cases of LT after HCT from various centers in the United States, Europe, and Asia. Twenty-six of the 61 cases (43%) involved patients age <18 years at the time of LT. BOS and GVHD of the lung were cited as the indication for LT in the majority of cases (80%; n = 49), followed by pulmonary fibrosis and interstitial lung disease (20%; n = 12). In publications reporting 3 or more cases with a follow-up interval ranging from the immediate postoperative period to 16 years, the survival rate was 71% (39 of 55). Most deaths were attributed to long-term complications of the lung allograft, including infections and BOS. Two deaths were related to recurrent or relapsed hematologic malignancy. LT can prolong survival in some
Basturk, Ahmet; Yılmaz, Aygen; Sayar, Ersin; Dinçhan, Ayhan; Aliosmanoğlu, İbrahim; Erbiş, Halil; Aydınlı, Bülent; Artan, Reha
Objective: The aim of our study was to evaluate our liver transplant pediatric patients and to report our experience in the complications and the long-term follow-up results. Materials and Methods: Patients between the ages of 0 and 18 years, who had liver transplantation in the organ transplantation center of our university hospital between 1997 and 2016, were included in the study. The age, sex, indications for the liver transplantation, complications after the transplantation, and long-term follow-up findings were retrospectively evaluated. The obtained results were analyzed with statistical methods. Results: In our organ transplantation center, 62 pediatric liver transplantations were carried out since 1997. The mean age of our patients was 7.3 years (6.5 months–17 years). The 4 most common reasons for liver transplantation were: Wilson’s disease (n=10; 16.3%), biliary atresia (n=9; 14.5%), progressive familial intrahepatic cholestasis (n=8; 12.9%), and cryptogenic cirrhosis (n=7; 11.3%). The mortality rate after transplantation was 19.6% (12 of the total 62 patients). The observed acute and chronic rejection rates were 34% and 4.9%, respectively. Thrombosis (9.6%) was observed in the hepatic artery (4.8%) and portal vein (4.8%). Bile leakage and biliary stricture rates were 31% and 11%, respectively. 1-year and 5-year survival rates of our patients were 87% and 84%, respectively. Conclusion: The morbidity and mortality rates in our organ transplantation center, regarding pediatric liver transplantations, are consistent with the literature. PMID:28149148
Lundmark, Martina; Lennerling, Annette; Almgren, Matilda; Forsberg, Anna
The aims of this study were two-fold: to develop the concept analysis by Allvin et al. from lung recipients' perspective of their post-transplant recovery process and to identify the recovery trajectories including critical junctions in the post-transplant recovery process after lung transplantation. Lung transplantation is an established treatment for patients with end-stage lung disease. The recovery process after lung transplantation is very demanding. Today, patients are expected to play an active role in their own recovery but require ongoing support during the process. A deductive, retrospective interview study using directed content analysis and Allvin's recovery concept analysis. Fifteen adult lung transplant recipients who were due their 12-month follow-up were consecutively included and interviewed during 2015. Patients who were medically unstable or had difficulties speaking Swedish were excluded from this multi-centre study. Allvin's concept analysis is partly applicable to the context of lung transplantation. The recipients' experience of the post-transplant recovery process could be confirmed in the main dimensions of the concept analysis, while several sub-dimensions were contradictory and were excluded. Six new sub-dimensions emerged; symptom management, adjusting to physical restraints, achieving an optimum level of psychological well-being, emotional transition, social adaptation and reconstructing daily occupation. The concept analysis by Allvin et al. was possible to expand to fit the lung transplantation context and a new contextual definition of post-transplant recovery after solid organ transplantation was developed. Recovery and health were viewed as two different things. © 2016 John Wiley & Sons Ltd.
Weber, Daniel J.
First performed in the 1960s with long-term successes achieved in the 1980s, lung transplantation remains the only definitive treatment option for end-stage lung disease. Chronic lung rejection, pathologically classified as obliterative bronchiolitis (OB) with its clinical correlate referred to as bronchiolitis obliterans syndrome, is the limiting factor than keeps 5-yr survival rates for lung transplant significantly worse than for other solid organ transplants. Initially, OB was largely attributed to immune responses to donor antigens, alloimmunity. However, more recent work has demonstrated the role of autoimmunity in the process of lung transplant rejection. IL-17 and autoantigens such as collagen type V and K-α1 tubulin have been implicated in the development of chronic rejection. Ultimately, this translational review discusses the role that autoimmunity plays in the development of OB and lung transplant rejection and then discusses options for therapeutic intervention. PMID:23262227
Okazaki, M; Krupnick, A S; Kornfeld, C G; Lai, J M; Ritter, J H; Richardson, S B; Huang, H J; Das, N A; Patterson, G A; Gelman, A E; Kreisel, D
Outcomes after lung transplantation are markedly inferior to those after other solid organ transplants. A better understanding of cellular and molecular mechanisms contributing to lung graft injury will be critical to improve outcomes. Advances in this field have been hampered by the lack of a mouse model of lung transplantation. Here, we report a mouse model of vascularized aerated single lung transplantation utilizing cuff techniques. We show that syngeneic grafts have normal histological appearance with minimal infiltration of T lymphocytes. Allogeneic grafts show acute cellular rejection with infiltration of T lymphocytes and recipient-type antigen presenting cells. Our data show that we have developed a physiological model of lung transplantation in the mouse, which provides ample opportunity for the study of nonimmune and immune mechanisms that contribute to lung allograft injury.
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
Haft, Jonathan W; Griffith, Bartley P; Hirschl, Ronald B; Bartlett, Robert H
Lung transplantation is the only treatment for patients with end-stage lung disease. However, the scarcity of donor organs illustrates the need for alternatives. Recent success in the use of ventricular assistance has stimulated research in technology designed as a bridge to lung transplantation. Some laboratories have demonstrated significant advances in the development of artificial lungs, and clinical applications are on the horizon. In preparation, we sought to gather information from the lung transplant community regarding issues related to testing and potential trials of artificial lungs. We constructed a survey and distributed it to lung transplant program directors recognized by the United Network for Organ Sharing. Topics included required animal studies, preferred designs, logistics of clinical trials, and patient diagnoses most appropriate for such a trial. The 31 programs responding to the survey performed 72% of all lung transplants in the United States in 1999. Ninety-seven percent supported a Phase I trial using an artificial lung as a bridge to lung transplantation. Additionally, 58% specifically supported a trial in which organ allocation would be prioritized to enrolled patients. Idiopathic pulmonary fibrosis was the diagnosis thought most appropriate for inclusion in initial clinical trials. Widespread support exists for the development and use of an artificial lung as a bridge to lung transplantation. Information from transplant centers regarding device design and application can influence laboratories developing artificial lungs, and such communication will be essential as this technology progresses from the bench-top to the bedside.
Villavicencio, Mauricio; Rossel, Víctor; Larrea, Ricardo; Peralta, Juan Pablo; Larraín, Ernesto; Sung Lim, Jong; Rojo, Pamela; Gajardo, Francesca; Donoso, Erika; Hurtado, Margarita
Heart transplantation is the therapy of choice for advance heart failure. Our group developed two transplant programs at Instituto Nacional del Tórax and Clínica Dávila. We report our clinical experience based on distinctive clinical policies. Fifty-three consecutive patients were transplanted between November 2008 and April 2013, representing 51% of all Chilean cases. Distinctive clinical policies include intensive donor management, generic immunosuppression and VAD (ventricular assist devices) insertion. Ischemic or dilated cardiomyopathy were the main indications (23 (43%) each), age 48 ± 13 years and 48 (91%) were male. Transplant listing Status: IA 14 (26%) (VAD or 2 inotropes), IB 14 (26%) (1 inotrope) and II25 (47%) (no inotrope). Mean waiting time 70 ± 83 days. Twelve (24%) were transplanted during VAD support (median support: 36 days). orthotopic bicaval transplant with ischemia time: 175 ± 54 min. Operative mortality: 3 (6%), all due to right ventricular failure. Re-exploration for bleeding 2 (4%), stroke 3 (6%), mediastinitis 0 (0%), pneumonia 4 (8%), and transient dialysis 6 (11%). Mean follow-up was 21 ± 14 months. Three-year survival was 86 ± 6%. One patient died of Pneumocystis jirovecii pneumonia and the other died suddenly (non-compliance). Freedom from rejection requiring specific therapy was 80 ± 7% at 3 years of follow-up. Four hundred eighty four endomyocardial biopsies were done: 11 (2.3%) had 2R rejection. All survivors are in NYHA (New York Heart Association) functional class I and all but one have normal biventricular function. Mid-term results are similar to those reported by the registry of the International Society for Heart and Lung Transplantation. This experience has a higher proportion of VAD support than previous national series. Rejection rates are low in spite of generic immunosuppression.
Borro, J M; Tarazona, V; Vicente, R; Cafarena, J M; Ramos, F; Sales, G; Galán, G; Lozano, C; Morant, P; Calvo, V; Morcillo, A; París, F
Since the first sequential double lung transplant was performed in 1986, such procedures have been increasing in number and the criteria used as indications for this type of surgery have broadened. Our aim was to reflect on the application of selection criteria and to describe the anesthetic and surgical techniques and postoperative follow-up of 72 patients who underwent this type of transplant surgery between March 1993 and December 1998. Actuarial survival five years after surgery was 74.4%. Among patients requiring transplantation after septic disease, actuarial survival was 90.8% for cystic fibrosis and 88.2% for bronchiectasis. Of the preoperative risk factors analyzed (prior surgery, pachypleuritis, multiresistant germs, poor nutrition, mechanical ventilation and corticoid therapy), only prior treatment with high doses of corticoids proved significant. Eleven patients have been diagnosed of bronchiolitis obliterans, four have died and only two continue to experience difficulties in daily living. The high survival rate and the restriction-free life after recovery lead us to consider sequential double lung transplantation to be the treatment of choice for all pulmonary diseases.
Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan
Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Using the Surveillance, Epidemiology, and End Results Registry linked to Medicare claims, we identified 597 patients aged 65 years or older with NSCLC who had received organ transplants (kidney, liver, heart, or lung) before cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Transplant recipients presented with earlier stage lung cancer (P = 0.002) and were more likely to have squamous cell carcinoma (P = 0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (P < 0.05), whereas lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and nontransplant patients. Non-lung solid organ transplant recipients who developed NSCLC had worse OS than nontransplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these 2 groups.
Tokman, Sofya; Singer, Jonathan P; Devine, Megan S; Westall, Glen P; Aubert, John-David; Tamm, Michael; Snell, Gregory I; Lee, Joyce S; Goldberg, Hilary J; Kukreja, Jasleen; Golden, Jeffrey A; Leard, Lorriana E; Garcia, Christine K; Hays, Steven R
Successful lung transplantation for patients with pulmonary fibrosis from telomerase mutations may be limited by systemic complications of telomerase dysfunction, including myelosuppression, cirrhosis, and malignancy. We describe clinical outcomes in 14 lung transplant recipients with telomerase mutations. Subjects underwent lung transplantation between February 2005 and April 2014 at 5 transplant centers. Data were abstracted from medical records, focusing on outcomes reflecting post-transplant treatment effects likely to be complicated by telomerase mutations. The median age of subjects was 60.5 years (interquartile range = 52.0-62.0), 64.3% were male, and the mean post-transplant observation time was 3.2 years (SD ± 2.9). A mutation in telomerase reverse transcriptase was present in 11 subjects, a telomerase RNA component mutation was present in 2 subjects, and an uncharacterized mutation was present in 1 subject. After lung transplantation, 10 subjects were leukopenic and 5 did not tolerate lymphocyte anti-proliferative agents. Six subjects developed recurrent lower respiratory tract infections, 7 developed acute cellular rejection (A1), and 4 developed chronic lung allograft dysfunction. Eight subjects developed at least 1 episode of acute renal failure and 10 developed chronic renal insufficiency. In addition, 3 subjects developed cancer. No subjects had cirrhosis. At data censorship, 13 subjects were alive. The clinical course for lung transplant recipients with telomerase mutations is complicated by renal disease, leukopenia with intolerance of lymphocyte anti-proliferative agents, and recurrent lower respiratory tract infections. In contrast, cirrhosis was absent, acute cellular rejection was mild, and development of chronic lung allograft dysfunction was comparable to other lung transplant recipients. Although it poses challenges, lung transplantation may be feasible for patients with pulmonary fibrosis from telomerase mutations. Copyright © 2015
Izbicki, Gabriel; Shitrit, David; Aravot, Dan; Fink, Gershon; Saute, Milton; Idelman, Leonid; Bakal, Ilana; Sulkes, Jaqueline; Kramer, Mordechai R
Historically, donor age above 55 years has been considered to be a relative contraindication for organ transplantation. The shortage of organs for transplantation has led to the expansion of the donor pool by accepling older donors. To compare the 1 year follow-up in patients after lung transplantation from older donors (> 50 years old) and in patients after transplantation from younger donors (< or = 50 years). The study group comprised all adult patients who underwent lung transplantation at the Rabin Medical Center between May 1997 and August 2001. Donors were classified into two groups according to their age: < or = 50 years (n = 20) and > 50 years (n = 9). Survival, number and total days of hospitalization, development of bronchiolitis obliterans syndrome, and pulmonary function tests, were examined 1 year after transplantation. We performed 29 lung transplantations in our center during the observed period. Donor age had no statistically significant impact on 1 year survival after lung transplantation. There was no statistically significant effect on lung function parameters, the incidence of hospitalization or the incidence of bronchiolitis obliterans between both donor age groups at 1 year after transplantation. Donor age did not influence survival or important secondary end-points 1 year after lung transplantation By liberalizing donor criteria of age up to 65 years, we can expand the donor pool, while assessing other possible mechanisms to increase donor availability.
Scedosporium spp. are filamentous fungi, and the 2 most important species are Scedosporium prolificans and Scedosporium apiospermum. S. apiospermum accounts for approximately 25% of non-Aspergillus filamentous fungi infections in organ transplant recipients. Scedosporium can colonize the sinuses and airways of lung recipients with underlying pulmonary diseases, such as bronchiectasis or cystic fibrosis before transplant, and develop invasive disease after lung transplantation. In fact, invasive diseases caused by S. apiospermum have been reported only rarely, in single lung transplant recipients and cystic fibrosis transplant patients. The treatment of scedosporiasis is complicated due to the difficulty in early diagnosis together with inherent resistance to amphotericin B. A case of disseminated S. apiospermum infection after single lung transplant in a patient with pulmonary fibrosis is reported. Leg mycetoma was the initial sign of this disseminated infection. In this case report, current treatment options are discussed, and a review of the literature of previously published cases of lung transplants is made. One conclusion based on this case is the risk of emergent molds related to antifungal prophylaxis. In addition, colonization by Scedosporium in transplant recipients should not be ignored, and target prophylaxis or suppressive therapy should be considered in all those cases with residual lesions in native lung or chronic rejection in transplanted lungs. Copyright © 2011 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.
Yamane, Masaomi; Okutani, Daisuke; Sugimoto, Seiichiro; Toyooka, Shinichi; Aoe, Motoi; Okazaki, Megumi; Sano, Yoshifumi; Date, Hiroshi
The living-donor lobar lung transplantation procedure has been developed clinically as an alternative approach for patients considered too ill to await cadaveric transplantation. With this procedure, 2 lobes are implanted in the recipient in place of whole right and left lungs, respectively. However, the shortage of graft volume can be a problem when compared with full-sized cadaveric grafts. In an attempt to solve this problem, we have developed a native lobe-preserving lobar transplant technique using a large animal model. We report a first successful case of a patient undergoing native lobe-preserving lobar lung transplantation for severe pulmonary emphysema.
Bozso, S J; Nagendran, Je; Gill, R S; Freed, D H; Nagendran, Ja
Increasing prevalence of obesity has led to a rise in the number of prospective obese heart and lung transplant recipients. The optimal management strategy of obese patients with end-stage heart and lung failure remains controversial. This review article discusses and provides a summary of the literature surrounding the impact of obesity on outcomes in heart and lung transplantation. Studies on transplant obesity demonstrate controversy in terms of morbidity and mortality outcomes and obesity pre-transplantation. However, the impact of obesity on outcomes seems to be more consistently demonstrated in lung rather than heart transplantation. The ultimate goal in heart and lung transplantation in the obese patient is to identify those at highest risk of complication that may warrant therapies to mitigate risk by addressing comorbid conditions.
Patterson, T F; Peters, J; Levine, S M; Anzueto, A; Bryan, C L; Sako, E Y; Miller, O L; Calhoon, J H; Rinaldi, M G
Systemic availability of itraconazole in lung transplantation was evaluated by serially measuring the bioactivity of itraconazole in lung transplant patients who received itraconazole for prophylaxis (n = 12) or therapy (n = 5). These patients also received concomitant antacid and H2 blocker therapy. In patients receiving itraconazole at 200 and 400 mg/day, the median concentrations in serum were 0.5 microgram/ml (range, < 0.05 to 2.7) and 3.5 micrograms/ml (< 0.5 to 14), respectively. The concentration following administration of 400 mg/day was > 2.5 micrograms/ml in 56% of samples, while only 4% of samples from patients who were administered 200 mg/day had levels over 2.5 micrograms/ml. This study documents that itraconazole can be absorbed in patients receiving concomitant antacid and H2 blocker therapy. However, the reduced and variable absorption suggests the importance of confirming drug delivery by measurement of concentrations in serum. PMID:8878612
Nakajima, Takahiro; Cypel, Marcelo; de Perrot, Marc; Pierre, Andrew; Waddell, Tom; Singer, Lianne; Roberts, Heidi; Keshavjee, Shaf; Yasufuku, Kazuhiro
Unexpected lung cancer is sometimes found in explanted lungs. The objective of this study was to review these patients and their outcomes to better understand and optimize management protocols for lung transplant candidates with pulmonary nodules. Retrospective analysis of pretransplant imaging and clinicopathologic characteristics of patients who were found to have lung cancer in their explanted lungs was performed. From January 2003 to December 2012, 13 of 853 lung transplant recipients were found to have unexpected lung cancer in their explanted lung (1.52%). Of them, 9 cases were for interstitial lung disease (2.8%; 9/321 recipients) and 4 cases were for chronic obstructive pulmonary disease (1.57%; 4/255 recipients). The median period between computed tomographic scan and lung transplantation was 2.40 months (range: 0.5-19.2). On computed tomographic scan, only 3 cases were shown to possibly have a neoplasm by the radiologist. The staging of these lung cancers was as follows: 3 cases of IA, 1 case of IB, 5 cases of IIA, 1 case of IIIA, and 3 cases of IV. Of 13 cases, 9 died owing to cancer progression. On the contrary, only 1 stage I case with small cell lung cancer showed cancer recurrence. The median survival time was 339 days, and the 3-year survival rate was 11.0%. In conclusion, most of the patients with unexpected lung cancer showed poor prognosis except for the early-stage disease. The establishment of proper protocol for management of such nodules is important to improve the management of candidates who are found to have pulmonary nodules on imaging. Copyright © 2015 Elsevier Inc. All rights reserved.
Vos, Robin; Yserbyt, Jonas; Decaluwe, Herbert; De Leyn, Paul; Verleden, Geert M.
Lung transplantation is an effective and safe therapy for carefully selected patients suffering from a variety of end-stage pulmonary diseases. Lung cancer negatively affects prognosis, particularly in patients who are no longer candidates for complete resection. Lung transplantation can be considered for carefully selected and well staged lung cancer patients with proven, lung-limited, multifocal, (minimally invasive) adenocarcinoma in situ (AIS) (previously called bronchioloalveolar cell carcinoma) causing respiratory failure. Despite a substantial risk of tumour recurrence (33–75%), lung transplantation may offer a survival benefit (50% at 5 years) with best palliation of their disease. Reports on lung transplantation for other low-grade malignancies are rare. Lung transplant candidates at higher risk for developing lung cancer [mainly previous smokers with chronic obstructive lung disease (COPD) and idiopathic pulmonary fibrosis (IPF) or older patients] should be thoroughly and repeatedly screened for lung cancer prior to listing, and preferably also during waiting list time if longer than 1 year, including the use of PET-CT scan and EBUS-assisted bronchoscopy in case of undefined, but suspicious pulmonary abnormalities. Double-lung transplantation should now replace single-lung transplantation in these high-risk patients because of a 6–9% prevalence of lung cancer developing in the remaining native lung. Patients with unexpected, early stage bronchial carcinoma in the explanted lung may have favourable survival without recurrence. Early PET-CT (at 3–6 months) following lung transplantation is advisable to detect early, subclinical disease progression. Donor lungs from (former) smokers should be well examined at retrieval. Suspicious nodules should be biopsied to avoid grafting cancer in the recipient. Close follow-up with regular visits and screening test in all recipients is needed because of the increased risk of developing a primary or secondary
Sternberg, David I; Shimbo, Daichi; Kawut, Steven M; Sarkar, Joydeep; Hurlitz, Georg; D'Ovidio, Frank; Lederer, David J; Wilt, Jessie S; Arcasoy, Selim M; Pinsky, David J; D'Armiento, Jeanine M; Sonett, Joshua R
During lung transplantation, cells in the pulmonary parenchyma are subjected to ischemia, hypothermic storage, and reperfusion injury. Platelets, whose granular contents include adhesion receptors, chemokines, and coactivating substances that activate inflammatory and coagulant cascades, likely play a critical role in the lung allograft response to ischemia and reperfusion. The platelet response to the pulmonary allograft, however, has never been studied. Here we report significant platelet activation immediately after lung transplantation. We performed a prospective cohort study comparing markers of platelet activation in patients undergoing lung transplantation and patients undergoing nontransplant thoracotomy. Plasma levels of soluble P-selectin, soluble CD40 ligand, and platelet-leukocyte conjugates were measured before surgery, after skin closure, and at 6 postoperative hours. Both soluble P-selectin and soluble CD40 ligand levels increased significantly after lung transplantation but not after thoracotomy. Additionally, platelet-monocyte conjugate fluorescence was significantly higher after lung transplantation than after thoracotomy alone. These findings suggest that platelet activation is significantly increased after lung transplantation beyond that expected from the postoperative state. The increase in circulating platelet-monocyte conjugates suggests an important interaction between platelets and inflammatory cells. Further research should examine whether platelet activation affects early graft function after lung transplantation.
Lung transplantation has been performed worldwide and recognized as an effective treatment for patients with various end-stage lung diseases. Shortage of lung donors is one of the main obstacles in most of the countries, especially in Japan. Every effort has been made to promote organ donation during the past 20 years. In 2010, Japanese transplant low was revised so that the family of the brain dead donors can make a decision for organ donation. Since then, the number of cadaveric lung donor has increased by 5-fold. However, the average waiting time is still more than 800 days resulting in considerable number of deaths on the waiting list. Lung transplantation in the use of donation after cardiac death (DCD) has now been increasingly performed in Europe, Australia and North America with promising results. However, controlled death is not permitted in Japan making it difficult to accept this strategy. Use of marginal donors is one of the strategies for organ shortage. In Japan, the rate of lung usage is now well over 60% because of careful donor management by medical consultants and aggressive use of marginal donors. Living-donor lobar lung transplantation (LDLLT) has been developed to offset the mismatch between supply and demand for those patients awaiting cadaveric lung transplantation (CLT) and it is often the most realistic option for very ill patients. Between 1998 and 2015, lung transplantation has been performed in 464 patients (55 children, 419 adults) at 9 lung transplant centers in Japan. CLT was performed in 283 patients (61%) and LDLLT was performed in 181 patients (39%). The 5-year survival was 72.3% and 71.6%, respectively. Of note, only seven children received CLT. In conclusion, lung transplantation in Japan has grown significantly with excellent results but the shortage of cadaveric lung donor remains to be an important unsolved problem. LDLLT is often the only realistic option for very ill patients especially for children. PMID:27651939
Jensen, Anja M B
This paper deals with the emotional challenges encountered by doctors and nurses caring for heart and lung transplant patients. Organ transplantation enables body parts from the dead to become usable in patients with no other life-saving option. These exchanges are not possible without transplant professionals carefully selecting, guiding and interacting with organ recipients before, during and after the transplant. Based on anthropological fieldwork at a Danish heart and lung transplant unit, the paper explores how doctors and nurses experience and handle the emotional challenges of their working life. By focusing on the everyday life of the transplant unit which, contrary to public understanding of transplant miracles, is sometimes characterised by sad cases and devastation, this paper argues that transplant professionals operate in the presence of death. Medically and emotionally they are at risk. They must take the difficult decisions of whether to admit critically ill patients onto the organ waiting list; face the distress of post-transplant sufferings and deaths; and deal with organ recipients who do not behave according to post-transplant recommendations. Drawing on a familiar metaphor for donated organs, it is suggested that transplant doctors and nurses are 'guardians of the gift'. Attention to the emotional burdens and rewards of this particular position enables new understandings of the practices of transplant medicine, of gift exchange theory, and of the role of emotion in medical practice.
Verleden, G M
Obliterative bronchiolitis (OB) or the clinical correlate bronchiolitis obliterans syndrome (BOS) is the main cause of late morbidity and mortality after heart-lung and lung transplantation. Although several risk factors for the development of OB/BOS have already been identified, very effective preventive therapy remains Utopian, although there has been much improvement in recent years. This paper attempts to summarize current experience in the medical treatment of OB/BOS, either by tackling the known risk factors for the development of OB/BOS or by changing the immunosuppressive drug regimen for treating established OB/BOS. The current treatment options, however, are rather anecdotal and mostly single-centre experiences. Therefore, multicentre studies are definitely needed to try to identify the most appropriate drug regimen either to prevent and to treat obliterative bronchiolitis/bronchiolitis obliterans syndrome.
Rueda, Pablo; Morales, Jose; Guzman, Enrique; Tellez, Jose L; Niebla, Benito A; Avalos, Alejandro; Patiño, Hilda
We present a case of unilateral lung transplantation in which a segment of the donor's descending aorta was used as a homograft for pulmonary artery augmentation in the donor lung. This technique can be used when the donor's lung artery has been cut at the base of the hilum during the harvesting procedure.
Armstrong, Hilary F; Gonzalez-Costello, Jose; Thirapatarapong, Wilawan; Jorde, Ulrich P; Bartels, Matthew N
To evaluate if patients have a change in percent of predicted heart rate reserve used at peak exercise (%HRR) after lung transplantation, even at matching workloads. Lung disease of obstructive, restrictive, and mixed types may be associated with an autonomic imbalance. Lung transplantation may improve the effects of pulmonary disease on cardiac function. However, the effect of lung transplantation on heart rate responses during exercise has not been investigated in detail. Retrospective review of patients who underwent lung transplantation. Pre and post transplant cardiopulmonary exercise tests were reviewed. The %HRR significantly improved by a median of 37% (p < 0.001) following lung transplantation. When matching workloads were analyzed, the %HRR also decreased from a median of 36% to 24% (p < 0.001). Corresponding to an increase in peak exercise capacity, percentage of heart rate reserve used improves significantly after lung transplantation, even at matching workloads, indicating a likely improvement in autonomic modulation. Copyright © 2015 Elsevier Inc. All rights reserved.
Brügger, Aurelia; Aubert, John-David
Patients awaiting lung transplantation are at risk of negative emotional and physical experiences. How do they talk about emotions? Semi-structured interviews were performed (15 patients). Categorical analysis focusing on emotion-related descriptions was organized into positive–negative–neutral descriptions: for primary and secondary emotions, evaluation processes, coping strategies, personal characteristics, emotion descriptions associated with physical states, (and) contexts were listed. Patients develop different strategies to maintain positive identity and attitude, while preserving significant others from extra emotional load. Results are discussed within various theoretical and research backgrounds, in emphasizing their importance in the definition of emotional support starting from the patient’s perspective. PMID:28070345
De Vito Dabbs, Annette; Kim, Yookyung; Vensak, Judith; Studer, Sean; Iacono, Aldo
The Questionnaire for Lung Transplant Patients was designed to assess symptoms and activity tolerance in lung transplant recipients during their post-transplant evaluations. The initial psychometric evaluation determined that the questionnaire was clinically useful, reliable, and valid. To report the results of further psychometric analyses in a new, expanded sample of lung transplant recipients and to demonstrate the iterative manner by which instruments are refined and tested. Internal consistency, test-retest stability, convergent validity, factorial validity, and group differences attributable to age, gender, and transplant type were determined in a pooled sample of 177 lung transplant recipients. Sensitivity to change over time was measured in a subsample (n = 51) who provided repeated measures data. The Questionnaire for Lung Transplant Patients and its subscales were internally consistent (Kuder Richardson reliability of 0.73-0.95). Test-retest stability was high (intraclass correlations >0.70). Symptoms showed a significant curvilinear pattern with a tendency to decrease over time before rising again at the 12-month measurement for the total questionnaire (F=6.8, P=.012) and 2 subscales--Respiratory (F=5.6, P=.022) and Activities of Daily Living (F=19.7, P<.001). Convergent construct validity correlations ranged from 0.29 to 0.53 and were consistent with theoretical expectations. Factorial analysis confirmed 3 domains that coincided with the Respiratory, General, and Activities of Daily Living subscales. The Questionnaire for Lung Transplant Patients is a reliable and valid measure for assessing physical symptoms and activity intolerance after lung transplantation in individual recipients, recipients in aggregate, and comparison groups, on one occasion and serially over time. These results will guide future refinement and testing of the Questionnaire for Lung Transplant Patients.
Nayak, Deepak Kumar; Saravanan, Prathab Balaji; Bansal, Sandhya; Naziruddin, Bashoo; Mohanakumar, Thalachallour
The field of organ transplantation has undoubtedly made great strides in recent years. Despite the advances in donor–recipient histocompatibility testing, improvement in transplantation procedures, and development of aggressive immunosuppressive regimens, graft-directed immune responses still pose a major problem to the long-term success of organ transplantation. Elicitation of immune responses detected as antibodies to mismatched donor antigens (alloantibodies) and tissue-restricted self-antigens (autoantibodies) are two major risk factors for the development of graft rejection that ultimately lead to graft failure. In this review, we describe current understanding on genesis and pathogenesis of antibodies in two important clinical scenarios: lung transplantation and transplantation of islet of Langerhans. It is evident that when compared to any other clinical solid organ or cellular transplant, lung and islet transplants are more susceptible to rejection by combination of allo- and autoimmune responses. PMID:28066448
In France, the "Agence de la biomédecine" distributes lung grafts. "Ideal" criteria for lung donor selection are not always respected, driven by the scarcity of suitable donor lungs (10% deaths while waiting). In single lung transplantation, three anastomoses are performed (bronchus near the lobar carina, pulmonary artery, left atrium). For double lung transplantation (twice as frequent around the world), two single lung transplantations are successively performed through two separate anterolateral thoracotomies, often without cardiopulmonary bypass. Heart lung transplantations are now rare (2% around the world). Postoperative mortality has improved (between 10 and 15%): less severe primary graft dysfunctions, treatable with ECMO, fewer bronchial complications, improvement in the diagnosis of hyperacute humoral rejection, improvement in antiviral prophylaxis.
Hathorn, Kelly E; Chan, Walter W; Lo, Wai-Kit
Lung transplantation is one of the highest risk solid organ transplant modalities. Recent studies have demonstrated a relationship between gastroesophageal reflux disease (GERD) and lung transplant outcomes, including acute and chronic rejection. The aim of this review is to discuss the pathophysiology, evaluation, and management of GERD in lung transplantation, as informed by the most recent publications in the field. The pathophysiology of reflux-induced lung injury includes the effects of aspiration and local immunomodulation in the development of pulmonary decline and histologic rejection, as reflective of allograft injury. Modalities of reflux and esophageal assessment, including ambulatory pH testing, impedance, and esophageal manometry, are discussed, as well as timing of these evaluations relative to transplantation. Finally, antireflux treatments are reviewed, including medical acid suppression and surgical fundoplication, as well as the safety, efficacy, and timing of such treatments relative to transplantation. Our review of the data supports an association between GERD and allograft injury, encouraging a strategy of early diagnosis and aggressive reflux management in lung transplant recipients to improve transplant outcomes. Further studies are needed to explore additional objective measures of reflux and aspiration, better compare medical and surgical antireflux treatment options, extend follow-up times to capture longer-term clinical outcomes, and investigate newer interventions including minimally invasive surgery and advanced endoscopic techniques. PMID:28507913
Thomas, Biju; Aurora, Paul; Spencer, Helen; Elliott, Martin; Rutman, Andrew; Hirst, Robert A; O'Callaghan, Christopher
It is unclear whether ciliary function following lung transplantation is normal or not. Our aim was to study the ciliary function and ultrastructure of epithelium above and below the airway anastomosis and the peripheral airway of children following lung transplantation. We studied the ciliary beat frequency (CBF) and beat pattern, using high speed digital video imaging and ultrastructure by transmission electron microscopy, of bronchial epithelium from above and below the airway anastomosis and the peripheral airway of 10 cystic fibrosis (CF) and 10 non-suppurative lung disease (NSLD) paediatric lung transplant recipients. Compared to epithelium below the anastomosis, the epithelium above the anastomosis in the CF group showed reduced CBF (median (interquartile range): 10.5 (9.0-11.4) Hz versus 7.4 (6.4-9.2) Hz; p<0.01) and increased dyskinesia (median (IQR): 16.5 (12.9-28.2)% versus 42.2 (32.6-56.4)%; p<0.01). In both CF and NSLD groups, compared with epithelium above the anastomosis, the epithelium below the anastomosis showed marked ultrastructural abnormalities (median duration post-transplant 7-12 months). Ciliary dysfunction is a feature of native airway epithelium in paediatric CF lung transplant recipients. The epithelium below the airway anastomosis shows profound ultrastructural abnormalities in both CF and NSLD lung transplant recipients, many months after transplantation.
Schreder, T; Gottlieb, J
End stage pulmonary emphysema is the most common indication for lung transplantation worldwide. The shortness of donor organs and the better natural prognosis compared to other diseases leading to transplantation such as pulmonary fibrosis and cystic fibrosis demands careful patient selection.Lung transplantation is considered in patients with declining lung function after receiving all conservative treatment options including smoking cessation and rehabilitation programmes. Preoperative evaluation using consensus criteria needs to be performed by a multidisciplinary team in specialized centres. Assessment of co-morbidities is crucial, as they may significantly increase transplant-related mortality. The largest survival advantage from lung transplantation has been shown for the subgroup of patients below 60 years of age presenting with end-stage obstructive lung disease (FEV1 < 20% predicted) and respiratory failure. Similarly, high risk patients with secondary pulmonary hypertension or cachexia (BMI < 20) will likely benefit from transplantation.The 5-year-survival rate averages 60 percent, with superior outcome following double versus single lung transplantation. A clear survival benefit can only be achieved in a subgroup of patients, whereas the impact on quality of life seems to be even more important in patients suffering from chronic obstructive pulmonary disease.
Liou, Theodore G.; Adler, Frederick R.; Cox, David R.; Cahill, Barbara C.
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 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, 315 patients had a significant risk of harm, 76 patients had an insignificant benefit, and 118 patients had an insignificant risk of harm
Liou, Theodore G.; Adler, Frederick R.; Cox, David R.; Cahill, Barbara C.
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
Hill, A; Thompson, R; Wallwork, J; Stableforth, D
The case history is presented of a patient with common variable immunodeficiency in whom heart lung transplantation has been carried out with success. Transplantation was the only long term therapeutic option in this patient due to the progressive respiratory failure resulting from bronchiectasis, emphysema, and granulomatous lung disease. PMID:9797766
Puri, Varun; Patterson, G Alexander; Meyers, Bryan F
Synopsis An ongoing debate exists between proponents of single or double lung transplant for end-stage pulmonary disease. Short- and long-term outcomes, as well as individual and societal benefits are some of the key considerations. We examine the evidence that directly compares these two approaches and informs the debate about the relative merits of single and bilateral transplant. PMID:25430429
Gal, Anthony A; Bryan, John A; Kanter, Kirk R; Lawrence, E Clinton
Pulmonary alveolar proteinosis is a disorder of unknown origin that occurs rarely after lung transplantation. We identified a patient with pulmonary alveolar proteinosis 66 days after undergoing single lung transplantation for idiopathic pulmonary fibrosis. We based the diagnosis on the presence of amorphous clumps or globules of acellular and finely granular material in bronchoalveolar lavage fluid (BALF). This material persisted for an 18.5-month period and was present in 9 of 14 lavage specimens. However, despite its presence in the native lung at autopsy, the material was seen in only 1 of 14 transbronchial lung biopsy specimens. Although uncommon, pulmonary alveolar proteinosis can be diagnosed readily in BALF by its distinctive cytopathologic features and should be considered in the differential diagnosis of pulmonary disease in lung transplant recipients.
Shitrit, David; Amital, Anat; Peled, Nir; Raviv, Yael; Medalion, Benjamin; Saute, Milton; Kramer, Mordechai R
The use of lung transplantation (LTX) to treat respiratory failure because of scleroderma is controversial. We present our experience, review the current literature, and suggest specific criteria for LTX in scleroderma. Of the 174 patients who underwent LTX at our center, seven (4%) had scleroderma-associated respiratory failure. A MEDLINE search of the English literature was performed for studies of LTX in patients with scleroderma between 1986 and 2006. A Kaplan-Meier survival curve was calculated over the time of the studies. The MEDLINE search yielded one large review and four small case series. The small case series were included in the review. The review and our series yield a total of 54 patients. Mean patient age was 47.1 yr; 59.3% were female. Pre-operative lung data were available for 24 patients: 22 (92%) had pulmonary fibrosis and 17 (71%) had pulmonary hypertension. Most patients (69%) underwent single-lung transplantation. Mean forced expiratory volume at one s after LTX was 67% (range 56-87%). There was no difference in infection and rejection rates between the patients with scleroderma and other LTX recipients. The two- and five-yr survival rates were 72% and 55%, respectively. LTX is a valid option in well-selected patients with scleroderma and pulmonary fibrosis, yielding good pulmonary function and acceptable morbidity and mortality.
Hennessy, Sara A.; Gillen, Jacob R.; Hranjec, Tjasa; Kozower, Benjamin D.; Jones, David R.; Kron, Irving L.; Lau, Christine L.
Background Chronic renal failure after lung transplantation is associated with significant morbidity. However, the significance of acute kidney injury (AKI) after lung transplantation remains unclear and poorly studied. We hypothesized that hemodialysis (HD)-dependent AKI after lung transplantation is associated with significant mortality. Materials and methods We performed a retrospective review of all patients undergoing lung transplantation from July 1991 to July 2009 at our institution. Recipients with AKI (creatinine > 3 mg/dL) were identified. We compared recipients without AKI versus recipients with and without HD-dependent AKI. Kaplan-Meier survival curves were compared by log rank test. Results Of 352 lung transplant recipients reviewed at our institution, 17 developed non–HD-dependent AKI (5%) and 16 developed HD-dependent AKI (4.6%). Cardiopulmonary bypass was significantly higher in patients with HD-dependent AKI. None of the recipients who required HD had recovery of renal function. The 30-day mortality was significantly greater in recipients requiring HD (63% versus 0%; P < 0.0001). One-year mortality after transplantation was significantly increased in recipients with HD-dependent AKI compared with those with non–HD-dependent AKI (87.5% versus 17.6%; P < 0.001). Conclusions Hemodialysis is associated with mortality after lung transplantation. Fortunately, AKI that does not progress to HD commonly resolves and has a better overall survival. Avoidance, if possible, of cardiopulmonary bypass may attenuate the incidence of AKI. Aggressive measures to identify and treat early postoperative renal dysfunction and prevent progression to HD may improve outcomes after lung transplantation. PMID:23481566
Vock, David M.; Pieper, Karen; Mark, Daniel B.; Palmer, Scott M.
Background: Quality of life (QOL) is an important but understudied outcome after lung transplantation. Previous cross-sectional, single-center studies suggest improved QOL, but few prior longitudinal multicenter data exist regarding the effect of transplantation on the patient’s QOL. Methods: We hypothesized that lung transplantation confers a 1-year QOL benefit in both physical and psychologic well-being; we further hypothesized that the magnitude of benefit would vary by sex, native disease, age, or type of transplant operation. To test these hypotheses, we conducted a secondary analysis using QOL data prospectively and serially measured with the Medical Outcomes Study 36-Item Short-Form Health Survey, version 2 (SF-36) in a multicenter cytomegalovirus prevention clinical trial. Linear mixed-effects models were used to assess the impact of transplantation on the recipient’s QOL. Results: Over the first year after lung transplantation, the SF-36 Physical Component Score significantly increased an average of 10.9 points from baseline levels (P < .0001). A positive benefit was observed for all native diseases; however, the magnitude varied slightly by native disease (P = .04) but not by sex (P = .35), age (P = .06), or transplant type (P = .30). In contrast, the SF-36 Mental Component Score did not change from baseline (P = .36) and remained well below population norms. Conclusions: Our results demonstrate that lung transplantation confers clinically important QOL benefits in physical domains but not in psychologic well-being. A better understanding of the barriers to psychologic well-being after transplant is critical to enhancing the benefits of lung transplantation. PMID:23188377
Lee, Janet T; Kelly, Rosemary F; Hertz, Marshall I; Dunitz, Jordan M; Shumway, Sara J
Clostridium difficile infection (CDI) and associated mortality in solid organ transplant recipients is rising, but data are scarce in lung transplant recipients. We aimed to characterize CDI and its effect on mortality in a large cohort of lung transplant recipients. Lung transplant recipients were identified from our transplant database from 2000 to 2011. Cox proportional hazard models were used to calculate hazard ratios for CDI and death after adjusting for potential confounders identified from bivariate analysis. We identified 388 patients (196 female, 192 male), with a median age of 56 years (range, 8-75 years), during the study period. CDI developed after transplant in 89 (22.9%), with 27 (7.0%) developing CDI during the initial hospitalization at a mean diagnosis of 12.7 ± 11.4 days. Incidence varied widely each year (median, 24%; range, 5%-32%), with the highest rates in 2007 to 2008. Post-operative length of stay was identified as a significant predictor of CDI (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03). Early CDI was an independent significant predictor of death (HR, 1.96; 95% CI, 1.14-3.36) as well as CDI anytime after transplant (HR, 1.61; 95% CI, 1.02-2.52). CDI rates varied widely from 2000 through 2011, with the highest rates in 2007 to 2008. Lung transplant recipients who developed CDI had a higher risk of death, especially when CDI occurred in the first 6 months after transplant. © 2013 International Society for Heart and Lung Transplantation. All rights reserved.
Cerón Navarro, José; de Aguiar Quevedo, Karol; Ansótegui Barrera, Emilio; Jordá Aragón, Carlos; Peñalver Cuesta, Juan Carlos; Mancheño Franch, Nuria; Vera Sempere, Francisco José; Padilla Alarcón, Jose
Lung transplantation (LT) is a therapeutic option with controversial results in chronic obstructive pulmonary disease (COPD). We aimed to analyze the outcomes of transplantation in terms of lung function and to identify prognostic factors. A retrospective analysis of 107 patients with COPD receiving lung transplants in the La Fe Hospital between 1991 and 2008 was performed. Preoperative variables, pulmonary function tests before and after LT, surgical procedure variables and long-term monitoring, expressed as mean or percentage, as applicable, were analyzed. Spirometric results before and after LT were analyzed. Linear or logistic regression were used for multivariate analysis depending on the variable. Ninety-four men (87.9%) and 13 women (12.1%) were transplanted, with a mean age±standard deviation of 52.58±8.05 years; 71% of LTs were double-lung transplantations. Spirometric values improved after LT: FVC: +1.22L (+34.9%), FEV1: +1.66L (+56.7%) and FEF25-75: +1.85L (+50.8%); P=.001. This functional improvement was maintained after 5 years only in the group with BODE score >7 (P=.001). Recipient height, type of LT, use of extracorporeal circulation during the surgical procedure, presence of bronchiolitis obliterans syndrome and the age and cause of death of the donor significantly influenced lung function over time. LT improves lung function in COPD patients. This improvement was maintained at 5years only in patients with BODE>7. Double lung transplantation provides better functional results than single-lung transplantation. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.
Vadnerkar, Aniket; Clancy, Cornelius J; Celik, Umit; Yousem, Samuel A; Mitsani, Dimitra; Toyoda, Yoshiya; Nguyen, Minh-Ly; Kwak, Eun J; Pilewski, Joseph; Silveira, Fernanda P; Crespo, Maria; Nguyen, M Hong
Little is known about the incidence or significance of mold infections in the explanted lungs of lung transplant recipients. We reviewed the histopathology of the explanted lungs from 304 patients who underwent lung transplantation at our institution from 2005 to 2007 and received alemtuzumab induction therapy and posttransplant voriconazole prophylaxis. Invasive mold infections were present in the explanted lungs of 5% (14 of 304) of patients, including chronic necrotizing pneumonias (n=7), mycetomas (n=4), and invasive fungal pneumonias (n=3). Only 21% (3 of 14) received immunosuppressive therapy within 1 year before lung transplantation, suggesting that lung damage itself predisposed patients to mold infections. The risk of mold infection was higher in patients with cystic fibrosis (11%, 4 of 35) than other underlying lung diseases (4%, 10 of 269). Pulmonary mold infections were not diagnosed or suspected in 57% (8 of 14) of patients. Despite secondary voriconazole prophylaxis, fungal infections developed in 43% (6 of 14) of patients with mold infections of the explanted lungs compared with 14% (42 of 290) of patients without mold infections (P=0.01). Three patients developed invasive fungal infections while on voriconazole prophylaxis and three developed fungal infections more than 8 months after the discontinuation of voriconazole. The mortality attributable to invasive fungal infections among patients with mold infections of the explanted lungs was 29% (4 of 14). Invasive mold infections in the explanted lungs are often not recognized before lung transplantation and are associated with poor outcomes.
Kusano, Kengo F
Pulmonary hypertension (PH) is a progressive disease characterized by sustained elevation in pulmonary arterial pressure and increased pulmonary vascular resistance, leading to right-sided ventricular failure. The untreated median survival period is 2-3 years from the time of diagnosis, with the cause of death usually being right-sided ventricular failure. However, outcomes have dramatically changed in recent years because of great advances in medical management of PH, including early diagnosis and new drugs such as prostaglandins, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. Long-term continuous intravenous prostacyclin therapy has shown excellent results in patients with PH. More recently, a molecular-targeted agent, imatinib mesylate, that acts by specifically inhibiting a certain enzyme that is characteristic of a particular cancer cell, rather than nonspecifically inhibiting and killing all rapidly dividing cells, has also been shown to have a potential role in the treatment of PH. This drug has been shown to reduce both pulmonary arterial smooth muscle cell hypertrophy and hyperplasia in a variety of disease processes. We summarize here recent topics regarding PH and advances in treatments for PH, particularly pulmonary arterial hypertension, including lung transplantation.
Rashtak, Shadi; Dierkhising, Ross A; Kremers, Walter K; Peters, Steve G; Cassivi, Stephen D; Otley, Clark C
Relative to other solid-organ transplantations, limited studies characterize skin cancer among lung-transplant recipients. We sought to assess the cumulative incidence, tumor burden, and risk factors for skin cancer among patients with lung transplantation. Medical records of patients at Mayo Clinic who had undergone lung transplantation between 1990 and 2011 were reviewed (N = 166). At 5 and 10 years posttransplantation the cumulative incidence was 31% and 47% for any skin cancer, 28% and 42% for squamous cell carcinoma, 12% and 21% for basal cell carcinoma, and 53% and 86% for death, respectively. Four patients died of metastatic squamous cell carcinoma. The cumulative incidence for a subsequent skin cancer of the same type 4 years after an initial skin cancer was 85% and 43% for squamous and basal cell carcinoma, respectively. Increasing age, male gender, skin cancer history, and more recent year of transplantation were associated with increased risk of skin cancer posttransplantation. Sirolimus was not associated with decreased risk, nor did voriconazole show an increased risk for skin cancer. Retrospective and tertiary single-center design of the study is a limitation. Skin cancers frequently occur in lung-transplant recipients. The risk of subsequent skin cancer is increased substantially in patients who develop a skin cancer after their transplantation. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Silhan, Leann L.; Shah, Pali D.; Chambers, Daniel C.; Snyder, Laurie D.; Riise, Gerdt C.; Wagner, Christa L.; Hellström-Lindberg, Eva; Orens, Jonathan B.; Mewton, Juliette F.; Danoff, Sonye K.; Arcasoy, Murat O.; Armanios, Mary
Lung transplantation is the only intervention that prolongs survival in idiopathic pulmonary fibrosis (IPF). Telomerase mutations are the most common identifiable genetic cause of IPF, and at times, the telomere defect manifests in extrapulmonary disease such as bone marrow failure. The relevance of this genetic diagnosis for lung transplant management has not been examined. We gathered an international series of telomerase mutation carriers who underwent lung transplant in the USA, Australia and Sweden. The median age at transplant was 52 years. Seven recipients are alive with a median follow-up of 1.9 years (range 6 months to 9 years); one died at 10 months. The most common complications were haematological, with recipients requiring platelet transfusion support (88%) and adjustment of immunosuppressives (100%). Four recipients (50%) required dialysis for tubular injury and calcineurin inhibitor toxicity. These complications occurred at significantly higher rates relative to historic series (p<0.0001). Our observations support the feasibility of lung transplantation in telomerase mutation carriers; however, severe post-transplant complications reflecting the syndromic nature of their disease appear to occur at higher rates. While these findings need to be expanded to other cohorts, caution should be exercised when approaching the transplant evaluation and management of this subset of pulmonary fibrosis patients. PMID:24833766
Silhan, Leann L; Shah, Pali D; Chambers, Daniel C; Snyder, Laurie D; Riise, Gerdt C; Wagner, Christa L; Hellström-Lindberg, Eva; Orens, Jonathan B; Mewton, Juliette F; Danoff, Sonye K; Arcasoy, Murat O; Armanios, Mary
Lung transplantation is the only intervention that prolongs survival in idiopathic pulmonary fibrosis (IPF). Telomerase mutations are the most common identifiable genetic cause of IPF, and at times, the telomere defect manifests in extrapulmonary disease such as bone marrow failure. The relevance of this genetic diagnosis for lung transplant management has not been examined. We gathered an international series of telomerase mutation carriers who underwent lung transplant in the U.S.A., Australia and Sweden. The median age at transplant was 52 years. Seven recipients are alive with a median follow-up of 1.9 years (range 6 months to 9 years); one died at 10 months. The most common complications were haematological, with recipients requiring platelet transfusion support (88%) and adjustment of immunosuppressives (100%). Four recipients (50%) required dialysis for tubular injury and calcineurin inhibitor toxicity. These complications occurred at significantly higher rates relative to historic series (p<0.0001). Our observations support the feasibility of lung transplantation in telomerase mutation carriers; however, severe post-transplant complications reflecting the syndromic nature of their disease appear to occur at higher rates. While these findings need to be expanded to other cohorts, caution should be exercised when approaching the transplant evaluation and management of this subset of pulmonary fibrosis patients. © ERS 2014.
Mohamed, Mohamed Shehata Ali
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.
Gracon, Adam S A; Wilkes, David S
Despite significant medical advances since the advent of lung transplantation, improvements in long-term survival have been largely unrealized. Chronic lung allograft dysfunction, in particular obliterative bronchiolitis, is the primary limiting factor. The predominant etiology of obliterative bronchiolitis involves the recipient's innate and adaptive immune response to the transplanted allograft. Current therapeutic strategies have failed to provide a definitive treatment paradigm to improve long-term outcomes. Inducing immune tolerance is an emerging therapeutic strategy that abrogates allograft rejection, avoids immunosuppression, and improves long-term graft function. The aim of this review is to discuss the key immunologic components of obliterative bronchiolitis, describe the state of establishing immune tolerance in transplantation, and highlight those strategies being evaluated in lung transplantation.
Cui, Ye; Liu, Kaifeng; Lamattina, Anthony Mark; Visner, Gary; El-Chemaly, Souheil
Lymphatic vessels are essential for the uptake of fluid, immune cells, macromolecules, and lipids from the interstitial space. During lung transplant surgery, the pulmonary lymphatic vessel continuum is completely disrupted, and, as a result, lymphatic drainage function is severely compromised. After transplantation, the regeneration of an effective lymphatic drainage system plays a crucial role in maintaining interstitial fluid balance in the lung allograft. In the meantime, these newly formed lymphatic vessels are commonly held responsible for the development of immune responses leading to graft rejection, because they are potentially capable of transporting antigen-presenting cells loaded with allogeneic antigens to the draining lymph nodes. However, despite remarkable progress in the understanding of lymphatic biology, there is still a paucity of consistent evidence that demonstrates the exact impacts of lymphatic vessels on lung graft function. In this review, we examine the current literature related to roles of lymphatic vessels in the pathogenesis of lung transplant rejection.
Coleman, Bernice; Blumenthal, Nancy; Currey, Judy; Dobbels, Fabienne; Velleca, Angela; Grady, Kathleen L; Kugler, Christiane; Murks, Catherine; Ohler, Linda; Sumbi, Christine; Luu, Minh; Dark, John; Kobashigawa, Jon; White-Williams, Connie
The role of nurses in cardiothoracic transplantation has evolved over the last 25 years. Transplant nurses work in a variety of roles in collaboration with multidisciplinary teams to manage complex pre- and post-transplantation issues. There is lack of clarity and consistency regarding required qualifications to practice transplant nursing, delineation of roles and adequate levels of staffing. A consensus conference with workgroup sessions, consisting of 77 nurse participants with clinical experience in cardiothoracic transplantation, was arranged. This was followed by subsequent discussion with the ISHLT Nursing, Health Science and Allied Health Council. Evidence and expert opinions regarding key issues were reviewed. A modified nominal group technique was used to reach consensus. Consensus reached included: (1) a minimum of 2 years nursing experience is required for transplant coordinators, nurse managers or advanced practice nurses; (2) a baccalaureate in nursing is the minimum education level required for a transplant coordinator; (3) transplant coordinator-specific certification is recommended; (4) nurse practitioners, clinical nurse specialists and nurse managers should hold at least a master's degree; and (5) strategies to retain transplant nurses include engaging donor call teams, mentoring programs, having flexible hours and offering career advancement support. Future research should focus on the relationships between staffing levels, nurse education and patient outcomes. Delineation of roles and guidelines for education, certification, licensure and staffing levels of transplant nurses are needed to support all nurses working at the fullest extent of their education and licensure. This consensus document provides such recommendations and draws attention to areas for future research. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Zaki, Khawaja S; Aryan, Zahra; Mehta, Atul C; Akindipe, Olufemi; Budev, Marie
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
Zhao, Y; Al-Kaade, S; Keller, C A; deMello, D E
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.
Reitz, B A; Gaudiani, V A; Hunt, S A; Wallwork, J; Billingham, M E; Oyer, P E; Baumgartner, W A; Jamieson, S W; Stinson, E B; Shumway, N E
Six patients received heart-lung transplants between March, 1981, and January, 1982. There were four women and two men between 26 and 45 years of age, three with primary pulmonary hypertension and three with congenital heart disease and pulmonary hypertension (Eisenmenger's syndrome). Immunosuppression was primarily with cyclosporin-A, with additional corticosteroid, azathioprine, and rabbit antihuman thymocyte globulin. Six episodes of allograft rejection in four patients (10, 11, 21, 24, 53, and 86 days after transplantation) were detected by means of transvenous endomyocardial biopsy. All patients experienced pulmonary edema early after transplantation (reimplantation response), and two patients required mechanical ventilatory support for allograft rejection at 10 and 11 days. Treatment of rejection consisted of intravenous methylprednisolone (four episodes) or augmented oral prednisone (two episodes), with resolution. No episode thought to be pulmonary rejection has occurred in the absence of cardiac findings. Four patients are alive from 6 to 15 months after transplantation and are functionally normal. Early experience with heart-lung transplantation suggests (1) that allograft rejection can be detected by cardiac findings and successfully treated by augmented corticosteroids, (2) that lung rejection does not occur in the absence of cardiac findings, (3) that the frequency and severity of rejection episodes are not greater than with standard cardiac transplantation, and (4) that the frequency of rejection episodes is highest within the first 60 days after transplantation.
Rosen, J B; Schecter, M G; Heinle, J S; McKenzie, E D; Morales, D L; Dishop, M K; Danziger-Isakov, L; Mallory, G B; Elidemir, O
Risk factors for Clostridium difficile diarrhea are antibiotic exposure, hospitalization, extreme ages, and immunodeficiency. Patients with CF have a high rate of colonization with C. difficile. We performed a retrospective chart review of patients at Texas Children's Hospital who underwent lung transplantation since the inception of our program in October 2002 until October 2008. There were 78 pediatric lung transplants performed at our institution during the study period. Four patients developed six total episodes of CDC for an overall incidence of 5.4%. CF was the underlying diagnosis in all four patients, leading to an incidence of 8.9% in patients with CF. Two patients developed colitis within the first four months following transplant, and the other two patients developed colitis more than three yr after transplantation. All four patients required hospitalization, and three patients were managed medically while one patient underwent diverting ileostomy. One experienced renal insufficiency and subsequently expired. Overall survival was 75% among patients with CDC following lung transplantation. CDC causes significant morbidity and mortality in children with CF who have undergone lung transplantation.
Toyooka, Shinichi; Waki, Naohisa; Okazaki, Megumi; Kato, Katsuya; Yamane, Masaomi; Oto, Takahiro; Sano, Yoshifumi; Date, Hiroshi
We describe a case of lung cancer in a living-donor lobar lung transplantation (LDLLT) recipient that was identified because of a recurrence in the mediastinum. The patient was a 55-year-old woman who had undergone bilateral LDLLT for nonspecific interstitial pneumonia. She developed dyspnea upon exertion at 15 months after transplantation and was diagnosed as suffering from chronic rejection. A computed tomography scan also revealed enlarged mediastinal lymph nodes (LNs) that were subsequently confirmed as poorly differentiated squamous cell carcinomas. Retrospectively, a small tumor was found in the explanted right lung tissue, the microscopic findings of which were similar to those of the mediastinal lesion. A whole body examination revealed no other lesions; thus we resected the LNs and subsequently irradiated the mediastinum. Recurrent disease appeared in her transplanted lungs 10 months after resection of the LNs, and she died of pneumonia with chronic rejection 2 years and 7 months after transplantation.
Angel, Luis F; Levine, Deborah J; Restrepo, Marcos I; Johnson, Scott; Sako, Edward; Carpenter, Andrea; Calhoon, John; Cornell, John E; Adams, Sandra G; Chisholm, Gary B; Nespral, Joe; Roberson, Ann; Levine, Stephanie M
One of the limitations associated with lung transplantation is the lack of available organs. To determine whether a lung donor-management protocol could increase the number of lungs for transplantation without affecting the survival rates of the recipients. We implemented the San Antonio Lung Transplant protocol for managing potential lung donors according to modifications of standard criteria for donor selection and strategies for donor management. We then compared information gathered during a 4-yr period, during which the protocol was used with information gathered during a 4-yr period before protocol implementation. Primary outcome measures were the procurement rate of lungs and the 30-d and 1-yr survival rates of recipients. We reviewed data from 711 potential lung donors. The mean rate of lung procurement was significantly higher (p < 0.0001) during the protocol period (25.5%) than during the pre-protocol period (11.5%), with an estimated risk ratio of 2.2 in favor of the protocol period. More patients received transplants during the protocol period (n = 121) than during the pre-protocol period (n = 53; p < 0.0001). Of 98 actual lung donors during the protocol period, 53 (54%) had initially been considered poor donors; these donors provided 64 (53%) of the 121 lung transplants. The type of donor was not associated with significant differences in recipients' 30-d and 1-yr survival rates or any clinical measures of adequate graft function. The protocol was associated with a significant increase in the number of lung donors and transplant procedures without compromising pulmonary function, length of stay, or survival of the recipients.
Weinkauf, J G; Puttagunta, L; Nador, R; Jackson, K; LaBranche, K; Kapasi, A; Mullen, J; Modry, D L; Stewart, K C; Thakrar, M; Doucette, K; Lien, D C
Talc lung granulomatosis results from the intravenous use of medication intended for oral use. Talc (magnesium silicate) acts as filler in some oral medications; when injected intravenously, it deposits in the lungs leading to airflow obstruction and impaired gas exchange. Allocation of donor lungs to previous intravenous drug users is controversial. After a careful selection process, 19 patients with talc lung granulomatosis have received lung allografts in our program. Long-term survival for these patients is excellent and our results suggest the previous use of intravenous drugs should not necessarily preclude lung transplantation.
Boyer, Nathan Lewis; Niven, Alexander; Edelman, Jeffery
A 25-year-old woman with a history of bilateral lung transplant secondary to cystic fibrosis presented with non-specific abdominal complaints and was found to have acute kidney injury, thrombocytopaenia and laboratory findings consistent with a microangiopathic haemolytic anaemia. Her thrombotic microangiopathy (TMA) was attributed to tacrolimus, which was discontinued and replaced with cyclosporine with resolution of her TMA and no subsequent complications. This is the fifth reported case of TMA associated with tacrolimus use in a lung transplant patient, and the third to be successfully managed with cyclosporine substitution. Clinicians must be aware of this uncommon, but likely under-reported complication of tacrolimus therapy in lung transplant recipients. Cyclosporine replacement may be used as a successful therapy to treat tacrolimus-associated TMA without increasing the risk of acute rejection that may be associated with other treatment strategies. PMID:23396921
Hartwig, M G; Ganapathi, A M; Osho, A A; Hirji, S A; Englum, B R; Speicher, P J; Palmer, S M; Davis, R D; Snyder, L D
The choice of a single or bilateral lung transplant for interstitial lung disease (ILD) is controversial, as surgical risk, long-term survival and organ allocation are competing factors. In an effort to balance risk and benefit, our center adopted a staged bilateral lung transplant approach for higher surgical risk ILD patients where the patient has a single lung transplant followed by a second single transplant at a later date. We sought to understand the surgical risk, organ allocation and early outcomes of these staged bilateral recipients as a group and in comparison to matched single and bilateral recipients. Our analysis demonstrates that staged bilateral lung transplant recipients (n = 12) have a higher lung allocation score (LAS), lower pulmonary function tests and a lower glomerular filtration rate prior to the first transplant compared to the second (p < 0.01). There was a shorter length of hospital stay for the second transplant (p = 0.02). The staged bilateral compared to the single and bilateral case-matched controls had comparable short-term survival (p = 0.20) and pulmonary function tests at 1 year. There was a higher incidence of renal injury in the conventional bilateral group compared to the single and staged bilateral groups. The staged bilateral procedure is a viable option in select ILD patients.
Rajagopal, Keshava; Hoeper, Marius M
Lung transplantation increasingly is being performed in recipients of higher risk and acuity. A subset of these patients has severely abnormal gas exchange and/or right ventricular dysfunction, such that artificial organ support strategies are required to bridge patients to lung transplantation. We review the rationales and currently used and potential strategies for bridging to lung transplantation and characterize bridging outcomes. Based on physiologic reasoning and a study of the existing literature, we provide a working strategy for bridging to lung transplantation.
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
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
Cassir, Nadim; Delacroix, Robin; Gomez, Carine; Secq, Véronique; Reynaud-Gaubert, Martine; Thomas, Pascal-Alexandre; Papazian, Laurent; Drancourt, Michel
Abstract Rationale: Solid organ transplant recipients, especially after lung transplantation, are at increased risk for Mycobacterium tuberculosis pulmonary tuberculosis due to lifelong immunosuppression. Patient concerns: A 41-year-old woman underwent a second bilateral lung transplantation that was complicated by fatal pulmonary tuberculosis. Diagnoses: Histological examination of a lung biopsy performed 6 weeks after retransplantation revealed a caseating granuloma and necrosis. Acid-fast bacilli were identified as rifampicin-susceptible M. tuberculosis by real-time polymerase chain reaction (PCR), confirmed by culture 2 weeks later. Interventions: Our investigation led us to highly suspect that the transplanted lungs were the source of M. tuberculosis transmission. Lessons: In order to optimize diagnosis and treatment for lung recipients with latent or active tuberculosis, regular assessment of lower respiratory samples for M. tuberculosis, particularly during the 12-month period posttransplant should be implemented. Regarding donor-derived transmission, screening donor grafts with latent tuberculosis by M. tuberculosis real-time PCR in lymphoid and adipose tissues is an option that should be considered. PMID:28353558
Weigt, S. Samuel; DerHovanessian, Ariss; Wallace, W. Dean; Lynch, Joseph P.; Belperio, John A.
Lung transplantation is a therapeutic option for patients with end-stage pulmonary disorders. Unfortunately, chronic lung allograft dysfunction (CLAD), most commonly manifest as bronchiolitis obliterans syndrome (BOS), continues to be highly prevalent and is the major limitation to long-term survival. The pathogenesis of BOS is complex and involves alloimmune and nonalloimmune pathways. Clinically, BOS manifests as airway obstruction and dyspnea that are classically progressive and ultimately fatal; however, the course is highly variable, and distinguishable phenotypes may exist. There are few controlled studies assessing treatment efficacy, but only a minority of patients respond to current treatment modalities. Ultimately, preventive strategies may prove more effective at prolonging survival after lung transplantation, but their remains considerable debate and little data regarding the best strategies to prevent BOS. A better understanding of the risk factors and their relationship to the pathological mechanisms of chronic lung allograft rejection should lead to better pharmacological targets to prevent or treat this syndrome. PMID:23821508
Snyder, L D; Gray, A L; Reynolds, J M; Arepally, G M; Bedoya, A; Hartwig, M G; Davis, R D; Lopes, K E; Wegner, W E; Chen, D F; Palmer, S M
As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value, providing an estimate of the effective donor pool. For broadly sensitized lung transplant candidates (cPRA ≥ 80%), our center adopted a pretransplant multi-modal desensitization protocol in an effort to decrease the cPRA and expand the donor pool. This desensitization protocol included plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19 days followed by intravenous immunoglobulin. Eight of 18 candidates completed therapy with the primary reasons for early discontinuation being transplant (by avoiding unacceptable antigens) or thrombocytopenia. In a mixed-model analysis, there were no significant changes in PRA or cPRA changes over time with the protocol. A sub-analysis of the median fluorescence intensity (MFI) change indicated a small decline that was significant in antibodies with MFI 5000-10,000. Nine of 18 candidates subsequently had a transplant. Posttransplant survival in these nine recipients was comparable to other pretransplant-sensitized recipients who did not receive therapy. In summary, an aggressive multi-modal desensitization protocol does not significantly reduce pretransplant HLA antibodies in a broadly sensitized lung transplant candidate cohort. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.
Ollech, Jacob E; Kramer, Mordechai R; Peled, Nir; Ollech, Ayelet; Amital, Anat; Medalion, Benjamin; Saute, Milton; Shitrit, David
Post-transplant diabetes mellitus (PTDM) is a common and potentially serious complication after solid organ transplantation. There are only a few data, however, about the incidence of DM in patients undergoing lung transplantation. The medical records of 119 consecutive patients who underwent lung transplantation from 1998 to September 2004 were reviewed. Patients were divided in three groups according to their diabetes status, including pre-transplant DM, the PTDM group and those without DM. Patient records and all laboratory data were reviewed and the clinical course of diabetes was monitored. All recipients were treated with tacrolimus based regimen. Mean follow-up for all patients was 25+/-10. Twenty-three patients had DM in the pre-lung transplantation (LTX) DM group. PTDM developed in 34 of the remaining 96 patients (35.4%) with an incidence of 20%, 23% after 6 months and 12 months post-transplant. No significant difference was noted between 12 and 24 months post-LTX. The patients who developed DM were older (57+/-15 vs 53+/-13 years, p=0.009), had increased BMI (26+/-5 vs 24+/-4, p=0.0001), shorter time from diagnosis to LTX (21+/-13 vs 28+/-18 months, p=0.007) more cytomegalovirus infection and more acute rejection and hyperglycemia in the first month after LTX. Four patients died in the PTDM group compared to nine patients in the no-DM group (12% vs 14%; p=0.72). Post-transplant diabetes is a common complication in lung transplant patients receiving tacrolimus-based immunosuppression. The risk for developing PTDM is greatest among older recipients, those obese, and among recipients with more rejections episodes.
Gordon, Ilyssa O; Bhorade, Sangeeta; Vigneswaran, Wickii T; Garrity, Edward R; Husain, Aliya N
The International Society for Heart and Lung Transplantation (ISHLT) guidelines on the interpretation of lung rejection in pulmonary allograft biopsy specimens were revised most recently in 2007. The goal of our study was to determine how these revisions, along with nuances in the interpretation and application of the guidelines, affect patient care. A Web-based survey was e-mailed to pathologists and pulmonologists identified as being part of the lung transplant team at institutions in the United States with active lung transplant programs as determined from the Organ Procurement and Transplantation Network Web site (http://optn.transplant.hrsa.gov/members/directory.asp). Grades B1 and B2 in asymptomatic patients would fall into the same treatment group under the 2007 classification, which combines B1 and B2 into B1R. Also, some pulmonologists would not interpret a pathologic diagnosis of lymphocytic bronchiolitis as grade B rejection, resulting in under-treatment of these patients. Regarding bronchiolitis obliterans, most pulmonologists would treat the patient differently if there were an active mononuclear inflammatory infiltrate, and most pathologists would comment on the presence of such an infiltrate, contrary to the 2007 guidelines, which discourage reporting this infiltrate. We also found discrepancies among pathologists in their interpretation of airway lymphocytic infiltrates, whether eosinophils can be present in bronchial-associated lymphoid tissue, and whether airway inflammation represents rejection or bacterial infection. The issue of grading and treating airway inflammation in pulmonary allograft biopsy specimens continues to be problematic, despite revised ISHLT guidelines. Clarification of guidelines for pathologists and pulmonologists using evidence-based criteria could lead to improved communication and patient care. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Roux, Antoine; Beaumont-Azuar, Laurence; Hamid, Abdul Monem; De Miranda, Sandra; Grenet, Dominique; Briend, Guillaume; Bonnette, Pierre; Puyo, Philippe; Parquin, François; Devaquet, Jerome; Trebbia, Gregoire; Cuquemelle, Elise; Douvry, Benoit; Picard, Clément; Le Guen, Morgan; Chapelier, Alain; Stern, Marc; Sage, Edouard
Many candidates for lung transplantation (LT) die on the waiting list, raising the question of graft availability and strategy for organ allocation. We report the experience of the new organ allocation program, "High Emergency Lung Transplantation" (HELT), since its implementation in our center in 2007. Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT from 1st July 2007 to 31th May 2012. HELT candidates had a higher impairment grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients had increased incidence of perioperative complications (e.g., perioperative bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, P = 0.0005). No significant difference was observed between HELT and non-HELT patients in mechanical ventilation duration (15.5 days vs. 11 days, P = 0.27), intensive care unit length of stay (15 days vs. 10 days, P = 0.22) or survival rate at 12 (81% vs. 80%), and 24 months post-LT (72.9% vs. 75.0%). Lastly, mortality on the waiting list was spectacularly reduced from 19% to 2% when compared to the non-HELT 2004-2007 group. Despite a more severe clinical status of patients on the waiting list, HELT provided similar results to conventional LT. These results were associated with a dramatic reduction in the mortality rate of patients on the waiting list.
Monemian, Sharifeh; Abedi, Heidarali; Naji, Saied Ali
Introduction: Heart transplantation is considered as a golden standard of treatment for advanced heart failure. After - transplantation health of patients is influenced by numerous issues which many of them are unknown to the treatment team including nurses. This research - with the aim of describing the life experiences of heart transplant patients - help us to get close to the patients private life and gain comprehensive and a general understanding of all aspects of their life. Methods: This study applied qualitative approach using phenomenology method. The purposive sampling was conducted and continued with 9 participants until information reached saturation point. The participants are the heart transplant recipients who had surgery in Esfahan's Heart Surgery Center of Shahid Chamran. Results: The extracted interviews were analyzed through Colaizzi method: The eleven extracted main concepts were included: Belief, tendencies of the recipient and family of donor, bewilderment, moment of facing with transplantation, satisfaction, vital organ, support, temperament, physical effects of transplantation, mental changes, paradox of life and death. Conclusion: In heart transplant patients, being in touch with peers and family support have an important role in putting up with the transplantation issue. Lack of social situation and social support were among the patients distresses. Lack of the necessary information about transplantation made patients dissatisfied with the heart transplantation. Regarding the research findings, training received by patients would not be suffice and lack of information has been made them face with problems; therefore, the nurse team of transplantation should play more an active role in training the patients. PMID:25861663
Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita
Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID:27683630
Layton, Aimee M; Armstrong, Hilary F; Baldwin, Matthew R; Podolanczuk, Anna J; Pieszchata, Nicole M; Singer, Jonathan P; Arcasoy, Selim M; Meza, Kimberly S; D'Ovidio, Frank; Lederer, David J
Frail lung transplant candidates are more likely to be delisted or die without receiving a transplant. Further knowledge of what frailty represents in this population will assist in developing interventions to prevent frailty from developing. We set out to determine whether frail lung transplant candidates have reduced exercise capacity independent of disease severity and diagnosis. Sixty-eight adult lung transplant candidates underwent cardiopulmonary exercise testing (CPET) and a frailty assessment (Fried's Frailty Phenotype (FFP)). Primary outcomes were peak workload and peak aerobic capacity (V˙O2). We used linear regression to adjust for age, gender, diagnosis, and lung allocation score (LAS). The mean ± SD age was 57 ± 11 years, 51% were women, 57% had interstitial lung disease, 32% had chronic obstructive pulmonary disease, 11% had cystic fibrosis, and the mean LAS was 40.2 (range 19.2-94.5). In adjusted models, peak workload decreased by 10 W (95% CI 4.7 to 14.6) and peak V˙O2 decreased by 1.8 mL/kg/min (95% CI 0.6 to 2.9) per 1 unit increment in FFP score. After adjustment, exercise tolerance was 38 W lower (95% CI 18.4 to 58.1) and peak V˙O2 was 8.5 mL/kg/min lower (95% CI 3.3 to 13.7) among frail participants compared to non-frail participants. Frailty accounted for 16% of the variance (R(2)) of watts and 19% of the variance of V˙O2 in adjusted models. Frailty contributes to reduced exercise capacity among lung transplant candidates independent of disease severity. Copyright © 2017 Elsevier Ltd. All rights reserved.
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
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).
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
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
Lobo, Leonard J; Noone, Peadar G
Cystic fibrosis is an inherited disease characterised by chronic respiratory infections associated with bronchiectasis. Lung transplantation has helped to extend the lives of patients with cystic fibrosis who have advanced lung disease. However, persistent, recurrent, and newly acquired infections can be problematic. Classic cystic fibrosis-associated organisms, such as Staphylococcus aureus and Pseudomonas aeruginosa, are generally manageable post-transplantation, and are associated with favourable outcomes. Burkholderia cenocepacia poses particular challenges, although other Burkholderia species are less problematic. Despite concerns about non-tuberculous mycobacteria, especially Mycobacterium abscessus, post-transplantation survival has not been definitively shown to be less than average in patients with these infections. Fungal species can be prevalent before and after transplantation and are associated with high morbidity, so should be treated aggressively. Appropriate viral screening and antiviral prophylaxis are necessary to prevent infection with and reactivation of Epstein-Barr virus and cytomegalovirus and their associated complications. Awareness of drug pharmacokinetics and interactions in cystic fibrosis is crucial to prevent toxic effects and subtherapeutic or supratherapeutic drug dosing. With the large range of potential infectious organisms in patients with cystic fibrosis, infection control in hospital and outpatient settings is important. Despite its complexity, lung transplantation in the cystic fibrosis population is safe, with good outcomes if the clinician is aware of all the potential pathogens and remains vigilant by means of surveillance and proactive treatment.
Wehman, Brody; Griffith, Bartley P; Balwan, Akshu; Kon, Zachary N; Suffredini, Dante A; Evans, Charles; Garcia, Jose P; Iacono, Aldo
Alemtuzumab is a commonly used induction agent for solid-organ transplantation. Its use in lung transplantation with reduced immunosuppressive regimens, however, has yet to be well characterized. From November 2006 to March 2008, 20 consecutive lung transplantation patients received alemtuzumab induction with a reduced maintenance immunosuppression regimen. Twenty consecutive case-controls who underwent transplantation between 2005 and 2006 were treated with a standard immunosuppression regimen without induction. Outcome variables were patient survival, acute rejection, infection, and bronchiolitis obliterans syndrome. Mean follow-up time was 1400 days in the alemtuzumab group and 1210 days in the control group. Double lung transplantation was performed in 21 patients (12 in the alemtuzumab group and 9 in the control group). There was no difference in survival between the alemtuzumab (n = 10) and control (n = 10) groups. There was also not a significant difference in time-adjusted death based on Kaplan-Meier analysis. The mean number of any grade of rejection event per patient was not significantly different (alemtuzumab 2.3 ± 2.7 vs. control 3.2 ± 2.35; P = .22). There was a trend toward the reduced incidence of infection requiring intravenous antibiotics per patient (alemtuzumab 2.4 vs. control 3.8; P = .08). The incidence of bronchiolitis obliterans syndrome was similar in both groups (alemtuzumab 55% vs. control 70%; P = .25). Alemtuzumab induction with reduced immunosuppression offers a comparable 5-year survival and rejection rate compared to standard-dose immunosuppression regimen.
Wang, Ziwei; Chen, Dong-Feng; Reinsmoen, Nancy L.; Finlen-Copeland, C. Ashley; Davis, W. Austin; Zaas, David W.; Palmer, Scott M.
Background: Long-term survival after lung transplant is limited by the development of chronic and progressive airflow obstruction, a condition known as bronchiolitis obliterans syndrome (BOS). While prior studies strongly implicate cellular rejection as a strong risk factor for BOS, less is known about the clinical significance of human leukocyte antigen (HLA) antibodies and donor HLA-specific antibodies in long-term outcomes. Methods: A single-center cohort of 441 lung transplant recipients, spanning a 10-year period, was prospectively screened for HLA antibodies after transplant using flow cytometry-based methods. The prevalence of and predictors for HLA antibodies were determined. The impact of HLA antibodies on survival after transplant and the development of BOS were determined using Cox models. Results: Of the 441 recipients, 139 (32%) had detectable antibodies to HLA. Of these 139, 54 (39%) developed antibodies specific to donor HLA. The detection of posttransplant HLA antibodies was associated with BOS (HR, 1.54; P = .04) and death (HR, 1.53; P = .02) in multivariable models. The detection of donor-specific HLA antibodies was associated with death (HR, 2.42; P < .0001). The detection of posttransplant HLA antibodies was associated with pretransplant HLA-antibody detection, platelet transfusions, and the development of BOS and cytomegalovirus pneumonitis. Conclusions: Approximately one-third of lung transplant recipients have detectable HLA antibodies, which are associated with a worse prognosis regarding graft function and patient survival. PMID:23328795
Pencheva, Ventsislava P.; Petrova, Daniela S.; Genov, Diyan K.; Georgiev, Ognian B.
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
Dan, J M; Crespo, M; Silveira, F P; Kaplan, R; Aslam, S
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.
Sáenz, A; Alvarez, L; Santos, M; López-Sánchez, A; Castillo-Olivares, J L; Varela, A; Segal, R; Casals, C
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.
Osho, Asishana A; Hirji, Sameer A; Castleberry, Anthony W; Mulvihill, Michael S; Ganapathi, Asvin M; Speicher, Paul J; Yerokun, Babatunde; Snyder, Laurie D; Davis, Robert D; Hartwig, Mathew G
Kidney transplantation has been advocated as a therapeutic option in lung recipients who develop end-stage renal disease (ESRD). This analysis outlines patterns of allograft survival following kidney transplantation in previous lung recipients (KAL). Data from the UNOS lung and kidney transplantation registries (1987-2013) were cross-linked to identify lung recipients who were subsequently listed for and/or underwent kidney transplantation. Time-dependent Cox models compared the survival rates in KAL patients with those waitlisted for renal transplantation who never received kidneys. Survival analyses compared outcomes between KAL patients and risk-matched recipients of primary, kidney-only transplantation with no history of lung transplantation (KTx). A total of 270 lung recipients subsequently underwent kidney transplantation (KAL). Regression models demonstrated a lower risk of post-listing mortality for KAL patients compared with 346 lung recipients on the kidney waitlist who never received kidneys (P<.05). Comparisons between matched KAL and KTx patients demonstrated significantly increased risk of death and graft loss (P<.05), but not death-censored graft loss, for KAL patients (P = .86). KAL patients enjoy a significant survival benefit compared with waitlisted lung recipients who do not receive kidneys. However, KAL patients do poorly compared with KTx patients. Decisions about KAL transplantation must be made on a case-by-case basis considering patient and donor factors. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Sugimoto, Seiichiro; Otani, Shinji; Ohki, Takashi; Kurosaki, Takeshi; Miyoshi, Kentaroh; Yamane, Masaomi; Miyoshi, Shinichiro; Oto, Takahiro
Single living-donor lobar lung transplantation provides acceptable results for critically ill children; however, an additional lung transplantation may be required in the future as the recipient grows. We describe a case of successful lung retransplantation in a grown-up patient after single lobar lung transplantation in childhood. A 23-year-old man underwent bilateral cadaveric lung retransplantation for chronic lung allograft dysfunction 13 years after right single living-donor lobar transplantation for idiopathic pulmonary arterial hypertension performed at the age of 10 years. The postoperative course was uneventful. The patient had received growth hormone therapy at a local hospital for 3 years until the development of chronic lung allograft dysfunction after the initial transplantation. Pediatric recipients undergoing single living-donor lobar lung transplantation should be cautiously followed for potential retransplantation.
Camboni, Daniele; Philipp, Alois; Arlt, Matthias; Pfeiffer, Michael; Hilker, Michael; Schmid, Christof
Lung transplantation is the only treatment option for patients suffering form end-stage respiratory failure. To date, no mechanical device is available to support patients on the waiting list up to months. Here, we summarize our experience with our first two patients, who were supported with a paracorporeal artificial lung (PAL) placed in parallel to the pulmonary circulation with connection to the pulmonary artery and to the left atrium. A low resistance membrane oxygenator (iLA, Novalung, Hirrlingen, Germany) was attached in both patients. Our first patient suffering from a pulmonary veno-occlusive disease was supported for 18 days until he died due to severe sepsis. Our second patient with a primary pulmonary hypertension of unknown origin was supported 62 days followed by successful lung transplantation. In conclusion, the experience obtained with these first two patients under PAL encourages further studies and introduction of this promising concept into clinical practice.
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
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. © 2014 Steunstichting ESOT.
Fink, Aliza K; Yanik, Elizabeth L; Marshall, Bruce C; Wilschanski, Michael; Lynch, Charles F; Austin, April A; Copeland, Glenn; Safaeian, Mahboobeh; Engels, Eric A
Previous studies demonstrated increased digestive tract cancers among individuals with cystic fibrosis (CF), particularly among lung transplant recipients. We describe cancer incidence among CF and non-CF lung recipients. We used data from the US transplant registry and 16 cancer registries. Standardized incidence ratios (SIRs) compared cancer incidence to the general population, and competing risk methods were used for the cumulative incidence of colorectal cancer. We evaluated 10,179 lung recipients (1681 with CF). Risk was more strongly increased in CF recipients than non-CF recipients for overall cancer (SIR 9.9 vs. 2.7) and multiple cancers including colorectal cancer (24.2 vs. 1.7), esophageal cancer (56.3 vs. 1.3), and non-Hodgkin lymphoma (61.8 vs. 9.4). At five years post-transplant, colorectal cancer was diagnosed in 0.3% of CF recipients aged <50 at transplant and 6.4% aged ≥50. CF recipients have increased risk for colorectal cancer, suggesting a need for enhanced screening. Copyright © 2016 European Cystic Fibrosis Society. All rights reserved.
Snyder, L. D.; Gray, A. L.; Reynolds, J. M.; Arepally, G. M.; Bedoya, A.; Hartwig, M. G.; Davis, R. D.; Lopes, K. E.; Wegner, W. E.; Chen, D. F.; Palmer, S. M.
As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value, providing an estimate of the effective donor pool. For broadly sensitized lung transplant candidates (cPRA ≥ 80%), our center adopted a pretransplant multimodal desensitization protocol in an effort to decrease the cPRA and expand the donor pool. This desensitization protocol included plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19 days followed by intravenous immunoglobulin. Eight of 18 candidates completed therapy with the primary reasons for early discontinuation being transplant (by avoiding unacceptable antigens) or thrombocytopenia. In a mixed-model analysis, there were no significant changes in PRA or cPRA changes over time with the protocol. A sub-analysis of the median fluorescence intensity (MFI) change indicated a small decline that was significant in antibodies with MFI 5000–10 000. Nine of 18 candidates subsequently had a transplant. Posttransplant survival in these nine recipients was comparable to other pretransplant-sensitized recipients who did not receive therapy. In summary, an aggressive multi-modal desensitization protocol does not significantly reduce pretransplant HLA antibodies in a broadly sensitized lung transplant candidate cohort. PMID:24666831
Boyd, S Y; Sako, E Y; Trinkle, J K; O'Rourke, R A; Zabalgoitia, M
Single-lung transplantation (SLT) is a viable option for patients with end-stage pulmonary disease. After successful SLT, pulmonary blood flow is preferentially shifted to the transplanted lung, creating a flow differential. Lack of flow differential may be indicative of potential vascular complications such as anastomotic stenosis or thrombosis. To assess the ability of transesophageal echocardiography (TEE) in estimating lung flow differential in patients undergoing SLT, biplane TEE was prospectively performed in 18 consecutive patients undergoing SLT early (24 to 72 hours), and in 10 of them late (3 to 6 months) after surgery. Right and left pulmonary vein flow were calculated as Qnu=A. VTI, where A, the pulmonary vein area, was derived as pi.(D/2)(2) and VTI is the velocity time integral of the pulmonary vein spectral display. Lung flow differential was calculated as the ratio of right (RQnu) or left (LQnu) pulmonary vein flow to total pulmonary venous flow (RQnu + LQnu). Lung perfusion imaging scintigraphy (technetium-99m) was used for comparison. Pulmonary vein velocity time integral of transplanted lung was significantly greater than that of native lung (34 +/- 9 vs 18 +/- 8 cm, p <0.001). Percent differential lung flow derived by perfusion imaging scintigraphy and by TEE showed a good correlation (r = 0.67, p <0.001). Pulmonary artery anastomoses were seen in all 12 right-lung recipients, and in 4 of the 6 left-lung recipients; no significant stenosis was noted in the arteries visualized. The pulmonary venous anastomoses were imaged in all patients. Small, nonocclusive pulmonary vein thrombi were seen in 1 patient. In conclusion, TEE is a useful method for calculating lung flow differential in patients undergoing SLT. In addition, TEE provides superb direct visualization of the venous and arterial anastomoses in most patients. Contrary to previous reports, the overall incidence of anastomotic complications is relatively low.
Levin, Kovi; Kotecha, Sakhee; Westall, Glen; Snell, Gregory
Optimization of lungs for organ donation is becoming increasingly important as donation rates stagnate despite growing waiting lists. Improving procurement and utilization of donated lungs has the ability to reduce mortality and time on the lung transplantation (LTx) waiting list. Additionally, assessment and optimization of donor lungs can reduce both early and late post-LTx morbidity and mortality, as well as reduce overall costs and resource utility. Areas covered: Strategies that we will discuss in detail include intensive care management practices, such as targeted ventilation protocols and therapeutic bronchoscopy, as well as the ever expanding possibilities within the arena of ex vivo lung perfusion (EVLP). Expert commentary: Donor lung quality is currently optimized both in vivo prior to organ procurement, and also via EVLP circuits. Despite good evidence demonstrating the utility of both approaches, data remain elusive as to whether EVLP is beneficial for all donor lungs prior to implantation, or instead as a tool by which we can evaluate and recondition sub-optimal donor lungs.
Arame, A; Rivera, C; Borik, W; Mangiameli, G; Abdennahder, M; Pricopi, C; Bagan, P; Badia, A; Le Pimpec Barthes, F; Riquet, M
The incidence of lung cancer is reputed to be higher and prognosis worse in solid organ transplant recipients than in the general population. Our purpose was to review the results of surgery in this group of patients. We retrospectively reviewed 49 male and 6 female patients; mean aged 60.6 years (38-85). Transplanted organ was heart (n = 37), kidney (n=12), liver (n = 5) and both-lungs (n = 1); 48 patients had smoking habits and 42 heavy comorbidities (76.4%). Lung cancer was diagnosed during surveillance (78.2%, n = 43) or because of symptoms (21.8%, n = 12). We reviewed TNM and other main characteristics, among them histology (squamous-cell-carcinoma n = 23, adenocarcinomas n = 24, others n = 8). Surgery consisted of: exploratory thoracotomy (n = 2), wedge resections (n = 6), segmentectomy (n = 1), lobectomy (n = 42), pneumonectomy (n = 4). Postoperative mortality was 7.4% (n = 4) and complication rate 34.5% (n = 19). Five-year survival rate was 46.4% (65.4% for stage I patients, n = 25). Among the 35 dead patients during follow-up, 14 died of their lung cancer (40%). Two had been re-operated from another lung cancer: one after 3 and 8 years who survived 16 years, and the other after 2 years who survived 70 months. Surgery results are good and postoperative events acceptable despite theoretically increased risks. This also supports performing a close follow-up of transplanted patients and particularly those with smoking history in view of detecting lung cancer appearing at an early stage. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Yanik, Gregory; Kitko, Carrie
Over the past 20 years, tremendous strides have been made to decrease treatment-related morbidity and mortality following allogeneic transplant, including management of acute and chronic lung injury. Within this context, three distinct entities are recognized, idiopathic pneumonia syndrome (IPS), bronchiolitis obliterans syndrome (BOS), and bronchiolitis obliterans organizing pneumonia (BOOP). Management options for each of these disorders are now reviewed. A recent pilot study and subsequent phase II trial suggest that tumor necrosis factor (TNF) inhibitors hold promise in treating IPS. A randomized phase III trial ended prematurely, without a definitive conclusion regarding TNF inhibitors established. Few prospective trials for BOS have been performed, with current therapy based on observational studies and small case reports. Therapy for BOOP is based upon minimal clinical evidence. Although corticosteroids remain the backbone of therapy for IPS, BOS, and BOOP, TNF inhibition may augment management of IPS and potentially BOS as well. Diagnostic criteria for IPS and BOS have been established, although optimal treatment strategies will ultimately require consensus monitoring and response criteria, coupled with an improved understanding of the pathophysiology underlying each disorder. For BOS and BOOP in particular, therapy has been based upon a paucity of data and anecdotal experiences.
Do, Young Woo; Jung, Hee Suk; Lee, Chang Young; Lee, Jin Gu; Youn, Young-Nam; Paik, Hyo Chae
Coronary artery disease has historically been a contraindication to lung transplantation. We report a successful combined bilateral lung transplantation and off-pump coronary artery bypass in a 62-year-old man. The patient had a progressive decline in lung function due to idiopathic pulmonary fibrosis and a history of severe occlusive coronary artery disease. PMID:27965924
Merlo, Christian A; Weiss, Eric S; Orens, Jonathan B; Borja, Marvin C; Diener-West, Marie; Conte, John V; Shah, Ashish S
The Lung Allocation Score (LAS) dramatically changed organ allocation in lung transplantation. The impact of this change on patient outcomes is unknown. The purpose of the study was to examine early mortality after lung transplantation under the LAS system. All patients undergoing first-time lung transplantation during the period from May 1, 2005 through April 30, 2008 were included in the study. The cohort was divided into quintiles by LAS. A high-risk group (LAS >46) was comprised of the highest quintile, Quintile 5, and a low-risk group (LAS < or =46) included the lower quintiles, Quintiles 1 through 4. A time-to-event analysis was performed for risk of death after transplantation using Kaplan-Meier survival and Cox proportional hazards models. There were 4,346 patients who underwent lung transplantation during the study period. Patients in the high-risk group (LAS >46) were more likely to have idiopathic pulmonary fibrosis (IPF; 52.9% vs 23.8%, p < 0.001) and diabetes (25.8% vs 16.8%, p < 0.001) and to require mechanical ventilatory support (15.4% vs 2.2%, p < 0.001) at the time of transplant as compared with patients in the low-risk group. One-year survival using the Kaplan-Meier product limit estimator was significantly worse in the high-risk group (75% vs 83%, p < 0.001 by log-rank test). Patients in the high-risk group were also found to have increased risk of death (hazard ratio 1.46, 95% confidence interval 1.24 to 1.73) compared with the low-risk group. Overall 1-year survival under the new LAS system appears to be similar to that in historic reports. However, risk of death was significantly increased among patients with LAS >46.
Shyu, Susan; Dew, Mary Amanda; Pilewski, Joseph M.; DeVito Dabbs, Annette J.; Zaldonis, Diana B.; Studer, Sean M.; Crespo, Maria M.; Toyoda, Yoshiya; Bermudez, Christian A.; McCurry, Kenneth R.
Background Induction therapy with alemtuzumab, followed by lower than conventional intensity posttransplant immunosuppression (e.g., tacrolimus monotherapy), has been associated with reduced morbidity and mortality in abdominal and heart transplantation. We examined 5-year outcomes in lung recipients receiving alemtuzumab in conjunction with reduced intensity posttransplant immunosuppression (early lower dose tacrolimus; lower dose steroids, with or without mycophenolate mofetil), compared to lung recipients receiving other induction agents or no induction in association with posttransplant immunosuppression. Methods A retrospective analysis was performed utilizing prospectively collected data from a single-site clinical database on 336 lung recipients (aged≥18) transplanted between 1998 and 2005, classified by induction type: alemtuzumab (n=127), Thymoglobulin (n=43), daclizumab (n=73), none (n=93). Survival analyses examined patient and graft survival, and freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, obliterative bronchiolitis (OB), bronchiolitis obliterans syndrome (BOS), and post-transplant lymphoproliferative disorder (PTLD). Results Five-year patient and graft survival differed by group (p=.046, p=.038, respectively). Alemtuzumab patient/graft survival rates were 59%/59%. Survival rates were 60%/44% for Thymoglobulin, 47%/46% for no-induction, and 44%/41% for daclizumab. Freedom from ACR, lymphocytic bronchiolitis, OB, and BOS differed by group (all p’s<.008); alemtuzumab recipients showed greater 5-year freedom from each outcome (30%/82%/86%/54%) than Thymoglobulin (20%/54%/62%/27%), daclizumab (19%/55%/70%/43%) and no-induction groups (18%/68%/69%/46%). The groups did not differ in PTLD rates (p=.864, ≥94% free of PTLD at 5 years). Effects were unchanged after controlling for potential covariates. Conclusions Alemtuzumab induction may be associated with improved outcomes in lung transplantation. Randomized controlled trials
Nau, Michael; Shrider, Emily A; Tobias, Joseph D; Hayes, Don; Tumin, Dmitry
Most lung transplant (LTx) recipients recover sufficient functional status to resume working, yet unemployment is common after LTx. Weak local labor markets may limit employment opportunities for LTx recipients. United Network for Organ Sharing data on first-time LTx recipients 18-60 years old who underwent transplant between 2010 and 2014 were linked to American Community Survey data on unemployment rates at the ZIP Code level. Multivariable competing-risks regression modeled the influence of dichotomous (≥8%) and continuous local unemployment rates on employment after LTx, accounting for the competing risk of mortality. For comparison, analyses were duplicated in a cohort of heart transplant (HTx) recipients who underwent transplant during the same period. The analysis included 3,897 LTx and 5,577 HTx recipients. Work after LTx was reported by 300 (16.3%) residents of low-unemployment areas and 244 (11.9%) residents of high-unemployment areas (p < 0.001). Multivariable analysis of 3,626 LTx recipients with complete covariate data found that high local unemployment rates limited employment after LTx (sub-hazard ratio = 0.605; 95% confidence interval = 0.477, 0.768; p < 0.001), conditional on not working before transplant. Employment after HTx was higher compared with employment after LTx, and not associated with local unemployment rates in multivariable analyses. LTx recipients of working age exhibit exceptionally low employment rates. High local unemployment rates exacerbate low work participation after LTx, and may discourage job search in this population. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Mitzel, Heather; Snyders, Michele
As demands for organs increase, transplant centers are now considering alternative resources. This paper looks at the experiences of one kidney transplant center as it developed its anonymous donor protocol. The authors review the historical use of living donors and discuss why the program initially considered this type of donor. The team members and the decision-making process are identified, including ethical dilemmas confronted by the team. Finally, the protocol and anticipated concerns are presented.
... html Antibiotic Doesn't Prevent Lung Complication After Stem Cell Transplant Findings were so dismal that clinical trial ... HealthDay News) -- An antibiotic treatment intended to lower stem cell transplant patients' risk of developing a respiratory complication ...
Hill, Charles; Maxwell, Bryan; Boulate, David; Haddad, Francois; Ha, Richard; Afshar, Kamyar; Weill, David; Dhillon, Gundeep S
Patients with idiopathic pulmonary arterial hypertension (IPAH) have improved survival after heart-lung transplantation (HLT) and double-lung transplantation (DLT). However, the optimal procedure for patients with IPAH undergoing transplantation remains unclear. We hypothesized that critically ill IPAH patients, defined by admission to the intensive care units (ICU), would demonstrate improved survival with HLT vs. DLT. All adult IPAH patients (>18 yr) in the Scientific Registry of Transplant Recipients (SRTR) database, who underwent either HLT or DLT between 1987 and 2012, were included. Baseline characteristics, survival, and adjusted survival were compared between the HLT and DLT groups. Similar analyses were performed for the subgroups as defined by the recipients' hospitalization status. A total of 928 IPAH patients (667 DLT, 261 HLT) were included in this analysis. The HLT recipients were younger, more likely to be admitted to the ICU, and have had their transplant in previous eras. Overall, the adjusted survivals after HLT or DLT were similar. For recipients who were hospitalized in the ICU, DLT was associated with worse outcomes (HR 1.827; 95% CI 1.018-3.279). In IPAH patients, the overall survival after HLT or DLT is comparable. HLT may provide improved outcomes in critically ill IPAH patients admitted to the ICU at time of transplantation.
Lack of bronchial hyperresponsiveness to methacholine and to isocapnic dry air hyperventilation in heart/lung and double-lung transplant recipients with normal lung histology. The Paris-Sud Lung Transplant Group.
Herve, P; Picard, N; Le Roy Ladurie, M; Silbert, D; Cerrina, J; Le Roy Ladurie, F; Chapelier, A; Dartevelle, P; Simonneau, G; Parquin, F
To investigate whether survivors of heart/lung and double-lung transplantations have normal or increased nonspecific bronchial responsiveness, nine heart/lung and four double-lung transplant recipients with normal lung histology underwent methacholine challenge and voluntary isocapnic dry air hyperventilation (VIH) in a randomized order at a mean time of 14.8 +/- 12.1 months after surgery. Transplant recipients were compared with 10 normal subjects and 11 patients with mild asthma. Asthmatic patients had a mean provocative concentration of methacholine inducing a 20% fall (PC20) in FEV1 of 3.4 +/- 3.6 mg/ml (SD). Seventy seven percent of the transplant recipients and 70% of the normal subjects had PC20 superior to 32 mg/ml. The percentage fall from baseline FEV1 after VIH was 12.6 +/- 10.4% in asthmatic patients as compared with 1.9 +/- 2.9% in transplant recipients (p = 0.002) and 0.45 +/- 1.2% in normal subjects (p = 0.001). The decrease in FEV1 after VIH was similar in transplant recipients and normal subjects (p = 0.14). These results show that heart/lung or double-lung transplant recipients with normal lung histology have a normal response to nonspecific bronchial stimulation.
Soresi, Simona; Sabashnikov, Anton; Weymann, Alexander; Zeriouh, Mohamed; Simon, André R.; Popov, Aron-Frederik
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
Chacón, C F; Vicente, R; Ramos, F; Porta, J; Lopez Maldonado, A; Ansotegui, E
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.
Mohite, Prashant N; Rosenberg, Alexander; Caballero, Clara Hernández; Soresi, Simona; Fatullayev, Javid; Reed, Anna; Popov, Aron-Frederik; Sabashnikov, Anton; Simon, André R
Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (LTx) is not uncommon, but it is not commonplace yet. We present a case of a 45-year-old man with cystic fibrosis with recent deterioration in lung function who was initially supported with veno-venous (VV) ECMO. However, he subsequently required conversion to veno-veno-arterial (VVA) ECMO. After 21 days of support, he underwent double lung transplantation, with an uneventful postoperative course. This case shows that, in patients with end-stage respiratory failure awaiting lung transplantation, extracorporeal life support may require escalation to improve gas exchange and address circulatory requirements.
Liu, Annaë; Bernard, Mélisande
Based on solid experience in renal transplant, new treatments aiming to decrease anti-human leukocyte antigen (HLA) antibodies in patients awaiting lung transplant have recently been developed. The off-label use of high-dose intravenous polyvalent immunoglobulins (IVIg) and/or plasmapheresis changes the economical weight of pharmaceutical cost before lung transplantation. Our objective was to assess the budgetary impact of pharmaceutical costs of desensitization therapy. Two observational studies were conducted in 2009 and 2010 at the Bichat Claude Bernard (BCB) hospital in France. The first assessed the real pharmaceutical costs, and identified cost drivers, of desensitized (D+) patients awaiting lung transplantation. The second compared pharmaceutical and clinical data between D+ and non-treated (D-) patients. The major cost drivers were IVIg, representing 89.7 % of pharmaceutical costs. The real cost of drugs was €4,392 ± 647 per hospitalization. Mean hospitalization and annual pharmaceutical costs per patient were significantly higher for D+ than for D- patients (€6,972 vs. 2,925 and €13,074 vs. 399). D+ patients had a significantly higher average number of annual hospitalizations than did D- patients. Total IVIg costs represented 98 % of the pharmaceutical costs for desensitization stays. Pharmaceutical costs represented 40 % of total hospitalization costs for D+ versus only 7 % for D-. New desensitization protocols can help to manage the immunological hurdle of anti-donor antibodies in lung transplantation. They are expensive and not yet correctly covered by national health insurance, as they are supported by hospital budgets. A medico-economical evaluation of IVIg use in this indication seems necessary.
Singer, Jonathan Paul; Chen, Joan; Katz, Patricia P; Blanc, Paul David; Kagawa-Singer, Marjorie; Stewart, Anita L.
Purpose Health-related quality of life (HRQL) domains vary across disease conditions and are determined by standards, values, and priorities internal to patients. Although the clinical goals of lung transplantation are to improve patient survival and HRQL, what defines HRQL in lung transplantation is unknown. Employing a qualitative approach, we aimed to identify HRQL domains important in lung transplantation. Methods We conducted semi-structured interviews in purposefully sampled lung transplant recipients (n=8) representing a spectrum of ages, gender, indications for transplantation, and time since transplantation as well as health-care practitioners representing a spectrum of practitioner types (n=9). Grounded Theory was used to identify HRQL domains important in lung transplantation, building on but going beyond domains already defined in the SF-36, the most commonly used instrument in this population. Results In addition to confirming the relevance of the eight SF-36 domains, we identified 11 novel HRQL domains. Palliation of respiratory symptoms was identified as important. After transplant surgery, new HRQL domains emerged including: distressing symptoms spanning multiple organ systems; worry about infection and acute rejection; treatment burden; and depression. Further, patients identified challenges to intimacy, changes in social relationships, and problems with cognitive functioning. Saliently, worry about limited life expectancy was pervasive and impaired life planning. Conclusions We found that HRQL in lung transplantation is defined by both generic and transplant-specific domains. Delineating and refining these domains can inform efforts to improve clinical outcomes and HRQL measurement in lung transplantation. PMID:25471287
Parsa, Saeed Alipour; Dousti, Amir; Naghashzadeh, Farah; Ataeinia, Bahar
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. PMID:27437285
Castleberry, Anthony W.; Bishawi, Muath; Worni, Mathias; Erhunmwunsee, Loretta; Speicher, Paul J.; Osho, Asishana A.; Snyder, Laurie D.; Hartwig, Matthew G.
Background Our objective was to identify potential avenues for resource allocation and patient advocacy to improve outcomes by evaluating the association between recipient sociodemographic and patient characteristics and medication nonadherence after lung transplantation. Methods States US adult, lung-only transplantations per the United Network for Organ Sharing database were analyzed from October 1996 through December 2006, based on the period during which nonadherence information was recorded. Generalized linear models were used to determine the association of demographic, disease, and transplantation center characteristics with early nonadherence (defined as within the first year after transplantation) as well as late nonadherence (years 2 to 4 after transplantation). Outcomes comparing adherent and nonadherent patients were also evaluated. Results Patients (n = 7,284) were included for analysis. Early and late nonadherence rates were 3.1% and 10.6%, respectively. Factors associated with early non-adherence were Medicaid insurance compared with private insurance (adjusted odds ratio [AOR] 2.45, 95% confidence interval [CI]: 1.16 to 5.15), and black race (AOR 2.38, 95% CI: 1.08 to 5.25). Medicaid insurance and black race were also associated with late nonadherence (AOR 2.38, 95% CI: 1.51 to 3.73 and OR 1.73, 95% CI: 1.04 to 2.89, respectively), as were age 18 to 20 years (AOR 3.41, 95% CI: 1.29 to 8.99) and grade school or lower education (AOR 1.88, 95% CI: 1.05 to 3.35). Early and late non-adherence were both associated with significantly shorter unadjusted survival (p < 0.001). Conclusions Identifying patients at risk of non-adherence may enable resource allocation and patient advocacy to improve outcomes. PMID:27624294
Castleberry, Anthony W; Bishawi, Muath; Worni, Mathias; Erhunmwunsee, Loretta; Speicher, Paul J; Osho, Asishana A; Snyder, Laurie D; Hartwig, Matthew G
Our objective was to identify potential avenues for resource allocation and patient advocacy to improve outcomes by evaluating the association between recipient sociodemographic and patient characteristics and medication nonadherence after lung transplantation. States US adult, lung-only transplantations per the United Network for Organ Sharing database were analyzed from October 1996 through December 2006, based on the period during which nonadherence information was recorded. Generalized linear models were used to determine the association of demographic, disease, and transplantation center characteristics with early nonadherence (defined as within the first year after transplantation) as well as late nonadherence (years 2 to 4 after transplantation). Outcomes comparing adherent and nonadherent patients were also evaluated. Patients (n = 7,284) were included for analysis. Early and late nonadherence rates were 3.1% and 10.6%, respectively. Factors associated with early nonadherence were Medicaid insurance compared with private insurance (adjusted odds ratio [AOR] 2.45, 95% confidence interval [CI]: 1.16 to 5.15), and black race (AOR 2.38, 95% CI: 1.08 to 5.25). Medicaid insurance and black race were also associated with late nonadherence (AOR 2.38, 95% CI: 1.51 to 3.73 and OR 1.73, 95% CI: 1.04 to 2.89, respectively), as were age 18 to 20 years (AOR 3.41, 95% CI: 1.29 to 8.99) and grade school or lower education (AOR 1.88, 95% CI: 1.05 to 3.35). Early and late nonadherence were both associated with significantly shorter unadjusted survival (p < 0.001). Identifying patients at risk of nonadherence may enable resource allocation and patient advocacy to improve outcomes. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Speicher, Paul J; Ganapathi, Asvin M; Englum, Brian R; Gulack, Brian C; Osho, Asishana A; Hirji, Sameer A; Castleberry, Anthony W; Snyder, Laurie D; Duane Davis, R; Hartwig, Matthew G
This study assessed treatment patterns and examined organ utilization in the setting of single-lung transplantation (SLT). The United Network for Organ Sharing database was queried for all SLTs performed from 1987 to 2011. Trends in utilization of the second donor lung were assessed, both from recipient and donor perspectives. Donors were stratified into 2 groups: those donating both lungs and those donating only 1 lung. Independent predictors of using only 1 donor lung were identified using multivariable logistic regression. We identified 10,361 SLTs originating from 7,232 unique donors. Of these donors, both lungs were used in only 3,129 (43.3%), resulting in more than 200 second donor lungs going unused annually since 2005, with no significant increase in use over time (p = 0.95). After adjustment, donor characteristics predicting the second donor lung going unused included B/AB blood groups (adjusted odds ratio [AOR]: 1.69 and 2.62, respectively; p < 0.001), smaller body surface area (AOR, 1.30; p = 0.02), lower donor partial pressure of arterial oxygen (AOR, 0.90 per 50 mm Hg increase; p < 0.001), pulmonary infection (AOR, 1.15; p = 0.04), extended criteria donor status (AOR, 1.66; p < 0.001), and death caused by head trauma (AOR, 1.57; p < 0.001) or anoxia (AOR, 1.53; p = 0.001). Among donors for SLT, less than half of all cases led to use of the second donor lung. Although anatomic, infectious, or other pathophysiologic issues prohibit 100% utilization, more aggressive donor matching efforts may be a simple method of increasing the utilization of this scarce resource, particularly for less common blood types. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Patriarchi, F; Rolla, M; Maccioni, F; Menichella, A; Scacchi, C; Ambrosini, A; Costantino, A; Quattrucci, S
C. difficile (C. d.) is the main cause of antibiotic-associated diarrhea and colitis. It is shown in literature a high asymptomatic carriage rate of C. d. in patients with cystic fibrosis (CF), though C. d.-related colitis is an uncommon complication in these patients, despite the use of multiple high-dose antibiotic regimes and the frequency of hospital admissions. Lung transplantation with the associated immunosuppression and aggressive antibiotic therapy may increase the risk of the clinical manifestation of C. d. In this paper, we describe three cases of severe C. d. colitis in patients with CF following lung transplantation and illustrate our experience in the diagnosis and management of these patients. © 2010 John Wiley & Sons A/S.
Savale, Laurent; Le Pavec, Jérôme; Mercier, Olaf; Mussot, Sacha; Jaïs, Xavier; Fabre, Dominique; O'Connell, Caroline; Montani, David; Stephan, François; Sitbon, Olivier; Simonneau, Gérald; Dartevelle, Philippe; Humbert, Marc; Fadel, Elie
Since 2006 and 2007, patients in France with severe pulmonary hypertension (PH) who are at imminent risk of death, despite optimal treatment in the intensive care unit, are placed on a high-priority list (HPL) for heart-lung transplantation (HLT) or double-lung transplantation (DLT). We assessed the effect of this approach on the waiting list and outcomes after transplantation. We conducted a single-center, retrospective, before-and-after study of consecutive patients with severe group 1, 1', or 4 PH listed for DLT or HLT between 2000 and 2013 (ie, 6 years before and 6 years after HPL implementation). We included 234 patients. HPL implementation resulted in a significant decrease of the cumulative incidence of death on the waiting list at 1 and 2 years (p < 0.0001). The cumulative incidence of transplantation increased significantly from 48% to 76% after 2 years (p < 0.0001). Overall survival after transplantation was not significantly different between the pre-HPL and post-HPL era. In the HPL period, patients on the regular list who received a transplant had a nonsignificant trend toward improved overall survival compared with those on the HPL who received a transplant (at 1, 2, 3, and 5 years: 85%, 77%, 72%, and 72% vs 67%, 61%, 58%, and 50%; p = 0.053). Finally, survival after listing improved significantly after HPL implementation (at 1, 2, 3, and 5 years: 69%, 62%, 58%, and 54% vs 54%, 45%, 34%, and 26% before the HPL; p < 0.001). HPL implementation was followed by higher survival of PH patients after registration on the DLT or HLT waiting list and by a higher cumulative incidence of transplantation among waiting-list patients. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Borro, J M; Ramos, F; Vicente, R; Sanchis, F; Morales, P; Caffarena, J M
We present a case of heart-lung transplantation complicated by bronchial perforation as the cause or consequence of prolonged lung infection. Periodic bronchoscopic and radiological follow-up showed resolution of the condition following adequate antibiotic and physiotherapeutic treatment.
Lee, James C.; Kawut, Steven M.; Shah, Rupal J.; Localio, A. Russell; Bellamy, Scarlett L.; Lederer, David J.; Cantu, Edward; Kohl, Benjamin A.; Lama, Vibha N.; Bhorade, Sangeeta M.; Crespo, Maria; Demissie, Ejigayehu; Sonett, Joshua; Wille, Keith; Orens, Jonathan; Shah, Ashish S.; Weinacker, Ann; Arcasoy, Selim; Shah, Pali D.; Wilkes, David S.; Ware, Lorraine B.; Palmer, Scott M.; Christie, Jason D.
Rationale: Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. Objectives: We sought to identify donor, recipient, and perioperative risk factors for PGD. Methods: We performed a 10-center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD at 48 or 72 hours post-transplant. The association of potential risk factors with PGD was analyzed using multivariable conditional logistic regression. Measurements and Main Results: A total of 1,255 patients from 10 centers were enrolled; 211 subjects (16.8%) developed grade 3 PGD. In multivariable models, independent risk factors for PGD were any history of donor smoking (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2–2.6; P = 0.002); FiO2 during allograft reperfusion (OR, 1.1 per 10% increase in FiO2; 95% CI, 1.0–1.2; P = 0.01); single lung transplant (OR, 2; 95% CI, 1.2–3.3; P = 0.008); use of cardiopulmonary bypass (OR, 3.4; 95% CI, 2.2–5.3; P < 0.001); overweight (OR, 1.8; 95% CI, 1.2–2.7; P = 0.01) and obese (OR, 2.3; 95% CI, 1.3–3.9; P = 0.004) recipient body mass index; preoperative sarcoidosis (OR, 2.5; 95% CI, 1.1–5.6; P = 0.03) or pulmonary arterial hypertension (OR, 3.5; 95% CI, 1.6–7.7; P = 0.002); and mean pulmonary artery pressure (OR, 1.3 per 10 mm Hg increase; 95% CI, 1.1–1.5; P < 0.001). PGD was significantly associated with 90-day (relative risk, 4.8; absolute risk increase, 18%; P < 0.001) and 1-year (relative risk, 3; absolute risk increase, 23%; P < 0.001) mortality. Conclusions: We identified grade 3 PGD risk factors, several of which are potentially modifiable and should be prioritized for future research aimed at preventative strategies. Clinical trial registered with www.clinicaltrials.gov (NCT
Anand-Kumar, Vinayak; Kung, Mary; Painter, Liz; Broadbent, Elizabeth
The majority of psychological studies with organ transplant recipients have examined negative psychological effects. This study aimed to further investigate the positive effects of organ transplantation and to construct a specific measurement instrument. The initial pool of 14 items for the Positive Effects of Transplant Scale (PETS) was derived from organ recipient interviews. A cross-sectional postal study included 87 heart, 46 lung and 193 liver transplant recipients. The PETS was subjected to principal components analysis (PCA) using varimax rotation, and associations with other measures investigated. PETS and an open-ended item about positive effects. Coding of the open-ended item revealed that the majority of recipients attributed positive life changes to the transplant experience. PCA of the PETS indicated three factors that accounted for 58.82% of the variance. The 12-item questionnaire assesses improvements in: (1) life philosophy, (2) gratitude and (3) health. The total PETS scores exhibited adequate internal consistency and validity. Most transplant patients report positive psychological effects, which suggests this may be an understudied area. The initial development of an assessment tool provides researchers and clinicians a way to assess the degree and nature of these life changes.
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.
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
Burton, J H; Marshall, J M; Munro, P; Moule, W; Snell, G I; Westall, G P
We describe the key components of an outpatient pediatric recovery and rehabilitation program set up within the adult lung transplant service at the Alfred Hospital, Melbourne. Following discharge, pediatric lung transplant recipients and their families participated in an intensive 3-month outpatient rehabilitation program. Weekly sessions included education regarding transplant issues, physiotherapy, and occupational therapy sessions. The overall aim of the program was to comprehensively address physical rehabilitation and psychosocial and educational needs. Sessions tailored to meet the individual needs of the child were presented at an appropriate cognitive level. Education sessions for both the children and parents focused on medications, identification of infection and rejection, nutrition, physiotherapy/rehabilitation, occupational roles and stress management, donor issues, psychosocial readjustment, and transition issues. Physiotherapy included a progressive aerobic and strength training program, postural reeducation, and core stability. We incorporate Age-appropriate play activities: running, dancing, jumping, ball skills, and so on. Occupational therapy sessions addressed the primary roles of patient, students, and player. Transitions such as returning to school, friends, and the community were explored. Issues discussed included adjustment to new health status, strategies to manage side effects of medications, and altered body image issues. Weekly multidisciplinary team meetings were used to discuss and plan the rehabilitation progress. School liaison and visits occurred prior to school commencement with follow-up offered to review the ongoing transition process. Both patients and parents have reported a high level of satisfaction with the rehabilitation program. We plan to formally evaluate the program in the future.
Kortchinsky, Talna; Mussot, Sacha; Rezaiguia, Saïda; Artiguenave, Margaux; Fadel, Elie; Stephan, François
After bilateral lung and heart-lung transplantation in adults with pulmonary hypertension, hemodynamic and oxygenation deficiencies are life-threatening complications that are increasingly managed with extracorporeal life support (ECLS). The primary aim of this retrospective study was to assess 30-day and 1-year survival rates in patients managed with vs without post-operative venoarterial ECLS in 2008-2013. The secondary endpoints were the occurrence rates of nosocomial infection, bleeding, and acute renal failure. Of the 93 patients with pulmonary hypertension who received heart-lung (n=29) or bilateral lung (n=64) transplants, 28 (30%) required ECLS a median of 0 [0-6] hours after surgery completion and for a median of 3.0 [2.0-8.5] days. Compared to ECLS patients, controls had higher survival at 30 days (95.0% vs 78.5%; P=.02) and 1 year (83% vs 64%; P=.005), fewer nosocomial infections (48% vs 79%; P=.0006), and fewer bleeding events (17% vs 43%; P=.008). The need for renal replacement therapy was not different between groups (11% vs 17%; P=.54). Venoarterial ECLS is effective in treating pulmonary graft dysfunction with hemodynamic failure after heart-lung or bilateral lung. However, ECLS use was associated with higher rates of infection and bleeding.
Xia, Y; Friedmann, P; Bello, R; Goldstein, D; D'Alessandro, D
Lung procurement is increasing during multiorgan recovery and substantially alters the explant process. This study evaluated whether lung donation by a heart donor affects survival in heart transplant recipients. Retrospective analysis of United Network for Organ Sharing (UNOS) adult heart transplantation data from 1998 to 2012 was performed. Lung donors (LDs) were defined as those having at least one lung procured and transplanted. Non-LDs had neither lung transplanted. Heart transplant recipients who had previous transplants, who had heterotopic transplants, who were waitlisted for other organs or who were temporarily delisted were excluded from the analysis. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed. Of 23 590 heart transplant recipients meeting criteria during the study period, 8638 (36.6%) transplants were from LDs. Donors in the LD group had less history of cigarette use (15.5% vs. 29.5%, p < 0.001). On univariate analysis, LDs were associated with improved patient survival (p < 0.001). On multivariate analysis, LDs were not significantly associated with patient survival (adjusted hazard ratio 0.98, 95% confidence interval 0.94-1.03). Analysis of the UNOS registry suggested that donor pulmonary status and lung procurement had no detrimental effect on survival in heart transplant recipients, supporting the present practice of using donor lungs whenever possible.
Wondergem, J.; Haveman, J.; van der Schueren, E.
The effect of thorax irradiation on lung metastases, either occurring spontaneously from a primary mammary adenocarcinoma (M8013X) transplanted on the leg or artificially induced by intravenous injection of tumor cells was studied. Increasing the interval between the moment at which lung metastases are supposed to originate and the thorax irradiation resulted in a rapid decrease of the effectiveness of this treatment in preventing the development of lung metastases. Increasing the radiation dose led to an increased number of cures; however, an increased number of mice dying of lethal lung damage was also observed. Irradiation of the lungs of mice with 5 or 10 Gy, 24 hours, 7 days or 14 days prior to i.v. injection with tumor cells, did not significantly increase the number of mice with lung metastases. Immunological resistance against the tumor played a role in our experiments with both spontaneous and artificial lung metastases.
Budding, K; van de Graaf, E A; Otten, H G
Lung transplantation (LTx) is the final treatment option for patients with endstage lung diseases including chronic obstructive pulmonary disease, cystic fibrosis, and interstitial lung disease. Survival after LTx is severely hampered by the development of the bronchiolitis obliterans syndrome (BOS) which is hallmarked by excessive fibrosis and scar tissue formation leading to small airway obliteration and eventually organ failure. The pathophysiology of BOS is incompletely understood. During the past years both anti-HLA and non-HLA antibodies have been identified that correlate with transplantation outcome. Also, the involvement of autoimmunity on BOS progression has been demonstrated, including autoantigens Type V collagen and K-alpha tubulin. Both allo- and autoantibodies binding to its respective antigen trigger the binding of C1q and sequential complement activation which can lead to either cell damage or activation, both processes which fit into the current model of BOS pathogenesis. In this review we will discuss both HLA, non-HLA and autoantibodies associated with disease progression, but also elaborate on the subsequent complement effector mechanisms, complement regulation, and the potential influence of regulatory mechanisms on graft survival. Copyright © 2014 Elsevier B.V. All rights reserved.
Arango Tomás, E; Cerezo Madueño, F; Salvatierra Velázquez, A
Atrial anastomosis in lung transplantation (LT) can present significant technical difficulties, especially when there is a very posterior left inferior pulmonary vein, in donor-recipient disproportion or excessive separation of the receptor's pulmonary veins owing to atrial dilatation; hence, its implementation requires excessive heart handling and longer ischemia time, which result in increased perioperative complications. This technique, which uses the recipient's superior pulmonary vein, avoids these problems, although it is not applicable in all cases because no pressure gradient at the suture level is required. Therefore, the suture diameter must be equal or greater than the sum of both graft pulmonary veins diameters. This retrospective study recorded the age/gender (donor and recipient), preoperative morbidity, type of surgery, perioperative, vascular complications, mortality, and postoperative stay. Descriptive and inferential statistical study was made by SPSS. We performed 82 LTs between January 2009 and June 2012, 18 with the new technique (14 men/4 women; 52 ± 15 years). There were 14 single lung and 4 double lung transplants. The new technique does not increase the ischemic times when compared with the classic technique. No vascular dehiscence, fistulas, or thrombosis were found. There were observed fewer vascular complications (P = .042). Early mortality was presented in 4 cases (22.2%). This new technique achieves the objectives described (no increases in ischemic time, fewer vascular complications). However, an absolute confirmation requires a study comparing similar technical LT given that the new resource was only used in highly complex procedures. Copyright © 2015 Elsevier Inc. All rights reserved.
Rodríguez, Diego A; Del Río, Francisco; Fuentes, Manuel E; Naranjo, Sara; Moradiellos, Javier; Gómez, David; Rubio, Juan José; Calvo, Elpidio; Varela, Andrés
Uncontrolled donation after cardiac death (DACD) has become an alternative to lung transplantation with encephalic-death donation. The main objective of this study is to describe the incidence of clinically relevant events in the period of thirty days after lung transplant with uncontrolled DACD and the influence of factors depending on the donor and donation process as well. Historical cohort study of 33 lung transplant receivers at Hospital Puerta de Hierro and Hospital Marqués de Valdecilla with 32 DACD from Hospital Clínico San Carlos from 2002 to 2008. We studied surgical and medical complications, primary graft dysfunction, acute rejection, pneumonia and mortality. We made an evaluation of the donor characteristics and donation procedure times (minutes). Median age of recipients was 50.5 years (interquartile range, 38.5-58). There were 28 males and 5 females. Cumulative incidence of events in the first month was: pneumonia 10 (31.3%); primary graft dysfunction 15 (46.9%); rejection 12 (37.5%); mortality 4 (12.1%); medical complications 25 (78.1%); and surgical complications 18 (56.3%). Median time of cardiac arrest was higher in those who presented pneumonia (15 vs. 7.5; p = 0.027). Median time of cold ischemia was higher in those who presented surgical complications and mortality (436 vs. 343.5; p = 0.04; 505 vs. 410; p = 0.033, respectively), and median of total ischemia times were longer in the recipients who died (828 vs. 695; p = 0.036). Uncontrolled DACD are a valid alternative for expanding the donor pool in order to mitigate the current shortage of lungs that are valid for transplantation. The incidence of complications is comparable with published data in the literature. Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.
Mayes, Jonathan; Niranjan, Gunaratnam; Dark, John; Clark, Stephen
This case describes the technique of using dual Novalungs (a pumpless extracorporeal system) to bridge a patient with idiopathic pulmonary hypertension to bilateral lung transplantation. A 41-year old lady with idiopathic pulmonary hypertension (with a possible veno-occlusive element) presented with symptoms of end-stage heart and lung failure. This was refractory to medical management with iloprost, sildenafil and bosentan. The patient was placed on the urgent waiting list for lung transplantation and central pulmonary artery to left atrial Novalung insertion was performed. Local anaesthetic was given before performing peripheral cardiopulmonary bypass due to the high risk of cardiac arrest. Two days later, donor organs became available and the patient was taken for double-lung transplantation. The pulmonary artery cannula was removed leaving a large defect. This was then closed using a bovine pericardial patch. Due to the damaged right superior pulmonary vein from Novalung cannulation, cardioplegia was given to facilitate an open atrial anastomosis. After 13 days in the intensive therapy unit, she was transferred to the ward. There were no further complications and she has been discharged home.
Tanaka, Y; Noda, K; Isse, K; Tobita, K; Maniwa, Y; Bhama, J K; D'Cunha, J; Bermudez, C A; Luketich, J D; Shigemura, N
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. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
Wang, Yeming; Chen, Jingyu; Wei, Dong; Zheng, Mingfeng; Zhang, Ji; Wu, Bo
Patients with suppurative lung diseases such as bronchiectasis and cystic fibrosis can be treated surgically, which leads to an asymmetric thorax, making lung transplant difficult in a volume-reduced hemithorax. We report a 52-year-old man with bronchiectasis and ventilation, dependent on a severe asymmetric thorax, who underwent bilateral lung transplant without cardiopulmonary bypass or extracorporeal membrane oxygenation support. This report suggests that bilateral lung transplant might be an efficient therapeutic option for such patients. Lung transplant is generally accepted as an effective way to deal with end-stage pulmonary diseases. Particularly, in patients with bronchiectasis or cystic fibrosis, single lung transplant may lead to infectious complications more easily. Thus, bilateral lung transplant is a better choice for such patients. However, some patients with bronchiectasis may have a history of surgical resection of target areas, which leads to an asymmetric thorax and makes lung transplant more difficult. We described 1 case of bilateral lung transplant for bronchiectasis in asymmetric thorax.
Chen, Fengshi; Oga, Toru; Yamada, Tetsu; Sato, Masaaki; Aoyama, Akihiro; Chin, Kazuo; Date, Hiroshi
The lung allocation score (LAS) system has been implemented to reduce waiting list time and mortality in the USA, but it remains uncertain how the LAS would reflect the impairment in health-related quality of life (HRQOL), which is another lung transplantation treatment goal to be improved in addition to survival. We thus investigated the relationships of the LAS with mortality and HRQOL in Japanese lung transplantation candidates. One hundred and two candidates for lung transplantation at Kyoto University Hospital between 2009 and 2013 were consecutively recruited to participate in this study. Their physiological measurements of pulmonary function and 6-min walking distance, as well as patient-reported measurements of HRQOL, dyspnoea and psychological status, were assessed. Among these 102 patients, 22 died during a mean follow-up of 11.6 months. The LAS was significantly correlated to mortality (P = 0.0026), although other physiological measurements were not. However, regarding its relationship with HRQOL, correlation coefficients between the LAS, Medical Outcomes Study 36-item short form and St George's Respiratory Questionnaire (SGRQ) were relatively low, with the highest at 0.31. Multivariate analyses showed that the LAS was less significantly related to the SGRQ total score than dyspnoea, and psychological status. The LAS was significantly related to mortality in lung transplant candidates in Japan, while, despite its multidimensional scoring, its relationship with health-related quality of life was only weak. Their severity assessment system may be more focused on patients' health and symptoms. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Chen, Fengshi; Chin, Kazuo; Ishii, Hisanari; Kubo, Hiroyasu; Miwa, Senri; Ikeda, Tadashi; Bando, Toru; Date, Hiroshi
Living-donor lobar lung transplantation (LDLLT) recipients often have hypercapnia preoperatively, which confers a risk of worsened hypercapnia intraoperatively. We reviewed our experience with continuous carbon dioxide partial pressure (PtcCO2) monitoring in LDLLT to evaluate its accuracy and feasibility. We also assessed preoperative and intraoperative carbon dioxide levels in LDLLT recipients. Twenty-six LDLLT recipients without pulmonary hypertension underwent preoperative nocturnal and intraoperative PtcCO2 monitoring, determined with a TOSCA-500 monitor. Maximal preoperative nocturnal PtcCO2 (72.7 ± 19.3 mmHg) was significantly correlated with preoperative resting arterial carbon dioxide partial pressure (PaCO2; 55.1 ± 11.6 mmHg, r(2)=0.84). PtcCO2 was more correlated with PaCO2 (range, 39-192 mmHg) during LDLLT (r(2)=0.93) than with end-tidal carbon dioxide partial pressure (r(2)=0.38). Intraoperative continuous PtcCO2 monitoring was useful for evaluating real-time carbon dioxide levels. Intraoperative PtcCO2 did not exceed maximal preoperative nocturnal PtcCO2 in 13 recipients (50%) but temporarily exceeded it in 11 recipients (42%). PtcCO2 was further elevated in 2 recipients (8%) requiring the early establishment of cardiopulmonary bypass. There were no complications related to PtcCO2 monitoring. PtcCO2 monitoring in LDLLT recipients is useful as a means for determining intraoperative carbon dioxide levels, which increase dramatically and can be predicted preoperatively and assessed in a timely manner.
Milford, Emily; Winslow, Caroline; Danhof, Rebecca
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 . 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.
Lung transplantation is now considered a valid option in the management of end-stage respiratory failure. The postoperative period remains a key stage that will influence the average long-term prognosis of the patients. Primary graft failure, postoperative bleeding, infection, acute rejection and complications linked to the surgery, and to vascular or bronchial anastomoses, are risk factors for mortality and morbidity. These must be taken care of quickly via collaboration with the surgical team. The immunosuppressive treatment essential for tolerance induction with regard to the transplanted organ will be introduced during the intraoperative period and continued for life. The combination of a calcineurin inhibitor, an antiproliferative agent and corticosteroids remains the conventional procedure. The role of new molecules as mTor inhibitors remains to be determined. Copyright © 2011. Published by Elsevier Masson SAS.
Udoji, Timothy N; Force, Seth D; Pelaez, Andres
Abstract A 33-year-old female patient with advanced idiopathic pulmonary artery hypertension underwent bilateral lung transplantation. The postsurgical course was complicated by prolonged mechanical ventilation and acute hypoxemia with recurrent episodes of pulmonary edema. An echocardiogram revealed improved right-sided pressures along with a dilated left atrium, a structurally normal mitral valve, and a new posterior-oriented severe mitral regurgitation. The patient's condition improved after treatment with arterial vasodilators and diuretics, and she has remained in World Health Organization functional class I after almost 36 months of follow-up. We hypothesize that cardiac ventricle remodeling and a geometric change in mitral valve apparatus after transplantation led to the hemodynamic changes and recurrent pulmonary edema seen in our patient. Our case is, to our knowledge, the second report of severe valvular regurgitation in a structurally normal mitral valve apparatus in the postoperative period and the first of a patient to be treated without valve replacement.
Jellinek, H; Klepetko, W; Hiesmayr, M
Eight days after single-lung transplantation for pulmonary hypertension, a patient presented with a hemothorax on the side of the transplanted lung that required acute thoracotomy. Pulmonary artery pressure had decreased from 78/32/58 mmHg prior to the transplant to 42/18/27 mmHg on the 2nd postoperative day. Therefore, a predominance of perfusion to the transplanted lung was expected. During induction of anesthesia, in spite of ventilation with pure oxygen the patient developed a hypoxic cardiac arrest (paO2 26 mmHg, 40% saturation measured by pulse oximetry) requiring external chest compression. Auscultation and chest movements suggested that the transplanted lung was not ventilated. Because blood flow went mainly to the transplanted lung, ventilation of the native lung was almost totally dead-space ventilation. To enable ventilation of the compressed transplanted lung, the patient was intubated using a single-lumen bronchial blocker tube to block the mainstem bronchus of the native lung. The transplanted lung could then be ventilated. Saturation increased and epinephrine re-established a stable circulation; 2500 ml blood were removed from the pleura without further complications. On the 7th postoperative day the patient was discharged from the intensive care unit without neurological deficits. A perfusion scan 28 days post-transplant revealed 89% of the perfusion going to the transplanted lung. Atelectasis of this lung resulted in a large intrapulmonary right-to-left shunt. Hypoxic pulmonary vasoconstriction could not ameliorate the shunt because of the high pulmonary vascular resistance of the native lung.(ABSTRACT TRUNCATED AT 250 WORDS)
Riera, Jordi; Caralt, Berta; López, Iker; Augustin, Salvador; Roman, Antonio; Gavalda, Joan; Rello, Jordi
The medical records of 170 adult patients who underwent lung transplantation between January 2010 and December 2012 were reviewed to assess the incidence, causative organisms, risk factors and outcomes of post-operative pneumonia and tracheobronchitis. 20 (12%) patients suffered 24 episodes of ventilator-associated pneumonia. The condition was associated with mean increases of 43 days in mechanical ventilation and of 35 days in hospital stay, and significantly higher hospital mortality (OR 9.0, 95% CI 3.2-25.1). Pseudomonas aeruginosa (eight out of 12 patients were multidrug-resistant) was the most common pathogen, followed by Enterobacteriaceae (one out of five patients produced extended-spectrum β-lactamases). Gastroparesis occurred in 55 (32%) patients and was significantly associated with pneumonia (OR 6.2, 95% CI 2.2-17.2). Ventilator-associated tracheobronchitis was associated with a mean increase of 28 days in mechanical ventilation and 30.5 days in hospital stay, but was not associated with higher mortality (OR 1.2, 95% CI 0.4-3.2). Pseudomonas aeruginosa (six out of 16 patients were multidrug resistant) was the most common pathogen, followed by Enterobacteriaceae (three out of 14 patients produced extended-spectrum β-lactamase). Patients with gastroparesis also had more episodes of ventilator-associated tracheobronchitis (40% versus 12%, p<0.001). In conclusion, ventilator-associated pneumonia following lung transplantation increased mortality. Preventing gastroparesis probably decreases the risk of pneumonia and tracheobronchitis. Multidrug-resistant bacteria frequently cause post-lung-transplantation pneumonia and tracheobronchitis. Copyright ©ERS 2015.
Sokai, Akihiko; Handa, Tomohiro; Chen, Fengshi; Tanizawa, Kiminobu; Aoyama, Akihiro; Kubo, Takeshi; Ikezoe, Kohei; Nakatsuka, Yoshinari; Oguma, Tsuyoshi; Hirai, Toyohiro; Nagai, Sonoko; Chin, Kazuo; Date, Hiroshi; Mishima, Michiaki
Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Hagiya, Hideharu; Yoshida, Hisao; Yamamoto, Norihisa; Kimura, Keigo; Ueda, Akiko; Nishi, Isao; Akeda, Yukihiro; Tomono, Kazunori
We report the first case of Mycoplasma hominis periaortic abscess after heart-lung transplantation. The absence of sternal wound infection delayed the diagnosis, but the patient successfully recovered with debridement surgeries and long-term antibiotic therapy. Owing to the difficulty in detection and the intrinsic resistance to beta-lactams, M. hominis infections are prone to being misdiagnosed and undertreated. M. hominis should be suspected in cases where conventional microbiological identification and treatment approaches fail. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Goldin, Jonathan G.; Brown, Matthew S.; McNitt-Gray, Michael F.; Greaser, Lloyd E.; Martin, Katherine; Sayre, James W.; Aberle, Denise R.
The purpose of this work was to develop an automated technique for calculating dynamic lung attenuation changes, through a forced expiratory maneuver, as a measure of split lung function. A total of ten patients post single lung transplantation (SLT) for emphysema were imaged using an Electron Beam CT Scanner; three were studied twice following stent placement. A single-slice flow study, using 100 msec exposures and 3 mm collimation, was performed at the level of the anastomosis during a forced expiration. Images were acquired every 500 msec for the first 3 seconds and every second for the last 4 seconds. An automated, knowledge-based system was developed to segment the chest wall, mediastinum, large airways and lung parenchyma in each image. Knowledge of the expected size, shape, topology and X-ray attenuation of anatomical structures were used to guide image segmentation involving attenuation thresholding, region-growing and morphology. From the segmented left and right parenchyma, the system calculated median attenuation (HU) and cross-sectional areas. These results were plotted against time for both the native and transplanted lungs. In five patients, significant shift of the attenuation/time curve to the right (slower flow) was detected, although the end expiration attenuation was not different. Following stent placement the curve shifted back to the left (faster flow).
Ménard, Armelle; Degrange, Sébastien; Peuchant, Olivia; Nguyen, Thi Diem Tien; Dromer, Claire; Maugein, Jeanne
Lung transplant recipients have an increased risk for actinomycetales infection secondary to immunosuppressive regimen. A case of pulmonary infection with bacteremia due to Tsukamurella tyrosinosolvens in a 54-year old man who underwent a double lung transplantation four years previously is presented. The identification by conventional biochemical assays was unsuccessful and hsp gene sequencing was used to identify Tsukamurella tyrosinosolvens.
Mohite, P N; Sabashnikov, A; García Sáez, D; Pates, B; Zeriouh, M; De Robertis, F; Simon, A R
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. © The Author(s) 2014.
Billings, Martha E.; Mulligan, Michael; Raghu, Ganesh
Lymphangioleiomyomatosis (LAM) is a rare cystic progressive lung disease with many extra-pulmonary manifestations which may complicate allograft function after transplantation. We present a LAM patient, one-year status-post bilateral lung transplant, with new dyspnea and declining spirometry without rejection, infection or recurrence. Investigation revealed acute constrictive pericarditis which has not previously been reported in LAM lung transplant patients. This represents a novel complication likely due to progression of extra-pulmonary LAM that should be considered in LAM transplant patients with dyspnea. PMID:19134542
Sottile, Peter D; Iturbe, David; Katsumoto, Tamiko R; Connolly, M Kari; Collard, Harold R; Leard, Lorriana A; Hays, Steven; Golden, Jeffrey A; Hoopes, Charles; Kukreja, Jasleen; Singer, Jonathan P
Background Lung disease (LD) is the leading cause of death in systemic sclerosis (SSc). The diagnosis of SSc-related LD (SSc-LD) is often a contraindication to lung transplantation (LT) due to concerns that extra-pulmonary involvement will yield worse outcomes. We sought to evaluate post-transplant outcomes in persons with SSc-LD with esophageal involvement compared to persons with non-connective tissue disease related interstitial lung disease (nCTD-ILD). Methods From 1998-2012, persons undergoing LT for SSc-LD were age and gender matched in a 2:1 fashion to controls undergoing LT for nCTD-ILD. Esophageal function was assessed by pH testing and manometry. We defined esophageal dysfunction as the presence of a DeMeester score >14 or dysmotility more severe than “mild non-specific disorder”. The primary outcome was post-transplant survival. Secondary outcomes included freedom from bronchiolitis obliterans syndrome (fBOS) and rates of acute rejection. Survival and fBOS were estimated with Kaplan-Meier methods. Acute rejection was compared with Students t-test. Results Survival was similar in 23 persons with SSc-LD and 46 controls who underwent LT (p=0.47). For the SSc-LD group, 1- and 5-year survival was 83% and 76% compared to 91% and 64% in the nCTD-ILD group. There were no differences in fBOS (p=0.83). Rates of acute rejection were less in SSc-ILD (p=0.05). Esophageal dysfunction was not associated with worse outcomes (p>0.55). Conclusions Persons with SSc-LD appear to have similar survival and fBOS as persons transplanted for nCTD-ILD. The risk of acute rejection after transplant may be reduced in persons with SSc-LD. Esophageal involvement does not appear to impact outcomes. PMID:23545509
Tikkanen, Jussi M; Singer, Lianne G; Kim, S Joseph; Li, Yanhong; Binnie, Matthew; Chaparro, Cecilia; Chow, Chung-Wai; Martinu, Tereza; Azad, Sassan; Keshavjee, Shaf; Tinckam, Kathryn
Despite increasing evidence about the role of donor-specific human leukocyte antigen (HLA) antibodies in transplant outcomes, the incidence and impact of de novo donor-specific antibodies (dnDSA) after lung transplantation remains unclear. To describe the incidence, characteristics, and impact of dnDSA after lung transplantation. We investigated a single-center cohort of 340 lung transplant recipients undergoing transplant during 2008 to 2011. All patients underwent HLA-antibody testing quarterly pretransplant and at regular intervals over the first 24 months after transplant. The patients received modified immunosuppression depending on their pretransplant sensitization status. Risk factors for dnDSA development, as well as the associations of dnDSA with patient survival and chronic lung allograft dysfunction (CLAD), were determined using multivariable analysis. The cumulative incidence of dnDSA was 47% at a median of 86 days (range, 44-185 d) after lung transplantation. Seventy-six percent of recipients with dnDSA had DQ-DSA. Male sex and the use of ex vivo lung perfusion were associated with an increased risk of dnDSA, whereas increased HLA-DQB1 matching was protective. DQ-dnDSA preceded or coincided with the diagnosis of CLAD in all cases. Developing dnDSA (vs. no dnDSA) was associated with a twofold increased risk of CLAD (hazard ratio, 2.04; 95% confidence interval, 1.13-3.69). This association appeared to be driven by the development of DQ-dnDSA. dnDSA are common after lung transplantation, with the majority being DQ DSA. DQ-dnDSA are associated with an increased risk of CLAD. Strategies to prevent or treat DQ-dnDSA may improve outcomes for lung transplant recipients.
Paraskeva, Miranda A; Edwards, Leah B; Levvey, Bronwyn; Stehlik, Josef; Goldfarb, Samuel; Yusen, Roger D; Westall, Glen P; Snell, Greg I
Recipient adolescent age for non-lung solid-organ transplantation is associated with higher rates of rejection, graft loss and mortality. Although there have been no studies specifically examining adolescent outcomes after lung transplantation (LTx), limited data from the International Society of Heart and Lung Transplantation (ISHLT) Registry suggest that a similar association may exist. Recently, adolescence has been defined as 10 to 24 years of age, taking into account the biologic and sociologic transitions that occur during this age interval. The ISHLT Registry was used to examine the survival outcomes of LTx recipients 10 to 24 years of age between 2005 and 2013. Given the developmental changes that occur in adolescence, survival outcomes for the tertiles of adolescence (10 to 14, 15 to 19 and 20 to 24 years old) were also examined. Adolescents made up 9% (n = 2,319) of the 24,730 LTxs undertaken during the study period. Kaplan-Meier survival estimates at 3 years showed lower adolescent survival (65%) when compared with younger children (73%, p = 0.006) and adults 25 to 34 (75%, p < 0.00001) and 35 to 49 (71%, p < 0.00001) years of age, without a significant survival difference compared with those 50 to 65 years old. Critically, 15- to 19-year-old recipients had the poorest outcomes, with reduced 1-year survival (82%) compared with those 10 to 14 years old (88%, p = 0.02), and reduced 3-year survival (59%) compared with those 10 to 14 (73%, p < 0.00001) and 20 to 24 (66%, p < 0.0001) years old. Adolescent LTx recipients have poorer overall survival when compared with younger children and adults, with those 15 to 19 years old having the highest risk of death. This survival disparity among age groups likely reflects the difficult period of adolescence and its biologic and social transitions, which may influence both immunologic function and adherence. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All
Tokman, S; Hays, S R; Leard, L E; Bush, E L; Kukreja, J; Kleinhenz, M E; Golden, J A; Singer, J P
Lung transplantation can be a life-saving measure for people with end-stage lung disease from systemic sclerosis. However, outcomes of lung transplantation may be compromised by gastrointestinal manifestations of systemic sclerosis, which can involve any part of the gastrointestinal tract. Esophageal and gastric disease can be managed by enteral feeding with the use of a gastrojejunal feeding tube. In this report, we describe the clinical courses of 2 lung transplant recipients with systemic sclerosis who experienced severe and prolonged barium-impaction ileus after insertion of a percutaneous gastrojejunal feeding tube.
Palacio, Federico; Reyes, Luis F.; Levine, Deborah J.; Sanchez, Juan F.; Angel, Luis F.; Fernandez, Juan F.; Levine, Stephanie M.; Rello, Jordi; Abedi, Ali
BACKGROUND: Limited data are available regarding the etiologic impact of health care-associated pneumonia (HCAP) in lung transplant recipients. Therefore, our aim was to evaluate the microbiologic differences between HCAP and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in lung transplant recipients with a radiographically confirmed diagnosis of pneumonia. METHODS: We performed a retrospective cohort study of lung transplant recipients with pneumonia at one transplant center over a 7-year period. Eligible patients included lung transplant recipients who developed a first episode of radiographically confirmed pneumonia ≥ 48 h following transplantation. HCAP, HAP, and VAP were classified according to the American Thoracic Society/Infectious Diseases Society of America 2005 guidelines. χ2 and Student t tests were used to compare categorical and continuous variables, respectively. RESULTS: Sixty-eight lung transplant recipients developed at least one episode of pneumonia. HCAP (n = 42; 62%) was most common, followed by HAP/VAP (n = 26; 38%) stratified in HAP (n = 20; 77%) and VAP (n = 6; 23%). Pseudomonas aeruginosa was the predominantly isolated organism (n = 22; 32%), whereas invasive aspergillosis was uncommon (< 10%). Multiple-drug resistant (MDR) pathogens were less frequently isolated in patients with HCAP compared with HAP/VAP (5% vs 27%; P = .009). Opportunistic pathogens were less frequently identified in lung transplant recipients with HCAP than in those with HAP/VAP (7% vs 27%; P = .02). Lung transplant recipients with HCAP had a similar mortality at 90 days (n = 9 [21%] vs n = 4 [15%]; P = .3) compared with patients with HAP/VAP. CONCLUSIONS: HCAP was the most frequent infection in lung transplant recipients. MDR pathogens and opportunistic pathogens were more frequently isolated in HAP/VAP. There were no differences in 30- and 90-day mortality between lung transplant recipients with HCAP and those with HAP/VAP. PMID:25742187
Tissot, Cecile; Habre, Walid; Soccal, Paola; Hug, Maja Isabel; Bettex, Dominique; Pellegrini, Michel; Aggoun, Yacine; Mornand, Anne; Kalangos, Afksendyios; Rimensberger, Peter; Beghetti, Maurice
Introduction The use of extracorporeal membrane oxygenation (ECMO) is considered a risk factor for, or even a potential contraindication to, lung transplantation. However, only a few pediatric cases have been described thus far. Case Presentation A 9-year-old boy with idiopathic pulmonary arterial hypertension developed cardiac arrest after the insertion of a central catheter. ECMO was used as a bridge to lung transplantation. However, after prolonged resuscitation, he developed medullary ischemia and medullary syndrome. After 6 weeks of ECMO and triple combination therapy for pulmonary hypertension, including continuous intravenous prostacyclin, he was weaned off support, and after 2 weeks, bilateral lung transplantation was performed. At 4 years post-transplant, he has minimal problems. The medullary syndrome has also alleviated. He is now back to school and can walk with aids. Conclusions Increasing evidence supports the use of ECMO as a bridge to LT, reporting good outcomes. In the modern era of PAH therapy, it is feasible to use prolonged ECMO support as a bridge to lung transplant, with the aim of weaning off this support; however, its use requires more experience and knowledge of long-term outcomes. PMID:27800456
Otani, Shinji; Westall, Glen P; Levvey, Bronwyn J; Marasco, Silvana; Lyon, Stuart; Snell, Gregory I
The superior vena cava (SVC) syndrome in cystic fibrosis (CF) patients is rare, but presents unique challenges in the peri-transplant period. We reviewed our experience of SVC syndrome in CF recipients undergoing lung transplantation. This is a retrospective case series from a single center chart-review. SVC obstruction is defined by clinically significant stenosis or obstruction of the SVC as detected by contrast studies. We identified SVC obstruction in seven post-transplant cases and one pre-transplant case. All eight patients had previous or current history of indwelling central venous catheters. Three recipients experienced operative complications. Five of the seven recipients suffered at least one episode of post-operative SVC obstruction or bleeding despite prophylactic anticoagulation. At a median follow-up of 29 months, six of the seven patients transplanted are well. Strategies are available to minimize the risks of intra/peri-operative acute life-threatening SVC obstruction in CF patients. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Abreu, Marcus da Matta; Pazetti, Rogerio; Almeida, Francine Maria de; Correia, Aristides Tadeu; Parra, Edwin Roger; Silva, Laís Pereira da; Vieira, Rodolfo de Paula; Pêgo-Fernandes, Paulo Manuel; Jatene, Fabio Biscegli
Ischemia-reperfusion injury (IRI) is one of the principal obstacles for the lung transplantation (LTx) success. Several strategies have been adopted to minimize the effects of IRI in lungs, including ex vivo conditioning of the grafts and the use of antioxidant drugs, such as methylene blue (MB). We hypothesized that MB could minimize the effects of IRI in a LTx rodent model. Forty rats were divided into four groups (n = 10) according to treatment (saline solution or MB) and graft cold ischemic time (3 or 6 h). All animals underwent unilateral LTx. Recipients received 2 mL of saline or MB intraperitoneally before transplantation. After 2 h of reperfusion, arterial blood and exhaled nitric oxide samples were collected and bronchoalveolar lavage performed. Then animals were euthanized, and histopathology analysis as well as cell counts and cytokine levels measurements in bronchoalveolar lavage fluid were performed. There was a significant decrease in exhaled nitric oxide, neutrophils, interleukin-6, and tumor necrosis factor-α in MB-treated animals. PaO2 and uric acid levels were higher in MB group. MB was able in attenuating IRI in this LTx model. Copyright © 2014 Elsevier Inc. All rights reserved.
Tabarelli, Walther; Bonatti, Hugo; Tabarelli, Dominique; Eller, Miriam; Müller, Ludwig; Ruttmann, Elfriede; Lass-Flörl, Cornelia; Larcher, Clara
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
Lynch, Joseph P.; Sayah, David M.; Belperio, John A.; Weigt, S. Sam
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
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
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.
Hashimoto, Kohei; Miyoshi, Kentaroh; Mizutani, Hisao; Otani, Shinji; Sugimoto, Seiichiro; Yamane, Masaomi; Oto, Takahiro
A 53-year-old man with pulmonary fibrosis associated with Erdheim-Chester disease achieved long-term survival after lung transplantation. Major clinical manifestations included lung and bone injuries, and other vital organs were functionally unaffected by the disease. After a careful observation for the disease progression, he underwent bilateral deceased-donor lung transplantation. He has returned to his normal social life and is doing well without recurrence of Erdheim-Chester disease in the lung allograft or progression in other organs 5 years after transplant. Lung transplantation is a potentially reasonable treatment option for Erdheim-Chester disease involving the lungs if the functions of other vital organs remain stable. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Eberlein, Michael; Reed, Robert M; Chahla, Mayy; Bolukbas, Servet; Blevins, Amy; Van Raemdonck, Dirk; Stanzi, Alessia; Inci, Ilhan; Marasco, Silvana; Shigemura, Norihisa; Aigner, Clemens; Deuse, Tobias
AIM To systematically review reports on deceased-donor-lobar lung transplantation (ddLLTx) and uniformly describe size matching using the donor-to-recipient predicted-total lung-capacity (pTLC) ratio. METHODS We set out to systematically review reports on ddLLTx and uniformly describe size matching using the donor-to-recipient pTLC ratio and to summarize reported one-year survival data of ddLLTx and conventional-LTx. We searched in PubMed, CINAHL via EBSCO, Cochrane Database of Systematic Reviews via Wiley (CDSR), Database of Abstracts of Reviews of Effects via Wiley (DARE), Cochrane Central Register of Controlled Trials via Wiley (CENTRAL), Scopus (which includes EMBASE abstracts), and Web of Science for original reports on ddLLTx. RESULTS Nine observational cohort studies reporting on 301 ddLLTx met our inclusion criteria for systematic review of size matching, and eight for describing one-year-survival. The ddLLTx-group was often characterized by high acuity; however there was heterogeneity in transplant indications and pre-operative characteristics between studies. Data to calculate the pTLC ratio was available for 242 ddLLTx (80%). The mean pTLCratio before lobar resection was 1.25 ± 0.3 and the transplanted pTLCratio after lobar resection was 0.76 ± 0.2. One-year survival in the ddLLTx-group ranged from 50%-100%, compared to 72%-88% in the conventional-LTx group. In the largest study ddLLTx (n = 138) was associated with a lower one-year-survival compared to conventional-LTx (n = 539) (65.1% vs 84.1%, P < 0.001). CONCLUSION Further investigations of optimal donor-to-recipient size matching parameters for ddLLTx could improve outcomes of this important surgical option. PMID:28280698
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
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
Pasupneti, Shravani; Dhillon, Gundeep; Reitz, Bruce; Khush, Kiran
Heart lung transplantation is a viable treatment option for patients with many end-stage heart and lung pathologies. However, given the complex nature of the procedure, it is imperative that patients are selected appropriately, and the clinician is aware of the many unique aspects in management of this population. This review seeks to describe updated organ selection policies, perioperative and postoperative management strategies, monitoring of graft function, and clinical outcomes for patients after combined heart-lung transplantation in the current era.
Adamali, Huzaifa I; Judge, Eoin P; Healy, David; Nolke, Lars; Redmond, Karen C; Bartosik, Waldemar; McCarthy, Jim
Objective Prior to 2005, Irish citizens had exclusively availed of lung transplantation services in the UK. Since 2005, lung transplantation has been available to these patients in both the UK and Ireland. We aimed to evaluate the outcomes of Irish patients undergoing lung transplantation in both the UK and Ireland. Design We retrospectively examined the outcome of Irish patients transplanted in the UK and Ireland. Lung allocation score (LAS) was used as a marker of disease severity. Results A total of 134 patients have undergone transplantation. 102 patients underwent transplantation in the UK and 32 patients in Ireland. In total, 52% were patients with cystic fibrosis, 19% had emphysema and 15% had idiopathic pulmonary fibrosis. In Ireland, 44% of the patients suffered from idiopathic pulmonary fibrosis, 31% had emphysema and 16% had cystic fibrosis. A total of 96 double sequential transplants and 38 single transplants have been performed. LAS of all patients undergoing lung transplantation was 37.8 (±1.02). The mean LAS for patients undergoing lung transplantation in Ireland was 44.7 (±3.1), and 35 (±0.4) for patients undergoing lung transplantation in the UK (p<0.05). The 5-year survival of all Irish citizens who had undergone lung transplantation was 73%. The 5-year survival of Irish patients transplanted in the UK was 69% and in Ireland was 91% and 73% at 5.01 years. Conclusions International collaboration can be achieved, as evidenced by the favourable outcomes seen in Irish citizens who undergo lung transplantation in both the UK and Ireland. Irish citizens undergoing lung transplantation in Ireland have a higher LAS score. Despite excellent outcomes, an intention-to-treat analysis of the treatment utility (transplant) indicates the limited effectiveness of lung transplantation in Ireland and emphasises the need for increased rates of lung transplantation. PMID:22457478
Tokman, Sofya; Singer, Jonathan P.; Devine, Megan S.; Westall, Glen P.; Aubert, John-David; Tamm, Michael; Snell, Gregory I.; Lee, Joyce S.; Goldberg, Hilary J.; Kukreja, Jasleen; Golden, Jeffrey A.; Leard, Lorriana E.; Garcia, Christine K.; Hays, Steven R.
Background Successful lung transplantation (LT) for patients with pulmonary fibrosis from telomerase mutations is limited by systemic complications of telomerase dysfunction including myelosuppression, cirrhosis, and malignancy. We describe clinical outcomes among 14 LT recipients with telomerase mutations. Methods Subjects underwent LT between February 2005 and April 2014 at 5 LT centers. We abstracted data from medical records, focusing on outcomes reflecting post-LT treatment effects likely to be complicated by telomerase mutations. Results The median age of subjects was 60.5 years (IQR 52.0–62.0), 64.3% were male, and the mean post-LT observation time was 3.2 years (SD ±2.9). Eleven subjects had a mutation in telomerase reverse transcriptase, 2 in telomerase RNA component, and 1 had an uncharacterized mutation. Ten subjects were leukopenic post-LT; leukopenia prompted cessation of mycophenolate mofetil in 5 and treatment with filgrastim in 4. Six subjects had recurrent lower respiratory tract infections (LRTI), 7 had acute cellular rejection (ACR) (A1), and 4 developed chronic lung allograft dysfunction (CLAD). Ten LT recipients developed chronic renal insufficiency and 8 experienced acute, reversible renal failure. Three developed cancer, none had cirrhosis. Thirteen subjects were alive at data censorship. Conclusions The clinical course for LT recipients with telomerase mutations is complicated by renal disease, leukopenia prompting a change in the immunosuppressive regimen, and recurrent LTRI. In contrast, cirrhosis was absent, ACR was mild, and development of CLAD was comparable to other LT populations. While posing challenges, lung transplantation may be feasible for patients with pulmonary fibrosis due to telomerase mutations. PMID:26169663
Bittner, Hartmuth B; Binner, Christian; Lehmann, Sven; Kuntze, Thomas; Rastan, Ardawan; Mohr, Friedrich W
Cardiopulmonary bypass (CPB) support is required in some lung transplantation (LTX) operations. CPB support and full-dose heparin increases the risks of bleeding and early graft dysfunction. We report our experiences of replacing CPB with heparin-bonded low-dose heparin extracorporeal membrane oxygenation (ECMO) support in LTX surgery. From 2003 to 2005 forty-seven patients were transplanted. Thirty-seven LTX patients were retrospectively evaluated for this study (10 patients were excluded due to heart-lung-, lung-kidney transplantation, LTX with bypass grafting, and ASD closure or emergency CPB support). Extracorporeal circulation support was necessary in 40% of the 37 LTX patients due to severe primary or secondary pulmonary hypertension (P or SPHTN), right heart dysfunction, or hemodynamic instability. There were seven LTX procedures with CPB and eight implantations with ECMO support. CPB (high-dose heparin) and ECMO support (ACT 160-220 s) was always set up through femoral veno-arterial canulation. All patients had limited access thoracotomies without transsection of the sternum. Normothermia was maintained in all patients. CPB patients: PPH 15%, COPD 15%, IPF with mean PAP>40 mmHg 70%. ECMO patients: PPH 13%, COPD 13%, IPF with severe PAP pressure elevation 74%. In patients undergoing LTX for PPH, the ECMO support was directly extended into the post-operative period. Packed red blood cell (PRBC) transfusion requirements during the operation and the first 24h were 13.25+/-1.6 PRBC units versus 5.1+/-2.8 PRBC units on CBP (p=0.02). Operative time was longer (p=0.11) in the ECMO LTX (451 min+/-76 vs 346+/-140). The increased 90-day mortality rate of the ECMO patients showed a trend toward significance (p=0.056), which was related to infectious complications (3 vs 1 patient). Severe graft ischemia/reperfusion injury occurred in 9% in the CPB versus 13% in the ECMO group. The 1-year survival was significantly reduced in ECMO patients (p=0.004, log-rank test). The
Washburn, W K; Bradley, J; Cosimi, A B; Freeman, R B; Hull, D; Jenkins, R L; Lewis, W D; Lorber, M I; Schweizer, R T; Vacanti, J P; Rohrer, R J
Liver transplantation for patients requiring life-support results in the lowest survival and highest costs. A ten year (1983-1993) regional experience with liver transplantation for critically ill patients was undertaken to ascertain the fate of several subgroups of patients. Of the 828 liver transplants performed at six transplant centers within the region over this period, 168 (20%) were done in patients who met today's criteria for a United Network of Organ Sharing (UNOS) status 1 (emergency) liver transplant candidate. Recipients were classified according to chronicity of disease and transplant number (primary-acute, primary-chronic, reTx-acute, reTx-chronic). Overall one-year survival was 50% for all status 1 recipients. The primary-acute subgroup (n = 63) experienced a 57% one-year survival compared with 50% for the primary-chronic (n = 51) subgroup (P = 0.07). Of the reTx-acute recipients (n = 43), 44% were alive at one year in comparison with 20% for the reTx-chronic (n = 11) group (P = 0.18). There was no significant difference in survival for the following: transplant center, blood group compatibility with donors, age, preservation solution, or graft size. For patients retransplanted for acute reasons (primary graft nonfunction (PGNF) or hepatic artery thrombosis [HAT]), survival was significantly better if a second donor was found within 3 days of relisting (52% vs. 20%; P = 0.012). Over the study period progressively fewer donor organs came from outside the region. No strong survival-based argument can be made for separating, in allocation priority, acute and chronic disease patients facing the first transplant as a status 1 recipient. Clearly patients suffering from PGNF or HAT do far better if retransplanted within 3 days. Establishing an even higher status for recipients with PGNF, perhaps drawing from a supraregional donor pool, would allow surgeons to accept more marginal donors, thus potentially expanding the pool, without significantly
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.
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
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.
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…
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.
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…
Fisichella, Piero Marco; Davis, Christopher S.; Shankaran, Vidya; Gagermeier, James; Dilling, Daniel; Alex, Charles G.; Kovacs, Elizabeth J.; Joehl, Raymond J.; Love, Robert B.
Background Evidence is increasingly convincing that lung transplantation is a risk factor of gastroesophageal reflux disease (GERD). However, it is still not known if the type of lung transplant (unilateral, bilateral, or retransplant) plays a role in the pathogenesis of GERD. Study Design The records of 61 lung transplant patients who underwent esophageal function tests between September 2008 and May 2010, were retrospectively reviewed. These patients were divided into 3 groups based on the type of lung transplant they received: unilateral (n=25); bilateral (n=30), and retransplant (n=6). Among these groups we compared: (1) the demographic characteristics (eg, sex, age, race, and body mass index); (2) the presence of Barrett esophagus, delayed gastric emptying, and hiatal hernia; and (3) the esophageal manometric and pH-metric profile. Results Distal and proximal reflux were more prevalent in patients with bilateral transplant or retransplant and less prevalent in patients after unilateral transplant, regardless of the cause of their lung disease. The prevalence of hiatal hernia, Barrett esophagus, and the manometric profile were similar in all groups of patients. Conclusions Although our data show a discrepancy in prevalence of GERD in patients with different types of lung transplantation, we cannot determine the exact cause for these findings from this study. We speculate that the extent of dissection during the transplant places the patients at risk for GERD. On the basis of the results of this study, a higher level of suspicion of GERD should be held in patients after bilateral or retransplantation. PMID:22318059
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
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
Shitrit, David; Gershman, Yvgeni; Peled, Nir; Medalion, Benjamin; Saute, Milton; Amital, Anat; Kramer, Mordechai R
Patients with end-stage lung disease very frequently die while awaiting lung transplantation. The aim of this study was to identify factors associated with mortality in patients referred for lung transplant assessment. The files of all consecutive patients listed for lung transplantation in Israel between 1997 and 2006 were reviewed and the data were compared statistically between those who survived to transplantation. A total of 229 patients were listed for lung transplantation, of whom 42 (18.3%) died while awaiting transplantation. Comparison of the patients who survived to transplantation with those who did not using univariate analysis revealed that the died-waiting group was significantly older, used steroids to a greater extent, had more IPF patients and less emphysematous, and lower mean oxygen saturation at rest (p=0.005). There were no between-group differences in comorbid diseases or pulmonary function measurements. The 6 min walk distance was strongly and inversely correlated with risk of death before transplantation (p=0.005). On multivariate analysis, only oxygen saturation at rest was a significant independent risk factor for death while awaiting transplantation (OR 0.886; C.I. 0.805-0.974). There are several risk factors for death in the Israeli population listed for LTX, including age, steroid use, emphysematous patients and lower saturation at rest.
Speicher, Paul J; Ganapathi, Asvin M; Englum, Brian R; Gulack, Brian C; Osho, Asishana A; Hirji, Sameer A; Castleberry, Anthony W; Snyder, Laurie D; Davis, R Duane; Hartwig, Matthew G
Background The purpose of this study was to assess treatment patterns and examine organ utilization in the setting of single lung transplantation (SLT). Methods The United Network for Organ Sharing database was queried for all SLTs performed from 1987–2011. Trends in utilization of the second donor lung were assessed, both from recipient and donor perspectives. Donors were stratified into two groups: those donating both lungs and those donating only one. Independent predictors of utilizing only one donor lung were identified using multivariable logistic regression. Results 10,361 SLTs were identified, originating from 7,232 unique donors. Of these donors, only 3,129 (43.3%) had both lungs utilized, resulting in over 200 second donor lungs going unused annually since 2005, with no significant increase in utilization over time (p=.95). Following adjustment, donor characteristics predicting the second donor lung going unused included B/AB blood groups (adjusted odds ratio [AOR]: 1.69 and 2.62, respectively, p<.001), lower body surface area (AOR 1.30, p=.02), lower donor pO2 (AOR 0.90 per 50 mmHg increase, p<.001), pulmonary infection (AOR 1.15, p=.04), extended criteria donor status (AOR 1.66, p<.001), and head trauma or anoxia cause of death (AOR 1.57 and 1.53, p<.001 and p=.001, respectively). Conclusions Among donors for SLT, less than half of all cases led to use of the second donor lung. While anatomic, infectious, or other pathophysiologic issues prohibit 100% utilization, more aggressive donor matching efforts may be a simple method of increasing the utilization of this scarce resource, particularly for less common blood types. PMID:25305097
Shepherd, Edward G.; Gee, Samantha W.
Pediatric lung transplantation is a life-saving intervention for children with irreversible end-stage lung disease. Access to transplant can be limited by geographic isolation from a center or the presence of comorbidities affecting transplant eligibility. Extracorporeal membrane oxygenation (ECMO)-supported patients are an uncommon but historically high-risk cohort of patients considered for lung transplant. We report the development of a service at our center to provide transport services to our hospital for patients unable to wean from ECMO support at their local institution for the purpose of evaluation for lung transplantation by our program. We developed a process for pre-transport consultation by the lung transplant physician team, standardized hand-off tools and equipment lists, and procedures for transitioning patients to transport ECMO machinery. Four patients have been transported to date including fixed wing (FW) and helicopter transports. All patients were successfully transported with either none or minor complications. Transport of ECMO-supported patients is a feasible method to increase access of patients with irreversible lung injured patients to evaluation for lung transplant. PMID:28275613
Amital, Anat; Shitrit, David; Raviv, Yael; Saute, Milton; Bakal, Ilana; Medalion, Benjamin; Kramer, Mordechai R
Impaired surfactant activity may contribute to primary graft dysfunction after lung transplantation. We assessed the role of surfactant treatment in lung transplant recipients with severe life threatening primary lung graft dysfunction. Five patients after lung transplantation: 4 after single-lung transplantation, for emphysema (n=3) or idiopathic pulmonary fibrosis (n=1), and 1 patient after double-lung transplantation for cystic fibrosis. All had severe life threatening primary graft dysfunction that failed to respond to conventional measures. Treatment consisted of bronchoscopic instillation of mammalian surfactant, 20-90cc, at 3 (n=1) or 7 days (n=4) after transplantation. There was a significant improvement in the ratio of partial arterial oxygen tension (PaO(2)) to fractional concentration of oxygen in inspired gas (FIO(2)), from a mean of 98.8+/-21.7 to 236.8+/-52.3 mmHg (p=0.0006), within hours of treatment. All were eventually discharged home and showed a satisfactory FEV(1) (44-67% predicted) at the 6-month follow-up. All patients were still alive 6 months or more after transplantation. Surfactant treatment improves oxygenation and may be life saving in patients with primary lung graft dysfunction.
Frazier, W Joshua; Shepherd, Edward G; Gee, Samantha W
Pediatric lung transplantation is a life-saving intervention for children with irreversible end-stage lung disease. Access to transplant can be limited by geographic isolation from a center or the presence of comorbidities affecting transplant eligibility. Extracorporeal membrane oxygenation (ECMO)-supported patients are an uncommon but historically high-risk cohort of patients considered for lung transplant. We report the development of a service at our center to provide transport services to our hospital for patients unable to wean from ECMO support at their local institution for the purpose of evaluation for lung transplantation by our program. We developed a process for pre-transport consultation by the lung transplant physician team, standardized hand-off tools and equipment lists, and procedures for transitioning patients to transport ECMO machinery. Four patients have been transported to date including fixed wing (FW) and helicopter transports. All patients were successfully transported with either none or minor complications. Transport of ECMO-supported patients is a feasible method to increase access of patients with irreversible lung injured patients to evaluation for lung transplant.
Schlendorf, Kelly H; Shah, Ashish S
The purpose of the review is to update our current understanding and utilization of immunogenetic tools in heart and lung transplant. Increasingly, complex patients have been managed perioperatively for heart and lung transplant using a variety of tests and techniques. Recent treatment regimens and listing strategies have exploited recent laboratory advances. However, the better characterization has led to an even more complex description of sensitized heart and lung candidates. Several recent studies have examined antibody strengths and behavior to guide clinical decision-making and examine postoperative outcomes. Finally, non-human leukocyte antigen antibodies have emerged as possible determinants of allograft outcome in heart and lung transplant. Heart and lung transplant candidates with preformed and de-novo posttransplant antibodies continue to represent a challenging and high-risk group of patients. Modern immunogenetic techniques have broadened our understanding and have revealed an even more complex relationship between antibodies, allografts, and outcomes.
Lisbona, R.; Hakim, T.S.; Dean, G.W.; Langleben, D.; Guerraty, A.; Levy, R.D. )
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.
Geltner, Christian; Lass-Flörl, Cornelia
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. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Wallinder, Andreas; Ricksten, Sven-Erik; Silverborn, Martin; Hansson, Christoffer; Riise, Gerdt C; Liden, Hans; Jeppsson, Anders; Dellgren, Göran
An increasing number of studies have shown that ex vivo lung perfusion (EVLP) is safe and that rejected donor lungs can be resuscitated and used for lung transplantation (LTx). Early clinical outcomes in patients transplanted with reconditioned lungs at our centre were reviewed and compared with those of contemporary non-EVLP controls. During 18 months starting January 2011, 11 pairs of donor lungs initially deemed unsuitable for transplantation underwent EVLP. Haemodynamic (pulmonary flow, vascular resistance and artery pressure) and respiratory (peak airway pressure and compliance) parameters were analysed during evaluation. Lungs that improved (n = 11) to meet International Society of Heart and Lung Transplantation criteria were transplanted and compared with patients transplanted with non-EVLP lungs (n = 47) during the same time period. Donor lungs were initially rejected due to either inferior PaO2/FiO2 ratio (n = 9), bilateral infiltrate on chest X-ray (n = 1) or ongoing extra corporeal membrane oxygenation (n = 1). The donor lungs improved from a mean PaO2/FiO2 ratio of 27.9 kPa in the donor to a mean of 59.6 kPa at the end of the EVLP (median improvement 28.4 kPa, range 21.0-50.7 kPa). Two single lungs were deemed unsuitable and not used for LTx. Eleven recipients from the regular waiting list underwent either single (n = 3) LTx or double (n = 8) LTx with EVLP-treated lungs. The median time to extubation (12 (range, 3-912) vs 6 (range, 2-1296) h) and median intensive care unit (ICU) stay (152 (range, 40-625) vs 48 (range, 22-1632) h) were longer in the EVLP group (P = 0.05 and P = 0.01, respectively). There were no differences in length of hospital stay (median 28 (range 25-93) vs 28 (18-209), P = 0.21). Two patients in the EVLP group and 6 in the control group had primary graft dysfunction >Grade 1 at 72 h postoperatively. Three patients in the control group died before discharge. All recipients of EVLP lungs were discharged alive from hospital. The use of
Huang, Jian Qun; Shahine, Lora K; Gupta, Nidhi; Westphal, Lynn M
Cystic fibrosis (CF) is one of the most common genetic disorders that can often lead to chronic pulmonary disease. Patients with respiratory failure due to CF may achieve a good quality of life after lung transplant, and many will desire to have children. A 26-year-old, nulliparous female with CF and double lung transplant presented for fertility treatment. She was successfully treated with controlled ovarian hyperstimulation and gestational surrogacy. Controlled ovarian hyperstimulation and gestational surrogacy is a safe option for patients with lung transplant to have a genetic child.
Hartwig, Mathew G.; Hayes, Don
Evolution in technology has resulted in rapid increase in utilization of extracorporeal membrane oxygenation (ECMO) as a bridge to recovery and/or transplantation. Although there is limited evidence for the use of ECMO, recent improvements in ECMO technology, personnel training, ambulatory practices on ECMO and lung protective strategies have resulted in improved outcomes in patients bridged to lung transplantation. This review provides an insight into the current outcomes and best practices for utilization of ECMO in the pre- and post-lung transplantation period. PMID:28275619
Julliard, Walker A; Meyer, Keith C; De Oliveira, Nilto C; Osaki, Satoru; Cornwell, Richard C; Sonetti, David A; Maloney, James D
Advanced lung disease (ALD) that requires lung transplantation (LTX) is frequently associated with pulmonary hypertension (PH). Whether the presence of PH significantly affects the outcomes following single-lung transplantation (SLT) remains controversial. Therefore, we retrospectively examined the outcomes of 279 consecutive SLT recipients transplanted at our centre, and the patients were split into four groups based on their mean pulmonary artery pressure values. Outcomes, including long-term survival and primary graft dysfunction, did not differ significantly for patients with versus without PH, even when PH was severe. We suggest that SLT can be performed safely in patients with ALD-associated PH.
Sharma, Nirmal S; Hartwig, Mathew G; Hayes, Don
Evolution in technology has resulted in rapid increase in utilization of extracorporeal membrane oxygenation (ECMO) as a bridge to recovery and/or transplantation. Although there is limited evidence for the use of ECMO, recent improvements in ECMO technology, personnel training, ambulatory practices on ECMO and lung protective strategies have resulted in improved outcomes in patients bridged to lung transplantation. This review provides an insight into the current outcomes and best practices for utilization of ECMO in the pre- and post-lung transplantation period.
Björkbom, Emil; Hämmäinen, Pekka; Schramko, Alexey
Approximately 10 to 25 lung transplant procedures are performed annually in Finland, and 1-year survival has been 95% over the last 10 years. Our aim was to find associations between perioperative fluid replacement therapies and postoperative patient outcomes, with special emphasis on the use of colloids and blood products. We retrospectively evaluated data from 100 patients who underwent lung transplant with cardiopulmonary bypass support in Finland from 2007 to 2013. Outcomes of interest were length of intensive care unit and hospital stays, time in ventilator, use of extracorporeal membrane oxygenation postoperatively, postoperative renal replacement therapy, postoperative graft failure, and 1-year mortality. Of 100 patients, 12 were on extracorporeal membrane oxygenation preoperatively. The 1-year mortality was 5/100 (5%), and the 3-year mortality was 7/100 (7%). Intraoperative fluid balance was positive (4762 a 3018 mL) but fell significantly postoperatively (below +1000 mL on postoperative day 1). During postoperative days 2 to 7, net fluid balance continued decreasing and stayed negative. Intraoperative use of hydroxyethyl starch and fresh frozen plasma were significantly higher in patients who died during follow-up versus those who survived (P < .05). Intraoperative use of fresh frozen plasma, but not red blood cells or platelets, correlated with graft failure (P = .012). Postoperative use of colloids or blood products did not correlate with mortality or graft failure. Patients who were on extracorporeal membrane oxygenation preoperatively stayed longer on ventilators and had longer intensive care unit and hospital stays (P < .001). Eight patients needed postoperative renal replacement therapy. Intraoperative use of fresh frozen plasma and hydroxyethyl starch is associated with increased mortality and graft failure. Postoperative use of colloids and red blood cells did not correlate with patient outcome. Use of extracorporeal membrane oxygenation
Cerón Navarro, José; de Aguiar Quevedo, Karol; Jordá Aragón, Carlos; Peñalver Cuesta, Juan C; Mancheño Franch, Nuria; Vera Sempere, Francisco; Padilla Alarcón, José
Lung transplantation (LT) has been considered an alternative therapeutic approach in terminal patients. However, this process in COPD is not controversy-free. This paper aimed to analyze 30-day mortality (PM) patterns and their risk factors in COPD patients undergoing LT. A retrospective cohort with 107 COPD patients, transplanted at the University La Fe Valencia, Spain, treated from January 1991 to December 2008. Demographics values, degree of dyspnoea, diagnosis, BODE index, single versus bilateral LT, cardio-pulmonary bypass, donor age, steroid dependence, presence of bronchiectasis, retrograde perfusion, transfusion of blood products, and PaO2/FiO2 were analyzed. Continuous variables were expressed as mean±SD and categorical variables as absolute frequency and percentage. A Cox regression model was used for multivariate analysis. Ninety-four men and 13 women of a mean age of 52.58±8.05 years were transplanted. Of all patients, 75% obtained a BODE score above 7. There were 76 bilateral LT. PM was established at 14%. Main causes of death were infection (53.3%) and surgical complications (33.3%). Presence of bronchiectasis and chronic use of corticosteroids, donor/recipient difference in size and presence of fat in retrograde perfusion fluid were important risk factors for PM. Moreover, PaO2/FiO2 ratio at 6h was a protective factor for the event, thus a higher ratio value, lowered the risk of PM. LT is a procedure with a high PM rate. Use of corticosteroids, the presence of bronchiectasis and fat emboli in the retrograde reperfusion, and PaO2/FiO2 significantly determine PM. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.
Penninga, Luit; Penninga, Elisabeth I; Møller, Christian H; Iversen, Martin; Steinbrüchel, Daniel A; Gluud, Christian
Lung transplantation is a well-accepted treatment for people with most end-stage lung diseases. Although both tacrolimus and cyclosporin are used as primary immunosuppressive agents in lung transplant recipients, it is unclear which of these drugs is better in reducing rejection and death without causing adverse effects. To assess the benefits and harms of tacrolimus versus cyclosporin for primary immunosuppression in lung transplant recipients. We searched the Cochrane Renal Group's Specialised Register to 10 April 2013 through contact with the Trials Search Co-ordinator using search terms relevant to this review. We also searched Science Citation Index Expanded and the Transplant Library to 20 April 2013. We included all randomised controlled trials (RCT) that compared any dose and duration of administration of tacrolimus versus cyclosporin as primary immunosuppressive treatment in lung transplant recipients. Our selection criteria required that all included patients received the same additional immunosuppressive therapy within each study. Three authors extracted data. For dichotomous data we used risk ratio (RR) and used mean difference (MD) for continuous data, each with 95% confidence intervals (CI). Methodological components of the included studies were used to assess risk of systematic errors (bias). Trial sequential analysis was used to assess risk of random errors (play of chance). We included three studies that enrolled a total of 413 adult patients that compared tacrolimus with microemulsion or oral solution cyclosporin. All studies were found to be at high risk of bias. Tacrolimus seemed to be significantly superior to cyclosporin regarding the incidence of bronchiolitis obliterans syndrome (RR 0.46, 95% CI 0.29 to 0.74), lymphocytic bronchitis score (MD -0.60, 95% CI -1.04 to -0.16), treatment withdrawal (RR 0.27, 95% CI 0.16 to 0.46), and arterial hypertension (RR 0.67, 95% CI 0.50 to 0.89). However, the finding for arterial hypertension was not
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; Mikkelsen, Mark E
Cognitive and psychiatric impairments are threats to functional independence, general health, and quality of life. Evidence regarding these outcomes after lung transplantation is limited. Determine the frequency of cognitive and psychiatric impairment after lung transplantation and identify potential factors associated with cognitive impairment after lung transplantation. 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. 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 physical rehabilitation (P = 0.04) was independently associated
Hayes, Don; Hayes, Kaitlyn T; Hayes, Hunter C; Tobias, Joseph D
Survival after lung transplantation (LTx) for patients with occupational lung disease (OLD) is not well studied. The United Network for Organ Sharing (UNOS) database was queried from 2005 to 2013 to assess survival after LTx in patients with silicosis and non-silicotic OLD compared to non-OLD patients. Of 7273 adult LTx recipients, 7227 (24 with silicosis and 29 with non-silicotic OLD) were included in our univariate and Kaplan-Meier function analysis and 6370 for multivariate Cox models. Univariate Cox models did not identify survival differences in silicosis (HR 0.717; 95 % CI 0.358-1.435; p = 0.347) and non-silicotic OLDs (HR 0.934; 95 % CI 0.486-1.798; p = 0.839). Kaplan-Meier function analysis did not identify a survival disadvantage for either silicosis or non-silicotic OLD (log-rank test: χ (2) 0.93, p = 0.627). Patients with non-silicotic OLD were at risk for worse survival for the first 2.5 years post-transplant; however, at the conclusion of the study, this group had the highest survival rate. Multivariate Cox models confirmed no increased risk for mortality for silicosis (HR 1.264; 95 % CI 0.631-2.534; p = 0.509) and non-silicotic OLD (HR 1.114; 95 % CI 0.578-2.147; p = 0.747). Long-term survival for adult patients with silicosis and non-silicotic OLD after LTx is not significantly different compared to the general lung transplant population.
Walsh, James R; Chambers, Daniel C; Davis, Rebecca J; Morris, Norman R; Seale, Helen E; Yerkovich, Stephanie T; Hopkins, Peter M A
Lung transplant recipients report reduced exercise capacity despite satisfactory graft function. We analysed changes in lung function, six-min walk distance (6MWD), and quadriceps strength in the first 26-wk post-transplant and examined what factors predict 6MWD recovery. All lung transplant recipients at a single institution between June 2007 and January 2011 were considered for inclusion. Lung function, 6MWD, and quadriceps strength corrected for body weight (QS%) were recorded pre- and two-, six-, 13-, and 26-wk post-transplant. Fifty recipients, of mean (± SD) age 42 (± 13) yr, were studied. Mean FEV1 % and 6MWD improved from 26.4% to 88.9% and from 397 to 549 m at 26 wk, respectively (both p < 0.001). QS% declined in the first two wk but had improved to above pre-transplant levels by 26 wk (p = 0.027). On multivariate analysis (n = 35), lower pre-transplant exercise capacity and greater recovery in muscle strength explained most of the improvement in exercise capacity. Delayed recovery of exercise capacity after lung transplantation is unrelated to delay in improvement in graft function, but occurs secondary to the slow recovery of muscle strength. Our findings show that additional controlled trials are needed to better understand the influence of exercise rehabilitation on improvement in exercise capacity post-transplantation.
Johnson, Scott B; Allred, Anna M; Cline, Adam M; Angel, Luis F; Sako, Edward Y; Baisden, Clinton E; Calhoon, John H
Associated comorbidities in potential lung transplant recipients may significantly impact operative morbidity and mortality. We undertook this review to specifically study whether patients who underwent associated cardiac procedures either before (as a prerequisite) or during their lung transplantation had different outcomes when compared with the overall cohort of lung transplant recipients. A retrospective chart review was performed of all patients who underwent lung transplantation at the University of Texas Health Science Center at San Antonio from January 1994 to June 2004. The records of these patients were analyzed for patient-days on the ventilator, hospital length of stay, operative morbidity and mortality, and long-term survival. The patients were then divided into two groups and compared: patients who had a cardiac intervention either prerequisite to or concurrent with their transplant (group C, n = 13) and patients who did not (group NC [no cardiac intervention], n = 120). Although the median length of stay was longer in group C when compared with group NC, the number of patient-days on the ventilator and the operative morbidity and mortality were similar for both groups. Likewise, overall long-term survival was not significantly different (Kaplan-Meier method, p = 0.70). Patients who are otherwise deemed to be good candidates for lung transplantation but are found to have an associated cardiac condition that could adversely affect their candidacy may still be considered for transplantation in selected cases if the cardiac abnormality can be addressed either before or during transplantation.
Osho, Asishana A; Castleberry, Anthony W; Yerokun, Babatunde A; Mulvihill, Michael S; Rucker, Justin; Snyder, Laurie D; Davis, Robert D; Hartwig, Matthew G
The purpose of this study was to identify risk factors and outcome implications for 30-day hospital readmission in lung transplant recipients. We conducted a retrospective cohort study of lung transplant cases from a single, high-volume lung transplant program between January 2000 and March 2012. Demographic and health data were reviewed for all patients. Risk factors for 30-day readmission (defined as readmission within 30 days of discharge from index lung transplant hospitalization) were modeled using logistic regression, with selection of parameters by backward elimination. The sample comprised 795 patients after excluding scheduled readmissions and in-hospital deaths. Overall 30-day readmission rate was 45.4% (n = 361). Readmission rates were similar across different diagnosis categories and procedure types. By univariate analysis, post-operative complications that predisposed to 30-day readmission included pneumonia, any infection, and atrial fibrillation (all p < 0.05). In the final multivariate model, occurrence of any post-transplant complication was the most significant risk factor for 30-day readmission (odds ratio = 1.764; 95% confidence interval, 1.259-2.470). Even for patients with no documented perioperative complication, readmission rates were still >35%. Kaplan-Meier analysis and multi-variate regression modeling to assess readmission as a predictor of long-term outcomes showed that 30-day readmission was not a significant predictor of worse survival in lung recipients. Occurrence of at least 1 post-transplant complication increases risk for 30-day readmission in lung transplant recipients. In this patient population, 30-day readmission does not predispose to adverse long-term survival. Quality indicators other than 30-day readmission may be needed to assess hospitals that perform lung transplantation. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Erasmus, M E; Hofstede, G J; Petersen, A H; Haagsman, H P; Oetomo, S B; Prop, J
We investigated whether pulmonary surfactant in rat lung transplants recovered during the first week post-transplantation, along with symptoms of the reimplantation response, and whether this recovery was affected by early surfactant treatment. The severity of pulmonary injury was varied by transplanting left lungs with 6-h and 20-h ischemia (n = 12 and 19, respectively). Half of the transplants were treated by instillation of surfactant before reperfusion. Lungs from sham operated, and normal rats (n = 4 and 5, respectively) served as controls. The pulmonary injury severely impaired lung transplant function; 10 of the worst affected animals died. After 1 wk, symptoms of reimplantation response and properties of pulmonary surfactant were assessed. If untreated, the reimplantation response had almost resolved in the 6-h but not in the 20-h ischemia group; pulmonary surfactant, however, continued to be deficient in both ischemia groups (low amounts of surfactant phospholipids and surfactant protein A [SP-A]). Surfactant treatment improved the recovery from injury in the 20-h ischemia group resulting in normal lung function and amounts of surfactant phospholipids. Amounts of SP-A were not improved by surfactant treatment. In conclusion, early surfactant treatment enhances recovery from transplantation injury and is persistently beneficial for pulmonary surfactant in lung transplants.
Song, Ruiping; Kubo, Masatoshi; Morse, Danielle; Zhou, Zhihong; Zhang, Xuchen; Dauber, James H.; Fabisiak, James; Alber, Sean M.; Watkins, Simon C.; Zuckerbraun, Brian S.; Otterbein, Leo E.; Ning, Wen; Oury, Tim D.; Lee, Patty J.; McCurry, Kenneth R.; Choi, Augustine M.K.
Successful lung transplantation has been limited by the high incidence of acute graft rejection. There is mounting evidence that the stress response gene heme oxygenase-1 (HO-1) and/or its catalytic by-product carbon monoxide (CO) confers cytoprotection against tissue and cellular injury. This led us to hypothesize that CO may protect against lung transplant rejection via its anti-inflammatory and antiapoptotic effects. Orthotopic left lung transplantation was performed in Lewis rat recipients from Brown-Norway rat donors. HO-1 mRNA and protein expression were markedly induced in transplanted rat lungs compared to sham-operated control lungs. Transplanted lungs developed severe intraalveolar hemorrhage, marked infiltration of inflammatory cells, and intravascular coagulation. However, in the presence of CO exposure (500 ppm), the gross anatomy and histology of transplanted lungs showed marked preservation. Furthermore, transplanted lungs displayed increased apoptotic cell death compared with the transplanted lungs of CO-exposed recipients, as assessed by TUNEL and caspase-3 immunostaining. CO exposure inhibited the induction of IL-6 mRNA and protein expression in lung and serum, respectively. Gene array analysis revealed that CO also down-regulated other proinflammatory genes, including MIP-1α and MIF, and growth factors such as platelet-derived growth factor, which were up-regulated by transplantation. These data suggest that the anti-inflammatory and antiapoptotic properties of CO confer potent cytoprotection in a rat model of lung transplantation. PMID:12819027
Kim, Hyojin; Jeon, Yoon Kyung; Lee, Hyun Joo; Kim, Young Tae; Chung, Doo Hyun
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.
Castleberry, A W; Martin, J T; Osho, A A; Hartwig, M G; Hashmi, Z A; Zanotti, G; Shaw, L K; Williams, J B; Lin, S S; Davis, R D
Coronary artery disease (CAD) is not uncommon among lung transplant candidates. Several small, single-center series have suggested that short-term outcomes are acceptable in selected patients who undergo coronary revascularization prior to, or concomitant with, lung transplantation. Our objective was to evaluate perioperative and intermediate-term outcomes in this patient population at our institution. We performed a retrospective, observational cohort analysis of 898 lung transplant recipients between 1997 and 2010. Pediatric, multivisceral, lobar or repeat transplantations were excluded, resulting in 791 patients for comparative analysis, of which 49 (median age 62, 79.6% bilateral transplant) underwent concurrent coronary artery bypass and 38 (median age 64, 63.2% bilateral transplant) received preoperative percutaneous coronary intervention (PCI). Perioperative mortality, overall unadjusted survival and adjusted hazard ratio for cumulative risk of death were similar among both revascularization groups as well as controls. The rate of postoperative major adverse cardiac events was also similar among groups; however, concurrent coronary artery bypass was associated with longer postoperative length of stay, more time in the intensive care unit and more postoperative days requiring ventilator support. These results suggest that patients with CAD need not be excluded from lung transplantation. Preferential consideration should be given to preoperative PCI when feasible. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.
Hadjiliadis, Denis; Chaparro, Cecilia; Reinsmoen, Nancy L; Gutierrez, Carlos; Singer, Lianne G; Steele, Mark P; Waddell, Thomas K; Davis, Robert D; Hutcheon, Michael A; Palmer, Scott M; Keshavjee, Shaf
The presence of antibodies to human leukocyte antigens (HLA) prior to transplantation has been linked to worse post-transplant outcomes in many solid organ transplants. The effect of these antibodies is less clear in lung transplant recipients, although previous studies have suggested an increased incidence of allograft dysfunction. A retrospective study of all first lung transplant recipients from the University of Toronto (November 1983-July 2001, n = 380) and Duke University (April 1992-June 2000, n = 276) was performed. Demographic data, survival information, and level of last pre-transplant panel reactive antibody (PRA) were collected. PRA level was measured by the complement-dependent cell cytotoxicity assay at both centers. Survival analysis was performed using the Kaplan-Meier method, and groups were compared with the Wilcoxon rank sum test. Of 656 lung transplant recipients, 101 (15.4%) had a PRA greater than 0, 37 (5.6%) had a PRA greater than 10%, and 20 (3.0%) had a PRA greater than 25%. Patients with a PRA greater than 25% had decreased median survival than did the rest of the patients (1.5 vs 5.2 years) and at 1 month (70% vs 90%), 1 year (65% vs 76%), and 5 years (31% vs 50%), respectively (p = 0.006, Wilcoxon's rank sum test) test). Significant elevation of PRA prior to lung transplantation is associated with worse survival, especially in the early post-transplant period. This may be due to a direct effect of anti-HLA antibodies on the allograft. The effectiveness of treatments such as plasmapheresis and intravenous immunoglobulin prior to transplantation needs to be evaluated.
Ehrsam, Jonas P; Benden, Christian; Seifert, Burkhardt; Opitz, Isabelle; Schneiter, Didier; Weder, Walter; Inci, Ilhan
As large registries show an increased risk for lung transplant recipients aged 60 years or more, few single centers report favorable outcomes for carefully selected older recipients without providing essential details. The purpose of our study was to determine variables that influence survival in the elderly. All adult bilateral first lung transplants between January 2000 and December 2014 were divided in 2 groups: those aged less than 60 years (N = 223) and those aged 60 years or more (N = 83). The Charlson-Deyo Index determined recipient comorbidities. The Oto Donor Score assessed donor lung quality. Recipients aged 60 years or more had a significant lower median survival compared with their younger counterparts (48 vs 112 months, respectively, P < .001). Recipient age was as an exponentially increasing univariate risk factor for mortality. By adjusting for variables in multivariate analysis, this trend was nonsignificant. The displacing variables were idiopathic pulmonary fibrosis (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.0-2.2), Charlson-Deyo Index 2 or greater (HR, 1.3; 95% CI, 1.0-1.8), systemic hypertension (HR, 1.7; 95% CI, 1.2-2.6), gastroesophageal reflux (HR, 1.9; 95% CI, 1.1-3.1), diverticulosis (HR, 1.7; 95% CI, 1.0-2.7), and an Oto Donor Score 8 or greater (HR, 1.5; 95% CI, 1.1-2.0). All of these risk factors were significantly more likely to occur in recipients aged 60 years or more, except for a tendency for high Charlson-Deyo Index. The comorbidity profile, underlying disease, and donor lung quality appear to be more important than age in reducing long-term survival. Older age serves as a marker for a complex constellation of factors that might be considered the relative or absolute contraindication to lung transplantation rather than age, per se. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Shlomi, Dekel; Shitrit, David; Bendayan, Daniele; Sahar, Gidon; Shechtman, Yitshak; Kramer, Mordechai R
Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-year-old woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin) tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis.
Shlomi, Dekel; Shitrit, David; Bendayan, Daniele; Sahar, Gidon; Shechtman, Yitshak; Kramer, Mordechai R
Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-year-old woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin) tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis. PMID:18686743
Gairard-Dory, A-C; Dégot, T; Hirschi, S; Schuller, A; Leclercq, A; Renaud-Picard, B; Gourieux, B; Kessler, R
Viral gastroenteritis causing diarrhea is a common complication observed in lung transplant recipients. Differently from the mild and typically self-limited disease seen in immunocompetent subjects, immunocompromised patients frequently have a more severe course. Norovirus and rotavirus are among the leading causes of severe gastroenteritis in transplant recipients. Specific treatment is unavailable, although good supportive treatment can significantly reduce morbidity. Previous studies have suggested that oral immunoglobulins may be used for the treatment of acute viral gastroenteritis after solid-organ transplantation. Herein, we conducted a retrospective chart review of 12 lung transplant recipients with norovirus-induced gastroenteritis who were treated with oral immunoglobulins for 2 days. Eleven patients were successfully treated, whereas 1 subject was only mildly improved. Four patients had at least 1 recurrence. No significant adverse effects were observed. We conclude that oral immunoglobulins may be clinically useful for lung transplant recipients with norovirus-induced gastroenteritis.
Marchetti, Nathaniel; Criner, Gerard J
Chronic obstructive pulmonary disease (COPD) is a common and morbid progressive disease where treatment is focused on improving dyspnea, reducing exacerbations, attenuating comorbidities, and improving quality of life. Surgical therapy can be beneficial to a carefully selected subset of individuals and is the subject of this review. The National Emphysema Treatment Trial (NETT) has not only demonstrated the efficacy of lung volume reduction surgery (LVRS) but has also provided many lessons regarding advanced emphysema. NETT demonstrated that LVRS improves exercise performance, quality of life, and pulmonary function in those with upper lobe predominant emphysema in the setting of advanced disease. Those with upper lobe predominant emphysema and low exercise tolerance also had a survival advantage compared with maximal medical therapy. Careful patient selection is paramount to success, as there clearly are patients in whom LVRS increases mortality. Giant bullae are rare, but bullectomy has been demonstrated to improve dyspnea and lung function in cases where the bulla occupies at least one-third of the hemithorax and compresses some adjacent lung tissue. For patients with chronic respiratory failure due to COPD who have not improved despite maximal surgical and medical therapy, lung transplantation remains an option in those without significant comorbid conditions.
Finsterwalder, Richard; Friedl, Heinz P.; Rauscher, Sabine; Gröger, Marion; Kocher, Alfred; Wagner, Christine; Wagner, Stephan N.; Fischer, Gottfried; Schultz, Marcus J.; Wiedemann, Dominik; Petzelbauer, Peter
Background Despite significant advances in organ preservation, surgical techniques and perioperative care, primary graft dysfunction is a serious medical problem in transplantation medicine in general and a specific problem in patients undergoing lung transplantation. As a result, patients develop lung edema, causing reduced tissue oxygenation capacity, reduced lung compliance and increased requirements for mechanical ventilatory support. Yet, there is no effective strategy available to protect the grafted organ from stress reactions induced by ischemia/reperfusion and by the surgical procedure itself. Methods We assessed the effect of a cingulin-derived peptide, XIB13 or a random peptide in an established rat model of allogeneic lung transplantation. Donor lungs and recipients received therapeutic peptide at the time of transplantation and outcome was analyzed 100min and 28 days post grafting. Results XIB13 improved blood oxygenation and reduced vascular leak 100min post grafting. Even after 28 days, lung edema was significantly reduced by XIB13 and lungs had reduced fibrotic or necrotic zones. Moreover, the induction of an allogeneic T cell response was delayed indicating a reduced antigen exchange between the donor and the host. Conclusions In summary, we provide a new tool to strengthen endothelial barrier function thereby improving outcomes in lung transplantation. PMID:26536466
Ison, Michael G; Sharma, Amita; Shepard, Jo-Anne O; Wain, John C; Ginns, Leo C
Influenza causes significant morbidity and mortality in lung transplant recipients and likely predisposes to obliterative bronchiolitis. Neuraminidase inhibitors shorten the duration of symptoms and virus shedding and the number of antibiotic-requiring complications in ambulatory immunocompetent patients, although the efficacy of these agents in lung transplant recipients has not been assessed previously. In this study, 9 lung transplant patients who were treated with oseltamivir for influenza infections were identified and analyzed retrospectively. Oseltamivir was well tolerated. Infection resolved in all patients and there were no deaths. Two patients developed pneumonia shortly after their influenza infection and both responded to antibiotic therapy. None of the patients had persistent abnormalities noted on chest imaging and most did not show significant changes on pulmonary function testing. Two patients with the lowest pulmonary function test (PFT) values pre-infection had persistent defects after infection. Oseltamivir is well tolerated in lung transplant recipients and may reduce the risk of complications, although further studies are warranted.
Dorgan, Daniel J; Hadjiliadis, Denis
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.
Alraiyes, Abdul Hamid; Inaty, Hanine; Machuzak, Michael S.
Background: Airway complications after lung transplant play an important role in patient survival. Early recognition and treatment of these complications are necessary to help ensure that patients who receive lung transplants have good outcomes. Case Report: A 61-year-old female with a history of pulmonary venous occlusive disease presented to our hospital for a double-lung transplant. Her postoperative course was complicated by severe primary graft dysfunction. Airway examination showed significant mucosal ischemia distal to the anastomosis bilaterally with diffuse narrowing of all distal bronchial segments. Repeat bronchoscopies with debridement of necrotic material and balloon dilatation of stenotic airways were performed to maintain airway patency. Conclusion: Post–lung transplant airway necrosis and stenosis mandate early identification and treatment. Repetitive bronchoscopies with sequential balloon dilatations are mandatory to prevent future airway stenosis and airway vanishing. PMID:28331451
Kirkby, Stephen; Robertson, Michael; Evans, Laura; Preston, Thomas J; Tobias, Joseph D; Galantowicz, Mark E; McKee, Christopher T; Hayes, Don
A combination of helium and oxygen (heliox) can facilitate gas exchange and limit peak inspiratory pressures through reduced resistance to gas flow and decreased turbulent flow. The combination of these gases has been used for a variety of upper and lower airway conditions, including patients who were spontaneously breathing, receiving noninvasive ventilation, as well as during mechanical ventilation. To date, there are no reports regarding the use of heliox in patients with bronchiolitis obliterans syndrome following lung transplantation. We report the use of such a combination of gases in 2 patients with bronchiolitis obliterans syndrome following lung transplantation as a supportive measure to facilitate ventilation during the initial treatment course for acute respiratory failure in the ICU. A heliox mixture was administered with noninvasive ventilation and with mechanical ventilation through the ventilator in a heart-lung transplant recipient and a lung transplant recipient, respectively.
Egan, Thomas; Blackwell, John; Birchard, Katherine; Haithcock, Benjamin; Long, Jason; Gazda, Stephen; Casey, Nissa; Thys, Caitlin
To address the lung donor shortage, we obtained institutional review board and US Food and Drug Administration approval to transplant lungs recovered from uncontrolled donation after circulatory determination of death donors (uDCDDs). To compare outcomes of recipients of lungs recovered from uDCDDs vs. brain-dead donors. After consent and screening, lungs recovered from uDCDDs were assessed by 4 hours ex vivo lung perfusion (EVLP) and computed tomography (CT) scan. Over the course of 29 months, 502 potential uDCDDs younger than 66 years were identified in a single county, with death declaration by emergency medical services and four emergency departments in this and two other countries. We determined reasons that lungs from these uDCDDs were not able to be transplanted: uDCDDs could not have lungs recovered (224), next-of-kin could not be found or refused to discuss (67), next-of-kin refused (48), medical examiner case (39), logistics/missed (35), and miscellaneous (35). There were 247 medical contraindications: 141 pulmonary and 106 nonpulmonary. Lungs were recovered from 31 uDCDDs. Thirteen lungs did not have EVLP: 5 injured lungs (one pulmonary embolism [PE] with perforated infarct, two motor vehicle crash with severe injuries, one adhesion, and one lightning strike), two large PE, two prolonged ischemic time, two obvious chronic obstructive pulmonary disease, one technical, and one consent withdrawn. Eighteen lungs had EVLP: 10 with immediate edema (three PE, three unknown down time, three long ischemic time, and one ruptured aneurysm into L pleural space, making long cardiopulmonary resuscitation ineffective), and one myocarditis, possible lung involvement. In three lungs, CT showed edema after EVLP: one poor flush and poor EVLP performance, one edema after myocardial infarction (MI) with 10-year history of chronic heart failure, and one edema with MI, resuscitated, arrested again. One concurrent pneumonia was diagnosed by bronchoscopy, CT, and cultures; one
He, W X; Jiang, C; Liu, X G; Huang, W; Chen, C; Jiang, L; Yang, B; Wu, K; Chen, Q K; Yang, Y; Yu, Y M; Jiang, G N
Objective: To assess short-term outcomes after lung transplantation with organs procured following brain death. Methods: Between April 2015 and July 2016, all 17 recipients after lung transplantation using organs from brain death donors (DBD) at Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine were enrolled in this study. All patients were male, aging (60±7) years, including 11 chronic obstructive pulmonary disease, 5 idiopathic pulmonary fibrosis, 1 silicosis. Seventeen donors were 16 males and 1 female, with 10 traumatic brain injury, 5 cerebrovascular accident and 2 sudden cardiac death. Of 17 recipients receiving DBD lung transplant, 16 were single lung transplant. Data were collected including intubation duration of mechanical ventilation, hospital length of stay, incidence of pulmonary infection bronchus anastomosis complications, primary graft dysfunction (PGD), and acute rejection, bronchiolitis obliterans syndrome (BOS) as well as mortality of 90-day after lung transplantation. Results: Median duration of intubation were 2 (2) days (M(QR)) in recipients after lung transplantation. The incidence of pulmonary infection and bronchus anastomosis complications were 15/17 and 5/17, respectively. Median length of stay in hospital were 56 (19) days. The ratio of readmission 1 month after discharge were 10/17. Mortality of 90-day post-transplant were 2/17. The incidence of PGD and BOS were 1/17 and 2/17, respectively. Conclusion: Recipients with DBD lung transplantation have an acceptable survival during short-term follow-up, but with higher incidences of complications related to infection post-transplantation.
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
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.
Yates, B; Murphy, D M; Fisher, A J; Gould, F K; Lordan, J L; Dark, J H; Corris, P A
In the present study, 4 patients with cystic fibrosis undergoing lung transplantation (from a total of 137) who developed fulminant pseudomembranous colitis are described. Initial presentation was variable and the mortality rate was 50% despite urgent colectomy. In one case the presenting abdominal distension was thought to be due to meconium ileus equivalent. It is concluded that Clostridium difficile colitis may be a difficult diagnosis in patients with cystic fibrosis and follows a fulminant course after lung transplantation.
Background Lung transplant recipients have an increased risk for actinomycetales infection secondary to immunosuppressive regimen. Case presentation A case of pulmonary infection with bacteremia due to Tsukamurella tyrosinosolvens in a 54-year old man who underwent a double lung transplantation four years previously is presented. Conclusion The identification by conventional biochemical assays was unsuccessful and hsp gene sequencing was used to identify Tsukamurella tyrosinosolvens. PMID:19909497
Fisichella, P. Marco; Davis, Christopher S.; Lundberg, Peter W.; Lowery, Erin; Burnham, Ellen L.; Alex, Charles G.; Ramirez, Luis; Pelletiere, Karen; Love, Robert B.; Kuo, Paul C.; Kovacs, Elizabeth J.
Background The goal of this study was to determine, in lung transplant patients, if laparoscopic antireflux surgery (LARS) is an effective means to prevent aspiration as defined by the presence of pepsin in the bronchoalveolar lavage fluid (BALF). Methods Between September 2009 and November 2010, we collected BALF from 64 lung transplant patients at multiple routine surveillance assessments for acute cellular rejection, or when clinically indicated for diagnostic purposes. The BALF was tested for pepsin by enzyme-linked immunosorbent assay (ELISA). We then compared pepsin concentrations in the BALF of healthy controls (n = 11) and lung transplant patients with and without gastroesophageal reflux disease (GERD) on pH-monitoring (n = 8 and n = 12, respectively), and after treatment of GERD by LARS (n = 19). Time to the development of bronchiolitis obliterans syndrome was contrasted between groups based on GERD status or the presence of pepsin in the BALF. Results We found that lung transplant patients with GERD had more pepsin in their BALF than lung transplant patients who underwent LARS (P = .029), and that pepsin was undetectable in the BALF of controls. Moreover, those with more pepsin had quicker progression to BOS and more acute rejection episodes. Conclusion This study compared pepsin in the BALF from lung transplant patients with and without LARS. Our data show that: (1) the detection of pepsin in the BALF proves aspiration because it is not present in healthy volunteers, and (2) LARS appears effective as a measure to prevent the aspiration of gastroesophageal refluxate in the lung transplant population. We believe that these findings provide a mechanism for those studies suggesting that LARS may prevent nonallogenic injury to the transplanted lungs from aspiration of gastroesophageal contents. PMID:22000170
Glanville, A R
New medical and scientific disciplines are often developed in haste with rampant enthusiasm and scant regard for the balance between action and thoughtful deliberation. Driven by the desire to prolong life and provide a better quality of life for desperately sick individuals, the twin modalities of lung transplantation and lung volume reduction therapy have only just reached their majority. Both are invested with the capacity to help and to harm so it is right to consider carefully their ethical and equitable distribution. Much has been learned in the last 20 years to assist in these deliberations. First, how can we ensure equity of access to transplant services and equality of outcomes? How do we balance resource allocation of a precious and scarce resource with individual recipient needs? Does the concept of distributive justice prevail in our daily work in this field? How do we honour the donor and their family? How do we as practitioners avoid ethical dilemmas related to personal bias and justifiable reward for services rendered? Finally, how do we learn to incorporate ethical forethought and planning guided by experts in the area into everyday behaviour?
Zhang, Xiaoqing; Xu, Jiandong; Zhang, Tao; Li, Yuping; Xie, Boxiong; Zhang, Wei; Lin, Shengtao; Ye, Ling; Liu, Yuan
Aims. The influence of interleukin-10 (IL-10) and interleukin-18 (IL-18) polymorphisms on tacrolimus pharmacokinetics had been described in liver and kidney transplantation. The expression of cytokines varied in different kinds of transplantation. The influence of IL-10 and IL-18 genetic polymorphisms on the pharmacokinetic parameters of tacrolimus remains unclear in lung transplantation. Methods. 51 lung transplant patients at Shanghai Pulmonary Hospital were included. IL-18 polymorphisms (rs5744247 and rs1946518), IL-10 polymorphisms (rs1800896, rs1800872, and rs3021097), and CYP3A5 rs776746 were genotyped. Dose-adjusted trough blood concentrations (C/D ratio, mg/kg body weight) in lung transplant patients during the first 4 postoperative weeks were calculated. Results. IL-18 rs5744247 allele C and rs1946518 allele A were associated with fast tacrolimus metabolism. Combined analysis showed that the numbers of low IL-18 mRNA expression alleles had positive correlation with tacrolimus C/D ratios in lung transplant recipients. The influence of IL-18 polymorphisms on tacrolimus C/D ratios was observed in CYP3A5 expresser recipients, but not in CYP3A5 nonexpresser recipients. No clinical significance of tacrolimus C/D ratios difference of IL-10 polymorphisms was found in our data. Conclusions. IL-18 polymorphisms may influence tacrolimus elimination in lung transplantation patients. PMID:28246425
Charles, Eric J; Huerter, Mary E; Wagner, Cynthia E; Sharma, Ashish K; Zhao, Yunge; Stoler, Mark H; Mehaffey, J Hunter; Isbell, James M; Lau, Christine L; Tribble, Curtis G; Laubach, Victor E; Kron, Irving L
Despite the critical need for donor lungs, logistic and geographic barriers hinder lung utilization. We hypothesized that lungs donated after circulatory death subjected to 6 hours of cold preservation after ex vivo lung perfusion (EVLP) would have similar outcomes after transplantation as lungs transplanted immediately after EVLP, and that both would perform superiorly compared with lungs transplanted immediately after procurement. Donor porcine lungs were procured after circulatory death and 15 minutes of warm ischemia. Three groups (n = 5 per group) were randomized: immediate left lung transplantation (Immediate group), EVLP for 4 hours followed by transplantation (EVLP group), or EVLP for 4 hours followed by 6 hours of cold preservation followed by transplantation (EVLP+Cold group). Lungs were reperfused for 2 hours before obtaining pulmonary vein samples for partial pressure of oxygen/fraction of inspired oxygen ratio calculations, airway pressures for compliance measurements, and wet/dry weight ratios. The partial pressure of oxygen/fraction of inspired oxygen ratios in the EVLP and EVLP+Cold groups were significantly improved compared with those in the Immediate group (429.7 ± 51.8 and 436.7 ± 48.2 versus 117.4 ± 22.9 mm Hg, respectively). In addition, dynamic compliance was significantly improved in the EVLP and EVLP+Cold groups compared with immediate group (26.2 ± 4.2 and 27.9 ± 3.5 versus 11.1 ± 2.4 mL/cmH2O, respectively). There were no differences in oxygenation capacity or dynamic compliance between the EVLP and EVLP+Cold groups. Inflammatory cytokine levels were significantly lower in the EVLP and EVLP+Cold groups. Lungs donated after circulatory death can be successfully transplanted as much as 6 hours after EVLP. Cold preservation of lungs after ex vivo assessment and rehabilitation may improve organ allocation, even to distant recipients, without compromising allograft function. Copyright © 2016 The Society of Thoracic Surgeons
In cystic fibrosis (CF) patients with end-stage pulmonary disease, lung transplantation (LTx) remains a life-extending therapy with good outcome in most patients. Despite early concern about chronic pretransplantation infections in the context of posttransplantation immunosuppression, typical CF-associated organisms such as Pseudomonas aeruginosa turned out to be quite well manageable and associated with favorable outcomes in transplanted CF patients, even in patients with highly resistant strains. However, the situation is less evident with other pathogens. Burkholderia cenocepacia is associated with reduced survival and regarded as a contraindication for LTx in most centers, other Burkholderia species are less problematic. Other resistant Gram-negative bacteria and methicillin-resistant staphylococcus aureus in CF patients are not regarded as a contraindication. Nontuberculous mycobacteria disease in CF patients does not preclude successful recovery after LTx, although postoperative complications can be expected in patients with Mycobacterium abscessus and specific management is indicated. Fungal species should be treated aggressively to limit morbidity after transplantation. Despite its complexity, LTx is safe in most CF patients, with good outcomes if the pathogens that are present are identified and adequately treated.
Morales, P; Torres, J; Pérez-Enguix, D; Solé, A; Pastor, A; Segura, A; Zurbano, F
Lymphoproliferative syndromes are the most common tumors in transplant recipients. More than 90% of posttransplantation lymphoproliferative syndromes (PTLS) are considered to be associated with Epstein-Barr virus, and 86% are of the B-cell line. Histopathology ranges from polymorphic-reactive to monomorphic forms. Clonality should be studied using molecular biology techniques. Clinically, a differentiation is usually made between early PTLS (occurring within 1 year after transplantation) and late PTLS, which occur as localized or disseminated nodal lymphomas. In localized forms, immunosuppression should be discontinued or decreased, and the involved area should be subsequently resected or irradiated. In disseminated cases, immunosuppression should be decreased and administration of acyclovir/ganciclovir should be considered. If this is not effective, treatment should be started with anti-CD20 monoclonal antibodies (rituximab). If no response occurs, use of chemotherapy, possibly with interferon, should be considered. Our aim was to report the incidence, clinical signs, and treatment in a series of patients undergoing lung transplantation (LTx).
Tian, Weijun; Liu, Yi; Zhang, Bai; Dai, Xiangchen; Li, Guang; Li, Xiaochun; Zhang, Zhixiang; Du, Caigan; Wang, Hao
Cold ischemia-reperfusion injury (IRI) is a major cause of graft failure in lung transplantation. Despite therapeutic benefits of mesenchymal stem cells (MSCs) in attenuating acute lung injury, their protection of lung transplants from cold IRI remains elusive. The present study was to test the efficacy of MSCs in the prevention of cold IRI using a novel murine model of orthotopic lung transplantation. Donor lungs from C57BL/6 mice were exposed to 6 h of cold ischemia before transplanted to syngeneic recipients. MSCs were isolated from the bone marrows of C57BL/6 mice for recipient treatment. Gas exchange was determined by the measurement of blood oxygenation, and lung injury and inflammation were assessed by histological analyses. Intravenously delivered MSC migration/trafficking to the lung grafts occurred within 4-hours post-transplantation. As compared to untreated controls, the graft arterial blood oxygenation (PaO2/FiO2) capacity was significantly improved in MSC-treated recipients as early as 4 h post-reperfusion and such improvement continued over time. By 72 h, oxygenation reached normal level that was not seen in controls. MSCs treatment conferred significant protection of the grafts from cold IRI and cell apoptosis, which is correlated with less cellular infiltration, a decrease in proinflammatory cytokines (TNF-α, IL-6) and toll-like receptor 4, and an increase in anti-inflammatory TSG-6 generation. MSCs provide significant protection against cold IRI in lung transplants, and thus may be a promising strategy to improve outcomes after lung transplantation.
Daimiel Naranjo, I; Alonso Charterina, S
Lung transplantation is the best treatment option in the final stages of diseases such as cystic fibrosis, pulmonary hypertension, chronic obstructive pulmonary disease, or idiopathic pulmonary fibrosis. Better surgical techniques and advances in immunosuppressor treatments have increased survival in lung transplant recipients, making longer follow-up necessary because complications can occur at any time after transplantation. For practical purposes, complications can be classified as early (those that normally occur within two months after transplantation), late (those that normally occur more than two months after transplantation), or time-independent (those that can occur at any time after transplantation). Many complications have nonspecific clinical and radiological manifestations, so the time factor is key to narrow the differential diagnosis. Imaging can guide interventional procedures and can detect complications early. This article aims to describe and illustrate the complications that can occur after lung transplantation from the clinical and radiological viewpoints so that they can be detected as early as possible. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.
Bravo, C; Gispert, P; Borro, J M; de la Torre, M; Cifrián Martínez, J M; Fernández Rozas, S; Zurbano Goñi, F
No studies have yet been performed to evaluate the prevalence of gastrointestinal (GI) complications in solid organ transplant recipients in Spain. An observational, cross-sectional study to evaluate the prevalence and management of GI complications in transplanted patients was conducted via a written questionnaire given to doctors at their practice. A total of 58 lung transplant recipients were included. Their mean age was 52.6 +/- 10.8 years; 65% of the patients were men; and the mean time since the transplant was 2.1 +/- 2.3 years. GI complications were seen in 48.6% of the lung transplant patients. Regarding the management, the most frequently used measure was the prescription of gastric protectors (70.5%). In seven patients, the immunosuppressive treatment was also modified (reduced, discontinued temporarily, or discontinued permanently); however, the figure is so low that no conclusions can be drawn from this result. The prevalence of GI complications in lung transplant was over 50%, and these complications affected patients' daily activities in most cases. In lung transplant recipients, there was a higher prevalence of nausea and abdominal pain and a lower of diarrhea and dyspepsia than what was observed in other type of transplant recipients.
Tanaka, Shin; Miyoshi, Kentaroh; Sugimoto, Seiichiro; Yamane, Masaomi; Kobayashi, Motomu; Oto, Takahiro
A successful outcome after lung transplant was achieved using lungs donated from a teenage boy who underwent prolonged mechanical ventilation. The donor experienced hypoxic brain damage and was declared brain dead 324 days after tracheal intubation. At the time of referral, the donor's lungs revealed diffuse radiologic infiltration and atelectasis but excellent function, with a PaO2/FiO2 ratio of 450. The lungs were transplanted to a 10-year-old girl with bronchiolitis obliterans. She developed grade 2 primary graft dysfunction, but recovered quickly. She is doing well and has not experienced any other critical adverse events 12 months after lung transplantation. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Mandich Crovetto, D; Alonso Charterina, S; Jiménez López-Guarch, C; Pont Vilalta, M; Pérez Núñez, M; de Pablo Gafas, A; Escribano Subías, P
To use multidetector computed tomography (MDCT) to evaluate the structural changes in the right heart and pulmonary arteries that occur in patients with severe pulmonary hypertension treated by double lung transplantation. This was a retrospective study of 21 consecutive patients diagnosed with severe pulmonary hypertension who underwent double lung transplantation at our center between 2010 and 2014. We analyzed the last MDCT study done before lung transplantation and the first MDCT study done after lung transplantation. We recorded the following variables: diameter of the pulmonary artery trunk, ratio of the diameter of the pulmonary artery trunk to the diameter of the ascending aorta, diameter of the right ventricle, ratio of the diameter of the left ventricle to the diameter of the right ventricle, and eccentricity index. Statistical analysis consisted of the comparison of the means of the variables recorded. In all cases analyzed, the MDCT study done a mean of 24±14 days after double lung transplantation showed a significant reduction in the size of the right heart chambers, with improved indices of ventricular interdependency index, and reduction in the size of the pulmonary artery trunk (p<0.001 for all the variables analyzed). Patients with pulmonary hypertension treated by double lung transplantation present early reverse remodeling of the changes in the structures of the right heart and pulmonary arterial tree. MDCT is useful for detecting these changes. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.
Esguerra-Gonzales, Angeli; Ilagan-Honorio, Monina; Kehoe, Priscilla; Fraschilla, Stephanie; Lee, Ai Jin; Madsen, Ashley; Marcarian, Taline; Mayol-Ngo, Kristina; Miller, Pamela S; Onga, Jay; Rodman, Betty; Ross, David; Shameem, Zeba; Nandy, Karabi; Toyama, Joy; Sommer, Susan; Tamonang, Cheryl; Villamor, Filma; Weigt, S Samuel; Gawlinski, Anna
The aim of this study is to compare the effects of chest physiotherapy (CPT) and high-frequency chest wall oscillation (HFCWO) on lung function in lung transplant recipients. Chest physiotherapy and HFCWO are routinely used after lung transplant to attenuate dyspnea, increase expiratory flow, and improve secretion clearance. In a two-group experimental, crossover design with repeated-measures, 45 lung transplant recipients (27 single, 18 bilateral; 64% male; mean age, 57 years) were randomized to receive CPT at 10:00 AM and 2:00 PM followed by HFCWO at 6:00 PM and 10:00 PM (n=22) or vice versa (n=23) on postoperative day 3. Dyspnea (modified Borg score), Spo2/FiO2, and peak expiratory flow (PEF) were measured pre-treatment and post-treatment. Data were analyzed using chi-square tests, t tests, and linear mixed effects models. There was no statistically significant treatment effect for dyspnea or PEF in patients who received HFCWO versus CPT. However, there was a significant treatment effect on the Spo2/FiO2 ratio (p<0.0001). Preliminary results suggest that lung function (measured by Spo2/FiO2) improves with HFWCO after lung transplantation. Although dyspnea and PEF did not differ significantly between treatment types, HFCWO may be an effective, feasible alternative to CPT. Copyright © 2014 Elsevier Inc. All rights reserved.
Chandrakantan, Arun; de Mattos, Angelo M; Naftel, David; Crosswy, Apryl; Kirklin, James; Curtis, John J
The use of cyclosporine and tacrolimus therapy in nonrenal (heart, heart/lung, lung, and liver) transplantation has resulted in improved patient and graft survival. Nephrotoxicity is one of the major side effects of tacrolimus and cyclosporine therapy and may lead to ESRD. The trend of referral of nonrenal solid-organ transplant recipients for kidney transplant evaluation at a large multiorgan transplant center was examined. Records of all patients who were referred for renal transplantation at the University of Alabama between January 1, 1993, and June 30, 2004, were reviewed. Eighty (0.96%) of 8318 individuals had previously undergone a nonrenal solid-organ transplant and were included in the study. The majority (72%) of patients had their nonrenal transplants performed at the University of Alabama. Twenty-two patients had their nonrenal transplant performed elsewhere and had fewer data available for analysis. From the period 1993-1996 to 2001-2004, an 11-fold increase in the absolute number of referrals of patients with nonrenal transplants was noted. Of patients who were referred for transplant evaluation, 25 became recipients of kidney transplants with a predominance of living-donor transplants. Referral for kidney transplant evaluation among nonrenal solid-organ transplant recipients is increasing and will exacerbate the existing shortage of deceased-donor kidneys that are available for transplantation. There was a trend for liver transplant recipients compared with other solid-organ recipients to develop ESRD at a greater rate.
Force, Seth D.; Kilgo, Pat; Neujahr, David C.; Pelaez, Andres; Pickens, Allan; Fernandez, Felix G.; Miller, Daniel L.; Lawrence, Clint
Background Single-lung transplantation (SLT) and bilateral lung transplantation (BLT) are both good options for patients with end-stage lung disease secondary to idiopathic pulmonary fibrosis. It is, however, unclear whether BLT offers any survival advantage over SLT. The purpose of our study was to evaluate a large group of patients to determine if either SLT or BLT officered a long-term survival advantage for patients with IPF. Methods This was an Institutional Review Board-approved retrospective analysis of the United Network of Organ Sharing database from 1987 to 2008. Survival was determined using Kaplan-Meir estimates and the effect of laterality was determined by Cox proportional hazards and propensity analyses. Results Lung transplantation for idiopathic pulmonary fibrosis was performed in 3,860 patients (2,431 SLTs and 1429 BLTs). Multivariate and propensity analysis failed to show any survival advantage for BLT (hazard ratio = 0.90, 95% confidence interval = 0.78 to 1.0, p = 0.11). One-year conditional survival favored BLT (hazard ratio 0.73, 95% confidence interval 0.60 to 0.87, p = 0.00064). Risk factors for early death included recipient age over 57 and donor age over 36 years. Conclusions Bilateral lung transplantation should be considered for younger patients with idiopathic pulmonary fibrosis and results may be optimized when younger donors are used. PMID:21172522
Ratnovsky, Anat; Kramer, Mordechai R; Elad, David
Single-lung transplantation may induce asynchronous performance between the respiratory muscles of the chest. The objective of this study was to investigate the influence of a single transplanted lung on respiratory muscle mechanics. The force and power of the sternomastoid, external intercostal and external oblique muscles were evaluated throughout a range of respiratory maneuvers in emphysematic patients with a single transplanted lung and compared with that of healthy subjects. A significant differences was observed between the force, work and power of the muscles on the two sides of the chest in emphysematic patients (P<0.05). The control group demonstrated higher averaged maximal force, work and power. The total work done during either inspiration or expiration by the external intercostal and external oblique muscles on the side of the transplanted lung were higher compared with that of the native lung side and compared with the control group. The asynchrony between the lungs after single-lung transplant leads to asynchronous muscle force and work and lesser muscle strength compared to healthy subjects.
Osho, Asishana A.; Castleberry, Anthony W.; Yerokun, Babatunde A.; Mulvihill, Michael S.; Rucker, Justin; Snyder, Laurie D.; Davis, Robert D.; Hartwig, Matthew G.
BACKGROUND The purpose of this study was to identify risk factors and outcome implications for 30-day hospital readmission in lung transplant recipients. METHODS We conducted a retrospective cohort study of lung transplant cases from a single, high-volume lung transplant program between January 2000 and March 2012. Demographic and health data were reviewed for all patients. Risk factors for 30-day readmission (defined as readmission within 30 days of discharge from index lung transplant hospitalization) were modeled using logistic regression, with selection of parameters by backward elimination. RESULTS The sample comprised 795 patients after excluding scheduled readmissions and in-hospital deaths. Overall 30-day readmission rate was 45.4% (n = 361). Readmission rates were similar across different diagnosis categories and procedure types. By univariate analysis, post-operative complications that predisposed to 30-day readmission included pneumonia, any infection, and atrial fibrillation (all p < 0.05). In the final multivariate model, occurrence of any post-transplant complication was the most significant risk factor for 30-day readmission (odds ratio = 1.764; 95% confidence interval, 1.259–2.470). Even for patients with no documented perioperative complication, readmission rates were still > 35%. Kaplan-Meier analysis and multi-variate regression modeling to assess readmission as a predictor of long-term outcomes showed that 30-day readmission was not a significant predictor of worse survival in lung recipients. CONCLUSIONS Occurrence of at least 1 post-transplant complication increases risk for 30-day readmission in lung transplant recipients. In this patient population, 30-day readmission does not predispose to adverse long-term survival. Quality indicators other than 30-day readmission may be needed to assess hospitals that perform lung transplantation. PMID:27932071
Mayeur, Nicolas; Srairi, Mohamed; Tetu, Laurent; Guilbeau Frugier, Céline; Fourcade, Olivier; Dahan, Marcel
Viral infections are frequent and severe in lung transplant recipients. They frequently occur during the first year after transplantation. We report on a rare case of bilateral adenovirus necrotizing pneumonia with a diffuse alveolar hemorrhage, 4 years after bilateral lung transplantation. The medical evolution was lethal in 72 hours because of respiratory, renal, and cardiac failure. Considering this case and the growing evidence on the severity of adenoviral infections, we call for controlled studies and therapeutic recommendations. Copyright © 2012 Elsevier Inc. All rights reserved.
San Segundo, David; Ballesteros, María Ángeles; Naranjo, Sara; Zurbano, Felipe; Miñambres, Eduardo; López-Hoyos, Marcos
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
Niggli, Fabian; Huber, Lars C; Benden, Christian; Schuurmans, Macé M
Human metapneumovirus (hMPV) causes serious respiratory tract infections in lung transplant recipients (LTRs). We evaluated the characteristics and adverse drug reactions (ADR) of oral ribavirin therapy for hMPV infections in LTRs. LTRs with respiratory symptoms or suspected infection of unknown origin were routinely sampled with nasopharyngeal swabs (NPS) for virological and bacteriological analysis as part of a diagnostic workup. Medical records of hMPV polymerase chain reaction (PCR)-positive LTRs at the University Hospital of Zurich were reviewed retrospectively. Between January 2012 and June 2014, 12 (80%) of 15 consecutive patients with documented hMPV infection received oral ribavirin therapy (800 mg/d, after 48 h: 400 mg/d). Mean duration of therapy was 28.6 days (range: 11-54). Mean duration of viral shedding was 16.3 days (range: 5-48). In general, oral ribavirin was well tolerated in LTRs. The most common ADR was moderate anaemia. All patients recovered from infection without immediate serious sequelae within 3 months of infection.
Castleberry, A. W.; Martin, J. T.; Osho, A. A.; Hartwig, M. G.; Hashmi, Z. A.; Zanotti, G.; Shaw, L. K.; Williams, J. B.; Lin, S. S.; Davis, R. D.
Coronary artery disease (CAD) is not uncommon among lung transplant candidates. Several small, single-center series have suggested that short-term outcomes are acceptable in selected patients who undergo coronary revascularization prior to, or concomitant with, lung transplantation. Our objective was to evaluate perioperative and intermediate-term outcomes in this patient population at our institution. We performed a retrospective, observational cohort analysis of 898 lung transplant recipients between 1997 and 2010. Pediatric, multivisceral, lobar or repeat transplantations were excluded, resulting in 791 patients for comparative analysis, of which 49 (median age 62, 79.6% bilateral transplant) underwent concurrent coronary artery bypass and 38 (median age 64, 63.2% bilateral transplant) received preoperative percutaneous coronary intervention (PCI). Perioperative mortality, overall unadjusted survival and adjusted hazard ratio for cumulative risk of death were similar among both revascularization groups as well as controls. The rate of postoperative major adverse cardiac events was also similar among groups; however, concurrent coronary artery bypass was associated with longer postoperative length of stay, more time in the intensive care unit and more postoperative days requiring ventilator support. These results suggest that patients with CAD need not be excluded from lung transplantation. Preferential consideration should be given to preoperative PCI when feasible. PMID:24102830
Shumway, N E
After ten years of experimental background, the first heart transplant at Stanford was performed on January 6, 1968. Six hundred and sixty-six patients have undergone 721 heart transplants since that date with an age range from five days to 64 years. The most common diagnosis has been cardiomyopathy with advanced coronary artery disease second. Current one and five year survival statistics are 81% and 60% respectively, with no difference in survival between the pediatric age group and adults. Percutaneous transvenous endomyocardial biopsy provides the gold standard for interpreting allograft rejection. At Stanford, 90 patients have undergone 91 heart-lung transplants since the first successful case in 1981. Twelve patients with cystic fibrosis have been transplanted and four of these recipients have been heart donors, the domino donor principle. Two double lung transplants have been performed utilising separate bronchial anastomoses. Fourteen patients have undergone 15 single lung transplants and three of these have been patients with the Eisenmenger syndrome where concomitant repair of the cardiac defect was carried out. One 12 year old patient received the right upper lobe of her mother as a total right lung transplant for bronchopulmonary dysplasia.
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.
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
Morisse-Pradier, H; Nove-Josserand, R; Philit, F; Senechal, A; Berger, F; Callet-Bauchu, E; Traverse-Glehen, A; Maury, J-M; Grima, R; Tronc, F; Mornex, J-F
Graft-versus-host disease (GVHD) is a classic and frequent multisystemic complication of bone marrow allografts. It has also been reported after the transplantation of solid organs such as the liver or gut. Recent cases of GVHD have been reported after lung and heart-lung transplant. Skin, liver, gastrointestinal tract and bone marrow are the organ preferentially affected by GVHD. Corticosteroid is the first line treatment of GVHD. The prognosis reported in solid organ transplants is poor with infectious complications favoured by immunosuppressive therapy. In this article, we report a case of a patient with cystic fibrosis who presented a probable GVHD 18 months after a lung transplant and a literature review of similar cases.
Alghamdi, Saad A; Nabi, Zahid G; Alkhafaji, Dania M; Askandrani, Sumaya A; Abdelsalam, Mohamed S; Shukri, Mohamed M; Eldali, Abdelmoneim M; Adra, Chaker N; Alkurbi, Lutfi A; Albaqumi, Mamdouh N
Transplant tourism is the term used for patients who travel abroad for transplantation. Transplant tourism has always been surrounded with controversy regarding how these organs were obtained, the donor's care after transplantation, and the recipient outcome. Many authors have found that the outcome of the recipients in transplant tourism is inferior to those transplanted in their own countries. However, most these studies were small, with the latest one including only 33 patients. Here, we describe the outcome of 93 patients who were transplanted abroad compared with local transplantation. All transplant patients who were followed up at our Nephrology Clinic from 1998 until 2008 were identified using our data base system. We selected patients transplanted from 2003 and forward because the computerized system for laboratory and electronic records began operation that year. A total of 165 patients were identified (93 in the tourist group and 72 in the local one). Transplant tourists had a higher rate of acute rejection in the first year compared with local transplantation (27.9% vs. 9.9, P=0.005), higher mean creatinine at 6 months and 1 year (120 vs. 101 micromol/L, P=0.0007, 113 vs. 98 micromol/L, P=0.008). There was no statistical difference in graft or patient survival in 1 or 2 years after transplantation. However, transplant tourist had a higher rate of cytomegalovirus infection (15.1% vs. 5.6%, P=0.05) and hepatitis C seroconversion (7.5% vs. 0%, P=0.02). Transplant tourists had a more complex posttransplantation course with higher incidence of acute rejection and infectious complications.
Bonser, Robert S; Taylor, Rhiannon; Collett, David; Thomas, Helen L; Dark, John H; Neuberger, James
The risk that a positive smoking history in lung donors could adversely affect survival of transplant recipients causes concern. Conversely, reduction of the donor pool by exclusion of donors with positive smoking histories could compromise survival of patients waiting to receive a transplant. We examined the consequences of donor smoking on post-transplantation survival, and the potential effect of not transplanting lungs from such donors. We analysed the effect of donor smoking on 3 year survival after first adult lung transplantation from brain-dead donors done between July 1, 1999, and Dec 31, 2010, by Cox regression modelling of data from the UK Transplant Registry. We estimated the effect of acceptance of lungs from donors with positive smoking histories on survival and compared it with the effect of remaining on the waiting list for a potential transplant from a donor with a negative smoking history donor, by analysing all waiting-list registrations during the same period with a risk-adjusted sequentially stratified Cox regression model. Of 1295 lung transplantations, 510 (39%) used lungs from donors with positive smoking histories. Recipients of such lungs had worse 3 year survival after transplantation than did those who received lungs from donors with negative smoking histories (unadjusted hazard ratio [HR] 1·46, 95% CI 1·20-1·78; adjusted HR 1·36, 1·11-1·67). Independent factors affecting survival were recipient's age, donor-recipient cytomegalovirus matching, donor-recipient height difference, donor's sex, and total ischaemic time. Of 2181 patients registered on the waiting list, 802 (37%) died or were removed from the list without receiving a transplant. Patients receiving lungs from donors with positive smoking histories had a lower unadjusted hazard of death after registration than did those who remained on the waiting list (0·79, 95% CI 0·70-0·91). Patients with septic or fibrotic lung disease registered in 1999-2003 had risk
Ruiz, Jesus; Herrero, María José; Bosó, Virginia; Megías, Juan Eduardo; Hervás, David; Poveda, Jose Luis; Escrivá, Juan; Pastor, Amparo; Solé, Amparo; Aliño, Salvador Francisco
Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc). The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC). In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%). Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation. PMID:26307985
Bahr, Nathan C.; Janssen, Katherine; Billings, Joanne; Loor, Gabriel; Green, Jaime S.
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
Japan's Ministry of Health will fund a major new heart transplantation project in an effort to resume heart transplants halted by a public outcry against the first such transplant 17 years ago. Opposition to organ donation, which has been attributed variously to Buddhist and Confucian views of the body and to Japanese cultural values, has resulted in the heaviest use of renal dialysis per capita in the world and to an interest in artificial heart research. Goals of the heart transplant project are first to win public support and then to promote research on animal transplants, organ preservation, a distribution system, immunological control mechanisms, and artificial hearts as backup devices.
Diamond, Joshua M.; Gries, Cynthia J.; McDonnough, Jamiela; Blanc, Paul D.; Shah, Rupal; Dean, Monica Y.; Hersh, Beverly; Wolters, Paul J.; Tokman, Sofya; Arcasoy, Selim M.; Ramphal, Kristy; Greenland, John R.; Smith, Nancy; Heffernan, Pricilla; Shah, Lori; Shrestha, Pavan; Golden, Jeffrey A.; Blumenthal, Nancy P.; Huang, Debbie; Sonett, Joshua; Hays, Steven; Oyster, Michelle; Katz, Patricia P.; Robbins, Hilary; Brown, Melanie; Leard, Lorriana E.; Kukreja, Jasleen; Bacchetta, Matthew; Bush, Errol; D’Ovidio, Frank; Rushefski, Melanie; Raza, Kashif; Christie, Jason D.; Lederer, David J.
Rationale: Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation. Objectives: To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates. Methods: In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case–control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively. Measurements and Main Results: Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24–33%) and 10% based on the SPPB (95% CI, 7–14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01–1.67) for FFP and 1.53 (95% CI, 1.19–1.59) for SPPB. Conclusions: Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death. PMID:26258797
Herrmann, Gudrun; Knudsen, Lars; Madershahian, Navid; Mühlfeld, Christian; Frank, Konrad; Rahmanian, Parwis; Wahlers, Thorsten; Wittwer, Thorsten; Ochs, Matthias
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
Shitrit, David; Bendayan, Daniele; Gidon, Sahar; Saute, Milton; Bakal, Ilana; Kramer, Mordechai R
Short-term improvement in lung function was observed in 5 of 6 lung transplant recipients with bronchiolitis obliterans syndrome (BOS) who were treated with oral azithromycin. We assessed the long-term effect (mean duration 10 months) of treatment with oral azithromycin in 11 lung transplant recipients with BOS. Mean forced expiratory volume in 1 second (FEV1) was 40 +/- 9% at initiation of azithromycin treatment, 39 +/- 10% after 1 month, 39 +/- 12% after 4 months, 38 +/- 10% after 7 months and 38 +/- 10% after 10 months, respectively (statistically non-significant for all data). We conclude that long-term administration with oral azithromycin does not reverse BOS in lung transplant recipients, but may slow progression of the disease.
Zurbano, L; Zurbano, F
The lung transplantation is a therapeutic procedure indicated for lung diseases that are terminal and irreversible (except lung cancer) despite the best medical current treatment. It is an emergent procedure in medical care. In this review, an analyse is made of the most frequent complications of lung transplant related to the graft (rejection and chronic graft dysfunction), immunosuppression (infections, arterial hypertension, renal dysfunction, and diabetes), as well as others such as gastrointestinal complications, osteoporosis. The most advisable therapeutic options are also included. Specific mention is made of the reviews and follow-up for monitoring the graft and the patients, as well as the lifestyle recommended to improve the prognosis and quality of life. An analysis is also made on the outcomes in the Spanish and international registries, their historical evolution and the most frequent causes of death, in order to objectively analyse the usefulness of the transplant.
Rabanal, J M; Real, M I; Williams, M
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.
Rubin, Adalberto Sperb; Nascimento, Douglas Zaione; Sanchez, Letícia; Watte, Guilherme; Holand, Arthur Rodrigo Ronconi; Fassbind, Derrick Alexandre; Camargo, José Jesus
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
Ishihara, Hiroki; Shimizu, Tomokazu; Unagami, Kohei; Hirai, Toshihito; Toki, Daisuke; Omoto, Kazuya; Okumi, Masayoshi; Imai, Yoichi; Ishida, Hideki; Tanabe, Kazunari
Post-transplant lymphoproliferative disorder is a serious complication of solid organ transplantation; however, few large studies have been performed in Asian institutions. We review our single-center experience with post-transplant lymphoproliferative disorder patients in Japan. We retrospectively evaluated patients with post-transplant lymphoproliferative disorder following kidney transplantation between January 1985 and December 2013. The patients were divided into early-onset post-transplant lymphoproliferative disorder (<1 year) and late-onset post-transplant lymphoproliferative disorder (≥1 year) groups. Thirteen patients had the disorder, an incidence rate of 0.75% (13/1730). Early-onset post-transplant lymphoproliferative disorder (N = 3) had not occurred for the last two decades. In the late-onset group (N = 10), the median time of onset was 108.7 months. The Kaplan-Meier 10-year overall survival rates were 76.9% and 95.4% in patients with and without the disorder, respectively (P = 0.0001). Post-transplant lymphoproliferative disorder significantly affected transplant recipients' mortality. Late-onset occurred even > 10 years after transplantation; therefore, long-term monitoring of patients is needed. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.
Courtwright, Andrew M.; Fried, Sabrina; Villalba, Julian A.; Moniodis, Anna; Guleria, Indira; Wood, Isabelle; Milford, Edgar; Mallidi, Hari H.; Hunninghake, Gary M.; Raby, Benjamin A.; Agarwal, Suneet; Camp, Philip C.; Rosas, Ivan O.; Goldberg, Hilary J.; El-Chemaly, Souheil
Background Patients with short telomere syndromes and pulmonary fibrosis have increased complications after lung transplant. However, the more general impact of donor and recipient telomere length in lung transplant has not been well characterized. Methods This was an observational cohort study of patients who received lung transplant at a single center between January 1st 2012 and January 31st 2015. Relative donor lymphocyte telomere length was measured and classified into long (third tertile) and short (other tertiles). Relative recipient lung telomere length was measured and classified into short (first tertile) and long (other tertiles). Outcome data included survival, need for modification of immunosuppression, liver or kidney injury, cytomegalovirus reactivation, and acute rejection. Results Recipient lung tissue telomere lengths were measured for 54 of the 79 patients (68.3%) who underwent transplant during the study period. Donor lymphocyte telomeres were measured for 45 (83.3%) of these recipients. Neither long donor telomere length (hazard ratio [HR] = 0.58, 95% confidence interval [CI], 0.12–2.85, p = 0.50) nor short recipient telomere length (HR = 1.01, 95% CI = 0.50–2.05, p = 0.96) were associated with adjusted survival following lung transplant. Recipients with short telomeres were less likely to have acute cellular rejection (23.5% vs. 58.8%, p = 0.02) but were not more likely to have other organ dysfunction. Conclusions In this small cohort, neither long donor lymphocyte telomeres nor short recipient lung tissue telomeres were associated with adjusted survival after lung transplantation. Larger studies are needed to confirm these findings. PMID:27589328
Courtwright, Andrew M; Fried, Sabrina; Villalba, Julian A; Moniodis, Anna; Guleria, Indira; Wood, Isabelle; Milford, Edgar; Mallidi, Hari H; Hunninghake, Gary M; Raby, Benjamin A; Agarwal, Suneet; Camp, Philip C; Rosas, Ivan O; Goldberg, Hilary J; El-Chemaly, Souheil
Patients with short telomere syndromes and pulmonary fibrosis have increased complications after lung transplant. However, the more general impact of donor and recipient telomere length in lung transplant has not been well characterized. This was an observational cohort study of patients who received lung transplant at a single center between January 1st 2012 and January 31st 2015. Relative donor lymphocyte telomere length was measured and classified into long (third tertile) and short (other tertiles). Relative recipient lung telomere length was measured and classified into short (first tertile) and long (other tertiles). Outcome data included survival, need for modification of immunosuppression, liver or kidney injury, cytomegalovirus reactivation, and acute rejection. Recipient lung tissue telomere lengths were measured for 54 of the 79 patients (68.3%) who underwent transplant during the study period. Donor lymphocyte telomeres were measured for 45 (83.3%) of these recipients. Neither long donor telomere length (hazard ratio [HR] = 0.58, 95% confidence interval [CI], 0.12-2.85, p = 0.50) nor short recipient telomere length (HR = 1.01, 95% CI = 0.50-2.05, p = 0.96) were associated with adjusted survival following lung transplant. Recipients with short telomeres were less likely to have acute cellular rejection (23.5% vs. 58.8%, p = 0.02) but were not more likely to have other organ dysfunction. In this small cohort, neither long donor lymphocyte telomeres nor short recipient lung tissue telomeres were associated with adjusted survival after lung transplantation. Larger studies are needed to confirm these findings.
Higenbottam, T.; Jackson, M.; Woolman, P.; Lowry, R.; Wallwork, J.
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.
Wawrzyńska, Liliana; Remiszewski, Paweł; Kurzyna, Marcin; Fijałkowska, Anna; Burakowski, Janusz; Dabrowski, Marek; Orłowski, Tadeusz; Roszkowski, Kazimierz; Dłutek, Piotr; Klepetko, Walter; Torbicki, Adam
We describe a case of 29 year old man, a first Polish patient with idiopathic arterial hypertension (IPAH) listed from Poland and successfully treated with lung transplantation in Vienna. Time from diagnosis to lung transplant was merely 11 months. Rapid clinical deterioration required treatment with most of currently approved or emerging methods, including oral and parenteral prostacyclin analogues administration by inhalation and chronic subcutaneous infusion. Atrial balloon septostomy was used to bridge the patient to transplant. We describe multiple problems in providing pharmacotherapy and in arranging logistics for lung transplantation. Peri- and multiple post-transplantation complications including dehiscence of right main bronchial anastomosis and its successful therapy are also presented. We consider good long term outcome as assessed 26 months post transplantation as an encouragement for other attempts at lung transplantation in patients with IPAH and for development of this method of therapy in Poland.
Cardozo, B.L.; Zoetelief, H.; van Bekkum, D.W.; Zurcher, C.; Hagenbeek, A.
High dose whole body irradiation is commonly included in conditioning regimens for bone marrow transplantation for treatment of patients with hematological malignancies. Interstitial pneumonitis is a major complication after BMT. When no infectious cause is found, it is classified as idiopathic IP (IIP). Total body irradiation is often associated with the induction of IIP; however, extrapolation of animal data from the experiments presented indicates that this is not the only factor contributing to IIP in man. Brown Norway (BN/Bi) rats were bilaterally irradiated to the lungs with 300 kV X rays at a high dose rate (HDR; 0.8 Gy/min) and at low dose rate (LDR; 0.05 Gy/min). The LD50 at 180 days was 13.3 Gy for HDR and 22.7 Gy for LDR. The ratios of LD/sub 50/180/ at 0.05 Gy/min to that at 0.8 Gy/min is 1.7, which indicates a great repair capacity of the lungs. Extrapolation of animal data to patient data leads to an estimated dose of about 15-16 Gy at a 50% radiation pneumonitis induction for low dose rate TBI. As the absorbed dose in the lungs of BMT patients rarely exceeds 10 Gy, additional factors might be involved in the high incidence of HP in man after BMT.
Ohsumi, Akihiro; Chen, Fengshi; Sakamoto, Jin; Nakajima, Daisuke; Hijiya, Kyoko; Motoyama, Hideki; Okita, Kenji; Horita, Kenta; Kikuchi, Ryutaro; Yamada, Tetsu; Bando, Toru; Date, Hiroshi
Warm ischemia-reperfusion injury related to donation after cardiac death is a crucial issue in transplantation. Because surfactant function deteriorates in lungs during warm ischemia, we hypothesized pre-recovery surfactant inhalation would mitigate warm ischemia-reperfusion injury. We rendered donor dogs cardiac dead and left them at room temperature. All animals received ventilation for 60 minutes starting at 240 minutes after cardiac arrest. The animals were divided into 2 groups: NS (normal saline, n = 7) group, which received aerosolized normal saline, and SF (surfactant; n = 5), which received aerosolized surfactant. The lungs were flushed and procured, and the left lung was transplanted into recipient dogs. At 45 minutes of reperfusion, the right pulmonary artery was ligated, and the left transplanted lung function was evaluated. In the NS group, 2 of 7 dogs died at 75 minutes after reperfusion, whereas all 5 animals in the SF group survived for 240 minutes after reperfusion. The SF group showed significantly better dynamic compliance, oxygenation, and wet-to-dry weight ratio. Furthermore, the SF group had higher levels of high-energy phosphates in the lung tissues and lower levels of interleukin-8, tumor necrosis factor-α, and protein in the bronchoalveolar lavage fluid. Histologically, the lungs in the SF group showed fewer signs of interstitial edema and hemorrhage and significantly less neutrophilic sequestration than those of the NS group. Our results indicated pre-recovery surfactant inhalation improved graft function, maintained adenine nucleotide levels, and prevented alveolar-capillary barrier leakage, resulting in the attenuation of warm ischemia-reperfusion injury. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Potena, Luciano; Solidoro, Paolo; Patrucco, Filippo; Borgese, Laura
Heart and lung transplantation are standard therapeutic strategies to improve survival and quality of life in selected patients with end-stage heart or lung diseases. Cytomegalovirus (CMV) is one the most clinically relevant and frequent post-transplant infectious agents, which may cause direct acute syndromes, and chronic indirect graft-related injury. Despite effective antiviral drugs being available to prevent and treat CMV infection, due to the immunosuppression burden and the specific characteristics of thoracic grafts, CMV infection remains a major clinical problem in heart and lung transplant recipients. We performed an extensive literature search focused on studies specifically including heart or lung transplantation, when available, or kidney transplant recipients when data on thoracic transplants were not available. We discuss the pros and cons supporting the use of currently available drugs and strategies for CMV prevention and treatment, highlighting current unmet needs. While (Val)Ganciclovir remains the cornerstone of anti-CMV therapy, prolonged universal prophylaxis may expose a large number of patients to an excess of drug toxicity. Additional drugs with lower toxicity may be available in the context of anti-CMV prophylaxis, and effective CMV-risk stratification, by means of novel immune monitoring assays, which may help to customize the therapeutic approach.
Mahmood, Kamran; Kraft, Bryan D.; Glisinski, Kristen; Hartwig, Matthew G.; Harlan, Nicole P.; Piantadosi, Claude A.; Shofer, Scott L.
Background Central airway stenosis (CAS) is common after lung transplantation and causes significant post-transplant morbidity. It is often preceded by extensive airway necrosis, related to airway ischemia. Hyperbaric oxygen therapy (HBOT) is useful for ischemic grafts and may reduce the development of CAS. Methods The purpose of this study was to determine whether HBOT could be safely administered to lung transplant patients with extensive necrotic airway plaques. Secondarily, we assessed any effects of HBOT on the incidence and severity of CAS. Patients with extensive necrotic airway plaques within 1–2 months after lung transplantation were treated with HBOT along with standard care. These patients were compared with a contemporaneous reference group with similar plaques who did not receive HBOT. Results Ten patients received HBOT for 18.5 (interquartile range, IQR 11–20) sessions, starting at 40.5 (IQR 34–54) days after transplantation. HBOT was well tolerated. Incidence of CAS was similar between HBOT-treated patients and reference patients (70% vs 87%, respectively; P=.34), but fewer stents were required in HBOT patients (10% vs 56%, respectively; P=.03). Conclusions This pilot study is the first to demonstrate HBOT safety in patients who develop necrotic airway plaques after lung transplantation. HBOT may reduce the need for airway stent placement in patients with CAS. PMID:27410718
Santacruz, Jose Fernando; Mehta, Atul C
Overall survival rates of lung transplantation have improved since the first human lung transplantation was performed. A decline in the incidence of airway complications (AC) had been a key feature to achieve the current outcomes. Several proposed risk factors to the development of airway complications have been identified, ranging from the surgical technique to the immunosuppressive regimen. There are essentially six different airway complications post-lung transplantation. The most frequently reported complication is bronchial stenosis. Other complications include bronchial dehiscence, exophytic excessive granulation tissue formation, tracheo-bronchomalacia, bronchial fistulas, and endobronchial infections. The management of post-transplant bronchial complications needs a multispecialty team approach. Prevention of some complications may be possible by early and aggressive medical management as well as by using certain surgical techniques for transplantation. Interventional bronchoscopic procedures, including balloon bronchoplasty, cryotherapy, laser photoresection, electrocautery, high-dose endobronchial brachytherapy, and bronchial stents are among the armamentarium. Also, medical management, like antibiotic prophylaxis and therapy for endobronchial infections, or noninvasive positive-pressure ventilation in case of bronchomalacia, are used to treat an AC. In some cases, different surgical approaches are occasionally required. In this article we review the risk factors, the clinical presentation, the diagnostic methods, as well as the management options of the most common AC after lung transplantation.
Levine, Deborah J; Glanville, Allan R; Aboyoun, Christina; Belperio, John; Benden, Christian; Berry, Gerald J; Hachem, Ramsey; Hayes, Don; Neil, Desley; Reinsmoen, Nancy L; Snyder, Laurie D; Sweet, Stuart; Tyan, Dolly; Verleden, Geert; Westall, Glen; Yusen, Roger D; Zamora, Martin; Zeevi, Adriana
Antibody-mediated rejection (AMR) is a recognized cause of allograft dysfunction in lung transplant recipients. Unlike AMR in other solid-organ transplant recipients, there are no standardized diagnostic criteria or an agreed-upon definition. Hence, a working group was created by the International Society for Heart and Lung Transplantation with the aim of determining criteria for pulmonary AMR and establishing a definition. Diagnostic criteria and a working consensus definition were established. Key diagnostic criteria include the presence of antibodies directed toward donor human leukocyte antigens and characteristic lung histology with or without evidence of complement 4d within the graft. Exclusion of other causes of allograft dysfunction increases confidence in the diagnosis but is not essential. Pulmonary AMR may be clinical (allograft dysfunction which can be asymptomatic) or sub-clinical (normal allograft function). This consensus definition will have clinical, therapeutic and research implications. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Berastegui, Cristina; Gómez-Ollés, Susana; Sánchez-Vidaurre, Sara; Culebras, Mario; Monforte, Victor; López-Meseguer, Manuel; Bravo, Carlos; Ramon, Maria-Antonia; Romero, Laura; Sole, Joan; Cruz, Maria-Jesus; Román, Antonio
The long-term success of lung transplantation (LT) is limited by chronic lung allograft dysfunction (CLAD). Different phenotypes of CLAD have been described, such as bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The purpose of this study was to investigate the levels of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) as markers of these CLAD phenotypes. BALF was collected from 51 recipients who underwent (bilateral and unilateral) LT. The study population was divided into three groups: stable (ST), BOS, and RAS. Levels of interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using the multiplex technology. BALF neutrophilia medians were higher in BOS (38%) and RAS (30%) than in ST (8%) (P=.008; P=.012). Regarding BALF cytokines, BOS and RAS patients showed higher levels of INF-γ than ST (P=.02; P=.008). Only IL-5 presented significant differences between BOS and RAS (P=.001). BALF neutrophilia is as a marker for both CLAD phenotypes, BOS and RAS, and IL-5 seems to be a potential biomarker for the RAS phenotype.
Damy, Thibaud; Burgel, Pierre-Régis; Pepin, Jean-Louis; Boelle, Pierre-Yves; Cracowski, Claire; Murris-Espin, Marlène; Nove-Josserand, Raphaele; Stremler, Nathalie; Simon, Tabassome; Adnot, Serge; Fauroux, Brigitte
Pulmonary hypertension (PH) may affect survival in cystic fibrosis (CF) and can be assessed on echocardiographic measurement of the pulmonary acceleration time (PAT). The study aimed at evaluating PAT as a tool to optimize timing of lung transplant in CF patients. Prospective multicenter longitudinal study of patients with forced expiratory volume in 1 second (FEV1) ≤60% predicted. Echocardiography, spirometry and nocturnal oximetry were obtained as part of the routine evaluation. We included 67 patients (mean FEV1 42±12% predicted), among whom 8 underwent lung transplantation during the mean follow-up of 19±6 months. No patients died. PAT was determined in all patients and correlated negatively with systolic pulmonary artery pressure (sPAP, r=-0.36, P=0.01). Patients in the lowest PAT tertile (<101 ms) had lower FEV1 and worse nocturnal oxygen saturation, and they were more often on the lung transplant waiting list compared to patients in the other tertiles. Kaplan-Meier curves showed a shorter time to lung transplantation in the lowest PAT tertile (P<0.001) but not in patients with sPAP>35 mmHg. By multivariate analysis, FEV(1)and nocturnal desaturation were the main determinants of reduced PAT. A PAT<101 ms reduction is a promising tool for timing of lung transplantation in CF.
Damy, Thibaud; Burgel, Pierre-Régis; Pepin, Jean-Louis; Boelle, Pierre-Yves; Cracowski, Claire; Murris-Espin, Marlène; Nove-Josserand, Raphaele; Stremler, Nathalie; Simon, Tabassome; Adnot, Serge; Fauroux, Brigitte
Pulmonary hypertension (PH) may affect survival in cystic fibrosis (CF) and can be assessed on echocardiographic measurement of the pulmonary acceleration time (PAT). The study aimed at evaluating PAT as a tool to optimize timing of lung transplant in CF patients. Prospective multicenter longitudinal study of patients with forced expiratory volume in 1 second (FEV1) ≤60% predicted. Echocardiography, spirometry and nocturnal oximetry were obtained as part of the routine evaluation. We included 67 patients (mean FEV1 42±12% predicted), among whom 8 underwent lung transplantation during the mean follow-up of 19±6 months. No patients died. PAT was determined in all patients and correlated negatively with systolic pulmonary artery pressure (sPAP, r=–0.36, P=0.01). Patients in the lowest PAT tertile (<101 ms) had lower FEV1 and worse nocturnal oxygen saturation, and they were more often on the lung transplant waiting list compared to patients in the other tertiles. Kaplan–Meier curves showed a shorter time to lung transplantation in the lowest PAT tertile (P<0.001) but not in patients with sPAP>35 mmHg. By multivariate analysis, FEV1and nocturnal desaturation were the main determinants of reduced PAT. A PAT<101 ms reduction is a promising tool for timing of lung transplantation in CF. PMID:22558523
Hirano, Yutaka; Sugimoto, Seiichiro; Mano, Toshifumi; Kurosaki, Takeshi; Miyoshi, Kentaroh; Otani, Shinji; Yamane, Masaomi; Kobayashi, Motomu; Miyoshi, Shinichiro; Oto, Takahiro
BACKGROUND Although administration of tacrolimus, whether by the enteric, sublingual, or continuous intravenous routes, has some limitations, twice-daily bolus intravenous tacrolimus administration has been shown to be beneficial in optimizing efficacy and safety after lung transplantation. However, at present, the duration of bolus intravenous tacrolimus administration is limited, and the effects of prolonged bolus intravenous tacrolimus administration remain unknown. Our study was aimed at assessing the safety and efficacy of prolonged twice-daily bolus intravenous tacrolimus administration in the early phase after lung transplantation. MATERIAL AND METHODS We retrospectively investigated the data of 62 recipients of lung transplantation who had received twice-daily bolus intravenous administration of tacrolimus, followed by oral tacrolimus, after lung transplantation at our institution between January 2011 and October 2015. RESULTS The median duration of bolus intravenous tacrolimus administration was 19 days (4-72 days). The target trough level was achieved in 89% of the patients by day 3. Acute kidney injury occurred in 27% of the patients during bolus intravenous tacrolimus. Two patients (3%) had neurotoxicity, necessitating discontinuation of tacrolimus. Suspected acute rejection requiring steroid pulse therapy occurred in 21% of patients during the follow-up period. Eight patients (13%) developed chronic lung allograft dysfunction during the follow-up period. The 1-year and 5-year survival rates after lung transplantation were 95% and 76%, respectively. CONCLUSIONS These results suggest that prolonged bolus intravenous tacrolimus administration in the early phase after lung transplantation is a safe and effective alternative to enteric, sublingual, or continuous intravenous administration.
Esguerra-Gonzalez, Angeli; Ilagan-Honorio, Monina; Fraschilla, Stephanie; Kehoe, Priscilla; Lee, Ai Jin; Marcarian, Taline; Mayol-Ngo, Kristina; Miller, Pamela S; Onga, Jay; Rodman, Betty; Ross, David; Sommer, Susan; Takayanagi, Sumiko; Toyama, Joy; Villamor, Filma; Weigt, S Samuel; Gawlinski, Anna
Background Chest physiotherapy and high-frequency chest wall oscillation (HFCWO) are routinely used after lung transplant to facilitate removal of secretions. To date, no studies have been done to investigate which therapy is more comfortable and preferred by lung transplant recipients. Patients who have less pain may mobilize secretions, heal, and recover faster. Objectives To compare effects of HFCWO versus chest physiotherapy on pain and preference in lung transplant recipients. Methods In a 2-group experimental, repeated-measures design, 45 lung transplant recipients (27 single lung, 18 bilateral) were randomized to chest physiotherapy (10 AM, 2 PM) followed by HFCWO (6 PM, 10 PM; group 1, n=22) or vice versa (group 2, n=23) on postoperative day 3. A verbal numeric rating scale was used to measure pain before and after treatment. At the end of the treatment sequence, a 4-item patient survey was administered to assess treatment preference, pain, and effectiveness. Data were analyzed with χ(2) and t tests and repeated-measures analysis of variance. Results A significant interaction was found between mean difference in pain scores from before to after treatment and treatment method; pain scores decreased more when HFCWO was done at 10 AM and 6 PM (P =.04). Bilateral transplant recipients showed a significant preference for HFCWO over chest physiotherapy (11 [85%] vs 2 [15%], P=.01). However, single lung recipients showed no significant difference in preference between the 2 treatments (11 [42%] vs 14 [54%]). Conclusions HFCWO seems to provide greater decreases in pain scores than does chest physiotherapy. Bilateral lung transplant recipients preferred HFCWO to chest physiotherapy. HFCWO may be an effective, feasible alternative to chest physiotherapy. (American Journal of Critical Care. 2013;22:115-125).
Lin, Xue; Li, Wenjun; Lai, Jiaming; Okazaki, Mikio; Sugimoto, Seiichiro; Yamamoto, Sumiharu; Wang, Xingan; Gelman, Andrew E.; Kreisel, Daniel
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
Theunissen, C; Knoop, C; Nonhoff, C; Byl, B; Claus, M; Liesnard, C; Estenne, M J; Struelens, M J; Jacobs, F
Despite a large carriage rate of Clostridium difficile among cystic fibrosis (CF) patients, C. difficile-associated disease (CDAD) is rather rare. In case of lung transplantation, the incidence and clinical aspects of CDAD in this patient population are not well known. We reviewed the medical files of all CF patients who presented with symptomatic C. difficile infection from January 1998 to December 2004 and compared the incidence, clinical aspects, severity of disease, and clinical outcome between non-transplanted and transplanted CF patients. Between 1998 and 2004, 106 adult CF patients were followed at our clinic. Forty-nine patients underwent lung transplantation; 15 before 1998 and 34 after 1998. The incidence density of CDAD was higher in transplanted CF patients as compared with non-transplanted CF patients (24.2 vs. 9.5 episodes/100,000 patient-days; risk ratio: 2.93 [1.41-6.08]; P=0.0044). Diarrhea was a very frequent feature, but was notably absent in 20% of the cases. Rates of moderate and severe colitis were similar in both groups. However, only transplanted patients developed complicated colitis. CT scan and endoscopy were performed more frequently in the transplant group. Two transplant recipients died because of CDAD. CF patients who undergo lung transplantation are at a higher risk of developing CDAD and seem to present more often atypical and/or complicated disease. CDAD should be part of the differential diagnosis in case of digestive symptoms, even in the absence of diarrhea, and requires early treatment.
Seiler, Annina; Jenewein, Josef; Martin-Soelch, Chantal; Goetzmann, Lutz; Inci, Ilhan; Weder, Walter; Schuurmans, Macé M; Benden, Christian; Brucher, Angela; Klaghofer, Richard
To (1) assess distinct clusters of psychological distress and health-related quality of life during the first 6 months following lung transplantation; (2) identify patients with poor psychosocial outcomes; and (3) determine potential predictors regarding psychological distress and health-related quality (HRQoL) of life at 6 months post-transplant. A total of 40 patients were examined for psychological distress (Symptom Checklist short version-9) and quality of life (EuroQOL five-dimension health-related quality of life questionnaire) during their first 6 months post-transplant. Hierarchical cluster analyses were performed to identify specific types of post-transplant outcomes in terms of psychological distress and HRQoL over the first six post-transplant months. Correlational analyses examined medical and psychosocial predictors of the outcome at 6 months post-transplant. Three distinctive clusters were identified, summarizing either groups of patients with (1) optimal (35%), (2) good (42%), and (3) poor outcome-clusters (23%). The latter tended to be older, to suffer from more severe disease, to have more co-morbidities, to have had a prolonged intensive care unit and/or hospital stay, to have more hospital admissions and were more frequently treated with antidepressants post-transplant. Disease severity, length of stay, quality of life two weeks post-transplant, hospital admissions and use of antidepressants were strong predictors of psychological distress and impaired health-related quality of life at six months of follow-up. Almost a quarter of the investigated patients suffered from elevated distress and substantially impaired HRQoL, with no improvements over time. Results underscore the psychosocial needs of patients with poor post-transplant outcomes.
Oishi, Hisashi; Okada, Yoshinori; Saiki, Yoshikatsu; Sado, Tetsu; Noda, Masafumi; Hoshikawa, Yasushi; Endo, Chiaki; Sakurada, Akira; Maeda, Sumiko; Akiba, Miki; Hoshi, Kunihiko; Kondo, Takashi
We report a case of bilateral lung transplantation (BLT) after preservation of the donor graft for 16 h 5 min with EP-TU, an extracellular phosphate-buffered lung preservation solution. The recipient was a 26-year-old woman with idiopathic pulmonary arterial hypertension and the graft ischemic time was prolonged significantly because of the time required to induce peripheral veno-arterial extracorporeal membrane oxygenation (V-A ECMO) under local anesthesia, and address the severe intrathoracic and pericardial adhesions from past surgery for partial anomalous pulmonary venous return, with concurrent annular plication of the tricuspid valve. After the operation, ECMO and continuous hemodiafiltration were started preemptively to protect the grafts against excessive edema. Postoperative chest X-ray showed diffuse bilateral infiltrates, which improved within a few days and she was weaned off ECMO on day 9. Successful BLT after a graft ischemic time of over 16 h has rarely been described in clinical lung transplantation.
Sugimoto, Seiichiro; Yamane, Masaomi; Miyoshi, Kentaroh; Kurosaki, Takeshi; Otani, Shinji; Miyoshi, Shinichiro; Oto, Takahiro
In cadaveric lung transplantation (LTx), a donor lung with an inadequate donor left atrial cuff is considered a "surgically marginal donor lung". The donor pericardium is commonly applied to reconstruct the inadequate donor left atrial cuff; however, in some cases, the donor pericardium is inadvertently removed during the lung procurement. We devised an alternative technique for reconstruction to overcome the absence of pericardium in a donor lung with an inadequate atrial cuff, using a patch of the donor pulmonary artery (PA) in single lung transplantation. In a recent case of lung transplantation in which the donor pericardium had been removed, we harvested a segment of the right PA distal to the main PA of the donor and used a PA patch to repair the inadequate donor left atrial cuff. No vascular complications were encountered in the recipient, who remains in good health after the transplantation.
In December 1966, the first pancreas transplant ever was performed at the University of Minnesota. R. Lillehei and W. Kelly, transplanted a kidney and a pancreas in a diabetic patient on dialysis, getting function of both organs. Since then, the technical and immunological advances in this transplant have resulted in graft and patient survival results as the rest of the abdominal solid organ transplants. The balance of these 50 years is that more than 50,000 diabetic patients have been transplanted in more than 200 centers around the world. In our country the first transplant was performed 34 years ago in Barcelona and now 12 centers perform about 100 transplants per year. Although advances in diabetes control have been very important, pancreas transplantation continues to be the only method that allows normalization of the carbohydrates metabolism to improve the quality of life and, above all, to increase the survival of these patients. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
Cortesini, R; Alfani, D; Berloco, P; Caricato, M; Casciaro, G; Cicalese, L; Iappelli, M; Pisani, G; Poli, L; Pretagostini, R
The Authors report their experience with multiorgan transplantation performed in 3 patients affected by multifocal cancer of the liver, either primitive (2 cases) or secondary (1 case). The rationale for this new approach was the unfeasible single liver transplantation taking into account the extracapsular diffusion of the neoplasia.
Wong, J Y; Chambers, A L; Fuller, J; Lacson, A; Mullen, J; Lien, D; Humar, A
Fungal respiratory infections in patients with CF are a significant concern both pre- and post-lung transplantation (LTx). Fungal infection is associated with increased mortality post-LTx, and in the past decade, the prevalence of fungal colonization in Canadian pediatric patients with CF has increased. The emergence of novel fungal pathogens is particularly challenging to the transplant community, as little is known regarding their virulence and optimal management. We present a case of a successful double-lung transplant in a pediatric patient with CF who was infected pretransplantation with a novel yeast, Blastobotrys rhaffinosifermentans. This patient was treated successfully with aggressive antifungal therapy post-transplantation, followed by extended fungal prophylaxis. The significance of fungal colonization and infection in children with CF pre- and post-LTx is reviewed.
Zurbano, L; Zurbano, F
Lung transplant is a therapeutic, medical-surgical procedure indicated for pulmonary diseases (except lung cancer), that are terminal and irreversible with current medical treatment. More than 3,500 lung transplants have been performed in Spain, with a rate of over 6 per million and increasing. In this review, an analysis is made of the types of transplants, their indications and contraindications, the procedures, immunosuppressive treatments, their side effects and medical interactions, current prophylaxis. A list of easily accessible literature references is also include, the majority being by national authors. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.
Turner, David A; Rehder, Kyle J; Bonadonna, Desiree; Gray, Alice; Lin, Shu; Zaas, David; Cheifetz, Ira M
Extracorporeal membrane oxygenation (ECMO) is increasingly implemented in patients with end-stage pulmonary disease as a bridge to lung transplant. Several centers have instituted an approach that involves physical rehabilitation and ambulation for patients supported with ECMO. Recent reports describe the successful use of ambulatory ECMO in patients with chronic respiratory illnesses being bridged to lung transplant. We describe the first case of a previously healthy pediatric patient with acute respiratory failure successfully supported with ambulatory ECMO as a bridge to lung transplant after an unsuccessful bridge to recovery. Although there are challenges associated with awake and ambulatory ECMO in children, this strategy represents an exciting breakthrough and a potential paradigm shift in ECMO management for pediatric acute respiratory failure. Copyright © 2014 by the American Academy of Pediatrics.
Abraham, Georgi; Reddy, Yuvaram N V; Amalorpavanathan, Joseph; Daniel, Dolly; Roy-Chaudhury, Prabir; Shroff, Sunil; Reddy, Yogesh
India with a population of 1.2 billion has a renal transplantation rate of 3.25 per million population. The major cause of chronic kidney disease is hypertension and diabetes. The crude and age-adjusted incidence rates of end-stage renal disease are estimated to be 151 and 232 per million population, respectively, in India. There was a remarkable lack of knowledge in the public about deceased organ donation until a decade ago. However, the role played by the media and nongovernmental organizations in partnership with the government has emphasized and implemented deceased donor transplantation in certain states in India-to mention particularly, the Tamil Nadu model. In the last 2 years, deceased organ donation has reached 1.3 per million population in Tamil Nadu, thereby effectively eliminating commercial transplantation. There is no religious bar for organ donation. A central transplant coordinator appointed by the government oversees legitimate and transparent allocation of deceased organs both in the public and private facilities as per the transplant waiting list. This model also takes care of the poor sections of society by conducting donation and transplantation through government-run public facilities free of cost. In the last 2 years, deceased donor transplantation has been performed through this network procuring organs such as the heart, heart valves, lung, liver, kidneys, cornea, and skin. The infrastructural lack of immunological surveillance-including donor-specific antibody monitoring, human leukocyte antigen typing, and panel reactive antibody except in a few tertiary care centers-prevents allocation according to the immunological status of the recipient. This private-public partnership promoting deceased donor transplantation has effectively eliminated commercialization in transplantation in the state of Tamil Nadu with a population of 72 million which is a model for other regions of South Asia and developing countries.
Courtwright, Andrew M; Salomon, Stacey; Lehmann, Lisa Soleymani; Brettler, Talya; Divo, Miguel; Camp, Phillip; Goldberg, Hilary J; Wolfe, David J
Psychiatric comorbidities such as mood, anxiety and adjustment disorders are common among individuals seeking lung transplantation. The objective of this study is to describe the association between these disorders and length of initial hospitalization and number of hospitalizations in the first year following transplantation. This was a retrospective cohort study of all lung transplantation patients between January 1, 2008 and July 1, 2014 at a large academic center. We evaluated whether pretransplantation mood, anxiety or adjustment disorders were associated with length and number of hospitalizations after transplant, adjusting for age, sex, native disease, forced expiratory volume in 1 s prior to transplantation, wait list time and lung allocation score. There were 185 patients who underwent transplantation during the 7.5-year study period of whom 125 (67.6%) had a mood, anxiety or adjustment disorder. Patients with an adjustment disorder had decreased length of initial hospitalization [B coefficient=-5.76; 95% confidence interval (CI)=-11.40 to -0.13; P=.04]. Patients with anxiety disorders had an increased number of hospitalizations in the first year following transplantation (rate ratio=1.41; 95% CI=1.06-1.88; P=.02). There was no association between mood disorders and length or number of hospitalizations. Mood, adjustment and anxiety disorders were not associated with time to initial rehospitalization. Among the three most common pretransplantation psychiatric disorders, only anxiety disorders are associated with increased hospitalization in the first year following lung transplant. Interventions designed to better control pretransplantation and posttransplantation anxiety may be associated with less frequent hospitalization. Copyright © 2016 Elsevier Inc. All rights reserved.
Hoffman, Mariana; Chaves, Gabriela; Ribeiro-Samora, Giane Amorim; Britto, Raquel Rodrigues
Objectives The aim of this systematic review of randomised controlled trials (RCTs), and quasi-experimental and retrospective studies is to investigate the effects of pulmonary rehabilitation (PR) in patients with advanced chronic disease on the waiting list for lung transplantation. Setting PR performed for inpatient or outpatient lung transplant candidates. Intervention PR programme including aerobic exercise training and/or resistance exercise training. Primary and secondary outcomes Quality of life and exercise capacity (primary outcomes). Survival rate after transplant surgery; pulmonary function; respiratory muscle strength; psychological aspects; upper and lower extremity muscle strength and adverse effects (secondary outcomes). Two review authors independently selected the studies, assessed study quality and extracted data. Studies in any language were included. Results This was a systematic review and studies were searched on the Cochrane Library, MEDLINE, EMBASE, CINAHL and PEDro. Experimental and retrospective studies evaluating the effects of PR in candidates for lung transplantation (>18 years old) with any lung diseases were included. 2 RCTs, and two quasi-experimental and two retrospectives studies, involving 1305 participants were included in the review. 5 studies included an enhancement reported in quality of life using the Short Form 36 questionnaire and showed improvements in some domains. All studies included exercise capacity evaluated through 6 min walk test and in five of them, there were improvements in this outcome after PR. Owing to the different characteristics of the studies, it was not possible to perform a meta-analysis. Conclusions Studies included in this review showed that PR is an effective treatment option for patients on the waiting list for lung transplantation and can improve quality of life and exercise capacity in those patients. Although individual studies reported positive effects of PR, this review shows that there is
Chaikriangkrai, Kongkiat; Jyothula, Soma; Jhun, Hye Yeon; Chang, Su Min; Graviss, Edward A.; Shuraih, Mossaab; Rami, Tapan G.; Dave, Amish S.; Valderrábano, Miguel
Objective To investigate incidence and timing, risk factors, prognostic significance, and electrophysiological mechanisms of atrial arrhythmia (AA) after lung transplantation. Background Although new-onset AA is common after thoracic surgery and is associated with poorer outcomes, prognostic and mechanistic data is sparse in lung transplant populations. Method A total of 293 consecutive isolated lung transplant recipients without known AA were retrospectively reviewed. Mean follow-up was 28±17 months. Electrophysiology studies (EPS) were performed in 25 patients with AA. Results The highest incidence of new-onset AA after lung transplantation occurred within 30 days postoperative AA, (25 % of all patients). In multivariable analysis, postoperative AA was associated with double lung transplantation (OR 2.79; p=0.005) and lower mean pulmonary artery pressure (OR 0.95; p=0.027). Patients with postoperative AA had longer hospital stays (21 days vs 12 days; p<0.001). Postoperative AA was independently associated with late AA (HR 13.52; p<0.001) but not mortality (HR 1.55; p=0.14). In EPS, there were 14 patients with atrial flutter alone and 11 with atrial flutter and fibrillation. Of all EPS patients, 20 (80%) had multiple AA mechanisms, including peritricuspid flutter (48%), perimitral flutter (36%), right atrial incisional reentry (24%), focal tachycardia from recipient pulmonary vein (PV) antrum (32 %), focal PV fibrillation (24%), and left atrial roof flutter (20%). Left atrial mechanisms were present in 80% (20/25) of EPS patients and originated from the anastomotic PV antrum. Conclusions Postoperative AA was independently associated with longer length of stay and late AA but not mortality. Pleomorphic PV antral arrhythmogenesis from native PV antrum is the main cause of AA after lung transplantation. PMID:26557726
el-Khatib, E.E.; Freeman, C.R.; Rybka, W.B.; Lehnert, S.; Podgorsak, E.B.
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.
Ganapathi, Asvin M; Speicher, Paul J; Castleberry, Anthony W; Englum, Brian R; Osho, Asishana A; Davis, R Duane; Hartwig, Matthew G
Lung transplantation in patients with prior lobectomy or pneumonectomy is not well understood. Using the United Network for Organ Sharing (UNOS) database, we address the impact of prior major lung resection on lung transplantation outcomes. Retrospective review of adult lung transplants from October 1999 to December 2011 in the UNOS database identified 15,300 lung transplants; 102 patients had undergone major lung resection, defined as prior pneumonectomy (n = 22) or lobectomy (n = 80). Propensity match with nonparametric 3:1 nearest-neighbor matching algorithm adjusted for treatment-level differences. After matching, the primary outcome (90-day mortality) and secondary outcome (airway dehiscence, need for dialysis, length of stay more than 25 days) were assessed with univariable and multivariable methods. Subanalysis of pneumonectomy and lobectomy individually compared with matched nonresection patients was done in a similar manner. The Kaplan-Meier method estimated long-term survival. After matching, no significant differences were noted between groups for recipient, donor, or operative characteristics. There were 10 double lung and 12 single lung transplants after pneumonectomy and 51 double lung and 29 single lung transplants after lobectomy. Mortality at 90 days was 13.9% (n = 14) for the resection group and 8.6% (n = 1,247) for the nonresection group (p = 0.09). After matching, a significant increase was noted in 90-day mortality (p = 0.017) and perioperative dialysis (p = 0.039) for the resection versus nonresection patients. Dialysis was significantly higher among pneumonectomy patients (p = 0.03). No long-term survival difference was observed (p = 0.514). After propensity-matching, resection was associated with increased 90-day mortality and dialysis. Careful patient selection is necessary with patients who have undergone prior major lung resection, given their increased risk of perioperative mortality and dialysis. Copyright © 2014 The Society
Izbicki, Gabriel; Shitrit, David; Schechtman, Itzhak; Bendayan, Danielle; Fink, Gershon; Sahar, Gideon; Saute, Milton; Ben-Gal, Tuvia; Kramer, Mordechai R
Pulmonary veno-occlusive disease, a rare cause of pulmonary hypertension, is characterized by extensive and diffuse occlusion of pulmonary veins by fibrous tissue. Although the diagnosis can be suspected by the presence of the classic clinical triad of severe pulmonary arterial hypertension, radiographic evidence of pulmonary hypertension and edema, and normal pulmonary artery occlusion pressure, the definitive diagnosis is histopathologic. The prognosis of pulmonary veno-occlusive disease is poor with most described patients dying within 2 years of diagnosis. Although anti-coagulation, oxygen, and vasodilator therapies are effective temporarily, the definitive treatment is lung transplantation. We describe the recurrence of pulmonary veno-occlusive disease at 3 months after heart-lung transplantation in a 26-year-old man. Recurrence after transplantation for this disease has not been reported previously, and lung transplantation was thought to be definitive treatment. With this 1st report of early recurrence of pulmonary veno-occlusive disease after heart-lung transplantation, we believe that extrapulmonary factors may play a role in the pathogenesis of this rare disease.
Yun, Jae Kwang; Choi, Se Hoon; Park, Seung-Il
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
Mets, Onno M; Roothaan, Suzan M; Bronsveld, Inez; Luijk, Bart; van de Graaf, Ed A; Vink, Aryan; de Jong, Pim A
Lung disease in cystic fibrosis (CF) involves excessive inflammation, repetitive infections and development of bronchiectasis. Recently, literature on emphysema in CF has emerged, which might become an increasingly important disease component due to the increased life expectancy. The purpose of this study was to assess the presence and extent of emphysema in endstage CF lungs. In explanted lungs of 20 CF patients emphysema was semi-quantitatively assessed on histology specimens. Also, emphysema was automatically quantified on pre-transplantation computed tomography (CT) using the percentage of voxels below -950 Houndfield Units and was visually scored on CT. The relation between emphysema extent, pre-transplantation lung function and age was determined. All CF patients showed emphysema on histological examination: 3/20 (15%) showed mild, 15/20 (75%) moderate and 2/20 (10%) severe emphysema, defined as 0-20% emphysema, 20-50% emphysema and >50% emphysema in residual lung tissue, respectively. Visually upper lobe bullous emphysema was identified in 13/20 and more diffuse non-bullous emphysema in 18/20. Histology showed a significant correlation to quantified CT emphysema (p = 0.03) and visual emphysema score (p = 0.001). CT and visual emphysema extent were positively correlated with age (p = 0.045 and p = 0.04, respectively). In conclusion, this study both pathologically and radiologically confirms that emphysema is common in end-stage CF lungs, and is age related. Emphysema might become an increasingly important disease component in the aging CF population.
Frist, W H; Lorenz, C H; Walker, E S; Loyd, J E; Stewart, J R; Graham, T P; Pearlstein, D P; Key, S P; Merrill, W H
Changes in right ventricular mass and ejection fraction after single-lung transplantation for pulmonary hypertension are poorly understood. To complement functional data provided by echocardiography, radionuclide ventriculography, and right heart catheterization, magnetic resonance imaging was used to assess right ventricular function in 5 single-lung transplant recipients with preoperative pulmonary hypertension and right ventricular dysfunction (right ventricular ejection fraction, 0.21 +/- 0.09). The right and left ventricular mass, ejection fraction, and mass ratio (left ventricular mass/right ventricular mass) were calculated from the magnetic resonance images. The mean pulmonary artery pressure fell from 72 +/- 18 to 21 +/- 8 mm Hg after transplantation. At 3 months after transplantation both the left ventricular and right ventricular ejection fractions approached normal values, as shown by both radionuclide ventriculography and magnetic resonance imaging, but the right ventricular mass remained abnormally high with slightly low mass ratios. By 1 year both the left ventricular and right ventricular masses had regressed to normal with near-normal mass ratios. Right ventricular performance returns to nearly normal early after transplantation, but the right ventricular mass regresses over a more prolonged time. Cine magnetic resonance imaging provides a noninvasive means of assessing changes in right ventricular function and mass after lung transplantation.
Yates, B; Murphy, D M; Fisher, A J; Gould, F K; Lordan, J L; Dark, J H; Corris, P A
Pseudomembranous colitis is an uncommon complication in patients with cystic fibrosis, despite the use of multiple high-dose antibiotic regimens and the frequency of hospital admissions. Four patients from a total of 137 patients with cystic fibrosis undergoing lung transplantation are described who developed fulminant pseudomembranous colitis. Initial presentation was variable and the mortality rate was 50% despite urgent colectomy. In one case the presenting abdominal distension was thought to be due to meconium ileus equivalent. It is concluded that Clostridium difficile colitis may be a difficult diagnosis in patients with cystic fibrosis and follows a fulminant course after lung transplantation.
Carley, Michelle; Schaff, Jacob; Lai, Terrance; Poppers, Jeremy
Vasoplegia syndrome, characterized by hypotension refractory to fluid resuscitation or high-dose vasopressors, low systemic vascular resistance, and normal-to-increased cardiac index, is associated with increased morbidity and mortality after cardiothoracic surgery. Methylene blue inhibits inducible nitric oxide synthase and guanylyl cyclase, and has been used to treat vasoplegia during cardiopulmonary bypass. However, because methylene blue is associated with increased pulmonary vascular resistance, its use in patients undergoing lung transplantion has been limited. Herein, we report the use of methylene blue to treat refractory vasoplegia during cardiopulmonary bypass in a patient undergoing double-lung transplantation.
de Camargo, Priscila Cilene León Bueno; Afonso, José Eduardo; Samano, Marcos Naoyuki; Acencio, Milena Marques Pagliarelli; Antonangelo, Leila; Teixeira, Ricardo Henrique de Oliveira Braga
Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4). The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients. PMID:25210966
Saldanha, Ian J; Akinyede, Oluwaseun; Robinson, Karen A
For people with cystic fibrosis and advanced pulmonary damage, lung transplantation is an available and viable option. However, graft rejection is an important potential consequence after lung transplantation. Immunosuppressive therapy is needed to prevent episodes of graft rejection and thus subsequently reduce morbidity and mortality in this population. There are a number of classes of immunosuppressive drugs which act on different components of the immune system. There is considerable variability in the use of immunosuppressive agents after lung transplantation in cystic fibrosis. While much of the research in immunosuppressive drug therapy has focused on the general population of lung transplant recipients, little is known about the comparative effectiveness and safety of these agents in people with cystic fibrosis. This is an update of a previously published review. To assess the effects of individual drugs or combinations of drugs compared to placebo or other individual drugs or combinations of drugs in preventing rejection following lung transplantation in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the potentially eligible study. We also searched the www.clinicaltrials.gov registry to obtain information on unpublished and ongoing studies.Date of latest search: 19 May 2015. Randomised and quasi-randomised studies. We independently assessed the studies identified from our searches for inclusion in the review. Should eligible studies be identified and included in future updates of the review, we will independently extract data and assess the risk of bias. While two studies met our inclusion criteria, we did not include them in the review because the investigators of the studies did not report any information specific to people with cystic fibrosis. Our attempts to obtain this information have not yet been successful. We will include any provided data in future
Kapila, Atul; Baz, Maher A; Valentine, Vincent G; Bhorade, Sangeeta M
Long-term outcomes after lung transplantation are limited due to chronic lung allograft dysfunction (CLAD). Bronchiolitis obliterans syndrome (BOS) is the most common form of obstructive CLAD and its definition derives from spirometric measurements. Given the importance of this diagnosis, both the accuracy and reliability of the definition of CLAD are crucial in understanding the pathophysiology of this disease to develop therapeutic options and influence outcome after lung transplantation. A web-based survey was designed and distributed to members of the Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) to better understand the accuracy and reliability of pulmonary function criteria in diagnosing BOS. Spirometric data from five patient scenarios that were discordant among reviewers regarding BOS determination from the Assessment of Immunosuppressive Regimen in Suppressing Acute and Chronic Rejection (AIRSAC) trial were randomly selected and summarized in this survey. Survey questions included the respondent's general understanding of the BOS definition, the determination of BOS, and difficulties with the current BOS definition. Eighty-seven respondents from the Pulmonary Council of the ISHLT responded to this survey. There was an overall 70% interobserver agreement regarding the presence or absence of BOS. Among those who agreed upon the presence of BOS, there was a 41% interobserver agreement regarding its time of onset. Despite this variability, the majority of respondents were not only familiar and agreed with the BOS criteria, they also felt confident in applying these criteria. Our survey identified potential limitations with the current criteria for diagnosing BOS. With recognition of the various CLAD phenotypes, further refinements of these diagnostic criteria will allow for an improved ability to identify and characterize patients who develop or are at risk for BOS, prognosticate outcomes, and, most importantly
Carneiro, Herman A; Coleman, Jeffrey J; Restrepo, Alejandro; Mylonakis, Eleftherios
Fusarium is a fungal pathogen of immunosuppressed lung transplant patients associated with a high mortality in those with severe and persistent neutropenia. The principle portal of entry for Fusarium species is the airways, and lung involvement almost always occurs among lung transplant patients with disseminated infection. In these patients, the immunoprotective mechanisms of the transplanted lungs are impaired, and they are, therefore, more vulnerable to Fusarium infection. As a result, fusariosis occurs in up to 32% of lung transplant patients. We studied fusariosis in 6 patients following lung transplantation who were treated at Massachusetts General Hospital during an 8-year period and reviewed 3 published cases in the literature. Cases were identified by the microbiology laboratory and through discharge summaries. Patients presented with dyspnea, fever, nonproductive cough, hemoptysis, and headache. Blood tests showed elevated white blood cell counts with granulocytosis and elevated inflammatory markers. Cultures of Fusarium were isolated from bronchoalveolar lavage, blood, and sputum specimens.Treatments included amphotericin B, liposomal amphotericin B, caspofungin, voriconazole, and posaconazole, either alone or in combination. Lung involvement occurred in all patients with disseminated disease and it was associated with a poor outcome. The mortality rate in this group of patients was high (67%), and of those who survived, 1 patient was treated with a combination of amphotericin B and voriconazole, 1 patient with amphotericin B, and 1 patient with posaconazole. Recommended empirical treatment includes voriconazole, amphotericin B or liposomal amphotericin B first-line, and posaconazole for refractory disease. High-dose amphotericin B is recommended for treatment of most cases of fusariosis. The echinocandins (for example, caspofungin, micafungin, anidulafungin) are generally avoided because Fusarium species have intrinsic resistance to them. Treatment
Balfoussia, Danai; Yerrakalva, Dharani; Hamaoui, Karim; Papalois, Vassilios
Solid organ transplant constitutes the definitive treatment for end-stage organ failure. Better organ preservation methods have enabled use of marginal grafts, thereby expanding the donor pool to meet the growing demand for organs. Static cold storage as a preservation method has been superseded largely by machine perfusion in kidney transplant, with work regarding its use in other organ transplants ongoing. We hope that machine perfusion will allow better graft preservation, and pretransplant assessment, and optimization. The most extensive laboratory, preclinical, and clinical research into machine perfusion organ preservation has focused on kidneys. Successful outcomes in its use in renal transplant have sparked interest for its development and application to the liver, pancreas, heart, and lungs. This article reviews the current state of machine perfusion in abdominal and thoracic organ transplant, focusing on the recent developments in assessing graft viability.
Higo, Hisao; Kurosaki, Takeshi; Ichihara, Eiki; Kubo, Toshio; Miyoshi, Kentaroh; Otani, Shinji; Sugimoto, Seiichiro; Yamane, Masaomi; Miyahara, Nobuaki; Kiura, Katsuyuki; Miyoshi, Shinichiro; Oto, Takahiro
Lung transplants have produced very favorable outcomes for patients with interstitial lung disease (ILD) in Japan. However, because of the severe donor lung shortage, patients must wait approximately 2.5 years before they can undergo transplantation and many candidates die before allocation. We reveal the clinical characteristics of Japanese patients with ILD who are candidates for lung transplants and the risk factors for early death while on the waiting list. We retrospectively reviewed the clinical data of patients registered in the Japan Organ Transplant Network from Okayama University Hospital who are candidates for cadaveric lung transplants for ILD between 1999 and 2015. Fifty-three patients with ILD were included (24 patients with idiopathic pulmonary fibrosis and 29 others). They had severe pulmonary dysfunction and low exercise tolerability. The median waiting time for transplantation was 462 days, and 22 patients died before allocation. Patients who died before 462 days without undergoing transplantation had more severe dyspnea, shorter 6-minute walk distance (6MWD), and lower performance status than those who waited ≥462 days. Japanese candidates for cadaveric lung transplants for ILD have severe pulmonary dysfunction. Severe dyspnea, short 6MWD, and low performance status are risk factors for early death while on the waiting list. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Schmack, Bastian; Weymann, Alexander; Mohite, Prashant; Garcia Saez, Diana; Zych, Bartlomiej; Sabashnikov, Anton; Zeriouh, Mohamed; Schamroth, Joel; Koch, Achim; Soresi, Simona; Ananiadou, Olga; De Robertis, Fabio; Karck, Matthias; Simon, Andre Ruediger; Popov, Aron Frederik
Lung transplantation remains the definite treatment for various end-stage lung diseases. Cold flush perfusion, the standard method for organ procurement has severe limitations. Organ Care System (OCS; TransMedics, Inc., Andover, USA) is an approved method to preserve hearts for transplantation that allows for greatly reduced cold ischemic time. Consequently, the use of an adapted OCS lung as a portable full ex-vivo lung perfusion system in lung transplantation is currently under close evaluation. Areas covered: The aim of this article is to review the advantages and the role of the OCS in the field of lung transplantation by reviewing the latest literature and evaluating this novel procurement technique in the context of conventional methods like cold flush and regular ex-vivo lung perfusion. Expert commentary: The use of OCS in the field of lung transplantation has great potential for improved patients outcomes and is justified in cases with (i) marginal donor lungs, (ii) foreseeable long time of transportation (iii) high-risk recipient or donor /recipient profiles, particularly in the setting of an overall increasing need for suitable donor organs. Results from two major multi-centre prospective studies are pending to objectively assess the possible advantages of this portable ex-vivo lung perfusion system.
Gundorova, R A; Chentsova, E V; Makarov, P V; Kugusheva, A É; Rakova, A V
Sometimes an urgent lamellar keratoplasty remains the only treatment option for corneal defect closure. When fresh donor tissue is absent as it is regular in recent years dried cornea transplantation becomes reasonable. In recent years in ocular trauma department 320 transplantations of dried on silicagel cornea were performed. Analysis of results allows to conclude that use of dried cornea is a promising surgical procedure to preserve the globe and in some cases to prepare the eye with severe trauma for subsequent optic surgery.
Postoperative antimicrobials after lung transplantation and the development of multidrug-resistant bacterial and Clostridium difficile infections: an analysis of 500 non-cystic fibrosis lung transplant patients.
Whiddon, Alexandra R; Dawson, Kyle L; Fuentes, Amaris; Perez, Katherine K; Peterson, Leif E; Kaleekal, Thomas
Broad-spectrum antimicrobials are given prophylactically post-transplant, although these agents are a risk factor for multidrug-resistant (MDR) infections and Clostridium difficile infection (CDI). This study aimed to determine whether an association exists between the duration of antimicrobials given early post-transplant and the development of MDR infections or CDI. A single-center retrospective analysis was performed on lung transplants from September 2009 to August 2014. Patients were excluded for cystic fibrosis (CF) or postoperative survival less than 30 d. Qualifying infections were defined as any new positive MDR bacterial culture or C. difficile assay from postoperative day 7-90 d after a broad-spectrum antimicrobial. A total of 500 patients, 61% male, were identified, median age of 62 yr. MDR infections occurred in 169 (34%) and CDI in 31 (6%). Non-ICU days were associated with a decreased risk of MDR/CDI (OR 0.891, p = 0.0002), and duration of Gram-positive antimicrobials (OR 1.073, p = 0.0219) was associated with an increased risk. One-third (34%) of non-CF lung transplants develop MDR infections and 6% develop CDI within 90 d of postoperative antimicrobials. The duration of Gram-positive antimicrobials may increase the risk of MDR/CDI, while early transfer from the ICU may have a protective effect. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Shitrit, David; Shitrit, Ariella Bar-Gil; Dickman, Ram; Sahar, Gidon; Saute, Milton; Kramer, Mordechai R
Lymphoproliferative disorder is a well-recognized complication of lung transplantation. Risk factors include Epstein-Barr virus infection and immunosuppression. The gastrointestinal manifestations of post-transplant lymphoproliferative disorder in lung transplant recipients have not been fully characterized. Case presentation and 16 previously reported cases of post-transplant lymphoproliferative disorder with gastrointestinal involvement are reviewed. Patient ages ranged from 25 to 65 (median, 52) years. Median time from lung transplantation to onset of posttransplant lymphoproliferative disorder was 36 (range, 1-109) months; 35 percent of cases (6/17) occurred within 18 months; Eighty-eight percent of patients (15/17) had positive Epstein-Barr virus serology before transplantation. In five patients (29 percent), the posttransplant lymphoproliferative disorder also involved sites other than the gastrointestinal tract. The most common gastrointestinal site of posttransplant lymphoproliferative disorder was the colon, followed by the small intestine and stomach. Clinical features included abdominal pain, nausea, and bloody diarrhea. Diagnosis was based on typical pathologic changes on gastrointestinal tract biopsy obtained mainly by colonoscopy. Treatment included a reduction in the immunosuppressive regimen in 15 of 17 cases (88 percent) and surgical resection in 10 (59 percent). One patient was untreated. Seven of 16 patients (44 percent) responded to treatment and 9 patients died. Median time from onset of posttransplant lymphoproliferative disorder to death was 70 (range, 10-85) days. Posttransplant lymphoproliferative disorder with gastrointestinal involvement is a unique entity that should be considered in all Epstein-Barr-Virus-positive lung transplant recipients who present with abdominal symptoms. Although immunosuppressive modulation and resection can lead to remission, the risk of death is 50 percent.
Chaikriangkrai, Kongkiat; Jyothula, Soma; Jhun, Hye Yeon; Estep, Jerry; Loebe, Matthias; Scheinin, Scott; Torre-Amione, Guillermo
This study examined the correlation between pre-operative coronary artery disease (CAD) and post-operative cardiovascular events in lung transplant recipients. Consecutive isolated lung transplant recipients from 2007 to 2013 in our institution were identified and categorized as having significant CAD (≥ 50% coronary stenosis in at least 1 artery or history of coronary revascularization) or no-mild CAD. Patient records and death index data were analyzed for a median of 2 years for death or cardiovascular events, including coronary, cerebrovascular, and peripheral artery events. The study comprised 280 patients (62% male) with mean age of 60 ± 10 years. Cardiovascular events occurred in 5.7% (16 of 280) of the entire cohort. Patients with significant CAD had a higher annualized rate of cardiovascular events than those with no-mild CAD (11.9% vs 0.6%; p < 0.001). Significant CAD was an independent predictor of cardiovascular events (hazard ratio, 20.32; 95% confidence interval, 5.79-71.26; p < 0.001) but not all-cause mortality (log-rank p = 0.66). Adding significant CAD to clinical risk factors gave incremental prognostic performance compared with clinical risk factors alone (p < 0.001 for increase in global chi-square). Selected lung transplant candidates with significant CAD can undergo transplantation with equal mortality risk to those without CAD but are at a higher risk of non-fatal cardiovascular events. These data support the current practice of accepting a selected group of patients with CAD for lung transplantation and suggest that they should be monitored early and treated to prevent cardiovascular complications. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Osho, Asishana A.; Castleberry, Anthony W.; Snyder, Laurie D.; Palmer, Scott M.; Ganapathi, Asvin M.; Hirji, Sameer A.; Lin, Shu S.; Davis, R. Duane; Hartwig, Matthew G.
Background Rates of repeat lung transplantation have increased since implementation of the lung allocation score (LAS). The purpose of this study is to compare survival between repeat (ReTx) and primary (LTx) lung transplant recipients in the LAS era. Methods We extracted data from 9,270 LTx and 456 ReTx recipients since LAS implementation, from the United Network for Organ Sharing registry. Propensity scoring was used to match ReTx and LTx recipients. Kaplan-Meier analysis compared survival between LTx and ReTx groups, with and without stratification based on time between first and second transplant. Multivariable Cox models estimated predictors of survival in lung recipients. Results Comparing all ReTx to LTx demonstrates a survival advantage for LTx that is diminished with propensity score matching (p = 0.174). Considering LTx against ReTx greater than 90 days after the initial procedure, there are similar survival results (p < 0.067). In contrast, ReTx within 90 days was associated with a survival disadvantage that persisted despite matching (p = 0.011). In ReTx populations, factors conferring worse outcomes include intensive care unit admission, unilateral transplantation, poor functional status, and primary graft dysfunction as the indication for retransplantation (p < 0.05). Conclusions Late lung retransplantation appears to be as beneficial as primary transplantation in propensity-matched patients. However, survival is severely diminished in those retransplanted less than 90 days after primary transplantation. The utility of early retransplantation needs to be carefully weighed in light of risks. PMID:25442999
Borro, José M; Delgado, María; Coll, Elisabeth; Pita, Salvador
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
Prabahar, M R; Soundararajan, P
Transplantation of human organs is undoubtedly one of the greatest medical breakthroughs of this century. However, few Indian patients are able to benefit from this medical advance. It is estimated that in India every year over 152,000 people are diagnosed to have end-stage renal failure needing renal transplantation. The Transplantation of Human Organs Act passed by the Indian parliament in 1994 was subsequently ratified by the state legislature of Tamil Nadu in May 1995. It accepted brain death as a form of death and prohibited commerce in organs. The first cadaveric kidney transplant in Sri Ramachandra medical college was performed in 1995 with 68 cadaveric kidney transplants thereafter. The mean age of the donors was 36 +/- 12.8 years. The mean cold ischemia time was 5.6 +/- 3.2 hours. As many as 14 donors displayed acute renal failure (serum creatinine more than 1.2 mg/dL). Immediate graft function was established in 34 patients (50%). Four had graft rupture, two of which were successfully repaired. Postoperatively 12 patients (17.6%) displayed delayed graft function requiring dialysis. During the first year, 18 patients (26.4%) experienced acute rejection episodes, of which 14 were cellular and four vascular rejection types. As many as eight patients were lost to follow-up within one year; the mean follow-up time was 968 +/- 86 days. Patient survival at 1 year was 88.2% and that of the graft 73.5%. The 5-year patient and graft survival rates were 61.7% and 58.8%, respectively. The mean serum creatinine of patients currently followed is 2.2 +/- 0.86 mg/dL. The rate of cadaver kidney transplantation in India is low despite initiatives by our university to promote donation. Creating a positive public attitude, early brain death identification, and certification, prompt consent for organ donation, adequate hospital infrastructure, and support logistics are prerequisites for successful organ transplantation.
Neujahr, D C; Uppal, K; Force, S D; Fernandez, F; Lawrence, C; Pickens, A; Bag, R; Lockard, C; Kirk, A D; Tran, V; Lee, K; Jones, D P; Park, Y
Aspiration of gastrointestinal contents has been linked to worse outcomes following lung transplantation but uncertainty exists about underlying mechanisms. We applied high-resolution metabolomics of bronchoalveolar lavage fluid (BALF) in patients with episodic aspiration (defined by bile acids in the BALF) to identify potential metabolic changes associated with aspiration. Paired samples, one with bile acids and another without, from 29 stable lung transplant patients were studied. Liquid chromatography coupled to high-resolution mass spectroscopy was used to interrogate metabolomic contents of these samples. Data were obtained for 7068 ions representing intermediary metabolites, environmental agents and chemicals associated with microbial colonization. A substantial number (2302) differed between bile acid positive and negative samples when analyzed by false discovery rate at q = 0.01. These included pathways associated with microbial metabolism. Hierarchical cluster analysis defined clusters of chemicals associated with bile acid aspiration that were correlated to previously reported biomarkers of lung injury including T cell granzyme B level and the chemoattractants CXCL9 and CXCL10. These data specifically link bile acids presence in lung allografts to inflammatory pathways known to segregate with worsening allograft outcome, and provide additional mechanistic insight into the association between reflux and lung allograft injury.
Geister, H; Simon, S
The ever-increasing negative balance between the offer of an demand for organs with regard to transplantation surgery is very problematic. The transplantation centres are confronted with an insolvable problem and for this reason the co-operation of hospitals, other than the transplantation centres, is of vital importance where the explantation of kidneys, under specified conditions, is concerned. There are reports of new experiences in the removal of organs through in-situ-perfusion and en-bloc-removals as well as combined consignments of organs and typing material. The favourable results personally achieved during the past 6 years have given cause to believe that other clinics or hospitals, other than the transplantation centres, will participate in the explantation or organs for the purpose of transplantation.
Jain, Anand; Baxi, Vaibhavi; Dasgupta, D
Summary Transplantation provides a near normal life and excellent rehabilitation compared to dialysis and is the preferred method of treatment for end stage renal disease patients. We describe our experiences through a retrospective analysis of anaesthesia management of 350 cases of both living related and cadaveric renal transplantation conducted between Jan 2004 - April 2008 at Jaslok Hospital And Research Center. Areas of our interest include preoperative patient status, fluid management, hemodynamic stability, anaesthesia management, and perioperative complications. Recent advances in surgical techniques; anaesthesia management and immunosuppressive drugs have made renal transplantation sale and predictable. Preoperative patient optimization, intraoperative physiological stability and postoperative care of renal transplant patients have contributed to the success of renal transplant programme in our hospital. PMID:20640138
DeCampos, K N; Keshavjee, S; Slutsky, A S; Liu, M
Physical factors play an important role in ischemia-reperfusion-induced injury of lung transplants. For example, rapid restoration of reperfusion resulted in severe pulmonary edema and deterioration of pulmonary function of lung explants in an ex vivo reperfusion system. This type of injury can be prevented by a stepwise increase in the perfusion flow rate, or by adding prostaglandin E1 (PGE1) to the blood perfusate during the first 10 minutes. However, the mechanisms of these protective effects are unknown. We noted a dramatic decrease in airway pressure rather than pulmonary arterial pressure in these studies, suggesting that lung recruitment may be an important factor in minimizing injury. In the present study, we examined the importance of alveolar recruitment in preventing rapid-reperfusion-induced lung injury. Rat lungs were flushed preserved with low potassium dextran solution for 12 hours at 4 degrees C. Lung explants were randomly divided into three groups: 1) untreated control; 2) lungs inflated to total lung capacity for 2 minutes; and 3) lungs ventilated for 10 minutes prior to reperfusion. Postpreservation lung function was assessed in an isolated rat lung reperfusion model. Rapid initiation of reperfusion led to severe pulmonary edema and significant pulmonary dysfunction. In inflation or ventilation groups, the injury was significantly attenuated. The PaO2 and shunt fractions in these lungs were comparable to normal lungs. A significant drop in airway pressure was observed in these two groups and the lung compliance in the inflation group was significantly better than other two groups. These results suggest that overcoming alveolar collapse with inflation or ventilation, may protect the lung from mechanical-stress-induced injury during reperfusion.
Shitrit, David; Ollech, Jacob E; Ollech, Ayelet; Bakal, Ilana; Saute, Milton; Sahar, Gideon; Kramer, Mordechai R
Itraconazole is often given for fungal prophylaxis to lung transplant recipients after transplantation. The aim of this study was to determine the extent of interaction between tacrolimus and itraconazole in lung transplant recipients and the efficacy of itraconazole prophylaxis. The study group included 40 lung transplant recipients followed for at least 12 months. All received prophylactic itraconazole, 200 mg twice a day, for the first 6 months after transplantation. Tacrolimus levels and dosage requirements were compared during and after itraconazole therapy. Rejection rate, fungal infection rate, and renal function were assessed. The mean cost per daily treatment of the itraconazole/tacrolimus combination and tacrolimus alone was calculated. The mean tacrolimus dose during itraconazole treatment was 3.26 +/- 2.1 mg/day compared with 5.74 +/- 2.9 mg/day after itraconazole was stopped (p < 0.0001) for a mean total daily dose elevation of tacrolimus of 76%. When the cost of itraconazole was taken into account, the average total daily cost of the combined treatment was US5.86 dollars less than the treatment with tacrolimus alone. No differences in the rejection or fungal infection rate, or in renal toxicity, were observed between the periods with and without itraconazole treatment, although less positive fungal isolates were identified during itraconazole therapy. Prophylaxis therapy with itraconazole is highly effective. Itraconazole reduces the dose of tacrolimus and therefore lowers the cost of therapy without causing an increase in rejection rate and with renal function preservation.
De Oliveira, Nilto C; Julliard, Walker; Osaki, Satoru; Maloney, James D; Cornwell, Richard D; Sonetti, David A; Meyer, Keith C
Survival for patients with idiopathic pulmonary fibrosis (IPF) and high lung allocation score (LAS) values may be significantly reduced in comparison to those with lower LAS values. To evaluate outcomes for high-risk IPF patients as defined by LAS values ≥46 (N=42) versus recipients with LAS values <46 (N=89). We retrospectively reviewed records of 131 consecutive patients with IPF who received lung transplants at our institution between 1999 and 2013. The mean LAS was significantly higher (59.5, interquartile range 43.9-75.9 vs. 39.3, interquartile range 37.7-44.3; p<0.01) for the high-risk cohort. The higher LAS cohort had significantly lower percent predicted forced vital capacity (FVC) versus recipients with LAS <46 (41.3±14.1% vs. 53.2±16.2%; p<0.01) and required more supplemental oxygen (7±5 vs. 4±2 L/min, p<0.01) prior to transplant versus recipients with LAS <46. Although the incidence of early post-LTX pulmonary complications was increased for the higher LAS group versus recipients with LAS <46, 30-day mortality and actuarial survival did not differ between the two cohorts. Although lung transplantation in patients with IPF and high LAS values is associated with increased risk of early post-transplant complications, long-term post-transplant survival for our high-LAS cohort was equivalent to that for the lower LAS recipients.
Duffy, Joseph S; Tumin, Dmitry; Pope-Harman, Amy; Whitson, Bryan A; Higgins, Robert S D; Hayes, Don
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.
Killian, Michael O
Few studies have identified the psychosocial characteristics of those children and their families associated with future non-adherence to immunosuppressive medications following a heart or lung transplant. UNOS data and medical records information were used to test the association between patient and family psychosocial characteristics and medication adherence. Medication adherence outcomes were obtained using the physician assessments in the UNOS data and measured through patient-level standard deviation scores of immunosuppressive medication blood levels. Complete data were collected on 105 pediatric heart and lung transplant recipients and their families. Multivariate, stepwise analyses were conducted with each adherence outcome. Physician reports of adherence were associated with age of the child at transplantation, parental education, two-parent families, significant psychosocial problems, and the pretransplant life support status of the child. The resulting model (χ(2) =28.146, df=5, P<.001) explained approximately 39.5% of the variance in physician reports of adherence (Nagelkerke r(2) =.395). Blood level standard deviation scores were predicted by age at transplant (F=5.624, P=.02, r(2) =.05). Results point to the difficulties experienced by children and families when undergoing a heart or lung transplantation. Efforts to develop standardized and evidence-based pretransplant psychosocial assessments in pediatric populations are suggested, especially those surrounding familial risk factors. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Song, Alice Tung Wan; Avelino-Silva, Vivian Iida; Pecora, Rafael Antonio Arruda; Pugliese, Vincenzo; D’Albuquerque, Luiz Augusto Carneiro; Abdala, Edson
Since 1963, when the first human liver transplantation (LT) was performed by Thomas Starzl, the world has witnessed 50 years of development in surgical techniques, immunosuppression, organ allocation, donor selection, and the indications and contraindications for LT. This has led to the mainstream, well-established procedure that has saved innumerable lives worldwide. Today, there are hundreds of liver transplant centres in over 80 countries. This review aims to describe the main aspects of LT regarding the progressive changes that have occurred over the years. We herein review historical aspects since the first experimental studies and the first attempts at human transplantation. We also provide an overview of immunosuppressive agents and their potential side effects, the evolution of the indications and contraindications of LT, the evolution of survival according to different time periods, and the evolution of methods of organ allocation. PMID:24833866
Mohammed, Aminu; Ulukpo, Onome; Force, Seth D.; Ramirez, Allan M.; Pelaez, Andres; Lawrence, E. Clinton; Larsen, Christian P.; Kirk, Allan D.
Background: Lung transplantation is associated with a high incidence of gastroesophageal reflux disease (GERD). The presence of GERD is considered a risk factor for the subsequent development of obliterative bronchiolitis (OB), and surgical correction of GERD by gastric fundoplication (GF) may be associated with increased freedom from OB. The mechanisms underlying a protective effect from OB remain elusive. The objective of this study was to analyze the flow cytometric properties of BAL cells in patients who have undergone GF early after transplant. Methods: In a single-center lung transplant center, eight patients with GERD who were in the first transplant year underwent GF. Prior to and immediately following GF, BAL cells were analyzed by polychromatic flow cytometry. Spirometry was performed before and after GF. Results: GF was associated with a significant reduction in the frequency of BAL CD8 lymphocytes expressing the intracellular effector marker granzyme B, compared with the pre-GF levels. Twenty-six percent of CD8 cells were granzyme Bhi pre-GF compared with 12% of CD8 cells post-GF (range 8%-50% pre-GF, 2%-24% post-GF, P = .01). In contrast, GF was associated with a significant interval increase in the frequency of CD8 cells with an exhausted phenotype (granzyme Blo, CD127lo, PD1hi) from 12% of CD8 cells pre-GF to 24% post-GF (range 1.7%-24% pre-GF and 11%-47% post-GF, P = .05). No significant changes in spirometry were observed during the study interval. Conclusions: Surgical correction of GF is associated with a decreased frequency of potentially injurious effector CD8 cells in the BAL of lung transplant recipients. PMID:20522573
Siebrasse, Erica A.; Pastrana, Diana V.; Nguyen, Nang L.; Wang, Annie; Roth, Mark J.; Holland, Steven M.; Freeman, Alexandra F.; McDyer, John; Buck, Christopher B.
We detected WU polyomavirus (WUPyV) in a bronchoalveolar lavage sample from lungs transplanted into a recipient with Job syndrome by using immunoassays specific for the WUPyV viral protein 1. Co-staining for an epithelial cell marker identified most WUPyV viral protein 1–positive cells as respiratory epithelial cells. PMID:25531075
Duarte, Rayssa Thompson; Linch, Graciele Fernanda da Costa; Caregnato, Rita Catalina Aquino
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
Duarte, Rayssa Thompson; Linch, Graciele Fernanda da Costa; Caregnato, Rita Catalina Aquino
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. 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. 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. 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.
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.
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
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
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.
Cantu, Edward; Diamond, Joshua M; Suzuki, Yoshikazu; Lasky, Jared; Schaufler, Christian; Lim, Brian; Shah, Rupal; Porteous, Mary; Lederer, David J; Kawut, Steven M; Palmer, Scott M; Snyder, Laurie D; Hartwig, Matthew G; Lama, Vibha N; Bhorade, Sangeeta; Bermudez, Christian; Crespo, Maria; McDyer, John; Wille, Keith; Orens, Jonathan; Shah, Pali D; Weinacker, Ann; Weill, David; Wilkes, David; Roe, David; Hage, Chadi; Ware, Lorraine B; Bellamy, Scarlett L; Christie, Jason D
Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted. We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. Data from the Lung Transplant Outcomes Group multi-centered cohort was used to compare variations to the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination. 1,179 subjects from 10 centers were enrolled from 2007-2012. Median length of follow-up was 4 years (IQR [2.4; 5.9]). No mortality differences were noted between No PGD (Grade 0) and Mild PGD (Grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours - p<0.001). Biomarker divergent discrimination was superior when collapsing Grades 0 and 1. Additional severity grades, use of mechanical ventilation, and transplant procedure type had minimal or no effect on mortality or biomarker discrimination. The PGD consensus definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination.
Sheerin, N.; Harrison, N. K.; Sheppard, M. N.; Hansell, D. M.; Yacoub, M.; Clark, T. J.
Histological examination of a lung removed at transplantation revealed multiple peripheral tumourlets and microcarcinoids in close association with bronchioles causing an obliterative bronchiolitis. This was an unexpected finding but explained the progressive airflow limitation which characterised the patient's clinical course. Images PMID:7701466
Pinsky, David J.; Naka, Yoshifumi; Chowdhury, Nepal C.; Liao, Hui; Oz, Mehmet C.; Michler, Robert E.; Kubaszewski, Eugeniusz; Malinski, Tadeusz; Stern, David M.
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.
Santana-Rodríguez, Norberto; Clavo, Bernardino; Llontop, Pedro; López, Ana; García-Castellano, José Manuel; Machín, Rubén P; Ponce, Miguel A; Fiuza, María D; García-Herrera, Ricardo; Brito, Yanira; Yordi, Nagib Atallah; Chirino, Ricardo
Ischemia-reperfusion injury (IRI) is a common complication after lung transplantation. There is evidence that reactive oxygen species are involved in its pathogenesis. We designed an experimental study to evaluate whether the administration of antioxidants to lung transplantation recipients protects against IRI and early acute rejection (AR). Twenty-five rats received left lung transplants after 6 h of ischemia. Fifty minutes before the reperfusion, groups of five rats received a single dose of desferrioxamine (20 mg/kg), estradiol (25 mg/kg), or melatonin (10 mg/kg). The animals were killed 48 h after surgery and the postoperative outcome, IRI, and AR were evaluated. The frequency of severe injury and of moderate-to-severe edema was higher in animals treated with estradiol than in the control group (P = 0.022 and P = 0.026, respectively). No significant changes in the degree of IRI or AR were observed in the groups treated with desferrioxamine or melatonin. In our study, treatment with the antioxidants melatonin or desferrioxamine before reperfusion had no effects on IRI damage or on AR frequency or severity. However, treatment with estradiol resulted in a worse postoperative outcome and in severe edema. Therefore, despite the antioxidant capacity of estradiol, it is recommended that an evaluation of these adverse effects of estradiol in human lung transplant recipients be performed.
Denton, Eve J; Rischin, Adam; McGiffin, David; Williams, Trevor J; Paraskeva, Miranda A; Westall, Glen P; Snell, Greg
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.
Berggren, Malin A M; Heinlen, Latisha; Isaksson, Asa; Nyström, Ulla; Ricksten, Anne
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.
Wray, Jo; Radley-Smith, Rosemary
With the increasing use and improved survival rates of heart and lung transplantation as treatments for children with end-stage heart or lung disease, attention is focusing on the longer term psychological implications of these procedures. This paper focuses on the changes in cognitive development and behaviour in a group of 47 children who were seen 12 months and 2 yr after transplantation. There were 24 boys and 23 girls, mean age at transplantation was 8.3 yr (s.d. 5.3 yr), with a range of 0.3-15.1 yr. Assessments were made of developmental level, cognitive ability and problem behaviours, using previously validated measures, and comparisons were made with physically healthy children. For children under three and a half years of age there was a decrease over time in scores on all developmental parameters, with the change reaching significance on the scale assessing eye-hand coordination and on the overall IQ. Whilst all scores were within the normal range, they were at a significantly lower level than those of the healthy children. In contrast, there were no changes over time on any measures of cognitive or academic ability for older children, with correlations between 12 month and 2 yr scores being highly significant. The rate of behaviour problems at home at 12 months was 22%, compared with 34% at 2 yr post-transplant, which was higher than that found in the healthy children. Conversely, there was a drop in the prevalence of behaviour problems at school from 23% at 12 months to 9% at 2 yr. It is concluded that a significant minority of children and adolescents experience psychological difficulties 2 yr after transplant, with particular areas of concern focusing on development in the younger children and the occurrence of behaviour problems at home across the age-range.
Borro, José M; Rama, Pablo; Rey, Teresa; Fernández-Rivera, Constantino
Advanced kidney disease is usually considered an absolute contraindication for lung transplantation due to the difficult management of these patients in the post-operative period. Combined lung-kidney transplantation, however, could offer an opportunity for selected patients with renal and pulmonary dysfunction. This study summarizes the long-term success of a double transplantation in a 38-year-old male patient with cystic fibrosis who presented respiratory and kidney failure. After a complicated post-operative period, the patient currently lives completely independently 46 months after the operation and he enjoys excellent pulmonary and renal function. Copyright © 2012 SEPAR. Published by Elsevier España, S.L. All rights reserved.
Yazicioglu, Alkin; Alici, Ibrahim Onur; Karaoglanoglu, Nurettin; Yekeler, Erdal
We present a 22-year-old woman with Kartagener syndrome and scoliosis who died 112 days after single lung transplant. The classic thoracic involvement of situs inversus totalis and the asymmetric arrangement of the thoracic vascular structures might be a pitfall for surgeon. Anatomic obstacles have forced the surgeon to perform a single transplant. The period of primary graft dysfunction in a single transplanted lung patient was a challenge; supporting the patient with a high flow and long period of extracorporeal membrane oxygenation might lead to a vanishing bronchus. Immotile cilia, a feature of Kartagener syndrome, were another challenge and patient needed several daily aspiration bronchoscopies. Vanishing bronchus is a gradual process with high mortality rates; commonly, stenosis is at the non anastomotic bronchial tree because of insufficient nourishment of the bronchial cartilages. Several repeat bronchoscopic balloon dilatations accompanied with medical treatment were unsuccessful.
Osho, Asishana A; Castleberry, Anthony W; Snyder, Laurie D; Ganapathi, Asvin M; Speicher, Paul J; Hirji, Sameer A; Stafford-Smith, Mark; Daneshmand, Mani A; Duane Davis, R; Hartwig, Matthew G
Historical concerns about lung transplantation in patients with a glomerular filtration rate (GFR) ≤ 50 ml/min/1.73 m(2) have not been validated. We hypothesize that a pre-transplant GFR ≤ 50 ml/min/1.73 m(2) represents a high mortality risk, especially in the setting of acute GFR decline. In addition, we explore the potential for improved risk stratification using a statistically derivable alternative cutoff. Adult, primary, lung recipients in the United Network for Organ Sharing database were analyzed (October 1987 to December 2011). Recursive partitioning identified the GFR value that provides maximal separation in 1-year mortality. Survival over/under the cutoffs was compared using stratified log-rank, Cox, and Kaplan-Meier methods, before and after 1:2 propensity score matching. Median GFR at time of transplant for 19,425 study patients was 94.2 ml/min/1.73 m(2) (quartile 1-quartile, 2 76.9-105.9 ml/min/1.73 m(2)). Recursive partitioning identified a GFR of 40.2 ml/min/1.73 m(2) as the ideal inflection point for predicting 1-year survival. Cutoffs demonstrated statistically significant effects on survival after 840 patients with a GFR ≤ 50 ml/min/1.73 m(2) (hazard ratio, 1.28; 95% confidence interval, 1.15-1.43) and 401 patients with a GFR ≤ 40.2 ml/min/1.73 m(2) (hazard ratio, 1.57; 95% confidence interval, 1.36-1.83) were matched with high GFR controls (p < 0.001). In 13,509 patients with available GFR at the time of listing and transplant, a pre-transplant GFR decline of ≥ 50% from baseline was associated with worse survival (p < 0.001). A pre-transplant GFR ≤ 50 ml/min/1.73 m(2) is associated with decreased survival. However, patients with GFR between 40 and 50 ml/min/1.73 m(2) do not suffer excessive post-transplant mortality and should not be automatically excluded from listing. Notably, outcomes are worse in patients with poor renal function and concomitant pre-transplant GFR decline. Strategies should be devised to detect and manage
Tumin, Dmitry; Foraker, Randi E; Tobias, Joseph D; Hayes, Don
The use of public insurance is associated with diminished survival in patients with cystic fibrosis (CF) following lung transplantation. No data exist on benefits of gaining private health insurance for post-transplant care among such patients previously using public insurance. The United Network for Organ Sharing database was used to identify first-time lung transplant