White donor, younger donor and double lung transplant are associated with better survival in sarcoidosis patients.

PubMed

Salamo, Oriana; Roghaee, Shiva; Schweitzer, Michael D; Mantero, Alejandro; Shafazand, Shirin; Campos, Michael; Mirsaeidi, Mehdi

2018-05-03

Sarcoidosis commonly affects the lung. Lung transplantation (LT) is required when there is a severe and refractory involvement. We compared post-transplant survival rates of sarcoidosis patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). We also explored whether the race and age of the donor, and double lung transplant have any effect on the survival in the post transplant setting. We analyzed 9,727 adult patients with sarcoidosis, COPD, and IPF who underwent LT worldwide between 2005-2015 based on United Network for Organ Sharing (UNOS) database. Survival rates were compared with Kaplan-Meier, and risk factors were investigated by Cox-regression analysis. 469 (5%) were transplanted because of sarcoidosis, 3,688 (38%) for COPD and 5,570 (57%) for IPF. Unadjusted survival analysis showed a better post-transplant survival rate for patients with sarcoidosis (p < 0.001, Log-rank test). In Cox-regression analysis, double lung transplant and white race of the lung donor showed to have a significant survival advantage. Since double lung transplant, those who are younger and have lower Lung Allocation Score (LAS) at the time of transplant have a survival advantage, we suggest double lung transplant as the procedure of choice, especially in younger sarcoidosis subjects and with lower LAS scores.

OPTN/SRTR 2011 Annual Data Report: lung.

PubMed

Valapour, M; Paulson, K; Smith, J M; Hertz, M I; Skeans, M A; Heubner, B M; Edwards, L B; Snyder, J J; Israni, A K; Kasiske, B L

2013-01-01

Lungs are allocated in part based on the Lung Allocation Score (LAS), which considers risk of death without transplant and posttransplant. Wait-list additions have been increasing steadily after an initial decline following LAS implementation. In 2011, the largest number of adult candidates were added to the waiting list in a single year since 1998; donation and transplant rates have been unable to keep pace with wait-list additions. Candidates aged 65 years or older have been added faster than candidates in other age groups. After an initial decline following LAS implementation, wait-list mortality increased to 15.7 per 100 wait-list years in 2011. Short- and long-term graft survival improved in 2011; 10-year graft failure fell to an all-time low. Since 1998, the number of new pediatric (aged 0-11 years) candidates added yearly to the waiting list has declined. In 2011, 19 pediatric lung transplants were performed, a transplant rate of 34.7 per 100 wait-list years. The percentage of patients hospitalized before transplant has not changed. Both graft and patient survival have continued to improve over the past decade. Posttransplant complications for pediatric lung transplant recipients, similar to complications for adult recipients, include hypertension, renal dysfunction, diabetes, bronchiolitis obliterans syndrome, and malignancy. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Isolated lung transplantation for end-stage lung disease: a viable therapy.

PubMed

Egan, T M; Westerman, J H; Lambert, C J; Detterbeck, F C; Thompson, J T; Mill, M R; Keagy, B A; Paradowski, L J; Wilcox, B R

1992-04-01

Since January 1990, we have performed 29 isolated lung transplantations in 28 patients with end-stage lung disease (12 single, 16 bilateral). Recipient diagnoses were: cystic fibrosis (11), chronic obstructive pulmonary disease (6), pulmonary fibrosis (6), eosinophilic granulomatosis (1), postinfectious lung disease (1), adult respiratory distress syndrome (1), and primary pulmonary hypertension (2). There have been four deaths, two in patients with pulmonary fibrosis and two in patients with primary pulmonary hypertension. Four patients have undergone transplantation while on ventilatory support for respiratory failure (2 with cystic fibrosis, 1 having redo lung transplantation with cystic fibrosis, and 1 with adult respiratory distress syndrome); all of these have survived. Six patients required cardiopulmonary bypass, which was associated with increased transfusion requirement. All patients 2 months after discharge have returned to an active life-style, except for 2 patients who currently await retransplantation. Preoperative pulmonary rehabilitation has resulted in significant improvement in exercise performance in all patients. Immunosuppression consists of cyclosporine, azathioprine, and antilymphoblast globulin (University of Minnesota), withholding systemic steroids in the early postoperative period. We have employed bronchial omentopexy in all but four transplants; there has been one partial bronchial dehiscence, two instances of bronchomalacia requiring internal stenting, and one airway stenosis. Cytomegalovirus disease has been seen frequently (15 cases), but has responded well to treatment with ganciclovir. Other complication shave included one drug-related prolonged postoperative ventilation, thrombosis of a left lung after bilateral lung transplantation requiring retransplantation, five episodes of unilateral phrenic nerve palsy after bilateral lung transplantation (4 resolved), and the requirement of massive transfusion (greater than 10 units) in 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung transplantation for cystic fibrosis.

PubMed

Mendeloff, E N

1998-07-01

Cystic fibrosis (CF) is an inherited disease in which the fundamental physiological defect is failure of cAMP regulation of chloride transport. More than 90% of patients with CF will die of chronic, suppurative, obstructive lung disease, with the median survival in the United States currently being 29 years of age. Currently, although other therapies are being aggressively investigated, bilateral lung transplantation offers the only hope for short-term and mid-term survival in patients with CF and end-stage pulmonary disease. Since 1989, 103 bilateral sequential lung transplants (BLT) for CF have been performed at our institution (46 pediatric, 48 adult, 9 redo) at a mean age of 21+/-10 years. Cardiopulmonary bypass was used in all but one pediatric (age <18) transplantation, and in 15% of adults. The hospital mortality rate was 4.9%, with 80% of early deaths related to infection. Bronchial anastomotic complications occurred with equal frequency in the pediatric and the adult populations (7.3%). One- and 3-year actuarial survival rates are 84% and 61%, respectively (no significant difference between pediatric and adult age groups; average follow-up 2.1+/-1.6 years). Mean forced expiratory volume in 1 second increased from 25%+/-9% pretransplantation to 79%+/-35% 1 year posttransplantation. Acute rejection occurred 1.7 times per patient-year, with the majority of these episodes taking place the first 6 months posttransplantation. Need for treatment of lower respiratory infections occurred 1.2 times per patient in the first year after transplantation. Actuarial freedom from bronchiolitis obliterans was 63% at 2 years and 43% at 3 years. Redo transplantation was performed only in the pediatric population, and was associated with an early mortality of 33%. Eight living donor transplants (4 primary transplants, 4 redo transplants) were performed with an early survival of 87.5%. Patients with end-stage CF can undergo BLT with morbidity and mortality comparable with that observed in pulmonary transplantation for other disease entities.

Lung transplantation in adults and children: putting lung function into perspective.

PubMed

Thompson, Bruce Robert; Westall, Glen Philip; Paraskeva, Miranda; Snell, Gregory Ian

2014-11-01

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. © 2014 Asian Pacific Society of Respirology.

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

PubMed

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

2016-01-01

Gaucher disease (GD), a lysosomal storage disorder, may result in end-stage lung disease. We report successful bilateral lung transplantation in a 49-year-old woman with GD complicated by severe pulmonary hypertension and fibrotic changes in the lungs. Before receiving the lung transplant, the patient was undergoing both enzyme replacement therapy (imiglucerase) and triple pulmonary hypertension treatment (epoprostenol, bosentan, and sildenafil). She had a history of splenectomy, severe bone disease, and renal involvement, all of which were related to GD and considered as relative contraindications for a lung transplantation. In the literature, lung transplantation has been suggested for severe pulmonary involvement in GD but has been reported only once in a child. To our knowledge, until now, no successful procedure has been reported in adults, and no reports deal with the severe potential posttransplantation complications specifically related to GD. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Graft downsizing during ex vivo lung perfusion: case report and technical notes.

PubMed

Nosotti, M; Rosso, L; Mendogni, P; Tosi, D; Palleschi, A; Righi, I; Froio, S; Valenza, F; Santambrogio, L

2014-09-01

Among patients with respiratory insufficiency awaiting lung transplantation, small adult patients have a lower opportunity of receiving size-matched pulmonary grafts, because of the shortage of donors, particularly those of small size. Reducing the size of an oversized graft is one of the methods to increase the donor pool; similarly, ex vivo lung perfusion is an emerging technique aimed toward the same purpose. We describe how we combined the 2 techniques (lobar transplantation plus contralateral nonanatomic graft reduction during ex vivo lung perfusion) to overcome graft shortage in a clinical case. For the 1st time, this case report demonstrates that surgical manipulation during ex vivo lung perfusion does not affect the functional improvement in a lung previously judged to be not suitable for transplantation. The 6-month follow-up results are similar to those of standard bilateral lung transplantation. Copyright © 2014 Elsevier Inc. All rights reserved.

OPTN/SRTR 2012 Annual Data Report: lung.

PubMed

Valapour, M; Skeans, M A; Heubner, B M; Smith, J M; Schnitzler, M A; Hertz, M I; Edwards, L B; Snyder, J J; Israni, A K; Kasiske, B L

2014-01-01

Lung transplants are increasingly used as treatment for end-stage lung diseases not amenable to other medical and surgical therapies. Lungs are allocated to adult and adolescent transplant candidates on the basis of age, geography, blood type compatibility, and the Lung Allocation Score, which reflects risk of wait-list mortality and probability of posttransplant survival. The overall median waiting time in 2012 was 4 months, and 65.3% of candidates underwent transplant within 1 year of listing; however, this proportion varied greatly by donation service area. Unadjusted median survival of lung transplant recipients was 5.3 years in 2012, and median survival conditional on living for 1 year posttransplant was 6.7 years. Among pediatric lung candidates in 2012, 32.1% were wait-listed for less than 1 year, 17.9% for 1 to less than 2 years, 16.7% for 2 to less than 4 years, and 33.3% for 4 or more years. Both graft and patient survival have continued to improve; survival rates for recipients aged 6-11 years are better than for younger recipients. Compared with recipients of other solid organ transplants, lung transplant recipients experienced the highest rates of rehospitalization for transplant complications: 43.7 per 100 patients in year 1 and 36.0 in year 2. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Pediatric lung transplantation

PubMed Central

2017-01-01

Pediatric lung transplantation has been undertaken since the 1980s, and it is today considered an accepted therapy option in carefully selected children with end-stage pulmonary diseases, providing carefully selected children a net survival benefit and improved health-related quality of life. Nowadays, >100 pediatric lung transplants are done worldwide every year. Here, specific pediatric aspects of lung transplantation are reviewed such as the surgical challenge, effects of immunosuppression on the developing pediatric immune system, and typical infections of childhood, as it is vital to comprehend that children undergoing lung transplants present a real challenge as children are not ‘just small adults’. Further, an update on the management of the pediatric lung transplant patient is provided in this review, and future challenges outlined. Indications for lung transplantation in children are different compared to adults, the most common being cystic fibrosis (CF). However, the primary diagnoses leading to pediatric lung transplantation vary considerably by age group. Furthermore, there are regional differences regarding the primary indication for lung transplantation in children. Overall, early referral, careful patient selection and appropriate timing of listing are crucial to achieve real survival benefit. Although allograft function is to be preserved, immunosuppressant-related side effects are common in children post-transplantation. Strategies need to be put into practice to reduce drug-related side effects through careful therapeutic drug monitoring and lowering of target levels of immunosuppression, to avoid acute-reversible and chronic-irreversible renal damage. Instead of a “one fits all approach”, tailored immunosuppression and a personalized therapy is to be advocated, particularly in children. Further, infectious complications are a common in children of all ages, accounting for almost 50% of death in the first year post-transplantation. However, chronic lung allograft dysfunction (CLAD) remains the major obstacle for improved long-term survival. PMID:28932575

Lung transplantation in infants and toddlers from 1990 to 2004 at St. Louis Children's Hospital.

PubMed

Elizur, A; Faro, A; Huddleston, C B; Gandhi, S K; White, D; Kuklinski, C A; Sweet, S C

2009-04-01

In a retrospective, single-center cohort study, outcomes of infants and toddlers undergoing lung transplant at St. Louis Children's Hospital between 1990 and 2004 were compared to older children. Patients with cystic fibrosis (exclusively older children) and those who underwent heart-lung, liver-lung, single lung or a second transplantation were excluded from comparisons. One hundred nine lung transplants were compared. Thirty-six were in infants <1 year old, 26 in toddlers 1-3 years old and 47 in children >3 years old. Graft survival was similar for infants and toddlers (p = 0.35 and p = 0.3, respectively) compared to children over 3 years old at 1 and 3 years after transplant. Significantly more infants (p < 0.0001 and p = 0.003) and toddlers (p = 0.002 and p = 0.03) were free from acute rejection and bronchiolitis obliterans compared to older patients. While most infants and toddlers had only minimal lung function impairment, and achieved normal to mildly delayed developmental scores, somatic growth remained depressed 5 years after transplant. Lung transplantation in infants and young children carries similar survival rates to older children and adults. Further insights into the unique immunologic aspects of this group of patients may elucidate strategies to prevent acute and chronic rejection in all age groups.

Immunogenicity of a combined schedule of 7-valent pneumococcal conjugate vaccine followed by a 23-valent polysaccharide vaccine in adult recipients of heart or lung transplants.

PubMed

Gattringer, R; Winkler, H; Roedler, S; Jaksch, P; Herkner, H; Burgmann, H

2011-10-01

A combined schedule of 7-valent pneumococcal conjugate vaccine (PCV7) followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) was evaluated retrospectively in 26 adult recipients of heart or lung transplants. PCV7 was immunogenic in these patients but there appeared to be no benefit from the additional PPV23 dose. © 2011 John Wiley & Sons A/S.

Outcomes after ABO-incompatible heart transplantation in adults: A registry study.

PubMed

Bergenfeldt, Henrik; Andersson, Bodil; Bućin, Dragan; Stehlik, Josef; Edwards, Leah; Rådegran, Göran; Nilsson, Johan

2015-07-01

In the past, ABO incompatibility was considered an absolute contraindication to heart transplantation (HT) in adults. Advances in ABO-incompatible HT in pediatric patients and ABO-incompatible abdominal transplantation in adult patients have led to clinical exploration of intentional ABO-incompatible HT in adults. However, it is not well known how outcomes in ABO-incompatible adult heart transplant recipients compare with outcomes in ABO-compatible recipients. We analyzed International Society for Heart and Lung Transplantation transplant registry data from heart donors and recipients ≥18 years old at the time of transplant for HT performed between 1988 and 2011. We compared baseline characteristics and post-transplant outcomes in ABO-incompatible and ABO-compatible HT. Death or retransplantation was the composite primary end-point. Among 76,663 adult patients undergoing HT between 1988 and June 30, 2011, 94 ABO-incompatible heart transplants were performed. The incidence of death or retransplantation in the ABO-incompatible group was higher than in the ABO-compatible group: 21% vs 9% at 30 days (hazard ratio = 2.38, p < 0.001) and 36% vs 19% at 1 year after transplant. However, ABO-incompatible grafts surviving past the first year after transplant had a similar incidence of failure compared with the ABO-compatible group. After 2005, the rate ABO-incompatible HT in adults increased, likely as a result of planned, intentional (rather than accidental) ABO-incompatible HT. In this group of patients, short-term and long-term incidence of death or retransplantation was similar to ABO-compatible recipients (p = 0.822): 7% at 30 days and 19% at 1 year after transplantation. We found no difference in incidence of death or retransplantation between ABO-compatible and ABO-incompatible HT in patients who underwent transplantation after 2005. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Short Stature and Access to Lung Transplantation in the United States. A Cohort Study

PubMed Central

Sell, Jessica L.; Bacchetta, Matthew; Goldfarb, Samuel B.; Park, Hanyoung; Heffernan, Priscilla V.; Robbins, Hilary A.; Shah, Lori; Raza, Kashif; D’Ovidio, Frank; Sonett, Joshua R.; Arcasoy, Selim M.

2016-01-01

Rationale: Anecdotally, short lung transplant candidates suffer from long waiting times and higher rates of death on the waiting list compared with taller candidates. Objectives: To examine the relationship between lung transplant candidate height and waiting list outcomes. Methods: We conducted a retrospective cohort study of 13,346 adults placed on the lung transplant waiting list in the United States between 2005 and 2011. Multivariable-adjusted competing risk survival models were used to examine associations between candidate height and outcomes of interest. The primary outcome was the time until lung transplantation censored at 1 year. Measurements and Main Results: The unadjusted rate of lung transplantation was 94.5 per 100 person-years among candidates of short stature (<162 cm) and 202.0 per 100 person-years among candidates of average stature (170–176.5 cm). After controlling for potential confounders, short stature was associated with a 34% (95% confidence interval [CI], 29–39%) lower rate of transplantation compared with average stature. Short stature was also associated with a 62% (95% CI, 24–96%) higher rate of death or removal because of clinical deterioration and a 42% (95% CI, 10–85%) higher rate of respiratory failure while awaiting lung transplantation. Conclusions: Short stature is associated with a lower rate of lung transplantation and higher rates of death and respiratory failure while awaiting transplantation. Efforts to ameliorate this disparity could include earlier referral and listing of shorter candidates, surgical downsizing of substantially oversized allografts for shorter candidates, and/or changes to allocation policy that account for candidate height. PMID:26554631

Outcome of heart-lung and bilateral sequential lung transplantation for cystic fibrosis: a UK national study.

PubMed

Ganesh, J S; Rogers, C A; Bonser, R S; Banner, N R

2005-06-01

Cystic fibrosis (CF) patients requiring transplantation for respiratory failure may undergo either heart-lung (HLT) or bilateral sequential lung (BSLT) transplantation. The choice of operation varies between surgeons, centres and countries. The current authors investigated whether operation type influenced outcome in adult CF patients transplanted in the UK between July 1995 and June 2002. Propensity scores for receipt of BSLT versus HLT were derived using logistic regression. Cox regression was used to compare survival. In total, 88 BSLTs and 93 HLTs were identified. Patient characteristics were similar overall, but HLT recipients were more likely to be on long-term oxygen therapy and to have had prior resuscitation. There were 72 deaths (29 BSLT and 43 HLT) within 4 yrs. There was a trend towards higher unadjusted survival following BSLT, but, after adjustment, no difference was found (hazard ratio = 0.77; 95% confidence interval 0.29-2.06). Time to the first rejection episode and infection rates were also similar. A total of 82% of hearts from HLT recipients were used as domino heart transplants. In conclusion, after adjusting for comorbidity, donor factors and ischaemia time, it was found that heart-lung and bilateral sequential lung transplantation achieved a similar outcome. The use of domino heart transplantation ameliorated the impact of heart-lung transplantation on total organ availability.

The impact of pan-resistant bacterial pathogens on survival after lung transplantation in cystic fibrosis: results from a single large referral centre.

PubMed

Dobbin, C; Maley, M; Harkness, J; Benn, R; Malouf, M; Glanville, A; Bye, P

2004-04-01

Reported actuarial one-year survival for patients with cystic fibrosis (CF) after lung transplant is 55-91%. Infection is the most common cause of early death. Colonization with Burkholderia cepacia complex is associated with reduced survival and international lung transplant referral guidelines support individual unit assessment policies for patients colonized with other pan-resistant bacteria. We examined local data on survival after transplant for CF to determine the impact of colonization with pan-resistant bacteria. A retrospective review of all CF patients from Royal Prince Alfred Hospital (RPAH), Sydney, who underwent lung transplantation at St Vincent's Hospital, Sydney, 1989-2002, was performed. Sixty-five patients were listed for lung transplantation with 54 (male: female=29:25) receiving transplants. Of the 11 patients (17%) who died on the waiting list, six were colonized with pan-resistant Pseudomonas aeruginosa. Thirty of the 54 transplanted patients had at least one pan-resistant organism before transplant. In 28 this included P. aeruginosa. Overall one-year survival was 92% with a median survival of 67 months. Overall survival for the pan-resistant group (N = 30) was not significantly different to survival in those with sensitive organisms (N = 24) (Logrank chi square = 1.6, P = 0.2). Three patients colonized with B. cepacia complex pre-transplant survive at 11, 40 and 60 months post-transplant. Infection contributed to 11 of the 18 post-transplant deaths, with pre-transplant-acquired bacterial pathogens responsible in two cases. Patients continued to acquire multiresistant bacteria post-transplantation. Lung transplant survival at St Vincent's Hospital for CF adults from RPAH compares favourably with international benchmarks. Importantly, colonization with pan-resistant bacteria pre-transplant did not appear to adversely affect survival post-transplant.

Long-term outcomes of lung transplant recipients with hepatitis C infection: a retrospective study of the U.S. transplant registry.

PubMed

Koenig, A; Stepanova, M; Saab, S; Ahmed, A; Wong, R; Younossi, Z M

2016-08-01

Chronic hepatitis C patients in need of a lung transplant are often considered ineligible due to their infection. To assess the association of hepatitis C virus (HCV) infection with long-term outcomes of lung transplants. From the Scientific Registry of Transplant Recipients (1995-2011), we selected all adults with and without HCV infection who underwent lung transplantation. A total of 17 762 lung transplant recipients were included (55.5% bilateral). Of those, 319 (1.83%) had positive HCV serology. The HCV-positive recipients were 1.6 years younger, less Caucasian and more African-American, and had a significantly higher rate of co-infection with hepatitis B virus (all P < 0.001). Post-transplant patients were discharged alive at similar rates regardless of HCV status: 88.4% in HCV+ vs. 90.3% in HCV- (P = 0.25). The mortality rates were also similar at 1 and 2 years after transplantation (20.7% in HCV+ vs. 19.2% in HCV- and 31.6% in HCV+ vs. 28.9% in HCV-, respectively; both P > 0.05), but at post-transplant year 3 year, mortality rate in HCV+ became significantly higher (42.5% vs. 36.4%, P = 0.04) and remained higher for the duration of the follow-up (mean 9.1 years, max 18.4 years). In multivariate survival analysis, after adjustment for confounders, being HCV+ was associated with higher mortality: adjusted hazard ratio 1.24 (1.04-1.46), P = 0.01. No association of HCV infection with time to graft loss was found (P = 0.92). Chronic HCV infection is associated with a moderate increase in post-lung transplant mortality. Treatment of HCV in lung transplant recipients may, therefore, result in improvement of post-transplant outcomes. © 2016 John Wiley & Sons Ltd.

Current status and problems of lung transplantation in Japan

PubMed Central

2016-01-01

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

Infections in liver and lung transplant recipients: a national prospective cohort.

PubMed

Gagliotti, Carlo; Morsillo, Filomena; Moro, Maria Luisa; Masiero, Lucia; Procaccio, Francesco; Vespasiano, Francesca; Pantosti, Annalisa; Monaco, Monica; Errico, Giulia; Ricci, Andrea; Grossi, Paolo; Nanni Costa, Alessandro

2018-03-01

Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients' characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country.

Bone Mineral Density and Fat-Soluble Vitamin Status in Adults with Cystic Fibrosis Undergoing Lung Transplantation: A Pilot Study.

PubMed

Hubert, Grace; Chung, Theresa Tam; Prosser, Connie; Lien, Dale; Weinkauf, Justin; Brown, Neil; Goodvin, Marianne; Jackson, Kathy; Tabak, Joan; Salgado, Josette; Alzaben, Abeer Salman; Mager, Diana R

2016-12-01

Patients with cystic fibrosis (CF) often experience low bone mineral density (BMD) pre- and post-lung transplantation (LTX). The study purpose was to describe BMD and micronutrient status in adults with CF pre- and post-LTX. Twelve patients with CF (29 ± 8 years) were recruited from the CF clinic at the University of Alberta Lung Transplant Program. BMD and vitamins A, D, E, K status, and parathyroid hormone were measured pre- and post-LTX. No significant differences pre- and post-LTX were observed at the different bone sites measured (lumber-spine, femoral-neck (FN), hip, and femoral-trochlea) (P > 0.05). BMD T-scores (<-2) was present in lumbar-spine, FN, hip, and femoral-trochlea in 33%, 17%, 17%, and 25% of individuals pre-LTX and 58%, 33%, 58%, and 33% of individuals post-LTX, respectively. More than 50% of patients had suboptimal vitamin K levels (PIVKA-II values >3 ng/mL) pre- and post-LTX. Adults with CF pre- and post-LTX had reduced BMD and suboptimal vitamin K status.

Single Versus Double Lung Retransplantation Does Not Affect Survival Based on Previous Transplant Type.

PubMed

Schumer, Erin M; Rice, Jonathan D; Kistler, Amanda M; Trivedi, Jaimin R; Black, Matthew C; Bousamra, Michael; van Berkel, Victor

2017-01-01

Survival following retransplantation with a single lung is worse than after double lung transplant. We sought to characterize survival of patients who underwent lung retransplantation based on the type of their initial transplant, single or double. The United Network for Organ Sharing database was queried for adult patients who underwent lung retransplantation from 2005 onward. Patients were excluded if they underwent more than one retransplantation. The patient population was divided into 4 groups based on first followed by second transplant type, respectively: single then single, double then single, double then double, and single then double. Descriptive analysis and Kaplan-Meier survival analysis were performed. A p value less than 0.05 was considered significant. A total of 410 patients underwent retransplantation in the study time period. Overall mean survival for all patients who underwent retransplantation was 1,213 days. Kaplan-Meier survival analysis demonstrated no difference in graft survival between the 4 study groups (p = 0.146). There was no significant difference in graft survival between recipients of retransplant with single or double lungs when stratified by previous transplant type. These results suggest that when retransplantation is performed, single lung retransplantation should be considered, regardless of previous transplant type, in an effort to maximize organ resources. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Three-year survival rates for all consecutive heart-only and lung-only transplants performed in Eurotransplant, 1997-1999.

PubMed

Smits, Jacqueline M A; Vanhaecke, Johan; Haverich, Axel; de Vries, Erwin; Smith, Mike; Rutgrink, Ellis; Ramsoebhag, Annemarie; Hop, Alinde; Persijn, Guido; Laufer, Gunther

2003-01-01

The definition of proper patient selection criteria remains a prominent item in constant need of attention. While the concept of gathering evidence in order to determine practice continues to be hopelessly ambiguous, it can never be emphasized too much that these univariate results are just a first foray into analysing predictors of survival; all following results should be regarded and interpreted in this perspective. HEART TRANSPLANT SURVIVAL: The 3-year survival rate for heart transplant recipients under age 16 was 83% versus 72% for adult recipients. Acutely retransplanted adult heart recipients had a 3-year survival rate of 36% compared with 72% for recipients of a first heart allograft. Patients suffering from DCM had the best survival rates at 3 years (74%) compared with patients suffering from CAD (70%) or from another end-stage heart disease (67%). With advancing age of the adult recipient, the mortality risk increased. Patients aged 16-40 had a 3-year survival rate of 77%, compared with 74%, 70% and 61% for transplant recipients aged 41-55, 56-65 and over age 65, respectively. The 3-year survival rates for adult recipients transplanted with an heart allograft from a donor aged under 16 or between 16-44 were 78% and 74%, compared with 66% and 63% for donors aged 45-55 and over 55, respectively. The 3-year survival rates for recipients of hearts with cold ischemic times under 2 hours, 2-3, 3-4, 4-5, 5-6 and more than 6 hours were 74%, 75%, 70%, 65%, 54% and 40%, respectively. Transplanting a female donor heart into a male recipient was associated with the worst prognosis: the 3-year survival rates were 73%, 71%, 66% and 76%, respectively, for the donor/recipient groups male/male, male/female, female/male and female/female, respectively. When the donor-to-recipient body weight ratio was below 0.8, the 3-year survival rate was 64%, compared to 72% for weight-matched pairs and 74% for patients who received a heart from an oversized donor (p=0.004). Better survival rates were obtained for better HLA-matched transplants. The 3-year survival rates were 75%, 89%, 78%, 78%, 69%, 72%, and 71% for HLA-A,-B,-DR zero, 1, 2, 3, 4, 5 and 6 mismatched groups, respectively (p=0.04). Survival was significantly associated with the CMV serologic status of the donor and recipient; the 3-year survival rates were: D+/R+, 71%; D+/R-, 69%; D- R-, 76%; and D-/R+, 76% (p=0.04). Patients in an ICU had a 3-year survival rate of 62%, compared to 72% for patients in a general ward and 74% for outpatients (p<0.0001). Patients that were on a VAD and there-upon transplanted had a 3-year survival rate of 65%, compared to 73% for patients without a VAD (p=0.004). Being on a ventilator was a major risk factor for death after transplantation; patients on ventilator support at the time of the transplant had a 3-year survival rate of 52% compared to 73% for the other patients (p<0.0001). LUNG TRANSPLANT SURVIVAL: The 3-year survival rate for children (73%) appeared to be better than the adult rate (61%; p=0.8). Adult lung transplant survival was significantly worse in the case of a repeat lung transplant; a 3-year retransplant survival rate of 42% was obtained compared with 61% for first transplants (p=0.049). With respect to the underlying end-stage lung disease, no statistically significant difference in long-term survival could be detected in this cohort. The 3-year survival rates were: 62% for COPD/Emphysema, 70% for CF, 58% for IPF, 64% for Alpha-1 ATD and 56% for PPH (p=0.2). Our data demonstrated no effect of the recipient's age on long-term lung transplant survival, except for 2 senior patients in this cohort. At 3-years the survival rates for recipients aged 16-40, 41-55 and 56-65 were 65%, 60% and 62%, respectively (p=0.05). The 3-year survival rates for transplants performed with lungs from donors aged under 16, 16-44, 45-55 and over 55 was 57%, 64%, 55% and 62%, respectively (p=0.1) No association between the duration of cold ischemic time and 3-year survival was observed; under 3 hours, 3-4, 4-5, 5-6 and over 6 hours of ischemia resulted in 3-year survival rates of 53%, 59%, 64%, 68% and 57%, respectively (p=0.2). Early posttransplant outcome tended to be better for gender-matched transplants, while transplanting a female donor lung into a male recipient was associated with the worst prognosis. The 3-year survival rates were 65% for male/male, 63% for male/female, 48% for female/male and 61% for female/female (p=0.009). No effect of donor-to-recipient weight match was observed in this Eurotransplant cohort; when the donor-to-recipient weight ratio was below 0.8, the 3-year survival rate was 57%, compared with 59% for weight-matched pairs and 64% for patients who received a lung from an oversized donor (p=0.5). Long-term survival after lung transplantation was influenced by HLA matching. The 3-year survival rates were 100%, 68%, 70%, 65%, 54% and 55% for the HLA-A,-B,-DR 1, 2, 3, 4, 5 and 6 mismatched groups, respectively (p=0.06). A donor CMV+ and recipient CMV- match was a risk factor for long-term mortality, with 3-year survival rates of 56% for D+/R+, 55% for D+/R-, 71% for D-/R- and 62% for D-/R+ transplants (p=0.046). En-bloc transplantation of both lungs yielded worse early results, but the 3-year survival rates for patients who underwent single (60%), bilateral sequential double lung (63%) and en-bloc double lung transplantation (56%) were not different (p=0.2). Ventilator dependency was associated with a significantly reduced survival at 3 years. Patients on a ventilator support at the time of the transplant had a 3-year survival rate of 48% compared with 63% for other patients (p=0.006).

Extracorporeal life support in lung and heart-lung transplantation for pulmonary hypertension in adults.

PubMed

Kortchinsky, Talna; Mussot, Sacha; Rezaiguia, Saïda; Artiguenave, Margaux; Fadel, Elie; Stephan, François

2016-09-01

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. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Radiopharmaceutical considerations for using Tc-99m MAA in lung transplant patients.

PubMed

Ponto, James A

2010-01-01

To elucidate radiopharmaceutical considerations for using technetium Tc-99m albumin aggregated (Tc-99m MAA) in lung transplant patients and to establish an appropriate routine dose and preparation procedure. Tertiary care academic hospital during May 2007 to May 2009. Nuclear pharmacist working in nuclear medicine department. Radiopharmaceutical considerations deemed important for the use of Tc-99m MAA in lung transplant patients included radioactivity dose, particulate dose, rate of the radiolabeling reaction (preparation time), and final radiochemical purity. Evaluation of our initial 12-month experience, published literature, and professional practice guidelines provided the basis for establishing an appropriate dose and preparation procedure of Tc-99m MAA for use in lung transplant patients. Radiochemical purity at typical incubation times and image quality in subsequent lung transplant patients imaged during the next 12 months. Based on considerations of radioactivity dose, particulate dose, rate of the radiolabeling reaction (preparation time), and final radiochemical purity, a routine dose consisting of 3 mCi (111 MBq) and 100,000 particles of Tc-99m MAA for planar perfusion lung imaging of adult lung transplant patients was established as reasonable and appropriate. MAA kits were prepared with a more reasonable amount of Tc-99m and yielded high radiochemical purity values in typical incubation times. Images have continued to be of high diagnostic quality. Tc-99m MAA used for lung transplant imaging can be readily prepared with high radiochemical purity to provide a dose of 3 mCi (111 GBq)/100,000 particles, which provides images of high diagnostic quality.

Practical Guidelines: Lung Transplantation in Patients with Cystic Fibrosis

PubMed Central

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

2014-01-01

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

Predictors of lung transplant survival in eurotransplant.

PubMed

Smits, J M A; Mertens, B J A; Van Houwelingen, H C; Haverich, A; Persijn, G G; Laufer, G

2003-11-01

This study was undertaken to assess the influence of patient/donor and center factors on lung transplantation outcome. Outcomes of all consecutive first cadaveric lung transplants performed at 21 Eurotransplant centers in 1997-99 were analyzed. The risk-adjusted center effect on mortality was estimated. A Cox model was built including donor and recipient age and gender, primary disease, HLA mismatches, patient's residence, cold ischemic time, donor's cause of death, serum creatinine, type of lung transplant, respiratory support status, clinical condition and percentage predicted FEV1. The center effect was calculated (expressed as the standardized difference between the observed and expected survival rates), and empirical and full Bayes methods were applied to evaluate between-center differences. A total of 590 adults underwent lung transplantation. The primary disease (p=0.01), HLA-mismatches (p = 0.02), clinical condition(p < 0.0001) and the patient's respiratory support status (p = 0.05) were significantly associated with survival. After adjusting for case-mix, no between-center differences could be found. An in-depth empirical Bayes analysis showed the between-center variation to be zero. Similar results were obtained from the full Bayes analysis. Based on these data, there is no scientific basis to support a hypothesis of possible association between center volume and lung survival rates.

An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK.

PubMed

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

2016-11-01

Many patients awaiting lung transplantation die before a donor organ becomes available. Ex vivo lung perfusion (EVLP) allows initially unusable donor lungs to be assessed and reconditioned for clinical use. The objective of the Donor Ex Vivo Lung Perfusion in UK lung transplantation study was to evaluate the clinical effectiveness and cost-effectiveness of EVLP in increasing UK lung transplant activity. A multicentre, unblinded, non-randomised, non-inferiority observational study to compare transplant outcomes between EVLP-assessed and standard donor lungs. Multicentre study involving all five UK officially designated NHS adult lung transplant centres. Patients aged ≥ 18 years with advanced lung disease accepted onto the lung transplant waiting list. The study intervention was EVLP assessment of donor lungs before determining suitability for transplantation. The primary outcome measure was survival during the first 12 months following lung transplantation. Secondary outcome measures were patient-centred outcomes that are influenced by the effectiveness of lung transplantation and that contribute to the health-care costs. Lungs from 53 donors unsuitable for standard transplant were assessed with EVLP, of which 18 (34%) were subsequently transplanted. A total of 184 participants received standard donor lungs. Owing to the early closure of the study, a non-inferiority analysis was not conducted. The Kaplan-Meier estimate of survival at 12 months was 0.67 [95% confidence interval (CI) 0.40 to 0.83] for the EVLP arm and 0.80 (95% CI 0.74 to 0.85) for the standard arm. The hazard ratio for overall 12-month survival in the EVLP arm relative to the standard arm was 1.96 (95% CI 0.83 to 4.67). Patients in the EVLP arm required ventilation for a longer period and stayed longer in an intensive therapy unit (ITU) than patients in the standard arm, but duration of overall hospital 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. 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 possible differences in lung injury between EVLP protocols needs evaluation. Current Controlled Trials ISRCTN44922411. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 20, No. 85. See the NIHR Journals Library website for further project information.

Comprehensive outcomes after lung retransplantation: a single center review.

PubMed

Halloran, Kieran; Aversa, Meghan; Tinckam, Kathryn; Martinu, Tereza; Binnie, Matthew; Chaparro, Cecilia; Chow, Chung-Wai; Waddell, Tom; McRae, Karen; Pierre, Andrew; de Perrot, Marc; Yasufuku, Kazuhiro; Cypel, Marcelo; Keshavjee, Shaf; Singer, Lianne G

2018-05-13

Lung retransplantation is an important therapy for a growing population of lung transplant recipients with graft failure, but detailed outcome data are lacking. We conducted a retrospective cohort study of adult lung retransplant in the Toronto Lung Transplant Program from 2001 to 2013 (n=38). We analyzed the post-operative course, graft function, renal function, microbiology, donor specific antibodies (DSA), quality of life and survival compared to a control cohort of primary transplant recipients matched for age and era. Indication for retransplant was chronic lung allograft dysfunction in most retransplant recipients (35/38, 82%). The post-operative course was more complex after retransplant than primary (ventilation time, 8 vs. 2 days, p<0.01; ICU stay 14 vs. 4 days, 0<0.01) and peak lung function was lower (FEV1 2.2L vs. 3L, p<0.01). Quality of life scores were comparable, as were renal function, microbiology and donor specific antibody formation. Median survival was 1988 days after primary and 1475 days after retransplant (p=0.39). Lung retransplantation is associated with a more complex post-operative course and lower peak lung function, but the long term medical profile is similar to primary transplant. Lung retransplantation can be beneficial for carefully selected candidates with allograft failure. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Survival in pediatric lung transplantation: The effect of center volume and expertise.

PubMed

Khan, Muhammad S; Zhang, Wei; Taylor, Rachel A; Dean McKenzie, E; Mallory, George B; Schecter, Marc G; Morales, David L S; Heinle, Jeffrey S; Adachi, Iki

2015-08-01

Institutional operative volume has been shown to impact outcomes of various procedures including lung transplantation (LTx). We sought to determine whether this holds true with pediatric LTx by comparing outcomes of adult centers (with larger overall volume) to those of pediatric centers (with smaller volume but more pediatric-specific experience). A retrospective analysis of the Organ Procurement and Transplant Network data was performed. Centers were categorized as either adult (LTx volume predominantly in adult patients), high-volume pediatric (HVP, ≥4 LTxs/year), or low-volume pediatric (LVP, <4 LTxs/year). Outcomes were compared in "younger children" (<12 years) and "older children and adolescents" (12 to 17 years). In total, 1,046 pediatric LTxs were performed between 1987 and 2012 at 62 centers (adult 51 [82%], HVP 3 [5%], LVP 8 [13%]). Although adult centers had larger overall LTx volume, their pediatric experiences were severely limited (median 1/year). In younger children, HVP centers were significantly better than LVP centers for patient survival (half-life: 7.3 vs 2.9 years, p = 0.002). Similarly, in older children and adolescents, HVP centers were significantly better than adult centers for patient survival (half-life: 4.6 vs 2.5 years, p = 0.001). Of note, even LVP centers tended to have longer patient survival than adult centers (p = 0.064). Multivariable analysis identified adult centers as an independent risk factor for graft failure (hazard ratio: 1.5, p < 0.001) as with LVP (hazard ratio: 1.3, p = 0.0078). Despite larger overall clinical volume, outcomes among pediatric LTx recipients in adult centers are not superior to those of pediatric centers. Not only center volume but pediatric-specific experience has an impact on outcomes in pediatric LTx. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

NonTuberculous Mycobacteria infection and lung transplantation in cystic fibrosis: a worldwide survey of clinical practice.

PubMed

Tissot, Adrien; Thomas, Matthew F; Corris, Paul A; Brodlie, Malcolm

2018-05-22

In people with cystic fibrosis infection with NonTuberculous Mycobacteria is of increasing prevalence. Mycobacterium abscessus complex is of particular concern and has been associated with adverse clinical outcomes. Optimal treatment usually requires multiple antibiotics for over 12 months. When considering lung transplantation for patients with NonTuberculous Mycobacteria potential benefits must be balanced against the risks of uncontrolled infection post-transplant and significant side-effects associated with treatment. In this survey we assessed current international practice with regard to assessing and listing patients for lung transplantation. We designed a questionnaire enquiring about local practice regarding screening for NonTuberculous Mycobacteria infection, specific contra-indications to transplantation, management and segregation of patients pre- and post-transplant. The survey was sent via e-mail to 37 paediatric and adult lung transplant centres across Europe, North America and Australia. We gathered complete questionnaires from 21 centres (57% response rate). Few centres (29%) have a clear written policy regarding NonTuberculous Mycobacteria. Sixteen (76%) centres require molecular identification of NonTuberculous Mycobacteria species. Only four centres would consider infection with M. abscessus complex in itself a contra-indication for listing, however 76% regard it as a relative contra-indication. Eighty-six percent require treatment pre-transplantation. Finally, only 61% of centres had a clear policy regarding segration of patients pre-transplant and 48% post-transplant. The issue of NonTuberculous Mycobacteria infection in people with cystic fibrosis requiring lung transplantation is well-recognized however current international recommendations are not detailed and there is variation in practice between centres. There is an urgent requirement for high quality clinical data to inform decision-making.

Reemergence of Lower-Airway Microbiota in Lung Transplant Patients with Cystic Fibrosis.

PubMed

Syed, Saad A; Whelan, Fiona J; Waddell, Barbara; Rabin, Harvey R; Parkins, Michael D; Surette, Michael G

2016-12-01

Chronic lung infections are a hallmark of cystic fibrosis; they are responsible for progressive airway destruction and ultimately lead to respiratory death or the requirement for life-saving bilateral lung transplant. Furthermore, recurrent isolation of airway pathogens such as Pseudomonas aeruginosa in the allograft after transplant is associated with adverse outcomes, including bronchiolitis obliterans syndrome and acute infections. Little information exists on the impact of bilateral lung transplant on the lower-airway microbiota. To compare, at a microbiome and single-pathogen level (P. aeruginosa), the bacterial communities in pre- and post-transplant samples. We retrospectively accessed our biobank of sputum samples and sputum-derived bacterial pathogens for patients who had matched samples, including those who were clinically stable before transplant, those who had a pulmonary exacerbation before transplant, and those who had pulmonary exacerbation after transplant. We used 16S ribosomal RNA gene sequencing to characterize the lower-airway microbiome of 14 adult transplant patients with cystic fibrosis. Genotyping and phenotyping of P. aeruginosa isolates from 12 of these patients with matched isolates was performed. Although α-diversity (richness and evenness) of patient microbiomes was similar before and after transplant, β- diversity (core microbiome composition) measures stratified patients evenly into two groups with more similar and more dissimilar communities. P. aeruginosa strains isolated before transplant were found to reemerge in 11 of 12 patients; however, phenotypic variation was observed. These findings indicate that recolonization by P. aeruginosa after transplant is almost always strain specific, suggesting a within-host source. The polymicrobial colonization of the airways after transplant does not always reflect the pretransplant sputum microbiota.

Frailty Phenotypes, Disability, and Outcomes in Adult Candidates for Lung Transplantation

PubMed Central

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.

2015-01-01

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

Intra-operative protective mechanical ventilation in lung transplantation: a randomised, controlled trial.

PubMed

Verbeek, G L; Myles, P S; Westall, G P; Lin, E; Hastings, S L; Marasco, S F; Jaffar, J; Meehan, A C

2017-08-01

Primary graft dysfunction occurs in up to 25% of patients after lung transplantation. Contributing factors include ventilator-induced lung injury, cardiopulmonary bypass, ischaemia-reperfusion injury and excessive fluid administration. We evaluated the feasibility, safety and efficacy of an open-lung protective ventilation strategy aimed at reducing ventilator-induced lung injury. We enrolled adult patients scheduled to undergo bilateral sequential lung transplantation, and randomly assigned them to either a control group (volume-controlled ventilation with 5 cmH 2 O, positive end-expiratory pressure, low tidal volumes (two-lung ventilation 6 ml.kg -1 , one-lung ventilation 4 ml.kg -1 )) or an alveolar recruitment group (regular step-wise positive end-expiratory pressure-based alveolar recruitment manoeuvres, pressure-controlled ventilation set at 16 cmH 2 O with 10 cmH 2 O positive end-expiratory pressure). Ventilation strategies were commenced from reperfusion of the first lung allograft and continued for the duration of surgery. Regular PaO 2 /F I O 2 ratios were calculated and venous blood samples collected for inflammatory marker evaluation during the procedure and for the first 24 h of intensive care stay. The primary end-point was the PaO 2 /F I O 2 ratio at 24 h after first lung reperfusion. Thirty adult patients were studied. The primary outcome was not different between groups (mean (SD) PaO 2 /F I O 2 ratio control group 340 (111) vs. alveolar recruitment group 404 (153); adjusted p = 0.26). Patients in the control group had poorer mean (SD) PaO 2 /F I O 2 ratios at the end of the surgical procedure and a longer median (IQR [range]) time to tracheal extubation compared with the alveolar recruitment group (308 (144) vs. 402 (154) (p = 0.03) and 18 (10-27 [5-468]) h vs. 15 (11-36 [5-115]) h (p = 0.01), respectively). An open-lung protective ventilation strategy during surgery for lung transplantation is feasible, safe and achieves favourable ventilation parameters. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

Can Stem Cells be Used to Generate New Lungs? Ex Vivo Lung Bioengineering with Decellularized Whole Lung Scaffolds

PubMed Central

Wagner, Darcy E.; Bonvillain, Ryan W.; Jensen, Todd J.; Girard, Eric D.; Bunnell, Bruce A.; Finck, Christine M.; Hoffman, Andrew M.; Weiss, Daniel J.

2013-01-01

For patients with end-stage lung diseases, lung transplantation is the only available therapeutic option. However, the number of suitable donor lungs is insufficient and lung transplants are complicated by significant graft failure and complications of immunosuppressive regimens. An alternative to classic organ replacement is desperately needed. Engineering of bioartificial organs using either natural or synthetic scaffolds is an exciting new potential option for generation of functional pulmonary tissue for human clinical application. Natural organ scaffolds can be generated by decellularization of native tissues; these acellular scaffolds retain the native organ ultrastructure and can be seeded with autologous cells toward the goal of regenerating functional tissues. Several decellularization strategies have been employed for lung, however, there is no consensus on the optimal approach. A variety of cell types have been investigated as potential candidates for effective recellularization of acellular lung scaffolds. Candidate cells that might be best utilized are those which can be easily and reproducibly isolated, expanded in vitro, seeded onto decellularized matrices, induced to differentiate into pulmonary lineage cells, and which survive to functional maturity. Whole lung cell suspensions, endogenous progenitor cells, embryonic and adult stem cells, and induced pluripotent stem (iPS) cells have been investigated for their applicability to repopulate acellular lung matrices. Ideally, patient-derived autologous cells would be used for lung recellularization as they have the potential to reduce the need for post-transplant immunosuppression. Several studies have performed transplantation of rudimentary bioengineered lung scaffolds in animal models with limited, short-term functionality but much further study is needed. PMID:23614471

Is Functional Independence Associated With Improved Long-Term Survival After Lung Transplantation?

PubMed

Osho, Asishana; Mulvihill, Michael; Lamba, Nayan; Hirji, Sameer; Yerokun, Babatunde; Bishawi, Muath; Spencer, Philip; Panda, Nikhil; Villavicencio, Mauricio; Hartwig, Matthew

2018-07-01

Existing research demonstrates superior short-term outcomes (length of stay, 1-year survival) after lung transplantation in patients with preoperative functional independence. The aim of this study was to determine whether advantages remain significant in the long-term. The United Network for Organ Sharing database was queried for adult, first-time, isolated lung transplantation records from January 2005 to December 2015. Stratification was performed based on Karnofsky Performance Status Score (3 groups) and on employment at the time of transplantation (2 groups). Kaplan-Meier and Cox analyses were performed to determine the association between these factors and survival in the long-term. Of 16,497 patients meeting criteria, 1,581 (9.6%) were almost completely independent at the time of transplant vs 5,662 (34.3%) who were disabled (completely reliant on others for activities of daily living). Cox models adjusting for recipient, donor, and transplant factors demonstrated a statistically significant association between disability at the time of transplant and long-term death (hazard ratio, 1.26; 95% confidence interval, 1.14 to 1.40; p < 0.001). There were 15,931 patients with available data on paid employment at the time of transplantation. Multivariable analysis demonstrated a statistically significant association between employment at the time of transplantation and death (hazard ratio, 0.86; 95% confidence interval, 0.75 to 0.91; p < 0.001). Preoperative functional independence and maintenance of employment are associated with superior long-term outcomes in lung recipients. The results highlight potential benefits of pretransplant functional rehabilitation for patients on the waiting list for lungs. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

PubMed

Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

2018-04-18

Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

Change of sleep quality from pre- to 3 years post-solid organ transplantation: The Swiss Transplant Cohort Study

PubMed Central

Denhaerynck, Kris; Huynh-Do, Uyen; Binet, Isabelle; Hadaya, Karine; De Geest, Sabina

2017-01-01

Background Poor sleep quality (SQ) is common after solid organ transplantation; however, very little is known about its natural history. We assessed the changes in SQ from pre- to 3 years post-transplant in adult heart, kidney, liver and lung recipients included in the prospective nation-wide Swiss Transplant Cohort Study. We explored associations with selected variables in patients suffering persistent poor SQ compared to those with good or variable SQ. Methods Adult single organ transplant recipients enrolled in the Swiss Transplant Cohort Study with pre-transplant and at least 3 post-transplant SQ assessment data were included. SQ was self-reported pre-transplant (at listing), then at 6, 12, 24 and 36 months post-transplant. A single SQ item was used to identify poor (0–5) and good sleepers (6–10). Between organ groups, SQ was compared via logistic regression analysis with generalized estimating equations. Within the group reporting persistently poor SQ, we used logistic regression or Kaplan-Meier analysis as appropriate to check for differences in global quality of life and survival. Results In a sample of 1173 transplant patients (age: 52.1±13.2 years; 65% males; 66% kidney, 17% liver, 10% lung, 7% heart) transplanted between 2008 and 2012, pre- transplant poor SQ was highest in liver (50%) and heart (49%) recipients. Overall, poor SQ decreased significantly from pre-transplant (38%) to 24 months post-transplant (26%) and remained stable at 3 years (29%). Patients reporting persistently poor SQ had significantly more depressive symptomatology and lower global quality of life. Conclusion Because self-reported poor SQ is related to poorer global quality of life, these results emphasize the need for further studies to find suitable treatment options for poor SQ in transplant recipients. PMID:29020112

Short- and long-term outcomes of 1000 adult lung transplant recipients at a single center.

PubMed

Kreisel, Daniel; Krupnick, Alexander S; Puri, Varun; Guthrie, Tracey J; Trulock, Elbert P; Meyers, Bryan F; Patterson, G Alexander

2011-01-01

Lung transplantation has become accepted therapy for end-stage pulmonary disease. The objective of this study was to review a single-institution experience of adult lung transplants. We reviewed 1000 adult lung transplants that were performed at Washington University between July 1988 and January 2009. Transplants were performed for emphysema (52%), cystic fibrosis (18.2%), pulmonary fibrosis (16.1%), and pulmonary vascular disease (7.2%). Overall recipient age was 48 ± 13 years with an increase from 43 ± 12 years (July 1988-November 1993) to 50 ± 14 years (June 2005-January 2009). Overall incidence of primary graft dysfunction was 22.1%. Hospital mortality was higher for patients who had primary graft dysfunction (primary graft dysfunction, 13.6%; no primary graft dysfunction, 4%; P < .001). Freedom from bronchiolitis obliterans syndrome was 84% at 1 year, 38.2% at 5 years, and 12.2% at 10 years. Survival at 1, 5, 10, and 15 years was 84%, 56.4%, 32.2%, and 17.8%, respectively. Five-year survival improved from 49.6% (July 1988-November 1993) to 62.1% (October 2001-June 2005). Primary graft dysfunction was associated with lower survival at 1, 5, and 10 years (primary graft dysfunction: 72.8%, 43.9%, and 18.7%, respectively; no primary graft dysfunction: 87.1%, 59.8%, and 35.7%, respectively, P < .001) and lower rates of freedom from bronchiolitis obliterans syndrome (primary graft dysfunction: 78%, 27.5%, and 8.5%, respectively; no primary graft dysfunction: 85.4%, 40.7%, and 13.1%, respectively, P = .007). Five-year survival has improved over the study period, but long-term outcomes are limited by bronchiolitis obliterans syndrome. Primary graft dysfunction is associated with higher rates of bronchiolitis obliterans syndrome and impaired short- and long-term survival. A better understanding of primary graft dysfunction and bronchiolitis obliterans syndrome is critical to improve outcomes. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Solid Organ Transplantation in Older Adults: Current Status and Future Research

PubMed Central

Abecassis, M.; Bridges, N.D.; Clancy, C.J.; Dew, M.A.; Eldadah, B.; Englesbe, M.J.; Flessner, M.F.; Frank, J.C.; Friedewald, J.; Gill, J; Gries, C.; Halter, J.B.; Hartmann, E.L.; Hazzard, W.R.; Horne, F.M.; Hosenpud, J.; Jacobson, P.; Kasiske, B.L.; Lake, J.; Loomba, R.; Malani, P.N.; Moore, T.M.; Murray, A.; Nguyen, M-H; Powe, N.R.; Reese, P.P.; Reynolds, H.; Samaniego, M.D.; Schmader, K.E.; Segev, D.L.; Shah, A.S.; Singer, L.G.; Sosa, J.A.; Stewart, Z.A.; Tan, J.C.; Williams, W.W.; Zaas, D.W.; High, K.P.

2012-01-01

An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans-disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK, and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas. PMID:22958872

Use of the donor lung after asphyxiation or drowning: effect on lung transplant recipients.

PubMed

Whitson, Bryan A; Hertz, Marshall I; Kelly, Rosemary F; Higgins, Robert S D; Kilic, Ahmet; Shumway, Sara J; D'Cunha, Jonathan

2014-10-01

With the relative paucity of acceptable donors for lung transplantation, criteria for extended donor consideration are being explored. We sought to evaluate the suitability of donors whose cause of death was asphyxiation or drowning (A/D) as a potential option to enlarge the donor pool. We queried the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research registry for lung transplantation from 1987 to 2010 to assess associations between cause of death and recipient survival using the Kaplan-Meier method. To adjust for potential confounders, we used a Cox proportional hazards model and a logistic regression model to evaluate incidence of rejection within the first year. There were 18,250 adult primary lung transplantations performed, with 309 A/D donors. There was no difference in survival between groups (log-rank, p = 0.52). There were no differences in demographics, length of stay, airway dehiscence, lung allocation score (LAS), or ischemic time in univariate analysis (all p > 0.05). The A/D lung recipients had fewer deaths from pulmonary causes (5.8% versus 9.5%; p = 0.02). Proportional hazards analysis was significant for double lung transplantation (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.8-0.9), height difference (HR, 1.002; 95% CI, 1.00-1.003), donor age greater than 50 years (HR, 0.89; 95% CI, 0.83-0.96), and recipient age greater than 55 years (HR, 0.8; 95% CI, 0.76-0.84). A/D cause of death did not impact survival in multivariate analysis. A/D as a donor cause of death was not associated with poor long-term survival or incidence of rejection in the first year after transplantation. Donor cause of death by A/D, when carefully evaluated and selected, should not automatically exclude the organ from transplant consideration. These results provide important justification for potentially broadening the donor pool safely. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Adult cardiothoracic transplant nursing: an ISHLT consensus document on the current adult nursing practice in heart and lung transplantation.

PubMed

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

2015-02-01

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.

Significance of single lung transplantation in the current situation of severe donor shortage in Japan.

PubMed

Miyoshi, Ryo; Chen-Yoshikawa, Toyofumi F; Hijiya, Kyoko; Motoyama, Hideki; Aoyama, Akihiro; Menju, Toshi; Sato, Toshihiko; Sonobe, Makoto; Date, Hiroshi

2016-02-01

Although bilateral lung transplantation is the procedure of choice internationally, single lung transplantation is preferred in Japan because of the severe donor shortage except in cases of contraindications to single lung transplantation. This study aimed to evaluate the clinical characteristics of single lung transplant recipients and outcomes of this procedure at one of the largest lung transplant centers in Japan. Between April 2002 and May 2015, 57 cadaveric lung transplantations (33 single and 24 bilateral) were performed in Kyoto University Hospital. The clinical characteristics of the lung transplant recipients and outcomes of these procedures, including overall survival and postoperative complications, were investigated. Overall, the 1-, 3-, and 5-year survival rates were 86, 77, and 72 %, respectively, with a median follow-up period of 1.9 years. There was no significant difference in survival between patients who underwent single lung transplantations and those who underwent bilateral lung transplantations (p = 0.92). The median waiting time was significantly shorter for single lung transplant patients than for bilateral lung transplant patients (p = 0.02). Native lung complications were seen in 14 out of 33 patients (42 %) who underwent single lung transplantation. There was no significant difference in survival between patients with and without postoperative native lung complications. Single lung transplantation has been performed with acceptable outcomes in our institution. In the current situation of severe donor shortage in Japan, single lung transplantation can remain the first choice of treatment except in cases of contraindications to single lung transplantation.

Chronic Stenotrophomonas maltophilia infection and mortality or lung transplantation in cystic fibrosis patients.

PubMed

Waters, Valerie; Atenafu, Eshetu G; Lu, Annie; Yau, Yvonne; Tullis, Elizabeth; Ratjen, Felix

2013-09-01

Chronic Stenotrophomonas maltophilia infection is an independent risk factor for severe pulmonary exacerbations in cystic fibrosis (CF) patients. The goal of this study was to determine the effect of chronic S. maltophilia infection on mortality and the need for lung transplantation in a longitudinal study of children and adults with CF. This was a cohort study of CF patients from the Hospital for Sick Children and St Michael's Hospital (Toronto, Canada) from 1997 to 2008. A Cox Regression model was used to estimate the hazard ratio (HR) to time of death or lung transplantation adjusting for age, gender, genotype, pancreatic status, CF related diabetes (CFRD), forced expiratory volume in 1 s (FEV1), body mass index, number of pulmonary exacerbations, Pseudomonas aeruginosa, Burkholderia cepacia complex, Aspergillus and chronic S. maltophilia infection. A total of 687 patients were followed over the 12 year study period; 95 patients underwent a lung transplantation (of which 26 died) and an additional 49 patients died (total 144 events). In a Cox Regression model adjusting for baseline FEV1, baseline infection with B. cepacia complex (HR 1.72, 95% CI 1.09-2.71) and baseline chronic S. maltophilia infection (HR 2.80, 95% CI 1.65-4.76) were significantly associated with death or lung transplant. However, in a time-varying model, infection with B. cepacia complex and chronic S. maltophilia infection were no longer significant. Baseline chronic S. maltophilia infection is associated with an almost three-fold increased risk of death or lung transplant in CF patients. It is still unclear, however, whether chronic S. maltophilia infection is simply a marker of severity of disease and ultimate mortality or whether it is causally related to disease progression. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Balloon atrial septostomy in pulmonary arterial hypertension: effect on survival and associated outcomes.

PubMed

Chiu, Joanne S; Zuckerman, Warren A; Turner, Mariel E; Richmond, Marc E; Kerstein, Diane; Krishnan, Usha; Torres, Alejandro; Vincent, Julie A; Rosenzweig, Erika B

2015-03-01

Pulmonary arterial hypertension (PAH) is a progressive disease that, without early identification and treatment, may lead to right heart failure, multi-organ dysfunction and early death. In severe PAH, in addition to maximal medical therapy, balloon atrial septostomy (BAS) may be used for palliation and as a bridge to lung transplantation. We present our contemporary institutional experience utilizing BAS in adult and pediatric patients with severe PAH. We performed a retrospective analysis of 46 BASs performed in 32 patients with PAH from 2002 to 2013. Data obtained included vital status, functional class, medications, hemodynamic measurements from right heart catheterizations and biomarkers. Lung transplantation-free and repeat-BAS-free survival was analyzed. Median age at BAS was 23 (range 1 to 56) years. The most common indications were symptomatic right heart failure (21 of 46 patients) and pre-syncope/syncope (19 of 46 patients); 69% of patients were WHO Functional Class III or IV pre-BAS. There were no procedural complications or deaths. There were no significant differences in biomarkers or hemodynamic findings between pre-BAS and 1 year or latest follow-up. Seven patients were successfully bridged to lung transplantation. Lung transplantation-free and repeat-BAS-free survival at 30 days, 1 year and 5 years was 87%, 61% and 32%, respectively. In our experienced center, BAS was shown to be safe in patients with severe PAH on maximal medical management, with no procedural deaths or complications. BAS was safely used as a bridge to lung transplantation or to alleviate right heart failure symptoms and/or syncope. Other potential benefits for end-organ function and overall survival remain to be determined. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

[The registry report of Japanese lung transplantation--2009].

PubMed

2010-07-01

To scrutinize the status of lung transplantation in Japan, the Japanese Society of Lung and Heart-Lung Transplantation started to collect and present registry data from 2005. This is the 5th official registry report of Japanese lung transplantation. The data of cadaveric lung transplantation and living-donor lobar transplantation performed by the end of 2008 were registered to the database and analyzed with respect to the number of transplants, recipient survival rates, recipient functional and working status, and cause of death after transplantation. Survival rates were calculated by the Kaplan-Meier method. Fifty-three (30 single and 23 bilateral) cadaveric lung transplantations and 77 living-donor lobar transplantations were performed by the end of 2008. Five-year survival rates of cadaveric single and bilateral lung transplantations were 61.9% and 62.5%, respectively, which were both superior to those in the International Registry (47.1% and 55.0%, respectively). Five-year and 10-year survival rates of living-donor lobar transplantation were excellent at 79.9% and 77.0%, respectively. The functional status of >80% of recipients was restored to Hugh-Jones I or II after transplantation. Infection was the leading cause of death after lung transplantation. The results of Japanese lung transplantation are so far satisfactory although we should note the small number of lung transplant cases in Japan. The Japanese Society of Lung and Heart-Lung Transplantation will continue to present the annual report of Japanese lung transplantation.

Registry of the Japanese Society of Lung and Heart-Lung Transplantation: the official Japanese lung transplantation report 2008.

PubMed

Shiraishi, Takeshi; Okada, Yoshinori; Sekine, Yasuo; Chida, Masayuki; Bando, Toru; Minami, Masato; Oto, Takahiro; Nagayasu, Takeshi; Date, Hiroshi; Kondo, Takashi

2009-08-01

The year 2008 marked the 10th anniversary of the Japanese lung transplantation program started in accordance with the Japanese Organ Transplant Law, which took effect in 1997. A total of 105 lung transplantations, including 39 deceased-donor transplants and 66 living-related transplants, had been performed as of the end of 2007. This article is the 2008 official report of the Japanese Society of Lung and Heart-Lung Transplantation. It summarizes the data for clinical lung transplantation during the period 1998-2007 and discusses the current status of Japanese lung transplantation. The overall 5-year survival rate was 67.0%: including 53.4% and 74.6% for deceased-donor lung transplantation and living-donor lobar lung transplantation groups, respectively. The total operation-related and 1-month mortality rates after surgery were 3.8% and 10.4%, respectively. These data are better, or at least acceptable, in comparison with the international registry data.

Registry of the Japanese society of lung and heart-lung transplantation: the official Japanese lung transplantation report 2012.

PubMed

Oto, Takahiro; Okada, Yoshinori; Bando, Toru; Minami, Masato; Shiraishi, Takeshi; Nagayasu, Takeshi; Chida, Masayuki; Okumura, Meinoshin; Date, Hiroshi; Miyoshi, Shinichiro; Kondo, Takashi

2013-04-01

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.

Lung transplantation: overall approach regarding its major aspects

PubMed Central

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

2015-01-01

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

Refining Low Physical Activity Measurement Improves Frailty Assessment in Advanced Lung Disease and Survivors of Critical Illness.

PubMed

Baldwin, Matthew R; Singer, Jonathan P; Huang, Debbie; Sell, Jessica; Gonzalez, Wendy C; Pollack, Lauren R; Maurer, Mathew S; D'Ovidio, Frank F; Bacchetta, Matthew; Sonett, Joshua R; Arcasoy, Selim M; Shah, Lori; Robbins, Hilary; Hays, Steven R; Kukreja, Jasleen; Greenland, John R; Shah, Rupal J; Leard, Lorriana; Morrell, Matthew; Gries, Cynthia; Katz, Patricia P; Christie, Jason D; Diamond, Joshua M; Lederer, David J

2017-08-01

The frail phenotype has gained popularity as a clinically relevant measure in adults with advanced lung disease and in critical illness survivors. Because respiratory disease and chronic illness can greatly limit physical activity, the measurement of participation in traditional leisure time activities as a frailty component may lead to substantial misclassification of frailty in pulmonary and critical care patients. To test and validate substituting the Duke Activity Status Index (DASI), a simple 12-item questionnaire, for the Minnesota Leisure Time Physical Activity (MLTA) questionnaire, a detailed questionnaire covering 18 leisure time activities, as the measure of low activity in the Fried frailty phenotype (FFP) instrument. In separate multicenter prospective cohort studies of adults with advanced lung disease who were candidates for lung transplant and older survivors of acute respiratory failure, we assessed the FFP using either the MLTA or the DASI. For both the DASI and MLTA, we evaluated content validity by testing floor effects and construct validity through comparisons with conceptually related factors. We tested the predictive validity of substituting the DASI for the MLTA in the FFP assessment using Cox models to estimate associations between the FFP and delisting/death before transplant in those with advanced lung disease and 6-month mortality in older intensive care unit (ICU) survivors. Among 618 adults with advanced lung disease and 130 older ICU survivors, the MLTA had a substantially greater floor effect than the DASI (42% vs. 1%, and 49% vs. 12%, respectively). The DASI correlated more strongly with strength and function measures than did the MLTA in both cohorts. In models adjusting for age, sex, comorbidities, and illness severity, substitution of the DASI for the MLTA led to stronger associations of the FFP with delisting/death in lung transplant candidates (FFP-MLTA hazard ratio [HR], 1.42; 95% confidence interval [CI], 0.55-3.65; FFP-DASI HR, 2.99; 95% CI, 1.03-8.65) and with mortality in older ICU survivors (FFP-MLTA HR, 2.68; 95% CI, 0.62-11.6; FFP-DASI HR, 5.71; 95% CI, 1.34-24.3). The DASI improves the construct and predictive validity of frailty assessment in adults with advanced lung disease or recent critical illness. This simple questionnaire should replace the more complex MLTA in assessing the frailty phenotype in these populations.

PARACOCCIDIOIDOMYCOSIS IN A RENAL TRANSPLANT RECIPIENT

PubMed Central

GÓES, Heliana Freitas de Oliveira; DURÃES, Sandra Maria Barbosa; LIMA, Caren dos Santos; de SOUZA, Mariana Boechat; VILAR, Enoi Aparecida Guedes; DALSTON, Marcos Olivier

2016-01-01

Paracoccidioidomycosis (PCM) is the most common endemic mycosis in Latin America. The etiological agents, which comprise two species, Paracoccidioides brasiliensis and P. lutzii, are thermodimorphic fungi that usually affect previously healthy adults. They primarily involve the lungs and then disseminate to other organs. Such mycosis is rare in organ transplant recipients; there have been only three cases reported in literature, until now. We report a case of PCM in a renal transplant recipient with an unusual dermatological presentation. PMID:26910451

Lung transplantation and interstitial lung disease.

PubMed

Alalawi, Raed; Whelan, Timothy; Bajwa, Ravinder S; Hodges, Tony N

2005-09-01

Interstitial lung disease includes a heterogeneous group of disorders that leads to respiratory insufficiency and death in a significant number of patients. Lung transplantation is a therapeutic option in select candidates. The indications, transplant procedure options, and outcomes continue to evolve. Various recipient comorbidities influence the choice of procedure in patients with interstitial lung disease. Single lung transplants are used as the procedure of choice and bilateral transplants are reserved for patients with suppurative lung disease and patients with pulmonary hypertension. Issues unique to patients with interstitial lung disease affect the morbidity, mortality and recurrence of the disease. Lung transplantation is an effective therapy for respiratory failure in interstitial lung disease with survival following transplant being similar to that achieved in transplant recipients with other diseases.

Lung Transplantation

MedlinePlus

A lung transplant removes a person's diseased lung and replaces it with a healthy one. The healthy lung comes from ... lung during a transplant. Other people get two. Lung transplants are used for people who are likely to ...

Single versus bilateral lung transplantation for idiopathic pulmonary fibrosis: a ten-year institutional experience.

PubMed

Meyers, B F; Lynch, J P; Trulock, E P; Guthrie, T; Cooper, J D; Patterson, G A

2000-07-01

Between July 1988 and July 1998, we performed 433 lung transplants. Forty-five patients had idiopathic pulmonary fibrosis, and operations for these patients included 32 single lung transplants and 13 bilateral sequential lung transplants. This study reviews this experience and compares single lung transplantation and bilateral lung transplantation for pulmonary fibrosis. We performed a retrospective review, including inpatient hospital charts, outpatient clinic records, and telephone contact with patients to verify current health status. Perioperative mortality was 4 (8.9%) patients. One patient underwent redo bilateral lung transplantation for reperfusion injury and graft failure after single lung transplantation. The median hospitalization was 22 days. Actuarial survival at 1 and 5 years was 75.5% and 53.5%, respectively, which was not significantly different from our survival for all recipients (85.5% and 56.4%, respectively). Seventeen (41%) of 41 operative survivors have died. Late causes of death included obliterative bronchiolitis with respiratory failure (9), malignancy (3), and cytomegalovirus pneumonitis (2). Hospital mortality was 3 (9.4%) of 32 after single lung transplantation and 1 (7.7%) of 13 after bilateral lung transplantation. There was no difference between single and bilateral lung transplantation with regard to hospital stay. Four (12.5%) of the 32 patients undergoing single lung transplantation required tracheostomy, whereas 3 (23%) of 13 recipients undergoing bilateral lung transplantation required tracheostomy. Single or bilateral lung transplantations offer viable therapy for patients with pulmonary fibrosis. We demonstrate no benefit of bilateral over single lung transplantation for patients with this diagnosis. Survival after transplantation appears better than that of historic control subjects receiving standard medical care at other institutions.

[Lung transplantation: supply and demand in France].

PubMed

Stern, M; Souilamas, R; Tixier, D; Mal, H

2008-10-01

For a decade lung transplantation has suffered from a lack of donor organs which aroused a national debate and led to planned action in collaboration with The French National Agency for Transplantation. Analysis of the stages of the process from potential donor to lung transplantation identified lung procurement as the main priority. An increase in the number of potential lung donors and revision of the acceptance criteria led to a doubling of the annual rate of lung transplantation in less than two years. In the near future we may solve the problem of donor family refusals and establish scientifically based criteria for lung acceptance to increase the rate of lung transplantation. Transplantation from non heart-beating donors and the reconditioning of ex vivo non acceptable lungs might supply additional organs to fulfill demand in the long term. The rate of lung transplantation activity in France doubled as the result of a dramatic increase of donor lung proposals. The current improvement in the results of lung transplantation might create new demands and generate future difficulties in the supply of donor lungs. New approaches, such as transplantation from non heart-beating donors and reconditioning ex vivo non acceptable lungs, should be examined in the near future.

Lung transplantation after allogeneic marrow transplantation in pediatric patients: the Memorial Sloan-Kettering experience.

PubMed

Heath, J A; Kurland, G; Spray, T L; Kernan, N A; Small, T N; Brochstein, J A; Gillio, A P; Boklan, J; O'Reilly, R J; Boulad, F

2001-12-27

Chronic lung disease and pulmonary failure are complications that can occur after bone marrow transplantation (BMT) and are associated with severe morbidity and mortality. We report on four patients who developed chronic, progressive, and irreversible lung disease 1 to 3 years after allogeneic BMT in childhood. These patients had chronic graft-versus-host disease (n=3) or radiation-related pulmonary fibrosis (n=1). Three patients underwent double lung transplants and one patient underwent a single lung transplant 2 to 14 years after BMT. All four patients tolerated the lung transplantation procedure well and showed significant clinical improvement with normalization of pulmonary function tests by 1 year posttransplant. One patient died from infectious complications 3 years after lung transplantation, and one patient died after chronic rejection of the transplanted lungs 6 years posttransplant. Two patients remain alive without significant respiratory impairment 2 and 7 years after lung transplantation. We conclude that lung transplantation offers a viable therapeutic option for patients who develop respiratory failure secondary to BMT.

Double- and single-lung transplantation: an analysis of twenty years of OPTN/UNOS registry data.

PubMed

Cai, Junchao

2007-01-01

1. Within the past 2 decades, the annual number of lung transplants, especially double-lung transplants, has steadily increased every year and exceeded 1,400 in the last 2 years. 2. Overall 1-, 5-, and 10-year graft survival rates for double-lung transplant recipients were 79.5%, 50.6%, and 30.4% respectively; those for left-lung transplant recipients were 76.0%, 41.8%, and 17.1%; and for right-lung transplant recipients were 78.3%, 44.8%, and 19.2%. 3. The improvement in long-term graft survival in the most recent transplant era was mainly due to improved one-year survival, more precisely, due to the increased early outcome within the first 2-3 months after transplantation. 4. A negative association between HLA mismatch and graft survival is statistically significant in both double and left-lung transplants. 5. Female COPD and ATD single-lung recipients had high long-term graft survival when they received right-lung transplants. While for male single-lung recipients, CF patients had better graft survival when they received left lung transplants; but PPH patients had higher graft survival when receiving right-lung transplants. This association between recipient gender and/or different original diseases and graft survival requires further investigation.

[Lung transplantation.].

PubMed

Guðmundsson, G

2000-09-01

Lung transplantation is an option in the treatment of end stage lung diseases, excluding lung cancer, that lead to short life expectancy and poor quality of life. Now they are mostly limited by shortage of donor organs and longterm complications. They are used for various lung diseases such as pulmonary vascular diseases, fibrosing diseases, chronic obstructive pulmonary diseases and diseases that cause chronic infections. Depending on the indication it is possible to perform heart and lung transplantation, single lung or double lung transplantation.Indications, contraindications, surgical methods, immunosuppression, complications and outcomes will be discussed. Survival is not as good as for other solid organ transplantation. Measurement of pulmonary function and quality of life improve with lung transplantation. Bronchiolitis obliterans is the most common complication and is the most limiting factor. A few Icelanders have undergone lung transplantation, most of them in Gothenburg, Sweden. The future of lung transplantation depends on limiting the incidence of bronchiolitis obliterans and finding more organ donors.

Plasma Soluble Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis

PubMed Central

Manichaikul, Ani; Sun, Li; Borczuk, Alain C.; Onengut-Gumuscu, Suna; Farber, Emily A.; Mathai, Susan K.; Zhang, Weiming; Raghu, Ganesh; Kaufman, Joel D.; Hinckley-Stukovsky, Karen D.; Kawut, Steven M.; Jelic, Sanja; Liu, Wen; Fingerlin, Tasha E.; Schwartz, David A.; Sell, Jessica L.; Rich, Stephen S.; Barr, R. Graham

2017-01-01

Rationale: The receptor for advanced glycation end products (RAGE) is underexpressed in idiopathic pulmonary fibrosis (IPF) lung, but the role of RAGE in human lung fibrosis remains uncertain. Objectives: To examine (1) the association between IPF risk and variation at rs2070600, a functional missense variant in AGER (the gene that codes for RAGE), and (2) the associations between plasma-soluble RAGE (sRAGE) levels with disease severity and time to death or lung transplant in IPF. Methods: We genotyped the rs2070600 single-nucleotide polymorphism in 108 adults with IPF and 324 race-/ethnicity-matched control subjects. We measured plasma sRAGE by ELISA in 103 adults with IPF. We used generalized linear and additive models as well as Cox models to control for potential confounders. We repeated our analyses in 168 (genetic analyses) and 177 (sRAGE analyses) adults with other forms of interstitial lung disease (ILD). Results: There was no association between rs2070600 variation among adults with IPF (P = 0.31). Plasma sRAGE levels were lower among adults with IPF and other forms of ILD than in control subjects (P < 0.001). The rs2070600 allele A was associated with a 49% lower sRAGE level (95% confidence interval [CI], 11 to 71%; P = 0.02) among adults with IPF. In adjusted analyses, lower sRAGE levels were associated with greater disease severity (14% sRAGE decrement per 10% FVC decrement; 95% CI, 5 to 22%) and a higher rate of death or lung transplant at 1 year (adjusted hazard ratio, 1.9 per logarithmic unit of sRAGE decrement; 95% CI, 1.2–3.3) in IPF. Similar findings were observed in a heterogeneous group of adults with other forms of ILD. Conclusions: Lower plasma sRAGE levels may be a biological measure of disease severity in IPF. Variation at the rs2070600 single-nucleotide polymorphism was not associated with IPF risk. PMID:28248552

Association of operative time of day with outcomes after thoracic organ transplant.

PubMed

George, Timothy J; Arnaoutakis, George J; Merlo, Christian A; Kemp, Clinton D; Baumgartner, William A; Conte, John V; Shah, Ashish S

2011-06-01

Recent emphasis on systems-based approaches to patient safety has led to several studies demonstrating worse outcomes associated with surgery at night. To evaluate whether operative time of day was associated with thoracic organ transplant outcomes, hypothesizing that it would not be associated with increased morbidity or mortality. We conducted a retrospective cohort study of adult heart and lung transplant recipients in the United Network for Organ Sharing database from January 2000 through June 2010. Primary stratification was by operative time of day (night, 7 PM-7 AM; day, 7 AM-7 PM). Primary end points were short-term survival, assessed by the Kaplan-Meier method at 30, 90, and 365 days. Secondary end points encompassed common postoperative complications. Risk-adjusted multivariable Cox proportional hazards regression examined mortality. A total of 27,118 patients were included in the study population. Of the 16,573 who underwent a heart transplant, 8346 (50.36%) did so during the day and 8227 (49.64%) during the night. Of the 10,545 who underwent a lung transplant, 5179 (49.11%) did so during the day and 5366 (50.89%) during the night. During a median follow-up of 32.2 months (interquartile range, 11.2-61.1 months), 8061 patients (28.99%) died. Survival was similar for organ transplants performed during the day and night. Survival rates at 30 days for heart transplants during the day were 95.0% vs 95.2% during the night (hazard ratio [HR], 1.05; 95% confidence interval, 0.83-1.32; P = .67) and for lung transplants during the day were 96.0% vs 95.5% during the night (HR, 1.22; 95% CI, 0.97-1.55; P = .09). At 90 days, survival rates for heart transplants were 92.6% during the day vs 92.7% during the night (HR, 1.05; 95% CI, 0.88-1.26; P = .59) and for lung transplants during the day were 92.7% vs 91.7% during the night (HR, 1.23; 95% CI, 1.04-1.47; P = .02). At 1 year, survival rates for heart transplants during the day were 88.0% vs 87.7% during the night (HR, 1.05; 95% CI, 0.91-1.21; P = .47) and for lung transplants during the day were 83.8% vs 82.6% during the night (HR, 1.08; 95% CI, 0.96-1.22; P = .19). Among lung transplant recipients, there was a slightly higher rate of airway dehiscence associated with nighttime transplants (57 of 5022 [1.1%] vs 87 of 5224 [1.7%], P = .02). Among patients who underwent thoracic organ transplants, there was no significant association between operative time of day and survival up to 1 year after organ transplant.

International collaboration: a retrospective study examining the survival of Irish citizens following lung transplantation in both the UK and Ireland.

PubMed

Adamali, Huzaifa I; Judge, Eoin P; Healy, David; Nolke, Lars; Redmond, Karen C; Bartosik, Waldemar; McCarthy, Jim; Egan, Jim J

2012-01-01

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. 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. 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. 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.

Double lung transplants have significantly improved survival compared with single lung transplants in high lung allocation score patients.

PubMed

Black, Matthew C; Trivedi, Jaimin; Schumer, Erin M; Bousamra, Michael; van Berkel, Victor

2014-11-01

Historically, double lung transplantation survival rates are higher than those of single lung transplantation, but in critically ill patients a single lung transplant, with less associated operative morbidity, could afford a better outcome. This article evaluates how survival is affected in patients who have a high lung allocation score (LAS) and receive a single versus a double lung transplant. The UNOS Thoracic Transplant Database for lung transplants from January 2005 to June 2012 was used for analysis. Propensity matching was used to minimize differences between the high and low LAS groups and between single and double lung transplants in the high LAS group. Within this database, there were 8,778 patients, of whom 8,050 had an LAS less than 75 and 728 had an LAS greater than or equal to 75. Kaplan-Meier survival curves stratified by high and low LAS, and by single versus double lung transplants, showed a marked decrease in survival (p<0.001) in those with a high LAS who received a single lung transplant when compared with those with a high LAS who received a double lung transplant. This was a much greater difference in survival than was present in the low LAS patient population. Despite a higher operative morbidity, patients who had a high LAS did substantially better in terms of survival if two lungs were transplanted rather than only one, with a larger difference in survival than for patients with a lower LAS. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Complications of Lung Transplantation: A Roentgenographic Perspective.

PubMed

Tejwani, Vickram; Panchabhai, Tanmay S; Kotloff, Robert M; Mehta, Atul C

2016-06-01

Lung transplantation is now an established treatment for a broad spectrum of end-stage pulmonary diseases. According to the International Society for Heart and Lung Transplantation Registry, more than 50,000 lung transplants have been performed worldwide, with nearly 11,000 lung transplant recipients alive in the United States. With the increasing application of lung transplantation, pulmonologists must be cognizant of common complications unique to the postlung transplant period and the associated radiologic findings. The aim of this review is to describe clinical manifestations and prototypical radiographic features of both common and rare complications encountered in lung transplant recipients. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Long-term impact of liver transplantation on respiratory function and nutritional status in children and adults with cystic fibrosis.

PubMed

Dowman, J K; Watson, D; Loganathan, S; Gunson, B K; Hodson, J; Mirza, D F; Clarke, J; Lloyd, C; Honeybourne, D; Whitehouse, J L; Nash, E F; Kelly, D; van Mourik, I; Newsome, P N

2012-04-01

Early liver transplant (LT) has been advocated for patients with cystic fibrosis liver disease (CFLD) and evidence of deterioration in nutritional state and respiratory function to prevent further decline. However, the impact of single LT on long-term respiratory function and nutritional status has not been adequately addressed. We performed a retrospective analysis of the outcomes of 40 (21 adult/19 pediatric) patients with CFLD transplanted between 1987 and 2009 with median follow-up of 47.8 months (range 4-180). One and five-year actuarial survival rates were 85%/64% for adult and 90%/85% for pediatric LT cohorts, respectively. Lung function remained stable until 4 years (FEV(1) % predicted; pretransplant 48.4% vs. 45.9%, 4 years posttransplant) but declined by 5 years (42.4%). Up to 4 years posttransplant mean annual decline in FEV(1) % was lower (0.74%; p = 0.04) compared with the predicted 3% annual decline in CF patients with comorbidity including diabetes. Number of courses of intravenous antibiotics was reduced following LT, from 3.9/year pretransplant to 1.1/year, 5 years posttransplant. Body mass index was preserved posttransplant; 18.0 kg/m(2) (range 15-24.3) pretransplant versus 19.6 kg/m(2) (range 16.4-22.7) 5 years posttransplant. In conclusion, LT is an effective treatment for selected patients with cirrhosis due to CFLD, stabilizing aspects of long-term lung function and preserving nutritional status. © Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

[Lung transplantation. State of the art].

PubMed

García-Covarrubias, Lisardo; Salerno, Tomas A; Panos, Anthony L; Pham, Si M

2007-01-01

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.

Long-term clinical outcomes of 'Prairie Epidemic Strain' Pseudomonas aeruginosa infection in adults with cystic fibrosis.

PubMed

Somayaji, Ranjani; Lam, John C; Surette, Michael G; Waddell, Barbara; Rabin, Harvey R; Sibley, Christopher D; Purighalla, Swathi; Parkins, Michael D

2017-04-01

Epidemic Pseudomonas aeruginosa (PA) plays an important role in cystic fibrosis (CF) lung disease. A novel strain, the 'Prairie Epidemic Strain' (PES), has been identified in up to 30% of patients in Prairie-based Canadian CF centres. To determine the incidence, prevalence and long-term clinical impact of PES infection. A cohort of adults with CF was followed from 1980 to 2014 where bacteria isolated from clinical encounters were prospectively collected. Strain typing was performed using pulse-field gel electrophoresis and multilocus sequence typing. Patients were divided into one of four cohorts: no PA, transient PA, chronic PA with unique strains and chronic PES. Proportional Cox hazard and linear mixed models were used to assess for CF-associated respiratory death or transplantation, and rates of %FEV 1 and body mass index (BMI) decline. 274 patients (51.7% male) were analysed: 44--no PA, 29--transient PA, 137--unique PA, 64--PES. A total of 92 patients (33.6%) died or underwent lung transplantation (2423.0 patient-years). PES infection was associated with greater risk of respiratory death or lung transplant compared with the no PA group (aHR, 3.94 (95% CI 1.18 to 13.1); p=0.03) and unique PA group (aHR, 1.75 (95% CI 1.05 to 2.92) p=0.03). Rate of lung function decline (%FEV 1 predicted) was greatest in the PES group (1.73%/year (95% CI 1.63% to 1.82%); p<0.001). BMI improved over time but at an attenuated rate in the PES group (p=0.001). Infection with PES was associated with increased patient morbidity through three decades and manifested in an increased risk of respiratory death and/or lung transplantation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Overview of Clinical Lung Transplantation

PubMed Central

Yeung, Jonathan C.; Keshavjee, Shaf

2014-01-01

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

Extracorporeal life support as a bridge to lung transplantation-experience of a high-volume transplant center.

PubMed

Hoetzenecker, Konrad; Donahoe, Laura; Yeung, Jonathan C; Azad, Sassan; Fan, Eddy; Ferguson, Niall D; Del Sorbo, Lorenzo; de Perrot, Marc; Pierre, Andrew; Yasufuku, Kazuhiro; Singer, Lianne; Waddell, Thomas K; Keshavjee, Shaf; Cypel, Marcelo

2018-03-01

Extracorporeal life support (ECLS) is increasingly used to bridge deteriorating patients awaiting lung transplantation (LTx), however, few systematic descriptions of this practice exist. We therefore aimed to review our institutional experience over the past 10 years. In this case series, we included all adults who received ECLS with the intent to bridge to LTx. Data were retrieved from patient charts and our institutional ECLS and transplant databases. Between January 2006 and September 2016, 1111 LTx were performed in our institution. ECLS was used in 71 adults with the intention to bridge to LTx; of these, 11 (16%) were bridged to retransplantation. The median duration of ECLS before LTx was 10 days (range, 0-95). We used a single dual-lumen venous cannula in 23 patients (32%). Nine of 13 patients (69%) with pulmonary hypertension were bridged by central pulmonary artery to left atrium Novalung. Twenty-five patients (35%) were extubated while on ECLS and 26 patients (37%) were mobilized. Sixty-three patients (89%) survived to LTx. Survival by intention to treat was 66% (1 year), 58% (3 years) and 48% (5 years). Survival was significantly shorter in patients undergoing ECLS bridge to retransplantation compared with first LTx (median survival, 15 months (95% CI, 0-31) versus 60 months (95% CI, 37-83); P = .041). In our center experience, ECLS bridge to first lung transplant leads to good short-term and long-term outcomes in carefully selected patients. In contrast, our data suggest that ECLS as a bridge to retransplantation should be used with caution. Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.

Update on medical complications involving the lungs.

PubMed

Zaas, David W

2009-10-01

Lung transplant is now an accepted treatment for end-stage lung disease with improving survival and an increasing number of transplants being performed every year. Recognition of the common medical complications after lung transplant is important for timely diagnosis and treatment. This review will highlight the clinical presentation, diagnosis, and treatment of several noninfectious pulmonary complications that are encountered in lung transplant recipients. The review focuses on several broad areas of medical complications after lung transplant, including native lung complications, malignancies, venous thromboembolism, drug toxicity, and pleural disease. Each of these problems is a significant cause of morbidity and mortality after lung transplant. We review the recent publications in these areas that have identified improved ways to diagnose and treat these complications. Despite its relatively short history, the field of lung transplantation has made significant progress over the past 25 years. The medical advances surrounding lung transplant are not only related to the surgical procedure and immunosuppression, but also to the ability of physicians to diagnose and treat the common complications after transplant. Improvements in the diagnosis and management of these posttransplant medical complications will hopefully lead to even greater survival after lung transplantation in the future.

History of Lung and Heart-Lung Transplantation, With Special Emphasis on German-Speaking Countries.

PubMed

Margreiter, R

2016-10-01

The first experimental lung transplants were performed in 1947 by the Russian surgeon V.P. Demikhov. Thereafter, various aspects associated with lung transplantation were studied by groups from Italy, France, and mainly the United States. The first clinical lung transplant took place in Jackson, Mississippi, in 1963 and was performed by D. Hardy. Until 1983, a total of 45 lung transplants were carried out at various centers, but only one patient transplanted in Ghent by F. Derom in 1968 survived for 10 months, whereas all other patients survived only hours to a few days. In 1983 at Toronto General Hospital, a single-lung transplant was performed that survived almost 7 years. From the same institution, the first long-term survivor after double-lung transplantation was reported in 1986. The first lobar transplant from a live donor was performed by V.A. Starnes at Stanford in 1990. The first heart-lung transplantation was performed in Houston by D.A. Cooley in 1968. Even though the girl who received this transplant survived only for 14 hours, this case showed that this kind of procedure can work. The first long-term survival was achieved by B. Reitz in 1981 in Stanford. In the German-speaking countries, successful lung and lung-heart transplants were reported between 1984 and 1993 and are described in detail. Copyright © 2016 Elsevier Inc. All rights reserved.

Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience

PubMed Central

Schwab, Kristin; Saggar, Rajeev; Duffy, Erin; Elashoff, David; Tseng, Chi-Hong; Weigt, Sam; Charan, Deepshikha; Abtin, Fereidoun; Johannes, Jimmy; Derhovanessian, Ariss; Conklin, Jeffrey; Ghassemi, Kevin; Khanna, Dinesh; Siddiqui, Osama; Ardehali, Abbas; Hunter, Curtis; Kwon, Murray; Biniwale, Reshma; Lo, Michelle; Volkmann, Elizabeth; Torres Barba, David; Belperio, John A.; Mahrer, Thomas; Furst, Daniel E.; Kafaja, Suzanne; Clements, Philip; Shino, Michael; Gregson, Aric; Kubak, Bernard; Lynch, Joseph P.; Ross, David

2016-01-01

Rationale: Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post–lung transplantation outcomes. Objectives: The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction. Methods: We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109). We evaluated post–lung transplant outcomes, including survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates. In addition, we defined severe esophageal dysfunction using esophageal manometry and esophageal morphometry criteria on the basis of chest computed tomography images. For patients with SSc referred for lung transplant but subsequently denied (n = 36), we queried the reason(s) for denial with respect to the concern for esophageal dysfunction. Measurements and Main Results: The 1-, 3-, and 5-year post–lung transplant survival for SSc was 94, 77, and 70%, respectively, and similar to the other groups. The remaining post–lung transplant outcomes evaluated were also similar between SSc and the other groups. Approximately 60% of the SSc group had severe esophageal dysfunction. Pre–lung transplant chest computed tomography imaging demonstrated significantly abnormal esophageal morphometry for SSc when compared with the matched group. Importantly, esophageal dysfunction was the sole reason for lung transplant denial in a single case. Conclusions: Relative to other lung transplant indications, our SSc group experienced comparable survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates, despite the high prevalence of severe esophageal dysfunction. Esophageal dysfunction rarely precluded active listing for lung transplantation. PMID:27078625

Mechanisms of Graft Rejection and Immune Regulation after Lung Transplant.

PubMed

Gauthier, Jason M; Li, Wenjun; Hsiao, Hsi-Min; Takahashi, Tsuyoshi; Arefanian, Saeed; Krupnick, Alexander S; Gelman, Andrew E; Kreisel, Daniel

2017-09-01

Outcomes after lung transplant lag behind those of other solid-organ transplants. A better understanding of the pathways that contribute to rejection and tolerance after lung transplant will be required to develop new therapeutic strategies that take into account the unique immunological features of lungs. Mechanistic immunological investigations in an orthotopic transplant model in the mouse have shed new light on immune responses after lung transplant. Here, we highlight that interactions between immune cells within pulmonary grafts shape their fate. These observations set lungs apart from other organs and help provide the conceptual framework for the development of lung-specific immunosuppression.

Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosis.

PubMed

Elborn, J Stuart; Bell, Scott C; Madge, Susan L; Burgel, Pierre-Regis; Castellani, Carlo; Conway, Steven; De Rijcke, Karleen; Dembski, Birgit; Drevinek, Pavel; Heijerman, Harry G M; Innes, J Alistair; Lindblad, Anders; Marshall, Bruce; Olesen, Hanne V; Reimann, Andreas L; Solé, Ampara; Viviani, Laura; Wagner, Thomas O F; Welte, Tobias; Blasi, Francesco

2016-02-01

The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major life-threatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly reccommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme. Copyright ©ERS 2016.

A review of the lung transplantation programme in Ireland 2005-2007.

PubMed

Bartosik, Waldemar; Egan, Jim J; Soo, Alan; Remund, Kaspar F; Nölke, Lars; McCarthy, James F; Wood, Alfred E

2009-05-01

Lung transplantation is a recognised surgical option for patients with end stage respiratory disease. We present data relating to the initiation of the Irish lung transplant programme in 2005. Seventeen patients: 7 male and 10 female have undergone lung transplantation. The indications for lung transplantation included COPD (n=8), idiopathic pulmonary fibrosis (n=5), bronchiolitis obliterans (n=2), lymphangioleiomyomatosis (n=1), and cystic fibrosis (n=1). Eleven single lungs transplants were completed, while six patients underwent double sequential lung transplantation. The immunosuppression regimen included basiliximab as induction therapy, with steroids, mycophenolate mofetil nd cyclosporine or tacrolimus. The operative mortality was zero. One patient died at 10 months post double lung transplantation secondary to bronchiolitis obliterans. Primary graft dysfunction was observed in two patients who required ventilatory support for 3 and 5 days respectively. Acute cellular rejection was observed in four patients (grade A2 n=3, grade A3 n=2). The cumulative 1-year survival was 94.1%, which compares favourably to an international standard of 78%. The initiation of a lung transplant programme in Ireland has been successfully undertaken and initially provided results comparable to established lung transplant programs.

Survival in Patients with Advanced Non-cystic Fibrosis Bronchiectasis Versus Cystic Fibrosis on the Waitlist for Lung Transplantation.

PubMed

Hayes, Don; Kopp, Benjamin T; Tobias, Joseph D; Woodley, Frederick W; Mansour, Heidi M; Tumin, Dmitry; Kirkby, Stephen E

2015-12-01

Survival in non-cystic fibrosis (CF) bronchiectasis is not well studied. The United Network for Organ Sharing database was queried from 1987 to 2013 to compare survival in adult patients with non-CF bronchiectasis to patients with CF listed for lung transplantation (LTx). Each subject was tracked from waitlist entry date until death or censoring to determine survival differences between the two groups. Of 2112 listed lung transplant candidates with bronchiectasis (180 non-CF, 1932 CF), 1617 were used for univariate Cox and Kaplan-Meier survival function analysis, 1173 for multivariate Cox models, and 182 for matched-pairs analysis based on propensity scores. Compared to CF, patients with non-CF bronchiectasis had a significantly lower mortality by univariate Cox analysis (HR 0.565; 95 % CI 0.424, 0.754; p < 0.001). Adjusting for potential confounders, multivariate Cox models identified a significant reduction in risk for death associated with non-CF bronchiectasis who were lung transplant candidates (HR 0.684; 95 % CI 0.475, 0.985; p = 0.041). Results were consistent in multivariate models adjusting for pulmonary hypertension and forced expiratory volume in one second. Non-CF bronchiectasis with advanced lung disease was associated with significantly lower mortality hazard compared to CF bronchiectasis on the waitlist for LTx. Separate referral and listing criteria for LTx in non-CF and CF populations should be considered.

Use of Lung Allografts from Brain-Dead Donors after Cardiopulmonary Arrest and Resuscitation

PubMed Central

Worni, Mathias; Osho, Asishana A.; Snyder, Laurie D.; Palmer, Scott M.; Pietrobon, Ricardo; Davis, R. Duane; Hartwig, Matthew G.

2013-01-01

Rationale: Patients who progress to brain death after resuscitation from cardiac arrest have been hypothesized to represent an underused source of potential organ donors; however, there is a paucity of data regarding the viability of lung allografts after a period of cardiac arrest in the donor. Objectives: To analyze postoperative complications and survival after lung transplant from brain-dead donors resuscitated after cardiac arrest. Methods: The United Network for Organ Sharing database records donors with cardiac arrest occurring after brain death. Adult recipients of lung allografts from these arrest/resuscitation donors between 2005 and 2011 were compared with nonarrest donors. Propensity score matching was used to reduce the effect of confounding. Postoperative complications and overall survival were assessed using McNemar’s test for correlated binary proportions and Kaplan–Meier methods. Measurements and Main Results: A total of 479 lung transplant recipients from arrest/resuscitation donors were 1:1 propensity matched from a cohort of 9,076 control subjects. Baseline characteristics in the 1:1-matched cohort were balanced. There was no significant difference in perioperative mortality, airway dehiscence, dialysis requirement, postoperative length of stay (P ≥ 0.38 for all), or overall survival (P = 0.52). A subanalysis of the donor arrest group demonstrated similar survival when stratified by resuscitation time quartile (P = 0.38). Conclusions: There is no evidence of inferior outcomes after lung transplant from brain-dead donors who have had a period of cardiac arrest provided that good lung function is preserved and the donor is otherwise deemed acceptable for transplantation. Potential expansion of the donor pool to include cardiac arrest as the cause of brain death requires further study. PMID:23777361

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

PubMed Central

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

2014-01-01

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

Solid organ allograft survival improvement in the United States: the long-term does not mirror the dramatic short-term success.

PubMed

Lodhi, S A; Lamb, K E; Meier-Kriesche, H U

2011-06-01

Organ survival in the short-term period post-transplant has improved dramatically over the past few decades. Whether this has translated to a long-term survival benefit remains unclear. This study quantifies the progression of nonrenal solid organ transplant outcomes from 1989 to 2009 in liver, lung, heart, intestine and pancreas transplants. Long-term graft survival was analyzed using data on adult solid organ transplant recipients from the UNOS/SRTR database and is reported as organ half-life and yearly attrition rates. Liver, lung, heart, intestine and pancreas half-lives have improved from 5.8 to 8.5, 1.7 to 5.2, 8.8 to 11, 2.1 to 3.6 and 10.5 to 16.7 years, respectively. Long-term attrition rates have not shown the same consistent improvement, with the yearly attrition rate 5-10 years post-transplant for liver, lung, heart and pancreas changing from 4.7 to 4.3, 10.9 to 10.1, 6.4 to 5.1 and 3.3 to 4.2, respectively. Attrition rates for intestine and pancreas transplantation alone display more variability due to smaller sample size but exhibit similar trends of improved first-year attrition and relatively stagnant long-term attrition rates. With first-year survival and attrition rates almost at a pinnacle, further progress in long-term survival will come from targeting endpoints beyond first-year rejection and survival rates. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Importance of the lung perfusion scintigraphy in single lung transplantation.

PubMed

Rodríguez Mesa, N V; Guerrero Cancio, M C; Cordero Jiménez, M D; Alvarez Velázquez, I K

2012-01-01

Lung perfusion scintigraphy (LPS) with (99m)Tc-MAA gives valuable information about patients who will undergo a single lung transplantation. This technique makes it possible to evaluate and quantify the relative function of both lungs to select the organ to be transplanted. Once the surgery has been performed, the LPS represents a diagnostic method to study the status of the transplanted organ. Two patients who underwent single lung transplantation were studied in our hospital. In both cases, a pre-operative LPS was performed before surgery for selection of the organ to be transplanted and the scintigraphy study was performed a few months after transplantation to establish the perfusion function of the transplanted lung. Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.

Strategies for safe donor expansion: donor management, donations after cardiac death, ex-vivo lung perfusion.

PubMed

Cypel, Marcelo; Keshavjee, Shaf

2013-10-01

The number of patients listed for lung transplantation largely exceeds the number of available transplantable organs because of both a shortage of organ donors and a low utilization rate of lungs from those donors. Two major innovations in recent years include the use of lungs from donations after cardiac death (DCD) and the use of ex-vivo lung perfusion (EVLP) to assess and improve injured donor lungs. DCD lung transplants now account for about 20% of lung transplants in many centres and outcomes after transplantation have been excellent with this source of donation. Clinical experience using EVLP has shown the method to be well tolerated and allow for reassessment and improvement in function from high-risk donor lungs. When these lungs were transplanted, low rates of primary graft dysfunction were achieved and long-term survival was comparable with standard transplantation. Preclinical studies have shown a great potential of EVLP as a platform for the delivery of novel therapies to repair injured donor lungs. A significant increase on the number of available lungs for transplantation is expected in the coming years with the wider use of DCD lungs and with organ-specific ex-vivo treatment strategies.

Lung Transplantation for Cystic Fibrosis

PubMed Central

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

2009-01-01

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

Technology and outcomes assessment in lung transplantation.

PubMed

Yusen, Roger D

2009-01-15

Lung transplantation offers the hope of prolonged survival and significant improvement in quality of life to patients that have advanced lung diseases. However, the medical literature lacks strong positive evidence and shows conflicting information regarding survival and quality of life outcomes related to lung transplantation. Decisions about the use of lung transplantation require an assessment of trade-offs: do the potential health and quality of life benefits outweigh the potential risks and harms? No amount of theoretical reasoning can resolve this question; empiric data are needed. Rational analyses of these trade-offs require valid measurements of the benefits and harms to the patients in all relevant domains that affect survival and quality of life. Lung transplant systems and registries mainly focus outcomes assessment on patient survival on the waiting list and after transplantation. Improved analytic approaches allow comparisons of the survival effects of lung transplantation versus continued waiting. Lung transplant entities do not routinely collect quality of life data. However, the medical community and the public want to know how lung transplantation affects quality of life. Given the huge stakes for the patients, the providers, and the healthcare systems, key stakeholders need to further support quality of life assessment in patients with advanced lung disease that enter into the lung transplant systems. Studies of lung transplantation and its related technologies should assess patients with tools that integrate both survival and quality of life information. Higher quality information obtained will lead to improved knowledge and more informed decision making.

True survival benefit of lung transplantation for cystic fibrosis patients: the Zurich experience.

PubMed

Hofer, Markus; Benden, Christian; Inci, Ilhan; Schmid, Christoph; Irani, Sarosh; Speich, Rudolf; Weder, Walter; Boehler, Annette

2009-04-01

Lung transplantation is the ultimate therapy for end-stage cystic fibrosis (CF) lung disease; however, the debate continues as to whether lung transplantation improves survival. We report post-transplant outcome in CF at our institution by comparing 5-year post-transplant survival with a calculated 5-year survival without lung transplantation, using a predictive 5-year survivorship model, and describe pre-transplant parameters influencing transplant outcome. CF patients undergoing lung transplantation at our center were included (1992 to 2007). Survival rates were calculated and compared, and univariate and multivariate Cox regression analyses were used for statistical assessment. Eighty transplants were performed in CF patients, 11 (13.8%) of whom were children. Mean age at transplant was 26.2 years (95% confidence interval: 24.4 to 28.0). The Liou raw score at transplant was -20 (95% confidence interval: -16 to -24), resulting in an estimated 5-year survival without transplantation of 33 +/- 14%, compared with a 5-year post-transplant survival of 68.2 +/- 5.6%. Further improvement was noted in the recent transplant era (since 2000), with a 5-year survival of 72.7 +/- 7.3%. Univariate analysis revealed that later year of transplant and diagnosis of diabetes influenced survival positively. Pediatric age had no negative impact. In the multivariate analysis, only diabetes influenced survival, in a positive manner. Lung transplantation performed at centers having experience with the procedure can offer a true survival benefit to patients with end-stage CF lung disease.

Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients

PubMed Central

Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan

2015-01-01

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

Heart and lung transplantation in the United States, 1996-2005.

PubMed

Garrity, E R; Moore, J; Mulligan, M S; Shearon, T H; Zucker, M J; Murray, S

2007-01-01

This article examines the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients data on heart and lung transplantation in the United States from 1996 to 2005. The number of heart transplants performed and the size of the heart waiting list continued to drop, reaching 2126 and 1334, respectively, in 2005. Over the decade, post-transplant graft and patient survival improved, as did the chances for survival while on the heart waiting list. The number of deceased donor lung transplants increased by 78% since 1996, reaching 1407 in 2005 (up 22% from 2004). There were 3170 registrants awaiting lung transplantation at the end of 2005, down 18% from 2004. Death rates for both candidates and recipients have been dropping, as has the time spent waiting for a lung transplant. Other lung topics covered are living donation, recent surgical advances and changes in immunosuppression regimens. Heart-lung transplantation has declined to a small (33 procedures in 2005) but important need in the United States.

Pediatric lung transplantation and end of life care in cystic fibrosis: Barriers and successful strategies.

PubMed

Dellon, Elisabeth; Goldfarb, Samuel B; Hayes, Don; Sawicki, Gregory S; Wolfe, Joanne; Boyer, Debra

2017-11-01

Pediatric lung transplantation has advanced over the years, providing a potential life-prolonging therapy to patients with cystic fibrosis. Despite this, many challenges in lung transplantation remain and result in worse outcomes than other solid organ transplants. As CF lung disease progresses, children and their caregivers are often simultaneously preparing for lung transplantation and end of life. In this article, we will discuss the current barriers to success in pediatric CF lung transplantation as well as approaches to end of life care in this population. © 2017 Wiley Periodicals, Inc.

Factors affecting graft survival within 1-year post-transplantation in heart and lung transplant: an analysis of the OPTN/UNOS registry.

PubMed

Ohe, Hidenori

2012-01-01

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.

Lung transplantation

PubMed Central

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

2015-01-01

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

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

PubMed

Egan, T M; Requard, J J

2015-08-01

In April 2014, the American Journal of Transplantation published a report on the first lung transplant in the United States recovered from an uncontrolled donation after circulatory determination of death donor (uDCDD), assessed by ex vivo lung perfusion (EVLP). The article identified logistical and ethical issues related to introduction of lung transplant from uDCDDs. In an open clinical trial, we have Food and Drug Administration and Institutional Review Board approval to transplant lungs recovered from uDCDDs judged suitable after EVLP. Through this project and other experiences with lung recovery from uDCDDs, we have identified solutions to many logistical challenges and have addressed ethical issues surrounding lung transplant from uDCDDs that were mentioned in this case report. Here, we discuss those challenges, including issues related to recovery of other solid organs from uDCDDs. Despite logistical challenges, uDCDDs could solve the critical shortage of lungs for transplant. Furthermore, by avoiding the deleterious impact of brain death and days of positive pressure ventilation, and by using opportunities to treat lungs in the decedent or during EVLP, lungs recovered from uDCDDs may ultimately prove to be better than lungs currently being transplanted from conventional brain-dead organ donors. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Effect of the lung allocation score on lung transplantation in the United States.

PubMed

Egan, Thomas M; Edwards, Leah B

2016-04-01

On May 4, 2005, the system for allocation of deceased donor lungs for transplant in the United States changed from allocation based on waiting time to allocation based on the lung allocation score (LAS). We sought to determine the effect of the LAS on lung transplantation in the United States. Organ Procurement and Transplantation Network data on listed and transplanted patients were analyzed for 5 calendar years before implementation of the LAS (2000-2004), and compared with data from 6 calendar years after implementation (2006-2011). Counts were compared between eras using the Wilcoxon rank sum test. The rates of transplant increase within each era were compared using an F-test. Survival rates computed using the Kaplan-Meier method were compared using the log-rank test. After introduction of the LAS, waitlist deaths decreased significantly, from 500/year to 300/year; the number of lung transplants increased, with double the annual increase in rate of lung transplants, despite no increase in donors; the distribution of recipient diagnoses changed dramatically, with significantly more patients with fibrotic lung disease receiving transplants; age of recipients increased significantly; and 1-year survival had a small but significant increase. Allocating lungs for transplant based on urgency and benefit instead of waiting time was associated with fewer waitlist deaths, more transplants performed, and a change in distribution of recipient diagnoses to patients more likely to die on the waiting list. Copyright © 2016 International Society for Heart and Lung Transplantation. All rights reserved.

Long-term outcomes of children after solid organ transplantation

PubMed Central

Kim, Jon Jin; Marks, Stephen D.

2014-01-01

Solid organ transplantation has transformed the lives of many children and adults by providing treatment for patients with organ failure who would have otherwise succumbed to their disease. The first successful transplant in 1954 was a kidney transplant between identical twins, which circumvented the problem of rejection from MHC incompatibility. Further progress in solid organ transplantation was enabled by the discovery of immunosuppressive agents such as corticosteroids and azathioprine in the 1950s and ciclosporin in 1970. Today, solid organ transplantation is a conventional treatment with improved patient and allograft survival rates. However, the challenge that lies ahead is to extend allograft survival time while simultaneously reducing the side effects of immunosuppression. This is particularly important for children who have irreversible organ failure and may require multiple transplants. Pediatric transplant teams also need to improve patient quality of life at a time of physical, emotional and psychosocial development. This review will elaborate on the long-term outcomes of children after kidney, liver, heart, lung and intestinal transplantation. As mortality rates after transplantation have declined, there has emerged an increased focus on reducing longer-term morbidity with improved outcomes in optimizing cardiovascular risk, renal impairment, growth and quality of life. Data were obtained from a review of the literature and particularly from national registries and databases such as the North American Pediatric Renal Trials and Collaborative Studies for the kidney, SPLIT for liver, International Society for Heart and Lung Transplantation and UNOS for intestinal transplantation. PMID:24860856

Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation

PubMed Central

El-Chemaly, Souheil; O’Brien, Kevin J.; Nathan, Steven D.; Weinhouse, Gerald L.; Goldberg, Hilary J.; Connors, Jean M.; Cui, Ye; Astor, Todd L.; Camp, Philip C.; Rosas, Ivan O.; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A.; Gahl, William A.

2018-01-01

Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants. PMID:29547626

Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation.

PubMed

El-Chemaly, Souheil; O'Brien, Kevin J; Nathan, Steven D; Weinhouse, Gerald L; Goldberg, Hilary J; Connors, Jean M; Cui, Ye; Astor, Todd L; Camp, Philip C; Rosas, Ivan O; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A; Gahl, William A; Gochuico, Bernadette R

2018-01-01

Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants.

Donor predicted post-operative forced expiratory volume in one second predicts recipients' best forced expiratory volume in one second following size-reduced lung transplantation.

PubMed

Inci, Ilhan; Irani, Sarosh; Kestenholz, Peter; Benden, Christian; Boehler, Annette; Weder, Walter

2011-01-01

The limited number of available grafts is one of the major obstacles of lung transplantation. Size-reduced lung transplantation allows the use of oversized grafts for small recipients. Optimal lung size matching is vital to achieve best functional outcome and avoid potential problems when using oversized grafts. We hypothesise that donor-predicted postoperative forced expiratory volume in 1s (ppoFEV1) correlates with the recipient best FEV1 after size-reduced lung transplant, being useful for the estimation of function outcome. All patients undergoing size-reduced or standard bilateral lung transplantation were included (1992-2007). Donor ppoFEV1 was calculated and corrected with respect to size reduction and correlated with recipient measured best FEV1 post-transplant. In addition, pre- and postoperative clinical data including surgical complications and outcome of all size-reduced lung transplant recipients were compared with standard lung transplant recipients. A total of 61 size-reduced lung transplant recipients (lobar transplants, n=20; anatomic or non-anatomic resection, n=41) were included and compared to 145 standard transplants. The mean donor-recipient height difference was statistically significant between the two groups (p=0.0001). The mean donor ppoFEV1 was comparable with recipient best FEV1 (2.7±0.6 vs 2.6±0.7 l). There was a statistically significant correlation between donor ppoFEV1 and recipient best FEV1 (p=0.01, r=0.688). The 30-day mortality rate and 3-month, 1- and 5-year survival rates were comparable between the two groups. In size-reduced lung transplantation, postoperative recipient best FEV1 could be predicted from donor-calculated and corrected FEV1 with respect to its size reduction. Compared to standard lung transplantation, equivalent morbidity, mortality and functional results could be obtained after size-reduced lung transplantation. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Incidence of late atrial fibrillation in bilateral lung versus heart transplants.

PubMed

Magruder, J Trent; Plum, William; Crawford, Todd C; Grimm, Joshua C; Borja, Marvin C; Berger, Ronald D; Tandri, Harikrishna; Calkins, Hugh; Cameron, Duke E; Mandal, Kaushik

2016-10-01

We compared the incidence of late-onset atrial fibrillation in orthotopic heart transplant recipients and bilateral orthotopic lung transplant recipients. We reviewed the records of all heart and lung transplant operations carried out in our institution between 1995 and 2015. We performed 1:1 propensity-matching based on patient age, sex, body mass index, and hypertension. Our primary outcome, late-onset atrial fibrillation, was defined as atrial fibrillation occurring after discharge following hospitalization for transplantation. Over the study period, 397 orthotopic heart transplants and 240 bilateral orthotopic lung transplants were performed. Propensity matching resulted in 173 pairs who were matched with respect to age, sex, body mass index, and preoperative hypertension. The median follow-up was 5.3 years for heart transplant patients and 3.1 years for lung transplant patients. Late-onset atrial fibrillation occurred in 11 heart transplant patients (5 of whom had biopsy-proven evidence of rejection) and 19 lung transplant patients (2 of whom had biopsy-proven evidence of rejection). On Kaplan-Meier analysis, the probability of late-onset atrial fibrillation at 5 years was 4.3% for heart transplant patients vs. 13.9% for lung transplant patients (log-rank p = 0.01). We documented an increased probability of late-onset atrial fibrillation among bilateral orthotopic lung transplant patients compared to orthotopic heart transplant patients. This was a hypothesis-generating study that suggests a potential role for cardiac autonomic innervation in the genesis of atrial fibrillation. © The Author(s) 2016.

Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

PubMed Central

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

2016-01-01

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

Continued increase in lung transplantation for coal workers' pneumoconiosis in the United States.

PubMed

Blackley, David J; Halldin, Cara N; Laney, A Scott

2018-05-06

Severe coal workers' pneumoconiosis (CWP) is increasingly common, and sometimes requires lung transplantation. Using Organ Procurement and Transplantation Network data, we updated the trend for CWP-related lung transplants, described CWP patients who have been waitlisted but not transplanted, and characterized the primary payer of medical costs for CWP-related and other occupational lung disease transplants. There have been at least 62 CWP-related lung transplants; 49 (79%) occurred in the last decade. The rate of these procedures has also increased. Twenty-seven patients were waitlisted but did not receive a transplant. Compared to other occupational lung diseases, transplants for CWP were more likely to be paid for by public insurance. The increase in the frequency and rate of lung transplantation for CWP is consistent with the rising prevalence of severe CWP among U.S. coal miners. Effective exposure controls and identification of early stage CWP remain essential for protecting these workers. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

Lung transplantation for non-cystic fibrosis bronchiectasis: analysis of a 13-year experience.

PubMed

Beirne, Paul Adrian; Banner, Nicholas R; Khaghani, Asghar; Hodson, Margaret E; Yacoub, Magdi H

2005-10-01

Lung transplantation is a well-established treatment for end-stage cystic fibrosis, and there are considerable data on medium- and long-term results. However, less information exists about transplantation for non-cystic fibrosis bronchiectasis. Between December 1988 and June 2001, 22 patients (12 men, 10 women) underwent transplantation for bronchiectasis not due to cystic fibrosis. Procedures were bilateral sequential single-lung transplants (BSSLTX) in 4 patients, en bloc double lung transplants (DLTX) in 5, heart-lung transplants (HLTX) in 6, and single-lung transplants (SLTX) in 7. Lifelong outpatient follow-up was continued at a minimum of every 6 months. One-year Kaplan-Meier survival for all patients was 68% (95% confidence interval [CI], 54%-91%), and 5-year survival was 62% (95% CI, 41-83%). One-year survival after SLTX was 57% (95% CI, 20%-94%) vs 73% (95% CI, 51-96%) for those receiving 2 lungs. At 6 months, mean forced expiratory volume in 1 second was 73% predicted (range, 58%-97%), and mean forced vital capacity was 68% predicted (range, 53%-94%) after receiving 2 lungs (n = 10); in the SLTX group at 6 months, mean forced expiratory volume in 1 second was 50% predicted (range, 34%-61%), and mean forced vital capacity was 53% predicted (range 46-63%) (n = 4). Survival and lung function after transplantation for non-cystic fibrosis bronchiectasis was similar to that after transplantation for cystic fibrosis. A good outcome is possible after single lung transplantation in selected patients.

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

PubMed Central

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

2016-01-01

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

Skeletal muscle strength and endurance in recipients of lung transplants.

PubMed

Mathur, Sunita; Levy, Robert D; Reid, W Darlene

2008-09-01

Exercise limitation in recipients of lung transplant may be a result of abnormalities in the skeletal muscle. However, it is not clear whether these abnormalities are merely a reflection of the changes observed in the pretransplant condition. The purpose of this paper was to compare thigh muscle volume and composition, strength, and endurance in lung transplant recipients to people with chronic obstructive pulmonary disease (COPD). Single lung transplant recipients (n=6) and people with COPD (n=6), matched for age, sex, and BMI participated in the study. Subjects underwent MRI to determine muscle size and composition, lower extremity strength testing and an isometric endurance test of the quadriceps. Lung transplant recipients had similar muscle volumes and intramuscular fat infiltration of their thigh muscles and similar strength of the quadriceps and hamstrings to people with COPD who had not undergone transplant. However, quadriceps endurance tended to be lower in transplant recipients compared to people with COPD (15 +/- 7 seconds in transplant versus 31 +/- 12 seconds in COPD, p = 0.08). Recipients of lung transplant showed similar changes in muscle size and strength as people with COPD, however muscle endurance tended to be lower in people with lung transplants. Impairments in muscle endurance may reflect the effects of immunosuppressant medications on skeletal muscle in people with lung transplant.

Clinical outcomes of lung transplant recipients with telomerase mutations.

PubMed

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

2015-10-01

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 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The 2018 ISHLT/APM/AST/ICCAC/STSW recommendations for the psychosocial evaluation of adult cardiothoracic transplant candidates and candidates for long-term mechanical circulatory support.

PubMed

Dew, Mary Amanda; DiMartini, Andrea F; Dobbels, Fabienne; Grady, Kathleen L; Jowsey-Gregoire, Sheila G; Kaan, Annemarie; Kendall, Kay; Young, Quincy-Robyn; Abbey, Susan E; Butt, Zeeshan; Crone, Catherine C; De Geest, Sabina; Doligalski, Christina T; Kugler, Christiane; McDonald, Laurie; Ohler, Linda; Painter, Liz; Petty, Michael G; Robson, Desiree; Schlöglhofer, Thomas; Schneekloth, Terry D; Singer, Jonathan P; Smith, Patrick J; Spaderna, Heike; Teuteberg, Jeffrey J; Yusen, Roger D; Zimbrean, Paula C

2018-04-27

The psychosocial evaluation is well-recognized as an important component of the multifaceted assessment process to determine candidacy for heart transplantation, lung transplantation, and long-term mechanical circulatory support (MCS). However, there is no consensus-based set of recommendations for either the full range of psychosocial domains to be assessed during the evaluation, or the set of processes and procedures to be used to conduct the evaluation, report its findings, and monitor patients' receipt of and response to interventions for any problems identified. This document provides recommendations on both evaluation content and process. It represents a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT) and the Academy of Psychosomatic Medicine, American Society of Transplantation, International Consortium of Circulatory Assist Clinicians, and Society for Transplant Social Workers. The Nursing, Health Science and Allied Health Council of the ISHLT organized a Writing Committee composed of international experts representing the ISHLT and the collaborating societies. This Committee synthesized expert opinion and conducted a comprehensive literature review to support the psychosocial evaluation content and process recommendations that were developed. The recommendations are intended to dovetail with current ISHLT guidelines and consensus statements for the selection of candidates for cardiothoracic transplantation and MCS implantation. Moreover, the recommendations are designed to promote consistency across programs in the performance of the psychosocial evaluation by proposing a core set of content domains and processes that can be expanded as needed to meet programs' unique needs and goals. Copyright © 2018 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Heart-lung transplant - slideshow

MedlinePlus

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

Impact of Obesity on Heart and Lung Transplantation: Does Pre-Transplant Obesity Affect Outcomes?

PubMed

Bozso, S J; Nagendran, Je; Gill, R S; Freed, D H; Nagendran, Ja

2017-03-01

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Under Utilization of Pancreas Transplants in Cystic Fibrosis Recipients in the United Network Organ Sharing (UNOS) Data 1987-2014.

PubMed

Usatin, D J; Perito, E R; Posselt, A M; Rosenthal, P

2016-05-01

Despite a high prevalence of pancreatic endocrine and exocrine insufficiency in cystic fibrosis (CF), pancreas transplantation is rarely reported. United Network for Organ Sharing (UNOS) data were used to examine utilization of pancreas transplant and posttransplant outcomes in CF patients. Between 1987-2014, CF patients (N = 4600) underwent 17 liver-pancreas, three lung-pancreas, one liver-lung pancreas, four kidney-pancreas, and three pancreas-only transplants. Of the 303 CF patients who received liver transplantation, 20% had CF-related diabetes (CFRD) before transplantation, and nine of those received a liver-pancreas transplant. Of 4241 CF patients who underwent lung transplantation, 33% had CFRD before transplantation, and three of those received a pancreas transplant. Of 49 CF patients who received a liver-lung transplant, 57% had CFRD before transplantation and one received a pancreas transplant. Posttransplantation diabetes developed in 7% of CF pancreas transplant recipients versus 24% of CF liver and 29% of CF lung recipients. UNOS has no data on pancreas exocrine insufficiency. Two-year posttransplantation survival was 88% after liver-pancreas transplant, 33% after lung-pancreas transplant, and 100% after pancreas-kidney and pancreas-only transplants. Diabetes is common pretransplantation and posttransplantation in CF solid organ transplant recipients, but pancreas transplantation remains rare. Further consideration of pancreas transplant in CF patients undergoing other solid organ transplant may be warranted. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Surgical lung biopsy in transplant patients with diffuse lung disease: how much worse when the lung is the graft?

PubMed

Bertolotti, Alejandro; Defranchi, Sebastián; Vigliano, Carlos; Haberman, Diego; Favaloro, Roberto

2013-07-01

There are no data that compare the clinical presentation and results of surgical lung biopsy (SLB) for diffuse lung disease (DLD) in lung transplant patients, in contrast to individuals with other type of solid organ grafts. Our objective was to compare the clinical picture, radiologic pattern, pathology results, and outcomes of SLB for DLD in these two subsets of patients. We retrospectively reviewed the clinical records of transplant patients undergoing SLB for DLD at our institution between 2004 and 2011. Patients with lung transplants and those with other transplants were compared. During the study period, 1,232 solid organ transplants were done at our institution. Of these, 49 patients (4%) had DLD that needed SLB for diagnosis, and 24 of these patients had a lung transplant. Dyspnea and a radiologic reticular pattern were more frequent in lung transplant patients, 21 of 24 vs 11 of 25 (p = 0.001) and 14 of 24 vs 7 of 25 (p = 0.03), respectively. Although postoperative complications and in-hospital deaths were more common in lung transplant patients, the differences were not statistically significant. Having the SLB performed for diagnosis, as opposed to being conducted for DLD that did not improve on medical treatment, had a protective effect on multivariate analysis (hazard ratio, 0.39; 95% confidence interval, 0.16 to 0.96; p = 0.042). A prior lung transplant was the only independent predictor of survival (hazard ratio, 4.62; 95% confidence interval, 1.53 to 13.92, p = 0.006). It is relatively uncommon for a solid organ transplant patient with DLD to require a SLB. Clinical and radiologic presentation differ in patients with lung transplants compared with other transplants. Postoperative outcomes are not significantly different between the groups. SLB performed early in the course of the disease might be beneficial. Having a lung transplant is a significant negative predictor of survival. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

WHAT MAKES A GOOD PEDIATRIC TRANSPLANT LUNG: INSIGHTS FROM IN VIVO LUNG MORPHOMETRY WITH HYPERPOLARIZED 3HE MRI (WHAT MAKES A GOOD PEDIATRIC TRANSPLANT LUNG)

PubMed Central

Fishman, Emily F.; Quirk, James D.; Sweet, Stuart C.; Woods, Jason C.; Gierada, David S.; Conradi, Mark S.; Siegel, Marilyn J.; Yablonskiy, Dmitriy A.

2016-01-01

Background Obtaining information on transplanted lung microstructure is an important part of the current care for monitoring transplant recipients. However, until now this information was only available from invasive lung biopsy. The objective of this study was to evaluate the use of an innovative non-invasive technique in vivo lung morphometry with hyperpolarized 3He MRI - to characterize lung microstructure in the pediatric lung transplant population. This technique yields quantitative measurements of acinar airways’ (alveolar ducts and sacs) parameters, such as acinar airways radii and alveolar depth. Methods Six pediatric lung transplant recipients with cystic fibrosis underwent in vivo lung morphometry MRI, pulmonary function testing, and quantitative CT. Results We found a strong correlation between lung lifespan and alveolar depth - patients with more shallow alveoli were likely to have a negative outcome sooner than those with larger alveolar depth. Combining morphometric results with CT we also determined mean alveolar wall thickness and found substantial increases in this parameter in some patients that negatively correlated with DLCO. Conclusion In vivo lung morphometry uniquely provides previously unavailable information on lung microstructure that may be predictive of a negative outcome and has a potential to aid in lung selection for transplantation. PMID:28120553

Coccidioidomycosis among persons undergoing lung transplantation in the coccidioidal endemic region.

PubMed

Chaudhary, Sachin; Meinke, Laura; Ateeli, Huthayfa; Knox, Kenneth S; Raz, Yuval; Ampel, Neil M

2017-08-01

Coccidioidomycosis, an endemic fungal infection, is more likely to be symptomatic and severe among those receiving allogeneic transplants. While several case series have been published for various transplanted organs, none has described the incidence and outcomes in those receiving lung transplants within the coccidioidal endemic region. Patients receiving a heart-lung, single-lung, or bilateral-lung transplantation at the University of Arizona between 1985 and 2009 were retrospectively reviewed. Coccidioidomycosis occurred post transplantation in 11 (5.8%) of 189 patients. All but one patient was diagnosed with pulmonary coccidioidomycosis and only one had a history of prior coccidioidomycosis. Two patients received transplants from donors found to have coccidioidomycosis at the time of transplantation and one death was directly attributed to coccidioidomycosis. The risk of developing active coccidioidomycosis was significantly higher if the patient did not receive some type of antifungal therapy post transplantation (P<.001). Within the coccidioidal endemic region, post-transplantation coccidioidomycosis was a definable risk among lung transplant recipients. Use of antifungals appeared to reduce this incidence of disease. Almost all cases resulted in pulmonary disease, suggesting that the lung is the primary site of infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed Central

Egan, T. M.; Requard, J. J.

2017-01-01

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

Implementation of a cystic fibrosis lung transplant referral patient decision aid in routine clinical practice: an observational study.

PubMed

Stacey, Dawn; Vandemheen, Katherine L; Hennessey, Rosamund; Gooyers, Tracy; Gaudet, Ena; Mallick, Ranjeeta; Salgado, Josette; Freitag, Andreas; Berthiaume, Yves; Brown, Neil; Aaron, Shawn D

2015-02-07

The decision to have lung transplantation as treatment for end-stage lung disease from cystic fibrosis (CF) has benefits and serious risks. Although patient decision aids are effective interventions for helping patients reach a quality decision, little is known about implementing them in clinical practice. Our study evaluated a sustainable approach for implementing a patient decision aid for adults with CF considering referral for lung transplantation. A prospective pragmatic observational study was guided by the Knowledge-to-Action Framework. Healthcare professionals in all 23 Canadian CF clinics were eligible. We surveyed participants regarding perceived barriers and facilitators to patient decision aid use. Interventions tailored to address modifiable identified barriers included training, access to decision aids, and conference calls. The primary outcome was >80% use of the decision aid in year 2. Of 23 adult CF clinics, 18 participated (78.2%) and 13 had healthcare professionals attend training. Baseline barriers were healthcare professionals' inadequate knowledge for supporting patients making decisions (55%), clarifying patients' values for outcomes of options (58%), and helping patients handle conflicting views of others (71%). Other barriers were lack of time (52%) and needing to change how transplantation is discussed (42%). Baseline facilitators were healthcare professionals feeling comfortable discussing bad transplantation outcomes (74%), agreeing the decision aid would be easy to experiment with (71%) and use in the CF clinic (87%), and agreeing that using the decision aid would not require reorganization of the CF clinic (90%). After implementing the decision aid with interventions tailored to the barriers, decision aid use increased from 29% at baseline to 85% during year 1 and 92% in year 2 (p < 0.001). Compared to baseline, more healthcare professionals at the end of the study were confident in supporting decision-making (p = 0.03) but continued to feel inadequate ability with supporting patients to handle conflicting views (p = 0.01). Most Canadian CF clinics agreed to participate in the study. Interventions were used to target identified modifiable barriers to using the patient decision aid in routine CF clinical practice. CF clinics reported using it with almost all patients in the second year.

Monitoring of early humoral immunity to identify lung recipients at risk for development of serious infections: A multicenter prospective study.

PubMed

Sarmiento, Elizabeth; Cifrian, Jose; Calahorra, Leticia; Bravo, Carles; Lopez, Sonia; Laporta, Rosalia; Ussetti, Piedad; Sole, Amparo; Morales, Carmen; de Pablos, Alicia; Jaramillo, Maria; Ezzahouri, Ikram; García, Sandra; Navarro, Joaquin; Lopez-Hoyos, Marcos; Carbone, Javier

2018-04-06

Infection is still a leading cause of death during the first year after lung transplantation. We performed a multicenter study among teaching hospitals to assess monitoring of early humoral immunity as a means of identifying lung recipients at risk of serious infections. We prospectively analyzed 82 adult lung recipients at 5 centers in Spain. Data were collected before transplantation and at 7 and 30 days after transplantation. Biomarkers included IgG, IgM, IgA, complement factors C3 and C4, titers of antibodies to pneumococcal polysaccharide antigens (IgG, IgA, IgM) and antibodies to cytomegalovirus (IgG), and serum B-cell activating factor (BAFF) levels. The clinical follow-up period lasted 6 months. Clinical outcomes were bacterial infections requiring intravenous anti-microbial agents, cytomegalovirus (CMV) disease, and fungal infections requiring therapy. We found that 33 patients (40.2%) developed at least 1 serious bacterial infection, 8 patients (9.8%) had CMV disease, and 10 patients (12.2%) had fungal infections. Lower IgM antibody levels against pneumococcal polysaccharide antigens at Day 7 (defined as <5 mg/dl) were a risk factor for serious bacterial infection (adjusted odds ratio [OR] 3.96; 95% confidence interval [CI] 1.39 to 11.26; p = 0.0099). At Day 7 after transplantation, IgG hypogammaglobulinemia (defined as IgG <600 mg/dl) was associated with a higher risk of CMV disease (after adjustment for CMV mismatch: OR 8.15; 95% CI 1.27 to 52.55; p = 0.028) and fungal infection (adjusted OR 8.03, 95% CI 1.51 to 42.72; p = 0.015). Higher BAFF levels before transplantation were associated with a higher rate of development of serious bacterial infection and acute cellular rejection. Early monitoring of specific humoral immunity parameters proved useful for the identification of lung recipients who are at risk of serious infections. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

A Multicenter Study on Long-Term Outcomes After Lung Transplantation Comparing Donation After Circulatory Death and Donation After Brain Death.

PubMed

van Suylen, V; Luijk, B; Hoek, R A S; van de Graaf, E A; Verschuuren, E A; Van De Wauwer, C; Bekkers, J A; Meijer, R C A; van der Bij, W; Erasmus, M E

2017-10-01

The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the initial standard use of donation after brain death (DBD) lungs. From the three lung transplant centers in the Netherlands, 130 DCD3 recipients were one-to-one nearest neighbor propensity score matched with 130 DBD recipients. The primary end points were primary graft dysfunction (PGD), posttransplant lung function, freedom from chronic lung allograft dysfunction (CLAD), and overall survival. PGD did not differ between the groups. Posttransplant lung function was comparable after bilateral lung transplantation, but seemed worse after DCD3 single lung transplantation. The incidence of CLAD (p = 0.17) nor the freedom from CLAD (p = 0.36) nor the overall survival (p = 0.40) were significantly different between both groups. The presented multicenter results are derived from a national context where one third of the lung transplantations are performed with DCD3 lungs. We conclude that the long-term outcome after lung transplantation with DCD3 donors is similar to that of DBD donors and that DCD3 donation can substantially enlarge the donor pool. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Long-term outcomes and management of lung transplant recipients.

PubMed

Costa, Joseph; Benvenuto, Luke J; Sonett, Joshua R

2017-06-01

Lung transplantation is an established treatment for patients with end-stage lung disease. Improvements in immunosuppression and therapeutic management of infections have resulted in improved long-term survival and a decline in allograft rejection. Allograft rejection continues to be a serious complication following lung transplantation, thereby leading to acute graft failure and, subsequently, chronic lung allograft dysfunction (CLAD). Bronchiolitis obliterans syndrome (BOS), the most common phenotype of CLAD, is the leading cause of late mortality and morbidity in lung recipients, with 50% having developed BOS within 5 years of lung transplantation. Infections in lung transplant recipients are also a significant complication and represent the most common cause of death within the first year. The success of lung transplantation depends on careful management of immunosuppressive regimens to reduce the rate of rejection, while monitoring recipients for infections and complications to help identify problems early. The long-term outcomes and management of lung transplant recipients are critically based on modulating natural immune response of the recipient to prevent acute and chronic rejection. Understanding the immune mechanisms and temporal correlation of acute and chronic rejection is thus critical in the long-term management of lung recipients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coming to terms with tissue engineering and regenerative medicine in the lung

PubMed Central

Tschumperlin, Daniel J.; Stenmark, Kurt R.

2015-01-01

Lung diseases such as emphysema, interstitial fibrosis, and pulmonary vascular diseases cause significant morbidity and mortality, but despite substantial mechanistic understanding, clinical management options for them are limited, with lung transplantation being implemented at end stages. However, limited donor lung availability, graft rejection, and long-term problems after transplantation are major hurdles to lung transplantation being a panacea. Bioengineering the lung is an exciting and emerging solution that has the ultimate aim of generating lung tissues and organs for transplantation. In this article we capture and review the current state of the art in lung bioengineering, from the multimodal approaches, to creating anatomically appropriate lung scaffolds that can be recellularized to eventually yield functioning, transplant-ready lungs. Strategies for decellularizing mammalian lungs to create scaffolds with native extracellular matrix components vs. de novo generation of scaffolds using biocompatible materials are discussed. Strengths vs. limitations of recellularization using different cell types of various pluripotency such as embryonic, mesenchymal, and induced pluripotent stem cells are highlighted. Current hurdles to guide future research toward achieving the clinical goal of transplantation of a bioengineered lung are discussed. PMID:26254424

[1990-1996: the experience of the La Fe Lung Transplant Group (Valencia)].

PubMed

Borro Maté, J M; Morales Marín, P; Lozano Ruiz, C; Tarrazona Hervás, V; Galán Gil, G; Calvo Medina, V; Morant Guillén, P; Ramos Briones, F; Vicente Guillén, R; Paris Romeu, F

1997-10-01

Objective to review the experience of the lung transplantation unit at Hospital La Fe (Valencia). Between February 1990 and March 1996 we performed 40 lung transplants. The following causes were most common: cystic fibrosis (9 cases), emphysema (8), pulmonary fibrosis (8) and bronchiectasis (7). Types of intervention were 27 double lung transplants (25 sequential and 9 blocked), 9 single lung transplants, and 4 heart-lung transplants. We then reviewed the 36 single and double lung transplants. The main exclusion criteria were age over 65 years, malignant disease, kidney or liver disease, severe or non reversible central nervous system disease, and drug addiction. Prior surgery, mechanical ventilation and the presence of Aspergillus were considered lower-order contraindications. Mean patient age was 37.7 years (14-59). Six patients were colonized by Aspergillus before transplantation. Five had undergone earlier surgery and two were mechanically ventilated before the transplant. The most common complication was respiratory infection, which was present in 6 of the 7 patients who died. Other complications in order of frequency were dehiscence and/or bronchial stenosis, corticoid myopathy and postoperative bleeding. The actuarial survival rate of single and double lung transplants was 67.85 after 3 years, and 87.5% in patients with cystic fibrosis. Lung transplantation is a well-established procedure that is gradually being extended to treat more conditions. The main obstacle is the scarcity of donors. The main challenge at present is bronchiolitis obliterans.

Use of Extracorporeal Membrane Oxygenation Prior to Lung Transplantation Does Not Jeopardize Short-term Survival.

PubMed

Lee, H J; Hwang, Y; Hwang, H Y; Park, I K; Kang, C H; Kim, Y W; Kim, Y T

2015-11-01

The use of pretransplantation extracorporeal membrane oxygenation (ECMO) has been considered to be a relative contraindication and a risk factor associated with poor outcomes in lung transplantation. However, with a donor shortage, use of ECMO before transplantation is often unavoidable. This study aimed to review our experiences of lung transplantation outcome with regards to the use of pretransplantation ECMO. We retrospectively reviewed the clinical data of patients who underwent lung transplantation at our institution. Clinical variables as well as ECMO-related data were analyzed with surgical outcomes. From 2006 to 2014, 27 patients underwent lung transplantation: 26 bilateral sequential lung transplants and 1 right-side single lung transplant. Of these, 12 (44.4%) received ECMO treatment during the pretransplantation waiting period. Pretransplantation ECMO patients showed higher body mass index scores (P = .047) and mechanical ventilation support (P < .001) than the non-ECMO group. All ECMO patients were weaned from ECMO after transplantation. The median ECMO runtime was 12 days. The survival-to-discharge rates of the 2 groups did not differ. Survival after lung transplantation at 1, 6, 12, and 24 months was 100%, 73.3%, 61.1%, and 61.1% in the ECMO group and 100%, 86.7%, 86.7%, and 66.0% in the non-ECMO group, respectively (P = .540). Use of pretransplantation ECMO did not jeopardize survival-to-discharge and short-term survival rates in our experience. Our result suggests pretransplantation ECMO can provide a chance of receiving lung transplantation to those who were classified as "too sick to be transplanted." Copyright © 2015 Elsevier Inc. All rights reserved.

Lung transplantation with lungs from older donors: recipient and surgical factors affect outcomes.

PubMed

Shigemura, Norihisa; Horai, Tetsuya; Bhama, Jay K; D'Cunha, Jonathan; Zaldonis, Diana; Toyoda, Yoshiya; Pilewski, Joseph M; Luketich, James D; Bermudez, Christian A

2014-10-27

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.

[Lung and heart-lung transplantation in respiratory tract diseases. Evaluation and development of the indications based on our first 15 cases].

PubMed

Couraud, L; Baudet, E; Martigne, C; Roques, X; Velly, J F; Laborde, N; Clerc, P

1989-01-01

Since January 1988, the Bordeaux group has performed 15 transplantations for lung disease: 9 heart-lung transplants, 1 heart + left lung, 1 double lung, 2 right lungs and 2 left lungs. The transplantations were performed for pulmonary emphysema (10 cases), pulmonary artery hypertension (2 cases), cystic fibrosis (1 case), pulmonary fibrosis (2 cases). Cardiopulmonary transplantation was not always performed because of associated heart failure but sometimes because of large intrahilar adenopathy or intractable bronchial infection. Pulmonary transplantation is recommended on the right side in cases of pulmonary fibrosis. One patient died postoperatively (ischaemia of the transplant). Four others died during the 2nd and 3rd months from poorly defined but probably infectious pulmonary syndromes. The tracheobronchial patency of the 10 survivors was 80% or 100% of the predicted value. The respiratory functional result was excellent in the short and intermediate term. Specific difficulties essentially consisted of pleural symphyses, hilar adenopathy, bronchial infection, steroid dependence of certain subjects, the difficulty of identifying the cause and treating lung opacities during the 2nd and 3rd months.

Lung transplantation for lymphangioleiomyomatosis: the European experience.

PubMed

Benden, Christian; Rea, Federico; Behr, Jürgen; Corris, Paul A; Reynaud-Gaubert, Martine; Stern, Marc; Speich, Rudolf; Boehler, Annette

2009-01-01

Lung transplantation has been accepted widely as therapy for end-stage pulmonary lymphangioleiomyomatosis (LAM); however, single-center and national experience is limited due to the rarity of LAM. We report the recent European experience of lung transplantation for LAM. A self-administered questionnaire was distributed to 30 European lung transplant centers to evaluate patients who underwent primary lung transplantation for LAM (1997 to 2007). Seventy percent of centers responded to the questionnaire. A total of 61 lung transplants were undertaken in women only, with mean age at transplant 41.3 years (SD 5.1). Centers performed a median of 2 (0 to 9) transplant operations. Severe pleural adhesions were the most common intra-operative complication. Early deaths (N = 6) were due to primary graft or multiple-organ failure or sepsis. Twelve recipients were diagnosed with bronchiolitis obliterans syndrome at a median of 20 months (range 10 to 86 months) post-transplant. LAM-related complications included renal angiomyolipoma and pneumothorax in the native lung. Recurrence of LAM occurred in 4 recipients. As of December 2007, actuarial Kaplan-Meier survival was 79% at 1 year and 73% at 3 years post-transplant. Post-transplant outcome for pulmonary LAM in the recent era appears to have improved compared with the previous era. LAM-related complications remain common, but recurrence of LAM in the allograft is rare.

Ex vivo lung perfusion: a comprehensive review of the development and exploration of future trends.

PubMed

Roman, Marius A; Nair, Sukumaran; Tsui, Steven; Dunning, John; Parmar, Jasvir S

2013-09-01

There is a critical mismatch between the number of donor lungs available and the demand for lungs for transplantation. This has created unacceptably high waiting-list mortality for lung transplant recipients. Currently (2012) in the United Kingdom, there are 216 patients on the lung transplant waiting list and 17 on heart and lung transplant list. The waiting times for suitable lungs average 412 days, with an increasing mortality and morbidity among the patients on the lung transplant list. Ex vivo lung perfusion (EVLP) has emerged as a technique for the assessment, resuscitation, and potential repair of suboptimal donor lungs. This is a rapidly developing field with significant clinical implications. In this review article, we critically appraise the background developments that have led to our current clinical practice. In particular, we focus on the human and animal experience, the different perfusion-ventilation strategies, and the impact of different perfusates and leukocyte filters. Finally, we examine EVLP as a potential research tool. This will provide insight into EVLP and its future development in the field of clinical lung transplantation.

Comprehensive evaluation of lung allograft function in infants after lung and heart-lung transplantation.

PubMed

Hayes, Don; Naguib, Aymen; Kirkby, Stephen; Galantowicz, Mark; McConnell, Patrick I; Baker, Peter B; Kopp, Benjamin T; Lloyd, Eric A; Astor, Todd L

2014-05-01

Limited data exist on methods to evaluate allograft function in infant recipients of lung and heart-lung transplants. At our institution, we developed a procedural protocol in coordination with pediatric anesthesia where infants were sedated to perform infant pulmonary function testing, computed tomography imaging of the chest, and flexible fiberoptic bronchoscopy with transbronchial biopsies. A retrospective review was performed of children aged younger than 1 year who underwent lung or heart-lung transplantation at our institution to assess the effect of this procedural protocol in the evaluation of infant lung allografts. Since 2005, 5 infants have undergone thoracic transplantation (3 heart-lung, 2 lung). At time of transplant, the mean ± standard deviation age was 7.2 ± 2.8 months (range, 3-11 months). Of 24 procedural sessions performed to evaluate lung allografts, 83% (20 of 24) were considered surveillance where the patients were completely asymptomatic. Of the surveillance procedures, 80% were performed as an outpatient, whereas 20% were done as inpatients during the lung or heart-lung transplant post-operative period before discharge home. Sedation was performed with propofol alone (23 of 24) or in addition to ketamine (1 of 24) infusion; mean sedation time was 141 ± 39 minutes (range, 70-214) minutes. Of the 16 outpatient procedures, patients were discharged after 14 (88%) on the same day, and after 2 (12%) were admitted for observation, with 1 being due to transportation issues and the other due to fever during the observation period. A comprehensive procedural protocol to evaluate allograft function in infant lung and heart-lung transplant recipients was performed safely as an outpatient. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Extracorporeal membrane oxygenation as a bridge to lung transplantation: A single-center experience in the present era.

PubMed

Todd, Emily M; Biswas Roy, Sreeja; Hashimi, A Samad; Serrone, Rosemarie; Panchanathan, Roshan; Kang, Paul; Varsch, Katherine E; Steinbock, Barry E; Huang, Jasmine; Omar, Ashraf; Patel, Vipul; Walia, Rajat; Smith, Michael A; Bremner, Ross M

2017-11-01

Extracorporeal membrane oxygenation has been used as a bridge to lung transplantation in patients with rapid pulmonary function deterioration. The reported success of this modality and perioperative and functional outcomes are varied. We retrospectively reviewed all patients who underwent lung transplantation at our institution over 1 year (January 1, 2015, to December 31, 2015). Patients were divided into 2 groups depending on whether they required extracorporeal membrane oxygenation support as a bridge to transplant; preoperative characteristics, lung transplantation outcomes, and survival were compared between groups. Of the 93 patients, 12 (13%) received bridge to transplant, and 81 (87%) did not. Patients receiving bridge to transplant were younger, had higher lung allocation scores, had lower functional status, and were more often on mechanical ventilation at listing. Most patients who received bridge to transplant (n = 10, 83.3%) had pulmonary fibrosis. Mean pretransplant extracorporeal membrane oxygenation support was 103.6 hours in duration (range, 16-395 hours). All patients who received bridge to transplant were decannulated immediately after lung transplantation but were more likely to return to the operating room for secondary chest closure or rethoracotomy. Grade 3 primary graft dysfunction within 72 hours was similar between groups. Lung transplantation success and hospital discharge were 100% in the bridge to transplant group; however, these patients experienced longer hospital stays and higher rates of discharge to acute rehabilitation. The 1-year survival was 100% in the bridge to transplant group and 91% in the non-bridge to transplant group (log-rank, P = .24). The 1-year functional status was excellent in both groups. Extracorporeal membrane oxygenation can be used to safely bridge high-acuity patients with end-stage lung disease to lung transplantation with good 30-day, 90-day, and 1-year survival and excellent 1-year functional status. Long-term outcomes are being studied. Copyright © 2017. Published by Elsevier Inc.

Experience with the first 50 ex vivo lung perfusions in clinical transplantation.

PubMed

Cypel, Marcelo; Yeung, Jonathan C; Machuca, Tiago; Chen, Manyin; Singer, Lianne G; Yasufuku, Kazuhiro; de Perrot, Marc; Pierre, Andrew; Waddell, Thomas K; Keshavjee, Shaf

2012-11-01

Normothermic ex vivo lung perfusion is a novel method to evaluate and improve the function of injured donor lungs. We reviewed our experience with 50 consecutive transplants after ex vivo lung perfusion. A retrospective study using prospectively collected data was performed. High-risk brain death donor lungs (defined as Pao(2)/Fio(2) <300 mm Hg or lungs with radiographic or clinical findings of pulmonary edema) and lungs from cardiac death donors were subjected to 4 to 6 hours of ex vivo lung perfusion. Lungs that achieved stable airway and vascular pressures and Pao(2)/Fio(2) greater than 400 mm Hg during ex vivo lung perfusion were transplanted. The primary end point was the incidence of primary graft dysfunction grade 3 at 72 hours after transplantation. End points were compared with lung transplants not treated with ex vivo lung perfusion (controls). A total of 317 lung transplants were performed during the study period (39 months). Fifty-eight ex vivo lung perfusion procedures were performed, resulting in 50 transplants (86% use). Of these, 22 were from cardiac death donors and 28 were from brain death donors. The mean donor Pao(2)/Fio(2) was 334 mm Hg in the ex vivo lung perfusion group and 452 mm Hg in the control group (P = .0001). The incidence of primary graft dysfunction grade 3 at 72 hours was 2% in the ex vivo lung perfusion group and 8.5% in the control group (P = .14). One patient (2%) in the ex vivo lung perfusion group and 7 patients (2.7%) in the control group required extracorporeal lung support for primary graft dysfunction (P = 1.00). The median time to extubation, intensive care unit stay, and hospital length of stay were 2, 4, and 20 days, respectively, in the ex vivo lung perfusion group and 2, 4, and 23 days, respectively, in the control group (P > .05). Thirty-day mortality (4% in the ex vivo lung perfusion group and 3.5% in the control group, P = 1.00) and 1-year survival (87% in the ex vivo lung perfusion group and 86% in the control group, P = 1.00) were similar in both groups. Transplantation of high-risk donor lungs after 4 to 6 hours of ex vivo lung perfusion is safe, and outcomes are similar to those of conventional transplants. Ex vivo lung perfusion improved our center use of donor lungs, accounting for 20% of our current lung transplant activity. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Ex Vivo Adenoviral Vector Gene Delivery Results in Decreased Vector-associated Inflammation Pre- and Post–lung Transplantation in the Pig

PubMed Central

Yeung, Jonathan C; Wagnetz, Dirk; Cypel, Marcelo; Rubacha, Matthew; Koike, Terumoto; Chun, Yi-Min; Hu, Jim; Waddell, Thomas K; Hwang, David M; Liu, Mingyao; Keshavjee, Shaf

2012-01-01

Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function. PMID:22453765

Lung Transplantation for Hypersensitivity Pneumonitis

PubMed Central

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.

2015-01-01

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

Bilateral versus single lung transplant for idiopathic pulmonary fibrosis.

PubMed

Lehmann, Sven; Uhlemann, Madlen; Leontyev, Sergey; Seeburger, Joerg; Garbade, Jens; Merk, Denis R; Bittner, Hartmuth B; Mohr, Friedrich W

2014-10-01

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.

Alveolar type II cell transplantation restores pulmonary surfactant protein levels in lung fibrosis.

PubMed

Guillamat-Prats, Raquel; Gay-Jordi, Gemma; Xaubet, Antoni; Peinado, Victor I; Serrano-Mollar, Anna

2014-07-01

Alveolar Type II cell transplantation has been proposed as a cell therapy for the treatment of idiopathic pulmonary fibrosis. Its long-term benefits include repair of lung fibrosis, but its success partly depends on the restoration of lung homeostasis. Our aim was to evaluate surfactant protein restoration after alveolar Type II cell transplantation in an experimental model of bleomycin-induced lung fibrosis in rats. Lung fibrosis was induced by intratracheal instillation of bleomycin. Alveolar Type II cells were obtained from healthy animals and transplanted 14 days after bleomycin was administered. Furthermore, one group transplanted with alveolar macrophages and another group treated with surfactant were established to evaluate the specificity of the alveolar Type II cell transplantation. The animals were euthanized at 21 days after bleomycin instillation. Lung fibrosis was confirmed by a histologic study and an evaluation of the hydroxyproline content. Changes in surfactant proteins were evaluated by mRNA expression, Western blot and immunofluorescence studies. The group with alveolar Type II cell transplantation was the only one to show a reduction in the degree of lung fibrosis and a complete recovery to normal levels of surfactant proteins. One of the mechanisms involved in the beneficial effect of alveolar Type II cell transplantation is restoration of lung surfactant protein levels, which is required for proper respiratory function. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Pulmonary rehabilitation in lung transplant candidates.

PubMed

Li, Melinda; Mathur, Sunita; Chowdhury, Noori A; Helm, Denise; Singer, Lianne G

2013-06-01

While awaiting lung transplantation, candidates may participate in pulmonary rehabilitation to improve their fitness for surgery. However, pulmonary rehabilitation outcomes have not been systematically evaluated in lung transplant candidates. This investigation was a retrospective cohort study of 345 pre-transplant pulmonary rehabilitation participants who received a lung transplant between January 2004 and June 2009 and had available pre-transplant exercise data. Data extracted included: 6-minute walk tests at standard intervals; exercise training details; health-related quality-of-life (HRQL) measures; and early post-transplant outcomes. Paired t-tests were used to examine changes in the 6MW distance (6MWD), exercise training volume and HRQL during the pre-transplant period. We evaluated the association between pre-transplant 6MWD and transplant hospitalization outcomes. The final 6MWD prior to transplantation was only 15 m less than the listing 6MWD (n = 200; p = 0.002). Exercise training volumes increased slightly from the start of the pulmonary rehabilitation program until transplant: treadmill, increase 0.69 ml/kg/min (n = 238; p < 0.0001); biceps resistance training, 18 lbs. × reps (n = 286; p < 0.0001); and quadriceps resistance training, 15 lbs. × reps (n = 278; p < 0.0001). HRQL measures declined. A greater final 6MWD prior to transplant correlated with a shorter length of stay in the hospital (n = 207; p = 0.003). Exercise capacity and training volumes are well preserved among lung transplant candidates participating in pulmonary rehabilitation, even in the setting of severe, progressive lung disease. Participants with greater exercise capacity prior to transplantation have more favorable early post-transplant outcomes. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Food allergies developing after solid organ transplant.

PubMed

Needham, J M; Nicholas, S K; Davis, C M

2015-12-01

The development of food allergy is an increasingly recognized form of morbidity after solid organ transplant. It occurs more commonly in liver transplant recipients, although it has also been reported in heart, lung, kidney, and intestinal transplants. Pediatric transplant recipients are more likely to develop symptoms compared to adults, and reports of frequency vary widely from 5% to 38% in pediatric liver transplant recipients. Multiple mechanisms have been proposed in the literature, although no single mechanism can yet account for all reported observations. As food allergy can have at worst potentially fatal consequences, and at best require lifestyle adjustment through food avoidance, it is important for recipients to be aware of the donor's food allergies and particularly in pediatrics, the possibility of completely de novo allergies. This review explores the recent reports surrounding food allergy after solid organ transplant, including epidemiology, proposed mechanisms, and implications for practice. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Scedosporium apiospermum disseminated infection in a single lung transplant recipient].

PubMed

Solé, Amparo

2011-01-01

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.

[Case report of rhabdoid tumor of the kidney occurring in own kidney following kidney transplantation from the living relative].

PubMed

Sato, Yasuyuki; Iizuka, Jyunpei; Imai, Kenji; Sawada, Yugo; Komatsu, Tomonori; Yago, Rie; Kondo, Tsunenori; Ishida, Hideki; Tanabe, Kazunari

2010-07-01

The patient was a 30-year-old man who had undergone living-donor kidney transplantation for renal failure caused by IgA nephropathy at age 29. On post-transplantation day 83, he visited our department with a chief complaint of asymptomatic hematuria. CT performed on post-transplantation day 95 revealed a tumor (size, 4 cm) in the right native kidney that had not been observed at the time of transplantation. CT performed on post-transplantation day 153 showed that the tumor had enlarged to 6 cm, while retrograde pyelogram performed on post-transplantation day 171 was negative for renal pelvic tumor. On post-transplantation day 193, radical right nephrectomy was performed. The tumor had directly invaded the diaphragm and the lower surface of the liver, and was histopathologically diagnosed as rhabdoid tumor of the kidney. As the pathological tissue was extremely malignant, hepatic posterior segmentectomy, right adrenalectomy, and lymph node dissection were further performed for metastases on post-transplantation day 200. On the 23rd day after radical right nephrectomy (post-transplantation day 216), the patient developed dyspnea. Chest CT showed pleural effusion, hemothorax in right lung and metastases in both lungs. The patient's general status gradually worsened thereafter, and he died on the 53rd day after radical right nephrectomy (post-transplantation day 246). Rhabdoid tumor of the kidney is a rare renal tumor that affects children, and only four adult cases have been reported to date. We report our experience with this rare case.

Imaging in lung transplants: Checklist for the radiologist.

PubMed

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

2014-10-01

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

Lower incidence of bronchiolitis obliterans in pediatric liver-lung transplant recipients with cystic fibrosis.

PubMed

Faro, Albert; Shepherd, Ross; Huddleston, Charles B; Lowell, Jeffrey; Gandhi, Sanjiv; Nadler, Michelle; Sweet, Stuart C

2007-06-15

Simultaneous liver-lung transplantation is an infrequent but technically feasible procedure in patients with end-stage lung disease and advanced liver disease. We characterize the outcomes of pediatric patients who underwent this procedure at our institution. We performed a retrospective, case-control study and reviewed the medical records of all patients referred to our transplant program from its inception. Seven patients were listed for simultaneous liver-lung transplant. The five patients who survived to transplant were matched to 13 controls who underwent isolated bilateral sequential lung transplant for underlying diagnosis, age at time of transplant, gender, and era of transplant. Outcome measures included patient and graft survival, occurrence of bronchiolitis obliterans (BO), and episodes of rejection. Of the five study patients who underwent liver-lung transplant, one died of multiorgan failure 11 days after transplant compared with 9 of 13 controls who died. The median survival for the study patients was 89 months (range, 0-112 months) compared with the controls, who had a median survival of 34 months (range, 0-118 months). The remaining four patients had bronchiolitis obliterans syndrome scores of 0 compared with 5 of 13 control patients (P=0.02). The rate of acute rejection per 100 patient days was 0.012 for the study patients compared with 0.11 for the controls (P=0.025). Simultaneous liver-lung transplantation is a technically feasible procedure with excellent long-term outcomes. The surviving study subjects remain free from bronchiolitis obliterans syndrome. These results suggest that the transplanted liver may bestow immunologic privilege to the lung allograft.

Waiting Narratives of Lung Transplant Candidates

PubMed Central

Yelle, Maria T.; Stevens, Patricia E.; Lanuza, Dorothy M.

2013-01-01

Before 2005, time accrued on the lung transplant waiting list counted towards who was next in line for a donor lung. Then in 2005 the lung allocation scoring system was implemented, which meant the higher the illness severity scores, the higher the priority on the transplant list. Little is known of the lung transplant candidates who were listed before 2005 and were caught in the transition when the lung allocation scoring system was implemented. A narrative analysis was conducted to explore the illness narratives of seven lung transplant candidates between 2006 and 2007. Arthur Kleinman's concept of illness narratives was used as a conceptual framework for this study to give voice to the illness narratives of lung transplant candidates. Results of this study illustrate that lung transplant candidates expressed a need to tell their personal story of waiting and to be heard. Recommendation from this study calls for healthcare providers to create the time to enable illness narratives of the suffering of waiting to be told. Narrative skills of listening to stories of emotional suffering would enhance how healthcare providers could attend to patients' stories and hear what is most meaningful in their lives. PMID:23476760

Waiting narratives of lung transplant candidates.

PubMed

Yelle, Maria T; Stevens, Patricia E; Lanuza, Dorothy M

2013-01-01

Before 2005, time accrued on the lung transplant waiting list counted towards who was next in line for a donor lung. Then in 2005 the lung allocation scoring system was implemented, which meant the higher the illness severity scores, the higher the priority on the transplant list. Little is known of the lung transplant candidates who were listed before 2005 and were caught in the transition when the lung allocation scoring system was implemented. A narrative analysis was conducted to explore the illness narratives of seven lung transplant candidates between 2006 and 2007. Arthur Kleinman's concept of illness narratives was used as a conceptual framework for this study to give voice to the illness narratives of lung transplant candidates. Results of this study illustrate that lung transplant candidates expressed a need to tell their personal story of waiting and to be heard. Recommendation from this study calls for healthcare providers to create the time to enable illness narratives of the suffering of waiting to be told. Narrative skills of listening to stories of emotional suffering would enhance how healthcare providers could attend to patients' stories and hear what is most meaningful in their lives.

A retrospective study of silicone stent placement for management of anastomotic airway complications in lung transplant recipients: short- and long-term outcomes.

PubMed

Dutau, Hervé; Cavailles, Arnaud; Sakr, Lama; Badier, Monique; Gaubert, Jean-Yves; Boniface, Stéphanie; Doddoli, Christophe; Thomas, Pascal; Reynaud-Gaubert, Martine

2010-06-01

Airway anastomotic complications remain a major cause of morbidity and mortality after lung transplantation (LT). Few data are available with regard to the use of silicone stents for these airway disorders. The aim of this retrospective study was to evaluate the clinical efficacy and safety of silicone stents for such an indication. Data of adult lung transplant recipients who had procedures performed between January 1997 and December 2007 at our institution were reviewed retrospectively. We included patients with post-transplant airway complications who required bronchoscopic intervention with a silicone stent. In 17 of 117 (14.5%) LT recipients, silicone stents were inserted at a mean time of 165 (range 5 to 360) days after surgery in order to palliate 23 anastomotic airway stenoses. Symptomatic improvement was noted in all patients, and mean forced expiratory volume in 1 second (FEV(1)) increased by 672 +/- 496 ml (p < 0.001) after stent insertion. The stent-related complication rate was 0.13/patient per month. The latter consisted of obstructive granulomas (n = 10), mucus plugging (n = 7) and migration (n = 7), which were of mild to moderate severity and were successfully managed endoscopically. Mean stent duration was 266 days (range 24 to 1,407 days). Successful stent removal was achieved in 16 of 23 cases (69.5%) without recurrence of stenosis. Overall survival was similar in patients with and without airway complications (p = 0.36). Silicone stents allow clinical and lung function improvement in patients with LT-related airway complications. Stent-related complications were of mild to moderate severity, and were appropriately managed endoscopically. Permanent resolution of airway stenosis was obtained in most patients, allowing definitive stent removal without recurrence. Copyright 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Transplantation after ex vivo lung perfusion: A midterm follow-up.

PubMed

Wallinder, Andreas; Riise, Gerdt C; Ricksten, Sven-Erik; Silverborn, Martin; Dellgren, Göran

2016-11-01

A large proportion of donor lungs are discarded due to known or presumed organ dysfunction. Ex vivo lung perfusion (EVLP) has proven its value as a tool for discrimination between reversible and irreversible donor lung pathology. However, the long-term outcome after transplantation of lungs after EVLP is essentially unknown. We report short-term and midterm outcomes of recipients who received transplants of EVLP-evaluated lungs. Single-center results of recipients of lungs with prior EVLP were compared with consecutive recipients of non-EVLP lungs (controls) during the same period. Short-term follow-up included time to extubation, time in the intensive care unit, and the presence of primary graft dysfunction at 72 hours postoperatively. Mortality and incidence of chronic lung allograft dysfunction were monitored for up to 4 years after discharge. During a 4-year period, 32 pairs of initially rejected donor lungs underwent EVLP. After EVLP, 22 double lungs and 5 single lungs were subsequently transplanted. During this period, 145 patients received transplants of conventional donor lungs that did not have EVLP and constituted the control group. Median time to extubation was 7 hours in the EVLP group and 6 hours in the non-EVLP control group (p = 0.45). Median intensive care unit stay was 4 days vs. 3 days, respectively (p = 0.15). Primary graft dysfunction grade > 1 was present in 14% in the EVLP group and in 12% in the non-EVLP group at 72 hours after transplant. Survival at 1 year was 92% in the EVLP group and 79% in the non-EVLP group. Cumulative survival and freedom from retransplantation or chronic rejection were also comparable between the 2 groups (p = 0.43) when monitored up to 4 years. Selected donor lungs rejected for transplantation can be used after EVLP. This technique is effective for selection of transplantable donor lungs. Patients who received lungs evaluated under EVLP have short-term and midterm outcomes comparable to recipients of non-EVLP donor lungs. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Clearance of Hepatitis C Virus Prior to Lung Transplantation: A Case Report.

PubMed

Shafii, A E; Harris, D D; Baz, M

2017-09-01

Hepatitis C virus (HCV) continues to be considered a relative contraindication to lung transplantation due to concerns of progression of liver disease with the introduction of immunosuppression. Since the recent introduction of effective antiviral therapy for HCV, new approaches in the management of the HCV-positive recipient are being utilized in liver transplantation to clear HCV pre- and post-transplant. Herein, we report use of ledipasvir/sofosbuvir for HCV clearance prior to lung transplantation in a patient with usual interstitial pneumonia. Listing for transplant was delayed until completion of HCV treatment, and he subsequently required extracorporeal membrane oxygenation as a bridge to transplantation due to progressive hypoxia. With antiviral cure rates exceeding 90%, HCV should no longer be considered a relative contraindication to lung transplant, and timing of antiviral treatment should consider the progressive nature of the recipient's lung disease. Copyright © 2017 Elsevier Inc. All rights reserved.

De Novo DQ Donor-Specific Antibodies Are Associated with Chronic Lung Allograft Dysfunction after Lung Transplantation.

PubMed

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

2016-09-01

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.

Effect of Single vs Bilateral Lung Transplantation on Plasma Surfactant Protein D Levels in Idiopathic Pulmonary Fibrosis

PubMed Central

Beers, Michael F.; Ahya, Vivek N.; Kawut, Steven M.; Sims, Karen D.; Lederer, David J.; Palmer, Scott M.; Wille, Keith; Lama, Vibha N.; Shah, Pali D.; Orens, Jonathan B.; Bhorade, Sangeeta; Crespo, Maria; Weinacker, Ann; Demissie, Ejigayehu; Bellamy, Scarlett; Christie, Jason D.; Ware, Lorraine B.

2011-01-01

Background: Serum levels of surfactant protein D (SP-D) have been suggested as reflecting epithelial damage in acute lung injury, COPD, and idiopathic pulmonary fibrosis (IPF). However, little is known about SP-D levels in the setting of lung transplantation. Methods: We examined plasma SP-D levels in 104 subjects from a prospective, multicenter cohort study of lung allograft recipients. Plasma SP-D was measured by enzyme-linked immunosorbent assay prior to transplant and daily for 3 days after transplant. Results: Subjects undergoing transplant for IPF had higher baseline SP-D levels (median, 325 ng/mL) compared with subjects with cystic fibrosis, COPD, and pulmonary hypertension (median, 100, 80, and 82 ng/mL, respectively; P = .0001). Among subjects with IPF undergoing bilateral transplant, SP-D levels declined rapidly postoperatively. In contrast, SP-D levels in subjects undergoing single lung transplant for IPF remained significantly higher than those of bilateral allograft recipients. Among subjects undergoing single lung transplant for IPF, the development of primary graft dysfunction (PGD) was associated with a subsequent rise in SP-D levels, whereas SP-D levels in IPF subjects undergoing bilateral transplant declined, even in the presence of grade 3 PGD. Importantly, single lung allograft recipients without PGD had higher postoperative SP-D levels than bilateral allograft recipients with PGD. Conclusions: Subjects undergoing lung transplant for IPF have significantly higher baseline plasma SP-D levels compared with those with other diagnoses. Plasma SP-D is likely a biomarker of the air-blood barrier integrity in the native IPF lung, but may be less useful as a biomarker of PGD after transplant. PMID:21349925

Early fundoplication is associated with slower decline in lung function after lung transplantation in patients with gastroesophageal reflux disease.

PubMed

Biswas Roy, Sreeja; Elnahas, Shaimaa; Serrone, Rosemarie; Haworth, Cassandra; Olson, Michael T; Kang, Paul; Smith, Michael A; Bremner, Ross M; Huang, Jasmine L

2018-06-01

Gastroesophageal reflux disease (GERD) is prevalent after lung transplantation. Fundoplication slows lung function decline in patients with GERD, but the optimal timing of fundoplication is unknown. We retrospectively reviewed patients who underwent fundoplication after lung transplantion at our center from April 2007 to July 2014. Patients were divided into 2 groups: early fundoplication (<6 months after lung transplantation) and late fundoplication (≥6 months after lung transplantation). Annual decline in percent predicted forced expiratory volume in 1 second (FEV 1 ) was analyzed. Of the 251 patients who underwent lung transplantation during the study period with available pH data, 86 (34.3%) underwent post-transplantation fundoplication for GERD. Thirty of 86 (34.9%) had early fundoplication and 56 of 86 (65.1%) had late fundoplication. Median time from lung transplantation to fundoplication was 4.6 months (interquartile range, 2.0-5.2) and 13.8 months (interquartile range, 9.0-16.1) for the early and late groups, respectively. The median DeMeester score was comparable between groups. One-, 3-, and 5-year actuarial survival rates in the early group were 90%, 70%, and 70%, respectively; in the late group, these rates were 91%, 66%, and 66% (log rank P = .60). Three- and 5-year percent predicted FEV 1 was lower in the late group by 8.9% (95% confidence interval, -30.2 to 12.38; P = .46) and 40.7% (95% confidence interval, -73.66 to -7.69; P = .019). A linear mixed model showed a 5.7% lower percent predicted FEV 1 over time in the late fundoplication group (P < .001). In this study, patients with early fundoplication had a higher FEV 1 5 years after lung transplantation. Early fundoplication might protect against GERD-induced lung damage in lung transplant recipients with GERD. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Improvement in health-related quality of life after lung transplantation

PubMed Central

Santana, Maria-Jose; Feeny, David; Jackson, Katherine; Weinkauf, Justin; Lien, Dale

2009-01-01

BACKGROUND/OBJECTIVE: Traditional survival outcomes do not reflect the effects on the health-related quality of life (HRQL) of patients. HRQL following lung transplantation has not been studied systematically. The Health Utilities Index (HUI) is a family (HUI2 and HUI3) of measures of HRQL that has not been previously used to assess HRQL in lung transplantation. The objective of the present study was to assess the impact of lung transplantation on patient’s HRQL using the HUI. METHODS: A total of 43 patients completed a battery of questionnaires before lung transplantation, and at three months and six months after lung transplantation. The 15-item questionnaire (HUI2 and HUI3) was used. Overall scores were based on a conventional scale (0.00 = dead, 1.00 = perfect health). Mental health was assessed by the Hospital Anxiety and Depression Scale. Adherence to medication and exercise were assessed by Morisky’s and Godin’s questionnaires, respectively. RESULTS: Sixty-five per cent of the patients were men, with a mean age of 53 years (range 18 to 67 years). The mean overall HUI3 score for the lung transplant candidates (0.57) was much lower than for the lung transplant recipients (0.82) at six months post-transplantation. This difference was clinically important and statistically significant (P<0.05 [paired ttest, degrees of freedom (df) = 35]). Differences in mean Hospital Anxiety and Depression Scale scores after transplantation were statistically significant (P<0.05 [paired t test, df=35]). After six months, transplant recipients were more adherent to medication (P<0.05 [χ2 test, df=1]). Recipients were able to increase the duration of exercise at all levels of intensity. CONCLUSION: Lung transplantation improved the patients’ HRQL and adherence to medication. Anxiety levels persisted six months after transplantation but depression levels had decreased significantly. PMID:19851533

Improvement in patient-reported outcomes after lung transplantation is not impacted by the use of extracorporeal membrane oxygenation as a bridge to transplantation.

PubMed

Kolaitis, Nicholas A; Soong, Allison; Shrestha, Pavan; Zhuo, Hanjing; Neuhaus, John; Katz, Patti P; Greenland, John R; Golden, Jeffrey; Leard, Lorriana E; Shah, Rupal J; Hays, Steven R; Kukreja, Jasleen; Kleinhenz, Mary Ellen; Blanc, Paul D; Singer, Jonathan P

2018-02-22

Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation. The impact of preoperative ECMO on health-related quality of life (HRQL) and depressive symptoms after lung transplantation remains unknown, however. In a single-center prospective cohort study, we assessed HRQL and depressive symptoms before and at 3, 6, and 12 months after lung transplantation using the Short Form 12 Physical and Mental Component Scores (SF12-PCS and SF12-MCS), Airway Questionnaire 20-Revised (AQ20R), EuroQol 5D (EQ5D), and Geriatric Depression Scale (GDS). Changes in HRQL were quantified by segmented linear mixed-effects models controlling for age, sex, diagnosis, preoperative forced expiratory volume in 1 second, 6-minute walk distance, and Lung Allocation Score. We compared changes in HRQL among subjects bridged with ECMO, subjects hospitalized but not on ECMO, and subjects called in for transplantation as outpatients. Out of 189 subjects, 17 were bridged to transplantation with ECMO. In all groups, improvements in HRQL following lung transplantation exceeded the minimally clinically important difference using the SF12-PCS, AQ20R, EQ5D, and GDS. HRQL defined by SF12-MCS did not change after transplantation. Improvements were generally similar among the groups, except for EQ5D, which showed a trend toward less benefit in the outpatients, possibly due to their better HRQL before lung transplantation. Subjects ill enough to require ECMO as a bridge to lung transplantation appear to achieve similar improvements in HRQL and depressive symptoms as those who do not. It is reassuring to both providers and patients that lung transplantation provides substantial improvements in HRQL, even for those patients who are critically ill in the run up to transplantation. Copyright © 2018 The American Association for Thoracic Surgery. All rights reserved.

Lung transplantation for cystic fibrosis: results, indications, complications, and controversies.

PubMed

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

2015-04-01

Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (∼50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Short-term outcomes of lung transplant recipients using organs from brain death donors].

PubMed

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

2016-12-01

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 ( Q R )) 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.

Clinical characteristics of Japanese candidates for lung transplant for interstitial lung disease and risk factors for early death while on the waiting list.

PubMed

Higo, Hisao; Kurosaki, Takeshi; Ichihara, Eiki; Kubo, Toshio; Miyoshi, Kentaroh; Otani, Shinji; Sugimoto, Seiichiro; Yamane, Masaomi; Miyahara, Nobuaki; Kiura, Katsuyuki; Miyoshi, Shinichiro; Oto, Takahiro

2017-07-01

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.

Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients.

PubMed

Dubberke, E R; Reske, K A; Olsen, M A; Bommarito, K; Cleveland, A A; Silveira, F P; Schuster, M G; Kauffman, C A; Avery, R K; Pappas, P G; Chiller, T M

2018-04-01

Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantitative evaluation of native lung hyperinflation after single lung transplantation for emphysema using three-dimensional computed tomography volumetry.

PubMed

Motoyama, H; Chen, F; Ohsumi, A; Hijiya, K; Takahashi, M; Ohata, K; Yamada, T; Sato, M; Aoyama, A; Bando, T; Date, H

2014-04-01

Although double lung transplantation is performed more frequently for emphysema, single lung transplantation (SLT) continues to be performed owing to limited donor organ availability. Native lung hyperinflation (NLH) is a unique complication following SLT for emphysema. Three-dimensional computed tomography (3D-CT) volumetry has been introduced into the field of lung transplantation, which we used to assess NLH in emphysema patients undergoing SLT. The primary purpose of this study was to confirm the effectiveness of 3D-CT volumetry in the evaluation of NLH following SLT for emphysema. In 5 emphysema patients undergoing SLT at Kyoto University Hospital, 3D-CT volumetry data, pulmonary function test results, and clinical and radiological findings were retrospectively evaluated. Three patients did not develop a significant mediastinal shift, whereas the other 2 patients developed a mediastinal shift. In the 3 patients without a mediastinal shift, 3D-CT volumetry did not show a significant increase in native lung volume. These patients had a history of sternotomy prior to lung transplantation and firm adhesion on the mediastinal side was detected during lung transplantation. One of 2 patients with a mediastinal shift developed severe dyspnea with significantly decreased pulmonary function, and 3D-CT volumetry showed a significant increase in the native lung volume. However, the other patient did not show any dyspnea and his native lung volume decreased postoperatively (preoperatively to 6 months postoperatively: +981 mL and -348 mL, respectively). Although bilateral lung transplantation has become preferable for emphysema patients owing to postoperative NLH with SLT, patients with a history of sternotomy prior to lung transplantation might be good candidates for SLT. 3D-CT volumetry may be a useful method for detection of NLH. Copyright © 2014 Elsevier Inc. All rights reserved.

Pediatric Lung Transplantation.

PubMed

Sweet, Stuart C

2017-06-01

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.

Disseminated Aspergillus fumigatus infection with consecutive mitral valve endocarditis in a lung transplant recipient.

PubMed

Scherer, Mirela; Fieguth, Hans-Gerd; Aybek, Tayfun; Ujvari, Zsolt; Moritz, Anton; Wimmer-Greinecker, Gerhard

2005-12-01

Aspergillus infection is a known complication of lung transplantation and remains associated with high mortality rates. The manifestation of the infection varies from simple colonization of the lung to disseminated complicated infections. Early Aspergillus infection has been rarely observed in a small number of lung transplant recipients; most cases occur during the late post-operative period. The pulmonary involvement has often been described as the first clinical localization of the disease. Although other various forms of Aspergillus infection are not uncommonly encountered after lung transplantation, Aspergillus mitral valve endocarditis is rare. We present a case of disseminated Aspergillus fumigatus infection with consecutive mitral valve endocarditis having developed 78 days after double-lung transplantation for cystic fibrosis.

Lung transplantation in patients with pulmonary emphysema.

PubMed

Paik, Hyo Chae; Hwang, Jung Joo; Lee, Doo Yun

2004-12-31

Lung transplantation is a viable option for patients with chronic obstructive pulmonary disease (COPD), and emphysema is the most common indication to undergo lung transplantation. A total of seven lung and one heart-lung transplantations were performed between July 1996 and June 2004 at the Yongdong Severance Hospital, and herein, three emphysema patients who underwent single lung transplantations are reviewed. There were 2 males and 1 female, with a mean age of 50 years (35, 57 and 58 years). They all underwent an operation, without cardiopulmonary bypass, and there was no operative mortality. The mean survival was 12 months (4 months, 15 months and 17 months) and all succumbed to death due to activation of pulmonary tuberculosis, post-transplantation lymphoproliferative disease and cytomegalovirus (CMV) gastritis associated with asphyxia. Infection was the most common postoperative complication, resulting in longer hospital stays, higher medical expenses and shorter survival rates, necessitating aggressive prophylactic management. The accumulation of experience, modifications to operative procedures and perioperative care may lead to improved early and long-term survival in patients with emphysema undergoing single or bilateral lung transplantations.

The number of lung transplants can be safely doubled using extended criteria donors; a single-center review.

PubMed

Meers, Caroline; Van Raemdonck, Dirk; Verleden, Geert M; Coosemans, Willy; Decaluwe, Herbert; De Leyn, Paul; Nafteux, Philippe; Lerut, Toni

2010-06-01

Relaxing the standard lung donor criteria may significantly increase the reported 15% organ yield but post-transplant recipient outcome should be carefully monitored. Charts from all consecutive deceased organ donors within our hospital network were reviewed over a 2-year period. Reasons for lung refusals and number of lungs transplanted were analysed. Hospital outcome including early recipient survival was compared between standard- and extended criteria donors. Out of 283 referrals, 164 (58%) qualified as donor of any organ. The majority (65.9%) of these effective donors were declined for lung donation because of chest X-ray abnormalities (20%), age >70 years (13%), poor oxygenation (10%), or aspiration (9%). Out of 56 (34.1%) accepted lung donors, 50 transplants were performed at our center, 23 from standard criteria donors versus 27 from extended criteria donors. There were no significant differences in hospital outcome and in early survival between lung recipients from both donor groups. Lung acceptance rate (34.1%) in our donor network is 10-20% higher than reported figures. The number of lung transplants in our center doubled by accepting extended criteria donors. This policy did not negatively influence our results after lung transplantation.

Atrial Fibrillation and Pulmonary Venous Electrical Conduction Recovery After Full Surgical Resection and Anastomosis of the Pulmonary Veins: Insights From Follow-Up and Ablation Procedures in Lung Transplant Recipients.

PubMed

Hussein, Ayman A; Panchabhai, Tanmay S; Budev, Marie M; Tarakji, Khaldoun; Barakat, Amr F; Saliba, Walid; Lindsay, Bruce; Wazni, Oussama M

2017-06-01

The authors report their experience with atrial fibrillation (AF) rates and ablation findings in lung transplant recipients. Pulmonary venous (PV) conduction recovery accounts for most failed atrial fibrillation (AF) catheter ablation procedures. Lung transplantation involves full surgical resection and replacement of the recipient's PVs with donor's PVs, which may represent the ultimate PV ablation. They followed 755 consecutive lung transplant recipients categorized based on transplant status (unilateral vs. bilateral) and pre-transplant AF. In patients without pre-transplant AF (n = 704), late AF (beyond 6 months after transplant) occurred in 2.5% and 3.3% of unilateral or bilateral lung transplants, respectively. In patients with pre-transplant AF (n = 51), AF recurred in 19.4% and 25.0% of bilateral and unilateral transplants, respectively. In a subset of patients who underwent left atrial ablations after transplant for recurrent refractory AF (n = 8), PV conduction recovery across the surgical anastomoses lines was observed in 22 of 26 previously disconnected PVs. Conduction recovery was observed in ≥1 vein in all but 1 patient. Re-isolation of the veins with additional substrate modification/flutter ablations successfully restored and maintained sinus rhythm in 7 of 8 patients. In lung transplant recipients who undergo full surgical resection of the PVs, a prior history of AF was associated with late AF, regardless of whether patients underwent single or bilateral lung transplantation. PV conduction recovery still occurred and was observed in most patients who underwent left atrial ablation procedures for recurrent AF. Copyright © 2017. Published by Elsevier Inc.

Lung Quality and Utilization in Controlled Donation After Circulatory Determination of Death Within the United States.

PubMed

Mooney, J J; Hedlin, H; Mohabir, P K; Vazquez, R; Nguyen, J; Ha, R; Chiu, P; Patel, K; Zamora, M R; Weill, D; Nicolls, M R; Dhillon, G S

2016-04-01

Although controlled donation after circulatory determination of death (cDCDD) could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remains low compared with donation after neurologic determination of death (DNDD). To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed, and the distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted odds ratio 0.101, 95% confidence interval [CI] 0.085-0.120). A minority of centers have performed cDCDD transplant, with higher volume centers generally performing more cDCDD transplants. There was no difference in center-to-donor distance or recipient survival (adjusted hazard ratio 1.03, 95% CI 0.78-1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared with DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

A novel patient-centered "intention-to-treat" metric of U.S. lung transplant center performance.

PubMed

Maldonado, Dawn A; RoyChoudhury, Arindam; Lederer, David J

2018-01-01

Despite the importance of pretransplantation outcomes, 1-year posttransplantation survival is typically considered the primary metric of lung transplant center performance in the United States. We designed a novel lung transplant center performance metric that incorporates both pre- and posttransplantation survival time. We performed an ecologic study of 12 187 lung transplant candidates listed at 56 U.S. lung transplant centers between 2006 and 2012. We calculated an "intention-to-treat" survival (ITTS) metric as the percentage of waiting list candidates surviving at least 1 year after transplantation. The median center-level 1-year posttransplantation survival rate was 84.1%, and the median center-level ITTS was 66.9% (mean absolute difference 19.6%, 95% limits of agreement 4.3 to 35.1%). All but 10 centers had ITTS values that were significantly lower than 1-year posttransplantation survival rates. Observed ITTS was significantly lower than expected ITTS for 7 centers. These data show that one third of lung transplant candidates do not survive 1 year after transplantation, and that 12% of centers have lower than expected ITTS. An "intention-to-treat" survival metric may provide a more realistic expectation of patient outcomes at transplant centers and may be of value to transplant centers and policymakers. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Transplant Pulmonary Interventions: Translating Lung Transplant Interventions to Nontransplant Patients.

PubMed

Sinha, Neeraj

2016-01-01

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.

Effect of pirfenidone on wound healing in lung transplant patients.

PubMed

Mortensen, Amber; Cherrier, Lauren; Walia, Rajat

2018-01-01

The drug pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor beta, a known contributor to wound healing. We evaluated whether patients taking pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether pirfenidone should be discontinued prior to listing to allow for a wash-out period. We retrospectively reviewed patients who underwent lung transplantation for pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January 2014 to December 2015. We describe 18 patients who took pirfenidone up to a month before transplant. Aside from one patient who experienced sternal dehiscence due to a surgical issue, all remaining patients did well with no evidence of airway dehiscence. Each of these 17 patients had been on pirfenidone for at least 30 days; nine patients had been on pirfenidone for over 90 days. Baseline characteristics including age, sex, body mass index, renal function, liver function, glucose level, pre-transplant corticosteroid use, and post-transplant immunosuppressant therapy were similar. In our experience, pirfenidone may be safely continued until lung transplantation. Only one patient in our series experienced impaired wound healing related to a surgical issue, even when pirfenidone was continued until lung transplantation. We found no evidence of impaired wound healing or airway complications after lung transplantation in patients who were treated with pirfenidone before lung transplantation.

Outcomes of lung transplantation in patients with scleroderma.

PubMed

Massad, Malek G; Powell, Charles R; Kpodonu, Jacques; Tshibaka, Cimenga; Hanhan, Ziad; Snow, Norman J; Geha, Alexander S

2005-11-01

Patients with pulmonary insufficiency due to scleroderma have long been considered suboptimal candidates for lung transplantation. This has been supported by small single-center experiences that did not reflect the entire U.S. experience. We sought to evaluate the outcome of patients with scleroderma who underwent lung transplantation. We conducted a retrospective review of 47 patients with scleroderma who underwent lung transplantation at 23 U.S. centers between 1987 and 2004 and were reported to the United Network for Organ Sharing. Women constituted 57% of the patients. The mean age was 46 years. Twenty-seven patients received single lung transplants (57%), and the remaining received double lung transplants. The mean cold ischemia time was 4.1 hours. There were 7 early deaths (< or =30 days) and 17 late deaths (> 30 days). The causes of early death were primary graft failure and a cardiac event in two patients each and bacterial infection and stroke in one patient each. Late mortality was due to infection in seven patients, respiratory failure in three, malignancy in two, and multisystem organ failure, rejection, pulmonary hypertension, and a cardiac event in one patient each. The causes of early and late death were not recorded for two patients. One patient received a second transplant owing to graft failure of the first. Twenty-three patients (49%) were alive at a mean follow-up of 24 months. The Kaplan-Meier 1- and 3-year survival rates were 67.6% and 45.9% respectively, which are not significantly different from those of 10,070 patients given transplants for other lung conditions during the same period (75.5% and 58.8% respectively, P = 0.25). Donor gender, recipient's age, and type of transplant did not affect survival. In carefully selected patients with scleroderma who have end-stage lung disease, lung transplantation is a valid life-saving therapeutic option. Available data suggest acceptable short-term morbidity and mortality and a long-term survival similar to that of patients given transplants for other lung conditions.

Outcomes of intensive care unit care in adults with cystic fibrosis.

PubMed

Sood, N; Paradowski, L J; Yankaskas, J R

2001-02-01

Cystic fibrosis (CF) causes progressive respiratory failure and death in more than 90% of patients. Mechanical ventilation has been discouraged in CF because of poor outcomes, but improved survival and the availability of lung transplantation have increased the indications for care of CF patients in the intensive care unit (ICU). We studied the outcomes of all CF patients admitted to the University of North Carolina Hospitals Medical ICU from January 1990 through December 1998. Seventy-six patients, ranging in ages from 17 to 45 yr (mean: 27 yr), and of whom 53% were female, had 136 admissions for exacerbations of CF with respiratory failure (RF, n = 65), hemoptysis (n = 33), antibiotic desensitization (n = 30), pneumothorax (n = 3), or other reasons (n = 5). Eighty-six percent of the patients with hemoptysis and all of those with desensitization and pneumothorax were alive 1 yr after ICU discharge. Of the 42 patients with RF, 37 (88%) required assisted ventilation. Twenty-three (55%) of the patients with RF survived to ICU discharge and 19 (45%) died. Seventeen (40%) of the patients with RF received lung transplants and 14 were alive 1 yr later. Without transplantation, three (7%) of the patients with RF were alive and three (7%) were dead 1 yr later. Sex, body mass index, and respiratory bacteria did not correlate with survival. We conclude that ICU care for adults with CF who have reversible complications is appropriate and effective. Ventilatory support is appropriate for some transplant candidates.

Barriers to Optimal Palliative Care of Lung Transplant Candidates

PubMed Central

Colman, Rebecca E.; Curtis, J. Randall; Nelson, Judith E.; Efferen, Linda; Hadjiliadis, Denis; Levine, Deborah J.; Meyer, Keith C.; Padilla, Maria; Strek, Mary; Varkey, Basil

2013-01-01

Background: The provision of effective palliative care is of great importance to patients awaiting lung transplantation. Although the prospect of lung transplantation provides hope to patients and their families, these patients are usually very symptomatic from their underlying disease. Methods: An e-mail questionnaire was sent to members of the American College of Chest Physicians’ Transplant NetWork and the Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT). The survey included questions about barriers to providing palliative care, the availability of palliative care services, and recommended strategies to improve palliative care for lung transplant candidates. Results: The 158 respondents represented approximately 65% of transplant programs in the ISHLT registry. Respondents were in practice a mean of 11.3 (± 9) years, 70% were pulmonologists, 17% were surgeons, and 13% were other care providers. Barriers were classified into domains including patient factors, family factors, physician factors, and institutional/transplant program/lung allocation system factors. Significant patient/family barriers included unrealistic patient/family expectations about survival, unwillingness to plan end-of-life care, concerns about abandonment or inappropriate care after enrollment in a palliative care program, and family disagreements about care goals. For institutional/program/allocation system barriers, only the requirement for weight loss or gain to meet program-specific BMI requirements was identified. Significant physician barriers included competing time demands and the seemingly contradictory goals of transplant vs palliative care. Strategies recommended to improve palliative care included routine advance care planning for patients awaiting transplantation, access to palliative care specialists, training of transplant physicians in symptom management, and regular meetings among transplant physicians, nurses, patients, and families. Conclusions: Physicians providing care to lung transplant candidates reported considerable barriers to the delivery and acceptance of palliative care and identified specific strategies to improve palliative care for lung transplant candidates. PMID:22922517

Lung transplantation in patients with cystic fibrosis.

PubMed

Morton, Judith; Glanville, Allan R

2009-10-01

Cystic fibrosis is one of the most common indications for lung transplantation worldwide and certainly the most common indication for all pediatric lung transplants and for bilateral lung transplantation irrespective of age. Outcomes are outstanding when compared with other indications for lung transplantation, and an increasing number of centers now report mean survival of greater than 10 years posttransplant. Hence it is important to concentrate on the broad panoply of potential systemic complications of cystic fibrosis and address proactively issues that may be associated with adverse outcomes. Optimum management of infectious, nutritional, diabetic, renal, bone, and gut complications is critical to long-term success so that recipients may realize their full potential. Timing of referral for consideration of active listing should allow sufficient time for the patient and lung transplant team to develop a productive working relationship based on best available evidence and mutual trust, which will culminate in a long-term successful outcome. Copyright Thieme Medical Publishers.

CMV driven CD8(+) T-cell activation is associated with acute rejection in lung transplantation.

PubMed

Roux, Antoine; Mourin, Gisèle; Fastenackels, Solène; Almeida, Jorge R; Iglesias, Maria Candela; Boyd, Anders; Gostick, Emma; Larsen, Martin; Price, David A; Sacre, Karim; Douek, Daniel C; Autran, Brigitte; Picard, Clément; Miranda, Sandra de; Sauce, Delphine; Stern, Marc; Appay, Victor

2013-07-01

Lung transplantation is the definitive treatment for terminal respiratory disease, but the associated mortality rate is high. Acute rejection of the transplanted lung is a key determinant of adverse prognosis. Furthermore, an epidemiological relationship has been established between the occurrence of acute lung rejection and cytomegalovirus infection. However, the reasons for this association remain unclear. Here, we performed a longitudinal characterization of CMV-specific T-cell responses and immune activation status in the peripheral blood and bronchoalveolar lavage fluid of forty-four lung transplant patients. Acute rejection was associated with high levels of cellular activation in the periphery, reflecting strong CMV-specific CD8(+) T-cell activity post-transplant. Peripheral and lung CMV-specific CD8(+) T-cell responses were very similar, and related to the presence of CMV in the transplanted organ. These findings support that activated CMV-specific CD8(+) T-cells in the lung may play a role in promoting acute rejection. Copyright © 2013 Elsevier Inc. All rights reserved.

First Danish experience with ex vivo lung perfusion of donor lungs before transplantation.

PubMed

Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold; Zemtsovski, Mikhail; Nilsson, Jens Christian; Seidelin, Casper Tobias; Perch, Michael; Iversen, Martin; Steinbrüchel, Daniel

2014-03-01

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.

The Psychosocial Assessment of Candidates for Transplantation: A Cohort Study of its Association With Survival Among Lung Transplant Recipients.

PubMed

Hitschfeld, Mario J; Schneekloth, Terry D; Kennedy, Cassie C; Rummans, Teresa A; Niazi, Shehzad K; Vasquez, Adriana R; Geske, Jennifer R; Petterson, Tanya M; Kremers, Walter K; Jowsey-Gregoire, Sheila G

2016-01-01

The United Network for Organ Sharing mandates a psychosocial assessment of transplant candidates before listing. A quantified measure for determining transplant candidacy is the Psychosocial Assessment of Candidates for Transplant (PACT) scale. This instrument's predictive value for survival has not been rigorously evaluated among lung transplantation recipients. We reviewed medical records of all patients who underwent lung transplantation at Mayo Clinic, Rochester from 2000-2012. A transplant psychiatrist had assessed lung transplant candidates for psychosocial risk with the PACT scale. Recipients were divided into high- and low psychosocial risk cohorts using a PACT score cutoff of 2. The main outcome variable was posttransplant survival. Mortality was analyzed using the Kaplan-Meier estimator and Cox proportional hazard models. This study included 110 lung recipients: 57 (51.8%) were females, 101 (91.8%) Whites, mean age: 56.4 years. Further, 7 (6.4%) recipients received an initial PACT score <2 (poor or borderline candidates) and later achieved a higher score, allowing transplant listing; 103 (93.6%) received initial scores ≥2 (acceptable, good or great candidates). An initial PACT score < 2 was modestly associated with higher mortality (adjusted hazard ratio = 2.73, p = 0.04). Lung transplant recipients who initially received a low score on the PACT scale, reflecting poor or borderline psychosocial candidacy, experienced greater likelihood of mortality. This primary finding suggests that the psychosocial assessment, as measured by the PACT scale, may provide additional mortality risk stratification for lung transplant candidates. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Aspergillus infection in lung transplant recipients with cystic fibrosis: risk factors and outcomes comparison to other types of transplant recipients.

PubMed

Helmi, Mohamed; Love, Robert B; Welter, Debbie; Cornwell, Richard D; Meyer, Keith C

2003-03-01

To characterize Aspergillus infections in lung transplant recipients with cystic fibrosis (CF). A retrospective analysis of 32 consecutive lung transplant recipients with CF who underwent bilateral lung transplant at the University of Wisconsin from 1994 to 2000 to determine the incidence, risk factors, and consequences of Aspergillus infection. The findings were compared to 101 non-CF recipients of lung transplants (93) and heart-lung transplants (8) for other transplant indications. A university hospital. Lung transplant recipients with CF or other indications for transplantation. None. Seventeen of 32 CF recipients (53%) had Aspergillus fumigatus isolated from their respiratory secretions prior to undergoing transplantation. Ten of these 17 (59%) recipients had A fumigatus persistently found in their respiratory secretions posttransplant vs 6 of 15 CF patients (40%) who had not been colonized pretransplant and 28 of 101 of the non-CF recipients (28%). Four of the preoperatively colonized CF recipients developed tracheobronchial aspergillosis (TBA) just distal to the bronchial anastomoses, and one recipient had dehiscence of the involved anastomosis. None of the CF recipients developed disseminated aspergillosis or pneumonia. Prophylactic antifungal therapy did not prevent TBA, and IV amphotericin B therapy was required to clear the infection in all four patients, with endobronchial debridement of necrotic tissue required in two of them. In contrast, 10 of the non-CF (10%) recipients developed Aspergillus infections posttransplant (TBA, 4 recipients; pneumonitis, 6 recipients), and only 3 patients had successful treatment and long-term survival (TBA, 2 patients; pneumonia, 1 patient). Donor lung ischemia time, cytomegalovirus infection or pneumonia, or pretransplant mechanical ventilation did not increase the risk of developing TBA in CF recipients. The risk of TBA for patients receiving lung transplants for CF warrants early surveillance bronchoscopy to detect TBA, particularly in recipients with pretransplant colonization.

Life after a lung transplant: a balance of joy and challenges.

PubMed

Graarup, Jytte; Mogensen, Elin Lindberg; Missel, Malene; Berg, Selina Kikkenborg

2017-11-01

To describe patients' experiences throughout the first four months post-lung transplant. Health professionals are familiar with the fact that patients' average survival after a lung transplant is about seven years and that 74% of these patients reject new organs within the first two years. By contrast, knowledge of these patients' perspectives after lung transplantation is scant. A qualitative study was conducted between May 2013-May 2014 in which 26 interviewees participated - four months post-transplant - based on a semistructured interview guide. The data were inductively analysed using a content thematic approach within a phenomenological and hermeneutic frame. The main findings in the study reveal that (1) having a lung transplant is an overwhelming experience, which for some patients includes (2) troubling physical and psychological challenges. The interviewees were happy to get another chance to live, although some of them suffered from medical side effects, postoperative complications and psychological problems. When asked about the future, interviewees stated that life could be described as (3) a balance of joy and challenges. They had received a new chance in life and were eager to fulfil their life hopes and dreams. At the same time, they were worried about the future. Having a lung transplant implies rules that have to be followed. What are the healthy choices they are supposed to make? And will there be a tomorrow? Having a lung transplant is described as an overwhelming experience because of the improvement in the physical function of the body. Patients were grateful to family, friends and healthcare professionals for supporting them. The first four months post-transplantation were described as both physically and psychologically challenging. Interviewees were aware of the prognosis for patients following lung transplantation. They expressed feelings of worry and insecurity but still had hopes and dreams. The patients are troubled by both physical and psychological challenges after lung transplantation. Several areas call for interventions from healthcare professionals during the early post-transplant period. © 2017 John Wiley & Sons Ltd.

Lung transplantation in the most critically-III: forging ahead.

PubMed

Mulvihill, Michael S; Hartwig, Matthew G; Daneshmand, Mani A

2017-09-01

Lung transplantation is the gold standard therapy for patients with end-stage lung disease. The use of the lung allocation score (LAS) has permitted improved allocation of scarce pulmonary allografts. Recently, Crawford et al. examined the experience in the United States in lung transplantation in candidates with the highest LAS, demonstrating that outcomes for candidates with the highest LAS scores have improved significantly. This editorial places these data in the broader context of thoracic transplantation, and highlights the critical need for ongoing examination of this critically-ill patient population.

Surgical risk factors associated with lung transplantation.

PubMed

Paradela, M; González, D; Parente, I; Fernández, R; De La Torre, M M; Delgado, M; García, J A; Fieira, E; Bonhome, C; Maté, J M B

2009-01-01

Despite years of experience with lung transplantation, perioperative morbidity rates remain high. The objective of this study was to analyze our series of lung transplant recipients, seeking to identify possible intra- and postoperative risk factors associated with mortality. We performed a descriptive, retrospective study of 224 consecutive patients undergoing lung transplantation over a period of 112 months; we excluded retransplant procedures. We gathered details of the surgical procedure and postoperative period in the recovery unit. Univariate analysis using the chi-square test identified variables associated with the incidence of mortality. From 1999 to 2008, we performed 224 lung transplants, including 66% in men and 34% in women. Their overall mean age was 49.9 +/- 13.5 years. The conditions that led to transplantation were pulmonary fibrosis (38.4%); chronic obstructive pulmonary disease emphysema (29%); cystic fibrosis (10.7%); bronchiectasis (8.9%); pulmonary hypertension (3.1%); and other diseases (9.9%). A total of 124 (55.4%) patients underwent single and 100 (44.6%) received sequential bilateral lung transplantations. Surgical risk factors were identified in 51.3% of the cases, the most frequent being hemorrhage (25.3%), followed by severe pulmonary hypertension (14.7%) and cardiopulmonary bypass (12.1%). Greater perioperative mortality was detected among patients with surgical risk factors, namely, significantly related to cardiopulmonary bypass, pulmonary hypertension, and air leak. A higher frequency of surgical risk factors was observed among patients with bilateral lung transplantations and longer procedures, but they were not associated with greater perioperative mortality. Reoperation was necessary in 16 patients (7.2%), mainly owing to bleeding, it was not significantly related to mortality risk. The incidence of surgical risk factors in lung transplantation was high, especially in bilateral lung transplantations and prolonged procedures. Postoperative bleeding requiring reoperation was not frequent and not associated with increased preoperative mortality in our series.

Clinical predictors and outcome implications of early readmission in lung transplant recipients.

PubMed

Osho, Asishana A; Castleberry, Anthony W; Yerokun, Babatunde A; Mulvihill, Michael S; Rucker, Justin; Snyder, Laurie D; Davis, Robert D; Hartwig, Matthew G

2017-05-01

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.

Predicting the Necessity for Extracorporeal Circulation During Lung Transplantation: A Feasibility Study.

PubMed

Hinske, Ludwig Christian; Hoechter, Dominik Johannes; Schröeer, Eva; Kneidinger, Nikolaus; Schramm, René; Preissler, Gerhard; Tomasi, Roland; Sisic, Alma; Frey, Lorenz; von Dossow, Vera; Scheiermann, Patrick

2017-06-01

The factors leading to the implementation of unplanned extracorporeal circulation during lung transplantation are poorly defined. Consequently, the authors aimed to identify patients at risk for unplanned extracorporeal circulation during lung transplantation. Retrospective data analysis. Single-center university hospital. A development data set of 170 consecutive patients and an independent validation cohort of 52 patients undergoing lung transplantation. The authors investigated a cohort of 170 consecutive patients undergoing single or sequential bilateral lung transplantation without a priori indication for extracorporeal circulation and evaluated the predictive capability of distinct preoperative and intraoperative variables by using automated model building techniques at three clinically relevant time points (preoperatively, after endotracheal intubation, and after establishing single-lung ventilation). Preoperative mean pulmonary arterial pressure was the strongest predictor for unplanned extracorporeal circulation. A logistic regression model based on preoperative mean pulmonary arterial pressure and lung allocation score achieved an area under the receiver operating characteristic curve of 0.85. Consequently, the authors developed a novel 3-point scoring system based on preoperative mean pulmonary arterial pressure and lung allocation score, which identified patients at risk for unplanned extracorporeal circulation and validated this score in an independent cohort of 52 patients undergoing lung transplantation. The authors showed that patients at risk for unplanned extracorporeal circulation during lung transplantation could be identified by their novel 3-point score. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of a lung transplantation donor-management protocol on lung donation and recipient outcomes.

PubMed

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

2006-09-15

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.

Unilateral lung transplantation for pulmonary fibrosis.

PubMed

1986-05-01

Improvements in immunosuppression and surgical techniques have made unilateral lung transplantation feasible in selected patients with end-stage interstitial lung disease. We report two cases of successful unilateral lung transplantation for end-stage respiratory failure due to pulmonary fibrosis. The patients, both oxygen-dependent, had progressive disease refractory to all treatment, with an anticipated life expectancy of less than one year on the basis of the rate of progression of the disease. Both patients were discharged six weeks after transplantation and returned to normal life. They are alive and well at 26 months and 14 months after the procedure. Pulmonary-function studies have shown substantial improvement in their lung volumes and diffusing capacities. For both patients, arterial oxygen tension is now normal and there is no arterial oxygen desaturation with exercise. This experience shows that unilateral lung transplantation, for selected patients with end-stage interstitial lung disease, provides a good functional result. Moreover, it avoids the necessity for cardiac transplantation, as required by the combined heart-lung procedure, and permits the use of the donor heart for another recipient.

Lung donor treatment protocol in brain dead-donors: A multicenter study.

PubMed

Miñambres, Eduardo; Pérez-Villares, Jose Miguel; Chico-Fernández, Mario; Zabalegui, Arturo; Dueñas-Jurado, Jose María; Misis, Maite; Mosteiro, Fernando; Rodriguez-Caravaca, Gil; Coll, Elisabeth

2015-06-01

The shortage of lung donors for transplantation is the main limitation among patients awaiting this type of surgery. We previously demonstrated that an intensive lung donor-treatment protocol succeeded in increasing the lung procurement rate. We aimed to validate our protocol for centers with or without lung transplant programs. A quasi-experimental study was performed to compare lung donor rate before (historical group, 2010 to 2012) and after (prospective group, 2013) the application of a lung management protocol for donors after brain death (DBDs) in six Spanish hospitals. Lung donor selection criteria remained unchanged in both periods. Outcome measures for lung recipients were early survival and primary graft dysfunction (PGD) rates. A total of 618 DBDs were included: 453 in the control period and 165 in the protocol period. Donor baseline characteristics were similar in both periods. Lung donation rate in the prospective group was 27.3%, more than twice that of the historical group (13%; p < 0.001). The number of lungs retrieved, grafts transplanted, and transplants performed more than doubled over the study period. No differences in early recipients' survival between groups were observed (87.6% vs. 84.5%; p = 0.733) nor in the rate of PGD. Implementing our intensive lung donor-treatment protocol increases lung procurement rates. This allows more lung transplants to be performed without detriment to either early survival or PGD rate. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Surveillance bronchoscopy in children during the first year after lung transplantation: Is it worth it?

PubMed

Benden, C; Harpur-Sinclair, O; Ranasinghe, A S; Hartley, J C; Elliott, M J; Aurora, P

2007-01-01

Since January 2002, routine surveillance bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy has been performed in all paediatric recipients of lung and heart-lung transplants at the Great Ormond Street Hospital for Children, London, UK, using a newly revised treatment protocol. To report the prevalence of rejection and bacterial, viral or fungal pathogens in asymptomatic children and compare this with the prevalence in children with symptoms. The study population included all paediatric patients undergoing single lung transplantation (SLTx), double lung transplantation (DLTx) or heart-lung transplantation between January 2002 and December 2005. Surveillance bronchoscopies were performed at 1 week, and 1, 3, 6 and 12 months after transplant. Bronchoscopies were classified according to whether subjects had symptoms, defined as the presence of cough, sputum production, dyspnoea, malaise, decrease in lung function or chest radiograph changes. Results of biopsies and BAL were collected, and procedural complications recorded. 23 lung-transplant operations were performed, 12 DLTx, 10 heart-lung transplants and 1 SLTx (15 female patients). The median (range) age of patients was 14.0 (4.9-17.3) years. 17 patients had cystic fibrosis. 95 surveillance bronchoscopies were performed. Rejection (> or =A2) was diagnosed in 4% of biopsies of asymptomatic recipients, and in 12% of biopsies of recipients with symptoms. Potential pathogens were detected in 29% of asymptomatic patients and in 69% of patients with symptoms. The overall diagnostic yield was 35% for asymptomatic children, and 85% for children with symptoms (p < 0.001). The complication rate for bronchoscopies was 3.2%. Many children have silent rejection or subclinical infection in the first year after lung transplantation. Routine surveillance bronchoscopy allows detection and targeted treatment of these complications.

The use of lung donors older than 55 years: a review of the United Network of Organ Sharing database.

PubMed

Bittle, Gregory J; Sanchez, Pablo G; Kon, Zachary N; Claire Watkins, A; Rajagopal, Keshava; Pierson, Richard N; Gammie, James S; Griffith, Bartley P

2013-08-01

Current lung transplantation guidelines stipulate that the ideal donor is aged younger than 55 years, but several institutions have reported that outcomes using donors aged 55 years and older are comparable with those of younger donors. We retrospectively reviewed the United Network for Organ Sharing (UNOS) database to identify all adult lung transplants between 2000 and 2010 in the United States. Patients were stratified by donor age 18 to 34 (reference), 35 to 54, 55 to 64, and ≥ 65 years. Primary outcomes included survival at 30 days and at 1, 3, and 5 years and rates of bronchiolitis obliterans syndrome (BOS). Survival was assessed using the Kaplan-Meier method. Risk factors for mortality were identified by multivariable Cox and logistic regression. We identified 10,666 recipients with median follow-up of 3 years (range, 0-10 years). Older donors were more likely to have died of cardiovascular or cerebrovascular causes, but there were no differences in recipient diagnosis, lung allocation score, or incidence of BOS as a function of donor age. The use of donors aged 55 to 64 years was not a risk factor for mortality at 1 year (odds ratio, 1.1; p = 0.304) or 3 years (odds ratio, 0.923; p = 0.571) compared with the reference group; however, use of donors aged > 65 years was associated with increased mortality at both time points (odds ratio, 2.8 and 2.4, p < 0.02). Outcomes after lung transplantation using donors aged 55 to 64 years were similar to those observed with donors meeting conventional age criteria. Donors aged ≥ 65 years, however, were associated with decreased intermediate-term survival, although there was no increased risk of BOS for this group. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation.

PubMed

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

2015-02-15

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

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop.

PubMed

Lama, Vibha N; Belperio, John A; Christie, Jason D; El-Chemaly, Souheil; Fishbein, Michael C; Gelman, Andrew E; Hancock, Wayne W; Keshavjee, Shaf; Kreisel, Daniel; Laubach, Victor E; Looney, Mark R; McDyer, John F; Mohanakumar, Thalachallour; Shilling, Rebecca A; Panoskaltsis-Mortari, Angela; Wilkes, David S; Eu, Jerry P; Nicolls, Mark R

2017-05-04

Lung transplantation, a cure for a number of end-stage lung diseases, continues to have the worst long-term outcomes when compared with other solid organ transplants. Preclinical modeling of the most common and serious lung transplantation complications are essential to better understand and mitigate the pathophysiological processes that lead to these complications. Various animal and in vitro models of lung transplant complications now exist and each of these models has unique strengths. However, significant issues, such as the required technical expertise as well as the robustness and clinical usefulness of these models, remain to be overcome or clarified. The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop in March 2016 to review the state of preclinical science addressing the three most important complications of lung transplantation: primary graft dysfunction (PGD), acute rejection (AR), and chronic lung allograft dysfunction (CLAD). In addition, the participants of the workshop were tasked to make consensus recommendations on the best use of these complimentary models to close our knowledge gaps in PGD, AR, and CLAD. Their reviews and recommendations are summarized in this report. Furthermore, the participants outlined opportunities to collaborate and directions to accelerate research using these preclinical models.

Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion

PubMed Central

Andreasson, Anders S.I.; Karamanou, Danai M.; Gillespie, Colin S.; Özalp, Faruk; Butt, Tanveer; Hill, Paul; Jiwa, Kasim; Walden, Hannah R.; Green, Nicola J.; Borthwick, Lee A.; Clark, Stephen C.; Pauli, Henning; Gould, Kate F.; Corris, Paul A.; Ali, Simi; Dark, John H.

2017-01-01

Abstract OBJECTIVES: Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. METHODS: In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. RESULTS: Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1β and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1β concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. CONCLUSIONS: This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study. PMID:28082471

Infusion of mesenchymal stem cells protects lung transplants from cold ischemia-reperfusion injury in mice.

PubMed

Tian, Weijun; Liu, Yi; Zhang, Bai; Dai, Xiangchen; Li, Guang; Li, Xiaochun; Zhang, Zhixiang; Du, Caigan; Wang, Hao

2015-02-01

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.

Acute pulmonary allograft rejection. Mechanisms, diagnosis, and management.

PubMed

King-Biggs, M B

1997-06-01

Rejection is a common complication following lung transplantation, and can lead to considerable short- and long-term morbidity. As numbers and survival rates of lung transplant recipients increase, it is apparent that acute rejection can occur months or years after transplantation, and may be resistant to standard therapies. Mechanisms of acute rejection have been well studied in other solid organ transplant recipients, and are beginning to be addressed in the lung recipient. This article addresses some of the common issues of diagnosis and management of acute rejection which arise frequently during the care of lung transplant recipients.

Extracorporeal membrane oxygenation as a bridge to lung transplant: midterm outcomes.

PubMed

Bermudez, Christian A; Rocha, Rodolfo V; Zaldonis, Diana; Bhama, Jay K; Crespo, Maria M; Shigemura, Norihisa; Pilewski, Joseph M; Sappington, Penny L; Boujoukos, Arthur J; Toyoda, Yoshiya

2011-10-01

Extracorporeal membrane oxygenation (ECMO) is used occasionally as a bridge to lung transplantation. The impact on mid-term survival is unknown. We analyzed outcomes after lung transplant over a 19-year period in patients who received ECMO support. From March 1991 to October 2010, 1,305 lung transplants were performed at our institution. Seventeen patients (1.3%) were supported with ECMO before lung transplant. Diagnoses included retransplantation (n = 6), pulmonary fibrosis (n = 6), cystic fibrosis (n = 4), and chronic obstructive pulmonary disease (n = 1). Fifteen patients underwent double lung transplant, one patient had single left lung transplant and one patient had a heart-lung transplant. Venovenous and venoarterial ECMO were implanted in eight and nine cases, respectively. Median duration of support was 3.2 days (range, 1 to 49 days). Mean patient follow-up was 2.3 years. Thirty-day, 1-year, and 3-year survivals were 81%, 74%, and 65%, respectively, for the supported patients and 93%, 78%, and 62% in the control group (p = 0.56). Two-year survival was not affected by ECMO type, with survival of five out of nine patients supported by venoarterial ECMO vs seven out of eight patients supported by venovenous ECMO (p = 0.17). At 1- year follow-up, allograft function for the ECMO-supported patients did not differ from the control group (forced expiratory volume in one second, 2.35 L vs 2.09 L, p = 0.39) (forced vital capacity, 3.06 L vs 2.71 L, p = 0.34). Extracorporeal membrane oxygenation as a bridge to lung transplantation is associated with higher perioperative mortality but acceptable mid-term survival in carefully selected patients. Late allograft function did not differ in patients who received ECMO support before lung transplant from those who did not receive ECMO. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Recipient selection process and listing for lung transplantation

PubMed Central

Dupont, Lieven; Yserbyt, Jonas; Schaevers, Veronique; Van Raemdonck, Dirk; Neyrinck, Arne; Vos, Robin

2017-01-01

Lung transplantation remains the ultimate treatment option for selected patients with end-stage (cardio) pulmonary disease. Given the current organ shortage, it is without any doubt that careful selection of potential transplant candidates is essential as this may greatly influence survival after the procedure. In this paper, we will review the current guidelines for referral and listing of lung transplant candidates in general, and in more depth for the specific underlying diseases. Needless to state that these are not absolute guidelines, and that decisions depend upon center’s activity, waiting list, etc. Therefore, every patient should be discussed with the transplant center before any definite decision is made to accept or decline a patient for lung transplantation. PMID:29221322

Lung transplantation in the United States, 1998-2007.

PubMed

McCurry, K R; Shearon, T H; Edwards, L B; Chan, K M; Sweet, S C; Valapour, M; Yusen, R; Murray, S

2009-04-01

This article highlights trends and changes in lung and heart-lung transplantation in the United States from 1998 to 2007. The most significant change over the last decade was implementation of the Lung Allocation Score (LAS) allocation system in May 2005. Subsequently, the number of active wait-listed lung candidates declined 54% from pre-LAS (2004) levels to the end of 2007; there was also a reduction in median waiting time, from 792 days in 2004 to 141 days in 2007. The number of lung transplants performed yearly increased through the decade to a peak of 1 465 in 2007; the greatest single year increase occurred in 2005. Despite candidates with increasingly higher LAS scores being transplanted in the LAS era, recipient death rates have remained relatively stable since 2003 and better than in previous years. Idiopathic pulmonary fibrosis became the most common diagnosis group to receive a lung transplant in 2007 while emphysema was the most common diagnosis in previous years. The number of retransplants and transplants in those aged > or =65 performed yearly have increased significantly since 1998, up 295% and 643%, respectively. A decreasing percentage of lung transplant recipients are children (3.5% in 2007, n = 51). With LAS refinement ongoing, monitoring of future impact is warranted.

Allogeneic blood transfusion in bilateral lung transplantation: impact on early function and mortality.

PubMed

Ong, Lay Ping; Thompson, Emily; Sachdeva, Ashwin; Ramesh, B C; Muse, Hazel; Wallace, Kirstie; Parry, Gareth; Clark, Stephen Charles

2016-02-01

Blood transfusion is associated with higher morbidity and mortality after general cardiothoracic surgery but its impact within the transplant population is unclear. We investigated the profile of blood product transfusion in the bilateral lung transplant population and its impact on function and mortality. Three hundred and eleven adult patients who underwent bilateral lung transplant between 2003 and 2013 were retrospectively reviewed. Patients were stratified according to pretransplant diagnoses and amount of blood products transfused within 24 h of transplant. All-cause mortality at the 1-year follow-up was analysed using a Cox proportional hazards regression model. One hundred and seventy-four male patients and 137 female patients (mean age = 41.4 ± 14.0 years) underwent bilateral lung transplant using cardiopulmonary bypass for cystic fibrosis (48.9%), fibrotic lung disease (12.2%), emphysema (27.0%), bronchiectasis (5.8%), pulmonary hypertension (1.3%) and others (4.5%). The median number of red blood cells in the first 24 h was 3 (0-40) units, fresh frozen plasma (FFP) = 2 (0-26) units and platelets = 1 (0-7) units. The unadjusted all-cause mortality at the 1-year follow-up did not appear to be different between patient subgroups stratified by the median number of units of red blood cells (P = 0.827) or FFP transfused (P = 0.456). However, 1-year mortality was adversely affected when more than the median number of units of platelets was transfused (P = 0.010). Upon adjustment for confounding variables, 1-year mortality was noted to be greater among patients transfused more than the median unit of platelets (adjusted hazard ratios: 2.3, 95% confidence interval: 1.15-4.61, P = 0.019) and those with longer bypass times (P = 0.046). No significant difference in the number of units transfused was noted when patients were stratified by pretransplant diagnosis. Predicted lung function at 3 and 6 months was not significantly affected by greater blood product use. Unlike general cardiothoracic surgery, blood transfusion had no effect on all-cause mortality, whereas a greater administration of platelets was observed to be associated with higher adjusted 1-year mortality. Transfusion rates were not significantly influenced by pretransplant diagnoses. Interestingly, lung function at 3 and 6 months was similar for patients who received more blood product transfusion. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Ocular complications in patients with lung transplants.

PubMed

Tarabishy, Ahmad B; Khatib, Omar F; Nocero, John R; Budev, Marie; Kaiser, Peter K

2011-09-01

To describe infectious and non-infectious ocular complications found in patients with lung transplants. 545 patients underwent lung transplantation from January 1998 to September 2008 at the Cleveland Clinic. Patients who underwent ophthalmic examination at the Cole Eye Institute after lung transplantation were included in the study. Diagnoses, treatments, surgeries, laboratory parameters of immune status and patient survival were examined. Of the 545 patients who received a lung transplant during the study period at the Cleveland Clinic, 46 (8.4%) patients underwent ophthalmology examination after a lung transplant. The most common ocular finding was posterior subcapsular cataract, found in 13/46 (28.3%) patients. Infectious ocular complications were present in 6/46 patients (13.0%) including fungal infections (rhino-orbital mucormycosis (n=1), disseminated Pseudallescheria boydii infection (n=2)), cytomegalovirus retinitis (n=1), varicella-zoster virus keratouveitis (n=1) and herpes zoster ophthalmicus (n=1). Five of six patients with infectious ocular complications died within 6 months of evaluation. Decreased absolute lymphocyte count was associated with infectious ocular complications (p=0.014). Many ocular conditions can occur in patients with lung transplants. Ocular infectious complications were uncommon but may be associated with increased mortality.

[Clinical and functional characteristics of patients prior to lung transplantation: report of experience at the Clínica Puerta de Hierro].

PubMed

Laporta, Rosalía; Ussetti, Piedad; Mora, Gema; López, Cristina; Gómez, David; de Pablo, Alicia; Lázaro, M Teresa; Carreño, M Cruz; Ferreiro, M José

2008-08-01

The time at which lung transplantation is indicated is determined by clinical and functional criteria that vary according to the particular disease. The aim of our study was to present the criteria according to which patients were placed on waiting lists for lung transplantation in our hospital. We analyzed retrospectively the clinical characteristics, lung function, heart function, and 6-minute walk test results of patients who had received a lung transplant in our hospital from January 2002 through September 2005. During the study period 100 lung transplants were performed. The mean age of the patients was 45 years (range, 15-67 years) and 57% were men. The diseases that most often led to a lung transplant were chronic obstructive pulmonary disease (COPD) (35%), pulmonary fibrosis (29%), and bronchiectasis (21%). Lung function values differed by disease: mean (SD) forced expiratory volume in 1 second (FEV1) was 20% (11%) and forced vital capacity (FVC) was 37% (15%) in patients with COPD; FEV1 was 41% (15%) and FVC, 40% (17%) in patients with pulmonary fibrosis; and FEV1 was 23% (7%) and FVC, 37% (10%) in patients with bronchiectasis. The patients who received lung transplants in our hospital were in advanced phases of their disease and met the inclusion criteria accepted by the various medical associations when they were placed on the waiting list.

International Society for Heart and Lung Transplantation Donation After Circulatory Death Registry Report.

PubMed

Cypel, Marcelo; Levvey, Bronwyn; Van Raemdonck, Dirk; Erasmus, Michiel; Dark, John; Love, Robert; Mason, David; Glanville, Allan R; Chambers, Daniel; Edwards, Leah B; Stehlik, Josef; Hertz, Marshall; Whitson, Brian A; Yusen, Roger D; Puri, Varun; Hopkins, Peter; Snell, Greg; Keshavjee, Shaf

2015-10-01

The objective of this study was to review the international experience in lung transplantation using lung donation after circulatory death (DCD). In this retrospective study, data from the International Society for Heart and Lung Transplantation (ISHLT) DCD Registry were analyzed. The study cohort included DCD lung transplants performed between January 2003 and June 2013, and reported to the ISHLT DCD Registry as of April 2014. The participating institutions included 10 centers in North America, Europe and Australia. The control group was a cohort of lung recipients transplanted using brain-dead donors (DBDs) during the same study period. The primary end-point was survival after lung transplantation. There were 306 transplants performed using DCD donors and 3,992 transplants using DBD donors during the study period. Of the DCD transplants, 94.8% were Maastricht Category III, whereas 4% were Category IV and 1.2% Category V (euthanasia). Heparin was given in 54% of the cases, donor extubation occurred in 90% of the cases, and normothermic ex vivo lung perfusion (EVLP) was used in 12%. The median time from withdrawal of life support therapy (WLST) to cardiac arrest was 15 minutes (5th to 95th percentiles of 5 to 55 minutes), and from WLST to cold flush was 33 minutes (5th to 95th percentiles of 19.5 to 79.5 minutes). Recipient age and medical diagnosis were similar in DCD and DBD groups (p = not significant [NS]). Median hospital length of stay was 18 days in DCD lung transplants and 16 days in DBD transplants (p = 0.016). Thirty-day survival was 96% in the DCD group and 97% in the DBD group. One-year survival was 89% in the DCD group and 88% in the DBD group (p = NS). Five-year survival was 61% in both groups (p = NS). The mechanism of donor death within the DCD group seemed to influence recipient early survival. The survival rates through 30 days were significantly different by donor mechanism of death (p = 0.0152). There was no significant correlation between the interval of WLST to pulmonary flush with survival (p = 0.11). This large study of international, multi-center experience demonstrates excellent survival after lung transplantation using DCD donors. It should be further evaluated whether the mechanism of donor death influences survival after DCD transplant. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2015-10-12

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.

Low-dose computed tomography volumetry for subtyping chronic lung allograft dysfunction.

PubMed

Saito, Tomohito; Horie, Miho; Sato, Masaaki; Nakajima, Daisuke; Shoushtarizadeh, Hassan; Binnie, Matthew; Azad, Sassan; Hwang, David M; Machuca, Tiago N; Waddell, Thomas K; Singer, Lianne G; Cypel, Marcelo; Liu, Mingyao; Paul, Narinder S; Keshavjee, Shaf

2016-01-01

The long-term success of lung transplantation is challenged by the development of chronic lung allograft dysfunction (CLAD) and its distinct subtypes of bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). However, the current diagnostic criteria for CLAD subtypes rely on total lung capacity (TLC), which is not always measured during routine post-transplant assessment. Our aim was to investigate the utility of low-dose 3-dimensional computed tomography (CT) lung volumetry for differentiating RAS from BOS. This study was a retrospective evaluation of 63 patients who had developed CLAD after bilateral lung or heart‒lung transplantation between 2006 and 2011, including 44 BOS and 19 RAS cases. Median post-transplant follow-up was 65 months in BOS and 27 months in RAS. The median interval between baseline and the disease-onset time-point for CT volumetry was 11 months in both BOS and RAS. Chronologic changes and diagnostic accuracy of CT lung volume (measured as percent of baseline) were investigated. RAS showed a significant decrease in CT lung volume at disease onset compared with baseline (mean 3,916 ml vs 3,055 ml when excluding opacities, p < 0.0001), whereas BOS showed no significant post-transplant change (mean 4,318 ml vs 4,396 ml, p = 0.214). The area under the receiver operating characteristic curve of CT lung volume for differentiating RAS from BOS was 0.959 (95% confidence interval 0.912 to 1.01, p < 0.0001) and the calculated accuracy was 0.938 at a threshold of 85%. In bilateral lung or heart‒lung transplant patients with CLAD, low-dose CT volumetry is a useful tool to differentiate patients who develop RAS from those who develop BOS. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Review of the International Society for Heart and Lung Transplantation Practice guidelines for management of heart failure in children.

PubMed

Colan, Steven D

2015-08-01

In 2004, practice guidelines for the management of heart failure in children by Rosenthal and colleagues were published in conjunction with the International Society for Heart and Lung Transplantation. These guidelines have not been updated or reviewed since that time. In general, there has been considerable controversy as to the utility and purpose of clinical practice guidelines, but there is general recognition that the relentless progress of medicine leads to the progressive irrelevance of clinical practice guidelines that do not undergo periodic review and updating. Paediatrics and paediatric cardiology, in particular, have had comparatively minimal participation in the clinical practice guidelines realm. As a result, most clinical practice guidelines either specifically exclude paediatrics from consideration, as has been the case for the guidelines related to cardiac failure in adults, or else involve clinical practice guidelines committees that include one or two paediatric cardiologists and produce guidelines that cannot reasonably be considered a consensus paediatric opinion. These circumstances raise a legitimate question as to whether the International Society for Heart and Lung Transplantation paediatric heart failure guidelines should be re-reviewed. The time, effort, and expense involved in producing clinical practice guidelines should be considered before recommending an update to the International Society for Heart and Lung Transplantation Paediatric Heart Failure guidelines. There are specific areas of rapid change in the evaluation and management of heart failure in children that are undoubtedly worthy of updating. These domains include areas such as use of serum and imaging biomarkers, wearable and implantable monitoring devices, and acute heart failure management and mechanical circulatory support. At the time the International Society for Heart and Lung Transplantation guidelines were published, echocardiographic tissue Doppler, 3 dimensional imaging, and strain and strain rate were either novel or non-existent and have now moved into the main stream. Cardiac magnetic resonance imaging (MRI) had very limited availability, and since that time imaging and assessment of myocardial iron content, delayed gadolinium enhancement, and extracellular volume have moved into the mainstream. The only devices discussed in the International Society for Heart and Lung Transplantation guidelines were extracorporeal membrane oxygenators, pacemakers, and defibrillators. Since that time, ventricular assist devices have become mainstream. Despite the relative lack of randomised controlled trials in paediatric heart failure, advances continue to occur. These advances warrant implementation of an update and review process, something that is best done under the auspices of the national and international cardiology societies. A joint activity that includes the International Society for Heart and Lung Transplantation, American College of Cardiology/American Heart Association, the Association for European Paediatric and Congenital Cardiology (AEPC), European Society of Cardiology, Canadian Cardiovascular Society, and others will have more credibility than independent efforts by any of these organisations.

Pulmonary fibrosis: rate of disease progression as a trigger for referral for lung transplantation

PubMed Central

Mackay, Laura S; Anderson, Rachel L; Parry, Gareth; Lordan, James; Corris, Paul A; Fisher, Andrew J

2007-01-01

Background Lung transplantation is the only treatment modality that provides a survival advantage in pulmonary fibrosis, but many patients deemed suitable will die awaiting lung transplantation. While donor organ shortage undoubtedly contributes to this, late referral to the transplant centre may also play a role. This study investigates factors influencing the chance of patients with pulmonary fibrosis reaching lung transplantation. Methods A single‐centre retrospective review of patient demographic data, assessment investigations and subsequent clinical outcomes was performed for patients with pulmonary fibrosis assessed for lung transplantation over a 5‐year period. Results Between March 1999 and March 2004, 129 patients with pulmonary fibrosis underwent formal transplant assessment. Sixty‐nine were accepted and listed for lung transplantation. Of these, 17 were transplanted, 37 died while waiting, 4 were removed from the list and 11 were still waiting at the conclusion of the study. The median waiting time on the list for those transplanted was 103 days (range 6–904) compared with 125 days (range 2–547) for those who died while on the list (p = 0.65). There was no significant difference in age, spirometry, total lung capacity, gas transfer measures or 6 min walk distance between those who died waiting and those transplanted. However, time from onset of symptoms to transplant assessment was significantly shorter in those who died on the waiting list (median 29 months (range 2–120)) than in those transplanted (median 46 months (range 6–204), p = 0.037). Conclusion Patients with pulmonary fibrosis who died awaiting transplantation had similar disease severity at assessment as those who achieved transplantation. However, the interval between symptom onset and transplant referral was significantly shorter in those who died while on the waiting list, suggesting they had more rapidly progressive disease. The rate of disease progression appears to be a more sensitive indicator for transplantation referral than any single physiological measure of disease severity and should act as an important trigger for early transplant referral. PMID:17573439

Angiotensin receptors as sensitive markers of acute bronchiole injury after lung transplantation.

PubMed

Nataatmadja, Maria; Passmore, Margaret; Russell, Fraser D; Prabowo, Sulistiana; Corley, Amanda; Fraser, John F

2014-08-01

Although lung transplantation is the only means of survival for patients with end-stage pulmonary disease, outcomes from this intervention are inferior to other solid organ transplants. The reason for the poor outcomes may be linked to an early reaction, such as primary graft dysfunction, and associated with marked inflammatory response, bronchiole injury, and later fibrotic responses. Mediators regulating these effects include angiotensin II and matrix metalloproteinases (MMPs). We investigated changes to these mediators over the course of cardiopulmonary bypass (CPB) and up to 72 h after lung transplantation, using immunohistochemistry, Western blot, and ELISA techniques. We found 4- and 16-fold increases in plasma angiotensin II and MMP-9, respectively, from pre-CPB to post-CPB. MMP-9 levels remained elevated 1 h after transplantation. MMP-2 levels were elevated 6-24 h after lung transplantation. Type 2 angiotensin II receptor (ATR2) expression was 3.5-fold higher in bronchoalveolar cells 1-6 h after transplantation than in controls. The study suggests that the combination of cardiopulmonary bypass and lung transplantation is associated with early changes in the angiotensin II receptor system and in MMPs, and that altered expression of these mediators may be a useful marker to examine pathological changes that occur in lungs during transplant surgery.

Role of gastroesophageal reflux disease in lung transplantation

PubMed Central

Hathorn, Kelly E; Chan, Walter W; Lo, Wai-Kit

2017-01-01

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

Lung cancer in patients with lung transplants.

PubMed

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

2012-09-01

The aim of our study was to describe the incidence of lung cancer in patients after lung transplantation (LT). We performed an observational, retrospective, descriptive study based on data from 340 patients undergoing lung transplantation between October 1993 and December 2010. We collected data about the donors, recipients, intra- and postoperative periods, and survivals. We identified 9 (2.6%) patients who developed lung cancer after LT. Their average age was 56 ± 9.3 years (range, 18-63). All cases were men with 8/9 (88.8%) having received a single lung transplant. All cancers developed in the native lung. The indications for transplantation were: emphysema type chronic obstructive pulmonary disease (COPD; n = 5), idiopathic pulmonary fibrosis (n = 3), or cystic fibrosis (n = 1); 77% of them were former smokers. All of the COPD patient were affected. The interval from transplantation to diagnosis was 53.3 ± 12 months (range 24-86). Survival after cancer diagnosis was 49.3 ± 6.3 (range = 0-180) months. LT was associated with a relatively high incidence of lung cancer, particularly in the native lung. In our series, lung cancer was related more to patients with emphysema-type COPD and a history of smoking. We believe that these patients should be closely followed to establish the diagnosis and apply early treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Post-transplant survival in idiopathic pulmonary fibrosis patients concurrently listed for single and double lung transplantation.

PubMed

Chauhan, Dhaval; Karanam, Ashwin B; Merlo, Aurelie; Tom Bozzay, P A; Zucker, Mark J; Seethamraju, Harish; Shariati, Nazly; Russo, Mark J

2016-05-01

Lung transplantation is a widely accepted treatment for patients with end-stage lung disease related to idiopathic pulmonary fibrosis (IPF). However, there are conflicting data on whether double lung transplant (DLT) or single lung transplant (SLT) is the superior therapy in these patients. The purpose of this study was to determine whether actuarial post-transplant graft survival among IPF patients concurrently listed for DLT and SLT is greater for recipients undergoing the former or the latter. The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant candidates with IPF listed between January 1, 2001 and December 31, 2009 (n = 3,411). The study population included 1,001 (29.3%) lung transplant recipients concurrently listed for DLT and SLT, all ≥18 years of age. The primary outcome measure was actuarial post-transplant graft survival, expressed in years. Among the study population, 433 (43.26%) recipients underwent SLT and 568 (56.74%) recipients underwent DLT. The analysis included 2,722.5 years at risk, with median graft survival of 5.31 years. On univariate (p = 0.317) and multivariate (p = 0.415) regression analyses, there was no difference in graft survival between DLT and SLT. Among IPF recipients concurrently listed for DLT and SLT, there is no statistical difference in actuarial graft survival between recipients undergoing DLT vs SLT. This analysis suggests that increased use of SLT for IPF patients may increase the availability of organs to other candidates, and thus increase the net benefit of these organs, without measurably compromising outcomes. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

A longitudinal study of patients' symptoms before and during the first year after lung transplantation.

PubMed

Lanuza, Dorothy M; Lefaiver, Cheryl A; Brown, Roger; Muehrer, Rebecca; Murray, Margaret; Yelle, Maria; Bhorade, Sangeeta

2012-01-01

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. A prospective, repeated measures design was used to describe the symptom experience of 85 lung transplant recipients between 2000 and 2005. The transplant symptom inventory was administered before and at one, three, six, nine, and 12 months post-transplant. Ridit analysis provided a unique method for describing symptom experiences and changes. After lung transplantation, significant (p<0.05) 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 time since transplant. 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 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" change or lack of change in patients' symptoms from pre- to post-lung transplant. © 2012 John Wiley & Sons A/S.

Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion.

PubMed

Andreasson, Anders S I; Karamanou, Danai M; Gillespie, Colin S; Özalp, Faruk; Butt, Tanveer; Hill, Paul; Jiwa, Kasim; Walden, Hannah R; Green, Nicola J; Borthwick, Lee A; Clark, Stephen C; Pauli, Henning; Gould, Kate F; Corris, Paul A; Ali, Simi; Dark, John H; Fisher, Andrew J

2017-03-01

Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1β and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1β concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.

Lung transplantation in patients who have undergone prior cardiothoracic procedures.

PubMed

Omara, Mohamed; Okamoto, Toshihiro; Arafat, Amr; Thuita, Lucy; Blackstone, Eugene H; McCurry, Kenneth R

2016-12-01

Patients who have undergone prior cardiothoracic procedures offer technical challenges that may affect post-transplant outcomes and be a reason to decline listing. Data are currently limited regarding the indication for lung transplantation among recipients who have had prior cardiothoracic procedures. Of 453 lung transplants performed at Cleveland Clinic from January 2005 to July 2010, 206 recipients (45%) had undergone prior cardiothoracic procedures: 157 lung only, 15 cardiac only, 10 cardiac + lung, 10 pleurodesis + lung, and 14 other. Chest tube placement was performed in 202 patients. Survival, post-transplant length of intensive care unit and hospital stays, primary graft dysfunction, and pulmonary function outcomes were compared with outcomes of patients not having prior procedures using propensity score adjustment. Short-term and long-term survival was similar between the 2 groups. Survival at 30 days, 1 year, and 5 years was 94%, 83%, and 55% for the prior cardiothoracic procedure group and 96%, 84%, and 53% for the no prior cardiothoracic procedure group (log-rank p = 0.9). Intensive care unit stay was longer (6 days vs 5 days, p = 0.02) in the prior cardiothoracic procedure group; this was particularly true for pleurodesis + lung (10 days, p = 0.05), although post-transplant hospital stay was similar (16 days, 16 days, and 22 days; p = 0.13). Primary graft dysfunction was not increased in the prior cardiothoracic procedure group. Forced expiratory volume in 1 second was similar for both groups but lower for thoracotomy and lung procedures using a bilateral chest tube (p < 0.05 each). A prior cardiothoracic procedure is not a contraindication for lung transplantation. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Comprehensive Care of the Lung Transplant Patient.

PubMed

Adegunsoye, Ayodeji; Strek, Mary E; Garrity, Edward; Guzy, Robert; Bag, Remzi

2017-07-01

Lung transplantation has evolved into a life-saving treatment with improved quality of life for patients with end-stage respiratory failure unresponsive to other medical or surgical interventions. With improving survival rates, the number of lung transplant recipients with preexisting and posttransplant comorbidities that require attention continues to increase. A partnership between transplant and nontransplant care providers is necessary to deliver comprehensive and optimal care for transplant candidates and recipients. The goals of this partnership include timely referral and assistance with transplant evaluation, optimization of comorbidities and preparation for transplantation, management of common posttransplant medical comorbidities, immunization, screening for malignancy, and counseling for a healthy lifestyle to maximize the likelihood of a good outcome. We aim to provide an outline of the main aspects of the care of candidates for and recipients of lung transplants for nontransplant physicians and other care providers. Copyright © 2016. Published by Elsevier Inc.

The Lung Microbiome After Lung Transplantation

PubMed Central

Becker, Julia B.; Poroyko, Valeriy

2014-01-01

Summary Lung transplantation survival remains significantly impacted by infections and the development of chronic rejection manifesting as bronchiolitis obliterans syndrome (BOS). Traditional microbiologic data has provided insight into the role of infections in BOS. Now, new non-culture-based techniques have been developed to characterize the entire population of microbes resident on the surfaces of the body, also known as the human microbiome. Early studies have identified that lung transplant patients have a different lung microbiome and have demonstrated the important finding that the transplant lung microbiome changes over time. Furthermore, both unique bacterial populations and longitudinal changes in the lung microbiome have now been suggested to play a role in the development of BOS. In the future, this technology will need to be combined with functional assays and assessment of the immune responses in the lung to help further explain the microbiome’s role in the failing lung allograft. PMID:24601662

Being a Living Donor: Risks

MedlinePlus

... bowel Fluid on the lungs Lung, Intestine, and Pancreas Pancreas, intestine, and lung living-donor transplants are very ... care of the live organ donor: lung, liver, pancreas, and intestine data and medical guidelines. Transplantation. 2006 ...

Lungs from donation after circulatory death donors: an alternative source to brain-dead donors? Midterm results at a single institution.

PubMed

Zych, Bartlomiej; Popov, Aron-Frederik; Amrani, Mohamed; Bahrami, Toufan; Redmond, Karen Christina; Krueger, Heike; Carby, Martin; Simon, André Ruediger

2012-09-01

Donor organ shortage remains to be the major limitation in lung transplantation, and donation after circulatory death (DCD) might represent one way to alleviate this problem. DCD was introduced to our institution in 2007 and has been a part of our clinical routine since then. Here, we present the mid-term results of lung transplantation from DCD in a single institution and compare the outcomes with the lung recipient cohort receiving lungs from donation after brain death (DBD). Since initiation of the DCD programme in March 2007, of the 157 lung transplantations performed, 26 (16.5%) were retrieved from DCD donors, with 25 double- and 1 single-lung transplants being performed. Results were compared with standard DBD transplantations. Analyses included, amongst others, donor characteristics, survival, prevalence of primary graft dysfunction, acute rejection, lung function tests during follow-up, onset of bronchiolitis obliterans syndrome (BOS) as well as duration of mechanical ventilation, hospital and intensive care unit length of stay. While there was no significant difference between lung function, BOS and survival between the two groups, lungs from DCD donors had a higher PaO(2) (median; interquartile range) 498.3 (451.5; 525) vs. DBD 442.5 (371.25; 502) kPa before retrieval (P = 0.009). There was also a longer total ischaemic time in the DCD vs. DBD group: 320 min (298.75; 393.25) vs. 285.5 min (240; 373) (P = 0.025). All other parameters were comparable. Medium-term results after lung transplantation with organs procured after circulatory death are comparable with those obtained after standard lung transplantation. Therefore, DCD could be used to significantly increase the donor pool.

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

PubMed Central

Lama, Vibha N.; Belperio, John A.; Christie, Jason D.; El-Chemaly, Souheil; Fishbein, Michael C.; Gelman, Andrew E.; Hancock, Wayne W.; Keshavjee, Shaf; Kreisel, Daniel; Looney, Mark R.; McDyer, John F.; Shilling, Rebecca A.; Panoskaltsis-Mortari, Angela; Wilkes, David S.; Eu, Jerry P.; Nicolls, Mark R.

2017-01-01

Lung transplantation, a cure for a number of end-stage lung diseases, continues to have the worst long-term outcomes when compared with other solid organ transplants. Preclinical modeling of the most common and serious lung transplantation complications are essential to better understand and mitigate the pathophysiological processes that lead to these complications. Various animal and in vitro models of lung transplant complications now exist and each of these models has unique strengths. However, significant issues, such as the required technical expertise as well as the robustness and clinical usefulness of these models, remain to be overcome or clarified. The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop in March 2016 to review the state of preclinical science addressing the three most important complications of lung transplantation: primary graft dysfunction (PGD), acute rejection (AR), and chronic lung allograft dysfunction (CLAD). In addition, the participants of the workshop were tasked to make consensus recommendations on the best use of these complimentary models to close our knowledge gaps in PGD, AR, and CLAD. Their reviews and recommendations are summarized in this report. Furthermore, the participants outlined opportunities to collaborate and directions to accelerate research using these preclinical models. PMID:28469087

Therapeutic approach to respiratory infections in lung transplantation.

PubMed

Clajus, Carolina; Blasi, Francesco; Welte, Tobias; Greer, Mark; Fuehner, Thomas; Mantero, Marco

2015-06-01

Lung transplant recipients (LTRs) are at life-long risk for infections and disseminated diseases owing to their immunocompromised state. Besides organ failure and sepsis, infection can trigger acute and chronic graft rejection which increases mortality. Medical prophylaxis and treatment are based on comprehensive diagnostic work-up including previous history of infection and airway colonisation to reduce long-term complications and mortality. Common bacterial pathogens include Pseudomonas and Staphylococcus, whilst Aspergillus and Cytomegalovirus (CMV) are respectively the commonest fungal and viral pathogens. Clinical symptoms can be various in lung transplant recipients presenting an asymptomatic to severe progress. Regular control of infection parameters, daily lung function testing and lifelong follow-up in a specialist transplant centre are mandatory for early detection of bacterial, viral and fungal infections. After transplantation each patient receives intensive training with rules of conduct concerning preventive behaviour and to recognize early signs of post transplant complications. Early detection of infection and complications are important goals to reduce major complications after lung transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

The prevalence and extent of gastroesophageal reflux disease correlates to the type of lung transplantation.

PubMed

Fisichella, Piero Marco; Davis, Christopher S; Shankaran, Vidya; Gagermeier, James; Dilling, Daniel; Alex, Charles G; Kovacs, Elizabeth J; Joehl, Raymond J; Love, Robert B

2012-02-01

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. 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. 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. 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.

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

PubMed

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

2012-06-01

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

Pretransplant Aspergillus colonization of cystic fibrosis patients and the incidence of post-lung transplant invasive aspergillosis.

PubMed

Luong, Me-Linh; Chaparro, Cecilia; Stephenson, Anne; Rotstein, Coleman; Singer, Lianne G; Waters, Valerie; Azad, Sassan; Keshavjee, Shaf; Tullis, Elizabeth; Husain, Shahid

2014-02-15

Invasive aspergillosis (IA) is an important cause of morbidity and mortality among patients undergoing lung transplant. Cystic fibrosis-lung transplant recipients (CF-LTRs) may be at greater risk of IA following lung transplantation because of the presence of Aspergillus in their airways before transplantation. This study evaluated the impact of pretransplant Aspergillus colonization on the risk for IA among CF-LTRs. A single-center retrospective cohort study of CF-LTRs was conducted between 2006 and 2010. Respiratory tract cultures before transplantation were reviewed to identify patients with pretransplant Aspergillus colonization. Patients with positive Aspergillus sputum culture or positive bronchoalvelolar lavage (BAL) galactomannan after transplantation were classified as having colonization or disease according to the International Society of Heart and Lung Transplantation criteria. A total of 93 CF patients underwent lung transplantation. Seventy percent (65/93) of CF-LTRs had pretransplant Aspergillus colonization. Thirty-six patients had positive intraoperative Aspergillus culture from the native lung BAL. Overall, 22.5% (20/93) of CF-LTRs developed IA. Median time to IA was 42 days following transplantation. Positive intraoperative Aspergillus culture (OR 4.36, 95% CI 1.35-14.05, P=0.01) and treatment for acute cellular rejection within 90 days after transplantation (OR 3.53, 95% CI 1.03-12.15, P=0.05) were independent risk factors for IA. Antifungal prophylaxis was administered to 61% (57/93) of CF-LTRs. One-year mortality rate was 16% (15/93). IA was not associated with increased risk of death (OR 2.10, 95% CI 0.62-7.06, P=0.23). Pretransplant Aspergillus colonization is frequent among CF-LTRs and a positive intraoperative Aspergillus culture produced a fourfold higher risk of developing IA.

Examining ABO compatible donors in double lung transplants during the era of lung allocation score.

PubMed

Taghavi, Sharven; Jayarajan, Senthil N; Furuya, Yuka; Komaroff, Eugene; Shiose, Akira; Leotta, Eros; Hisamoto, Kazuhiro; Patel, Namrata; Cordova, Francis; Criner, Gerard; Guy, T Sloane; Toyoda, Yoshiya

2014-10-01

The short-term and long-term effect of using ABO compatible donors in the era of lung allocation score is unknown. This study determined if carefully selected ABO compatible donors could be used in double lung transplantation (DLT) with good outcomes. The United Network for Organ Sharing database was retrospectively reviewed for adult DLT from May 2005 to December 2011. Of 6,655 double lung transplants, 493 (7.4%) were with ABO compatible donors and 6,162 (92.6%) were with ABO identical donors. In multivariate analysis, use of ABO compatible donors was not associated with mortality at 30 days (HR, 1.16; 95% CI, 0.76 to 1.79, p = 0.49), 1 year (HR, 1.10; 95% CI, 0.86 to 1.42, p = 0.46), and 5 years (HR, 1.06; 95% CI, 0.83 to 1.34, p = 0.65). Variables associated with mortality at 5 years were donor female sex, donor age 60 years or greater, prolonged ischemic time, increasing recipient creatinine, recipient age, race mismatch, and mechanical ventilation or extracorporeal membrane oxygenation as a bridge to transplantation. Length of stay was longer in the ABO compatible group (30.9 vs 25.9 days, p = 0.001). Acute rejection episodes on index hospitalization (8.8 vs. 8.9%, p = 1.00), peak posttransplant forced expiratory volume in 1 second (FEV1) (82.7 vs 79.7%, p = 0.053), and decrement in FEV1 over time were not different (p = 0.13). Freedom from bronchiolitis obliterans syndrome was similar (1,475 vs 1,454 days, p = 0.17). The use of ABO compatible donors in the era of lung allocation score was not associated with short-term or long-term mortality and resulted in equivalent posttransplant lung function. A DLT with carefully selected ABO compatible donors can result in excellent outcomes. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Lung Cancer and Lung Transplantation.

PubMed

Brand, Timothy; Haithcock, Benjamin

2018-02-01

Lung transplantation remains a viable option for patients with endstage pulmonary disease. Despite removing the affected organ and replacing both lungs, the risk of lung malignancies still exists. Regardless of the mode of entry, lung cancer affects the prognosis in these patients and diligence is required. Copyright © 2017 Elsevier Inc. All rights reserved.

Lung transplantation in Hong Kong: 12 years of experience.

PubMed

Wong, Chi Fong; Fung, Siu Leung; Yan, See Wan; Lee, Joseph; Cheng, Lik Cheung; Chiu, Clement S W

2008-11-01

A lung transplant programme was launched in August 1994 at Grantham Hospital in Hong Kong with the first single-lung transplant performed in July 1995. A retrospective study was undertaken of all patients who had undergone lung transplantation and their outcomes analysed. Data were collected from hospital and outpatient records. There were 12 transplants (two single-lung and 10 double-lung) performed in the 12 years to December 2006. No postoperative or early mortality was observed. In addition to the usual complications there were two cases of early pulmonary tuberculosis and one rare case of delayed fungal sternotomy infection. The 1-year, 3-year and 5-year survival rates were 100%, 100% and 76.2%, respectively. All fatalities were related to the consequences of chronic rejection or its treatment. Despite the limited experience and the small case volume, the survival of patients was good and comparable with international experience.

Prolonged Barium-Impaction Ileus in Two Lung Transplant Recipients With Systemic Sclerosis: Case Report.

PubMed

Tokman, S; Hays, S R; Leard, L E; Bush, E L; Kukreja, J; Kleinhenz, M E; Golden, J A; Singer, J P

2015-12-01

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of sinus surgery on lung transplantation outcomes in cystic fibrosis.

PubMed

Leung, Man-Kit; Rachakonda, Leelanand; Weill, David; Hwang, Peter H

2008-01-01

In cystic fibrosis (CF) patients who are candidates for lung transplant, pretransplant sinus surgery has been advocated to avoid bacterial seeding of the transplanted lungs. This study reviews the 17-year experience of pretransplant sinus surgery among CF patients at a major transplant center. Retrospective chart review was performed in all CF patients who underwent heart-lung or lung transplantation at Stanford Medical Center between 1988 and 2005. Postoperative culture data from bronchoalveolar lavage (BAL) and sinus aspirates were evaluated, in addition to survival data. Eighty-seven CF transplant recipients underwent pretransplant sinus surgery; 87% (n=59/68) of patients showed recolonization of the lung grafts with Pseudomonas on BAL cultures. The median postoperative time to recolonization was 19 days. Bacterial floras cultured from sinuses were similar in type and prevalence as the floras cultured from BAL. When compared with published series of comparable cohorts in which pretransplant sinus surgery was not performed, there was no statistically significant difference in the prevalence of Pseudomonas recolonization. Times to recolonization also were similar. Survival rates in our cohort were similar to national survival rates for CF lung transplant recipients. Despite pretransplant sinus surgery, recolonization of lung grafts occurs commonly and rapidly with a spectrum of flora that mimics the sinus flora. Survival rates of CF patients who undergo prophylactic sinus surgery are similar to those from centers where prophylactic sinus surgery is not performed routinely. Pretransplant sinus surgery does not appear to prevent lung graft recolonization and is not associated with overall survival benefit.

Heart-lung transplantation: pediatric indications and outcomes

PubMed Central

2014-01-01

As indications for heart-lung transplant (HLT) have changed to some degree in the past 30 years, this treatment is being used less frequently in children due to more advanced care of severe heart and lung disease. This is fortunate as the outcomes for HLT are poor compared to other solid organ transplants and this is mainly due to the poorer outcome of the lung graft. PMID:25132980

Upper lobe fibrosis: a novel manifestation of chronic allograft dysfunction in lung transplantation.

PubMed

Pakhale, Smita Sakha; Hadjiliadis, Denis; Howell, David N; Palmer, Scott M; Gutierrez, Carlos; Waddell, Thomas K; Chaparro, Cecilia; Davis, R Duane; Keshavjee, Shaf; Hutcheon, Michael A; Singer, Lianne G

2005-09-01

Lung transplantation is an established treatment modality for a number of chronic lung diseases. Long-term survival after lung transplantation is limited by chronic allograft dysfunction, usually manifested by bronchiolitis obliterans syndrome. We describe a case series with upper lobe fibrosis, a novel presentation of chronic allograft dysfunction. We reviewed lung transplants at the Toronto General Hospital and Duke University Hospital from 1990 to 2002 and identified patients with upper lobe fibrosis. Thirteen of 686 patients (6 women) developed upper lobe fibrosis (Toronto, 9; Duke, 4); 12 of 13 had bilateral transplants. The median age at diagnosis was 42 years (range, 19-70). Primary diagnoses were cystic fibrosis, 6; emphysema, 4; sarcoidosis, 1; and pulmonary fibrosis, 2 patients. Radiographic diagnosis was made at a median of 700 days post-transplant (range, 150-2,920). Pulmonary function tests demonstrated predominantly a progressively worsening restrictive pattern. Open lung biopsy specimens revealed dense interstitial fibrosis, with occasional features of obliterative bronchitis, bronchiolitis obliterans obstructive pneumonia, and aspiration. Nine patients died at a median follow-up of 2,310 days (range, 266-3,740), 8 due to respiratory failure. Upper lobe fibrosis is a novel presentation of chronic allograft dysfunction in lung transplant recipients and is differentiated from bronchiolitis obliterans syndrome on the basis of physiologic and radiologic findings.

Rehabilitation and transition after lung transplantation in children.

PubMed

Burton, J H; Marshall, J M; Munro, P; Moule, W; Snell, G I; Westall, G P

2009-01-01

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.

Acute native lung hyperinflation is not associated with poor outcomes after single lung transplant for emphysema.

PubMed

Weill, D; Torres, F; Hodges, T N; Olmos, J J; Zamora, M R

1999-11-01

Single-lung transplantation for emphysema may be complicated by acute native lung hyperinflation (ANLH) with hemodynamic and ventilatory compromise. Some groups advocate the routine use of independent lung ventilation, double-lung transplant, or right-lung transplant with or without contralateral lung volume reduction surgery in high-risk patients. The goal of this study was to determine the incidence of ANLH and identify its potential predictors. We reviewed 51 consecutive single-lung transplants for emphysema. Symptomatic ANLH was defined as mediastinal shift and diaphragmatic flattening on chest x-ray with hemodynamic or respiratory failure requiring cardiopressor agents or independent lung ventilation. Preoperative and postoperative physiologic and hemodynamic data were analyzed from both recipients and donors. Sixteen patients developed radiographic ANLH; 8 were symptomatic, 2 severely so. We could not identify high-risk patients before transplant by pulmonary function tests, predicted donor total lung capacity (TLC)/actual recipient TLC ratio, pulmonary artery pressures, or the side transplanted. There was a trend toward an increased incidence of symptomatic ANLH in patients with bullous emphysema on chest computed tomography, but this was accounted for primarily by patients with alpha1-antitrypsin deficiency (4/13 vs 4/38 with chronic obstructive pulmonary disease, P = 0.10). No patient required cardiopulmonary bypass or inhaled nitric oxide intraoperatively. Patients with acute native lung hyperinflation did not have increased reperfusion edema as measured by chest x-ray score or PaO2/F(I)O2 ratio. Compared to patients without ANLH, symptomatic patients had longer ventilator times (64.9+/-14.6 hours vs 40.4+/-3.9, P = 0.02, ANOVA) and longer lengths of stay (19.3+/-2.1 days vs 13.7+/-1.3, P = 0.07), but 30-day survival was 100%. Two symptomatic patients required independent lung ventilation or inhaled nitric oxide; the others were managed with decreased minute ventilation, early extubation, and cardiopressor agents. No patient required early lung volume reduction surgery or retransplantation. Acute native lung hyperinflation had no effect on FEV1 or 6-minute walk results at 1 year; survival at 1, 2, or 3 years; or the rate of acute rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. Acute native lung hyperinflation is common radiographically but is rarely clinically severe. Although there was a trend toward an increase in symptomatic ANLH in patients with bullous emphysema, a high-risk group could not be identified preoperatively. Our results do not support the routine use of bilateral lung transplant, the exclusive use of right single-lung transplant, simultaneous lung volume reduction surgery, or independent lung ventilation for patients with emphysema. Management strategies should be employed that limit overdistension of the native lung and lead to early extubation.

Is total hip arthroplasty safely performed in lung transplant patients? Current experience from a retrospective study of the Zurich lung transplant cohort.

PubMed

Schmitt, Jürgen W; Benden, Christian; Dora, Claudio; Werner, Clément M L

2016-01-01

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.

The Eurotransplant Study on Twin Lung Transplants (ESOTWIN): 90 paired single-lung transplants from the same donor.

PubMed

Smits, Jacqueline M A; Melman, Sonja; Mertens, Bart J A; Laufer, Gunther; Persijn, Guido G; Van Raemdonck, Dirk

2003-12-15

Despite its reduced benefit for a single recipient, the transplantation of two single-lung allografts as opposed to one bilateral lung transplant has the indisputable advantage of maximizing the number of patients that benefit from a single donor. In the period 1997 to 1999, 90 paired single-lung transplants (SLTx) from 45 donors were performed in 16 lung centers in Eurotransplant, with a complete follow-up of 1 year. No significant differences between left- and right-lung allograft recipients were observed regarding age, sex, primary disease, number of human leukocyte antigen mismatches, cold ischemic time, and donor-to-recipient cytomegalovirus match. Early posttransplant outcome, as assessed by oxygenation index at 12, 24, and 48 hr, also did not differ significantly, and there were no differences in time to extubation and time spent in the intensive care unit. In the first month, six left- and three right-lung allograft recipients died. Bronchiolitis obliterans syndrome developed in 5 of 39 left-lung and 10 of 42 right-lung allograft recipients. If the retrieval team was different from the transplanting team, a significantly worse 1-year posttransplant survival rate was seen in patients who underwent left SLTx compared with those who underwent right SLTx (62% vs. 92%, respectively; P=0.04). More fatal posttransplant complications occur in patients undergoing left SLTx compared with right SLTx. A less optimistic assessment of the left lung by the not-implanting retrieval team is warranted.

[Infection in lung transplantation].

PubMed

Gavaldà, Joan; Román, Antonio

2007-12-01

Lung transplantation is now considered an established therapeutic option for patients with severe respiratory failure. Nevertheless, complications are frequent and can lead to intermediate- or long-term graft dysfunction and decreased survival. According to the registry of the International Society for Heart and Lung Transplantation, survival rates in these patients at one, two, and five years are 74%, 65%, and 47%, respectively. The main obstacle to long-term success of lung transplantation, however, is chronic rejection, which is characterized histologically as bronchiolitis obliterans and occurs in up to two-thirds of patients. One of the most important risk factors for the development of bronchiolitis obliterans, in addition to the number of previous acute rejection episodes and the incidence of persistent rejection, is cytomegalovirus infection and disease. Moreover, recent evidence has indicated a role for respiratory viruses as risk factors for the development of chronic rejection in lung transplant recipients. Infectious complications are a frequent cause of morbidity and mortality in these patients and are the cause of death in nearly half of them. Bacterial infection is the most frequent infectious complication in lung transplant patients. Among the total of infections, 35%-66% are bacterial and 50%-85% of patients present at least one episode. CMV is the second most frequent cause of infectious complications following lung transplantation. Despite the use of various preventive strategies, the risk of developing CMV disease in lung transplant recipients is over 5% during the first year. This is the only type of solid organ transplant in which the etiology of fungal infection is characteristically Aspergillus spp., in contrast to others in which infection by Candida spp. is most common. The incidence of invasive aspergillosis is about 4%.

Posttransplantation lymphoproliferative disorder in lung transplant recipients: a 15-year single institution experience.

PubMed

Muchtar, Eli; Kramer, Mordechai R; Vidal, Liat; Ram, Ron; Gurion, Ronit; Rosenblat, Yivgenia; Bakal, Ilana; Shpilberg, Ofer

2013-10-15

Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication after solid-organ transplantation. Historically, most cases of PTLD among lung transplant recipients occurred within the first year from transplantation and were associated with Epstein-Barr virus (EBV) infection. However, there are increasing reports on a late-onset form of PTLD. We reviewed all charts of patients undergoing either lung or heart-lung transplantation in a tertiary transplantation center between the years 1997 and 2012 and compared clinical and pathologic parameters between early- and late-onset PTLD. Ten patients with PTLD were identified. Median (range) time from transplantation to PTLD diagnosis was 41 (4-128) months. Three patients developed early PTLD. All were pretransplantation EBV seronegative and asymptomatic when diagnosed during surveillance chest imaging. In contrast, the seven patients with late-onset PTLD were all EBV seropositive before transplantation and were symptomatic at diagnosis. Although early-onset PTLD uniformly involved the transplanted lung, this was relatively rare in late-onset PTLD (3 of 3 vs. 1 of 7). All patients were initially treated with reduction of immunosuppression, with at least one additional treatment modality used, mainly chemoimmunotherapy. Eight patients attained complete remission. With a median follow-up of 17 months, 8 patients died, mainly from treatment-related causes rather than disease progression. Our cohort of lung transplant recipients demonstrates a trend of late-onset PTLD with the majority of patients who died of treatment-related causes rather than disease progression. Therefore, substantial efforts should be focused on treatment-related mortality reduction.

Heart transplantation in the setting of complex congenital heart disease and physiologic single lung.

PubMed

Zuckerman, Warren A; Richmond, Marc E; Lee, Teresa M; Bacha, Emile A; Chai, Paul J; Chen, Jonathan M; Addonizio, Linda J

2015-12-01

To highlight the success of heart transplantation in patients with complex congenital heart disease and physiologic single lung by providing an update on the world's largest reported cohort. Demographic, perioperative, postoperative, and outcomes data were collected retrospectively on all patients undergoing heart transplant to single lung at Columbia University Medical Center since 1992, and compared with all other patients undergoing transplants performed for single ventricle or tetralogy of Fallot during that time. Twenty-two patients (mean age, 20.6 years; range, 5 months-47 years) underwent heart transplant to single lung. Compared with controls (n = 67), the single lung group had more male patients and a greater proportion of tetralogy compared with single ventricle patients, although the single lung group had fewer post-Fontan patients. Age, weight, and body surface area were similar between the groups as were use of mechanical circulatory support and mechanical ventilation before transplant. Median time to extubation, time on inotropes, and length of stay were similar. There were 3 perioperative deaths, including a patient who died during postoperative day 1 from primary graft failure, likely related to a combination of elevated pulmonary vascular resistance and volume load. There were 5 additional mortalities during intermediate- and long-term follow-up, none of which were related to single-lung physiology. There was no significant survival difference between the groups. In patients with complex congenital heart disease and single lung physiology, heart transplant alone remains an excellent option, with comparable outcomes to patients undergoing transplant with similar cardiac anatomy and dual lung physiology. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

[Unilateral lung transplant in a case of terminal pulmonary fibrosis].

PubMed

Santillán-Doherty, P

1990-01-01

Up to 1980, less than 40 lung transplants had been reported worldwide without any success. The factors influencing these poor results were related to complications at the bronchial anastomosis and ineffective immunosuppressive regimens. The development of new immunosuppressive drugs has permitted the reevaluation of lung transplantation as a therapeutic option. The success with heart-lung transplantation stimulated the development of clinical human single-lung and double-lung transplantation. However the world experience is still scarce. In our institution we have developed experimental work leading to the establishment of a lung transplant program. This paper describes our first single lung transplant patient. The patient, a 33 year old man with end-stage pulmonary fibrosis, was totally oxygen dependant, maintaining arterial blood oxygen levels below 40 mmHg without oxygen supplementation and confined to a wheelchair. A single left lung transplant was performed from a young brain-dead donor. The bronchial anastomosis was protected with an omental flap. The immunosuppressive regimen was based on cyclosporin A and azathioprine from the beginning, adding prednisone on the third postoperative week. There has been only one episode suggestive of acute rejection which was managed with methylprednisolone. On the 9th postoperative week the patient developed a bronchial stenoses at the anastomotic site which required dilation and stenting with an endobronchial silastic stent. His clinical course has been uneventful since then. His ventilatory parameters showed an increase of vital capacity from 900 to 2100 mL and his FEV1 from 700 to 1500 mL. His gas exchange has been normal with arterial blood gas oxygen above 60 mmHg and oxygen saturation above 94%.(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants.

PubMed

Minari, A; Husni, R; Avery, R K; Longworth, D L; DeCamp, M; Bertin, M; Schilz, R; Smedira, N; Haug, M T; Mehta, A; Gordon, S M

2002-12-01

Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. The 2,046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. We identified 33 cases of IA (28% disseminated) in 2,046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1,000 patient-years (33 cases/6,813 pt-years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1,000-pt year vs. heart 0.4% (3/686) or 1.4 per 1,000-pt year vs. liver 0.7% (3/439) or 2.1 per 1,000-pt year vs. renal 0.4% (3/733) or 1.2 per 1,000-pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.

The impact of the lung allocation score on short-term transplantation outcomes: a multicenter study.

PubMed

Kozower, Benjamin D; Meyers, Bryan F; Smith, Michael A; De Oliveira, Nilto C; Cassivi, Stephen D; Guthrie, Tracey J; Wang, Honkung; Ryan, Beverly J; Shen, K Robert; Daniel, Thomas M; Jones, David R

2008-01-01

The lung allocation score restructured the distribution of scarce donor lungs for transplantation. The algorithm ranks waiting list patients according to medical urgency and expected benefit after transplantation. The purpose of this study was to evaluate the impact of the lung allocation score on short-term outcomes after lung transplantation. A multicenter retrospective cohort study was performed with data from 5 academic medical centers. Results of patients undergoing transplantation on the basis of the lung allocation score (May 4, 2005 to May 3, 2006) were compared with those of patients receiving transplants the preceding year before the lung allocation score was implemented (May 4, 2004, to May 3, 2005). The study reports on 341 patients (170 before the lung allocation score and 171 after). Waiting time decreased from 680.9 +/- 528.3 days to 445.6 +/- 516.9 days (P < .001). Recipient diagnoses changed with an increase in idiopathic pulmonary fibrosis and a decrease in emphysema and cystic fibrosis (P = .002). Postoperatively, primary graft dysfunction increased from 14.1% (24/170) to 22.9% (39/171) (P = .04) and intensive care unit length of stay increased from 5.7 +/- 6.7 days to 7.8 +/- 9.6 days (P = .04). Hospital mortality and 1-year survival were the same between groups (5.3% vs 5.3% and 90% vs 89%, respectively; P > .6) This multicenter retrospective review of short-term outcomes supports the fact that the lung allocation score is achieving its objectives. The lung allocation score reduced waiting time and altered the distribution of lung diseases for which transplantation was done on the basis of medical necessity. After transplantation, recipients have significantly higher rates of primary graft dysfunction and intensive care unit lengths of stay. However, hospital mortality and 1-year survival have not been adversely affected.

What can happen after lung transplantation and the importance of the time since transplantation: radiological review of post-transplantation complications.

PubMed

Daimiel Naranjo, I; Alonso Charterina, S

2016-01-01

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.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2010-05-31

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

Aspergillus Colonization of the Lung Allograft is a Risk Factor for Bronchiolitis Obliterans Syndrome

PubMed Central

Weigt, S. Samuel; Elashoff, Robert M.; Huang, Cathy; Ardehali, Abbas; Gregson, Aric L.; Kubak, Bernard; Fishbein, Michael C.; Saggar, Rajeev; Keane, Michael P.; Saggar, Rajan; Lynch, Joseph P.; Zisman, David A.; Ross, David J.; Belperio, John A.

2014-01-01

Multiple infections have been linked with the development of bronchiolitis obliterans syndrome (BOS) post-lung transplantation. Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We hypothesized that Aspergillus colonization may promote the development of BOS and may decrease survival post-lung transplantation. We reviewed all lung transplant recipients transplanted in our center between 1/2000 and 6/2006. Bronchoscopy was performed according to a surveillance protocol and when clinically indicated. Aspergillus colonization was defined as a positive culture from bronchoalveolar lavage or two sputum cultures positive for the same Aspergillus species, in the absence of invasive pulmonary Aspergillosis. We found that Aspergillus colonization was strongly associated with BOS and BOS related mortality in Cox regression analyses. Aspergillus colonization typically preceded the development of BOS by a median of 261 days (95% CI 87 to 520). Furthermore, in a multivariate Cox regression model, Aspergillus colonization was a distinct risk factor for BOS, independent of acute rejection. These data suggest a potential causative role for Aspergillus colonization in the development of BOS post-lung transplantation and raise the possibility that strategies aimed to prevent Aspergillus colonization may help delay or reduce the incidence of BOS. PMID:19459819

A longitudinal study of patients’ symptoms before and during the first year after lung transplantation

PubMed Central

Lanuza, Dorothy M.; Lefaiver, Cheryl A.; Brown, Roger; Muehrer, Rebecca; Murray, Margaret; Yelle, Maria; Bhorade, Sangeeta

2012-01-01

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

Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection

PubMed Central

Cui, Ye; Liu, Kaifeng; Monzon-Medina, Maria E.; Padera, Robert F.; Wang, Hao; George, Gautam; Toprak, Demet; Abdelnour, Elie; D’Agostino, Emmanuel; Goldberg, Hilary J.; Perrella, Mark A.; Forteza, Rosanna Malbran; Rosas, Ivan O.; Visner, Gary; El-Chemaly, Souheil

2015-01-01

Lung transplantation is the only viable option for patients suffering from otherwise incurable end-stage pulmonary diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Despite aggressive immunosuppression, acute rejection of the lung allograft occurs in over half of transplant recipients, and the factors that promote lung acceptance are poorly understood. The contribution of lymphatic vessels to transplant pathophysiology remains controversial, and data that directly address the exact roles of lymphatic vessels in lung allograft function and survival are limited. Here, we have shown that there is a marked decline in the density of lymphatic vessels, accompanied by accumulation of low-MW hyaluronan (HA) in mouse orthotopic allografts undergoing rejection. We found that stimulation of lymphangiogenesis with VEGF-C156S, a mutant form of VEGF-C with selective VEGFR-3 binding, alleviates an established rejection response and improves clearance of HA from the lung allograft. Longitudinal analysis of transbronchial biopsies from human lung transplant recipients demonstrated an association between resolution of acute lung rejection and decreased HA in the graft tissue. Taken together, these results indicate that lymphatic vessel formation after lung transplantation mediates HA drainage and suggest that treatments to stimulate lymphangiogenesis have promise for improving graft outcomes. PMID:26485284

Surgeon's viewpoint on lung transplantation in cystic fibrosis patients - preliminary report.

PubMed

Kubisa, Bartosz; Piotrowska, Maria; Milczewska, Justyna; Bielewicz, Michał; Pieróg, Jarosław; Kozak, Anna; Czarnecka, Michalina; Wójcik, Norbert; Wasilewski, Piotr; Feledyk, Grzegorz; Kubisa, Anna; Brykczyński, Mirosław; Sielicki, Piotr; Grodzki, Tomasz

2015-01-01

The surgeon's viewpoint on a patient with cystic fibrosis differs from that of a pediatrician or internist. The problems a cystic fibrosis specialist encounters are different from those faced by the surgeon who takes over the patient in a very advanced, often terminal stage of the disease. Hence, the main problem for the surgeon is the decision concerning the surgery (lung transplantation, pneumonectomy, lobectomy). It is, therefore, important to lay down fundamental and appropriate rules concerning the indications and contraindications for lung transplantation, especially in patients with cystic fibrosis. The aim of this study was to analyze the methods of qualifying and preparing patients for surgery, as well as carrying out the procedure of transplantation and postoperative short and long-term care. The investigation was carried out on 16 patients with cystic fibrosis. Three were operated on and 10 were on the waiting list for transplantation. Two patients on the waiting list died, one patient was disqualified from transplantation. During qualification for lung transplantation, strict indications, contraindications and other factors (such as blood type, patient's height, coexisting complications) were taken under consideration. All the 3 patients after lung transplantation are alive and under our constant surveillance. Ten patients await transplantation, though four of them are suspended due to hepatitis C infection. Two patients on the waiting list died: one from respiratory insufficiency and the other in the course of bridge to-transplant veno-venous extracorporeal membrane oxygenation due to hepatic failure. One patient has been disqualified because of cachexia. Since lung transplantation is the final treatment of the end-stage pulmonary insufficiency in cystic fibrosis patients, the number of such procedures in cystic fibrosis is still too low in Poland. The fast development of these procedures is highly needed. It is necessary to develop better cooperation between different disciplines and specialists, especially between pediatricians and surgeons. The correct choice of the suitable moment for lung transplantation is crucial for the success of the procedure.

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

PubMed

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

2010-01-01

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

Early results in transplantation of initially rejected donor lungs after ex vivo lung perfusion: a case-control study.

PubMed

Wallinder, Andreas; Ricksten, Sven-Erik; Silverborn, Martin; Hansson, Christoffer; Riise, Gerdt C; Liden, Hans; Jeppsson, Anders; Dellgren, Göran

2014-01-01

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 EVLP seems safe and indicates that lungs otherwise refused for LTx can be recovered and subsequently used for transplantation, although time to extubation and ICU stay were longer for the EVLP group.

Emerging Research Directions in Adult Congenital Heart Disease: A Report from a National Heart, Lung, and Blood Institute/Adult Congenital Heart Association Working Group

PubMed Central

Gurvitz, Michelle; Burns, Kristin M.; Brindis, Ralph; Broberg, Craig S.; Daniels, Curt J.; Fuller, Stephanie M.P.N.; Honein, Margaret A.; Khairy, Paul; Kuehl, Karen S.; Landzberg, Michael J.; Mahle, William T.; Mann, Douglas L.; Marelli, Ariane; Newburger, Jane W.; Pearson, Gail D.; Starling, Randall C.; Tringali, Glenn R.; Valente, Anne Marie; Wu, Joseph C.; Califf, Robert M.

2016-01-01

Congenital heart disease (CHD) is the most common birth defect, affecting about 0.8% of live births. Advances in recent decades have allowed >85% of children with CHD to survive to adulthood, creating a growing population of adults with CHD. Little information exists regarding survival, demographics, late outcomes, and comorbidities in this emerging group, and multiple barriers impede research in adult CHD (ACHD). The National Heart, Lung, and Blood Institute and the Adult Congenital Heart Association convened a multidisciplinary Working Group to identify high-impact research questions in ACHD. This report summarizes the meeting discussions in the broad areas of CHD-related heart failure, vascular disease and multisystem complications. High-priority subtopics identified included heart failure in tetralogy of Fallot, mechanical circulatory support/transplantation, sudden cardiac death, vascular outcomes in coarctation of the aorta, late outcomes in single ventricle disease, cognitive and psychiatric issues, and pregnancy. PMID:27102511

Successful Single-Lung Transplant for Severe Lung Graft-Versus-Host Disease Two Years After Sibling Allograft for Acute Lymphoblastic Leukemia: A Case Report.

PubMed

Irhimeh, M R; Musk, M; Cooney, J P

2016-11-01

Bone marrow transplantation (BMT) has been performed as a successful life-saving treatment for hematological and neoplastic diseases. Despite the predictable long-term survival rates in BMT, pulmonary complications reduce the survival rates significantly mainly because of chronic graft-versus-host disease (GVHD). This report briefly discusses a successful lung transplantation case for severe lung GVHD after allograft for acute lymphoblastic leukemia. This case report supports the scarce evidence in the literature for the importance of lung transplantation as a therapeutic option for patients who develop respiratory failure secondary to BMT. Copyright © 2016. Published by Elsevier Inc.

Efficacy of extracorporeal membrane oxygenation as a bridge to lung transplantation.

PubMed

Toyoda, Yoshiya; Bhama, Jay K; Shigemura, Norihisa; Zaldonis, Diana; Pilewski, Joseph; Crespo, Maria; Bermudez, Christian

2013-04-01

Preoperative extracorporeal membrane oxygenation (ECMO) is a risk factor for poor outcome and currently considered a contraindication to lung transplantation. The lung allocation score system was introduced in May 2005 and prioritizes lung allocation to those with the greatest respiratory impairment. The purpose of this study is to determine whether ECMO as a bridge to lung transplantation is an acceptable option to support those in respiratory failure until donor lungs become available in the lung allocation score era. A retrospective review of 715 consecutive lung transplants performed between May 2005 and September 2011 was conducted using a prospectively collected institutional registry database. Twenty-four lung transplants (3.4%) were performed in the 31 patients with attempted pretransplant ECMO; 7 patients who received ECMO patients did not survive or were deemed unfit for transplantation. These patients were compared with a control group of 691 patients who did not receive pretransplant ECMO. The duration of pretransplant ECMO was 171 ± 242 hours (median, 91 hours). Venovenous ECMO was used for respiratory failure in 15 patients, whereas venoarterial ECMO was used for circulatory collapse due to pulmonary hypertension in 9 patients. Patients in the retransplant ECMO group were younger (46 ± 15 years vs 57 ± 14 years, P < .01) compared with the control group, with no difference in recipient gender (male/female: 10/14 vs 380/311), donor age (33 ± 14 years vs 36 ± 15 years), or donor gender (male/female: 10/14 vs 352/339). Emphysema was less common (1, 4% vs 260, 38%, P < .01), and cystic fibrosis (5, 21% vs 72, 10%, P = .09), redo lung transplant (3, 13% vs 28, 4%, P = .08), and bronchiectasis (2, 8% vs 6, 1%, P = .03) were more common in the pretransplant ECMO group. Patients in the pretransplant ECMO group had a significantly higher lung allocation score (87 ± 9 vs 44 ± 15, P < .01). All patients in the pretransplant ECMO group underwent double lung transplants on pump (cardiopulmonary bypass/ECMO), and single lung transplants were performed in 171 patients (25%) and pump was used in 243 patients (35%) in the control group. The cardiopulmonary bypass time was longer in the pretransplant ECMO group (277 ± 69 minutes vs 225 ± 89 minutes, P = .02), with no difference in ischemic time (343 ± 93 minutes vs 330 ± 98 minutes, P = .54). Cadaveric lobar lung transplants were performed because of the urgency to overcome size mismatch with an oversized donor more frequently in 25% (n = 6, no mortality with the longest follow-up at 6 years) of patients in the pretransplant ECMO group versus 0.3% (n = 2) of patients in the control group (P < .01). Post-transplant ECMO was used for primary graft dysfunction in 13 patients (54%) in the pretransplant ECMO group and 41 patients (6%) in the control group (P < .01). The median hospital stay was 46 days in the pretransplant ECMO group versus 27 days in the control group (P = .16). The actuarial survivals after lung transplants at 1, 3, 6, 12, and 24 months were 96%, 88%, 83%, 74%, and 74%, respectively, in the pretransplant ECMO group, and 97%, 94%, 90%, 83%, and 74%, respectively, in the control group (P = .787). Although the incidence of primary graft dysfunction requiring post-transplant ECMO is higher and the hospital stay is longer in patients receiving pretransplant ECMO, the graft survival is good (2-year survival, 74%). ECMO is efficacious as a bridge to lung transplantation with good post-lung transplant outcomes. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Geographic disparities in donor lung supply and lung transplant waitlist outcomes: A cohort study.

PubMed

Benvenuto, Luke J; Anderson, David R; Kim, Hanyoung P; Hook, Jaime L; Shah, Lori; Robbins, Hilary Y; D'Ovidio, Frank; Bacchetta, Matthew; Sonett, Joshua R; Arcasoy, Selim M

2017-12-21

Despite the Final Rule mandate for equitable organ allocation in the United States, geographic disparities exist in donor lung allocation, with the majority of donor lungs being allocated locally to lower-priority candidates. We conducted a retrospective cohort study of 19 622 lung transplant candidates waitlisted between 2006 and 2015. We used multivariable adjusted competing risk survival models to examine the relationship between local lung availability and waitlist outcomes. The primary outcome was a composite of death and removal from the waitlist for clinical deterioration. Waitlist candidates in the lowest quartile of local lung availability had an 84% increased risk of death or removal compared with candidates in the highest (subdistribution hazard ratio [SHR]: 1.84, 95% confidence interval [CI]: 1.51-2.24, P < .001). The transplantation rate was 57% lower in the lowest quartile compared with the highest (SHR: 0.43, 95% CI: 0.39-0.47). The adjusted death or removal rate decreased by 11% with a 50% increase in local lung availability (SHR: 0.89, 95% CI: 0.85-0.93, P < .001) and the adjusted transplantation rate increased by 19% (SHR: 1.19, 95% CI: 1.17-1.22, P < .001). There are geographically disparate waitlist outcomes in the current lung allocation system. Candidates listed in areas of low local lung availability have worse waitlist outcomes. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Lung Quality and Utilization in Controlled Donation after Circulatory Determination of Death Donors within the United States

PubMed Central

Mooney, Joshua J; Hedlin, Haley; Mohabir, Paul K; Vazquez, Rodrigo; Nguyen, John; Ha, Richard; Chiu, Peter; Patel, Kapilkumar; Zamora, Martin R.; Weill, David; Nicolls, Mark R; Dhillon, Gundeep S

2016-01-01

While controlled donation after circulatory determination of death (cDCDD) donors could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remain low compared to donation after neurologic determination of death (DNDD) donors. To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed and distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted OR 0.101, CI 0.085–0.120). A minority of centers have performed cDCDD transplant with higher volume centers generally performing more cDCDD transplants. There was no difference in center to donor distance or recipient survival (adjusted HR 1.03, CI 0.78–1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared to DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization. PMID:26844673

Acute kidney injury after liver, heart, and lung transplants: dialysis modality, predictors of renal function recovery, and impact on survival.

PubMed

Pham, Phuong-Thu T; Slavov, Carmen; Pham, Phuong-Chi T

2009-07-01

Recipients of nonrenal organ transplants including the liver, heart, and lung are at risk for developing acute kidney injury (AKI) and chronic kidney disease (CKD). Underlying hepatic or cardiopulmonary failure, prolonged intraoperative hemodynamic instability, and the use of calcineurin inhibitors and nephrotoxic medications have all been suggested to be contributory. The incidence of perioperative AKI has been reported to occur in 17% to 95% in liver transplant recipients, 5% to 30% in heart transplant recipients, and 5% to 60% in recipients of lung transplants. Among those who develop AKI, renal replacement therapy is required in 5% to 35%, 5% to 15%, and 8% to 10% in liver, heart, and lung transplant recipients, respectively. The current article presents an overview of the literature on the choice of dialysis modality and its associated advantages and disadvantages in the management of AKI after liver, heart, and lung transplants. Predictive factors for renal function recovery and the impact of AKI and CKD on survival will also be discussed.

IL-17–dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants

PubMed Central

Burlingham, William J.; Love, Robert B.; Jankowska-Gan, Ewa; Haynes, Lynn D.; Xu, Qingyong; Bobadilla, Joseph L.; Meyer, Keith C.; Hayney, Mary S.; Braun, Ruedi K.; Greenspan, Daniel S.; Gopalakrishnan, Bagavathi; Cai, Junchao; Brand, David D.; Yoshida, Shigetoshi; Cummings, Oscar W.; Wilkes, David S.

2007-01-01

Bronchiolitis obliterans syndrome (BOS), a process of fibro-obliterative occlusion of the small airways in the transplanted lung, is the most common cause of lung transplant failure. We tested the role of cell-mediated immunity to collagen type V [col(V)] in this process. PBMC responses to col(II) and col(V) were monitored prospectively over a 7-year period. PBMCs from lung transplant recipients, but not from healthy controls or col(IV)-reactive Goodpasture’s syndrome patients after renal transplant, were frequently col(V) reactive. Col(V)-specific responses were dependent on both CD4+ T cells and monocytes and required both IL-17 and the monokines TNF-α and IL-1β. Strong col(V)-specific responses were associated with substantially increased incidence and severity of BOS. Incidences of acute rejection, HLA-DR mismatched transplants, and induction of HLA-specific antibodies in the transplant recipient were not as strongly associated with a risk of BOS. These data suggest that while alloimmunity initiates lung transplant rejection, de novo autoimmunity mediated by col(V)-specific Th17 cells and monocyte/macrophage accessory cells ultimately causes progressive airway obliteration. PMID:17965778

Heart-lung transplantation for cystic fibrosis and subsequent domino heart transplantation.

PubMed

Yacoub, M H; Banner, N R; Khaghani, A; Fitzgerald, M; Madden, B; Tsang, V; Radley-Smith, R; Hodson, M

1990-01-01

Between September 1984 and October 1988, 27 patients underwent combined heart-lung transplantation for treatment of end-stage respiratory disease caused by cystic fibrosis. The actuarial patient survival was 78% at 1 year and 72% at 2 years. Bacterial respiratory infections were common in the early postoperative period and necessitated vigorous medical therapy. The dose of cyclosporine required in these patients was higher than in conventional transplant recipients, and this contributed to an increased cost of postoperative care. Lung function was greatly improved after transplantation, and long-term survivors achieved an excellent quality of life. Lymphoproliferative disorders developed in two patients; these disorders regressed after a reduction in immunosuppression. Two patients required retransplantation: one because of obliterative bronchiolitis and the other because of recurrent respiratory infections associated with a moderate tracheal stenosis and severe deterioration in lung function. A modification of the technique used for heart-lung transplantation allowed 20 hearts from cystic fibrosis patients to be used for subsequent heart transplantation. Immediate heart function was satisfactory in all cases. The actuarial survival of the recipients of these domino heart transplants was 75% at 1 year. No coronary artery disease was present in the 12 patients who have undergone coronary angiography at 1 year.

Lung transplantation in idiopathic pulmonary fibrosis: a systematic review of the literature

PubMed Central

2014-01-01

Background Idiopathic pulmonary fibrosis (IPF) is a distinct form of interstitial pneumonia with unknown origin and poor prognosis. Current pharmacologic treatments are limited and lung transplantation is a viable option for appropriate patients. The aim of this review was to summarize lung transplantation survival in IPF patients overall, between single (SLT) vs. bilateral lung transplantation (BLT), pre- and post Lung Allocation Score (LAS), and summarize wait-list survival. Methods A systematic review of English-language studies published in Medline or Embase between 1990 and 2013 was performed. Eligible studies were those of observational design reporting survival post-lung transplantation or while on the wait list among IPF patients. Results Median survival post-transplantation among IPF patients is estimated at 4.5 years. From ISHLT and OPTN data, one year survival ranged from 75% - 81%; 3-year: 59% - 64%; and 5-year: 47% - 53%. Post-transplant survival is lower for IPF vs. other underlying pre-transplant diagnoses. The proportion of IPF patients receiving BLT has steadily increased over the last decade and a half. Unadjusted analyses suggest improved long-term survival for BLT vs. SLT; after adjustment for patient characteristics, the differences tend to disappear. IPF patients account for the largest proportion of patients on the wait list and while wait list time has decreased, the number of transplants for IPF patients has increased over time. OPTN data show that wait list mortality is higher for IPF patients vs. other diagnoses. The proportion of IPF patients who died while awaiting transplantation ranged from 14% to 67%. While later transplant year was associated with increased survival, no significant differences were noted pre vs. post LAS implementation; however a high LAS vs low LAS was associated with decreased one-year survival. Conclusions IPF accounts for the largest proportion of patients awaiting lung transplants, and IPF is associated with higher wait-list and post-transplant mortality vs. other diagnoses. Improved BLT vs. SLT survival may be the result of selection bias. Survival pre- vs. post LAS appears to be similar except for IPF patients with high LAS, who have lower survival compared to pre-LAS. Data on post-transplant morbidity outcomes are sparse. PMID:25127540

Application of ET-Kyoto solution in clinical lung transplantation.

PubMed

Omasa, Mitsugu; Hasegawa, Seiki; Bando, Toru; Hanaoka, Nobuharu; Yoshimura, Takashi; Nakamura, Takayuki; Wada, Hiromi

2004-01-01

We have developed a new organ preservation solution called extracellular-type trehalose-containing Kyoto (ET-Kyoto) solution. ET-Kyoto solution has been applied in clinical lung transplantation. The patient was a 49-year-old woman with diffuse panbronchiolitis. She underwent bilateral lobar lung transplantation from living donors. Each lobe was flushed with ET-Kyoto solution. After reperfusion, PaO(2) with inhalation of 100% oxygen was more than 500 Torr. Posttransplantation course was uneventful. Despite the relatively short ischemic time of this case report, ET-Kyoto solution may be feasible and safely applied in clinical lung transplantation.

Controlled ovarian hyperstimulation and gestational surrogacy in a patient with lung transplant: a case report.

PubMed

Huang, Jian Qun; Shahine, Lora K; Gupta, Nidhi; Westphal, Lynn M

2010-01-01

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.

Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post-lung transplantation survival.

PubMed

Newton, Chad A; Kozlitina, Julia; Lines, Jefferson R; Kaza, Vaidehi; Torres, Fernando; Garcia, Christine Kim

2017-08-01

Prior studies have shown that patients with pulmonary fibrosis with mutations in the telomerase genes have a high rate of certain complications after lung transplantation. However, few studies have investigated clinical outcomes based on leukocyte telomere length. We conducted an observational cohort study of all patients with pulmonary fibrosis who underwent lung transplantation at a single center between January 1, 2007, and December 31, 2014. Leukocyte telomere length was measured from a blood sample collected before lung transplantation, and subjects were stratified into 2 groups (telomere length <10th percentile vs ≥10th percentile). Primary outcome was post-lung transplant survival. Secondary outcomes included incidence of allograft dysfunction, non-pulmonary organ dysfunction, and infection. Approximately 32% of subjects had a telomere length <10th percentile. Telomere length <10th percentile was independently associated with worse survival (hazard ratio 10.9, 95% confidence interval 2.7-44.8, p = 0.001). Telomere length <10th percentile was also independently associated with a shorter time to onset of chronic lung allograft dysfunction (hazard ratio 6.3, 95% confidence interval 2.0-20.0, p = 0.002). Grade 3 primary graft dysfunction occurred more frequently in the <10th percentile group compared with the ≥10th percentile group (28% vs 7%; p = 0.034). There was no difference between the 2 groups in incidence of acute cellular rejection, cytopenias, infection, or renal dysfunction. Telomere length <10th percentile was associated with worse survival and shorter time to onset of chronic lung allograft dysfunction and thus represents a biomarker that may aid in risk stratification of patients with pulmonary fibrosis before lung transplantation. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Evolution of body weight parameters up to 3 years after solid organ transplantation: The prospective Swiss Transplant Cohort Study.

PubMed

Beckmann, Sonja; Nikolic, Nataša; Denhaerynck, Kris; Binet, Isabelle; Koller, Michael; Boely, Elsa; De Geest, Sabina

2017-03-01

Obesity and weight gain are serious concerns after solid organ transplantation (Tx); however, no unbiased comparison regarding body weight parameter evolution across organ groups has yet been performed. Using data from the prospective nationwide Swiss Transplant Cohort Study, we compared the evolution of weight parameters up to 3 years post-Tx in 1359 adult kidney (58.3%), liver (21.7%), lung (11.6%), and heart (8.4%) recipients transplanted between May 2008 and May 2012. Changes in mean weight and body mass index (BMI) category were compared to reference values from 6 months post-Tx. At 3 years post-Tx, compared to other organ groups, liver Tx recipients showed the greatest weight gain (mean 4.8±10.4 kg), 57.4% gained >5% body weight, and they had the highest incidence of obesity (38.1%). After 3 years, based on their BMI categories at 6 months, normal weight and obese liver Tx patients, as well as underweight kidney, lung and heart Tx patients had the highest weight gains. Judged against international Tx patient data, the majority of our Swiss Tx recipients' experienced lower post-Tx weight gain. However, our findings show weight gain pattern differences, both within and across organ Tx groups that call for preventive measures. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Staphylococcus via an Interaction with the ELR+ CXC Chemokine ENA-78 is Associated with BOS

PubMed Central

Gregson, Aric L; Wang, Xiaoyan; Injean, Patil; Weigt, S Sam; Shino, Michael; Sayah, David; DerHovanessian, Ariss; Lynch, Joseph P; Ross, David J; Saggar, Rajan; Ardehali, Abbas; Li, Gang; Elashoff, Robert; Belperio, John A

2014-01-01

Staphylococcus aureus is the most commonly isolated gram-positive bacterium after lung transplantation and has been associated with poor post-transplant outcomes, but its effect on BOS and death in the context of the allograft inflammatory environment has not been studied. A three-state Cox semi-Markovian model was used to determine the influence of allograft S. aureus and the ELR+ CXC chemokines on the survival rates and cause-specific hazards for movement from lung transplant (State 1) to BOS (State 2), from transplant (State 1) to death (State 3), and from BOS (State 2) to death (State 3). Acute rejection, pseudomonas pneumonia, BALF CXCL5 and its interaction with S. aureus all increased the likelihood of transition from transplant to BOS. Transition to death from transplant was facilitated by pseudomonas infection and single lung transplant. Movement from BOS to death was affected by the interaction between aspergillus, pseudomonas and CXCL5, but not S. aureus. S. aureus isolation had state specific effects after lung transplantation and only in concert with elevated BALF CXCL5 concentrations did it augment the risk of BOS. Pseudomonas and elevated BALF concentrations of CXCL5 continued as significant risk factors for BOS and death after BOS in lung transplantation. PMID:25683785

Lung Transplantation in the Management of Patients with LAM:Baseline Data from the NHLBI LAM Registry

PubMed Central

Ryu, Jay; Beck, Gerald; Moss, Joel; Lee, Jar-Chi; Finlay, Geraldine; Brown, Kevin; Chapman, Jeffrey; McMahan, June; Olson, Eric; Ruoss, Stephen; Sherer, Susan; Maurer, Janet R; Ryu, Jay; Beck, Gerald; Moss, Joel; Lee, Jar-Chi; Finlay, Geraldine; Brown, Kevin; Chapman, Jeffrey; McMahan, June; Olson, Eric; Ruoss, Steven

2008-01-01

Background In 1997, the National Heart, Lung, and Blood Institute of the National Institutes of Health established a Registry to better characterize the demographic, clinical, physiologic and radiographic features of patients with LAM. We report here data collected at enrollment from patients who had either undergone transplant prior to enrollment, underwent transplant during the 5-year study, or were evaluated/waitlisted for lung transplant during the 5-year study. Methods The LAM Registry enrolled patients from six clinical centers between August 1998 and October 2001. On entry patients filled out questionnaires covering medical history, symptoms, treatment and quality of life (SF-36 and St. George’s Respiratory Questionnaire). Enrollees underwent blood laboratory work, arterial blood gases and pulmonary function testing. Follow-up was at six month and/or yearly intervals. Diagnoses were confirmed by biopsy or typical clinical presentation plus CT findings confirmed by independent expert radiologists. A total of 243 women were enrolled. Of those 13 (5.3%) had been transplanted at time of entry (Group A), 21 (8.6%) were transplanted during the study (Group B) and 48 (19.8%) were either waitlisted for transplant or underwent evaluation after enrollment during the study period (Group C). The remaining 161 (66.3%) registrants were neither considered for nor listed for transplant during the Registry period (Group D). Results One-third of patients in a large sample of LAM patients had either been transplanted or were being considered for transplant. At enrollment, patients who had already been transplanted and those not in need of transplant (Groups A and D) had better pulmonary function and quality of life scores compared to patients who subsequently underwent lung transplant during the Registry period (Group B). Conclusion In this large registry of LAM patients, lung transplantation appears to be associated both with significantly improved lung function and quality of life compared to patients with advanced disease. PMID:18096481

Pre- and post- transplantation lung cancer in heart transplant recipients.

PubMed

Pricopi, Ciprian; Rivera, Caroline; Varnous, Shaida; Arame, Alex; Le Pimpec Barthes, Françoise; Riquet, Marc

2015-05-01

Heart transplantation after lung cancer surgery can be questionable because of the high risk of cancer recurrence. We report the results of two patients. The first underwent right lobectomy in 2008 for pT1N0 adenocarcinoma, heart-transplantation in 2010, and surgery for synchronous adenocarcinoma and squamous-cell carcinoma in 2012. The second underwent left segmentectomy for pT1aN0 adenosquamous carcinoma and transplantation in 1995 and then surgery for pT1aN1 adenocarcinoma in 2013. Posttransplantation lung cancer histologic analysis results were different in both cases, demonstrating the absence of metastatic recurrence. Thus, early stage lung cancer might not be a contraindication to heart transplantation, nor are long delays be necessary before registering on a waiting list. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Antibody-mediated rejection of the lung: A consensus report of the International Society for Heart and Lung Transplantation.

PubMed

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

2016-04-01

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.

Lung Allocation Score: A Single-Center Simulation.

PubMed

Rosso, L; Palleschi, A; Tosi, D; Mendogni, P; Righi, I; Carrinola, R; Montoli, M; Damarco, F; Rossetti, V; Morlacchi, L C; Nosotti, M

2016-03-01

The lung allocation score (LAS) was introduced in the United States in May 2005 with the main goal of reducing the waiting list mortality of patients with end-stage lung diseases, but also to enhance the lung transplant benefit and improve the management of urgent candidates. Several papers have reported that LAS resulted in a reduction of the waiting list mortality but no significant survival benefit was noted. We evaluate the usefulness of LAS as a predictor for lung transplantation outcome in 123 patients listed for lung transplantation in an Italian center. Primary endpoints were waiting list mortality and posttransplant mortality at 1 year; secondary endpoints included perioperative circulatory support, cardiopulmonary bypass, primary graft dysfunction, and long-term survival after transplantation. We observed the absence of correlation between LAS and waiting list mortality. The LAS did not affect the long-term survival in our population. High LAS was predictive of primary graft dysfunction of grade 3 in the first 72 hours after transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Porcine pulmonary auto-transplantation for ex vivo therapy as a model for new treatment strategies.

PubMed

Krüger, Marcus; Zinne, Norman; Biancosino, Christian; Höffler, Klaus; Rajab, Taufiek K; Waldmann, Karl-Heinz; Jonigk, Danny; Avsar, Murat; Haverich, Axel; Hoeltig, Doris

2016-09-01

Lung auto-transplantation is the surgical key step in experiments involving ex vivo therapy of severe or end-stage lung diseases. Ex vivo therapy has become a clinical reality because of systems such as the Organ Care System (OCS) Lung, which is the only commercially available portable lung perfusion system. However, survival experiments involving porcine lung auto-transplantation pose special surgical and anaesthesiological challenges. This current study was designed to describe the development of surgical techniques and aneasthesiological management strategies that facilitate lung auto-transplantation survival surgery including a follow-up period of 4 days. Left pneumonectomy was performed in 12 Mini-Lewe miniature pigs. After ex vivo treatment of the harvested lungs within the OCS Lung for 2 h, the lungs were retransplanted into the same animal (auto-transplantation). Four animals were used to develop the optimal techniques and establish an experimental protocol. According to the final protocol, eight additional animals were operated. The follow-up period was 4 days. There were four severe intraoperative surgical complications [anatomical variant of the superior vena cava (two times), a complication related to the bronchial anastomosis and a complication related to the pulmonary arterial anastomosis]. The major postoperative problems were hyperkalaemia, prolonged recovery from anaesthesia and pulmonary oedema after reperfusion. Establishment of the surgical technique showed that using a pericardial tube to facilitate the anastomosis of the thin left superior pulmonary vein should be considered to prevent thrombosis. However, routine use of the patch technique to construct venous and arterial anastomoses is not necessary. Furthermore, traction on the venous anastomoses can be avoided by performing the bronchial anastomosis first. Lung auto-transplantation is a feasible experimental model for ex vivo therapy of lung diseases and is applicable for experimental questions concerning human lung transplantation. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

[Graft-versus-host disease, a rare complication of lung transplantation].

PubMed

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

2016-02-01

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. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Physical activity levels early after lung transplantation.

PubMed

Wickerson, Lisa; Mathur, Sunita; Singer, Lianne G; Brooks, Dina

2015-04-01

Little is known of the early changes in physical activity after lung transplantation. The purposes of this study were: (1) to describe physical activity levels in patients up to 6 months following lung transplantation and (2) to explore predictors of the change in physical activity in that population. This was a prospective cohort study. Physical activity (daily steps and time spent in moderate-intensity activity) was measured using an accelerometer before and after transplantation (at hospital discharge, 3 months, and 6 months). Additional functional measurements included submaximal exercise capacity (measured with the 6-Minute Walk Test), quadriceps muscle torque, and health-related quality of life (measured with the Medical Outcomes Study 36-Item Short-Form Health Survey 36 [SF-36] and the St George's Respiratory Questionnaire). Thirty-six lung transplant recipients (18 men, 18 women; mean age=49 years, SD=14) completed posttransplant measurements. Before transplant, daily steps were less than a third of the general population. By 3 months posttransplant, the largest improvement in physical activity had occurred, and level of daily steps reached 55% of the general population. The change in daily steps (pretransplant to 3 months posttransplant) was inversely correlated with pretransplant 6-minute walk distance (r=-.48, P=.007), daily steps (r=-.36, P=.05), and SF-36 physical functioning (SF-36 PF) score (r=-.59, P=.0005). The SF-36 PF was a significant predictor of the change in physical activity, accounting for 35% of the variation in change in daily steps. Only individuals who were ambulatory prior to transplant and discharged from the hospital in less than 3 months were included in the study. Physical activity levels improve following lung transplantation, particularly in individuals with low self-reported physical functioning. However, the majority of lung transplant recipients remain sedentary between 3 to 6 months following transplant. The role of exercise training, education, and counseling in further improving physical activity levels in lung transplant recipients should be further explored. © 2015 American Physical Therapy Association.

Successful extracorporeal membrane oxygenation therapy as a bridge to sequential bilateral lung transplantation for a patient after severe paraquat poisoning.

PubMed

Tang, Xiao; Sun, Bing; He, Hangyong; Li, Hui; Hu, Bin; Qiu, Zewu; Li, Jie; Zhang, Chunyan; Hou, Shengcai; Tong, Zhaohui; Dai, Huaping

2015-11-01

Paraquat is a widely used herbicide that can cause severe to fatal poisoning in humans. The irreversible and rapid progression of pulmonary fibrosis associated with respiratory failure is the main cause of death in the later stages of poisoning. There are infrequent reports of successful lung transplants for cases of severe paraquat poisoning. We expect that this successful case will provide a reference for other patients in similar circumstances. A 24-year-old female was sent to the hospital approximately 2 hours after ingesting 50 ml of paraquat. She experienced rapidly aggravated pulmonary fibrosis and severe respiratory failure. On the 34th day after ingestion, she underwent intubation and invasive mechanical ventilation. The patient was evaluated for lung transplantation, and veno-venous extracorporeal membrane oxygenation (ECMO) was established as a bridge to lung transplantation on the 44th day. On the 56th day, she successfully underwent a bilateral sequential lung transplantation. Through respiratory and physical rehabilitation and nutrition support, the patient was weaned from mechanical ventilation and extubated on the 66th day. On the 80th day, she was discharged. During the 1-year follow-up, the patient was found to be in good condition, and her pulmonary function improved gradually. We suggest that lung transplantation may be an effective treatment in the end stages of paraquat-induced pulmonary fibrosis and consequential respiratory failure. For patients experiencing a rapid progression to a critical condition in whom lung transplantation cannot be performed immediately (e.g., while awaiting a viable donor or toxicant clearance), ECMO should be a viable bridge to lung transplantation.

Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis.

PubMed

Ishibashi, Naoya; Watanabe, Tatsuaki; Kanehira, Masahiko; Watanabe, Yui; Hoshikawa, Yasushi; Notsuda, Hirotsugu; Noda, Masafumi; Sakurada, Akira; Ohkouchi, Shinya; Kondo, Takashi; Okada, Yoshinori

2018-03-15

Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.

The role of transbronchial cryobiopsy in lung transplantation.

PubMed

Montero, M Angeles; de Gracia, Javier; Culebras, Mario; Mugnier, Jacqueline; Álvarez, Antonio; Berastegui, Cristina; Ortiz-Villalón, Cristian

2018-05-19

Lung transplant monitoring is usually assessed by forceps transbronchial biopsies. These types of biopsies show limited reliability and high degree of variability due to insufficient material and compression artefact, which lead to misinterpretation and eventually mistreatment of the transplanted patients. The following study was undertaken to assess the diagnostic yield, histological quality and safety of cryobiopsy in comparison with conventional forceps biopsy for sampling lung tissue in transplant recipients. From January to December 2011, 81 consecutive transbronchial biopsies (41 forceps and 40 cryoprobe) were indicated in single or bilateral lung transplantation recipients with clinical acute or chronic lung injury. Lung samples obtained by cryoprobe were larger (8.5±6.5mm FB group vs 22.1±12.5 CB group; P < 0.0001) and had no crush artefacts (P = 0.002), allowed us to increase the diagnosis of acute (P = 0,0657) and chronic cellular rejection P = 0,0053). Transbronchial cryoprobe bronchoscopy allows harvesting of larger and more expanded lung tissue samples by increasing the diagnostic yield in the monitoring of the lung allograft by means of a safe procedure. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Monitoring of experimental rat lung transplants by high-resolution flat-panel volumetric computer tomography (fpVCT).

PubMed

Greschus, Susanne; Kuchenbuch, Tim; Plötz, Christian; Obert, Martin; Traupe, Horst; Padberg, Winfried; Grau, Veronika; Hirschburger, Markus

2009-01-01

Noninvasive assessment of experimental lung transplants with high resolution would be favorable to exclude technical failure and to follow up graft outcome in the living animal. Here we describe a flat-panel Volumetric Computed Tomography (fpVCT) technique using a prototype scanner. Lung transplantation was performed in allogeneic as well as in corresponding syngeneic rat strain combinations. At different time points post-transplantation, fpVCT was performed. Lung transplants can be visualized in the living rat with high-spatial resolution. FpVCT allows a detailed analysis of the lung and the bronchi. Infiltrates developing during rejection episodes can be diagnosed and follow-up studies can easily be performed. With fpVCT it is possible to control the technical success of the surgical procedure. Graft rejection can be visualized individually in the living animal noninvasively, which is highly advantageous for studying the pathogenesis of chronic rejection or to monitor new therapies.

Lung Transplantation in a Patient with Fibrosing Alveolitis

PubMed Central

Hugh-Jones, P.; Macarthur, A. M.; Cullum, P. A.; Mason, S. A.; Crosbie, W. A.; Hutchison, D. C. S.; Winterton, M. C.; Smith, A. P.; Mason, B.; Smith, L. A.

1971-01-01

The transplantation of the right lung into a man aged 40 who was suffering from cryptogenic fibrosing alveolitis is described. Before transplantation he had been dependent on oxygen, even at rest, for 24 hours a day for almost two years. The donor was a boy of 16 years who had had a fatal cerebral haemorrhage. The transplanted lung functioned perfectly from the time of operation until the patient's sudden death two months later from an overwhelming haemoptysis apparently from a small peribronchial abscess rupturing into the pulmonary artery. By the third postoperative week the patient had been able to walk unaided and without distress outdoors. The problem of differentiating infection from incipient rejection is discussed. We conclude that clinically successful lung transplantation can be achieved, but only if the problems of lung function, infection, and immunosuppression can all be overcome. ImagesFIG 1FIG. 3FIG. 4FIG. 5FIG. 6 PMID:4105315

Transforming the "unacceptable" donor: outcomes from the adoption of a standardized donor management technique.

PubMed

Wheeldon, D R; Potter, C D; Oduro, A; Wallwork, J; Large, S R

1995-01-01

Donor management remains one of the most neglected areas of transplantation. A comprehensive donor management regimen has been developed. The results of the application of this strategy form the basis of this report. Full hemodynamic data were collected from 150 multiorgan donors between October 1990 and August 1993. The data were collected at the time of donor team arrival, after insertion of a pulmonary artery floatation catheter and immediately before cardiac excision. Fifty-two donors (35%) fell well outside our minimum acceptance criteria on arrival. Twenty-one of fifty-two had a mean arterial pressure less than 55 mm Hg (mean 47 mm Hg) despite inotropic support in most cases; 10 of 52 had a central venous pressure greater than 15 mm Hg (mean 18.0 mm Hg); 2 of 52 had a high inotrope requirement greater than 20 micrograms/kg/min (mean 25 micrograms/kg/min). After the insertion of a pulmonary artery floatation catheter, an additional 13 of 52 donors were found to have a pulmonary capillary wedge pressure greater than 15 mm Hg (mean 19.8 mm Hg), and the final 6 of 52 had a low left ventricular stroke work index, less than 15 gm (mean 12.8 gm). After optimal management, including hormone replacement 44 of 52 donors yielded transplantable organs (29 hearts, 15 heart and lung blocks). Thirty-seven of forty-four patients (84%) were alive and well from 13 to 48 months after transplantation. There were five early deaths (11%) caused by infection (heart), adult respiratory distress syndrome (heart), arrhythmia (heart), cerebrovascular event (heart and lung), and infection (heart, lung, and liver). Two late deaths (5%) occurred as a result of tamponade (3 months, heart) and infection (14 months, heart and lung). Eight of fifty-two organs were still unsuitable for transplantation after optimum management during the splanchnic dissection as a result of inotrope dependency (n = 4), left ventricular hypertrophy (n = 2), and coronary artery disease (n = 2). The data indicate that, of the organs which initially fall outside our transplant acceptance criteria, 92% are capable of functional resuscitation. Conversely, superficial assessment may not show compromised function. Optimizing cardiovascular performance also has important implications for the viability of all transplantable organs. This aggressive approach to donor management has resulted in the transplantation of 44 donor hearts that may otherwise have been turned down or inappropriately managed.

DECT Ventilation Imaging

ClinicalTrials.gov

2018-03-21

For Oncologic Patients; Potentially Operable Lung Tumor; With a Recent (Less Than 1 Month) VQ Scan; For Lung Transplant Recipients; Single of Bilateral Lung Transplant; From 5 Months Onwards; With Recent (Less Than 1 Month) Respiratory Functional Explorations

Maintenance of airway epithelium in acutely rejected orthotopic vascularized mouse lung transplants.

PubMed

Okazaki, Mikio; Gelman, Andrew E; Tietjens, Jeremy R; Ibricevic, Aida; Kornfeld, Christopher G; Huang, Howard J; Richardson, Steven B; Lai, Jiaming; Garbow, Joel R; Patterson, G Alexander; Krupnick, Alexander S; Brody, Steven L; Kreisel, Daniel

2007-12-01

Lung transplantation remains the only therapeutic option for many patients suffering from end-stage pulmonary disease. Long-term success after lung transplantation is severely limited by the development of bronchiolitis obliterans. The murine heterotopic tracheal transplantation model has been widely used for studies investigating pathogenesis of obliterative airway disease and immunosuppressive strategies to prevent its development. Despite its utility, this model employs proximal airway that lacks airflow and is not vascularized. We have developed a novel model of orthotopic vascularized lung transplantation in the mouse, which leads to severe vascular rejection in allogeneic strain combinations. Here we characterize differences in the fate of airway epithelial cells in nonimmunosuppressed heterotopic tracheal and vascularized lung allograft models over 28 days. Up-regulation of growth factors that are thought to be critical for the development of airway fibrosis and interstitial collagen deposition were similar in both models. However, while loss of airway epithelial cells occurred in the tracheal model, airway epithelium remained intact and fully differentiated in lung allografts, despite profound vascular rejection. Moreover, we demonstrate expression of the anti-apoptotic protein Bcl-2 in airway epithelial cells of acutely rejected lung allografts. These findings suggest that in addition to alloimmune responses, other stimuli may be required for the destruction of airway epithelial cells. Thus, the model of vascularized mouse lung transplantation may provide a new and more physiologic experimental tool to study the interaction between immune and nonimmune mechanisms affecting airway pathology in lung allografts.

Results of clinical lung transplant from uncontrolled non-heart-beating donors.

PubMed

de Antonio, David Gómez; Marcos, Roberto; Laporta, Rosalía; Mora, Gema; García-Gallo, Cristina; Gámez, Pablo; Córdoba, Mar; Moradiellos, Javier; Ussetti, Piedad; Carreño, María C; Núñez, José R; Calatayud, Joaquín; Del Río, Francisco; Varela, Andrés

2007-05-01

The scarcity of grafts for lung transplant and the growing number of candidates expecting an organ has led to an increase of deaths in patients waiting for lung transplantation. Non-heart-beating donors (NHBD) represent a promising source of grafts for those who are involved in clinical lung transplantation. We present the results of our series of 17 out-of-hospital NHBD lung transplantations performed since 2002. We have collected data from 17 donors and recipients involved in NHBD lung transplants since 2002, as well as data referring to the type of procedure and peri-operative events. We describe the incidence of post-operative complications with special attention to primary graft disfunction (PGD), bronchial healing, bronchiolitis obliterans syndrome (BOS), and survival. We used Kaplan-Meier method to obtain the survival curve. G2-G3 PGD was reported in 9 patients (53%), with a complete restoration of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio in 170 hours for G2 and 168 hours for G3. There were no deaths directly related to PGD. Acute rejection was detected in 7 patients (41%), 4 of which exceeded grade 1. The incidence of BOS after transplantation was 1 (7%) of 14 patients during the first year, 2 (11%) of 9 in the second year, and 2 (50%) of 4 in the third year. Hospital mortality rate was 17%. The survival rates were 82% at 3 months, 69%, at 1 year, and 58% at 3 years. Mid-term results confirm the adequacy of uncontrolled NHBD as a promising complementary source of lung donors for clinical transplant.

A neutrophil elastase inhibitor improves lung function during ex vivo lung perfusion.

PubMed

Harada, Masaaki; Oto, Takahiro; Otani, Shinji; Miyoshi, Kentaroh; Okada, Masanori; Iga, Norichika; Nishikawa, Hitoshi; Sugimoto, Seiichiro; Yamane, Masaomi; Miyoshi, Shinichiro

2015-12-01

Ex vivo lung perfusion (EVLP) has been used not only for graft evaluation but also for graft reconditioning prior to lung transplantation. Inflammatory cells such as neutrophils may cause additional graft injury during EVLP. Neutrophil elastase inhibitors protect lungs against neutrophil-induced lung injury, such as acute respiratory distress syndrome. This study aimed to investigate the effect of a neutrophil elastase inhibitor during EVLP. EVLP was performed for 4 h in bilateral pig lungs that had previously experienced warm ischemia for 2 h with or without a neutrophil elastase inhibitor (treated and control groups, respectively; n = 6). Following EVLP, the left lung was transplanted into a recipient pig, and this was followed by observation for 4 h. Pulmonary functions were observed both during EVLP and during the early post-transplant stage. During EVLP, decreases in neutrophil elastase levels (P < 0.001), the wet-dry weight ratio (P < 0.05), and pulmonary vascular resistance (P < 0.01) and increases in the PaO2/FiO2 ratio (P < 0.01) and pulmonary compliance (P < 0.05) were observed in the treated group. After transplantation, decreased pulmonary vascular resistance (P < 0.05) was observed in the treated group. A neutrophil elastase inhibitor attenuated the inflammatory response during EVLP and may decrease the incidence of lung reperfusion injury after transplantation.

Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non-heart-beating donors.

PubMed

Dong, Boming; Stewart, Paul W; Egan, Thomas M

2013-08-01

We sought to determine whether ventilation of lungs after death in non-heart-beating donors with carbon monoxide during warm ischemia and ex vivo lung perfusion and after transplant would reduce ischemia-reperfusion injury and improve lung function. One hour after death, Sprague-Dawley rats were ventilated for another hour with 60% oxygen (control group) or 500 ppm carbon monoxide in 60% oxygen (CO-vent group; n=6/group). Then, lungs were flushed with 20 mL cold Perfadex, stored cold for 1 hour, then warmed to 37 °C in an ex vivo lung perfusion circuit perfused with Steen solution. At 37 °C, lungs were ventilated for 15 minutes with alveolar gas with or without 500 ppm carbon monoxide, then perfusion-cooled to 20 °C, flushed with cold Perfadex and stored cold for 2 hours. The left lung was transplanted using a modified cuff technique. Recipients were ventilated with 60% oxygen with or without carbon monoxide. One hour after transplant, we measured blood gases from the left pulmonary vein and aorta, and wet-to-dry ratio of both lungs. The RNA and protein extracted from graft lungs underwent real-time polymerase chain reaction and Western blotting, and measurement of cyclic guanosine monophosphate by enzyme-linked immunosorbent assay. Carbon monoxide ventilation begun 1 hour after death reduced wet/dry ratio after ex vivo lung perfusion. After transplantation, the carbon monoxide-ventilation group had better oxygenation; higher levels of tissue cyclic guanosine monophosphate, heme oxidase-1 expression, and p38 phosphorylation; reduced c-Jun N-terminal kinase phosphorylation; and reduced expression of interleukin-6 and interleukin-1β messenger RNA. Administration of carbon monoxide to the deceased donor and non-heart-beating donor lungs reduces ischemia-reperfusion injury in rat lungs transplanted from non-heart-beating donors. Therapy to the deceased donor via the airway may improve post-transplant lung function. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

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

PubMed

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

2010-06-01

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

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

PubMed Central

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

2010-01-01

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

Starting a Lung Transplant Program

PubMed Central

Eberlein, Michael; Geist, Lois; Keech, John; Zabner, Joseph; Gruber, Peter J.; Iannettoni, Mark D.; Parekh, Kalpaj

2015-01-01

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

Successful use of alternate waste nitrogen agents and hemodialysis in a patient with hyperammonemic coma after heart-lung transplantation.

PubMed

Berry, G T; Bridges, N D; Nathanson, K L; Kaplan, P; Clancy, R R; Lichtenstein, G R; Spray, T L

1999-04-01

Lethal hyperammonemic coma has been reported in 2 adults after lung transplantation. It was associated with a massive elevation of brain glutamine levels, while plasma glutamine levels were normal or only slightly elevated. In liver tissue, glutamine synthetase activity was markedly reduced, and the histologic findings resembled those of Reye syndrome. The adequacy of therapy commonly used for inherited disorders of the urea cycle has not been adequately evaluated in patients with this form of secondary hyperammonemia. To determine whether hemodialysis, in conjunction with intravenous sodium phenylacetate, sodium benzoate, and arginine hydrochloride therapy, would be efficacious in a patient with hyperammonemic coma after solid-organ transplantation. Case report. A children's hospital. A 41-year-old woman with congenital heart disease developed a hyperammonemic coma with brain edema 19 days after undergoing a combined heart and lung transplantation. Ammonium was measured in plasma. Amino acids were quantitated in plasma and cerebrospinal fluid by column chromatography. The effectiveness of therapy was assessed by measuring plasma ammonium levels and intracranial pressure and performing sequential neurological examinations. The patient had the anomalous combination of increased cerebrospinal fluid and decreased plasma glutamine levels. To our knowledge, she is the first patient with this complication after solid-organ transplantation to survive after combined therapy with sodium phenylacetate, sodium benzoate, arginine hydrochloride, and hemodialysis. Complications of the acute coma included focal motor seizures, which were controlled with carbamazepine, and difficulty with short-term memory. The aggressive use of hemodialysis in conjunction with intravenous sodium phenylacetate, sodium benzoate, and arginine hydrochloride therapy may allow survival in patients after solid-organ transplantation. An acute acquired derangement in extra-central nervous system glutamine metabolism may play a role in the production of hyperammonemia in this illness that resembles Reye syndrome, and, as in other hyperammonemic disorders, the duration and degree of elevation of brain glutamine levels may be the important determining factors in responsiveness to therapy.

Ischaemia-reperfusion injury in orthotopic mouse lung transplants – a scanning electron microscopy study

PubMed Central

Draenert, Alice; Marquardt, Klaus; Inci, Ilhan; Soltermann, Alex; Weder, Walter; Jungraithmayr, Wolfgang

2011-01-01

Lung ischaemia-reperfusion (I/R) injury remains a major cause of graft failure in lung transplantation (Tx). With the implementation of orthotopic lung Tx in mice, a physiological model on the base of a perfused and ventilated graft became available for the investigation of I/R injury. Using the scanning electron microscopy (SEM) technique, we here present an analysis of early and late morphological changes of pulmonary I/R injury. Syngeneic lungs were orthotopically transplanted between C57BL/6 mice. Grafts were exposed to 2 h of cold ischaemia. Transplants and right lungs were examined by SEM with corresponding haematoxylin–eosin histology 30 min and 4 h after reperfusion. Thirty minutes after reperfusion, the alveolar surface of transplants showed a discontinued lining of surfactant, while the lining of the non-transplanted lung was normal. Within the graft, leucocytes displayed an irregular surface with development of pseudopodia, and microvilli were detected on the membrane of pneumocytes. At 4 h after reperfusion, leucocytes significantly increased in numbers within the alveolar space. Also, the number of microvilli on pneumocytes increased significantly. Similar to these, the endothelium of vessels increasingly developed microvilli from 30 min towards 4 h after reperfusion. The airways of transplanted grafts showed mild changes with thickening of the bronchial epithelium and a destruction of kinocilia. Taken together, SEM detects pathological events of I/R that are previously not described in normal histology. These findings may influence the interpretation of studies investigating the I/R injury in the mouse model of lung Tx. PMID:21272104

Unilateral donor lung dysfunction does not preclude successful contralateral single lung transplantation.

PubMed

Puskas, J D; Winton, T L; Miller, J D; Scavuzzo, M; Patterson, G A

1992-05-01

Single lung transplantation remains limited by a severe shortage of suitable donor lungs. Potential lung donors are often deemed unsuitable because accepted criteria (both lungs clear on the chest roentgenogram, arterial oxygen tension greater than 300 mm Hg with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 5 cm H2O, and no purulent secretions) do not distinguish between unilateral and bilateral pulmonary disease. Many adequate single lung grafts may be discarded as a result of contralateral aspiration or pulmonary trauma. We have recently used intraoperative unilateral ventilation and perfusion to assess single lung function in potential donors with contralateral lung disease. In the 11-month period ending October 1, 1990, we performed 18 single lung transplants. In four of these cases (22%), the donor chest roentgenogram or bronchoscopic examination demonstrated significant unilateral lung injury. Donor arterial oxygen tension, (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) was below the accepted level in each case (246 +/- 47 mm Hg, mean +/- standard deviation). Through the sternotomy used for multiple organ harvest, the pulmonary artery to the injured lung was clamped. A double-lumen endotracheal tube or endobronchial balloon occlusion catheter was used to permit ventilation of the uninjured lung alone. A second measurement of arterial oxygen tension (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) revealed excellent unilateral lung function in all four cases (499.5 +/- 43 mm Hg; p less than 0.0004). These single lung grafts (three right, one left) were transplanted uneventfully into four recipients (three with pulmonary fibrosis and one with primary pulmonary hypertension). Lung function early after transplantation was adequate in all patients. Two patients were extubated within 24 hours. There were two late deaths, one caused by rejection and Aspergillus infection and the other caused by cytomegalovirus 6 months after transplantation. Two patients are alive and doing well. We conclude that assessment of unilateral lung function in potential lung donors is indicated in selected cases, may be quickly and easily performed, and may significantly increase the availability of single lung grafts.

Epidemic Pseudomonas aeruginosa infection in patients with cystic fibrosis is not a risk factor for poor clinical Outcomes following lung transplantation.

PubMed

Pritchard, Julia; Thakrar, Mitesh V; Somayaji, Ranjani; Surette, Michael G; Rabin, Harvey R; Helmersen, Doug; Lien, Dale; Purighalla, Swathi; Waddell, Barbara; Parkins, Michael D

2016-05-01

Epidemic strains of Pseudomonas aeruginosa (ePA) causing infection in cystic fibrosis (CF) have been commonly identified from clinics around the world. ePA disproportionally impacts CF patient pre-transplant outcomes manifesting in increased exacerbation frequency, worsened treatment burden and increased rate of lung function decline, and disproportionally leads to death and/or transplantation. As other CF factors such as pre-transplant infection with multi-resistant organisms, and isolation of P. aeruginosa in the post transplant graft, may impact post-transplant outcomes, we sought to determine if infection with ePA similarly adversely impact post-transplant outcomes. Between 1991-2014, 53 CF patients from our center received lung transplants. Bacterial strain typing was performed retrospectively on isolates collected prior to transplantation. Comprehensive chart reviews were performed to obtain baseline patient characteristics and post-transplant outcomes. Of the 53 transplanted patients, 57% of patients were infected with ePA prior to transplant; the other 43% of patients had unique strains of P. aeruginosa. Mean age at transplant was 29.0years for ePA and 33.3years for unique (p=0.04). There were no differences in overall survival (HR=0.75, 95% CI 0.31-1.79), bronchiolitis obliterans syndrome (BOS) free survival (HR 1.43, 95% CI 0.54-4.84) or all other assessed outcomes including exacerbation frequency, chronic renal failure, acute cellular rejections, Aspergillus infection, airway stenosis, and post-transplant lymphoproliferative disorder. Unlike pre-transplant outcomes, CF patients infected with ePA do not experience worse post-transplant outcomes than those infected with unique strains. Therefore, lung transplantation should be considered for all patients with P. aeruginosa infection and end stage lung disease, irrespective of infection with ePA. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Impact of HLA compatibility on lung transplant survival and evidence for an HLA restriction phenomenon: a collaborative transplant study report.

PubMed

Opelz, Gerhard; Süsal, Caner; Ruhenstroth, Andrea; Döhler, Bernd

2010-10-27

Data concerning the impact of human leukocyte antigen (HLA) compatibility on lung transplant survival rates are limited. Using the Collaborative Transplant Study database, 5-year graft outcome according to HLA mismatch was examined in 8020 deceased donor lung transplants performed during 1989 to 2009. Graft survival rates showed a stepwise decrease as the combined number of HLA-A+B+DR mismatches increased from one to six (P<0.001). Surprisingly, the 28 grafts with 0 mismatches at all 3 loci had a 1-year survival rate of only 49.7%, significantly lower than for 1, 2, 3, 4, 5, or 6 mismatches (P=0.002, <0.001, <0.001, <0.001, 0.002, and 0.003, respectively). Multivariate regression analysis confirmed that, paradoxically, transplantation of grafts with zero HLA-A+B+DR mismatches was associated with a 19% increase in relative risk of failure. Donor lung preservation for up to 12 hr was not associated with inferior graft survival versus shorter preservation times (P=0.60). Our data show that a high number of HLA mismatches or zero mismatches impacts unfavorably on lung transplant survival.

Concomitant pulmonary infection with Nocardia transvalensis and Aspergillus ustus in lung transplantation.

PubMed

Cabada, Miguel M; Nishi, Shawn P; Lea, Alfred S; Schnadig, Vicki; Lombard, Gisele A; Lick, Scott D; Valentine, Vincent G

2010-08-01

Lung infections with Nocardia and Aspergillus spp in lung transplant recipients (LTRs) create diagnostic and therapeutic challenges. The present case illustrates the difficulties in identifying these pathogens in LTRs. A high degree of clinical suspicion and aggressive early management are required to ensure good outcomes. Although prospective data on treating these conditions are scarce, the empiric use of combination broad-spectrum anti-microbials initially seems prudent. Copyright (c) 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Multidetector computed tomography shows reverse cardiac remodeling after double lung transplantation for pulmonary hypertension.

PubMed

Mandich Crovetto, D; Alonso Charterina, S; Jiménez López-Guarch, C; Pont Vilalta, M; Pérez Núñez, M; de Pablo Gafas, A; Escribano Subías, P

2016-01-01

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.

Utility of C4d immunostaining in the first year after pediatric and young adult heart transplantation.

PubMed

Xu, Ying; Galambos, Csaba; Reyes-Múgica, Miguel; Miller, Susan A; Zeevi, Adriana; Webber, Steven A; Feingold, Brian

2013-01-01

C4d assessment of endomyocardial biopsies (EMBs) after heart transplantation (HTx) has been widely adopted to aid in the diagnosis of antibody-mediated rejection (AMR), yet it remains unclear whether or not to assess all patients routinely and with what frequency/duration. In this study we sought to evaluate the utility of routine C4d immunostaining in the first year after pediatric and young adult HTx. We reviewed pre-transplant alloantibody and clinical data, including serial EMB reports, on all 51 patients who received HTx at our center since we instituted routine C4d staining of all first-year EMBs. C4d was considered positive if diffuse capillary staining (≥ 2(+)) was present. Rare/focal capillary staining or absence of staining was considered negative. Twenty-six of 406 first-year EMBs (6%) were C4d(+) in 6 (12%) patients. Sixty-five percent of all C4d(+) EMBs occurred by 30 days post-transplant. Five of 6 patients had pre-transplant donor-specific antibody (DSA) ≥ 4,000 MFI. The sixth patient had neither pre-transplant anti-HLA antibodies nor a positive donor-specific cytotoxicity crossmatch (DSXM), but there was clinical concern for AMR. Among the entire cohort, 5 of 10 patients with pre-transplant DSA ≥ 4,000 MFI and/or a positive DSXM were C4d(+) compared with only 1 of 41 without (50% vs 2%; p = 0.001). In the first year after HTx, C4d(+) occurred early and only in children and young adults with pre-transplant DSA or with clinical suspicion of AMR. Although our data suggest that assessment limited to the first 90 days post-transplant in patients with pre-transplant DSA ≥ 4,000 MFI may be appropriate in the absence of clinical concern for AMR, further research is needed to determine the optimum strategy for post-transplant surveillance. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Lung Transplantation in Cystic Fibrosis and the Impact of Extracorporeal Circulation.

PubMed

Jauregui, Alberto; Deu, Maria; Romero, Laura; Roman, Antonio; Moreno, Antonio; Armengol, Manuel; Solé, Juan

2018-03-10

Lung disease is the major cause of death among cystic fibrosis (CF) patients, affecting 80% of the population. The impact of extracorporeal circulation (ECC) during transplantation has not been fully clarified. This study aimed to evaluate the outcomes of lung transplantation for CF in a single center, and to assess the impact of ECC on survival. We performed a retrospective observational study of all trasplanted CF patients in a single center between 1992 and 2011. During this period, 64 lung transplantations for CF were performed. Five- and 10-year survival of trasplanted patients was 56.7% and 41.3%, respectively. Pre-transplantation supplemental oxygen requirements and non-invasive mechanical ventilation (NIMV) do not seem to affect survival (P=.44 and P=.63, respectively). Five- and 10-year survival among patients who did not undergo ECC during transplantation was 75.69% and 49.06%, respectively, while in those did undergo ECC during the procedure, 5- and 10-year survival was 34.14% and 29.87%, respectively (P=.001). PaCO 2 is an independent risk factor for the need for ECC. The survival rates of CF patients undergoing lung transplantation in our hospital are similar to those described in international registries. Survival is lower among patients receiving ECC during the procedure. PaCO 2 is a risk factor for the need for ECC during lung transplantation. Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Donor-acquired fat embolism syndrome after lung transplantation.

PubMed

Jacob, Samuel; Courtwright, Andrew; El-Chemaly, Souheil; Racila, Emilian; Divo, Miguel; Burkett, Patrick; Fuhlbrigge, Anne; Goldberg, Hilary J; Rosas, Ivan O; Camp, Phillip

2016-05-01

Fat embolism is a known complication of severe trauma and closed chest cardiac resuscitation both of which are more common in the lung transplant donor population and can lead to donor-acquired fat embolism syndrome (DAFES). The objective was to review the diagnosis and management of DAFES in the lung transplantation literature and at our centre. We performed a literature review on DAFES using the Medline database. We then reviewed the transplant record of Brigham and Women's Hospital, a large academic hospital with an active lung transplant programme, for cases of DAFES. We identified 2 cases of DAFES in our centre, one of which required extracorporeal membrane oxygenation (ECMO) for successful management. In contrast to the broader literature on DAFES, which emphasizes unsuccessfully treated cases, both patients survived. DAFES is a rare but likely underappreciated early complication of lung transplant as it can mimic primary graft dysfunction. Aggressive interventions, including ECMO, may be necessary to achieve a good clinical outcome following DAFES. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Impact of Donor Arterial Partial Pressure of Oxygen on Outcomes After Lung Transplantation in Adult Cystic Fibrosis Recipients.

PubMed

Hayes, Don; Kopp, Benjamin T; Kirkby, Stephen E; Reynolds, Susan D; Mansour, Heidi M; Tobias, Joseph D; Tumin, Dmitry

2016-08-01

Donor PaO2 levels are used for assessing organs for lung transplantation (LTx), but survival implications of PaO2 levels in adult cystic fibrosis (CF) patients receiving LTx are unclear. UNOS registry data spanning 2005-2013 were used to test for associations of donor PaO2 with patient survival and bronchiolitis obliterans syndrome (BOS) in adult (age ≥ 18 years) first-time LTx recipients diagnosed with CF. The analysis included 1587 patients, of whom 1420 had complete data for multivariable Cox models. No statistically significant differences among donor PaO2 categories of ≤200, 201-300, 301-400, or >400 mmHg were found in univariate survival analysis (log-rank test p = 0.290). BOS onset did not significantly differ across donor PaO2 categories (Chi-square p = 0.480). Multivariable Cox models of patient survival supported the lack of difference across donor PaO2 categories. Interaction analysis found a modest difference in survival between the two top categories of donor PaO2 when examining patients with body mass index (BMI) in the lowest decile (≤16.5 kg/m(2)). Donor PaO2 was not associated with survival or BOS onset in adult CF patients undergoing LTx. Notwithstanding statistically significant interactions between donor PaO2 and BMI, there was no evidence of post-LTx survival risk associated with donor PaO2 below conventional thresholds in any subgroup of adults with CF.

Esophageal Dysmotility, Gastro-esophageal Reflux Disease, and Lung Transplantation: What Is the Evidence?

PubMed

Wood, Richard K

2015-12-01

Lung transplantation is an effective and life-prolonging therapy for patients with advanced lung disease (ALD). However, long-term patient survival following lung transplantation is primarily limited by development of an inflammatory and fibrotic process involving the lung allograft known as bronchiolitis obliterans syndrome (BOS). Although the precise cause of BOS remains uncertain and is likely multifactorial, chronic aspiration of gastro-duodenal contents is one possible contributing factor. Multiple small, cross-sectional studies performed over the past two decades have reported a high prevalence of gastro-esophageal reflux disease (GERD) and esophageal dysmotility in the ALD population and several investigations suggest the prevalence may increase following lung transplantation. More recent studies evaluating the direct effect of gastro-duodenal contents on airways have demonstrated a possible biologic link between GERD and BOS. Despite the recent advances in our understanding of BOS, further investigations are needed to establish GERD as a causative factor in its development. This review will discuss the existing literature that has identified an association of GERD with ALD and post-transplant populations, with a focus on recent advances in the field.

How to optimize the lung donor.

PubMed

Sales, Gabriele; Costamagna, Andrea; Fanelli, Vito; Boffini, Massimo; Pugliese, Francesco; Mascia, Luciana; Brazzi, Luca

2018-02-01

Over the last two decades, lung transplantation emerged as the standard of care for patients with advanced and terminal lung disease. Despite the increment in lung transplantation rates, in 2016 the overall mortality while on waiting list in Italy reached 10%, whereas only 39% of the wait-list patients were successfully transplanted. A number of approaches, including protective ventilatory strategy, accurate management of fluid balance, and administration of a hormonal resuscitation therapy, have been reported to improve lung donor performance before organ retrieval. These approaches, in conjunction with the use of ex-vivo lung perfusion technique contributed to expand the lung donor pool, without affecting the harvest of other organs and the outcomes of lung recipients. However, the efficacy of issues related to the ex-vivo lung perfusion technique, such as the optimal ventilation strategy, the ischemia-reperfusion induced lung injury management, the prophylaxis of germs transmission from donor to recipient and the application of targeted pharmacologic therapies to treat specific donor lung injuries are still to be explored. The main objective of the present review is to summarize the "state-of-art" strategies to optimize the donor lungs and to present the actual role of ex-vivo lung perfusion in the process of lung transplant. Moreover, different approaches about the technique reported in literature and several issues that are under investigation to treat specific donor lung injury will be discussed.

Conservation of small-airway function by tacrolimus/cyclosporine conversion in the management of bronchiolitis obliterans following lung transplantation.

PubMed

Revell, M P; Lewis, M E; Llewellyn-Jones, C G; Wilson, I C; Bonser, R S

2000-12-01

We studied serial lung function in 11 patients with bronchiolitis obliterans syndrome who were treated with tacrolimus conversion following lung or heart-lung transplantation. Our results show that tacrolimus conversion slows the decline of lung function in bronchiolitis obliterans syndrome. The attenuation continues for at least 1 year following conversion.

Stem cell therapy: the great promise in lung disease.

PubMed

Siniscalco, Dario; Sullo, Nikol; Maione, Sabatino; Rossi, Francesco; D'Agostino, Bruno

2008-06-01

Lung injuries are leading causes of morbidity and mortality worldwide. Pulmonary diseases such as asthma or chronic obstructive pulmonary disease characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions, or idiopathic pulmonary fibrosis characterized by excessive matrix deposition and destruction of the normal lung architecture, have essentially symptomatic treatments and their management is costly to the health care system.Regeneration of tissue by stem cells from endogenous, exogenous, and even genetically modified cells is a promising novel therapy. The use of adult stem cells to help with lung regeneration and repair could be a newer technology in clinical and regenerative medicine. In fact, different studies have shown that bone marrow progenitor cells contribute to repair and remodeling of lung in animal models of progressive pulmonary hypertension.Therefore, lung stem cell biology may provide novel approaches to therapy and could represent a great promise for the future of molecular medicine. In fact, several diseases can be slowed or even blocked by stem cell transplantation.

Patient factors associated with lung transplant referral and waitlist for patients with cystic fibrosis and pulmonary fibrosis.

PubMed

Liu, Yuan; Vela, Monica; Rudakevych, Tanya; Wigfield, Christopher; Garrity, Edward; Saunders, Milda R

2017-03-01

Since 2005, the Lung Allocation Score (LAS) has prioritized patient benefit and post-transplant survival, reducing waitlist to transplant time to <200 days and decreasing mortality on the waitlist. A current challenge is the wait for the waitlist-the time between the patient's transplant-eligible diagnosis and waitlist registration. We investigated whether sociodemographic (age, sex, race, insurance, marital status, median household income) and clinical (forced expiratory volume in 1 second [FEV 1 ] percent of predicted, body mass index, depression/anxiety, alcohol/substance misuse, absolute/relative contraindications) factors influenced referral and waitlist registration. We conducted a retrospective cohort study through chart review of hospitalized patients on the University of Chicago general medicine service from 2006 to 2014 who met transplant-eligible criteria and ICD-9 billing codes for cystic fibrosis (CF) and pulmonary fibrosis (PF). We analyzed the times from transplant eligibility to referral, work-up and waitlisting using Kaplan-Meier curves and log-rank tests. Overall, the referral rate for transplant-eligible patients was 64%. Of those referred, approximately 36% reach the lung transplant waitlist. Referred CF patients were significantly more likely to reach the transplant waitlist than PF patients (CF 60% vs PF 22%, p < 0.05). In addition, CF patients had a shorter wait from transplant eligibility to waitlist than PF patients (329 vs 2,369 days, respectively [25th percentile], p < 0.05). Patients with PF and CF both faced delays from eligibility to referral and waitlist. Quality improvement efforts are needed to better identify and refer appropriate patients for lung transplant evaluation. Targeted interventions may facilitate more efficient evaluation completion and waitlist appearance. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Lung transplant recipients holding companion animals: impact on physical health and quality of life.

PubMed

Irani, S; Mahler, C; Goetzmann, L; Russi, E W; Boehler, A

2006-02-01

Since lung transplant recipients are susceptible to infections and inhaled pollution, many centers warn against pets. However, data supporting this recommendation are lacking. Our program is less restrictive regarding pets. This study, for the first time, investigates the association of pets with physiological and psychological parameters in these patients. A questionnaire concerning pets was sent to 104 lung transplant recipients. Lung function tests, levels of exhaled nitric oxide (FE(NO)), need for antibiotic treatments and hospitalizations, creatinine clearance, body mass index (BMI) and demographic data were assessed. Additionally, the questionnaire of life satisfaction (FLZ), a question on summarized life satisfaction (LS), the life orientation test (LOT), the hospital anxiety depression scale (HADS) and the social support questionnaire (F-SozU) were assessed. Response rate was 86%. Fifty-two percent defined themselves as pet owners, whereas 48% did not. The two groups did not differ in demographic or physiological data. Significant differences in FLZ (79/65, p = 0.04), in LS (4.3/3.9, p = 0.01), LOT (32/29, p = 0.006) and F-SozU (4.5/4.2, p = 0.04) were found in favor of pet owners. In lung transplant recipients keeping pets the frequency of somatic complications is not higher compared to lung transplant recipients without pets. After lung transplantation, pets are associated with a better quality of life.

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

PubMed Central

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

2010-01-01

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

Early diagnosis of fungal infections in lung transplant recipients, colonization versus invasive disease?

PubMed

Herrera, Sabina; Husain, Shahid

2018-05-21

The diagnosis of invasive aspergillosis remains challenging in solid organ transplants in general, and in lung transplant recipients, in particular, because of colonization. Lung transplant recipients may be over treated with antifungal drugs because of the lack of appropriate diagnostic tools. A review of the new developments of diagnostic tools and whether this help distinguishing colonization from invasive disease is presented. Efforts are being made to develop new tools that will allow us to identify which patients will develop IPA, and those who will be able to control the disease.

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

PubMed

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

2014-06-01

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

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

PubMed

Scheuher, Cynthia

2016-01-01

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

Ischaemia-reperfusion injury in orthotopic mouse lung transplants - a scanning electron microscopy study.

PubMed

Draenert, Alice; Marquardt, Klaus; Inci, Ilhan; Soltermann, Alex; Weder, Walter; Jungraithmayr, Wolfgang

2011-02-01

Lung ischaemia-reperfusion (I/R) injury remains a major cause of graft failure in lung transplantation (Tx). With the implementation of orthotopic lung Tx in mice, a physiological model on the base of a perfused and ventilated graft became available for the investigation of I/R injury. Using the scanning electron microscopy (SEM) technique, we here present an analysis of early and late morphological changes of pulmonary I/R injury. Syngeneic lungs were orthotopically transplanted between C57BL/6 mice. Grafts were exposed to 2 h of cold ischaemia. Transplants and right lungs were examined by SEM with corresponding haematoxylin-eosin histology 30 min and 4 h after reperfusion. Thirty minutes after reperfusion, the alveolar surface of transplants showed a discontinued lining of surfactant, while the lining of the non-transplanted lung was normal. Within the graft, leucocytes displayed an irregular surface with development of pseudopodia, and microvilli were detected on the membrane of pneumocytes. At 4 h after reperfusion, leucocytes significantly increased in numbers within the alveolar space. Also, the number of microvilli on pneumocytes increased significantly. Similar to these, the endothelium of vessels increasingly developed microvilli from 30 min towards 4 h after reperfusion. The airways of transplanted grafts showed mild changes with thickening of the bronchial epithelium and a destruction of kinocilia. Taken together, SEM detects pathological events of I/R that are previously not described in normal histology. These findings may influence the interpretation of studies investigating the I/R injury in the mouse model of lung Tx. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

Steroid withdrawal in lung transplant recipients.

PubMed

Borro, J M; Solé, A; De la Torre, M; Pastor, A; Tarazona, V

2005-11-01

Many of the long-term complications in lung transplantations are secondary effects of immunosuppression. Corticosteroids are partially responsible for the development of osteoporosis, raised blood pressure, diabetes, muscular disorders, gastric ulcers, and other conditions. We analyzed the long-term result of steroid withdrawal in our lung transplant recipients. When respiratory function stabilized, to avoid secondary effects, steroid treatment was withdrawn in 34 of the 375 lung transplant patients in our centers We evaluated the characteristics of the donors and recipients, their compatibility, the pre, and post-steroid withdrawal complications, and type of immunosuppressant. The mean age of patients was 42 +/- 7 years and of donors, 25 +/- 9 years. The primary diseases were: 15 emphysema, six pulmonary fibrosis, 10 cystic fibrosis, and three primary pulmonary hypertension. Twenty seven patients had double lung transplants and seven single lung. The mean steroid withdrawal period was 881 +/- 237 days posttransplantation. The most frequent treatment regimen at the time of steroid withdrawal was cyclosporine, azathioprine, and minimal steroid doses. Six recipients had to be restarted on steroids one patient who required a kidney transplant, three cases due to an infectious process with a differential diagnosis of rejection, and two cases due to loss of FEV1 (forced expiratory volume in 1 s), suggestive of chronic rejection. There was an improvement in blood pressure in five patients, in plasma cholesterol and triglyceride levels in eight patients, and insulin withdrawal in two diabetic patients. Steroid treatment may be suspended 2 to 3 years, posttransplant in selected lung transplant recipients. The usual patient profile shows few rejection episodes with cyclosporine and azathioprine immunosuppression. What is notable is the low mean age of donors. Close clinical monitoring and lung function testing are of major importance in the weeks following steroid withdrawal.

Outcome of influenza infection managed with oseltamivir in lung transplant recipients.

PubMed

Ison, Michael G; Sharma, Amita; Shepard, Jo-Anne O; Wain, John C; Ginns, Leo C

2008-03-01

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.

Telephone-Based Coping Skills Training for Patients Awaiting Lung Transplantation

ERIC Educational Resources Information Center

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

2006-01-01

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

Cystic Fibrosis Associated with Worse Survival After Liver Transplantation.

PubMed

Black, Sylvester M; Woodley, Frederick W; Tumin, Dmitry; Mumtaz, Khalid; Whitson, Bryan A; Tobias, Joseph D; Hayes, Don

2016-04-01

Survival in cystic fibrosis patients after liver transplantation and liver-lung transplantation is not well studied. To discern survival rates after liver transplantation and liver-lung transplantation in patients with and without cystic fibrosis. The United Network for Organ Sharing database was queried from 1987 to 2013. Univariate Cox proportional hazards, multivariate Cox models, and propensity score matching were performed. Liver transplant and liver-lung transplant were performed in 212 and 53 patients with cystic fibrosis, respectively. Univariate Cox proportional hazards regression identified lower survival in cystic fibrosis after liver transplant compared to a reference non-cystic fibrosis liver transplant cohort (HR 1.248; 95 % CI 1.012, 1.541; p = 0.039). Supplementary analysis found graft survival was similar across the 3 recipient categories (log-rank test: χ(2) 2.68; p = 0.262). Multivariate Cox models identified increased mortality hazard among cystic fibrosis patients undergoing liver transplantation (HR 2.439; 95 % CI 1.709, 3.482; p < 0.001) and liver-lung transplantation (HR 2.753; 95 % CI 1.560, 4.861; p < 0.001). Propensity score matching of cystic fibrosis patients undergoing liver transplantation to non-cystic fibrosis controls identified a greater mortality hazard in the cystic fibrosis cohort using a Cox proportional hazards model stratified on matched pairs (HR 3.167; 95 % CI 1.265, 7.929, p = 0.014). Liver transplantation in cystic fibrosis is associated with poorer long-term patient survival compared to non-cystic fibrosis patients, although the difference is not due to graft survival.

Predictors of employment participation following lung transplant.

PubMed

Cumming, Kate; O'Brien, Lisa; Harris, Jane

2016-10-01

Limited information about return to productive activities after lung transplantation has been published. The purpose of our study was to identify issues relating to occupational engagement in employment after surgery. We conducted a cross-sectional study of surviving lung transplant recipients from one transplant service in Australia. We used descriptive statistics, chi-square tests and Cox regression to analyse the data. A total of 100 lung transplant recipients completed the assessment (83.3% of 120 eligible surviving recipients). The mean age of respondents was 50 ± 13 years; 45% of the sample were men. Cystic fibrosis and chronic obstructive pulmonary disease were the most frequent pre-transplant diagnoses. Fifty-five percent of participants identified employment or alternate occupational engagement prior to transplant. Of those respondents who had not retired from work prior to transplant, 44.2% identified engagement in paid employment after transplantation. Participants who obtained paid employment post-transplantation were more likely to have completed high school (P = 0.05) or worked as managers (P < 0.0001). Occupational therapists should be actively involved in pre- and post-transplantation goal setting and intervention to support return to work. Pre-transplant, participation in any amount of voluntary or paid employment or study will maintain networks, skills, and confidence. Post-transplant, while physician encouragement is known as a key predictor of return to work, occupational therapist support can address function and activity components of work participation. © 2016 Occupational Therapy Australia.

Tsukamurella tyrosinosolvens - An unusual case report of bacteremic pneumonia after lung transplantation

PubMed Central

2009-01-01

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

Fungal infection by Mucorales order in lung transplantation: 4 case reports.

PubMed

Neto, F M F D; Camargo, P C L B; Costa, A N; Teixeira, R H O B; Carraro, R M; Afonso, J E; Campos, S V; Samano, M N; Fernandes, L M; Abdalla, L G; Pêgo-Fernandes, P M

2014-01-01

Mucorales is a fungus that causes systemic, highly lethal infections in immunocompromised patients. The overall mortality of pulmonary mucormycosis can reach 95%. This work is a review of medical records of 200 lung transplant recipients between the years of 2003 and 2013, in order to identify the prevalence of Mucorales in the Lung Transplantation service of Heart Institute (InCor), Hospital das Clínicas da Universidade de São Paulo, Brazil, by culture results from bronchoalveolar lavage and necropsy findings. We report 4 cases found at this analyses: 3 in patients with cystic fibrosis and 1 in a patient with bronchiectasis due to Kartagener syndrome. There were 2 unfavorable outcomes related to the presence of Mucorales, 1 by reduction of immunosuppression, another by invasive infection. Another patient died from renal and septic complications from another etiology. One patient was diagnosed at autopsy just 5 days after lung transplantation, with the Mucor inside the pulmonary vein with a precise, well-defined involvement only of donor's segment, leading to previous colonization hypothesis. There are few case reports of Mucorales infection in lung transplantation in the literature. Surveillance for the presence of Mucor can lead to timely fungal treatment and reduce morbidity and mortality in the immunocompromised patients, especially lung transplant recipients. Copyright © 2014 Elsevier Inc. All rights reserved.

Postoperative Swallowing Assessment After Lung Transplantation.

PubMed

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

2017-07-01

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.

ENHANCED GENE DELIVERY IN PORCINE VASCULATURE TISSUE FOLLOWING INCORPORATION OF ADENO-ASSOCIATED VIRUS NANOPARTICLES INTO POROUS SILICON MICROPARTICLES

PubMed Central

McConnell, Kellie I.; Rhudy, Jessica; Yokoi, Kenji; Gu, Jianhua; Mack, Aaron; Suh, Junghae; La Francesca, Saverio; Sakamoto, Jason; Serda, Rita E.

2014-01-01

There is an unmet clinical need to increase lung transplant successes, patient satisfaction and to improve mortality rates. We offer the development of a nanovector-based solution that will reduce the incidence of lung ischemic reperfusion injury (IRI) leading to graft organ failure through the successful ex vivo treatment of the lung prior to transplantation. The innovation is in the integrated application of our novel porous silicon (pSi) microparticles carrying adeno-associated virus (AAV) nanoparticles, and the use of our ex vivo lung perfusion/ventilation system for the modulation of pro-inflammatory cytokines initiated by ischemic pulmonary conditions prior to organ transplant that often lead to complications. Gene delivery of anti-inflammatory agents to combat the inflammatory cascade may be a promising approach to prevent IRI following lung transplantation. The rationale for the device is that the microparticle will deliver a large payload of virus to cells and serve to protect the AAV from immune recognition. The microparticle-nanoparticle hybrid device was tested both in vitro on cell monolayers and ex vivo using either porcine venous tissue or a pig lung transplantation model, which recapitulates pulmonary IRI that occurs clinically post-transplantation. Remarkably, loading AAV vectors into pSi microparticles increases gene delivery to otherwise non-permissive endothelial cells. PMID:25180449

Lung transplantation in the spotlight: Reasons for high-cost procedures.

PubMed

Vogl, Matthias; Warnecke, Gregor; Haverich, Axel; Gottlieb, Jens; Welte, Tobias; Hatz, Rudolf; Hunger, Matthias; Leidl, Reiner; Lingner, Heidrun; Behr, Juergen; Winter, Hauke; Schramm, Rene; Zwissler, Bernhard; Hagl, Christian; Strobl, Nicole; Jaeger, Cornelius; Preissler, Gerhard

2016-10-01

Hospital treatment costs of lung transplantation are insufficiently analyzed. Accordingly, it remains unknown, whether current Diagnosis Related Groups, merely accounting for 3 ventilation time intervals and length of hospital stay, reproduce costs properly, even when an increasing number of complex recipients are treated. Therefore, in this cost determination study, actual costs were calculated and cost drivers identified. A standardized microcosting approach allowed for individual cost calculations in 780 lung transplant patients taken care of at Hannover Medical School and University of Munich from 2009 to 2013. A generalized linear model facilitated the determination of characteristics predictive for inpatient costs. Lung transplantation costs varied substantially by major diagnosis, with a mean of €85,946 (median €52,938 ± 3,081). Length of stay and ventilation time properly reproduced costs in many cases. However, complications requiring prolonged ventilation or reinterventions were identified as additional significant cost drivers, responsible for high costs. Diagnosis Related Groups properly reproduce actual lung transplantation costs in straightforward cases, but costs in complex cases may remain underestimated. Improved grouping should consider major diagnosis, a higher gradation of ventilation time, and the number of reinterventions to allow for more reasonable reimbursement. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Epidemiology, outcomes, and mortality predictors of invasive mold infections among transplant recipients: a 10-year, single-center experience.

PubMed

Neofytos, D; Treadway, S; Ostrander, D; Alonso, C D; Dierberg, K L; Nussenblatt, V; Durand, C M; Thompson, C B; Marr, K A

2013-06-01

The epidemiology of invasive mold infections (IMI) in transplant recipients differs based on geography, hosts, preventative strategies, and methods of diagnosis. We conducted a retrospective observational study to evaluate the epidemiology of proven and probable IMI, using prior definitions, among all adult hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients in the era of "classic" culture-based diagnostics (2000-2009). Epidemiology was evaluated before and after an initiative was begun to increase bronchoscopy in HSCT recipients after 2005. In total, 106 patients with one IMI were identified. Invasive aspergillosis (IA) was the most common IMI (69; 65.1%), followed by mucormycosis (9; 8.5%). The overall rate of IMI (and IA) was 3.5% (2.5%) in allogeneic HSCT recipients. The overall incidence for IMI among lung, kidney, liver, and heart transplant recipients was 49, 2, 11, and 10 per 1000 person-years, respectively. The observed rate of IMI among human leukocyte antigen-matched unrelated and haploidentical HSCT recipients increased from 0.6% annually to 3.0% after bronchoscopy initiation (P < 0.05). The 12-week mortality among allogeneic HSCT, liver, kidney, heart, and lung recipients with IMI was 52.4%, 47.1%, 27.8%, 16.7%, and 9.5%, respectively. Among allogeneic HSCT (odds ratio [OR]: 0.07, P = 0.007) and SOT (OR: 0.22, P = 0.05) recipients with IA, normal platelet count was associated with improved survival. Male gender (OR: 14.4, P = 0.007) and elevated bilirubin (OR: 5.7, P = 0.04) were significant predictors of mortality for allogeneic HSCT and SOT recipients with IA, respectively. During the era of culture-based diagnostics, observed rates of IMI were low among all transplants except lung transplant recipients, with relatively higher mortality rates. Diagnostic aggressiveness and host variables impact the reported incidence and outcome of IMI and likely account for institutional variability in multicenter studies. Definitions to standardize diagnoses among SOT recipients are needed. © 2013 John Wiley & Sons A/S.

Employment after lung transplantation--a single-center cross-sectional study.

PubMed

Suhling, Hendrik; Knuth, Christine; Haverich, Axel; Lingner, Heidrun; Welte, Tobias; Gottlieb, Jens

2015-03-27

359 lung transplantations were performed in Germany in 2013. The main goals of lung transplantation are to prolong survival and improve the quality of life. Both of these goals can be reflected in a return to employment. We report the first study of employment after lung transplantation in Germany. We evaluated the findings of a single-center, questionnaire-based cross-sectional investigation of the social and economic situation of 531 patients (September 2009 to March 2010) and obtained 5-year follow-up data in December 2014. 38% of the patients were employed after lung transplantation. They took a mean of ten sick days off from work each year; they did not have infections or organ rejection any more frequently than other patients. The fiveyear follow-up data showed no difference in the overall survival rate of employed and unemployed patients. Employment was associated with a better quality of life (80% [interquartiles: 70%, 95%]) versus 75% [interquartiles: 50%, 85%], p = 0.001). Factors associated with a return to employment included a higher educational level (odds ratio [OR] 2.6, 95%confidence interval [CI] 1.7-4, p = 0.001) and better physical fitness (OR 2, 95%CI 1.3-3.2, p = 0.001). The rate of return to work after lung transplantation in Germany is similar to the rates observed in other countries. The findings of this study imply that employment improves the quality of life and does not endanger health. Thus, patients who have received lung transplants should be advised to return to work if possible.

Trend in lung transplantation in the U.S.: an analysis of the UNOS registry.

PubMed

Freitas, Maria Cecilia S

2010-01-01

The number of lung transplants continues to increase in the U.S. The most significant change over the last decade occurred after the 2005 implementation of LAS. When the percentage of patients being transplanted increased even further, while time-to-transplant and the number of patients dying on the waiting list significantly declined. As a result of implementation of LAS in 2005, IPF recipients became the largest group to receive a lung transplant. And the number of transplants for patients age 60 and over has increased significantly. The number of DL transplants performed yearly increased while the number of SL transplants has remained relatively consistent throughout the last decade. Though the gender distribution of recipients has fluctuated each year, the proportion of females receiving lung transplant has decreased. Of the deceased-donor DL and SL transplant recipients, 69% had a cold ischemia time between 3-6 hrs. And 79% of primary DL and SL transplant recipients had a 0% PRA. 6. A higher number of HLA mismatches impacts unfavorably on graft survival rates; yet, surprisingly, zero HLA A-B-DR MM also have an unfavorable impact; Recipients with less than two hours of cold ischemia-time (n = 815, 4.3%) have the worst five-year graft survival; PRA levels greater than 25% have an unfavorable impact on graft survival.

OPTN/SRTR 2016 Annual Data Report: Lung.

PubMed

Valapour, M; Lehr, C J; Skeans, M A; Smith, J M; Carrico, R; Uccellini, K; Lehman, R; Robinson, A; Israni, A K; Snyder, J J; Kasiske, B L

2018-01-01

In 2016, 2692 candidates aged 12 years or older were added to the lung transplant waiting list; 2345 transplants were performed, the largest number of any prior year. The median waiting time for listed candidates in 2016 was 2.5 months, and waiting times were shortest for group D candidates. The transplant rate increased to 191.9 transplants per 100 waitlist years in 2016, with a slight decrease in waitlist mortality to 15.1 deaths per 100 waitlist years. Short-term survival continued to improve, with a 6-month death rate of 6.6% and a 1-year death rate of 10.8% among recipients in 2015 compared with 8.0% and 13.3%, respectively, among recipients in 2014. Long-term survival rates remained unchanged; 55.6% of recipients were alive at 5 years. In 2016, 23 new candidates aged 0-11 years were added to the waiting list and 16 lung transplants were performed. Incidence of posttransplant mortality for lung transplant recipients aged 0-11 years who underwent transplant in 2014-2015 was 13.8% at 6 months and 19.6% at 1 year. Changes in waitlist and transplant demographic features continued to evolve following implementation of the revised lung allocation score in 2015. Some early trends that may be attributable to the revised LAS are shorter waiting times, stabilization of the number of group D candidates listed for transplant, and convergence of LAS with lower prevalence of extremely high scores.  .

OPTN/SRTR 2015 Annual Data Report: Lung.

PubMed

Valapour, M; Skeans, M A; Smith, J M; Edwards, L B; Cherikh, W S; Uccellini, K; Israni, A K; Snyder, J J; Kasiske, B L

2017-01-01

In 2015, 2409 active candidates aged 12 years or older were added to the lung transplant waiting list; 2072 transplants were performed, the most of any year. The median waiting time for candidates listed in 2015 was 3.4 months; the shortest waiting time was for diagnosis group D. Despite the highest recorded transplant rate of 157 per 100 waitlist years, waitlist mortality continued a steady decade-long rise to a high of 16.5 deaths per 100 waitlist years. Measures of short- and long-term survival showed no trend toward improved overall survival in the past 5 years, except that 6-month death rates decreased from 9.4% in 2005 to 7.9% in 2014. At 5 years posttransplant, 55.5% of recipients remained alive. In 2015, 23 new child (ages 0-11 years) candidates were added to the list; 17 transplants were performed. Incidence of death was 6.1% at 6 months and 8.2% at 1 year for transplants in 2013-2014. Important policy changes will affect access to transplant. In February 2015, OPTN implemented a comprehensive revision of the lung allocation score to better reflect mortality risk. Broader geographic sharing of donor lungs for pediatric candidates and allowance for selected transplants across blood types for candidates aged younger than 2 years have been approved and are expected to improve pediatric access to transplant. The impact of these changes on lung transplant trends will be observed in the coming years. .

Successful cardiac transplantation outcomes in patients with adult congenital heart disease.

PubMed

Menachem, Jonathan N; Golbus, Jessica R; Molina, Maria; Mazurek, Jeremy A; Hornsby, Nicole; Atluri, Pavan; Fuller, Stephanie; Birati, Edo Y; Kim, Yuli Y; Goldberg, Lee R; Wald, Joyce W

2017-09-01

The purpose of our study is (1) to characterise patients with congenital heart disease undergoing heart transplantation by adult cardiac surgeons in a large academic medical centre and (2) to describe successful outcomes associated with our multidisciplinary approach to the evaluation and treatment of adults with congenital heart disease (ACHD) undergoing orthotopic heart transplantation (OHT). Heart failure is the leading cause of death in patients with ACHD leading to increasing referrals for OHT. The Penn Congenital Transplant Database comprises a cohort of patients with ACHD who underwent OHT between March 2010 and April 2016. We performed a retrospective cohort study of the 20 consecutive patients. Original cardiac diagnoses include single ventricle palliated with Fontan (n=8), dextro-transposition of the great arteries after atrial switch (n=4), tetralogy of Fallot (n=4), pulmonary atresia (n=1), Ebstein anomaly (n=1), unrepaired ventricular septal defect (n=1) and Noonan syndrome with coarctation of the aorta (n=1). Eight patients required pretransplant inotropes and two required pretransplant mechanical support. Nine patients underwent heart-liver transplant and three underwent heart-lung transplant. Three patients required postoperative mechanical circulatory support. Patients were followed for an average of 38 months as of April 2016, with 100% survival at 30 days and 1 year and 94% overall survival (19/20 patients). ACHD-OHT patients require highly specialised, complex and multidisciplinary healthcare. The success of our programme is attributed to using team-based, patient-centred care including our multidisciplinary staff and specialists across programmes and departments. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Lung transplantation from initially rejected donors after ex vivo lung reconditioning: the French experience.

PubMed

Sage, Edouard; Mussot, Sacha; Trebbia, Grégoire; Puyo, Philippe; Stern, Marc; Dartevelle, Philippe; Chapelier, Alain; Fischler, Marc

2014-11-01

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.

[The results of the evaluation of 208 patients referred in the first 4 years to a lung transplantation program. The Lung Transplantation Group of Hospital Vall d'Hebron].

PubMed

Morell, F; Román, A; Bravo, C; Nicolau, F; Martí, S

1996-01-01

Retrospective analysis of the patients referred for possible lung transplants between 1990 and 1994. Between 1990 and 1994 the Lung Transplant Program at Hospital Vall d'Hebron received 208 referrals from all over Spain. The cases most often involved a combination of bronchiectasia and cystic fibrosis (29%), chronic obstructive pulmonary disease (25%) and pulmonary fibrosis (16.5%). Internationally established guidelines for lung transplantation were used to screen the cases and the results have been analyzed retrospectively. After first evaluating the report sent by the patient's pneumonologist, 100 patients (49%) were considered candidates for further hospital study. Of the 100, 53 (25%) were finally placed on an active waiting list. Twenty-seven (12.9%) of the 53 received transplants, 6 died while waiting, and the others remained on the waiting list on 31 December 1994. Mortality among the rejected patients between the first visit until the end of the study, excluding those who were not yet classified as serious cases and those who were terminally ill, was 36/123 (29%). Actuarial survival rates at 12 and 24 months for transplanted patients were 64 and 49%, respectively. After following the currently accepted screening methods, one in 4 patients referred for possible lung transplantation was finally given a place on the active waiting list. The series studied here is noteworthy for the relatively low number of patients with chronic obstructive pulmonary disease in comparison with other programs, although we expect the number to increase in the coming years.

[Lung transplant therapy for suppurative diseases].

PubMed

de Pablo, A; López, S; Ussetti, P; Carreño, M C; Laporta, R; López García-Gallo, C; Ferreiro, M J

2005-05-01

Lung transplantation is a valid therapeutic approach for patients with bronchiectasis. The objective of the present study was to evaluate our experience with bronchiectasis patients and compare the results in patients with cystic fibrosis to results in those with bronchiectasis caused by other processes. We carried out a retrospective study of bronchiectasis patients treated by lung transplantation in order to analyze demographic, functional and microbiological characteristics before and after transplantation, and survival. From 1991 to 2002 lung transplants were performed on 171 patients, 44 of whom had suppurative lung disease (27 had cystic fibrosis and 17 had bronchiectasis caused by other processes). There were no significant differences in the demographic variables between the 2 groups. At transplantation, lung function variables showed severe bronchial obstruction (mean [SD] forced expiratory volume in 1 second of 808 [342] mL and forced vital capacity of 1,390 [611] mL) and respiratory insufficiency (PaO2 at 52 [10] mm Hg and PaCO2 at 48 [9] mm Hg). Only PaO2 was significantly lower in patients with bronchiectasis from causes other than cystic fibrosis. Airway colonization was present in 91% of the patients; Pseudomonas spp germs were detected in 64% of the cases and were multiresistant in 9%. In the early postoperative period germs were isolated in 59% of the cases, half of which involved the same germ as had been isolated before transplantation. One year after lung transplantation, 34% of the patients continued to have bronchial colonization. Survival at 1 year was 79% and at 5 years, 49%, with no significant difference between the patients with cystic fibrosis and those with other suppurative diseases, nor between the patients with and without Pseudomonas colonization. Only 2 patients had died of bacterial pneumonia at 1 month after transplantation. Although airway colonization in patients with suppurative diseases complicates postoperative management, the results in terms of survival are good.

Atrial arrhythmias after lung transplant: underlying mechanisms, risk factors, and prognosis.

PubMed

Orrego, Carlos M; Cordero-Reyes, Andrea M; Estep, Jerry D; Seethamraju, Harish; Scheinin, Scott; Loebe, Matthias; Torre-Amione, Guillermo

2014-07-01

Atrial arrhythmias (AAs) early after lung transplant are frequent and have a significant impact on morbidity and mortality. However, the pathogenesis of AAs after lung transplant remains incompletely understood. In this study we aimed to determine the prevalence of atrial fibrillation (AF) and other AAs, as well as risk factors, clinical outcomes and possible underlying mechanisms associated with AAs after lung transplant. A retrospective analysis was performed on 382 patients who underwent lung transplantation from 2000 to 2010. A 12-lead electrocardiogram (ECG) was obtained and AAs classified as AF and other AAs (atrial flutter [AFL] and supraventricular tachycardia [SVT]). Multivariate logistic regression analysis was performed to determine predictors, and Kaplan-Meier survival curves were constructed. The incidence of AAs was 25%; 17.8% developed AF and 7.6% other AAs (AFL/SVT). The major indication for transplant was idiopathic pulmonary fibrosis (IPF, 35%). Significant predictors of AF were as follows: age; IPF; left atrial enlargement; diastolic dysfunction; and history of coronary artery disease (CAD). Risk factors for other AAs (AFL/SVT) were: age; right ventricle dysfunction; right ventricular enlargement; and elevated right atrial pressure (RAP). One-year mortality was higher in the arrhythmia group (21.5% arrhythmia vs 15.7% no-arrhythmia group; p < 0.05). In addition, patients treated with anti-arrhythmic medications had higher mortality (p < 0.05). AAs are common after lung transplantation. Risk factors for developing either AF or other AAs (AFL/SVT) are different. The development of early AAs post-transplant is associated with prolonged post-operative stay and increased mortality. A rate-control strategy should be used as first-line therapy and anti-arrhythmic agents reserved for those patients who do not respond to the initial treatment. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Caregivers’ perspectives on decision making about lung transplantation in cystic fibrosis

PubMed Central

Dellon, Elisabeth P.; Shores, Mitchell D.; Nelson, Katherine I.; Wolfe, Joanne; Noah, Terry L.; Hanson, Laura C.

2013-01-01

Context Lung transplantation extends survival for some patients with advanced cystic fibrosis, but it is complicated, has many potential risks, and its outcomes are difficult to predict. No standards exist for informed decision making about transplantation. Objective To assess decision making from the perspective of caregivers of patients who faced the transplant decision before dying of cystic fibrosis or transplant complications. Design Semistructured interviews with descriptive and qualitative content analysis. Participants Twenty-eight caregivers of patients with cystic fibrosis who received care at our center and died between 1996 and 2006. Results Of 28 patients who considered lung transplantation, 19 (68%) received transplants, 6 (21%) died while waiting for transplant, and 3 (11%) declined transplant. Three caregivers (11%) thought that the patient did not fully understand the reason for transplant referral. Five (18%) thought that the patient did not fully understand potential risks. Ten (36%) thought that alternatives were not fully understood. The only alternatives to transplant identified, progressive illness and the possibility of earlier death without transplant, were unacceptable to most. Thirteen caregivers (46%) reported that the patient thought that declining transplant was not an option. Caregivers described the decision as “easy” for 19 (68%), often expressing a sentiment of “do or die.” Those who described the decision as “easy” recalled fewer elements of informed decision making. Conclusions From caregivers’ reports, patients with cystic fibrosis may not fully understand risks of and alternatives to lung transplantation. Because a strong desire to prolong life necessitates honest communication about potential outcomes, interventions are needed to facilitate high-quality decision making. PMID:20050454

Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation

PubMed Central

Ruiz, Jesus; Herrero, María José; Bosó, Virginia; Megías, Juan Eduardo; Hervás, David; Poveda, Jose Luis; Escrivá, Juan; Pastor, Amparo; Solé, Amparo; Aliño, Salvador Francisco

2015-01-01

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

[What the family doctor must know about lung transplant (Part 1)].

PubMed

Zurbano, L; Zurbano, F

2017-09-01

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.

Lung transplantation for respiratory failure; Belgium amongst the world leaders.

PubMed

Van Raemdonck, D; Verleden, G M

2011-01-01

Lung transplantation is a life-saving treatment option in carefully selected patients with end-stage lung disease. Life expectancy after this form of treatment has progressively increased with a current survival of 90% after 1 year, 70% after 5 years, and 50% after 10 years in experienced centers. Apart from a survival benefit, this treatment aims to improve the quality of life. Bilateral lung transplantation is the type of operation that is performed most frequently because of superior survival results, especially when chronic rejection develops. Single lung transplantation is now reserved for older patients with pulmonary fibrosis. Heart-lung transplantation is rarely done, only in patients with Eisenmenger's syndrome or complex congenital heart disease. Belgium is one of the world leaders in terms of number of deceased organ donors with a lung recovery rate of about 35%. With a total of 8.3 lung transplants per million population, Belgium is currently the number 1 in the world. The procedure nowadays is performed in 4 University Hospitals (UA-KUL-ULB-UCL) in the country. Between 1983 and 2009, nearly 1000 proedures were performed. The most common indication was emphysema, followed by cystic fibrosis, pulmonary fibrosis, pulmonary arterial hypertension, and Eisenmenger's syndrome. Further application of this treatment option is hampered by several problems such as donor organ shortage, primary graft dysfunction, chronic rejection presenting as bronchiolitis obliterans syndrome, and side effect of chronic immunosuppression. In the Laboratory for Experimental Thoracic Surgery and the Laboratory for Pneumology at the Katholieke Universiteit Leuven, intensive research is done by our group looking for new methods to increase the lung donor pool and to prevent and to treat chronic rejection.

The role of innate immunity in acute allograft rejection after lung transplantation.

PubMed

Palmer, Scott M; Burch, Lauranell H; Davis, R Duane; Herczyk, Walter F; Howell, David N; Reinsmoen, Nancy L; Schwartz, David A

2003-09-15

Although innate immunity is crucial to pulmonary host defense and can initiate immune and inflammatory responses independent of adaptive immunity, it remains unstudied in the context of transplant rejection. To investigate the role of innate immunity in the development of allograft rejection, we assessed the impact of two functional polymorphisms in the toll-like receptor 4 (TLR4) associated with endotoxin hyporesponsiveness on the development of acute rejection after human lung transplantation. Patients and donors were screened for the TLR4 Asp299Gly and Thr399Ile polymorphisms by polymerase chain reaction using sequence-specific primers. The rate of acute rejection at 6 months was significantly reduced in recipients, but not in donors, with the Asp299Gly or Thr399Ile alleles as compared with wild type (29 vs. 56%, respectively, p = 0.05). This association was confirmed in Cox proportional hazards and multivariate logistic regression models. Our results suggest activation of innate immunity in lung transplant recipients through TLR4 contributes to the development acute rejection after lung transplantation. Therapies directed at inhibition of innate immune responses mediated by TLR4 may represent a novel and effective means to prevent acute rejection after lung transplantation.

[Anesthesia in single and bilateral sequential lung transplantation. Lung Transplantation Group].

PubMed

Della Rocca, G; Coccia, C; Pugliese, F; Pompei, L; Ruberto, F; Costa, M G; Venuta, F; Rendina, E A; De Giacomo, T; Pietropaoli, P; Gasparetto, A

2000-04-01

Anesthesia for lung transplantation: intraoperative complications and long term results. 52 patients were scheduled for 16 single lung transplantations (SLT) (9 fibrosis and 7 emphysema) and 36 bilateral sequential lung transplantations (DLT) (4 bronchiectasis, 6 emphysema, 3 fibrosis, 22 cystic fibrosis and 1 pulmonary hypertension). Anesthesia was induced with propofol or midazolam, and fentanyl or alfentanil. As muscle relaxant vecuronium bromide was used. Anesthesia was maintained with isoflurane, fentanyl in boluses or sufentanil continuous infusion in O2 100%. Prostaglandin E1 (20-300 ng/kg/min), inhaled nitric oxide (10-40 ppm), dobutamine (5-15 mcg/kg/min), norepinephrine (0.05-3 mcg/kg/min) and ephedrine (5-10 mg per bolus) were used for hemodynamic management. In 2 patients inhaled areosolized prostacyclin were administered. Mean pulmonary arterial pressure (mPA) and pulmonary vascular resistance (PVRI) increased after pulmonary artery clamping during first lung (mPA: 3347 nel DLT, 3643 nel SLT; PVRI; 375488 nel DLT, 377420 nel SLT) and second lung implantation (mPA: 3746; PVRI: 263553) and decreased after reperfusion of the first (mPA: 4737 nel DLT, 4329 nel SLT; PVRI: 488263 nel DLT, 420233 nel SLT) and the second lung (mPA: 4629; PVRI: 553260). Only in 9 cases (7 DLT and 2 SLT) C-P bypass was used. With a strong drug support with pulmonary vasodilators, positive inotropic and systemic vasoconstrictor drugs, in most patients we transplanted C-P bypass can be avoided. Intraoperative deaths were not observed. Two years actuarial survival is 65% for DLT and 60% for SLT.

Banff study of pathologic changes in lung allograft biopsy specimens with donor-specific antibodies.

PubMed

Wallace, William Dean; Li, Ning; Andersen, Claus B; Arrossi, A Valeria; Askar, Medhat; Berry, Gerry J; DeNicola, Matthew M; Neil, Desley A; Pavlisko, Elizabeth N; Reed, Elaine F; Remmelink, Myriam; Weigt, S Sam; Weynand, Birgit; Zhang, Jennifer Q; Budev, Marie M; Farver, Carol F

2016-01-01

The diagnosis of antibody-mediated rejection (AMR) in the lung transplant is still an area under investigation. We performed a blinded multicenter study to determine if any statistically significant histologic findings in transbronchial biopsy specimens from lung transplant patients correlate with the presence of donor-specific antibodies (DSAs). We asked 9 pathologists with experience in lung transplantation to evaluate 161 lung transplant biopsy specimens for various histologic parameters. The findings were correlated with antibody status positive for DSAs, positive for non-DSAs, and no antibodies (NABs) present. The significance of each histologic variable was reviewed. We found no statistically significant association with acute cellular rejection, airway inflammation, or bronchiolitis obliterans and the presence or absence of antibodies. However, biopsy specimens with DSAs had a statistically significant difference vs NABs in the setting of acute lung injury, with or without diffuse alveolar damage (p = 0.0008), in the presence of capillary neutrophilic inflammation (p = 0.0014), and in samples with endotheliitis (p = 0.0155). In samples with complement 4d staining, there was a trend but no statistically significant difference between specimens associated with DSAs and specimens with NABs. Capillary inflammation, acute lung injury, and endotheliitis significantly correlated with DSAs. The infrequently observed diffuse staining for complement 4d limits the usefulness of this stain. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Growing experience with extracorporeal membrane oxygenation as a bridge to lung transplantation.

PubMed

Shafii, Alexis E; Mason, David P; Brown, Chase R; Vakil, Nakul; Johnston, Douglas R; McCurry, Kenneth R; Pettersson, Gosta B; Murthy, Sudish C

2012-01-01

Extracorporeal membrane oxygenation (ECMO) is rarely used as a bridge to lung transplantation (BTT) because of its associated morbidity and mortality. However, recent advancements in perfusion technology and critical care have revived interest in this application of ECMO. We retrospectively reviewed our utilization of ECMO as BTT and evaluated our early and midterm results. Nineteen patients were placed on ECMO with the intent to transplant of which 14 (74%) were successfully transplanted. Early and midterm survival of transplanted patients was 75% (1 year) and 63% (3 years), respectively, with the most favorable results observed in interstitial lung disease patients supported in the venovenous configuration. Extracorporeal membrane oxygenation-bridged transplant survival rates were equivalent to nonbridged recipients, but early morbidity and mortality are high and the failure to bridge to transplant is significant. Overall, successfully bridged patients can derive a tangible benefit, albeit with considerable consumption of resources.

Heart-lung transplantation in cystic fibrosis: predictions for the next decade in England and Wales.

PubMed

Elborn, J S; Shale, D J; Britton, J R

1994-02-01

Heart-lung transplantation has become an established treatment for end stage respiratory failure secondary to cystic fibrosis. The success of this form of treatment, and the increasing survival of such patients, suggests there will be an increased need for transplantation over the next decade. We have used cystic fibrosis population predictions and all cause mortality data to estimate the number of cardio-pulmonary deaths, due to cystic fibrosis, over the next decade and to estimate the number of such patients who are likely to benefit from heart-lung transplantation. We estimate that there will be between 85 and 127 potential transplant recipients with cystic fibrosis each year over the next decade. During 1990, 1991 and 1992 there were less than 40 transplants each year in such patients. These data emphasize the need to expand transplantation services and to maintain the availability of donor organs.

[Lung transplantation].

PubMed

Santillán-Doherty, Patricio; Jasso-Victoria, Rogelio; Olmos-Zúñiga, Raúl; Sotres-Vega, Avelina; Argote-Greene, Luis Marcelo; Escalante-Tattersfield, Tomás; Villalba-Caloca, Jaime

2005-01-01

Lung transplantation (LT) has evolved to become an important alternative in the management of patients with end-stage pulmonary disease and chronic respiratory failure. The beginnings of this technique can be traced back to the experiments of Carrel and Guthrie over a hundred years ago. However, it was not until 1963 when the first clinical experience was performed by Hardy. Clinical success did not arrive until the 1980's thanks to the works of the Toronto Lung Transplant Group. Well established criteria have been described in order to consider a patient as a potential candidate to receive a lung. Several diseases are capable of causing terminal lung damage and in general they can be classified according to their origin as obstructive (COPD, emphysema), restrictive (fibrosis), chronic infectious (cystic fibrosis, bronquiectasis), and vascular (primary pulmonary hypertension). The most frequent diagnosis is COPD. Clinically relevant modes of LT include the implant of one lung (single LT), or both lungs (bilateral sequential LT). Transplantation of the cardiopulmonary block is reserved for special situations and lobar transplantation is still considered experimental. Donor condition is essential to the success of LT. The potential donor patient frequently suffers deterioration in lung function due to edema formation or infection and both complications restrict lung's using for transplantation. Lung preservation is also limited to a short period of time which rarely exceeds 6 hours in spite of specially-designed preservative solutions such as the low potassium dextran. Outcome after LT shows current one-year survival between 65-70% with reduction to 40-45% after five years. Mortality within the first year is usually related to primary graft failure and infection. Long-term survival depends on controlling infectious problems due to immunosuppression as well as the development of bronchilitis obliterans as a manifestation of chronic rejection. LT is a therapeutic modality reserved for selected patients with chronic respiratory failure due to end-stage lung disease.

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

PubMed

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

2014-10-01

Patients with pulmonary hypertension are some of the most challenging for an anaesthesiologist to manage. Pulmonary hypertension in patients undergoing surgical procedures is associated with high morbidity and mortality due to right ventricular failure, arrhythmias and ischaemia leading to haemodynamic instability. Lung transplantation is the only therapeutic option for end-stage lung disease. Patients undergoing lung transplantation present a variety of challenges for anaesthesia team, but pulmonary hypertension remains the most important. The purpose of this article is to review the anaesthetic management of pulmonary hypertension during lung transplantation, with particular emphasis on the choice of anaesthesia, pulmonary vasodilator therapy, inotropic and vasopressor therapy, and the most recent intraoperative monitoring recommendations to optimize patient care. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

An official American Thoracic Society/International Society for Heart and Lung Transplantation/Society of Critical Care Medicine/Association of Organ and Procurement Organizations/United Network of Organ Sharing Statement: ethical and policy considerations in organ donation after circulatory determination of death.

PubMed

Gries, Cynthia J; White, Douglas B; Truog, Robert D; Dubois, James; Cosio, Carmen C; Dhanani, Sonny; Chan, Kevin M; Corris, Paul; Dark, John; Fulda, Gerald; Glazier, Alexandra K; Higgins, Robert; Love, Robert; Mason, David P; Nakagawa, Thomas A; Shapiro, Ron; Shemie, Sam; Tracy, Mary Fran; Travaline, John M; Valapour, Maryam; West, Lori; Zaas, David; Halpern, Scott D

2013-07-01

Donation after circulatory determination of death (DCDD) has the potential to increase the number of organs available for transplantation. Because consent and management of potential donors must occur before death, DCDD raises unique ethical and policy issues. To develop an ethics and health policy statement on adult and pediatric DCDD relevant to critical care and transplantation stakeholders. A multidisciplinary panel of stakeholders was convened to develop an ethics and health policy statement. The panel consisted of representatives from the American Thoracic Society, Society of Critical Care Medicine, International Society for Heart and Lung Transplantation, Association of Organ Procurement Organizations, and the United Network of Organ Sharing. The panel reviewed the literature, discussed important ethics and health policy considerations, and developed a guiding framework for decision making by stakeholders. A framework to guide ethics and health policy statement was established, which addressed the consent process, pre- and post mortem interventions, the determination of death, provisions of end-of-life care, and pediatric DCDD. The information presented in this Statement is based on the current evidence, experience, and clinical rationale. New clinical research and the development and dissemination of new technologies will eventually necessitate an update of this Statement.

Microarray expression profiles of genes in lung tissues of rats subjected to focal cerebral ischemia-induced lung injury following bone marrow-derived mesenchymal stem cell transplantation.

PubMed

Hu, Yue; Xiong, Liu-Lin; Zhang, Piao; Wang, Ting-Hua

2017-01-01

Ischemia-induced stroke is the most common disease of the nervous system and is associated with a high mortality rate worldwide. Cerebral ischemia may lead to remote organ dysfunction, particular in the lungs, resulting in lung injury. Nowadays, bone marrow-derived mesenchymal stem cells (BMSCs) are widely studied in clinical trials as they may provide an effective solution to the treatment of neurological and cardiac diseases; however, the underlying molecular mechanisms remain unknown. In this study, a model of permanent focal cerebral ischemia-induced lung injury was successfully established and confirmed by neurological evaluation and lung injury scores. We demonstrated that the transplantation of BMSCs (passage 3) via the tail vein into the lung tissues attenuated lung injury. In order to elucidate the underlying molecular mechanisms, we analyzed the gene expression profiles in lung tissues from the rats with focal cerebral ischemia and transplanted with BMSCs using a Gene microarray. Moreover, the Gene Ontology database was employed to determine gene function. We found that the phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) were downregulated in the BMSC transplantation groups, compared with the control group. These results suggested that BMSC transplantation may attenuate lung injury following focal cerebral ischemia and that this effect is associated with the downregulation of TGF-β, PDGF and the PI3K-AKT pathway.

Single lung transplantation from a brain-dead donor for a patient with idiopathic pulmonary fibrosis. A breakthrough after new legislation in Japan.

PubMed

Miyoshi, S; Minami, M; Ohta, M; Okumura, M; Takeda, S; Matsuda, H

2001-06-01

Two single lung transplants from a single cadaveric donor were successfully conducted at 2 institutions on March 29, 2000, the first such procedure in Japan under newly introduced legislation. Our patient was a 48-year-old woman with idiopathic pulmonary fibrosis who underwent left single-lung transplantation under cardiopulmonary support. The donor lung was preserved in 4 degrees C modified Euro-Collins solution. Total ischemic time was 5 hours and 37 minutes. The postoperative course was uneventful. The patient was discharged on postoperative day 62 with satisfactory respiratory function.

Airway Pressure Release Ventilation During Ex Vivo Lung Perfusion Attenuates Injury

PubMed Central

Mehaffey, J. Hunter; Charles, Eric J.; Sharma, Ashish K.; Money, Dustin; Zhao, Yunge; Stoler, Mark H; Lau, Christine L; Tribble, Curtis G.; Laubach, Victor E.; Roeser, Mark E.; Kron, Irving L.

2016-01-01

Objective Critical organ shortages have resulted in Ex Vivo Lung Perfusion (EVLP) gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of Donation after Circulatory Death (DCD) organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation (APRV) during EVLP improves lung function after transplantation. Methods Two groups (n=4 animals/group) of porcine DCD donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of EVLP rehabilitation with either standard conventional volume-based ventilation or pressure-based APRV. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for PaO2/FiO2 ratios, airway pressures for calculation of compliance, and percent wet weight gain during EVLP and reperfusion were measured. Results APRV during EVLP significantly improved left-lung oxygenation at 2-hours (561.5±83.9 vs 341.1±136.1 mmHg) and 4-hours (569.1±18.3 vs 463.5±78.4 mmHg). Similarly, compliance was significantly higher at 2-hours (26.0±5.2 vs 15.0±4.6 mL/cmH2O) and 4-hours (30.6±1.3 vs 17.7±5.9 mL/cmH2O) after transplantation. Finally, APRV significantly reduced lung edema development on EVLP based on percentage weight gain (36.9±14.6 vs 73.9±4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. Conclusions Pressure-directed APRV ventilation strategy during EVLP improves rehabilitation of severely injured DCD lungs. After transplant these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared to lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical EVLP protocols, could advance the field of DCD lung rehabilitation to expand the lung donor pool. PMID:27742245

Adipose Gene Expression Profile Changes With Lung Allograft Reperfusion.

PubMed

Diamond, Joshua M; Arcasoy, Selim; McDonnough, Jamiela A; Sonett, Joshua R; Bacchetta, Matthew; D'Ovidio, Frank; Cantu, Edward; Bermudez, Christian A; McBurnie, Amika; Rushefski, Melanie; Kalman, Laurel H; Oyster, Michelle; D'Errico, Carly; Suzuki, Yoshikazu; Giles, Jon T; Ferrante, Anthony; Lippel, Matthew; Singh, Gopal; Lederer, David J; Christie, Jason D

2017-01-01

Obesity is a risk factor for primary graft dysfunction (PGD), a form of lung injury resulting from ischemia-reperfusion after lung transplantation, but the impact of ischemia-reperfusion on adipose tissue is unknown. We evaluated differential gene expression in thoracic visceral adipose tissue (VAT) before and after lung reperfusion. Total RNA was isolated from thoracic VAT sampled from six subjects enrolled in the Lung Transplant Body Composition study before and after allograft reperfusion and quantified using the Human Gene 2.0 ST array. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed enrichment for genes involved in complement and coagulation cascades and Jak-STAT signaling pathways. Overall, 72 genes were upregulated and 56 genes were downregulated in the postreperfusion time compared with baseline. Long pentraxin-3, a gene and plasma protein previously associated with PGD, was the most upregulated gene (19.5-fold increase, p = 0.04). Fibronectin leucine-rich transmembrane protein-3, a gene associated with cell adhesion and receptor signaling, was the most downregulated gene (4.3-fold decrease, p = 0.04). Ischemia-reperfusion has a demonstrable impact on gene expression in visceral adipose tissue in our pilot study of nonobese, non-PGD lung transplant recipients. Future evaluation will focus on differential adipose tissue gene expression and the development of PGD after transplant. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Improvements of the surgical technique on the established mouse model of orthotopic single lung transplantation.

PubMed

Zheng, Zhikun; Wang, Jianjun; Huang, Xia; Jiang, Ke; Nie, Jun; Qiao, Xinwei; Li, Jinsong

2013-01-01

A wide range of knockout and transgenic murine models for the study of nonimmune and immune mechanisms in lung transplants are available nowadays, but the microsurgical techniques are difficult to learn. We describe methods to simplify techniques and facilitate learning. Traditional procedures were implemented to perform lung transplants in 30 cases (group 1). Improved techniques which included cuff without tail, broadening of the cuff diameter for bronchus, establishment of one tunnel between three structures, innovative technology of the vascular anastomosis and placement of the chest tube post-operation were used to perform lung transplants in 30 cases (group 2). The improved techniques considerably shorten operative times (96.75 ± 6.16 min and 85.32 ± 6.98 min in groups 1 and 2, respectively). The survival rates in the recipient animals were 86.7% and 96.7% in groups 1 and 2, respectively. Chest X-rays and macroscopic changes of transplanted recipients showed that grafts were well inflated on postoperative day 30. There was no significant difference of the arterial oxygen tension (PaO2) between two groups (115.9 ± 7.11 mm Hg and 116.3 ± 6.87 mm Hg in groups 1 and 2, respectively). Histologically, no lung injury was seen in grafts. We described the modified procedures of orthotopic left lung transplants in mice, which could shorten operative time and increase survival rate.

Immune function monitoring in lung transplantation using adenosine triphosphate production: time trends and relationship to postoperative infection.

PubMed

Takahashi, Mamoru; Ohsumi, Akihiro; Ohata, Keiji; Kondo, Takeshi; Motoyama, Hideki; Hijiya, Kyoko; Aoyama, Akihiro; Date, Hiroshi; Chen-Yoshikawa, Toyofumi F

2017-06-01

The ImmuKnow (IK) assay is a comprehensive immune function test that involves measuring adenosine triphosphate produced by the cluster of differentiation 4+ T lymphocytes in peripheral blood. The aim of this study was to analyze the time trends of IK values and assess the relationship between IK values and infections in lung transplants. We prospectively collected 178 blood samples from 22 deceased-donor lung transplant (DDLT) recipients and 17 living-donor lobar lung transplant (LDLLT) recipients. A surveillance IK assay was performed postoperatively, then after 1 week and 1, 3, 6, and 12 months. Time trends of IK values in stable recipients peaked 1 week after DDLT (477 ± 247 ATP ng/ml), and 1 month after LDLLT (433 ± 134 ng/ml), followed by a gradual decline over 1 year. The mean IK values in infections were significantly lower than those in the stable state (119 vs 312 ATP ng/ml, p = 0.0002). IK values increased sharply after lung transplantation and then decreased gradually over time in the first year, suggesting a natural history of immune function. IK values were also significantly reduced during infections. These results may provide new insights into the utility of immune monitoring after lung transplantation.

Constrictive (obliterative) bronchiolitis.

PubMed

Schlesinger, C; Veeraraghavan, S; Koss, M N

1998-09-01

Constrictive bronchiolitis (CB), also termed in lung transplant patients obliterative bronchiolitis, is inflammation and fibrosis occurring predominantly in the walls and contiguous tissues of membranous and respiratory bronchioles with resultant narrowing of their lumens. CB is found in a variety of settings, most often as a complication of lung and heart-lung transplantation (affecting 34% to 39% of patients, usually in the first 2 years after transplantation) and bone marrow transplantation, but also in rheumatoid arthritis, after inhalation of toxic agents such as nitrogen dioxide, after ingestion of certain drugs such as penicillamine and ingestion of the East Asian vegetable Sauropus androgynous, and as a rare complication of adenovirus, influenza type A, measles, and Mycoplasma pneumoniae infections in children. In lung transplants, CB is the single most important factor leading to death thereafter. In one study, the overall mortality rate was 25%. However, at the same time, 87% of patients who were asymptomatic and diagnosed solely by transbronchial biopsy had resolution or stabilization of disease. Decreases in FEV1 from baseline can be used to clinically support CB in transplant patients; the term bronchiolitis obliterans syndrome is used to denote this clinical dysfunction, and a grading system has been established for it that is now widely used in the literature. Significant risk factors for the development of CB in lung transplants include alloantigen-dependent and -independent mechanisms. In the former group are late acute rejection and HLA mismatches at the A loci; in the latter are ischemia/reperfusion injuries to airways that result from the transplantation surgery and cytomegalovirus infection.

[Post-transplantation lymphoproliferative disorder in childhood].

PubMed

Stréhn, Anita; Szőnyi, László; Kriván, Gergely; Kovács, Lajos; Reusz, György; Szabó, Attila; Rényi, Imre; Kovács, Gábor; Dezsőfi, Antal

2014-02-23

Among possible complications of transplantation the post-transplant lymphoproliferative disease due to immunosuppressive therapy is of paramount importance. In most cases the direct modulating effect of Epstein-Barr virus on immune cells can be documented. The aim of the authors was to evaluate the incidence os post-transplant lymphoproliferative diseases in pediatric transplant patients in Hungary. The study group included kidney, liver and lung transplant children followed up at the 1st Department of Pediatrics, Semmelweis University, Budapest and stem cell transplant children at Szent László Hospital, Budapest. Data were collected from 78 kidney, 109 liver and 17 lung transplant children as well as from 243 children who underwent allogenic stem cell transplantation. Between 1998 and 2012, 13 children developed post-transplant lymphoproliferative disorder (8 solid organ transplanted and 5 stem cell transplanted children). The diagnosis was based on histological findings in all cases. Mortality was 3 out of the 8 solid organ transplant children and 4 out of the 5 stem cell transplant children. The highest incidence was observed among lung transplant children (17.6%). These data indicate that post-transplant lymphoproliferative disease is a rare but devastating complication of transplantation in children. The most important therapeutic approaches are reduction of immunosuppressive therapy, chemotherapy and rituximab. Early diagnosis may improve clinical outcome and, therefore, routine polymerase chain reaction screening for Epstein-Barr virus of high risk patients is recommended.

Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation.

PubMed

Lo, Wai-Kit; Goldberg, Hilary J; Boukedes, Steve; Burakoff, Robert; Chan, Walter W

2018-02-01

Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.

Should lung transplantation be performed for patients on mechanical respiratory support? The US experience.

PubMed

Mason, David P; Thuita, Lucy; Nowicki, Edward R; Murthy, Sudish C; Pettersson, Gösta B; Blackstone, Eugene H

2010-03-01

The study objectives were to (1) compare survival after lung transplantation in patients requiring pretransplant mechanical ventilation or extracorporeal membrane oxygenation with that of patients not requiring mechanical support and (2) identify risk factors for mortality. Data were obtained from the United Network for Organ Sharing for lung transplantation from October 1987 to January 2008. A total of 15,934 primary transplants were performed: 586 in patients on mechanical ventilation and 51 in patients on extracorporeal membrane oxygenation. Differences between nonsupport patients and those on mechanical ventilation or extracorporeal membrane oxygenation support were expressed as 2 propensity scores for use in comparing risk-adjusted survival. Unadjusted survival at 1, 6, 12, and 24 months was 83%, 67%, 62%, and 57% for mechanical ventilation, respectively; 72%, 53%, 50%, and 45% for extracorporeal membrane oxygenation, respectively; and 93%, 85%, 79%, and 70% for unsupported patients, respectively (P < .0001). Recipients on mechanical ventilation were younger, had lower forced vital capacity, and had diagnoses other than emphysema. Recipients on extracorporeal membrane oxygenation were also younger, had higher body mass index, and had diagnoses other than cystic fibrosis/bronchiectasis. Once these variables, transplant year, and propensity for mechanical support were accounted for, survival remained worse after lung transplantation for patients on mechanical ventilation and extracorporeal membrane oxygenation. Although survival after lung transplantation is markedly worse when preoperative mechanical support is necessary, it is not dismal. Thus, additional risk factors for mortality should be considered when selecting patients for lung transplantation to maximize survival. Reduced survival for this high-risk population raises the important issue of balancing maximal individual patient survival against benefit to the maximum number of patients. Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Pediatric heart-lung transplantation for cystic fibrosis.

PubMed

Maynard, L C

1994-01-01

To describe the preoperative and postoperative experience of children who have undergone heart-lung transplantation for cystic fibrosis. Retrospective descriptive study. Paediatric Surgical Unit, Harefield Hospital, Middlesex, Great Britain. Twelve children less than 15 years of age (mean age 11 years 10 months; range 7 to 14 years), six boys and six girls, who received heart-lung transplants between September 1987 and March 1991. All 12 children were alive and well 1 year after surgery, although one girl had undergone retransplantation in the eighth postoperative month. Actuarial survival rate was 66% at 2 years. Early results suggest that heart-lung transplantation is a successful therapeutic option for children with cystic fibrosis. Cystic fibrosis-related postoperative complications were malabsorption of immunosuppressive drugs, meconium ileus equivalent, and persisting infection in the upper respiratory tract. These and general complications of acute rejection and infection did not prevent 66% of the group from returning to their normal schooling within the first postoperative year. Obliterative bronchiolitis remains the most serious late complication after lung transplantation, and further research is needed into treatment and prevention.

Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion.

PubMed

Koike, Terumoto; Yeung, Jonathan C; Cypel, Marcelo; Rubacha, Matthew; Matsuda, Yasushi; Sato, Masaaki; Waddell, Thomas K; Liu, Mingyao; Keshavjee, Shaf

2011-12-01

Plasma lactate has been used as a marker of poor prognosis in clinical conditions. However, the relationship between lactate production and lung function during acellular normothermic ex vivo lung perfusion (EVLP) is unclear. We investigated the kinetics of lactate metabolism during EVLP and the correlation of this marker with outcomes after transplant. Human donor lungs in our clinical EVLP trial (CLs; n = 28) and rejected donor lungs for experimental use (Els; n = 8) were perfused ex vivo using the Toronto technique. Lactate level, lactate/pyruvate (L/P) ratio, and glucose level in the perfusate were measured. In CLs, we examined the relationship between lactate metabolism during EVLP and early post-transplant outcomes. The hypoxia-inducible factor 1 sub-unit 1α (HIF-1α) level in lung tissue was examined in ELs. We performed double-lung EVLP in CLs and single-lung EVLP in ELs. In CLs, the lactate and L/P ratios at the end of EVLP had no correlation with early post-transplant outcomes despite lactate elevation during EVLP. Although lactate elevation was also present in all ELs, we were able to identify 2 groups based on L/P ratio at the end of EVLP. The group with the high L/P ratio had higher airway pressure during EVLP and higher HIF-1α in lung tissue at the end of EVLP. Lactate increases seen in the EVLP perfusate most often represent physiologic lactate production by the lung in a setting with reduced lactate clearance. Thus, patients who underwent transplantation after EVLP had good outcomes despite lactate elevation during EVLP. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Quality of life in caregivers providing care for lung transplant candidates.

PubMed

Lefaiver, Cheryl A; Keough, Vicki A; Letizia, Marijo; Lanuza, Dorothy M

2009-06-01

Caregivers are essential members of the health care team who provide care, valued at more than $250 billion each year, to millions of persons who require assistance with health and daily care. Patients with respiratory diseases who are waiting for a lung transplant are required to have an identified caregiver. The caregivers are rarely studied. To explore the relationships among the health status of caregivers of lung transplant candidates, caregivers' reaction to caregiving, and caregivers' perceived quality of life. This descriptive study examined the quality of life of lung transplant caregivers from a multidimensional perspective. Twenty-nine dyads of lung transplant candidates and their caregivers were recruited from a Midwestern medical center. Data were collected by self-report: caregivers completed the Quality of Life Index, SF-12 health survey, Profile of Mood States-Short Form, and the Caregiver Reaction Assessment. Caregivers reported favorable levels of quality of life, physical health, and mood during the pretransplant waiting phase. However, problem areas for caregivers during this time included fatigue, depression, and the financial impact of the transplant. Data analyses indicated that depression, caregiver general health, impact on finances, and lack of family support had the greatest effect on caregivers' quality of life. Nurses are urged to recognize the role of caregivers in the transplant process, ask about and listen to caregivers' needs, and include caregivers in the plan of care.

[The first national program of pediatric lung transplantation: the experience in pediatric intensive care].

PubMed

Frías Pérez, M; Montero Schiemann, C; Ibarra de la Rosa, I; Ulloa Santamaría, E; Muñoz Bonet, J; Velasco Jabalquinto, M; Pérez Navero, J; Lama Martínez, R; Santos Luna, F; Salvatierra Velázquez, A; López Pujol, J

1999-06-01

The aim of this study was to analyze the postoperative progress and medical management in the Pediatric Intensive Care Unit (PICU) of patients that underwent bilateral lung transplant. From April 1997 to June 1998, 10 pediatric lung transplants were performed at the Hospital Reina Sofía (Córdoba, Spain). There were 4 males and 6 females (mean age 11.5 years, range 5 to 15 years). Indications for transplantation were cystic fibrosis (n = 9) and one pulmonary fibrosis secondary to viral infection. Before the transplant, two patients required mechanical ventilation for acute respiratory decompensation and one patient was ventilator-dependent. Immunosuppression consisted of corticosteroids, azathioprine and cyclosporine or tacrolimus. Post-transplantation management included early extubation, when possible, optimal fluid balance to prevent lung edema, low aggressive mechanical ventilation and adequate treatment of complications, such as rejection and infection. There were no peri-operative mortalities. The mean stay in the PICU was 28 days (median: 17 days) and the mean time on mechanical ventilation was 19 days (median: 5.5 days). The most frequent complications were rejection (n = 8), hyperglycemia (n = 6), renal failure (n = 4), arterial hypertension (n = 4) and respiratory infections (n = 3). There were no airway complications. Even if the post-operative period in pediatric lung transplant patients is difficult, the results have been good with an important improvement in the quality of life of these patients has been achieved.

Postoperative weight gain during the first year after kidney, liver, heart, and lung transplant: a prospective study.

PubMed

Kugler, Christiane; Einhorn, Ina; Gottlieb, Jens; Warnecke, Gregor; Schwarz, Anke; Barg-Hock, Hannelore; Bara, Christoph; Haller, Hermann; Haverich, Axel

2015-03-01

Studies of all types of organ transplant recipients have suggested that weight gain, expressed as an increase in body mass index (BMI), after transplant is common. To describe weight gain during the first year after transplant and to determine risk factors associated with weight gain with particular attention to type of transplant. A prospective study of 502 consecutive organ transplant recipients (261 kidney, 73 liver, 29 heart, 139 lung) to identify patterns of BMI change. Measurements were made during regular outpatient clinical visits at 2, 6, and 12 months after transplant. Data were retrieved from patients' charts and correlated with maintenance corticosteroid doses. Overall, mean BMI (SD; range) was 23.9 (4.5; 13.6-44.1) at 2 months and increased to 25.4 (4.0; 13.0-42.2) by the end of the first postoperative year. BMI levels organized by World Health Organization categories showed a trend toward overweight/obesity in kidney (53.4%), liver (51.5%), heart (51.7%), and lung (33.1%) patients by 12 months after transplant. BMI changed significantly (P= .05) for all organ types and between all assessment points, except in kidney recipients. Maintenance corticosteroid doses were not a predictor of BMI at 12 months after transplant for most patients. Weight gain was common among patients undergoing kidney, liver, heart, and lung transplant; however, many showed BMI values close to normality at the end of the first year after transplant. In most cases, increased BMI levels were related to obesity before transplant and not to maintenance corticosteroid therapy.

Timing of referral for lung transplantation for cystic fibrosis: overemphasis on FEV1 may adversely affect overall survival.

PubMed

Doershuk, C F; Stern, R C

1999-03-01

(1) Report our experience with referral for lung transplantation. (2) Review survival in cvstic fibrosis (CF) patients without lung transplantation after FEV1 remains < 30% predicted for 1 years. Retrospective review. A university hospital CF center. (1) Forty-five patients referred for lung transplantation evaluation, and (2) 178 patients without Burkholderia sp infection, with the above FEVl criterion. Survival. (1) One- and 2-year survival after transplantation was 55% and 45%, respectively. However, among patients without transplants with FEVl < 30% predicted, median survival, 1986 to 1990, ie, before the transplant era, was 4.6 years with 25% living > 9 years (before 1986, 25% lived > 6 vears). (2) Survival after transplantation was not correlated to any of the following: age, sex, genotype, FEVI percent predicted, insulin-dependent diabetes mellitus, or with waiting time before transplantation, and did not seem to be correlated to serum bicarbonate or percent ideal body weight. Four of five patients already infected with Burkholderia species died within 5 months of transplantation; the fifth died at 17 months. All five died of pulmonary or extrapulmonarv infection with Burkholderia species Use of FEV! < 30% predicted to automatically establish transplantation eligibility could lead to decreased overall survival for CF patients. Referral for evaluation and transplantation should also be based on oxygen requirement, rate of deterioration, respiratory microbiology, quality of life, frequency of IV antibiotic therapy, and other considerations. If pulmonary status has unexpectedly improved when the patient is at or near the top of the waiting list, total survival may be improved by "inactivating the patient" until progression is again evident.

Long-term (postnatal day 70) outcome and safety of intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells in neonatal hyperoxic lung injury.

PubMed

Ahn, So Yoon; Chang, Yun Sil; Kim, Soo Yoon; Sung, Dong Kyung; Kim, Eun Sun; Rime, So Yub; Yu, Wook Joon; Choi, Soo Jin; Oh, Won Il; Park, Won Soon

2013-03-01

This study was performed to evaluate the long-term effects and safety of intratracheal (IT) transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in neonatal hyperoxic lung injury at postnatal day (P)70 in a rat model. Newborn Sprague Dawley rat pups were subjected to 14 days of hyperoxia (90% oxygen) within 10 hours after birth and allowed to recover at room air until sacrificed at P70. In the transplantation groups, hUCB-MSCs (5×10⁵) were administered intratracheally at P5. At P70, various organs including the heart, lung, liver, and spleen were histologically examined, and the harvested lungs were assessed for morphometric analyses of alveolarization. ED-1, von Willebrand factor, and human-specific nuclear mitotic apparatus protein (NuMA) staining in the lungs and the hematologic profile of blood were evaluated. Impaired alveolar and vascular growth, which evidenced by an increased mean linear intercept and decreased amount of von Willebrand factor, respectively, and the hyperoxia-induced inflammatory responses, as evidenced by inflammatory foci and ED-1 positive alveolar macrophages, were attenuated in the P70 rat lungs by IT transplantation of hUCB-MSCs. Although rare, donor cells with human specific NuMA staining were persistently present in the P70 rat lungs. There were no gross or microscopic abnormal findings in the heart, liver, or spleen, related to the MSCs transplantation. The protective and beneficial effects of IT transplantation of hUCB-MSCs in neonatal hyperoxic lung injuries were sustained for a prolonged recovery period without any long-term adverse effects up to P70.

Impact of gastroesophageal reflux and delayed gastric emptying on pediatric lung transplant outcomes.

PubMed

Jamie Dy, Fei; Freiberger, Dawn; Liu, Enju; Boyer, Debra; Visner, Gary; Rosen, Rachel

2017-08-01

Gastroesophageal reflux disease is thought to predispose to adverse lung allograft outcomes. However, little is known about the burden of gastroesophageal reflux (GER) and gastroparesis in pediatric patients. In this study we describe the burden of reflux and gastroparesis in children undergoing lung transplant, and evaluates their impact on allograft survival and rejection incidence. This study is a retrospective analysis of pediatric lung transplant recipients who had combined pH and multichannel intraluminal impedance testing (pH-MII) and gastric-emptying scans (GES). Hazard ratios with 95% confidence intervals (CIs) estimated from Cox proportional hazard models were used to examine the associations between reflux parameters and adverse allograft outcomes. Covariates considered in the multivariate analysis included abnormal pH-MII testing, abnormal GES and Nissen fundoplication status. Kaplan-Meier curves were created, with log-rank testing employed to assess differences between groups. Thirty lung transplant recipients, aged 1 to 21 years, were identified. Eight of 30 patients (27%) had abnormal reflux by impedance, and 12 (40%) had abnormal pH-metry. Of 19 patients tested, 5 (26.3%) had evidence of gastric dysmotility; however, the severity of GER did not trend with delays in gastric emptying. Neither reflux burden by pH-MII testing nor fundoplication status impacted survival or rejection. However, delayed gastric emptying appeared significantly linked to the development of chronic lung allograft dysfunction, independent of GER. In children, reflux burden and fundoplication status do not impact lung transplant outcomes, but gastric dysmotility may be linked to allograft dysfunction in children. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2014-06-01

This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2 /FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40-84] vs. 39 [36-46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). © 2014 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

Non-tuberculous Mycobacterial Infections in Thoracic Transplant Candidates and Recipients.

PubMed

Rao, Mana; Silveira, Fernanda P

2018-05-12

To review and discuss the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of non-tuberculous mycobacteria (NTM) in thoracic transplantation. Non-tuberculous mycobacteria are ubiquitous but are an uncommon cause of disease after solid organ transplantation. The incidence of infection is higher in thoracic transplant recipients than in abdominal transplant recipients, with most cases seen after lung transplantation. It is associated with increased morbidity and, occasionally, mortality. Infection in the pre-transplant setting can occur in lung transplant candidates, often posing a dilemma regarding transplant listing. Disease manifestations are diverse, and pulmonary disease is the most common. Diagnosis requires a high index of suspicion. Treatment requires a multiple-drug combination and is limited by drug-drug interactions and tolerability. Mycobacterium abscessus is a challenge in lung transplant recipients, due to its intrinsic resistance and propensity to relapse even after prolonged therapy. Mycobacterium chimaera is an emerging pathogen associated with contamination of heater-cooler units and is described to cause disease months after cardiothoracic surgery. NTM infections in thoracic organ transplant recipients are uncommon but are associated with substantial morbidity and mortality. Data from larger multicenter studies is needed to better define the epidemiology of NTM in thoracic transplantation, best treatment options, and the management of infected transplant candidates.

Lung Transplant in Patients with Scleroderma Compared with Pulmonary Fibrosis. Short- and Long-Term Outcomes.

PubMed

Crespo, Maria M; Bermudez, Christian A; Dew, Mary Amanda; Johnson, Bruce A; George, M Patricia; Bhama, Jay; Morrell, Matthew; D'Cunha, Jonathan; Shigemura, Norihisa; Richards, Thomas J; Pilewski, Joseph M

2016-06-01

Patients with advanced lung disease due to systemic sclerosis have long been considered suboptimal and often unacceptable candidates for lung transplant. To examine post-lung transplant survival of patients with systemic sclerosis compared with patients with pulmonary fibrosis and to identify risk factors for 1-year mortality. In a retrospective cohort study, we compared post-lung transplant outcomes of 72 patients with scleroderma with those of 311 patients with pulmonary fibrosis between June 2005 and September 2013 at our institution. Actuarial survival estimates were calculated using Kaplan-Meier curves. In Cox regression models, we determined risk factors for post-transplant mortality, controlling for whether patients had scleroderma or pulmonary fibrosis. Post-transplant survival did not differ significantly between scleroderma and pulmonary fibrosis at year 1 (81% scleroderma vs. 79% pulmonary fibrosis; P = 0.743), at year 5 conditional on 1-year survival (66% vs. 58%; P = 0.249), or overall (P = 0.385). In multivariate analysis, body mass index greater than or equal to 35 kg/m(2) predicted poor 1-year survival in pulmonary fibrosis (hazard ratio, 2.76; P = 0.003). Acute cellular rejection-free survival did not differ significantly between the scleroderma and pulmonary fibrosis cohorts. Patients with scleroderma had significantly better bronchiolitis obliterans syndrome stage 1 or higher-free survival than did patients with pulmonary fibrosis. Our findings that 1- and 5-year survival rates of patients with scleroderma were similar to those of patients with pulmonary fibrosis indicate that lung transplant is a reasonable treatment option in selected patients with scleroderma.

Cytomegalovirus infections in lung and hematopoietic cell transplant recipients in the Organ Transplant Infection Prevention and Detection Study: A multi-year, multicenter prospective cohort study.

PubMed

Avery, Robin K; Silveira, Fernanda P; Benedict, Kaitlin; Cleveland, Angela A; Kauffman, Carol A; Schuster, Mindy G; Dubberke, Erik R; Husain, Shahid; Paterson, David L; Chiller, Tom; Pappas, Peter

2018-03-07

Most studies of post-transplant CMV infection have focused on either solid organ or hematopoietic cell transplant (HCT) recipients. A large prospective cohort study involving both lung and HCT recipients provided an opportunity to compare the epidemiology and outcomes of CMV infections in these 2 groups. Patients were followed up for 30 months in a 6-center prospective cohort study. Data on demographics, CMV infections, tissue-invasive disease, recurrences, rejection, and immunosuppression were recorded. The overall incidence of CMV infection was 83/293 (28.3%) in the lung transplant group and 154/444 (34.7%) in the HCT group (P = .0706). Tissue-invasive CMV disease occurred in 8/83 (9.6%) of lung and 6/154 (3.9%) of HCT recipients with CMV infection, respectively (P = .087). Median time to CMV infection was longer in the lung transplant group (236 vs 40 days, P < .0001), likely reflecting the effects of prophylaxis vs preemptive therapy. Total IgG levels of < 350 mg/dL in lung recipients and graft vs host disease (GvHD) in HCT recipients were associated with increased CMV risk. HCT recipients had a higher mean number of CMV episodes (P = .008), although duration of viremia was not significantly different between the 2 groups. CMV infection was not associated with reduced overall survival in either group. Current CMV prevention strategies have resulted in a low incidence of tissue-invasive disease in both lung transplant and HCT, although CMV viremia is still relatively common. Differences between the lung and HCT groups in terms of time to CMV and recurrences of CMV viremia likely reflect differences in underlying host immunobiology and in CMV prevention strategies in the modern era. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Extracorporeal membrane oxygenation support and post-heart transplant outcomes among United States adults.

PubMed

Zalawadiya, Sandip; Fudim, Marat; Bhat, Geetha; Cotts, William; Lindenfeld, JoAnn

2017-01-01

Patients supported with extracorporeal membrane oxygenation (ECMO) are given priority listing status for heart transplant (HT). Data on post-HT outcomes for adults with ECMO support at the time of HT are limited. We analyzed data from the United Network for Organ Registry (UNOS) registry for 157 ECMO-supported adults (age ≥ 18 years) undergoing HT after January 1, 2000. Data at the time of HT were examined for their association with post-transplant mortality using multivariable Cox proportional hazard analyses. Patients (69.4% males; mean age, 46.0 ± 15.6 years; 15.9% African Americans) were monitored for median of 0.55 years (interquartile range, 0.04-4.5). Seventy patients (44.6%) died during follow-up (survival at 1 year was 57.8%), of which 43 (61.4%) died within 30 days post-HT. For patients surviving the first 30 days after transplant, long-term survival was acceptable (82.3% at 1 year and 76.2% at 5 years). Prevalence of immediate post-HT complications, such as stroke and need for dialysis, were 10.1% and 28.1%, respectively. Post-HT survival did not differ between those who received an allograft before and after January 1, 2009 (univariate hazard ratio, 0.84; 95% confidence interval, 0.51-1.38; p = 0.48). Among the predictors identified for 30-day and long-term mortality were recipient history of renal insufficiency (RI; defined as estimated glomerular filtration rate < 45 ml/min/1.73 m 2 or dialysis) and mechanical ventilation (MV; interaction p < 0.05); those with both MV and RI had significantly poorer post-transplant survival (29.4% and 12.5% for 30-day and 1-year survival, respectively) compared with those without (78.7% and 71.4% for 30-day and 1-year survival, respectively). Post-HT mortality did not change for ECMO-supported adults in the contemporary era, and those with RI and MV had significantly poorer post-transplant survival. A critical review of priority listing status for ECMO-supported patients is warranted for optimal allocation and outcomes of cardiac allografts. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

[Lung transplant].

PubMed

Espinosa, M; Rodil, R; Goikoetxea, M J; Zulueta, J; Seijo, L M

2006-01-01

A lung transplant is usually the final therapeutic option for patients with respiratory insufficiency. In spite of the many advances in immunology and the management of complications, mortality and morbidity associated with this transplant are far higher than with others. Acute rejection is an almost universal problem in the first year, while obliterative bronchitis reduces long term survival. Respiratory infections also play a significant role in the complications associated with lung transplants due to the constant exposure of the graft to the outside. However, the success of this therapeutic option, which basically depends on a suitable selection of donor and recipient, are evident, above all with respect to quality of life.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higenbottam, T.; Jackson, M.; Woolman, P.

1989-07-01

As a result of clinical heart-lung transplantation, the lungs are denervated below the level of the tracheal anastomosis. It has been questioned whether afferent vagal reinnervation occurs after surgery. Here we report the cough frequency, during inhalation of ultrasonically nebulized distilled water, of 15 heart-lung transplant patients studied 6 wk to 36 months after surgery. They were compared with 15 normal subjects of a similar age and sex. The distribution of the aerosol was studied in five normal subjects using /sup 99m/technetium diethylene triamine pentaacetate (/sup 99m/Tc-DTPA) in saline. In seven patients, the sensitivity of the laryngeal mucosa to instilledmore » 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.« less

Correction of Spinal Deformity on a Lung Transplantation Recipient.

PubMed

Andrés Peiró, José Vicente; Granell, Joan Bagó; Moret, Montserrat Feliu; Galdó, Antonio Moreno

2017-01-01

The coexistence of lung disease and scoliosis entails a dramatic situation. There are no papers reporting scoliosis surgery in patients who suffered lung transplantation. To describe the case of a patient who underwent surgery to correct progressive spinal deformity after two consecutive lung transplants. Case report, including review of patient records, imaging and pulmonary function tests, and literature review. A 9-year-old woman diagnosed of idiopathic pulmonary fibrosis and progressive scoliosis underwent lung transplant. Retransplantation of right lung was performed at the age of 14 due to chronic rejection. When she was 16, respiratory function was stable and spinal deformity severely impaired her quality of life. Patient and family demanded a surgical correction. At that moment, she had severe osteoporosis and immunosuppression as a result of anti-rejection therapy. The pattern was a severe double thoracic curve T1-T6 89° and T7-L1 139°. To correct it, a posterior instrumented spine fusion from T2 to L4 using a hybrid configuration was performed. No significant complications occurred in perioperative, postoperative, and midterm follow-up periods. Solid fusion was achieved and patient was satisfied with surgery. Unfortunately, chronic lung graft rejection worsened her long-term general status. Scoliosis surgery on lung transplant recipients is feasible, regardless of potential complications related to immunosuppression and osteoporosis. The goal is to improve quality of life. Copyright © 2016 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Ferret lung transplant: an orthotopic model of obliterative bronchiolitis.

PubMed

Sui, H; Olivier, A K; Klesney-Tait, J A; Brooks, L; Tyler, S R; Sun, X; Skopec, A; Kline, J; Sanchez, P G; Meyerholz, D K; Zavazava, N; Iannettoni, M; Engelhardt, J F; Parekh, K R

2013-02-01

Obliterative bronchiolitis (OB) is the primary cause of late morbidity and mortality following lung transplantation. Current animal models do not reliably develop OB pathology. Given the similarities between ferret and human lung biology, we hypothesized an orthotopic ferret lung allograft would develop OB. Orthotopic left lower lobe transplants were successfully performed in 22 outbred domestic ferrets in the absence of immunosuppression (IS; n = 5) and presence of varying IS protocols (n = 17). CT scans were performed to evaluate the allografts. At intervals between 3-6 months the allografts were examined histologically for evidence of acute/chronic rejection. IS protects allografts from acute rejection and early graft loss. Reduction of IS dosage by 50% allowed development of controlled rejection. Allografts developed infiltrates on CT and classic histologic acute rejection and lymphocytic bronchiolitis. Cycling of IS, to induce repeated episodes of controlled rejection, promoted classic histologic hallmarks of OB including fibrosis-associated occlusion of the bronchiolar airways in all allografts of long-term survivors. In conclusion, we have developed an orthotopic lung transplant model in the ferret with documented long-term functional allograft survival. Allografts develop acute rejection and lymphocytic bronchiolitis, similar to humans. Long-term survivors develop histologic changes in the allografts that are hallmarks of OB. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Ex Vivo Lung Perfusion: Establishment and Operationalization in Iran.

PubMed

Shafaghi, Shadi; Abbasi Dezfuli, Azizollah; Ansari Aval, Zahra; Sheikhy, Kambiz; Farzanegan, Behrooz; Mortaz, Esmaeil; Emami, Habib; Aigner, Clemens; Hosseini-Baharanchi, Fatemeh Sadat; Najafizadeh, Katayoun

2017-02-01

Although the number of lung transplants is limited because of general shortage of organ donors, ex vivo lung perfusion is a novel method with 2 main benefits, including better evaluation of lung potential and recovery of injured lungs. The main aim of this study was to establish and operationalize ex vivo lung perfusion as the first experience in Iran. This was a prospective operational research study on 5 cases, including 1 pig from Vienna Medical University and 4 patients from Masih Daneshvari Hospital. All organ donations from brain dead donors were evaluated according to lung transplant or ex vivo lung perfusion criteria from May 2013 to July 2015 in Tehran, Iran. If a donor did not have any sign of severe chest trauma or pneumonia but had poor oxygenation due to possible atelectasis or neurogenic pulmonary edema, their lungs were included for ex vivo lung perfusion. A successful trend in the difference between the pulmonary arterial Po2 and the left atrial Po2 was observed, as well as an increasing pattern in other functional parameters, including dynamic lung compliance and a decreasing trend in pulmonary vascular resistance. These initial trials indicate that ex vivo lung perfusion can lead to remarkable progress in lung transplant in Iran. They also provide several important pieces of guidance for successful ex vivo lung perfusion, including the necessity of following standard lung retrieval procedures and monitoring temperature and pressure precisely. The development of novel methods can provide opportunities for further research studies on lungs of deceased donors and lead to undiscovered findings. By keeping this science up to date in Iran and developing such new and creative methods, we can reveal effective strategies to promote the quality of donor lungs to support patients on transplant wait lists.

Asymptomatic Pulmonary Allograft Kaposi Sarcoma: A Case Report.

PubMed

Nannini, Nazarena; Rebusso, Alessandro; Lunardi, Francesca; Loy, Monica; Calabrese, Francesca; Battistella, Lucia; Schiavon, Marco; Rea, Federico; Calabrese, Fiorella

2017-08-01

Solid-organ transplant recipients are at high risk of developing malignancies. A greater risk of Kaposi sarcoma has been reported in lung recipients in our country, particularly in those from Southern Italy, probably due to the high prevalence of Human herpes virus 8 infection. Kaposi sarcoma affecting only the lung allograft is extremely rare. We describe a case of a lung recipient who developed Kaposi sarcoma only in the graft, 22 months after transplant. The patient, a 65-year-old man from Southern Italy, underwent bilateral lung transplant for idiopathic pulmonary fibrosis in January 2009. He developed mild/moderate acute cellular rejection (≥A2) in 4 of 6 scheduled transbronchial biopsies thus was treated with increased immunosuppressive therapy, shifting from cyclosporine to tacrolimus and mycophenolate mofetil. In July 2010, a high-resolution computed tomography scan showed small bilateral lung nodules, despite a generally good condition. After 2 months, his condition worsened with a severe weight loss. A positron emission tomography scan showed mild metabolic activity in the lesions with no other localizations. In October 2010, a lung biopsy was performed, with results showing typical histologic and immunohistochemical features of Kaposi sarcoma. Molecular tissue evaluations and serologic analyses were positive for Human herpes virus 8. The patient's immunosuppressive therapy was suspended, and he started liposomal doxorubicin treatment; however, after the first cycle, he developed severe respiratory dysfunction. The patient died 27 months after lung transplant for neoplasm. Our report highlights the importance of considering Kaposi sarcoma in the differential diagnosis for lung nodules in lung transplant recipients, even in the absence of any initial specific symptom or cutaneous lesion.

Prevalence of Chagas Disease among Solid Organ-Transplanted Patients in a Nonendemic Country.

PubMed

Salvador, Fernando; Sánchez-Montalvá, Adrián; Sulleiro, Elena; Moreso, Francesc; Berastegui, Cristina; Caralt, Mireia; Pinazo, María-Jesús; Moure, Zaira; Los-Arcos, Ibai; Len, Oscar; Gavaldà, Joan; Molina, Israel

2018-03-01

Reactivation of Chagas disease in the chronic phase may occur after solid organ transplantation, which may result in high parasitemia and severe clinical manifestations such as myocarditis and meningoencephalitis. The aim of the present study is to describe the prevalence of Chagas disease among solid organ-transplanted patients in a tertiary hospital from a nonendemic country. A cross-sectional study was performed at Vall d'Hebron University Hospital (Barcelona, Spain) from April to September 2016. Chagas disease screening was performed through serological tests in adult patients coming from endemic areas that had received solid organ transplantation and were being controlled in our hospital during the study period. Overall, 42 patients were included, 20 (47.6%) were male and median age was 50.5 (23-73) years. Transplanted organs were as follows: 18 kidneys, 17 lungs, and 7 livers. Three patients had Chagas disease, corresponding to a prevalence among this group of solid organ-transplanted patients of 7.1%. All three patients were born in Bolivia, had been diagnosed with Chagas disease and received specific treatment before the organ transplantation. We highly recommend providing screening tests for Chagas disease in patients with or candidates for solid organ transplantation coming from endemic areas, early treatment with benznidazole, and close follow-up to prevent clinical reactivations.

Bioengineered Lungs: A Challenge and An Opportunity.

PubMed

Farré, Ramon; Otero, Jordi; Almendros, Isaac; Navajas, Daniel

2018-01-01

Lung biofabrication is a new tissue engineering and regenerative development aimed at providing organs for potential use in transplantation. Lung biofabrication is based on seeding cells into an acellular organ scaffold and on culturing them in an especial purpose bioreactor. The acellular lung scaffold is obtained by decellularizing a non-transplantable donor lung by means of conventional procedures based on application of physical, enzymatic and detergent agents. To avoid immune recipient's rejection of the transplanted bioengineered lung, autologous bone marrow/adipose tissue-derived mesenchymal stem cells, lung progenitor cells or induced pluripotent stem cells are used for biofabricating the bioengineered lung. The bioreactor applies circulatory perfusion and mechanical ventilation with physiological parameters to the lung during biofabrication. These physical stimuli to the organ are translated into the stem cell local microenvironment - e.g. shear stress and cyclic stretch - so that cells sense the physiological conditions in normally functioning mature lungs. After seminal proof of concept in a rodent model was published in 2010, the hypothesis that lungs can be biofabricated is accepted and intense research efforts are being devoted to the topic. The current experimental evidence obtained so far in animal tests and in ex vivo human bioengineered lungs suggests that the date of first clinical tests, although not immediate, is coming. Lung bioengineering is a disrupting concept that poses a challenge for improving our basic science knowledge and is also an opportunity for facilitating lung transplantation in future clinical translation. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Extracorporeal Life Support in Critically Ill Adults

PubMed Central

Muratore, Christopher S.

2014-01-01

Extracorporeal life support (ECLS) has become increasingly popular as a salvage strategy for critically ill adults. Major advances in technology and the severe acute respiratory distress syndrome that characterized the 2009 influenza A(H1N1) pandemic have stimulated renewed interest in the use of venovenous extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal to support the respiratory system. Theoretical advantages of ECLS for respiratory failure include the ability to rest the lungs by avoiding injurious mechanical ventilator settings and the potential to facilitate early mobilization, which may be advantageous for bridging to recovery or to lung transplantation. The use of venoarterial ECMO has been expanded and applied to critically ill adults with hemodynamic compromise from a variety of etiologies, beyond postcardiotomy failure. Although technology and general care of the ECLS patient have evolved, ECLS is not without potentially serious complications and remains unproven as a treatment modality. The therapy is now being tested in clinical trials, although numerous questions remain about the application of ECLS and its impact on outcomes in critically ill adults. PMID:25046529

Two Decades of Lung Retransplantation: A Single-Center Experience.

PubMed

Hall, David J; Belli, Erol V; Gregg, Jon A; Salgado, Juan C; Baz, Maher A; Staples, E Denmark; Beaver, Thomas M; Machuca, Tiago N

2017-04-01

Lung retransplantation (ReTx) comprises an increasing share of lung transplants and recently has shown improved outcomes. The aim of this study was to identify risk factors affecting overall survival after pulmonary ReTx. The United Network for Organ Sharing database was used to identify patients undergoing lung transplantation at our institution from 1995 to 2014. Of the total 542 lung transplants performed, 87 (16.1%) were ReTxs. The primary outcome was overall survival. Multivariate Cox regression models were used to assess the effect of recipient and donor characteristics on survival. Of the patients who underwent ReTx, median survival was 2 years. Predictors of worse survival include recipient age between 50 and 60 years (relative risk, 4.3; p = 0.02) or older than 60 years (relative risk, 10.2; p < 0.001), and time to ReTx of less than 2 years (relative risk, 3.8; p = 0.01). ReTx for bronchiolitis obliterans syndrome had longer median survival than for restrictive chronic lung allograft dysfunction (2.7 years vs 0.9 years; p = 0.055). Overall survival of ReTx patients after initiation of the lung allocation score was not significantly different (p = 0.21). Lung ReTx outcomes are significantly worse than for primary transplantation but may be appropriate in well-selected patients with certain diagnoses. Lung ReTx in patients older than 50 years or within 2 years of primary lung transplantation was associated with decreased survival. Further work is warranted to identify patients who benefit most from ReTx. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Ex vivo administration of trimetazidine improves post-transplant lung function in pig model.

PubMed

Cosgun, Tugba; Iskender, Ilker; Yamada, Yoshito; Arni, Stephan; Lipiski, Miriam; van Tilburg, Koen; Weder, Walter; Inci, Ilhan

2017-07-01

Ex vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model. Pig lungs were retrieved and stored for 24 h at 4°C, followed by 4 h of EVLP. Allografts were randomly allocated to 2 groups ( n  = 5 each). TMZ (5 mg/kg) was added to the prime solution prior to EVLP. After EVLP, left lungs were transplanted and recipients were observed for 4 h. Allograft gas exchange function and lung mechanics were recorded hourly throughout reperfusion. Microscopic lung injury and inflammatory and biochemical parameters were assessed. There was a trend towards better oxygenation during EVLP in the TMZ group ( P  = 0.06). After transplantation, pulmonary gas exchange was significantly better during the 4-h reperfusion period and after isolation of the allografts for 10 min ( P  < 0.05). Tissue thiobarbituric acid levels, myeloperoxidase activity and protein concentrations in bronchoalveolar lavage samples were significantly lower in the TMZ group at the end of EVLP ( P  < 0.05). Ex vivo treatment of donor lungs with TMZ significantly improved immediate post-transplant lung function. Further studies are warranted to understand the effect of this strategy on long-term lung function. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

High azathioprine dose and lip cancer risk in liver, heart, and lung transplant recipients: A population-based cohort study.

PubMed

Na, Renhua; Laaksonen, Maarit A; Grulich, Andrew E; Meagher, Nicola S; McCaughan, Geoffrey W; Keogh, Anne M; Vajdic, Claire M

2016-06-01

Iatrogenic immunosuppression is a risk factor for lip cancer but the determinants are unknown. We sought to quantify the association between the type, dose, and duration of iatrogenic immunosuppression and lip cancer risk in solid organ transplant recipients. We conducted a population-based cohort study of all adult Australian liver, heart, and lung transplant recipients from 1984 to 2006 (n = 4141). We abstracted longitudinal data from medical records and ascertained incident lip cancer (n = 58) and deaths (n = 1434) by linkage with national registries. We estimated multivariable hazard ratios (HR) for lip cancer using the Fine and Gray proportional subdistribution hazards model, accounting for death as a competing risk. Lip cancer risk (n = 58) increased with high mean daily dose of azathioprine (HR 2.28, 95% confidence interval [CI] 1.18-4.38), longer duration of immunosuppression (HR 9.86, 95% CI 2.10-46.3), increasing year of age at transplantation (HR 1.14, 95% CI 1.04-1.25), earlier transplantation era (HR 8.73, 95% CI 1.11-68.7), and history of smoking (HR 2.71, 95% CI 1.09-6.70). Data on potential confounders such as personal solar ultraviolet radiation exposure were not available. Higher doses of azathioprine increase lip cancer risk, with implications for managing immunosuppressed populations and our understanding of the relationship between solar ultraviolet radiation and lip cancer. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Can lung function measurements be used to predict which patients will be at risk of developing interstitial pneumonitis after bone marrow transplantation?

PubMed

Milburn, H J; Prentice, H G; du Bois, R M

1992-06-01

Lung function often deteriorates after bone marrow transplantation for haematological malignancies. Whether pulmonary function measurements are useful for monitoring patients' progress after transplantation and for alerting clinicians to the development of pneumonitis is uncertain. Serial pulmonary function measurements were made in 39 patients with a haematological malignancy, and the values from 18 recipients of T cell depleted allogeneic (n = 17) or autologous (n = 1) bone marrow transplants who developed interstitial pneumonitis were compared retrospectively with values from 21 recipients of allogeneic (n = 17) or autologous (n = 4) transplants who did not develop pneumonitis. Lung function was measured at the onset of a further 18 episodes of pneumonitis. Measurements made before transplantation showed no difference in forced expiratory volume in one second (FEV1), transfer factor for carbon monoxide (TLCO), or total lung capacity between the two groups, but the forced vital capacity (FVC) was slightly higher in those who developed pneumonitis (mean (SD)% predicted 104 (12)) than in those who did not (93 (17%)). Six weeks and three months after transplantation all pulmonary function measurements had fallen slightly in both groups but TLCO had fallen considerably more in those who later developed pneumonitis, being 71% (SD 11%) and 77% (7%) of pretransplant values in patients who later developed pneumonitis compared with 109% (38%) and 96% (26%) in those who did not. All lung function measurements were significantly lower at the onset of pneumonitis than three months after transplantation, even in patients with no abnormal signs and a normal chest radiograph. Serial measurements of gas transfer before and after bone marrow transplantation may be useful for predicting which patients will be at risk of developing pneumonitis and may help to diagnose pneumonitis in breathless patients with no abnormal signs.

Transfusion-related acute lung injury (TRALI) in graft by blood donor antibodies against host leukocytes.

PubMed

Goodwin, Jodi; Tinckam, Kathryn; denHollander, Neal; Haroon, Ayesha; Keshavjee, Shaf; Cserti-Gazdewich, Christine M

2010-09-01

It is unknown the extent to which transfusion-related acute lung injury (TRALI) contributes to primary graft dysfunction (PGD), the leading cause of death after lung transplantation. In this case of suspected transfusion-associated acute bilateral graft injury in a 61-year-old idiopathic pulmonary fibrosis patient, recipient sera from before and after transplantation/transfusion, as well as the sera of 22 of the 24 implicated blood donors, were individually screened by Luminex bead assay for the presence of human leukocyte antigen (HLA) antibodies, with recipient and lung donor HLA typing to explore for cognate relationships. A red-cell-unit donor-source anti-Cw6 antibody, cognate with the HLA type of the recipient, was identified. This is the second reported case of TRALI in the setting of lung transplantation, and the first to show an associated interaction between donor antibodies (in a low-plasma volume product) with recipient leukocytes (rather than graft antigens); therefore, it should be considered in the differential diagnosis of PGD. Copyright 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

[Extracorporeal membrane oxygenation in primary graft dysfunction in a paediatric double lung transplant: presentation of a case].

PubMed

López-Cantero, M; Grisolía, A L; Vicente, R; Moreno, I; Ramos, F; Porta, J; Torregrosa, S

2014-04-01

Primary graft dysfunction is a leading cause of morbimortality in the immediate postoperative period of patients undergoing lung transplantation. Among the treatment options are: lung protective ventilatory strategies, nitric oxide, lung surfactant therapy, and supportive treatment with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery of lung function or re-transplant. We report the case of a 9-year-old girl affected by cystic fibrosis who underwent double-lung transplantation complicated with a severe primary graft dysfunction in the immediate postoperative period and refractory to standard therapies. Due to development of multiple organ failure, it was decided to insert arteriovenous ECMO catheters (pulmonary artery-right atrium). The postoperative course was satisfactory, allowing withdrawal of ECMO on the 5th post-surgical day. Currently the patient survives free of rejection and with an excellent quality of life after 600 days of follow up. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Systemic Inhibition of NF-κB Activation Protects from Silicosis

PubMed Central

Di Giuseppe, Michelangelo; Gambelli, Federica; Hoyle, Gary W.; Lungarella, Giuseppe; Studer, Sean M.; Richards, Thomas; Yousem, Sam; McCurry, Ken; Dauber, James; Kaminski, Naftali; Leikauf, George; Ortiz, Luis A.

2009-01-01

Background Silicosis is a complex lung disease for which no successful treatment is available and therefore lung transplantation is a potential alternative. Tumor necrosis factor alpha (TNFα) plays a central role in the pathogenesis of silicosis. TNFα signaling is mediated by the transcription factor, Nuclear Factor (NF)-κB, which regulates genes controlling several physiological processes including the innate immune responses, cell death, and inflammation. Therefore, inhibition of NF-κB activation represents a potential therapeutic strategy for silicosis. Methods/Findings In the present work we evaluated the lung transplant database (May 1986–July 2007) at the University of Pittsburgh to study the efficacy of lung transplantation in patients with silicosis (n = 11). We contrasted the overall survival and rate of graft rejection in these patients to that of patients with idiopathic pulmonary fibrosis (IPF, n = 79) that was selected as a control group because survival benefit of lung transplantation has been identified for these patients. At the time of lung transplantation, we found the lungs of silica-exposed subjects to contain multiple foci of inflammatory cells and silicotic nodules with proximal TNFα expressing macrophage and NF-κB activation in epithelial cells. Patients with silicosis had poor survival (median survival 2.4 yr; confidence interval (CI): 0.16–7.88 yr) compared to IPF patients (5.3 yr; CI: 2.8–15 yr; p = 0.07), and experienced early rejection of their lung grafts (0.9 yr; CI: 0.22–0.9 yr) following lung transplantation (2.4 yr; CI:1.5–3.6 yr; p<0.05). Using a mouse experimental model in which the endotracheal instillation of silica reproduces the silica-induced lung injury observed in humans we found that systemic inhibition of NF-κB activation with a pharmacologic inhibitor (BAY 11-7085) of IκBα phosphorylation decreased silica-induced inflammation and collagen deposition. In contrast, transgenic mice expressing a dominant negative IκBα mutant protein under the control of epithelial cell specific promoters demonstrate enhanced apoptosis and collagen deposition in their lungs in response to silica. Conclusions Although limited by its size, our data support that patients with silicosis appear to have poor outcome following lung transplantation. Experimental data indicate that while the systemic inhibition of NF-κB protects from silica-induced lung injury, epithelial cell specific NF-κB inhibition appears to aggravate the outcome of experimental silicosis. PMID:19479048

Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation

PubMed Central

Hsu, Joe L.; Manouvakhova, Olga V.; Clemons, Karl V.; Inayathullah, Mohammed; Tu, Allen B.; Sobel, Raymond A.; Tian, Amy; Nazik, Hasan; Pothineni, Venkata R.; Pasupneti, Shravani; Jiang, Xinguo; Dhillon, Gundeep S.; Bedi, Harmeet; Rajadas, Jayakumar; Haas, Hubertus; Aurelian, Laure; Stevens, David A.; Nicolls, Mark R.

2018-01-01

Invasive pulmonary disease due to the mold Aspergillus fumigatus can be life-threatening in lung transplant recipients, but the risk factors remain poorly understood. To study this process, we used a tracheal allograft mouse model that recapitulates large airway changes observed in patients undergoing lung transplantation. We report that microhemorrhage-related iron content may be a major determinant of A. fumigatus invasion and, consequently, its virulence. Invasive growth was increased during progressive alloimmune-mediated graft rejection associated with high concentrations of ferric iron in the graft. The role of iron in A. fumigatus invasive growth was further confirmed by showing that this invasive phenotype was increased in tracheal transplants from donor mice lacking the hemochromatosis gene (Hfe−/−). The invasive phenotype was also increased in mouse syngrafts treated with topical iron solution and in allograft recipients receiving deferoxamine, a chelator that increases iron bioavailability to the mold. The invasive growth of the iron-intolerant A. fumigatus double-knockout mutant (ΔsreA/ΔcccA) was lower than that of the wild-type mold. Alloimmune-mediated microvascular damage and iron overload did not appear to impair the host’s immune response. In human lung transplant recipients, positive staining for iron in lung transplant tissue was more commonly seen in endobronchial biopsy sections from transplanted airways than in biopsies from the patients’ own airways. Collectively, these data identify iron as a major determinant of A. fumigatus invasive growth and a potential target to treat or prevent A. fumigatus infections in lung transplant patients. PMID:29467298

Correlation between sinus and lung cultures in lung transplant patients with cystic fibrosis.

PubMed

Choi, Kevin J; Cheng, Tracy Z; Honeybrook, Adam L; Gray, Alice L; Snyder, Laurie D; Palmer, Scott M; Abi Hachem, Ralph; Jang, David W

2018-03-01

Lung transplantation has revolutionized the treatment of end-stage pulmonary disease due to cystic fibrosis. However, infection of the transplanted lungs can lead to serious complications, including graft failure and death. Although many of these patients have concurrent sinusitis, it is unclear whether bacteria from the sinuses can infect the allograft. This is a single-institution retrospective study of all patients who underwent lung transplantation for cystic fibrosis from 2005 to 2015 at Duke University Hospital. Pre- and posttransplant nasal and pulmonary cultures obtained via nasal endoscopy and bronchoalveolar lavage (BAL), respectively, were analyzed. A total of 141 patients underwent 144 lung transplants. Sinus cultures were available for 76 patients (12 pretransplant, 42 posttransplant, 22 both pre- and posttransplant). Pretransplant BAL cultures were available for 139 patients, and posttransplant BAL cultures were available for all patients. Pseudomonas aeruginosa (PsA) and methicillin-resistant Staphylococcus aureus (MRSA) were the most common organisms cultured. There was a significant correlation between pretransplant sinus and posttransplant BAL cultures for PsA (p = 0.003), MRSA (p = 0.013), and Burkholderia cepacia (p = 0.001). There was a high correlation between pretransplant sinus cultures and posttransplant BAL cultures for PsA, MRSA, and Burkholderia sp. This suggests that the paranasal sinuses may act as a reservoir for allograft colonization in patients with cystic fibrosis. Further studies are needed to determine whether treatment of sinusitis affects allograft colonization and transplant outcomes. © 2017 ARS-AAOA, LLC.

Early lung retrieval from traumatic brain-dead donors does not compromise outcomes following lung transplantation.

PubMed

Moreno, Paula; Alvarez, Antonio; Illana, Jennifer; Espinosa, Dionisio; Baamonde, Carlos; Cerezo, Francisco; Algar, Francisco Javier; Salvatierra, Angel

2013-06-01

To determine whether lung retrieval from traumatic donors performed within 24 h of brain death has a negative impact on early graft function and survival after lung transplantation (LT), when compared with those retrieved after 24 h. Review of lung transplants performed from traumatic donors over a 17-year period. Recipients were distributed into two groups: transplants from traumatic donor lungs retrieved within 24 h of brain death (Group A), and transplants from traumatic donor lungs retrieved after 24 h of brain death (Group B). Demographic data of donors and recipients, early graft function, perioperative complications and mortality were compared between both groups. Among 356 lung transplants performed at our institution, 132 were from traumatic donors (70% male, 30% female). Group A: 73 (55%); Group B: 59 (45%). There were 53 single, 77 double, and 2 combined LT. Indications were emphysema in 41 (31%), pulmonary fibrosis in 31 (23%), cystic fibrosis in 38 (29%), bronchiectasis in 9 (7%) and other indications in 13 patients (10%). Donor and recipient demographic data, need or cardiopulmonary bypass, postoperative complications and Intensive Care Unit and hospital stay did not differ between groups. Primary graft dysfunction (A vs B): 9 (16%) vs 13 (26%) P = 0.17. PaO2/FiO2 24 h post-transplant (A vs B): 303 mmHg vs 288 mmHg (P = 0.57). Number of acute rejection episodes (A vs B): 0.93 vs 1.49 (P = 0.01). Postoperative intubation time (A vs B): 99 vs 100 h (P = 0.99). 30-day mortality (A vs B): 7 (10%) vs 2 (3.5%) (P = 0.13). Freedom from bronchiolitis obliterans syndrome (A vs B): 82, 72, 37, 22 vs 78, 68, 42, 15%, at 3, 5, 10 and 15 years, respectively (P = 0.889). Survival (A vs B): 65, 54, 46, 42 and 27 vs 60, 50, 45, 43 and 29% at 3, 5, 7, 10 and 15 years, respectively (P = 0.937). In our experience, early lung retrieval after brain death from traumatic donors does not adversely affect early and long-term outcomes after LT.

Severe Aspergillus endocarditis in a lung transplant recipient with a five-year survival.

PubMed

Philippe, B; Grenet, D; Honderlick, P; Longchampt, E; Dupont, B; Picard, C; Stern, M

2010-06-01

We report the case of a patient with cystic fibrosis who underwent lung transplant and developed Aspergillus endocarditis and cutaneous relapse. Long-term survival was achieved with surgical and prolonged antifungal treatment. This case report emphasizes the recommendation of life-long antifungal treatment in transplant recipients who survive an episode of fungal endocarditis.

A 47-Year-Old Man With Fever, Dry Cough, and a Lung Mass After Redo Lung Transplantation.

PubMed

Chaddha, Udit; Patil, Pradnya D; Omar, Ashraf; Walia, Rajat; Panchabhai, Tanmay S

2018-06-01

A 47-year-old man who was a redo double lung transplant recipient (cytomegalovirus [CMV] status: donor positive/recipient positive; Epstein-Barr virus status: donor positive/recipient positive) presented to the hospital with 1 week of generalized malaise, low-grade fevers, and dry cough. His redo lung transplantation was necessitated by bronchiolitis obliterans syndrome, and his previous lung transplantation 5 years earlier was for silicosis-related progressive massive fibrosis. He denied any difficulty breathing or chest pain. There was no history of GI or urinary symptoms, and the patient had no anorexia, weight loss, night sweats, sick contacts, or history of travel. He had a history of 1 earlier episode of CMV viremia that was treated with valganciclovir. His immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisone, and his infection prophylaxis included trimethoprim-sulfamethoxazole, itraconazole, and valganciclovir. Results of a chest radiograph 8 weeks earlier were normal. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

[Indications of lung transplantation: Patients selection, timing of listing, and choice of procedure].

PubMed

Morisse Pradier, H; Sénéchal, A; Philit, F; Tronc, F; Maury, J-M; Grima, R; Flamens, C; Paulus, S; Neidecker, J; Mornex, J-F

2016-02-01

Lung transplantation (LT) is now considered as an excellent treatment option for selected patients with end-stage pulmonary diseases, such as COPD, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary arterial hypertension. The 2 goals of LT are to provide a survival benefit and to improve quality of life. The 3-step decision process leading to LT is discussed in this review. The first step is the selection of candidates, which requires a careful examination in order to check absolute and relative contraindications. The second step is the timing of listing for LT; it requires the knowledge of disease-specific prognostic factors available in international guidelines, and discussed in this paper. The third step is the choice of procedure: indications of heart-lung, single-lung, and bilateral-lung transplantation are described. In conclusion, this document provides guidelines to help pulmonologists in the referral and selection processes of candidates for transplantation in order to optimize the outcome of LT. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Bronchiolitis with airflow obstruction in adults].

PubMed

Fournier, M; Marceau, A; Dauriat, G; Camuset, J; Groussard, O

2004-04-01

The purpose of this paper is twofold: to describe the clinical and anatomical characteristics of bronchiolitis associated with airflow obstruction in adults; to present through a clinical approach, a classification of the main aetiologies or pathological frames associated with that entity. The constrictive bronchiolitis type is the most frequently encountered. On clinical grounds, cough, crackles, and a progressive dyspnea develop usually within a few weeks. Radiological signs of bronchiolar abnormalities are best visualized on high resolution expiratory CT scan. The decrease in maximal airflows and oxygen tension is of limited amplitude and poorly reversible with bronchodilators. Diagnosis is easily performed when a causative event, or the clinical context, can be delineated: inhalation of toxic fumes, diffuse bronchiectasis, rheumatoid arthritis, lung or bone marrow transplantation. Delayed formation of bronchiectasis in the central airways is common. The treatment is not standardized; corticosteroids are usually prescribed as a first line therapy; the benefit of the addition of, or substitution with immunosuppressive drugs has not been adequately evaluated, but is, on the mean, of limited amplitude. Recent advances in the identification of inhaled agents toxic for the distal airways help in establishing appropriate measures of prevention. When the aetiology of the bronchiolitis cannot be suspected, extensive search of a causative agent should be performed, including microbial and mineral analysis of bronchoalveolar products. Negative results should lead to perform a surgical lung biopsy. The study of chronic rejection processes in animal models of lung transplantation, the identification of inhibitory factors of bronchiolar fibrogenesis, and the efficacy of some anti-cytokines on inflammatory processes could result in new therapeutic approaches.

Longitudinal dose and type of immunosuppression in a national cohort of Australian liver, heart, and lung transplant recipients, 1984-2006.

PubMed

Na, Renhua; Laaksonen, Maarit A; Grulich, Andrew E; Webster, Angela C; Meagher, Nicola S; McCaughan, Geoffrey W; Keogh, Anne M; Vajdic, Claire M

2015-11-01

Unconfounded comparative data on the type and dose of immunosuppressive agents among solid organ transplant recipients are sparse, as are data on longitudinal immunosuppressive therapy since transplantation. We addressed this issue in a population-based cohort of Australian liver (n = 1895), heart (n = 1220), and lung (n = 1059) transplant recipients, 1984-2006. Data on immunosuppressive therapy were retrospectively collected at discharge, three months, and one, five, 10, and 15 yr after first transplant. We computed unadjusted and adjusted estimates for the association between the type and dose of immunosuppressive therapy and organ type. After adjustment for confounders, use of induction antibody and maintenance corticosteroids was more common in heart and lung compared to liver recipients (p < 0.001), and antibody therapy for rejection more common in liver recipients (p < 0.001). Liver recipients were more likely to receive calcineurin inhibitor monotherapy, with or without corticosteroids, compared to heart and lung recipients (p < 0.001). Liver recipients consistently received lower doses of azathioprine than heart and lung recipients (p < 0.001). These differences in immunosuppression may partly explain variations in immunosuppression-related morbidity by transplanted organ, for example, malignancy risk. Longitudinal changes in the type and the dose of immunosuppressive therapy over time since transplantation also demonstrate the need for time-dependent data in observational research. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chronic infection sustained by a Pseudomonas aeruginosa High-Risk clone producing the VIM-1 metallo-β-lactamase in a cystic fibrosis patient after lung transplantation.

PubMed

Pollini, Simona; Mugnaioli, Claudia; Dolce, Daniela; Campana, Silvia; Neri, Anna Silvia; Taccetti, Giovanni; Rossolini, Gian Maria

2018-02-12

The significance of chronic lung infection by multidrug-resistant (MDR) pathogens in Cystic Fibrosis (CF) transplanted patients remains controversial, and the available information is overall limited. Here we describe the case of a chronic infection, sustained by a metallo-β-lactamase (MBL)-producing P. aeruginosa strain, in a CF patient following lung transplantation. Twelve P. aeruginosa isolates collected from a CF patient over a 15-years follow-up period after lung transplantation were analysed for their antibiotic susceptibility profile, MBL production and clonal relatedness. Available clinical and microbiological records were reviewed. The transplanted CF patient was chronically infected by an MBL-producing P. aeruginosa strain which harboured a bla VIM-1 determinant inserted into a novel class 1 integron. The strain exhibited an MDR phenotype and belonged to the globally widespread ST235 epidemic clonal lineage, which however is not a typical CF-associated epidemic clone. Despite the chronic infection, the long-term outcome of this patient during the post-transplant period was characterized by the absence of acute exacerbations and by a mostly stable pulmonary function. This report provides one of the few descriptions of MBL-producing P. aeruginosa infections in CF patients, and the first description of such an infection after lung transplantation in these patients. Infection with the MBL-producing strain apparently did not significantly affect the patient pulmonary function. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies.

PubMed

Cozzi, E; Calabrese, F; Schiavon, M; Feltracco, P; Seveso, M; Carollo, C; Loy, M; Cardillo, M; Rea, F

2017-02-01

Preexisting donor-specific anti-HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ET A R) and the angiotensin II receptor type 1 (AT 1 R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti-ET A R and anti-AT 1 R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Patients' experiences of everyday life after lung transplantation.

PubMed

Thomsen, Doris; Jensen, Birte Østergaard

2009-12-01

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.

Scintigraphic results in patients with lung transplants: a prospective comparative study.

PubMed

Humplik, B I; Sandrock, D; Aurisch, R; Richter, W-St; Ewert, R; Munz, D L

2005-04-01

We addressed the feasibility of scintigraphy in the postoperative monitoring of lung transplants. 37 patients (22 women, 15 men, 37 +/- 15 years) in good clinical condition were examined after lung transplantation. Scintigraphic procedures for assessing ventilation (133Xe), perfusion (99mTc microspheres) and aerosol-inhalation (99mTc aerosol) were performed for all patients. The findings were compared with those of established diagnostic modalities. All lung transplants showed homogeneous ventilation but with a non-physiologic difference of over 20% between both pulmonary lobes in one-third of the cases. There was a difference between the impairement of perfusion and ventilation in the presence of an impaired Euler-Liljestrand reflex in 14/37 (38%) patients. Furthermore, bronchoscopy and aerosol-inhalation scans often did not correlate, e. g. a bronchoscopically evident stenosis was not necessarily associated with an increased activity, and vice versa. Although peripheral mucociliary clearance was preserved after transplantation, stasis in central airways resulted in significantly impaired global clearance. Ventilation and perfusion scintigraphy reveal in a significant number of lung recipients pathologic findings and therefore can be recommended for postoperative monitoring. From a clinical point of view aerosol-inhalation scintigraphy (clearance) is not of any additional value.

Airway complications have a greater impact on the outcomes of living-donor lobar lung transplantation recipients than cadaveric lung transplantation recipients.

PubMed

Sugimoto, Seiichiro; Yamane, Masaomi; Otani, Shinji; Kurosaki, Takeshi; Okahara, Shuji; Hikasa, Yukiko; Toyooka, Shinichi; Kobayashi, Motomu; Oto, Takahiro

2018-04-21

Airway complications (ACs) after living-donor lobar lung transplantation (LDLLT) could have different features from those after cadaveric lung transplantation (CLT). We conducted this study to compare the characteristics of ACs after LDLLT vs. those after CLT and investigate their impact on outcomes. We reviewed, retrospectively, data on 163 recipients of lung transplantation, including 83 recipients of LDLLT and 80 recipients of CLT. The incidence of ACs did not differ between LDLLT and CLT. The initial type of AC after LDLLT was limited to stenosis in all eight patients, whereas that after CLT consisted of stenosis in three patients and necrosis in ten patients (p = 0.0034). ACs after LDLLT necessitated significantly earlier initiation of treatment than those after CLT (p = 0.032). The overall survival rate of LDLLT recipients with an AC was significantly lower than that of those without an AC (p = 0.030), whereas the overall survival rate was comparable between CLT recipients with and those without ACs (p = 0.25). ACs after LDLLT, limited to bronchial stenosis, require significantly earlier treatment and have a greater adverse impact on survival than ACs after CLT.

Successful prolonged ex vivo lung perfusion for graft preservation in rats.

PubMed

Noda, Kentaro; Shigemura, Norihisa; Tanaka, Yugo; Bhama, Jay K; D'Cunha, Jonathan; Luketich, James D; Bermudez, Christian A

2014-03-01

Ex vivo lung perfusion (EVLP) strategies represent a new frontier in lung transplantation technology, and there have been many clinical studies of EVLP in lung transplantation. The establishment of a reliable EVLP model in small animals is crucial to facilitating translational research using an EVLP strategy. The main objective of this study was to develop a reproducible rat EVLP (R-EVLP) model that enables prolonged evaluation of the explanted lung during EVLP and successful transplantation after EVLP. The donor heart-lung blocks were procured with cold low-potassium dextran solution and immersed in the solution for 1 h at 4 °C. And then, the heart-lung blocks were flushed retrogradely and warmed up to 37 °C in a circuit perfused antegradely with acellular perfusate. The perfusate was deoxygenated with a gas mixture (6% O2, 8% CO2, 86% N2). The perfusion flow was maintained at 20% of the entire cardiac output. At 37 °C, the lungs were mechanically ventilated and perfusion continued for 4 h. Every hour, the perfused lung was evaluated for gas exchange, dynamic lung compliance (Cdyn) and pulmonary vascular resistance (PVR). R-EVLP was performed for 4 h. Pulmonary oxygenation ability (pO2/pCO2) was stable for 4 h during EVLP. It was noted that Cdyn and PVR were also stable. After 4 h of EVLP, pO2 was 303 ± 19 mmHg, pCO2 was 39.6 ± 1.2 mmHg, PVR was 1.75 ± 0.10 mmHg/ml/min and Cdyn was 0.37 ± 0.03 ml/cmH2O. Lungs that were transplanted after 2 h of R-EVLP resulted in significantly better post-transplant oxygenation and compliance when compared with those after standard cold static preservation. Our R-EVLP model maintained stable lung oxygenation, compliance and vascular resistance for up to 4 h of perfusion duration. This reliable model should facilitate further advancement of experimental work using EVLP.

Neurobehavioral Functioning and Survival Following Lung Transplantation

PubMed Central

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.

2014-01-01

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. Trial registry: ClinicalTrials.gov; No.: NCT00113139; URL: www.clinicaltrials.gov PMID:24233282

Clinical outcome following lung transplantation in patients with cystic fibrosis colonised with Burkholderia cepacia complex: results from two French centres.

PubMed

Boussaud, V; Guillemain, R; Grenet, D; Coley, N; Souilamas, R; Bonnette, P; Stern, M

2008-08-01

Infection with Burkholderia cepacia complex (BCC) is a life threatening complication of cystic fibrosis (CF), often seen as a contraindication for lung transplantation. A long term retrospective study was conducted of all patients with CF undergoing lung transplants from January 1990 to October 2006 in two French centres allowing transplantation in patients colonised with BCC. 22 of the 247 lung transplant patients with CF were infected with BCC (B. cenocepacia genomovar III (n = 8), B. multivorans genomovar II (n = 11), B. vietnamiensis genomovar V (n = 2) and B. stabilis genomovar IV (n = 1)). BCC colonisation was not associated with any significant excess mortality (HR 1.5, 95% CI 0.7 to 3.2; p = 0.58). However, early mortality rates tended to be higher in the BCC group than in the non-BCC group (3 month survival: 85% vs 95%, respectively; log rank p = 0.05). Univariate analysis showed that the risk of death was significantly higher for the eight patients infected with B. cenocepacia than for the other 14 colonised patients (HR 3.2, 95% CI 1.1 to 5.9; p = 0.04). None of the other risk factors tested-primary graft failure, late extubation, septicaemia-had a significant effect. The 5 year cumulative incidence rate of bronchiolitis obliterans syndrome was not significantly higher in the BCC group than in the non-BCC group (38% vs 24%, respectively; p = 0.35). Our results suggest that BCC infection with a non-genomovar III organism may not be associated with excess mortality after lung transplantation in patients with CF and should not be seen as sufficient reason to exclude lung transplantation. However, colonisation with B. cenocepacia remains potentially detrimental.

Long-term success of combined kidney-lung transplantation in a patient with cystic fibrosis.

PubMed

Borro, José M; Rama, Pablo; Rey, Teresa; Fernández-Rivera, Constantino

2013-06-01

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.

Preconditioning allows engraftment of mouse and human embryonic lung cells, enabling lung repair in mice.

PubMed

Rosen, Chava; Shezen, Elias; Aronovich, Anna; Klionsky, Yael Zlotnikov; Yaakov, Yasmin; Assayag, Miri; Biton, Inbal Eti; Tal, Orna; Shakhar, Guy; Ben-Hur, Herzel; Shneider, David; Vaknin, Zvi; Sadan, Oscar; Evron, Shmuel; Freud, Enrique; Shoseyov, David; Wilschanski, Michael; Berkman, Neville; Fibbe, Willem E; Hagin, David; Hillel-Karniel, Carmit; Krentsis, Irit Milman; Bachar-Lustig, Esther; Reisner, Yair

2015-08-01

Repair of injured lungs represents a longstanding therapeutic challenge. We show that human and mouse embryonic lung tissue from the canalicular stage of development (20-22 weeks of gestation for humans, and embryonic day 15-16 (E15-E16) for mouse) are enriched with progenitors residing in distinct niches. On the basis of the marked analogy to progenitor niches in bone marrow (BM), we attempted strategies similar to BM transplantation, employing sublethal radiation to vacate lung progenitor niches and to reduce stem cell competition. Intravenous infusion of a single cell suspension of canalicular lung tissue from GFP-marked mice or human fetal donors into naphthalene-injured and irradiated syngeneic or SCID mice, respectively, induced marked long-term lung chimerism. Donor type structures or 'patches' contained epithelial, mesenchymal and endothelial cells. Transplantation of differentially labeled E16 mouse lung cells indicated that these patches were probably of clonal origin from the donor. Recipients of the single cell suspension transplant exhibited marked improvement in lung compliance and tissue damping reflecting the energy dissipation in the lung tissues. Our study provides proof of concept for lung reconstitution by canalicular-stage human lung cells after preconditioning of the pulmonary niche.

Guardians of 'the gift': the emotional challenges of heart and lung transplant professionals in Denmark.

PubMed

Jensen, Anja M B

2017-04-01

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.

Clinical lung transplantation from uncontrolled non-heart-beating donors revisited.

PubMed

Gomez-de-Antonio, David; Campo-Cañaveral, Jose Luis; Crowley, Silvana; Valdivia, Daniel; Cordoba, Mar; Moradiellos, Javier; Naranjo, Jose Manual; Ussetti, Piedad; Varela, Andrés

2012-04-01

The aim of our study is to review and update the long-term results from our previously published series of lung transplantation in uncontrolled non-heart-beating donors (NHBDs). A prospective collection of data was undertaken from all lung transplants performed among uncontrolled NHBDs between 2002 and December 2009. The statistical analysis was performed using SPSS software and survival was estimated using the Kaplan-Meier method. Twenty-nine lung transplants were performed. Mean total ischemic times for the first and second lung were 575 minutes (SD 115.6) and 701 minutes (SD 111.3), respectively. Primary graft dysfunction (PGD) G1, G2 and G3 occurred in 5 cases (17%), 5 cases (17%) and 11 cases (38%), respectively. Overall hospital mortality rate was 17% (5 patients). Statistical analysis revealed a statistically significant association of mortality with ischemic times and with PGD. In terms of overall survival, 3-month, 1-year, 2-year and 5-year survival rates were 78%, 68%, 57% and 51%, respectively, and the conditional survival rates in those who survived the first 3 months were 86%, 72% and 65%, respectively. The cumulative incidence of bronchiolitis obliterans syndrome (BOS) was 11%, 35% and 45% at 1, 3 and 5 years, respectively. Lung transplantation from uncontrolled non-heart-beating donors shows acceptable results for both mid- and long-term survival and BOS; however, the higher rates of PGD and its impact on early mortality must make us more demanding with respect to the acceptance criteria and methods of evaluation used with these donors. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Ex vivo lung perfusion.

PubMed

Reeb, Jeremie; Cypel, Marcelo

2016-03-01

Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats.

PubMed

Kawamura, Tomohiro; Huang, Chien-Sheng; Tochigi, Naobumi; Lee, Sungsoo; Shigemura, Norihisa; Billiar, Timothy R; Okumura, Meinoshin; Nakao, Atsunori; Toyoda, Yoshiya

2010-12-27

Successful abrogation of ischemia/reperfusion (I/R) injury of lung grafts could significantly improve short- and long-term outcomes for lung transplant (LTx) recipients. Hydrogen gas has potent antioxidant and antiapoptotic properties and has been recently used in number of experimental and clinical studies. The purpose of this research was to investigate whether inhaled hydrogen gas could reduce graft I/R injury during lung transplantation. Orthotopic left LTxs were performed in syngenic Lewis rats. Grafts were perfused with and stored in low potassium dextran solution at 4°C for 6 hr. The recipients received 100% O2 or 98% O2 with 2% N2, 2% He, or 2% H2 during surgery and 1 hr after reperfusion. The effects of hydrogen were assessed by functional, pathologic, and molecular analysis. Gas exchange was markedly impaired in animals exposed to 100% O2, 2% N2, or 2% He. Hydrogen inhalation attenuated graft injury as indicated by significantly improved gas exchange 2 hr after reperfusion. Graft lipid peroxidation was significantly reduced in the presence of hydrogen, demonstrating antioxidant effects of hydrogen in the transplanted lungs. Lung cold I/R injury causes the rapid production and release of several proinflammatory mediators and epithelial apoptosis. Exposure to 2% H2 significantly blocked the production of several proinflammatory mediators and reduced apoptosis with induction of the antiapoptotic molecules B-cell lymphoma-2 and B-cell lymphoma-extra large. Treatment of LTx recipients with inhaled hydrogen can prevent lung I/R injury and significantly improve the function of lung grafts after extended cold preservation, transplant, and reperfusion.

Zbtb7a induction in alveolar macrophages is implicated in anti-HLA-mediated lung allograft rejection.

PubMed

Nayak, Deepak K; Zhou, Fangyu; Xu, Min; Huang, Jing; Tsuji, Moriya; Yu, Jinsheng; Hachem, Ramsey; Gelman, Andrew E; Bremner, Ross M; Smith, Michael A; Mohanakumar, Thalachallour

2017-07-12

Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection. A cohort of human lung transplant recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a expression long before clinical diagnosis of chronic rejection compared to nonrejecting lung transplant recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs), and selective disruption of Zbtb7a in AMs resulted in less bronchiolar occlusion, low immune responses to lung-restricted self-antigens, and high protection from chronic rejection in mice. Additionally, in an allogeneic cell transfer protocol, antigen presentation by AMs was Zbtb7a-dependent where AMs deficient in Zbtb7a failed to induce antibody and T cell responses. Collectively, we demonstrate that AMs play an essential role in antibody-induced pathogenesis of chronic rejection by regulating early inflammation and lung-restricted humoral and cellular autoimmunity. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Induction of MHC-mismatched Mouse Lung Allograft Acceptance with Combined Donor Bone Marrow: Lung Transplant using a 12-Hour Nonmyeloablative Conditioning Regimen

PubMed Central

Vulic, Ante; Panoskaltsis-Mortari, Angela; McDyer, John F.; Luznik, Leo

2016-01-01

Background Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. Methods Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low dose total body irradiation and posttransplant (donor) bone marrow and splenocyte infusion followed by posttransplantation cyclophosphamide (PTTT-PTB/PTCy). Results Our results show that C57BL/6 recipients of BALB/c lung allografts undergoing this complete short-duration nonmyeloablative conditioning regimen had durable lung allograft acceptance. Mice that lacked 1 or more components of this regimen exhibited significant graft loss. Mechanistically, animals with lung allograft acceptance had established higher levels of donor chimerism, lymphocyte responses which were attenuated to donor antigens but maintained to third-party antigens, and clonal deletion of donor-reactive host Vβ T cells. Frequencies of Foxp3+ T regulatory cells were comparable in both surviving and rejected allografts implying that their perturbation was not a dominant cell-regulatory mechanism. Donor chimerism was indispensable for sustained tolerance, as evidenced by acute rejection of allografts in established chimeric recipients of PTTT-PTB/PTCy following a chimerism-ablating secondary recipient lymphocyte infusion. Conclusion Together, these data provide proof-of-concept for establishing lung allograft tolerance with tandem donor bone marrow transplantation (BMT) using a short-duration nonmyeloablative conditioning regimen and PTCy. PMID:27861294

Desensitization strategies in adult heart transplantation-Will persistence pay off?

PubMed

Chih, Sharon; Patel, Jignesh

2016-08-01

Strategies are needed to enable successful heart transplantation in highly sensitized patients. Immunologic challenges from sensitization to human leukocyte antigen (HLA) reduce access to compatible donors, extend waiting times to transplant, and increase the risks of antibody-mediated rejection and cardiac allograft vasculopathy after transplant. The prime goal of desensitization is to increase access to transplantation through expansion of the donor organ pool. Existing therapies are directed at key components of the humoral immune response with newer biologically based regimens able to target plasma cells as the source of antibody production, as well as complement activation that has a central role in antibody-mediated injury. Despite the emergence of early promising results for these agents, a significant knowledge gap remains with the current data for desensitization, extrapolated mostly from non-heart solid-organ transplants and small observational studies. Notably, no approach has demonstrated significant and sustainable reductions in HLA antibody pre-transplant, and the ideal desensitization strategy remains elusive. In addition, clinical tools to evaluate the humoral response and efficacy of therapy are limited, focusing almost exclusively on HLA antibody detection. Importantly, desensitization is associated with significant costs and potential risks, and overall long-term outcomes and cost-effectiveness have not been sufficiently evaluated. Investigation is ongoing into the development of a clinically effective desensitization strategy in heart transplantation. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Comorbidities impacting on prognosis after lung transplant.

PubMed

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

2014-01-01

The aim of this review is to give an overview of the clinical circumstances presenting before lung transplant that may have negative repercussions on the long and short-term prognosis of the transplant. Methods for screening and diagnosis of common comorbidities with negative impact on the prognosis of the transplant are proposed, both for pulmonary and extrapulmonary diseases, and measures aimed at correcting these factors are discussed. Coordination and information exchange between referral centers and transplant centers would allow these comorbidities to be detected and corrected, with the aim of minimizing the risks and improving the life expectancy of transplant receivers. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Constrictive (obliterative) bronchiolitis: diagnosis, etiology, and a critical review of the literature.

PubMed

Schlesinger, C; Meyer, C A; Veeraraghavan, S; Koss, M N

1998-10-01

Constrictive bronchiolitis (CB) (or obliterative bronchiolitis) designates inflammation and fibrosis occurring predominantly in the walls and contiguous tissues of membranous and respiratory bronchioles, with resultant narrowing of their lumens. It differs from bronchiolitis obliterans-organizing pneumonia in its histopathology and clinical course. Most cases of CB occur in the setting of organ transplants, particularly lung and heart-lung transplants, but also in bone marrow transplants. Other bona fide cases are rare: infection, particularly viral infection, appears to be a well-documented precursor to CB in children, but not in immunocompetent adults. Constrictive bronchiolitis also has been reported in the course of rheumatoid arthritis, in certain other autoimmune diseases such as pemphigus vulgaris, after inhalation of toxic gases such as nitrogen oxide, after ingestion of certain drugs or medicinal agents such as Sauropus androgynous, and as a cryptogenic illness. Recent reports suggest that CB, as defined by clinical criteria (that is, bronchiolitis obliterans syndrome), is very common in lung allograft recipients who survive more than 5 years and, although it is associated with significant mortality, it also can be clinically stable. Furthermore, with the current practice of close monitoring of these patients, it appears that CB may now be diagnosed at an earlier stage, at which resolution, or at least stabilization of progression, is possible. A histopathologic diagnosis of CB in lung transplant and other patients may be difficult to make due to the patchy distribution of lesions, the technical difficulty in obtaining tissue in late lesions with extensive fibrosis, and the failure to recognize lesions. With regard to the last of these, in early stages of disease, CB may be subtle and easily missed in routine hematoxylin-eosin-stained specimens, while in advanced stages the disease may be equally difficult to diagnose if the patchy scarring in the lung is interpreted as nonspecific. The relative loss of bronchioles and the relationship of the scars to contiguous arteries should signal the need for elastic stains to look for the residual elastica of the bronchioles amidst the foci of fibrosis. Increasingly, clinical grounds, including pulmonary functions studies and high-resolution computed tomography findings, are proving to be relatively sensitive methods of detecting CB. Finally, the progressive airway destruction in chronic transplantation rejection appears to be a T-cell-mediated process. The "active" form of constrictive bronchiolitis, with attendant lymphocytic inflammation of the airways, likely precedes the "inactive" or scarred form of constrictive bronchiolitis.

Is There an Age Limit to Lung Transplantation?

PubMed

Biswas Roy, Sreeja; Alarcon, Diana; Walia, Rajat; Chapple, Kristina M; Bremner, Ross M; Smith, Michael A

2015-08-01

Lung transplantation in patients older than 65 years is increasingly common, but questions remain regarding risk vs benefit and procedure choice. We identified short-term and long-term outcomes in older single-lung transplant (SLT) and bilateral-lung transplant (BLT) recipients. We performed a retrospective review of United Network for Organ Sharing data for patients who underwent lung transplantation between May 2005 and December 2012. Patients were grouped by age, and we calculated short-term and long-term survival rates and compared survival distributions. Of the 11,776 patients who received lung transplants, 9,317 (79%) were aged 12 to 64 years, 1,902 (16%) were 65 to 69, 486 (4%) were 70 to 74, and 71 (1%) were 75 to 79. Short-term survival was similar across all age groups and procedure types except those aged 75 to 79, who had lower short-term survival for BLT. Those aged 12 to 64 had higher 5-year survival for SLT and BLT than all other groups (p < 0.001), and BLT offered a long-term survival advantage over SLT in this group (p < 0.0001). Older age groups trended toward better long-term survival for BLT compared with SLT (65 to 69, p = 0.059; 70 to 74, p = 0.079). Although data were lacking for 5-year survival for those aged 75 to 79, the 3-year survival for BLT in this group was inferior. Lung transplant can be offered to select older patients up to age 74 with acceptable outcomes. SLT may be preferred for elderly patients, but BLT offers acceptable long-term outcomes without significant short-term risk. Patients older than 75 have acceptable short-term outcomes for SLT, but long-term outcomes for SLT and BLT in this group are poor. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Lung retransplantation in children: appropriate when selectively applied.

PubMed

Scully, Brandi B; Zafar, Farhan; Schecter, Marc G; Rossano, Joseph W; Mallory, George B; Heinle, Jeffrey S; Morales, David L S

2011-02-01

Lung retransplantation (re-LTx) in children has been associated with lower survival rates compared with primary lung transplantation. However, improving survival for primary LTx has led to more patients presenting for re-LTx. Therefore, an analysis of the UNOS (United Network of Organ Sharing) database to evaluate the effectiveness of pediatric lung retransplantation in the United States was completed. The UNOS registry was queried for pediatric re-LTx patients from May 1988 to May 2008. There were 81 (10%) re-LTx out of a total 802 pediatric lung transplants. Median age and weight at re-LTx were 14 (range, 0 to 18) years and 32 (4 to 58) kg. Indications for re-LTx were obliterative bronchiolitis in 50 patients (62%), primary graft failure in 8 (10%), and other in 23 (28%). The Kaplan-Meier graft survival for re-LTx patients was worse than for primary transplant patients (p < 0.001, graft half-life 0.9 vs 4.0 years), especially if re-LTx was done less than 1 year after primary transplant (graft half-life 0.25 years). Graft survival in patients who underwent re-LTx greater than 1 year after primary transplant was not statistically different than for primary LTx patients (p = 0.21; graft half-life 2.8 vs 4.0 years), and if re-LTx greater than 1 year posttransplant occurred in patients who were not ventilator dependent, survival was further improved (p = 0.68; graft half-life 4.7 vs 4.0 years). Pediatric lung retransplantation within the first year after primary transplant does not appear advisable. Pediatric re-LTx greater than 1 year after primary transplantation may be a reasonable strategy for end-stage graft failure. Patients greater than 1 year posttransplant and not ventilator dependent appear an even more compelling group in which to consider lung retransplantation. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival.

PubMed

Gallagher, Harry M; Sarwar, Ghulam; Tse, Tracy; Sladden, Timothy M; Hii, Esmond; Yerkovich, Stephanie T; Hopkins, Peter M; Chambers, Daniel C

2015-11-01

Erratic tacrolimus blood levels are associated with liver and kidney graft failure. We hypothesized that erratic tacrolimus exposure would similarly compromise lung transplant outcomes. This study assessed the effect of tacrolimus mean and standard deviation (SD) levels on the risk of chronic lung allograft dysfunction (CLAD) and death after lung transplantation. We retrospectively reviewed 110 lung transplant recipients who received tacrolimus-based immunosuppression. Cox proportional hazard modeling was used to investigate the effect of tacrolimus mean and SD levels on survival and CLAD. At census, 48 patients (44%) had developed CLAD and 37 (34%) had died. Tacrolimus SD was highest for the first 6 post-transplant months (median, 4.01; interquartile range [IQR], 3.04-4.98 months) before stabilizing at 2.84 μg/liter (IQR, 2.16-4.13 μg/liter) between 6 and 12 months. The SD then remained the same (median, 2.85; IQR, 2.00-3.77 μg/liter) between 12 and 24 months. A high mean tacrolimus level 6 to 12 months post-transplant independently reduced the risk of CLAD (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.63-0.86; p < 0.001) but not death (HR, 0.96; 95% CI, 0.83-1.12; p = 0.65). In contrast, a high tacrolimus SD between 6 and 12 months independently increased the risk of CLAD (HR, 1.46; 95% CI, 1.23-1.73; p < 0.001) and death (HR, 1.27; 95% CI, 1.08-1.51; p = 0.005). Erratic tacrolimus levels are a risk factor for poor lung transplant outcomes. Identifying and modifying factors that contribute to this variability may significantly improve outcomes. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Pre-transplant donor HLA-specific antibodies: characteristics causing detrimental effects on survival after lung transplantation.

PubMed

Smith, John D; Ibrahim, Mohamed W; Newell, Helen; Danskine, Anna J; Soresi, Simona; Burke, Margaret M; Rose, Marlene L; Carby, Martin

2014-10-01

The impact of Luminex-detected HLA antibodies on outcomes after lung transplantation is unclear. Herein we have undertaken a retrospective study of pre-transplant sera from 425 lung transplants performed between 1991 and 2003. Pre-transplant sera, originally screened by complement-dependent cytotoxicity (CDC) assays, were retrospectively tested for the presence of HLA-specific antibodies using HLA-coated Luminex beads and C4d deposition on Luminex beads. The results were correlated with graft survival at 1 year. Twenty-seven patients were retrospectively identified as having been transplanted against donor-specific HLA antibodies (DSA) and 36 patients against non-donor-specific HLA antibodies (NDSA). DSA-positive patients had 1-year survival of 51.9% compared with 77.8% for NDSA and 71.8% for antibody-negative patients (p = 0.029). One-year survival of patients with complement-fixing DSA was 12.5% compared with 62.5% for non-complement-fixing DSA, 75.8% for non-complement-fixing NDSA and 71.8% for antibody-negative patients (p < 0.0001). DSA-positive patients with mean fluorescence intensity (MFI) >5,000 had 1-year survival of 33.3% compared with 71.4% for MFI 2,000 to 5000 and 62.5% for MFI <2,000 (p = 0.0046). Multivariable analysis revealed DSA to be an independent predictor of poor patient survival within 1 year (p = 0.0010, hazard ratio [HR] = 3.569) as well as complement-fixing DSA (p < 0.0001, HR = 11.083) and DSA with MFI >5,000 (p = 0.0001, HR = 5.512). Pre-formed DSA, particularly complement-fixing DSA, and high MFI are associated with poor survival within the first year after lung transplantation. Risk stratification according to complement fixation or MFI levels may allow for increased transplantation in sensitized patients. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

[Isolated lung transplantation--evaluation of patients and initial results].

PubMed

Speich, R; Böhler, A; Zollinger, A; Stocker, R; Vogt, P; Carrel, T; Lang, T; Schmid, R; Stöhr, S; Vogt, P R

1995-04-22

Between November 1992 and May 1994 we performed 10 single and 5 double lung transplants in patients with end-stage lung diseases due to lymphangioleiomyomatosis (4), cystic fibrosis (3), pulmonary hypertension (3), pulmonary fibrosis (3) and chronic obstructive lung disease (2). In the 13 patients (87%) surviving for median 245 (19-567) days, FEV1 improved from median 640 ml to 1410 ml and the 12-minute walk distance from median 315 to 1100 meters. 10 patients (77%) enjoy a good or even excellent quality of life. 2 patients died 11 and 62 days postoperatively, due to multi-organ failure and invasive pulmonary aspergillosis respectively. The main postoperative problems are fungal and cytomegalovirus infections and chronic rejection in the form of bronchiolitis obliterans. In Switzerland as elsewhere, lung transplantation has become an established modality for the management of end-stage diseases of the lung and pulmonary circulation.

Cystic fibrosis lung transplantation.

PubMed

Braun, Andrew T; Merlo, Christian A

2011-11-01

This review summarizes recently published investigations on issues pertaining to cystic fibrosis (CF) lung transplantation. We specifically focus on indications and candidate selection as well as infectious and noninfectious issues specific to CF lung transplant recipients. Recent studies have focused on candidate adequacy in high-risk CF patients. We review the current literature on individuals who develop respiratory failure requiring mechanical ventilation and those patients with a pretransplant diagnosis of pulmonary hypertension. Furthermore, the management of peri-operative infectious issues is reviewed including recurrent infections with multidrug-resistant bacterial, mycobacterial, and fungal organisms. Other CF-specific issues addressed include common comorbidities such as CF-related diabetes, gastroesophageal reflux, CF liver disease, and bone metabolism. Lung transplantation is a limited, but potentially life-saving therapeutic option for patients with CF. Optimal candidate selection and awareness of CF-specific issues in the pretransplant and posttransplant setting may lead to better long-term outcomes. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

Human umbilical cord blood-derived mesenchymal stem cells attenuate hyperoxia-induced lung injury in neonatal rats.

PubMed

Chang, Yun Sil; Oh, Wonil; Choi, Soo Jin; Sung, Dong Kyung; Kim, Soo Yoon; Choi, Eun Yang; Kang, Saem; Jin, Hye Jin; Yang, Yoon Sun; Park, Won Soon

2009-01-01

Recent evidence suggests mesenchymal stem cells (MSCs) can downmodulate bleomycin-induced lung injury, and umbilical cord blood (UCB) is a promising source for human MSCs. This study examined whether intratracheal or intraperitoneal transplantation of human UCB-derived MSCs can attenuate hyperoxia-induced lung injury in immunocompetent newborn rats. Wild-type Sprague-Dawley rats were randomly exposed to 95% oxygen or air from birth. In the transplantation groups, a single dose of PKH26-labeled human UCB-derived MSCs was administered either intratracheally (2 x 10(6) cells) or intraperitoneally (5 x 10(5) cells) at postnatal day (P) 5. At P14, the harvested lungs were examined for morphometric analyses of alveolarization and TUNEL staining, as well as the myeoloperoxidase activity, the level of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and transforming growth factor (TGF)-beta mRNA, alpha-smooth muscle actin (SMA) protein, and collagen levels. Differentiation of MSCs to the respiratory epithelium was also evaluated both in vitro before transplantation and in vivo after transplantation. Despite one fourth dosage of MSCs, significantly more PKH26-labeled donor cells were recovered with intratracheal administration than with intraperitoneal administration both during normoxia and hyperoxia. The hyperoxia-induced increase in the number of TUNEL-positive cells, myeloperoixdase activity, and the level of IL-6 mRNA were significantly attenuated with both intratracheal and intraperitoneal MSCs transplantation. However, the hyperoxia-induced impaired alveolarization and increased the level of TNF-alpha and TGF-beta mRNA, alpha-SMA protein, and collagen were significantly attenuated only with intratracheal MSCs transplantation. MSCs differentiated into respiratory epithelium in vitro and a few PKH26-positive donor cells were colocalized with pro surfactant protein C in the damaged lungs. In conclusion, intratracheal transplantation of human UCB-derived MSCs is more effective than intraperitoneal transplantation in attenuating the hyperoxia-induced lung injury in neonatal rats.

Impact of pretransplant anti-HLA antibodies on outcomes in lung transplant candidates.

PubMed

Kim, Miae; Townsend, Keri R; Wood, Isabelle G; Boukedes, Steve; Guleria, Indira; Gabardi, Steven; El-Chemaly, Souheil; Camp, Phillip C; Chandraker, Anil K; Milford, Edgar L; Goldberg, Hilary J

2014-05-15

The prevalence of anti-HLA antibodies in lung transplant candidates and their impact on waitlist and transplant outcomes is not known. We examined the prevalence of pretransplant anti-HLA antibodies at varying thresholds and evaluated their impact on outcomes before and after lung transplantation. We performed a single-center retrospective cohort study including all patients listed for lung transplantation between January 2008 and August 2012. Per protocol, transplant candidates were assessed by solid phase LABscreen mixed Class I and II and LABscreen Single Antigen assays. Among 224 patients, 34% had anti-HLA antibodies at mean fluorescent intensity (MFI) greater than or equal to 3,000 (group III), and 24% had antibodies at MFI 1,000 to 3,000 (group II). Ninety percent of the patients with pretransplant anti-HLA antibodies had class I antibodies, whereas only seven patients developed class II alone. Patients in group III were less likely to receive transplants than patients without any anti-HLA antibodies (group I) (45.5 vs. 67.7%, P = 0.005). Wait time to transplant was longer in group III than group I, although this difference did not meet statistical significance, and waitlist mortality was similar. Among transplant recipients, antibody-mediated rejection (AMR) was more frequent in group III than in group II (20% vs. 0%, P = 0.01) or group I (6.3%, P = 0.05). The presence of anti-HLA antibodies at the high MFI threshold (>3,000) was associated with lower transplant rate and higher rates of AMR. Screening for anti-HLA antibodies using the 3,000 MFI threshold may be important in managing transplant candidates and recipients.

Payer leverage and hospital compliance with a benchmark: a population-based observational study

PubMed Central

Hollingsworth, John M; Krein, Sarah L; Miller, David C; DeMonner, Sonya; Hollenbeck, Brent K

2007-01-01

Background Since 1976, Medicare has linked reimbursement for hospitals performing organ transplants to the attainment of certain benchmarks, including transplant volume. While Medicare is a stakeholder in all transplant services, its role in renal transplantation is likely greater, given its coverage of end-stage renal disease. Thus, Medicare's transplant experience allows us to examine the role of payer leverage in motivating hospital benchmark compliance. Methods Nationally representative discharge data for kidney (n = 29,272), liver (n = 7,988), heart (n = 3,530), and lung (n = 1,880) transplants from the Nationwide Inpatient Sample (1993 – 2003) were employed. Logistic regression techniques with robust variance estimators were used to examine the relationship between hospital volume compliance and Medicare market share; generalized estimating equations were used to explore the association between patient-level operative mortality and hospital volume compliance. Results Medicare's transplant market share varied by organ [57%, 28%, 27%, and 18% for kidney, lung, heart, and liver transplants, respectively (P < 0.001)]. Volume-based benchmark compliance varied by transplant type [85%, 75%, 44%, and 39% for kidney, liver, heart, and lung transplants, respectively (P < 0.001)], despite a lower odds of operative mortality at compliant hospitals. Adjusting for organ supply, high market leverage was independently associated with compliance at hospitals transplanting kidneys (OR, 143.00; 95% CI, 18.53 – 1103.49), hearts (OR, 2.84; 95% CI, 1.51 – 5.34), and lungs (OR, 3.24; 95% CI, 1.57 – 6.67). Conclusion These data highlight the influence of payer leverage–an important contextual factor in value-based purchasing initiatives. For uncommon diagnoses, these data suggest that at least 30% of a provider's patients might need to be "at risk" for an incentive to motivate compliance. PMID:17640364

Should Jehovah's Witness patients be listed for heart transplantation?

PubMed

Elmistekawy, Elsayed; Mesana, Thierry G; Ruel, Marc

2012-10-01

This best evidence topic in Cardiac Surgery was written according to a structured protocol. The question addressed was: for [Jehovah's Witness patients with end-stage heart failure] can these patients undergo a [heart transplantation] without an increased rate of mortality. Altogether, 133 papers were found using the reported search strategy. Of those, 29 papers represented the best evidence to answer the clinical question. Five papers focusing on patients of the Jehovah's Witness (JW) faith who had end-stage heart failure were published. Successful heart transplantation was performed in a total of seven patients without mortality, re-exploration or blood transfusion. One patient had left ventricular reduction surgery twice and another patient had bypass surgery several years after transplantation. Other successful organ transplantations were also reported, including lung, liver, kidney and pancreas in both adult and paediatric patients of the JW faith, with comparable mortality and morbidity to non-JW patients. A publication bias is likely; nevertheless, we conclude that although there are no large studies directly focused on heart transplantation in JW patients, a multidisciplinary team approach to such surgery can make it technically feasible and without an increased mortality risk in suitable candidates. Therefore, such patients may be considered for heart transplantation under selected and favourable circumstances.

Amiodarone use in patients listed for heart transplant is associated with increased 1-year post-transplant mortality.

PubMed

Cooper, Lauren B; Mentz, Robert J; Edwards, Leah B; Wilk, Amber R; Rogers, Joseph G; Patel, Chetan B; Milano, Carmelo A; Hernandez, Adrian F; Stehlik, Josef; Lund, Lars H

2017-02-01

Pre-transplant amiodarone use has been postulated as a risk factor for morbidity and mortality after orthotopic heart transplantation (OHT). We assessed pre-OHT amiodarone use and tested the hypothesis that it is associated with impaired post-OHT outcomes. We performed a retrospective cohort analysis of adult OHT recipients from the registry of the International Society for Heart and Lung Transplantation (ISHLT). All patients had been transplanted between 2005 and 2013 and were stratified by pre-OHT amiodarone use. We derived propensity scores using logistic regression with amiodarone use as the dependent variable, and assessed the associations between amiodarone use and outcomes with Kaplan-Meier analysis after matching patients 1:1 based on propensity score, and with Cox regression with adjustment for propensity score. Of the 14,944 OHT patients in the study cohort, 32% (N = 4,752) received pre-OHT amiodarone. Amiodarone use was higher in recent years (29% in 2005 to 2007, 32% in 2008 to 2010, 35% in 2011 to 2013). Amiodarone-treated patients were older and more frequently had a history of sudden cardiac death (27% vs 13%) and pre-OHT mechanical circulatory support. Key donor characteristics and allograft ischemia times were similar between groups. In propensity-matched analyses, amiodarone-treated patients had higher rates of cardiac reoperation (15% vs 13%) and permanent pacemaker (5% vs 3%) after OHT and before discharge. Amiodarone-treated patients also had higher 1-year mortality (hazard ratio 1.15, 95% confidence interval 1.02 to 1.30), but the risks of early graft failure, retransplantation and rehospitalization were similar between groups. Amiodarone use before OHT was independently associated with increased 1-year mortality. The need for amiodarone therapy should be carefully and continuously assessed in patients awaiting OHT. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

High-resolution computed tomography findings of pulmonary tuberculosis in lung transplant recipients.

PubMed

Giacomelli, Irai Luis; Schuhmacher Neto, Roberto; Nin, Carlos Schuller; Cassano, Priscilla de Souza; Pereira, Marisa; Moreira, José da Silva; Nascimento, Douglas Zaione; Hochhegger, Bruno

2017-01-01

Respiratory infections constitute a major cause of morbidity and mortality in solid organ transplant recipients. The incidence of pulmonary tuberculosis is high among such patients. On imaging, tuberculosis has various presentations. Greater understanding of those presentations could reduce the impact of the disease by facilitating early diagnosis. Therefore, we attempted to describe the HRCT patterns of pulmonary tuberculosis in lung transplant recipients. From two hospitals in southern Brazil, we collected the following data on lung transplant recipients who developed pulmonary tuberculosis: gender; age; symptoms; the lung disease that led to transplantation; HRCT pattern; distribution of findings; time from transplantation to pulmonary tuberculosis; and mortality rate. The HRCT findings were classified as miliary nodules; cavitation and centrilobular nodules with a tree-in-bud pattern; ground-glass attenuation with consolidation; mediastinal lymph node enlargement; or pleural effusion. We evaluated 402 lung transplant recipients, 19 of whom developed pulmonary tuberculosis after transplantation. Among those 19 patients, the most common HRCT patterns were ground-glass attenuation with consolidation (in 42%); cavitation and centrilobular nodules with a tree-in-bud pattern (in 31.5%); and mediastinal lymph node enlargement (in 15.7%). Among the patients with cavitation and centrilobular nodules with a tree-in-bud pattern, the distribution was within the upper lobes in 66.6%. No pleural effusion was observed. Despite treatment, one-year mortality was 47.3%. The predominant HRCT pattern was ground-glass attenuation with consolidation, followed by cavitation and centrilobular nodules with a tree-in-bud pattern. These findings are similar to those reported for immunocompetent patients with pulmonary tuberculosis and considerably different from those reported for AIDS patients with the same disease.

Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation.

PubMed

Hsu, Joe L; Manouvakhova, Olga V; Clemons, Karl V; Inayathullah, Mohammed; Tu, Allen B; Sobel, Raymond A; Tian, Amy; Nazik, Hasan; Pothineni, Venkata R; Pasupneti, Shravani; Jiang, Xinguo; Dhillon, Gundeep S; Bedi, Harmeet; Rajadas, Jayakumar; Haas, Hubertus; Aurelian, Laure; Stevens, David A; Nicolls, Mark R

2018-02-21

Invasive pulmonary disease due to the mold Aspergillus fumigatus can be life-threatening in lung transplant recipients, but the risk factors remain poorly understood. To study this process, we used a tracheal allograft mouse model that recapitulates large airway changes observed in patients undergoing lung transplantation. We report that microhemorrhage-related iron content may be a major determinant of A. fumigatus invasion and, consequently, its virulence. Invasive growth was increased during progressive alloimmune-mediated graft rejection associated with high concentrations of ferric iron in the graft. The role of iron in A. fumigatus invasive growth was further confirmed by showing that this invasive phenotype was increased in tracheal transplants from donor mice lacking the hemochromatosis gene ( Hfe -/- ). The invasive phenotype was also increased in mouse syngrafts treated with topical iron solution and in allograft recipients receiving deferoxamine, a chelator that increases iron bioavailability to the mold. The invasive growth of the iron-intolerant A. fumigatus double-knockout mutant (Δ sreA /Δ cccA ) was lower than that of the wild-type mold. Alloimmune-mediated microvascular damage and iron overload did not appear to impair the host's immune response. In human lung transplant recipients, positive staining for iron in lung transplant tissue was more commonly seen in endobronchial biopsy sections from transplanted airways than in biopsies from the patients' own airways. Collectively, these data identify iron as a major determinant of A. fumigatus invasive growth and a potential target to treat or prevent A. fumigatus infections in lung transplant patients. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

GI complications after lung transplantation in patients with cystic fibrosis.

PubMed

Gilljam, Marita; Chaparro, Cecilia; Tullis, Elizabeth; Chan, Charles; Keshavjee, Shaf; Hutcheon, Michael

2003-01-01

Lung transplantation is now available for patients with cystic fibrosis (CF) and end-stage lung disease. While pulmonary graft function is often considered the major priority following transplantation, the nonpulmonary complications of this systemic disease also continue. We examined the GI complications in a cohort of patients who underwent transplantation. This was a retrospective study of all patients with CF who underwent transplantation between March 1988 and December 1998 in Toronto. Medical records were reviewed, and a short questionnaire was mailed to patients who were alive as of December 1998. There were 80 bilateral lung transplants performed in 75 patients. The questionnaire was distributed to 43 patients, of whom 27 patients (63%) responded. Pancreatic insufficiency requiring enzyme intake was evident in 72 of 75 patients (96%) at the time of surgery. Of three pancreatic-sufficient patients (4%), pancreatic insufficiency was diagnosed in two patients later. Biliary cirrhosis was diagnosed in three patients prior to transplantation. Distal intestinal obstruction syndrome (DIOS) was recorded for 15 patients (20%). Ten patients had a single episode, of which eight episodes occurred early in the postoperative period. Five patients had recurrent episodes. All were medically treated, except for two patients who underwent surgery. Other complications included cholecystitis (n = 3), mucocele of the appendix (n = 1), peptic ulcer disease (n = 3), and colonic carcinoma (n = 1). GI complications after lung transplantation are common in patients with CF, and attention should be paid to the risk for DIOS in the early postoperative period. Prevention and early medical treatment are important in order to avoid acute surgery. Close collaboration with the CF clinic, in order to diagnose and treat CF-related complications, is recommended.

Use of telehealth technology for home spirometry after lung transplantation: a randomized controlled trial.

PubMed

Sengpiel, Juliane; Fuehner, Thomas; Kugler, Christiane; Avsar, Murat; Bodmann, Isabelle; Boemke, Annelies; Simon, Andre; Welte, Tobias; Gottlieb, Jens

2010-12-01

Complications often occur during the early phase after lung transplantation, and rapid diagnosis is vital. Home spirometry is used to detect early changes in graft function. Bluetooth-equipped cell phones are easy to use and facilitate data transfer from home spirometry. To explore use of home spirometry with Bluetooth data transfer in outpatient lung transplant recipients. Single-center prospective randomized controlled trial. Intervention-Fifty-six patients were randomized either to home spirometry with data transfer via Bluetooth-equipped cell phones or to home spirometry alone before discharge after lung transplantation. In the Bluetooth group, results were transferred to a database capable of generating alarm messages. Time from onset of symptoms to physician consultation during the first 6 months after lung transplantation was the primary end point. Adherence to home spirometry was 97.2% in the Bluetooth group and 95.3% in the home spirometry alone group (P = .73). Median time to first consultation (P = .60) and frequency of consultation (P = .06) did not differ significantly in the 2 groups. Mean scores on the Hospital Anxiety and Depression Scale were lower in patients in the Bluetooth group (1.5; range, 0.0-4.0) than in the home spirometry alone group (4.0; range, 2.0-6.0; P = .04). Home spirometry with data transfer is feasible and safe in lung transplant recipients. Compared with home spirometry alone, additional data transfer was equally effective regarding the time interval from symptom onset to consultation. Patients in the Bluetooth group reported less anxiety, which may improve emotional well-being.

Suicidal hanging donors for lung transplantation

PubMed Central

Ananiadou, Olga; Schmack, Bastian; Zych, Bartlomiej; Sabashnikov, Anton; Garcia-Saez, Diana; Mohite, Prashant; Weymann, Alexander; Mansur, Ashham; Zeriouh, Mohamed; Marczin, Nandor; De Robertis, Fabio; Simon, Andre Rüdiger; Popov, Aron-Frederik

2018-01-01

Abstract In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group. Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed. No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P < .001, P = .022 and P = .0042, respectively). Recipient preoperative and perioperative characteristics were comparable. Postoperatively in group 1 there was a higher incidence of extracorporeal life support (27.3 vs 9.1%, P = .019). There were no significant differences in chronic lung allograft dysfunction-free survival between group 1 and 2: 92.3 vs 94% at 1 year and 65.9 vs 75.5% at 3 years (P = .99). The estimated cumulative survival rate was also similar between groups: 68.2 vs 83.2% at 1 year and 68.2% versus 72% at 3 years (P = .3758). Hanging as a donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation. PMID:29620623

Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study.

PubMed

Kumar, Deepali; Michaels, Marian G; Morris, Michele I; Green, Michael; Avery, Robin K; Liu, Catherine; Danziger-Isakov, Lara; Stosor, Valentina; Estabrook, Michele; Gantt, Soren; Marr, Kieren A; Martin, Stanley; Silveira, Fernanda P; Razonable, Raymund R; Allen, Upton D; Levi, Marilyn E; Lyon, G Marshall; Bell, Lorraine E; Huprikar, Shirish; Patel, Gopi; Gregg, Kevin S; Pursell, Kenneth; Helmersen, Doug; Julian, Kathleen G; Shiley, Kevin; Bono, Bartholomew; Dharnidharka, Vikas R; Alavi, Gelareh; Kalpoe, Jayant S; Shoham, Shmuel; Reid, Gail E; Humar, Atul

2010-08-01

There are few data on the epidemiology and outcomes of influenza infection in recipients of solid-organ transplants. We aimed to establish the outcomes of pandemic influenza A H1N1 and factors leading to severe disease in a cohort of patients who had received transplants. We did a multicentre cohort study of adults and children who had received organ transplants with microbiological confirmation of influenza A infection from April to December, 2009. Centres were identified through the American Society of Transplantation Influenza Collaborative Study Group. Demographics, clinical presentation, treatment, and outcomes were assessed. Severity of disease was measured by admission to hospital and intensive care units (ICUs). The data were analysed with descriptive statistics. Proportions were compared by use of chi(2) tests. We used univariate analysis to identify factors leading to pneumonia, admission to hospital, and admission to an ICU. Multivariate analysis was done by use of a stepwise logistic regression model. We analysed deaths with Kaplan-Meier survival analysis. We assessed 237 cases of medically attended influenza A H1N1 reported from 26 transplant centres during the study period. Transplant types included kidney, liver, heart, lung, and others. Both adults (154 patients; median age 47 years) and children (83; 9 years) were assessed. Median time from transplant was 3.6 years. 167 (71%) of 237 patients were admitted to hospital. Data on complications were available for 230 patients; 73 (32%) had pneumonia, 37 (16%) were admitted to ICUs, and ten (4%) died. Antiviral treatment was used in 223 (94%) patients (primarily oseltamivir monotherapy). Seven (8%) patients given antiviral drugs within 48 h of symptom onset were admitted to an ICU compared with 28 (22.4%) given antivirals later (p=0.007). Children who received transplants were less likely to present with pneumonia than adults, but rates of admission to hospital and ICU were similar. Influenza A H1N1 caused substantial morbidity in recipients of solid-organ transplants during the 2009-10 pandemic. Starting antiviral therapy early is associated with clinical benefit as measured by need for ICU admission and mechanical ventilation. None. 2010 Elsevier Ltd. All rights reserved.

Fusarium Infection in Lung Transplant Patients

PubMed Central

Carneiro, Herman A.; Coleman, Jeffrey J.; Restrepo, Alejandro; Mylonakis, Eleftherios

2013-01-01

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 should ideally be based on the Fusarium isolate, susceptibility testing, and host-specific factors. Prognosis of fusariosis in the immunocompromised is directly related to a patient’s immune status. Prevention of Fusarium infection is recommended with aerosolized amphotericin B deoxycholate, which also has activity against other important fungi. PMID:21200188

Another Piece of the Antibody Puzzle: Observations from the HALT study\\.

PubMed

Snyder, Laurie D; Tinckam, Kathryn J

2018-06-04

In the rapidly evolving domain of clinical transplantation immunobiology, the interrogation and interpretation of HLA antibodies and their associated clinical consequences are in the spotlight. In lung transplant, HLA antibodies, in particular donor specific antibodies (DSA), are a determining component of the lung transplant antibody mediated rejection (AMR) definition (1). DSA after lung transplant are widely regarded as poor prognosticator, though sparse data to date necessitate ongoing discourse and continued investigation into incidence, timing and treatment. Prior studies reported a wide range of DSA incidence with differing consequences on a background of highly variable timing, methods, antibody analytic strategies and clinical definitions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A global perspective of lung transplantation: Part 1 - Recipient selection and choice of procedure

PubMed Central

Khaghani, Asghar

Lung transplantation has grown considerably in recent years and its availability has spread to an expanding number of countries worldwide. Importantly, survival has also steadily improved, making this an increasingly viable procedure for patients with end-stage lung disease and limited life expectancy. In this first of a series of articles, recipient selection and type of transplant operation are reviewed. Pulmonary fibrotic disorders are now the most indication in the U.S., followed by chronic obstructive pulmonary disease and cystic fibrosis. Transplant centers have liberalized criteria to include older and more critically ill candidates. A careful, systematic, multi-disciplinary selection process is critical in identifying potential barriers that may increase risk and optimize long-term outcomes. PMID:29043255

Case Report: Successful Lung Transplantation from a Donor Seropositive for Trypanosoma cruzi Infection (Chagas Disease) to a Seronegative Recipient.

PubMed

Salvador, Fernando; Sánchez-Montalvá, Adrián; Sulleiro, Elena; Berastegui, Cristina; Jauregui, Alberto; Pont, Teresa; Los-Arcos, Ibai; Len, Óscar; Gavaldà, Joan; Molina, Israel

2017-10-01

The increasing shortage of organs for transplantation has prompted transplant programs to investigate the use of extended criteria donors, such as those with transmissible infectious diseases. Successful cases of organ transplantation (mostly kidney and liver) from Trypanosoma cruzi seropositive donors to seronegative recipients have been reported. We present a case of lung transplantation from a donor serologically positive for Chagas disease to a seronegative recipient, and provide a review of the literature. Left single lung transplantation was performed in a 44-year-old Spanish woman presenting with interstitial lung disease in February 2016. The deceased donor was a Colombian immigrant living in Spain who was serologically positive for Chagas disease. Oral administration of 5 mg/kg/day benznidazole divided in three doses for 60 days was given for specific Chagas disease prophylaxis after transplantation. Periodic follow-up with serological reverse transcription polymerase chain reaction to detect T. cruzi DNA were performed until 6 months after the end of treatment. All results were negative, indicating that transmission of T. cruzi had not occurred. In a review of the literature, two similar cases were identified in Argentina and the United States. In both cases T. cruzi infection was detected posttransplant in the recipients, after which they were treated with benznidazole. The course of the patient described herein confirms that lungs from donors with chronic T. cruzi infection can be used successfully as allografts, and that posttransplant prophylaxis with benznidazole may reduce the probability of transmission of T. cruzi to the recipient.

Lung Abscess: An Early Complication of Lung Transplantation in a Patient with Cystic Fibrosis.

PubMed

Markelić, I; Jakopović, M; Klepetko, W; Džubur, F; Hećimović, A; Makek, M J; Samaržija, M; Dugac, A V

2017-01-01

A 22-year-old woman with cystic fibrosis (CF) developed lung abscess, as a rare complication caused by multidrug-resistant (MDR) Acinetobacter baumannii infection, after lung transplantation (LT). After 6 months of long-term antibiotic therapy, the abscess was successfully eliminated. In reviewed published literature, no previous report was found describing this kind of complication caused by MDR A. baumannii in post-LT patient with CF. In our experience, lung abscess in LT recipients with CF can be successfully treated with prolonged antibiotic therapy.

[Anesthetic complications in sequential bipulmonary transplantation in patients with cystic fibrosis. Apropos of 6 cases].

PubMed

López, L M; Vicente, R; Ramos, F; Palacios, L; Calvo, A; Hernández, S; Borro, J M; Morales, P; Montero, R

1996-03-01

Cystic fibrosis (CF) is a disease characterized mainly by altered exocrine gland function that eventually produces irreversible dysfunction of the pancreas and lungs. The respiratory insufficiency that develops in CF patients in the advanced stages of disease can only be corrected at this time by lung or heart-lung transplantation. We describe our experience with 6 terminal phase CF patients who underwent sequential double lung transplantation (SDLT). Anesthesia was intravenous, with exhaustive hemodynamic and respiratory monitoring. During surgery the most frequently encountered hemodynamic complications were low minute volume, arterial hypotension and irregular heart rate. The main respiratory complications were hypoxemia, hypercapnia and pulmonary edema of the implanted lung, which developed in all cases to varying degrees related to the organ's state of preservation and duration of ischemia. Other complications were the need for extracorporeal circulation in 1 case, oliguria and blood loss requiring multiple transfusions. The most critical moments were at the time of clamping the pulmonary artery, the period after revascularization of the donated lung, and at the start of patient ventilation through the first implanted lung so that the second could be implanted. Although our series is small, it is of interest given the limited Spanish experience with lung transplantation in CF patients, and the good early results obtained, which are similar to those reported for other diseases.

Repeated human leukocyte antigen mismatches in lung re-transplantation.

PubMed

Sommer, Wiebke; Hallensleben, Michael; Ius, Fabio; Kühn, Christian; Tudorache, Igor; Avsar, Murat; Salman, Jawad; Siemeni, Thierry; Greer, Mark; Gottlieb, Jens; Boethig, Dietmar; Blasczyk, Rainer; Haverich, Axel; Warnecke, Gregor

2017-02-01

The role of HLA-sensitization in the absence of detectable DSA in lung re-transplantation is unclear. Antigens of the second donor matching the HLA typing of the first donor are considered 'unacceptable', by some tissue typing laboratories, especially in kidney re-transplantation. Thus, we performed a retrospective analysis of all lung re-transplantations focussing on the impact of HLA-homologies between the first and the second donor ('unacceptable' antigens; repeated HLA mismatch) on patient and graft survival. A total of 132 lung re-transplantations were performed at our centre between 1985 and 2014, of which 120 with complete HLA data were analysed. 55.8% of the recipients received re-transplants with repeated HLA mismatched antigens whereas 43.2% of the re-transplants were transplanted without repeated HLA mismatched antigens. Postoperative survival showed no difference between re-transplant procedures with or without repeated HLA mismatches (p=0.99). While neither homologies on the HLA-A, -B, -C, or -DR locus, nor the addition of several locus homologies (p=0.72) had an impact on survival, unexpectedly, repeated HLA mismatching on the HLA-DQ locus was correlated with better survival. Re-transplantations with repeated HLA mismatches did not result in more development of CLAD as compared to recipients without repeated HLA mismatches (p=0.99). Neither the number of repeated HLA mismatched antigens (p=0.52) nor the HLA locus (HLA-A(p=0.34), HLA-B(p=0.97), HLA-C (p=0.80), HLA-DR(p=0.49) and HLA-DQ(p=0.07)) had an impact on the development of CLAD after re-transplantation. Transplantation with repeated HLA mismatches due to sensitization by a previous transplantation in the absence of detectable HLA-antibodies does not have a negative impact on patient or graft survival. Copyright © 2016 Elsevier B.V. All rights reserved.

Lung transplant

MedlinePlus

... ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 106. Solomon M, Grasemann H, Keshavjee S. Pediatric lung transplantation. Pediatr Clin North Am . 2010;57(2):375-391. PMID: 20371042 www.ncbi.nlm.nih.gov/pubmed/20371042 . Review Date 4/12/2017 Updated by: Mary C. Mancini, MD, ...

Bronchial blood supply after lung transplantation without bronchial artery revascularization.

PubMed

Nicolls, Mark R; Zamora, Martin R

2010-10-01

This review discusses how the bronchial artery circulation is interrupted following lung transplantation and what may be the long-term complications of compromising systemic blood flow to allograft airways. Preclinical and clinical studies have shown that the loss of airway microcirculations is highly associated with the development of airway hypoxia and an increased susceptibility to chronic rejection. The bronchial artery circulation has been highly conserved through evolution. Current evidence suggests that the failure to routinely perform bronchial artery revascularization at the time of lung transplantation may predispose patients to develop the bronchiolitis obliterans syndrome.

Methylene Blue for Vasoplegia When on Cardiopulmonary Bypass During Double-Lung Transplantation.

PubMed

Carley, Michelle; Schaff, Jacob; Lai, Terrance; Poppers, Jeremy

2015-10-15

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.

Carbon monoxide protects rat lung transplants from ischemia-reperfusion injury via a mechanism involving p38 MAPK pathway.

PubMed

Kohmoto, J; Nakao, A; Stolz, D B; Kaizu, T; Tsung, A; Ikeda, A; Shimizu, H; Takahashi, T; Tomiyama, K; Sugimoto, R; Choi, A M K; Billiar, T R; Murase, N; McCurry, K R

2007-10-01

Carbon monoxide (CO) provides protection against oxidative stress via anti-inflammatory and cytoprotective actions. In this study, we tested the hypothesis that a low concentration of exogenous (inhaled) CO would protect transplanted lung grafts from cold ischemia-reperfusion injury via a mechanism involving the mitogen-activated protein kinase (MAPK) signaling pathway. Lewis rats underwent orthotopic syngeneic or allogeneic left lung transplantation with 6 h of cold static preservation. Exposure of donors and recipients (1 h before and then continuously post-transplant) to 250 ppm CO resulted in significant improvement in gas exchange, reduced leukocyte sequestration, preservation of parenchymal and endothelial cell ultrastructure and reduced inflammation compared to animals exposed to air. The beneficial effects of CO were associated with p38 MAPK phosphorylation and were significantly prevented by treatment with a p38 MAPK inhibitor, suggesting that CO's efficacy is at least partially mediated by activation of p38 MAPK. Furthermore, CO markedly suppressed inflammatory events in the contralateral naïve lung. This study demonstrates that perioperative exposure of donors and recipients to CO at a low concentration can impart potent anti-inflammatory and cytoprotective effects in a clinically relevant model of lung transplantation and support further evaluation for potential clinical use.

[What the family doctor must know about lung transplantation. Complications, health promotion, and outcomes (Part 2)].

PubMed

Zurbano, L; Zurbano, F

2017-10-01

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. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Burkholderia cepacia, cystic fibrosis and outcomes following lung transplantation: experiences from a single center in Brazil.

PubMed

de Souza Carraro, Danila; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Iuamoto, Leandro Ryuchi; Braga, Karina Andrighetti de Oliveira; Oliveira, Lea Campos de; Sabino, Ester Cerdeira; Rossi, Flavia; Pêgo-Fernandes, Paulo Manuel

2018-03-12

To evaluate the impact of Burkholderia cepacia complex colonization in cystic fibrosis patients undergoing lung transplantation. We prospectively analyzed clinical data and respiratory tract samples (sputum and bronchoalveolar lavage) collected from suppurative lung disease patients between January 2008 and November 2013. We also subtyped different Burkholderia cepacia complex genotypes via DNA sequencing using primers against the recA gene in samples collected between January 2012 and November 2013. From 2008 to 2013, 34 lung transplants were performed on cystic fibrosis patients at our center. Burkholderia cepacia complex was detected in 13 of the 34 (38.2%) patients. Seven of the 13 (53%) strains were subjected to genotype analysis, from which three strains of B. metallica and four strains of B. cenocepacia were identified. The mortality rate was 1/13 (7.6%), and this death was not related to B. cepacia infection. The results of our study suggest that colonization by B. cepacia complex and even B. cenocepacia in patients with cystic fibrosis should not be considered an absolute contraindication to lung transplantation in Brazilian centers.

Local allocation of lung donors results in transplanting lungs in lower priority transplant recipients.

PubMed

Russo, Mark J; Meltzer, David; Merlo, Aurelie; Johnson, Elizabeth; Shariati, Nazly M; Sonett, Joshua R; Gibbons, Robert

2013-04-01

Under the current lung allocation system, if organs are accepted for a candidate within the local donor service area (DSA), they are never offered to candidates at the broader regional level who are potentially more severely ill, even if the nonlocal candidate has a higher lung allocation score (LAS). The purpose of this study was to determine the frequency with which organs were allocated to a local lung recipient while a blood group-matched and size-matched candidate with a higher LAS existed in the same region. United Network for Organ Sharing (UNOS) provided deidentified patient-level data. The study population included all locally allocated organs for double-lung transplants (DLTs) performed in 2009 in the United States (n=580). All occurrences of an ABO blood group-matched, height-matched (±10 cm), double-lung candidate in the same region, with a higher LAS than the local candidate who actually received the organs, were calculated; these occurrences were termed events. In 2009, 3,454 events occurred when a local DLT recipient candidate received a DLT while a DLT candidate in the same region had a higher LAS. With a mean of 5.96 events per transplant, this impacted 480 (82.8%) of the 580 DLTs. Further, 555 (16.1%) of these events involved 1 (or more) of the 185 regional candidates who ultimately did not receive transplants and died while on the waiting list. This analysis suggests that the locally based lung allocation system results in a high frequency of events whereby an organ is allocated to a lower-priority candidate while an appropriately matched higher priority candidate exists regionally. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Lung transplant of extrahospitalary donor after cardiac death.

PubMed

Mateos Rodríguez, Alonso A; Navalpotro Pascual, José Maria; del Río Gallegos, Francisco

2013-04-01

Non-heart-beating donors (NHBDs) have to meet the predefined criteria for organ donation including death from irreversible cessation of the beating heart. The Maastricht conference defined 4 NHBD categories to differentiate their viability and ethical-legal support. In Spain, NHBDs who originate from an out-of-hospital setting correspond to type II donors. These are patients who have had a cardiac arrest outside hospital and, after failed CPR attempts, are transferred with hemodynamic support measures to the hospital for organ donation. The Hospital Clínico San Carlos also has a lung donation program in collaboration with the Hospital Puerta de Hierro in Madrid and the Hospital Marques de Valdecilla in Santander. The objective of this study is to describe the results of lung transplantation of after cardiac death program, specifically the section regarding lung extraction donation. Twenty potential lung donors were obtained during the study. Most patients were male (19 cases), with a mean age of 42 years (36.5-49.5 years). A total of 33 lungs were donated (18 right and 15 left lungs). Most extractions were multiorganic (19 cases). One liver, 19 kidneys, 2 pancreas, and 19 corneas were obtained from these donors; bone tissue was obtained from all donors. The transplantation was bipulmonary in 13 cases and unipulmonary in 7. Thirty days after transplantation, 2 recipients died, 1 died of stroke associated with bilateral pneumonia and 1 died of hypovolemic shock resulting from hemothorax. The remaining 18 patients were progressing well at 30 days. Our data suggest that lung transplantation from patients after extrahospitalary cardiac death is feasible. Copyright © 2013 Elsevier Inc. All rights reserved.

Low-flow venovenous CO₂ removal in association with lung protective ventilation strategy in patients who develop severe progressive respiratory acidosis after lung transplantation.

PubMed

Ruberto, F; Bergantino, B; Testa, M C; D'Arena, C; Zullino, V; Congi, P; Paglialunga, S G; Diso, D; Venuta, F; Pugliese, F

2013-09-01

Primary graft dysfunction (PGD) might occur after lung transplantation. In some severe cases, conventional therapies like ventilatory support, administration of inhaled nitric oxide (iNO), and intravenous prostacyclins are not sufficient to provide an adequate gas exchange. The aim of our study was to evaluate the use of a lung protective ventilation strategy associated with a low-flow venovenous CO2 removal treatment to reduce ventilator-associated injury in patients that develop severe PGD after lung transplantation. From January 2009 to January 2011, 3 patients developed PGD within 24 hours after lung transplantation. In addition to conventional medical treatment, including hemodynamic support, iNO and prostaglandin E1 (PGE1), we initiated a ventilatory protective strategy associated with low-flow venovenous CO2 removal treatment (LFVVECCO2R). Hemodynamic and respiratory parameters were assessed at baseline as well as after 3, 12, 24, and 48 hours. No adverse events were registered. Despite decreased baseline elevated pulmonary positive pressures, application of a protective ventilation strategy with LFVVECCO2R reduced PaCO2 and pulmonary infiltrates as well as increased pH values and PaO2/FiO2 ratios. Every patient showed simultaneous improvement of clinical and hemodynamic conditions. They were weaned from mechanical ventilation and extubated after 24 hours after the use of the low-flow venovenous CO2 removal device. The use of LFVVECCO2R together with a protective lung ventilation strategy during the perioperative period of lung transplantation may be a valid clinical strategy for patients with PGD and severe respiratory acidosis occured despite adequate mechanical ventilation. Copyright © 2013 Elsevier Inc. All rights reserved.

Inhibition of the purinergic pathway prolongs mouse lung allograft survival.

PubMed

Liu, Kaifeng; Vergani, Andrea; Zhao, Picheng; Ben Nasr, Moufida; Wu, Xiao; Iken, Khadija; Jiang, Dawei; Su, Xiaofeng; Fotino, Carmen; Fiorina, Paolo; Visner, Gary A

2014-08-01

Lung transplantation has limited survival with current immunosuppression. ATP is released from activated T cells, which act as costimulatory molecules through binding to the purinergic receptor P2XR7. We investigated the role of blocking the ATP/purinergic pathway, primarily P2XR7, using its inhibitor oxidized ATP (oATP) in modulating rejection of mouse lung allografts. Mouse lung transplants were performed using mice with major histocompatibility complex mismatch, BALB/c to C57BL6. Recipients received suramin or oATP, and lung allografts were evaluated 15 to ≥ 60 days after transplantation. Recipients were also treated with oATP after the onset of moderate to severe rejection to determine its ability to rescue lung allografts. Outcomes measures included lung function, histology, thoracic imaging, and allo-immune responses. Blocking purinergic receptors with the nonselective inhibitor suramin or with the P2XR7-selective inhibitor oATP reduced acute rejection and prolonged lung allograft survival for ≥ 60 days with no progression in severity. There were fewer inflammatory cells within lung allografts, less rejection, and improved lung function, which was maintained over time. CD4 and CD8 T cells were reduced within lung allografts with impaired activation with prolonged impairment of CD8 responses. In vitro, oATP reduced CD8 activation of Th1 inflammatory cytokines IFN-γ and TNF-α and cytolytic machinery, granzyme B. Cotreatment with immunosuppressive agents, cyclosporine, rapamycin, or CTLA-4Ig resulted in no additive benefits, and oATP alone resulted in better outcomes than cyclosporine alone. This study illustrates a potential new pathway to target in hopes of prolonging survival of lung transplant recipients.

Attained Functional Status Moderates Survival Outcomes of Return to Work After Lung Transplantation.

PubMed

Tumin, Dmitry; Kirkby, Stephen E; Tobias, Joseph D; Hayes, Don

2016-06-01

Returning to work is a desirable outcome of lung transplantation that is selective on attained functional status. Survival implications of post-transplant employment are unclear. The United Network for Organ Sharing registry was queried for first-time lung transplants performed from May 2005 to March 2015 in patients ages 18-64. Attainment of normal functional status post-transplant, defined as a 100 % score on the Karnofsky Performance Scale (KPS), was examined as moderating 5-year survival outcomes of work resumption, using Cox proportional hazards models. Supplemental analysis examined attainment of forced expiratory volume in 1 s (FEV1) ≥80 % predicted as moderating survival implications of post-transplant employment. Of 10,066 patients, 1824 (18 %) returned to work, while 9078 contributed follow-up data on functional status. Multivariable analysis demonstrated a protective effect of work resumption among patients who did not attain normal functional status before returning to work (HR = 0.62; 95 % CI = 0.51, 0.76; p < 0.001). This association was attenuated among transplant recipients who reached 100 % KPS while still unemployed (p < 0.001). Similarly, post-transplant survival was favorably associated with 5-year survival among patients who did not attain at least 80 % predicted FEV1 before returning to work (HR = 0.71; 95 % CI = 0.59, 0.86; p < 0.001). Early return to work after lung transplantation may benefit patients experiencing mild functional limitations. Timing the resumption of employment to coincide with attainment of maximal functional status around 1 year post transplant should be considered.

Balancing rejection and infection with respect to age, race, and gender: clues acquired from 17 years of cardiac transplantation data.

PubMed

George, James F; Pamboukian, Salpy V; Tallaj, José A; Naftel, David C; Myers, Susan L; Foushee, Margaret T; Brown, Robert N; Pajaro, Octavio E; McGiffin, David C; Kirklin, James K

2010-09-01

Donor and recipient risk factors for rejection and infection have been well characterized. The contribution of demographic factors, especially age at the time of transplantation to morbidity and mortality due to rejection and infection, is much less well understood. Using parametric hazard analysis and multivariate risk-factor equations for infection and rejection events, we quantitatively determined the relationship of fundamental demographic variables (age, race and gender) to infection and rejection. These analyses were conducted with respect to date of transplant and age at the time of transplantation. The patient group consisted of all primary heart transplants performed at the University of Alabama at Birmingham during the years 1990 to 2007 (n = 526). Risk factors for rejection within 12 months post-transplantation were date of transplant (p < 0.0001) and age at the time of transplantation (young adults 10 to 30 years of age, p < 0.0001). Risk factors for infection were date of transplant (p < 0.0001) and age at the time of transplantation (young children and older adults, p < 0.0001). There were three immunosuppressive eras in 1990 to 2007. Notably, although the proportion of patients experiencing rejection and infection events decreased during each successive immunosuppressive era, the relative relationship of infection to rejection, as well as age at the time of transplantation, remained similar into the most recent era. The maximal frequency of rejection events and rejection death occurred among patients transplanted at ages 10 to 30 years. Conversely, the frequency of infection events was minimal within the same group. In the oldest and youngest patients receiving transplants, infection was the predominant cause of death and rates of rejection events decreased. These data show that evolving immunosuppressive strategies have successfully reduced rejection and infection frequencies, and those patients transplanted at 30 to 60 years of age have the lowest frequency of rejection/infection events. However, individuals transplanted at younger or older ages, especially non-white recipients in the 10- to 30-year age group, experience significantly more infection or rejection. Therefore, programs should increase the level of surveillance in these patients and consider modification of immunosuppressive regimens in order to lower the frequency of infection and rejection events. Copyright 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Pre-lung transplant measures of reflux on impedance are superior to pH testing alone in predicting early allograft injury

PubMed Central

Lo, Wai-Kit; Burakoff, Robert; Goldberg, Hilary J; Feldman, Natan; Chan, Walter W

2015-01-01

AIM: To evaluate pre-lung transplant acid reflux on pH-testing vs corresponding bolus reflux on multichannel intraluminal impedance (MII) to predict early allograft injury. METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined MII-pH-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-pH testing and early allograft injury. Area under the receiver operating characteristic (ROC) curve (c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six pH-testing parameters and their corresponding MII measures were specified a priori. The pH parameters were upright, recumbent, and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright, recumbent, and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time. RESULTS: Thirty-two subjects (47% men, mean age: 55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis (46.9%) represented the most common pulmonary diagnosis leading to transplantation. Baseline demographics, pre-transplant cardiopulmonary function, number of lungs transplanted (unilateral vs bilateral), and post-transplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve, or c-statistic, of each acid reflux parameter on pre-transplant pH-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition, the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux: overall reflux exposure (HR = 1.18, 95%CI: 1.01-1.36, P = 0.03), recumbent reflux exposure (HR = 1.25, 95%CI: 1.04-1.50, P = 0.01) and bolus clearance (HR = 1.09, 95%CI: 1.01-1.17, P = 0.02), but not with any pH-testing parameter measuring acid reflux alone. CONCLUSION: Pre-transplant MII measures of bolus reflux perform better than their pH-testing counterparts in predicting early allograft injury post-lung transplantation. PMID:26290637

Donation after cardiac death: a 29-year experience.

PubMed

Bellingham, Janet M; Santhanakrishnan, Chandrasekar; Neidlinger, Nikole; Wai, Philip; Kim, Jim; Niederhaus, Silke; Leverson, Glen E; Fernandez, Luis A; Foley, David P; Mezrich, Joshua D; Odorico, Jon S; Love, Robert B; De Oliveira, Nilto; Sollinger, Hans W; D'Alessandro, Anthony M

2011-10-01

To report the long-term outcomes of 1218 organs transplanted from donation after cardiac death (DCD) donors from January 1980 through December 2008. One-thousand two-hundred-eighteen organs were transplanted into 1137 recipients from 577 DCD donors. This includes 1038 kidneys (RTX), 87 livers (LTX), 72 pancreas (PTX), and 21 DCD lungs. The outcomes were compared with 3470 RTX, 1157 LTX, 903 PTX, and 409 lung transplants from donors after brain death (DBD). Both patient and graft survival is comparable between DBD and DCD transplant recipients for kidney, pancreas, and lung after 1, 3, and 10 years. Our findings reveal a significant difference for patient and graft survival of DCD livers at each of these time points. In contrast to the overall kidney transplant experience, the most recent 16-year period (n = 396 DCD and 1,937 DBD) revealed no difference in patient and graft survival, rejection rates, or surgical complications but delayed graft function was higher (44.7% vs 22.0%; P < .001). In DCD LTX, biliary complications (51% vs 33.4%; P < .01) and retransplantation for ischemic cholangiopathy (13.9% vs 0.2%; P < .01) were increased. PTX recipients had no difference in surgical complications, rejection, and hemoglobin A1c levels. Surgical complications were equivalent between DCD and DBD lung recipients. This series represents the largest single center experience with more than 1000 DCD transplants and given the critical demand for organs, demonstrates successful kidney, pancreas, liver, and lung allografts from DCD donors. Copyright © 2011 Mosby, Inc. All rights reserved.

The Presence of Pretransplant HLA Antibodies Does Not Impact the Development of Chronic Lung Allograft Dysfunction or CLAD-Related Death.

PubMed

Zazueta, Oscar E; Preston, Sara E; Moniodis, Anna; Fried, Sabrina; Kim, Miae; Townsend, Keri; Wood, Isabelle; Boukedes, Steve; Guleria, Indira; Camp, Phillip; El-Chemaly, Souheil; Rosas, Ivan O; Chandraker, Anil; Milford, Edgar; Goldberg, Hilary J

2017-09-01

Development of donor-specific antibodies (DSA) after lung transplantation is associated with antibody mediated rejection, acute cellular rejection, and bronchiolitis obliterans syndrome; however, the significance of circulating antibodies before transplant remains unclear. We performed a retrospective cohort study including recipients of primary lung transplants between 2008 and 2012. We assessed the impact of circulating HLA and noncytotoxic DSA detected before transplant on development of Chronic Lung Allograft Dysfunction (CLAD) or CLAD-related death. 30% of subjects had circulating class I antibodies alone, 4% Class II, and 14.4% class I and class II at mean fluorescent intensity greater than 1000. Nine percent of the subjects had DSA class I, 9% class II, and 2.4% both DSA classes 1 and 2. Neither the presence of circulating antibodies (adjusted hazard ratio, 0.87; 95% confidence interval, 0.50-1.54) nor the presence of DSA (adjusted hazard ratio, 1.56; 95% confidence interval, 0.77-3.18) before transplant at mean fluorescent intensity greater than 1000 was associated with the development of CLAD or CLAD-related death. Although in previous studies we have shown an increased incidence of antibody-mediated rejection in patients with pretransplant DSA, neither the presence of HLA antibodies nor DSA translated to an increased risk of allograft dysfunction or death if prospective crossmatch testing was negative. Prospective studies are needed to define the impact of pretransplant sensitization on lung transplant recipients.

Fatal disseminated Rasamsonia infection in cystic fibrosis post-lung transplantation.

PubMed

Hong, Gina; White, Marissa; Lechtzin, Noah; West, Natalie E; Avery, Robin; Miller, Heather; Lee, Richard; Lovari, Robert J; Massire, Christian; Blyn, Lawrence B; Liang, Xinglun; Sutton, Deanna A; Fu, Jianmin; Wickes, Brian L; Wiederhold, Nathan P; Zhang, Sean X

2017-03-01

Disseminated fungal infections are a known serious complication in individuals with cystic fibrosis (CF) following orthotopic lung transplantation. Aspergillus fumigatus and Scedosporium species are among the more common causes of invasive fungal infection in this population. However, it is also important for clinicians to be aware of other emerging fungal species which may require markedly different antifungal therapies. We describe the first laboratory-documented case of a fatal disseminated fungal infection caused by Rasamsonia aegroticola in a 21-year-old female CF patient status post-bilateral lung transplantation, which was only identified post-mortem. Molecular analysis revealed the presence of the identical Rasamsonia strains in the patient's respiratory cultures preceding transplantation. We propose that the patient's disseminated fungal disease and death occurred as a result of recrudescence of Rasamsonia infection from her native respiratory system in the setting of profound immunosuppression post-operatively. Since Rasamsonia species have been increasingly recovered from the respiratory tract of CF patients, we further review the literature on these fungi and discuss their association with invasive fungal infections in the CF lung transplant host. Our report suggests Rasamsonia species may be important fungal pathogens that may have fatal consequences in immunosuppressed CF patients after solid organ transplantation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Tissue-associated self-antigens containing exosomes: Role in allograft rejection.

PubMed

Sharma, Monal; Ravichandran, Ranjithkumar; Bansal, Sandhya; Bremner, Ross M; Smith, Michael A; Mohanakumar, T

2018-06-15

Exosomes are extracellular vesicles that express self-antigens (SAgs) and donor human leukocyte antigens. Tissue-specific exosomes can be detected in the circulation following lung, heart, kidney and islet cell transplantations. We collected serum samples from patients who had undergone lung (n = 30), heart (n = 8), or kidney (n = 15) transplantations to isolate circulating exosomes. Exosome purity was analyzed by Western blot, using CD9 exosome-specific markers. Tissue-associated lung SAgs, collagen V (Col-V) and K-alpha 1 tubulin (Kα1T), heart SAgs, myosin and vimentin, and kidney SAgs, fibronectin and collagen IV (Col-IV), were identified using western blot. Lung transplant recipients diagnosed with bronchiolitis obliterans syndrome had exosomes with higher expression of Col-V (4.2-fold) and Kα1T (37.1-fold) than stable. Exosomes isolated from heart transplant recipients diagnosed with coronary artery vasculopathy had a 3.9-fold increase in myosin and a 4.7-fold increase in vimentin compared with stable. Further, Kidney transplant recipients diagnosed with transplant glomerulopathy had circulating exosomes with a 2-fold increased expression of fibronectin and 2.5-fold increase in Col-IV compared with stable. We conclude that circulating exosomes with tissue associated SAgs have the potential to be a noninvasive biomarker for allograft rejection. Copyright © 2018. Published by Elsevier Inc.

Suicidal hanging donors for lung transplantation: Is this chapter still closed? Midterm experience from a single center in United Kingdom.

PubMed

Ananiadou, Olga; Schmack, Bastian; Zych, Bartlomiej; Sabashnikov, Anton; Garcia-Saez, Diana; Mohite, Prashant; Weymann, Alexander; Mansur, Ashham; Zeriouh, Mohamed; Marczin, Nandor; De Robertis, Fabio; Simon, Andre Rüdiger; Popov, Aron-Frederik

2018-04-01

In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group.Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed.No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P < .001, P = .022 and P = .0042, respectively). Recipient preoperative and perioperative characteristics were comparable. Postoperatively in group 1 there was a higher incidence of extracorporeal life support (27.3 vs 9.1%, P = .019). There were no significant differences in chronic lung allograft dysfunction-free survival between group 1 and 2: 92.3 vs 94% at 1 year and 65.9 vs 75.5% at 3 years (P = .99). The estimated cumulative survival rate was also similar between groups: 68.2 vs 83.2% at 1 year and 68.2% versus 72% at 3 years (P = .3758).Hanging as a donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation.

Recipient-Matching of Passenger Leukocytes Prolongs Survival of Donor Lung Allografts in Miniature Swine

PubMed Central

Madariaga, Maria Lucia L.; Michel, Sebastian G.; La Muraglia, Glenn M.; Sihag, Smita; Leonard, David A.; Farkash, Evan A.; Colvin, Robert B.; Cetrulo, Curtis L.; Huang, Christene A.; Sachs, David H.; Madsen, Joren C.; Allan, James S.

2014-01-01

Background Allograft rejection continues to be a vexing problem in clinical lung transplantation, and the role played by passenger leukocytes in the rejection or acceptance of an organ is unclear. Here we tested whether recipient-matching of donor graft passenger leukocytes would impact graft survival in a preclinical model of orthotopic left lung transplantation. Methods In the experimental group (Group 1), donor lungs were obtained from chimeric swine, in which the passenger leukocytes (but not the parenchyma) were MHC-matched to the recipients (n=3). In the control group (Group 2), both the donor parenchyma and the passenger leukocytes were MHC-mismatched to the recipients (n = 3). Results Lungs harvested from swine previously rendered chimeric by hematopoietic stem cell transplantation using recipient-type cells showed a high degree of passenger leukocyte chimerism by immunohistochemistry and flow cytometry. The chimeric lungs containing passenger leukocytes matched to the lung recipient (Group 1) survived on average 107 days (range 80–156). Control lung allografts (Group 2) survived on average 45 days (range 29–64; p<0.05). Conclusion Our data indicate that recipient-matching of passenger leukocytes significantly prolongs lung allograft survival. PMID:25757217

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

PubMed

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

2016-04-26

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

Immune mechanisms in the pathogenesis of bronchiolitis obliterans syndrome after lung transplantation.

PubMed

Jaramillo, Andrés; Fernández, Félix G; Kuo, Elbert Y; Trulock, Elbert P; Patterson, G A; Mohanakumar, T

2005-02-01

Lung transplantation is recognized as the only viable treatment option in a variety of end-stage pulmonary diseases. However, the long-term survival after lung transplantation is limited by the development of obliterative bronchiolitis, and its clinical correlate bronchiolitis obliterans syndrome (BOS), which is considered to represent chronic lung allograft rejection. Histopathologically, BOS is an inflammatory process that leads to fibrous scarring of the terminal and respiratory bronchioles and subsequent total occlusion of the airways. The specific etiology and pathogenesis of BOS are not well understood. The current premise is that BOS represents a common lesion in which different inflammatory insults such as ischemia-reperfusion, rejection, and infection can lead to a similar histological and clinical outcome. However, the low incidence of BOS in non-transplanted individuals and the observation that early development of BOS is predicted by the frequency and severity of acute rejection episodes indicate that alloimmune-dependent mechanisms play a crucial role in the pathogenesis of BOS. The evidence presented in this review indicates that BOS is the result of humoral and cellular immune responses developed against major histocompatibility complex molecules expressed by airway epithelial cells of the lung allograft. This process is aggravated by alloimmune-independent mechanisms such as ischemia-reperfusion and infection. Currently, treatment of BOS is frequently unsuccessful. Therefore, a better understanding of the immunopathogenesis of BOS is of paramount importance toward improving long-term patient and graft survival after lung transplantation.

Lung transplantation for emphysema: impact of age on short- and long-term survival.

PubMed

Inci, Ilhan; Schuurmans, Macé; Ehrsam, Jonas; Schneiter, Didier; Hillinger, Sven; Jungraithmayr, Wolfgang; Benden, Christian; Weder, Walter

2015-12-01

Overall, emphysema (EMP) is the most common indication for lung transplantation. The majority of patients present with chronic obstructive pulmonary disease (COPD) and less frequently with alpha-1 antitrypsin deficiency (A1ATD). We analysed the results of lung transplants performed for EMP in order to identify the impact of age on short- and long-term outcome. A retrospective analysis was undertaken of the 108 consecutive lung transplants for EMP performed at our institution from November 1992 to August 2013 (77 COPD, 31 A1ATD). Retransplantations were excluded. The median age was 56 years (range 31-68). Thirty-day mortality rate was 3.7%. One- and 5-year survival rates in COPD and A1ATD recipients were comparable (P = 0.8). The 1- and 5-year survival rates for recipients aged <60 years old were significantly better than the age group of ≥60 years (91 and 79 vs 84 and 54%, P = 0.05). Since 2007, the 1- and 5-year survival for these two age groups were 96 and 92 vs 86 and 44%, respectively, P = 0.04, log-rank test). For the following parameters, we were not able to find any difference to affect survival rates: use of intraoperative extracorporeal membrane oxygenation, waiting list time, sex, graft size reduction, body mass index and diagnosis. In multivariate analysis, age at transplantation (≥60 years old) (HR 2.854; 95% confidence interval (CI) 1.338-6.08, P = 0.008) and unilateral lung transplantation (HR 15.2; 95% CI 3.2-71.9, P = 0.009) were independent risk factors for mortality. COPD and A1ATD recipients have similar overall long-term survival. Recipients aged ≥60 years and unilateral lung transplants were risk factors for mortality. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds

NASA Astrophysics Data System (ADS)

Wu, Tsai-Jung; Tzeng, Yan-Kai; Chang, Wei-Wei; Cheng, Chi-An; Kuo, Yung; Chien, Chin-Hsiang; Chang, Huan-Cheng; Yu, John

2013-09-01

Lung stem/progenitor cells are potentially useful for regenerative therapy, for example in repairing damaged or lost lung tissue in patients. Several optical imaging methods and probes have been used to track how stem cells incorporate and regenerate themselves in vivo over time. However, these approaches are limited by photobleaching, toxicity and interference from background tissue autofluorescence. Here we show that fluorescent nanodiamonds, in combination with fluorescence-activated cell sorting, fluorescence lifetime imaging microscopy and immunostaining, can identify transplanted CD45-CD54+CD157+ lung stem/progenitor cells in vivo, and track their engraftment and regenerative capabilities with single-cell resolution. Fluorescent nanodiamond labelling did not eliminate the cells' properties of self-renewal and differentiation into type I and type II pneumocytes. Time-gated fluorescence imaging of tissue sections of naphthalene-injured mice indicates that the fluorescent nanodiamond-labelled lung stem/progenitor cells preferentially reside at terminal bronchioles of the lungs for 7 days after intravenous transplantation.

Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation: A Mechanism in Chronic Lung Allograft Dysfunction.

PubMed

Borthwick, L A; Suwara, M I; Carnell, S C; Green, N J; Mahida, R; Dixon, D; Gillespie, C S; Cartwright, T N; Horabin, J; Walker, A; Olin, E; Rangar, M; Gardner, A; Mann, J; Corris, P A; Mann, D A; Fisher, A J

2016-06-01

Bacterial infections after lung transplantation cause airway epithelial injury and are associated with an increased risk of developing bronchiolitis obliterans syndrome. The damaged epithelium is a source of alarmins that activate the innate immune system, yet their ability to activate fibroblasts in the development of bronchiolitis obliterans syndrome has not been evaluated. Two epithelial alarmins were measured longitudinally in bronchoalveolar lavages from lung transplant recipients who developed bronchiolitis obliterans syndrome and were compared to stable controls. In addition, conditioned media from human airway epithelial cells infected with Pseudomonas aeruginosa was applied to lung fibroblasts and inflammatory responses were determined. Interleukin-1 alpha (IL-1α) was increased in bronchoalveolar lavage of lung transplant recipients growing P. aeruginosa (11.5 [5.4-21.8] vs. 2.8 [0.9-9.4] pg/mL, p < 0.01) and was significantly elevated within 3 months of developing bronchiolitis obliterans syndrome (8.3 [1.4-25.1] vs. 3.6 [0.6-17.1] pg/mL, p < 0.01), whereas high mobility group protein B1 remained unchanged. IL-1α positively correlated with elevated bronchoalveolar lavage IL-8 levels (r(2)  = 0.6095, p < 0.0001) and neutrophil percentage (r(2)  = 0.25, p = 0.01). Conditioned media from P. aeruginosa infected epithelial cells induced a potent pro-inflammatory phenotype in fibroblasts via an IL-1α/IL-1R-dependent signaling pathway. In conclusion, we propose that IL-1α may be a novel therapeutic target to limit Pseudomonas associated allograft injury after lung transplantation. © Copyright 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

Mycobacterium abscessus infection in transplant recipients.

PubMed

Morales, P; Gil, A; Santos, M

2010-10-01

Mycobacterium abscessus is a ubiquitous, rapidly growing mycobacterium that colonizes organic surfaces. It is a potential pathogen, especially in immunosuppressed patients, including transplant recipients in whom disease can range from localized cutaneous lesions to disseminated infections. The purpose of this study was to describe the 12-year impact from January 1997 to December 2009 of M. abscessus infection among solid organ and bone marrow transplantations performed in adults and children. Information was obtained from the database of our Microbiology Department concerning samples, culture methods, and in vitro susceptibility testing. Isolates were classified as contaminants (C), colonization (CL), or disease (D) following standard criteria. We reviewed the medical records of affected subjects. M abscessus was isolated in 76 patients (28 C, 18 CL, and 30 D), including 11 recipients, namely 8 (73%) classified as disease displaying 1 bone marrow case and solid organ cases--4 (50%) pulmonary (2 after cystic fibrosis), 2 renal, and 1 heart transplant patients. All were adults. The localization of infection showed 2 disseminated cases, both of whom shows cutaneous primary lesions, and 6 localized in 3 cases cutaneous and in 3, respiratory. Diseases caused by M abscessus have increased in the last 5 years, possibly due to the greater number of transplants and the more focused search for the lesions. Most isolates were from lung cases, especially those with infections prior to transplantation. Respiratory and cutaneous samples were predominant, with skin lesions being an important site of primary symptom previous to dissemination of infection. Although the optimal regimen remains undefined, a favorable outcome depended mainly on a rapid diagnosis and inception of treatment following susceptibility test results. Copyright © 2010 Elsevier Inc. All rights reserved.

Combined double lung-liver transplantation for cystic fibrosis without cardio-pulmonary by-pass.

PubMed

Corno, V; Dezza, M C; Lucianetti, A; Codazzi, D; Carrara, B; Pinelli, D; Parigi, P C; Guizzetti, M; Strazzabosco, M; Melzi, M L; Gaffuri, G; Sonzogni, V; Rossi, A; Fagiuoli, S; Colledan, M

2007-10-01

Sequential bilateral single lung-liver transplantation (SBSL-LTx) is a therapeutic option for patients with end stage lung and liver disease (ESLLD) due to cystic fibrosis (CF). A few cases have been reported, all of them were performed with the use of cardio-pulmonary by-pass (CPB). We performed SBSL-LTx in three young men affected by CF. All the recipients had respiratory failure and portal hypertension with hypersplenism. Along with lung transplants, two patients received a whole liver graft and one an extended right graft from an in situ split liver. During transplantation neither CPB nor veno-venous by-pass (VVB) were employed. Immunosuppression was based on basiliximab, tacrolimus, steroids and azathioprine. The three recipients are alive with a median follow-up of 670 days (range 244-1,533). Combined SBSL-LTx is a complex but effective procedure for the treatment of ESLLD due to CF, not necessarily requiring the use of CPB or VVB.

The clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation.

PubMed

Mizota, Toshiyuki; Matsukawa, Shino; Fukagawa, Hiroshi; Daijo, Hiroki; Tanaka, Tomoharu; Chen, Fengshi; Date, Hiroshi; Fukuda, Kazuhiko

2015-08-01

We examined the clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation (post-HSCT), focusing on ventilatory management. We aimed to determine the incidence of oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction in post-HSCT lung transplant recipients, and to explore factors associated with their development. Nineteen consecutive patients who underwent lung transplantation post-HSCT at Kyoto University Hospital (Japan) were retrospectively studied. Data regarding patient characteristics, preoperative examination, and clinical course during anesthetic induction were analyzed. The incidence of oxygen desaturation (SpO2 < 90 %) during anesthetic induction and severe respiratory acidosis (pH < 7.2) after anesthetic induction were 21.1 and 26.3 %, respectively. Reduced dynamic compliance (Cdyn) during mechanical ventilation was significantly associated with oxygen desaturation during anesthetic induction (p = 0.01), as well as severe respiratory acidosis after anesthetic induction (p = 0.01). The preoperative partial pressure of carbon dioxide in arterial blood (PaCO2; r = -0.743, p = 0.002) and body mass index (BMI; r = 0.61, p = 0.021) significantly correlated with Cdyn, and multivariate analysis revealed that both PaCO2 and BMI were independently associated with Cdyn. Oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction frequently occur in post-HSCT lung transplant recipients. Low Cdyn may, at least partially, explain oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction. Moreover, preoperative hypercapnia and low BMI were predictive of low Cdyn.

Decrease of Airway Allergies After Lung Transplantation Is Associated With Reduced Basophils and Eosinophils.

PubMed

Niedzwiecki, M; Yamada, Y; Inci, I; Weder, W; Jungraithmayr, W

2016-01-01

Allergies are hypersensitive reactions of the immune system on antigen exposure similar to immune reactions after transplantation (Tx). Their activity can change after Tx. The lung as a transplantable organ is challenged two-fold, by antigens from the blood and the air environment. Herein we analyzed if airway allergies change after lung Tx. We systematically reviewed patients' airway allergies before and after lung Tx between 1992 and 2014. The course of lymphocytes, thrombocytes, and leukocytes, among them neutrophils, eosinophils, and basophils, was analyzed in patients in whom airway allergies have changed and in whom they did not change. From 362 lung transplanted patients, 44 patients had suffered from allergies before Tx (12.2%). In 20 of these patients (45.5%), airway allergies disappeared completely within 1 year after lung Tx and were persistently absent thereafter. In these patients, basophils and eosinophils decreased significantly (P < .0012); in contrast, cells did not decrease in patients whose allergies did not disappear. Leukocytes overall, and in particular, neutrophils, decreased significantly in patients whose allergy disappeared (P < .014, P < .012, respectively). Airway allergies disappeared in almost half of cases after lung Tx. Along with this reduction, basophils and eosinophils decreased as potentially responsible cells for this phenomenon. These findings may stimulate intensified research on basophils and eosinophils as major drivers of airway allergies. Copyright © 2016 Elsevier Inc. All rights reserved.

The depletion of donor macrophages reduces ischaemia-reperfusion injury after mouse lung transplantation.

PubMed

Tsushima, Yukio; Jang, Jae-Hwi; Yamada, Yoshito; Schwendener, Reto; Suzuki, Kenji; Weder, Walter; Jungraithmayr, Wolfgang

2014-04-01

Macrophages (M) are one of the most important cells of the innate immune system for first line defense. Upon transplantation (Tx), M play a prominent role during lung ischaemia reperfusion (I/R) injury. Here, we hypothesize that the depletion of donor M ameliorates the post-transplant lung I/R injury. Orthotopic single-lung Tx was performed between syngeneic BALB/c mice after a cold ischaemic time of 8 h and a reperfusion time of 10 h. Prior to graft implantation, alveolar macrophages of donor lungs were selectively depleted applying the 'suicide technique' by intratracheal application of clodronate liposomes (experimental, n = 6) vs the application of empty liposomes (control, n = 6). Cell count (number of F4/80(+)-macrophages) and graft injury were evaluated by histology and immunohistochemistry, and levels of lactat dehydrogenase (LDH) (apoptosis assay), enzyme linked immunosorbent assay for nuclear protein high-mobility-group-protein B1 (HMGB1), tumor necrosis factor alpha (TNF-α) and transforming growth factor beta1 (TGF-β1) in plasma were analysed. Clodronate liposomes successfully reduced 70% of M from donor lungs when compared with grafts treated with empty liposome only. M-depleted transplants showed improved histology and revealed considerably less graft damage when compared with control recipients (LDH, P = 0.03; HMGB1, P = 0.3). Oxygenation capacity was ameliorated in M-depleted transplants, if not significant (P = 0.114); however, wet/dry ratio did not differ between groups (P = 0.629). The inflammatory response was significantly reduced in M-depleted mice when compared with control recipients (TNF-α, P = 0.042; TGF-β1, P = 0.039). The selective depletion of M in donor lung transplants can be successfully performed and results in a sustained anti-inflammatory response upon I/R-injury. The beneficial effect of this preconditioning method should be further evaluated as a promising tool for the attenuation of I/R prior to graft implantation in clinical Tx.

Short-term outcomes of cadaveric lung transplantation in ventilator-dependent patients

PubMed Central

2009-01-01

Introduction Survival after cadaveric lung transplantation (LTx) in respiratory failure recipients who were already dependent on ventilation support prior to transplantation is poor, with a relatively high rate of surgical mortality and morbidity. In this study, we sought to describe the short-term outcomes of bilateral sequential LTx (BSLTx) under extracorporeal membrane oxygenation (ECMO) support in a consecutive series of preoperative respiratory failure patients. Methods Between July 2006 and July 2008, we performed BSLTx under venoarterious (VA) ECMO support in 10 respiratory failure patients with various lung diseases. Prior to transplantation, 6 patients depended on invasive mechanical ventilation support and the others (40%) needed noninvasive positive pressure ventilation to maintain adequate gas exchange. Their mean age was 40.9 years and the mean observation period was 16.4 months. Results Except for 1 ECMO circuit that had been set up in the intensive care unit for pulmonary crisis 5 days prior to transplantation, most ECMO (90%) circuits were set up in the operating theater prior to pneumonectomy of native lung during transplantation. Patients were successfully weaned off ECMO circuits immediately after transplantation in 8 cases, and within 1 day (1/10 patients) and after 9 days (1/10 patients) due to severe reperfusion lung edema following transplantation. The mean duration of ECMO support in those successfully weaned off in the operating theater (n = 8) was 7.8 hours. The average duration of intensive care unit stay (n = 10) was 43.1 days (range, 35 to 162 days) and hospital stay (n = 10) was 70 days (range, 20 to 86 days). Although 4 patients (40%) had different degrees of complicated postoperative courses unrelated to ECMO, all patients were discharged home postoperatively. The mean forced vital capacity and the forced expiratory volume in 1 second both increased significantly postoperatively. The cumulative survival rates at 3 months and at 12 months post-transplantation were 100% and 90%. Conclusions Although BSLTx in this critical population has varied surgical complications and prolonged length of postoperative ICU and hospital stays, all the patients observed in this study could tolerate the transplant procedures under VA ECMO support with promising pulmonary function and satisfactory short-term outcome. PMID:19660110

Epidemiology, clinical manifestations, and outcomes of Scedosporium infections among solid organ transplant recipients.

PubMed

Johnson, L S; Shields, R K; Clancy, C J

2014-08-01

Few studies of Scedosporium infections following solid organ transplantation have been performed in the era of induction immunosuppression and widespread antifungal prophylaxis. We performed a single-center, retrospective study of transplant recipients from 2000 through 2010 who had a positive Scedosporium culture. Among 27 patients, 67% (n = 18) and 33% (n = 9) were infected with Scedosporium apiospermum and Scedosporium prolificans, respectively. A total of 67% received induction immunosuppression and 74% received prior antifungal therapy. Isolates were broadly resistant to antifungals. Of these patients, 59% (n = 16) were colonized by Scedosporium, and 41% (n = 11) had disease (scedosporiosis). No significant clinical differences were seen between species. Colonization occurred exclusively in the lungs of lung transplant recipients (LTR). Scedosporiosis followed lung transplantation in 55%, and other organ transplants (multivisceral [18%]; and heart, liver, small intestine [9% each]) in 45%. Scedosporiosis was preceded by colonization in 36%. Diseases included pneumonia (64%), mediastinitis (18%), and fungemia/disseminated infections (18%). The 6-month outcomes were death in 55%, progression in 18%, stability in 9%, and resolution in 18%. Patients who died had earlier onset scedosporiosis post transplant (median: 80.5 vs. 1388 days; P = 0.04), and were more likely to have mediastinitis or disseminated infections than pneumonia (100% vs. 29%; P = 0.06). The 3 patients who developed scedosporiosis >1 year post transplant survived. All patients who survived were treated with a voriconazole-containing regimen. LTR were most susceptible to Scedosporium colonization and scedosporiosis, particularly within the lungs. Death was common with scedosporiosis in the first year after all types of organ transplants, consistent with profound immunosuppression and antifungal resistance, but not encountered thereafter. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hypoxic Gene Expression of Donor Bronchi Linked to Airway Complications after Lung Transplantation.

PubMed

Kraft, Bryan D; Suliman, Hagir B; Colman, Eli C; Mahmood, Kamran; Hartwig, Matthew G; Piantadosi, Claude A; Shofer, Scott L

2016-03-01

Central airway stenosis (CAS) after lung transplantation has been attributed in part to chronic airway ischemia; however, little is known about the time course or significance of large airway hypoxia early after transplantation. To evaluate large airway oxygenation and hypoxic gene expression during the first month after lung transplantation and their relation to airway complications. Subjects who underwent lung transplantation underwent endobronchial tissue oximetry of native and donor bronchi at 0, 3, and 30 days after transplantation (n = 11) and/or endobronchial biopsies (n = 14) at 30 days for real-time polymerase chain reaction of hypoxia-inducible genes. Patients were monitored for 6 months for the development of transplant-related complications. Compared with native endobronchial tissues, donor tissue oxygen saturations (Sto2) were reduced in the upper lobes (74.1 ± 1.8% vs. 68.8 ± 1.7%; P < 0.05) and lower lobes (75.6 ± 1.6% vs. 71.5 ± 1.8%; P = 0.065) at 30 days post-transplantation. Donor upper lobe and subcarina Sto2 levels were also lower than the main carina (difference of -3.9 ± 1.5 and -4.8 ± 2.1, respectively; P < 0.05) at 30 days. Up-regulation of hypoxia-inducible genes VEGFA, FLT1, VEGFC, HMOX1, and TIE2 was significant in donor airways relative to native airways (all P < 0.05). VEGFA, KDR, and HMOX1 were associated with prolonged respiratory failure, prolonged hospitalization, extensive airway necrosis, and CAS (P < 0.05). These findings implicate donor bronchial hypoxia as a driving factor for post-transplantation airway complications. Strategies to improve airway oxygenation, such as bronchial artery re-anastomosis and hyperbaric oxygen therapy merit clinical investigation.

A newly developed solution enhances thirty-hour preservation in a canine lung transplantation model.

PubMed

Liu, C J; Ueda, M; Kosaka, S; Hirata, T; Yokomise, H; Inui, K; Hitomi, S; Wada, H

1996-09-01

Ischemia and reperfusion cause the production of oxygen free radicals. These damage grafts or disrupt normal vascular homeostatic mechanisms, with a parallel reduction in endothelial nitric oxide and adenosine 3',5'-cyclic monophosphate levels. We hypothesized that lung preservation failure may be related to these events. To improve lung preservation, we prepared a new ET-Kyoto solution, which contains N-acetylcysteine (a radical scavenger), nitroglycerin (to elevate the nitric oxide level), and dibutyryl adenosine 3',5'-cyclic monophosphate (to elevate the adenosine 3',5'-cyclic monophosphate level) and examined its efficacy in a canine single-lung transplantation model. Lungs were flushed with new ET-Kyoto solution (group I, n = 9), basal ET-Kyoto solution (group II, n = 6), basal ET-Kyoto solution plus ethanol and propylene glycol (solvents of nitroglycerin; group III, n = 6), or low-potassium dextran glucose solution (group IV, n = 6), and stored at 4 degrees C for 30 hours. After left single-lung transplantation, the right main bronchus and right pulmonary artery were ligated and the functions of the transplanted lung were assessed for 6 hours. Arterial oxygen tension was significantly higher in group I than in groups II, III, and IV (p < 0.05). Peak inspiratory pressure and wet-to-dry lung weight ratio were significantly lower in group I than in groups II and IV (p < 0.01). Histologic and ultrastructural studies showed better preservation in group I than in groups II, III, and IV. We conclude that the new ET-Kyoto solution provides enhanced 30-hour lung preservation.

Airway pressure release ventilation during ex vivo lung perfusion attenuates injury.

PubMed

Mehaffey, J Hunter; Charles, Eric J; Sharma, Ashish K; Money, Dustin T; Zhao, Yunge; Stoler, Mark H; Lau, Christine L; Tribble, Curtis G; Laubach, Victor E; Roeser, Mark E; Kron, Irving L

2017-01-01

Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation. Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured. Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H 2 O vs 15.0 ± 4.6 mL/cm H 2 O) and 4 hours (30.6 ± 1.3 mL/cm H 2 O vs 17.7 ± 5.9 mL/cm H 2 O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Lung transplant curriculum in pulmonary/critical care fellowship training.

PubMed

Hayes, Don; Diaz-Guzman, Enrique; Berger, Rolando; Hoopes, Charles W

2013-01-01

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.

Morbidity and Mortality of Live Lung Donation: Results from the RELIVE study

PubMed Central

Yusen, R.D.; Hong, B.A.; Messersmith, E.E.; Gillespie, B.W.; Lopez, B.M.; Brown, K.L.; Odim, J.; Merion, R.M.; Barr, M.L.

2014-01-01

The Renal and Lung Living Donors Evaluation Study (RELIVE) assesses outcomes of live lung (lobectomy) donors. This is a retrospective cohort study at University of Southern California (USC) and Washington University (WASHU) Medical Centers (1993–2006), using medical records to assess morbidity and national databases to ascertain post-donation survival and lung transplantation. Serious complications were those requiring significant treatment, potentially life-threatening, or leading to prolonged hospitalization. The 369 live lung donors (287 USC, 82 WASHU) were predominantly white, non-Hispanic, and male; 72% had a biological relationship to the recipient, and 30% were recipient parents. Serious complications occurred in 18% of donors; 2.2% underwent reoperation, and 6.5% had an early rehospitalization. The two centers had significantly different incidences of serious complications (p<0.001). No deaths occurred and no donors underwent lung transplantation during 4,000+ person-years of follow-up (death: minimum 4, maximum 17 years; transplant: minimum 5, maximum 19). Live lung donation remains a potential option for recipients when using deceased donor lungs lacks feasibility. However, the use of two live donors for each recipient and the risk of morbidity associated with live lung donation do not justify this approach when deceased lung donors remain available. Center effects and long-term outcomes require further evaluation. PMID:25039865

Normothermic ex-vivo preservation with the portable Organ Care System Lung device for bilateral lung transplantation (INSPIRE): a randomised, open-label, non-inferiority, phase 3 study.

PubMed

Warnecke, Gregor; Van Raemdonck, Dirk; Smith, Michael A; Massard, Gilbert; Kukreja, Jasleen; Rea, Federico; Loor, Gabriel; De Robertis, Fabio; Nagendran, Jayan; Dhital, Kumud K; Moradiellos Díez, Francisco Javier; Knosalla, Christoph; Bermudez, Christian A; Tsui, Steven; McCurry, Kenneth; Wang, I-Wen; Deuse, Tobias; Lesèche, Guy; Thomas, Pascal; Tudorache, Igor; Kühn, Christian; Avsar, Murat; Wiegmann, Bettina; Sommer, Wiebke; Neyrinck, Arne; Schiavon, Marco; Calebrese, Fiorella; Santelmo, Nichola; Olland, Anne; Falcoz, Pierre-Emanuel; Simon, Andre R; Varela, Andres; Madsen, Joren C; Hertz, Marshall; Haverich, Axel; Ardehali, Abbas

2018-05-01

Severe primary graft dysfunction (PGD) of grade 3 (PGD3) is a common serious complication following lung transplantation. We aimed to assess physiological donor lung preservation using the Organ Care System (OCS) Lung device compared with cold static storage. In this non-inferiority, randomised, controlled, open-label, phase 3 trial (INSPIRE) recipients were aged 18 years or older and were registered as standard criteria primary double lung transplant candidates. Eligible donors were younger than 65 years old with a ratio of partial pressure of oxygen in arterial blood to the fraction of inspired oxygen of more than 300 mm Hg. Transplant recipients were randomly assigned (1:1) with permuted blocks, stratified by centre, to receive standard criteria donor lungs preserved in the OCS Lung device (OCS arm) or cold storage at 4°C (control arm). The composite primary effectiveness endpoint was absence of PGD3 within the first 72 h after transplant and 30-day survival in the per-protocol population, with a stringent 4% non-inferiority margin. Superiority was tested upon meeting non-inferiority. The primary safety endpoint was the mean number of lung graft-related serious adverse events within 30 days of transplant. We did analyses in the per-protocol and intention-to-treat populations. This trial is registered with ClinicalTrials.gov, number NCT01630434. Between Nov 17, 2011, and Nov 24, 2014, we randomly assigned 370 patients, and 320 (86%) underwent transplantation (n=151 OCS and n=169 control); follow-up was completed in Nov 24, 2016. The primary endpoint was met in 112 (79·4%) of 141 patients (95% CI 71·8 to 85·8) in the OCS group compared with 116 (70·3%) of 165 patients (62·7 to 77·2) in the control group (non-inferiority point estimate -9·1%; 95% CI -∞ to -1·0; p=0·0038; and superiority test p=0·068). Patient survival at day 30 post-transplant was 135 (95·7%) of 141 patients (95% CI 91·0-98·4) in the OCS group and 165 patients (100%; 97·8-100·0) in the control group (p=0·0090) and at 12 months was 126 (89·4%) of 141 patients (83·1-93·9) for the OCS group compared with 146 (88·1%) of 165 patients (81·8-92·8) for the control group. Incidence of PGD3 within 72 h was reported in 25 (17·7%) of 141 patients in the OCS group (95% CI 11·8 to 25·1) and 49 (29·7%) of 165 patients in the control group (22·8 to 37·3; superiority test p=0·015). The primary safety endpoint was met (0·23 lung graft-related serious adverse events in the OCS group compared with 0·28 events in the control group [point estimate -0·045%; 95% CI -∞ to 0·047; non-inferiority test p=0·020]). In the intention-to-treat population, causes of death at 30 days and in hospital were lung graft failure or lung infection (n=2 for OCS vs n=7 for control), cardiac causes (n=4 vs n=1), vascular or stroke (n=3 vs n=0), metabolic coma (n=0 vs n=2), and generalised sepsis (n=0 vs n=1). The INSPIRE trial met its primary effectiveness and safety endpoints. Although no short-term survival benefit was reported, further research is needed to see whether the reduced incidence of PGD3 within 72 h of a transplant might translate into earlier recovery and improved long-term outcomes after lung transplantation. TransMedics Inc. Copyright © 2018 Elsevier Ltd. All rights reserved.

Annual literature review of donor-specific HLA antibodies after organ transplantation.

PubMed

Kaneku, Hugo

2011-01-01

The literature review of post-transplant DSA published in 2011 shows: Observations after kidney and lung transplant in non-sensitized transplant recipients show that monitoring post-transplant HLA antibodies offers limited benefit in predicting acute rejection episodes. It remains to be seen if a different monitoring schedule and/ or studying other organs may show otherwise. Nevertheless, others have shown that monitoring post-transplant antibodies does identify patients at higher risk for chronic rejection. Studies in kidney, heart, and liver patients transplanted in the presence of preformed DSA show that detecting these antibodies early after transplant identifies a group of patients with greater risk for allograft dysfunction. New and larger studies using bortezomib and eculizumab to treat acute antibody-mediated rejection confirm earlier observations that these two therapies are effective in treating and preventing rejections. In general, identification of HLAantibodies and DSA after transplant is associated with higher rates of rejection and poor allograft survival in all organs examined. IgM antibodies appear to play an important role after lung transplants.

Airway mucosal bioelectric potential difference in cystic fibrosis after lung transplantation.

PubMed

Wood, A; Higenbottam, T; Jackson, M; Scott, J; Stewart, S; Wallwork, J

1989-12-01

Bioelectrical potential difference (PD) across the respiratory mucosa is raised in cystic fibrosis (CF). We have recorded airway potentials from seven patients with CF who had undergone heart-lung transplantation and from eight patients without CF who had had transplants for cardiovascular disease; comparison of these populations controls for the effects of denervation and immunosuppressive treatment. Six patients without CF who had not had transplants formed an additional control. PD was recorded during routine fiberoptic bronchoscopy, using a Ringer's-perfused exploring bridge connected across a high impedance amplifier to an intravenous reference bridge. Bronchial lavage and sputum culture revealed no evidence of infection. Bronchial PD was similar in all three groups of patients at equivalent sites. However, nasal PD was raised in the CF group (mean value, 44 mV +/- 3.9 SE) compared with the patients who had transplants for cardiovascular disease (mean, 18 mV +/- 1.1 SE), and the control patients (mean, 15 mV +/- 1.2 SE). We conclude that the epithelial defects that result in raised airway potentials in CF do not recur in the transplanted lung.

Cytomegalovirus Viral Load in Bronchoalveolar Lavage to Diagnose Lung Transplant Associated CMV Pneumonia.

PubMed

Lodding, Isabelle Paula; Schultz, Hans Henrik; Jensen, Jens-Ulrik; Kirkby, Nikolai; Perch, Michael; Andersen, Claus; Lundgren, Jens D; Iversen, Martin

2018-02-01

The diagnostic yield for cytomegalovirus (CMV) polymerase chain reaction (PCR) viral load in bronchoalveolar lavage (BAL) or in plasma to diagnose CMV pneumonia in lung transplant recipients remains uncertain and was investigated in a large cohort of consecutive lung transplant recipients. Bronchoscopies within the first year of lung transplantation with CMV detectable in BAL by PCR (ie, viral load, ≥273 IU/mL) were included (66 recipients; 145 bronchoscopies); at each bronchoscopy episode, 2 independent experts reviewed clinical and laboratory information to determine whether the patient at that time fulfilled the criteria for CMV pneumonia per current international recommendations. Corresponding plasma CMV PCR viral load determined at time of the bronchoscopy (n = 126) was also studied. Optimal CMV PCR viral load cutoff for CMV pneumonia diagnosis was determined using receiver operating characteristics. CMV was detected in BAL with CMV PCR in 145 episodes, and 34 (23%) of these episodes fulfilled the criteria for CMV pneumonia. The area under the curve-receiver operating characteristics for CMV in BAL was 90% at the optimum cutoff (4545 IU/mL) with a corresponding sensitivity of 91% and specificity of 77% (in plasma the corresponding values were 274 IU/mL, 63% and 76%, respectively). CMV PCR viral load in BAL had a high performance to diagnose CMV pneumonia in lung transplant recipients; plasma CMV viral load did not reliably aid as a diagnostic tool.

Estradiol worsens the syndrome of ischemia-reperfusion injury in an experimental lung transplantation model.

PubMed

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

2011-06-01

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.

Lung transplantation for patients older than 65 years: is it a feasible option?

PubMed

Machuca, T N; Camargo, S M; Schio, S M; Lobato, V; Sanchez, L B; Perin, F; Felicetti, J C; Camargo, J J

2011-01-01

Advanced age has been a relative contraindication to lung transplantation. However, the exact age limit for this procedure has not yet been established. The aim of this work is to present our experience with this particular group. This retrospective review included medical charts of patients who underwent lung transplantation at our institution from January 2004 to February 2009: namely, 112 cadaveric lung transplants with 12 patients (10.7%) >65 years old. There were 9 male patients and the overall mean age was 68 years (range 66-72). The indications were pulmonary fibrosis in 8 and emphysema in 4 cases. Four patients had mild coronary artery disease and 4 systemic hypertension. All of the procedures were unilateral and only 2 required extracorporeal circulation. Only 5 patients received blood product transfusions intraoperatively; the mean ischemic time was 222 minutes. Four patients developed primary graft dysfunction, the mean requirement for mechanical ventilation was 30 hours, and the mean intensive care unit stay, 11 days. Postoperative complications were respiratory infections (n = 8), catheter-related infection (n = 1), atrial fibrillation (n = 2). The mean hospital stay was 28 days and the 1-year survival was 75%. Lung transplantation is a feasible option for well-selected patients with end-stage pulmonary disease who are >65 years old. Our study reinforces the modern trend for unilateral procedures in this situation. Copyright © 2011 Elsevier Inc. All rights reserved.

Gastroesophageal reflux symptoms are not sufficient to guide esophageal function testing in lung transplant candidates.

PubMed

Posner, S; Zheng, J; Wood, R K; Shimpi, R A; Hartwig, M G; Chow, S-C; Leiman, D A

2018-05-01

Gastroesophageal reflux disease and esophageal dysmotility are prevalent in patients with advanced lung disease and are associated with graft dysfunction following lung transplantation. As a result, many transplant centers perform esophageal function testing as part of the wait-listing process but guidelines for testing in this population are lacking. The aim of this study is to describe whether symptoms of gastroesophageal reflux correlate with abnormal results on pH-metry and high-resolution manometry and can be used to identify those who require testing. We performed a retrospective cohort study of 226 lung transplant candidates referred for high-resolution manometry and pH-metry over a 12-month period in 2015. Demographic data, results of a standard symptom questionnaire and details of esophageal function testing were obtained. Associations between the presence of symptoms and test results were analyzed using Fisher's exact tests and multivariable logistic regression. The most common lung disease diagnosis was interstitial lung disease (N = 131, 58%). Abnormal pH-metry was seen in 116 (51%) patients and the presence of symptoms was significantly associated with an abnormal study (p < 0.01). Dysmotility was found in 98 (43%) patients, with major peristaltic or esophageal outflow disorders in 45 (20%) patients. Symptoms were not correlated with findings on esophageal high-resolution manometry. Fifteen of 25 (60%) asymptomatic patients had an abnormal manometry or pH-metry. These results demonstrate that in patients with advanced lung disease, symptoms of gastroesophageal reflux increase the likelihood of elevated acid exposure on pH-metry but were not associated with dysmotility. Given the proportion of asymptomatic patients with abnormal studies and associated post-transplant risks, a practice of universal high-resolution manometry and pH-metry testing in this population is justifiable.

Use of Lung Allografts From Donation After Cardiac Death Donors: A Single-Center Experience.

PubMed

Costa, Joseph; Shah, Lori; Robbins, Hilary; Raza, Kashif; Sreekandth, Sowmya; Arcasoy, Selim; Sonett, Joshua R; D'Ovidio, Frank

2018-01-01

Lung transplantation remains the only treatment for end-stage lung disease. Availability of suitable lungs does not parallel this growing trend. Centers using donation after cardiac death (DCD) donor lungs report comparable outcomes with those from brain-dead donors. Donor assessment protocols and consistent surgical teams have been advocated when considering using the use of DCD donors. We present our experience using lungs from Maastricht category III DCD donors. Starting 2007 to July 2016, 73 DCD donors were assessed, 44 provided suitable lungs that resulted in 46 transplants. A 2012 to October 2016 comparative cohort of 379 brain-dead donors were assessed. Recipient and donor characteristics and primary graft dysfunction (PGD) and survival were monitored. Seventy-three DCD (40% dry run rate) donors assessed yielded 46 transplants (23 double, 6 right, and 17 left). Comparative cohort of 379 brain-dead donors yielded 237 transplants (112 double, 43 right, and 82 left). One- and 3-year recipient survival was 91% and 78% for recipients of DCD lungs and 91% and 75% for recipients of lungs from brain-dead donors, respectively. PGD 2 and 3 in DCD recipients at 72 hours was 4 of 46 (9%) and 6 of 46 (13%), respectively. Comparatively, brain-dead donor recipient cohort at 72 hours with PGD 2 and 3 was 23 of 237 (10%) and 41 of 237 (17%), respectively. Our experience reaffirms the use of lungs from DCD donors as a viable source with favorable outcomes. Recipients from DCD donors showed equivalent PGD rate at 72 hours and survival compared with recipients from brain-dead donors. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Chronic effects of air pollution on lung function after lung transplantation in the Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) study.

PubMed

Benmerad, Meriem; Slama, Rémy; Botturi, Karine; Claustre, Johanna; Roux, Antoine; Sage, Edouard; Reynaud-Gaubert, Martine; Gomez, Carine; Kessler, Romain; Brugière, Olivier; Mornex, Jean-François; Mussot, Sacha; Dahan, Marcel; Boussaud, Véronique; Danner-Boucher, Isabelle; Dromer, Claire; Knoop, Christiane; Auffray, Annick; Lepeule, Johanna; Malherbe, Laure; Meleux, Frederik; Nicod, Laurent; Magnan, Antoine; Pison, Christophe; Siroux, Valérie

2017-01-01

An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs).The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6 months. The levels of air pollutants (nitrogen dioxide (NO 2 ), particulate matter with an aerodynamic cut-off diameter of x µm (PM x ) and ozone (O 3 )) at the patients' home address were averaged in the 12 months before each spirometry test. The effects of air pollutants on forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) in % predicted were estimated using mixed linear regressions. We assessed the effect modification of macrolide antibiotics in this relationship.Increased 12-month levels of pollutants were associated with lower levels of FVC % pred (-2.56%, 95% CI -3.86--1.25 for 5 µg·m -3 of PM 10 ; -0.75%, 95% CI -1.38--0.12 for 2 µg·m -3 of PM 2.5 and -2.58%, 95% CI -4.63--0.53 for 10 µg·m -3 of NO 2 ). In patients not taking macrolides, the deleterious association between PM and FVC tended to be stronger and PM 10 was associated with lower FEV 1 Our study suggests a deleterious effect of chronic exposure to air pollutants on lung function levels in LTRs, which might be modified with macrolides. Copyright ©ERS 2017.

Restrictive allograft syndrome (RAS): a novel form of chronic lung allograft dysfunction.

PubMed

Sato, Masaaki; Waddell, Thomas K; Wagnetz, Ute; Roberts, Heidi C; Hwang, David M; Haroon, Ayesha; Wagnetz, Dirk; Chaparro, Cecilia; Singer, Lianne G; Hutcheon, Michael A; Keshavjee, Shaf

2011-07-01

Bronchiolitis obliterans syndrome (BOS) with small-airway pathology and obstructive pulmonary physiology may not be the only form of chronic lung allograft dysfunction (CLAD) after lung transplantation. Characteristics of a form of CLAD consisting of restrictive functional changes involving peripheral lung pathology were investigated. Patients who received bilateral lung transplantation from 1996 to 2009 were retrospectively analyzed. Baseline pulmonary function was taken as the time of peak forced expiratory volume in 1 second (FEV(1)). CLAD was defined as irreversible decline in FEV(1) < 80% baseline. The most accurate threshold to predict irreversible decline in total lung capacity and thus restrictive functional change was at 90% baseline. Restrictive allograft syndrome (RAS) was defined as CLAD meeting this threshold. BOS was defined as CLAD without RAS. To estimate the effect on survival, Cox proportional hazards models and Kaplan-Meier analyses were used. Among 468 patients, CLAD developed in 156; of those, 47 (30%) showed the RAS phenotype. Compared with the 109 BOS patients, RAS patients showed significant computed tomography findings of interstitial lung disease (p < 0.0001). Prevalence of RAS was approximately 25% to 35% of all CLAD over time. Patient survival of RAS was significantly worse than BOS after CLAD onset (median survival, 541 vs 1,421 days; p = 0.0003). The RAS phenotype was the most significant risk factor of death among other variables after CLAD onset (hazard ratio, 1.60; confidential interval, 1.23-2.07). RAS is a novel form of CLAD that exhibits characteristics of peripheral lung fibrosis and significantly affects survival of lung transplant patients. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Immunosuppressive drug therapy for preventing rejection following lung transplantation in cystic fibrosis.

PubMed

Saldanha, Ian J; Akinyede, Oluwaseun; Robinson, Karen A

2018-06-18

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 and the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP) to obtain information on unpublished and ongoing studies.Date of latest search: 29 May 2018. 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. We will use GRADE to summarize our results through a summary of findings table for each comparison we present in the review. While five studies addressed the interventions of interest, 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 updates of the review. The lack of currently available evidence makes it impossible to draw conclusions about the comparative efficacy and safety of the various immunosuppressive drugs among people with cystic fibrosis after lung transplantation. A 2013 Cochrane Review comparing tacrolimus with cyclosporine in all lung transplant recipients (not restricted to those with cystic fibrosis) reported no significant difference in mortality and risk of acute rejection. However, tacrolimus use was associated with lower risk of broncholitis obliterans syndrome and arterial hypertension and higher risk of diabetes mellitus. It should be noted that this wider review contained only a small number of included studies (n = 3) with a high risk of bias. Additional randomised studies are required to provide evidence for the benefit and safety of the use of immunosuppressive therapy among people with cystic fibrosis after lung transplantation.

Albinism and lung fibrosis in a young man - the first case of adult Hermansky-Pudlak Syndrome reported in Malaysia.

PubMed

Liza, A F; Aziah, A M

2012-12-01

A young gentleman of Indian descent with oculacutaneous albinism (OCA) was found to have severe pulmonary fibrosis at first presentation. Following investigations, he was diagnosed with Hermansky-Pudlak Syndrome (HPS). It is a genetic condition characterised by albinism, bleeding diathesis and multisystem disorder observed in individuals of particular descents. Although there is no curative treatment apart from lung transplantation, preventive measures to minimise pulmonary insult may change the natural history of the disease. Therefore HPS should be actively sought, monitored and risk factors addressed in individuals with OCA and bleeding diathesis particularly those of Indian descent as they may develop serious complications such as pulmonary fibrosis in the future.

Host-Pathogen Interactions and Chronic Lung Allograft Dysfunction.

PubMed

Belperio, John; Palmer, Scott M; Weigt, S Sam

2017-09-01

Lung transplantation is now considered to be a therapeutic option for patients with advanced-stage lung diseases. Unfortunately, due to post-transplant complications, both infectious and noninfectious, it is only a treatment and not a cure. Infections (e.g., bacterial, viral, and fungal) in the immunosuppressed lung transplant recipient are a common cause of mortality post transplant. Infections have more recently been explored as factors contributing to the risk of chronic lung allograft dysfunction (CLAD). Each major class of infection-(1) bacterial (Staphylococcus aureus and Pseudomonas aeruginosa); (2) viral (cytomegalovirus and community-acquired respiratory viruses); and (3) fungal (Aspergillus)-has been associated with the development of CLAD. Mechanistically, the microbe seems to be interacting with the allograft cells, stimulating the induction of chemokines, which recruit recipient leukocytes to the graft. The recipient leukocyte interactions with the microbe further up-regulate chemokines, amplifying the influx of allograft-infiltrating mononuclear cells. These events can promote recipient leukocytes to interact with the allograft, triggering an alloresponse and graft dysfunction. Overall, interactions between the microbe-allograft-host immune system alters chemokine production, which, in part, plays a role in the pathobiology of CLAD and mortality due to CLAD.

[Chronic rejection: Differences and similarities in various solid organ transplants].

PubMed

Suhling, H; Gottlieb, J; Bara, C; Taubert, R; Jäckel, E; Schiffer, M; Bräsen, J H

2016-01-01

In this paper, chronic rejections after transplantation of the lungs, heart, liver, and kidney are described. Chronic allograft dysfunction (CAD) plays an important role in all of these transplantations and has a significant influence on patient survival. The pathophysiological reasons for CAD varies greatly in the various organs.Chronic lung allograft dysfunction (CLAD) is the most important determinant of survival and quality of life after lung transplantation. Diagnosis is based on lung function, especially forced expiratory flow in 1 s (FEV1) decline. Prevention, early detection, and rapid treatment are extremely important. Azithromycin and extracorporeal photopheresis are commonly used for treatment because they usually positively influence the progression of lung remodeling.The expression for chronic rejection of the heart is cardiac allograft vasculopathy (CAV). Immunological and nonimmunological factors are important for its development. Due to limited therapeutic options, prevention is of utmost importance (administration of mTOR inhibitors and minimizing cardiovascular risk factors).The mid- and long-term survival rates after liver transplantation have hardly changed in recent decades, which is an indication of the difficulty in diagnosing chronic graft dysfunction. Chronic ductopenic rejection accounts for a small proportion of late graft dysfunction. Idiopathic posttransplant hepatitis and de novo autoimmune hepatitis are important in addition to recurrence of the underlying disease that led to transplantation.Chronic allograft nephropathy is the result of severe rejection which cumulates in increasing fibrosis with remodeling. The earliest possible diagnosis and therapy is currently the only option. Diagnosis is based on evidence of donor-specific antibodies and histological findings.

The Prevalence of Pneumocystis jiroveci in Bronchoalveolar Lavage Specimens of Lung Transplant Recipients Examined by the Nested PCR.

PubMed

Izadi, Morteza; Jonaidi Jafari, Nematollah; Sadraei, Javid; Mahmoodzadeh Poornaki, Abbas; Rezavand, Babak; Zarrinfar, Hossein; Abdi, Jahangir; Mohammadi, Younes

2014-12-01

The use of immune suppressive drugs for organ transplant recipients predisposes them to opportunistic infections, especially by fungal agents. Pneumocystis jiroveci, as an opportunistic pathogen, endangers the patients' life in those with immune system disorders. Early detection of latent Pneumocystis infection in susceptible patients may help choose the optimal treatment for these patients. The aim of this study was to identify and determine the colonization of latent P. jiroveci infection among lung transplant recipients. This cross-sectional descriptive study was conducted on lung transplant recipients. Bronchoalveolar lavage (BAL) specimens were collected from 32 patients undergoing bronchoscopy. The samples were aseptically homogenized by 10 mM dithiothreitol, and their DNA was extracted. The mtLSUrRNA gene of P. jiroveci was amplified using nested PCR in two stages. Nested PCR was performed using external primers of pAZ-102-E and pAZ102-H followed by using the PCR product of the first stage and internal primers of pAZ-102-E and pAZ102-L2. The genome of P. jiroveci was revealed by a 346 bp PCR product in the initial amplification and a 120 bp product in the nested PCR. The results showed that seven BAL specimens (21.9%) from lung transplant recipients were positive for P. jiroveci. In molecular epidemiology studies, nested PCR has higher sensitivity than PCR. Results of this study support the colonization of P. jiroveci in patients receiving lung transplantation. Patients who are carriers of P. jiroveci are at a higher risk of P. jiroveci pneumonia.

Influence of donor–recipient gender mismatch on graft function and survival following lung transplantation†

PubMed Central

Alvarez, Antonio; Moreno, Paula; Illana, Jennifer; Espinosa, Dionisio; Baamonde, Carlos; Arango, Elisabet; Algar, Francisco Javier; Salvatierra, Angel

2013-01-01

OBJECTIVES In current practice, donors and recipients are not matched for gender in lung transplantation. However, some data have suggested a possible effect of gender combinations on lung transplant outcomes. We examined whether donor–recipient (D/R) gender mismatch is related to adverse outcomes after lung transplantation in terms of early and long-term graft function and survival. METHODS We reviewed 256 donors and lung transplant recipients over a 14-year period. Patients were distributed into four groups: Group A (D/R: female/female), Group B (D/R: male/male), Group C (D/R: female/male), Group D (D/R: male/female). Donor and recipient variables were compared among groups, including early graft function, 30-day mortality, freedom from bronchiolitis obliterans syndrome (BOS), and long-term survival. RESULTS Group A: 57 (22%), Group B: 99 (39%), Group C: 62 (24%), Group D: 38 (15%) transplants (P = 0.001). Donor age was 29 ± 14, 27 ± 12, 33 ± 13 and 23 ± 12 years for Groups A, B, C and D, respectively (P = 0.004). Recipient age was 31 ± 15, 44 ± 17, 42 ± 16 and 30 ± 16 years for Groups A, B, C and D, respectively (P = 0.000). PaO2/FiO2 (mmHg) 24 h post-transplant was: Group A: 276 ± 144, Group B: 297 ± 131, Group C: 344 ± 133 and Group D: 238 ± 138 (P = 0.015). Primary graft dysfunction developed in 23, 14, 17 and 21% of recipients from Groups A, B, C and D, respectively (P = 0.45). Operative mortality was 4.4, 6.5, 5.2 and 2%, for recipients from Groups A, B, C and D, respectively (P = 0.66). Freedom from BOS was 73, 59 and 36% for gender-matched transplants vs 76, 67 and 40% for gender-mismatched transplants at 3, 5 and 10 years, respectively (P = 0.618), without differences among groups. A non-significant survival benefit was observed for female recipients, irrespective of the donor gender. CONCLUSIONS Donor–recipient gender mismatch does not have a negative impact on early graft function and mortality following lung transplantation. There is a trend towards a survival benefit for female recipients, irrespective of the donor gender. PMID:23322094

Clinical outcomes of lung-transplant recipients treated by voriconazole and caspofungin combination in aspergillosis.

PubMed

Thomas, A; Korb, V; Guillemain, R; Caruba, T; Boussaud, V; Billaud, E; Prognon, P; Begué, D; Sabatier, B

2010-02-01

Invasive pulmonary aspergillosis (IPA) is a serious cause of death among immune-compromised patients such as organ-transplant recipients. Recently, voriconazole has been approved for first-line therapy in IPA. Theoretically, optimal voriconazole blood level (superior to 1 mg/L according to recent studies) should be reached within 24 h. In practice, a significantly longer time seems to be needed in lung-transplant recipients. Therefore, caspofungin is now used in combination with voriconazole to provide cover against Aspergillus spp. infection during this gap. The first aim of this study was to investigate Aspergillus spp. infection treated with this combination and the atter's tolerability. The median time for attainment of apparently active blood levels in lung transplant recipients were compared between those with cystic fibrosis and those without. Lung-transplant recipients who received a combination of voriconazole and caspofungin between 2002 and 2008 as primary therapy were identified retrospectively. The median number of days to reach active voriconazole blood levels was compared between cystic fibrosis and other patients by Student's t-test. Statistical significance was defined by P-value <0.05. Four patients were treated for Aspergillus colonization before transplantation and their culture were negative at 90 days. Eleven patients were treated for proven or probable invasive aspergillosis and 14 of them had a complete response. Hallucinations (n = 2) and significant hepatic toxicity (n = 2) were reported. Among the 15 studied transplant recipients, a median of 12.3 days was observed for active voriconazole blood levels to be reached. With cystic fibrosis patients, time tended to be longer than with other recipients (14.9 days vs. 8.3 days). Tacrolimus blood levels (between 5 and 15 ng/mL) may have been increased by voriconazole. This retrospective study describes practical experience in the management of this rare and severe disease in a referral centre for cystic fibrosis lung transplantation. Voriconazole and caspofungin combination was acceptably safe and was associated with good clinical outcomes in almost all patients. We showed that in 15 lung-transplant recipients a median of 12.3 days was required for voriconazole to reach high enough blood levels. Caspofungin in combination with voriconazole provides cover against Aspergillus infection during the period when voriconazole may be at subtherapeutic levels with good tolerability.

Superficial herpes simplex virus wound infection following lung transplantation.

PubMed

Karolak, Wojtek; Wojarski, Jacek; Zegleń, Sławomir; Ochman, Marek; Urlik, Maciej; Hudzik, Bartosz; Wozniak-Grygiel, Elzbieta; Maruszewski, Marcin

2017-08-01

Surgical site infections (SSIs) are infections of tissues, organs, or spaces exposed by surgeons during performance of an invasive procedure. SSIs are classified into superficial, which are limited to skin and subcutaneous tissues, and deep. The incidence of deep SSIs in lung transplant (LTx) patients is estimated at 5%. No reports have been published as to the incidence of superficial SSIs specifically in LTx patients. Common sense would dictate that the majority of superficial SSIs would be bacterial. Uncommonly, fungal SSIs may occur, and we believe that no reports exist as to the incidence of viral wound infections in LTx patients, or in any solid organ transplant patients. We report a de novo superficial wound infection with herpes simplex virus following lung transplantation, its possible source, treatment, and resolution. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Infectious pulmonary complications in lung transplant recipients.

PubMed

Chan, Kevin M; Allen, Samuel A

2002-12-01

Pulmonary infections are the most common cause of morbidity in the lung transplant population. Prompt recognition and treatment is necessary to prevent poor outcomes. An understanding of the temporal relationship between immunosuppression and the risk for developing infection can assist the clinician with appropriate treatment. Bacterial pneumonia is common within the first 4 months after transplantation whereas cytomegalovirus (CMV) infection or disease becomes prevalent after the discontinuation of prophylaxis in at-risk patients. Fungal infections, especially aspergillosis, can be fatal if not treated early and the risk for infection is present throughout the transplant period. Community-acquired viral infections present with upper-respiratory symptoms and wheezing that may lead to a chronic decline in lung function. Suspicion of a pulmonary infection in these immunosuppressed individuals should lead to an urgent diagnostic bronchoscopy and empiric antimicrobial therapy. Copyright 2002, Elsevier Science (USA). All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eun-Young Kang; Patz, E.F. Jr.; Mueller, N.L.

Our goal was to assess the CT findings of cytomegalovirus (CMV) pneumonia in transplant patients. The study included 10 transplant patients who had chest CT scan and pathologically proven isolated pulmonary CMV infection. Five patients had bone marrow transplant and five had solid organ transplant. The CT scans were retrospectively reviewed for pattern and distribution of disease and the CT findings compared with the findings on open lung biopsy (n = 9) and autopsy (n = 1). Nine of 10 patients had parenchymal abnormalities apparent at CT and I had normal CT scans. The findings in the nine patients includedmore » small nodules (n = 6), consolidation (n = 4), ground-glass attenuation (n = 4), and irregular lines (n = 1). The nodules had a bilateral and symmetric distribution and involved all lung zones. The consolidation was most marked in the lower lung zones. The CT findings of CMV pneumonia in transplant patients are heterogeneous. The most common patterns include small nodules and areas of consolidation. 13 refs., 4 figs., 1 tab.« less

Psychosocial and financial aspects of lung transplantation.

PubMed

Smolin, T L; Aguiar, L J

1996-09-01

This article summarizes the many psychosocial phases a patient will encounter during his or her transplantation experience and the ways the social worker can assist during this time. These include supportive services such as facilitating support groups and orientation programs, counseling, and crisis intervention. Also of importance is the financing of lung transplantation and its many associated costs, such as immunosuppressive medications and temporary housing. With the rise in managed care, the role of the transplant financial coordinator is of increasing importance from both a fiscal perspective and customer service standpoint for both the patient and the institution.

Looking Beyond Respiratory Cultures: Microbiome-Cytokine Signatures of Bacterial Pneumonia and Tracheobronchitis in Lung Transplant Recipients.

PubMed

Shankar, J; Nguyen, M H; Crespo, M M; Kwak, E J; Lucas, S K; McHugh, K J; Mounaud, S; Alcorn, J F; Pilewski, J M; Shigemura, N; Kolls, J K; Nierman, W C; Clancy, C J

2016-06-01

Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia-colonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Respiratory infections in patients with cystic fibrosis undergoing lung transplantation.

PubMed

Lobo, Leonard J; Noone, Peadar G

2014-01-01

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lung transplantation for high-risk patients with idiopathic pulmonary fibrosis.

PubMed

De Oliveira, Nilto C; Julliard, Walker; Osaki, Satoru; Maloney, James D; Cornwell, Richard D; Sonetti, David A; Meyer, Keith C

2016-10-07

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.

Local Origin of Mesenchymal Cells in a Murine Orthotopic Lung Transplantation Model of Bronchiolitis Obliterans

PubMed Central

Mimura, Takeshi; Walker, Natalie; Aoki, Yoshiro; Manning, Casey M.; Murdock, Benjamin J.; Myers, Jeffery L.; Lagstein, Amir; Osterholzer, John J.; Lama, Vibha N.

2016-01-01

Bronchiolitis obliterans is the leading cause of chronic graft failure and long-term mortality in lung transplant recipients. Here, we used a novel murine model to characterize allograft fibrogenesis within a whole-lung microenvironment. Unilateral left lung transplantation was performed in mice across varying degrees of major histocompatibility complex mismatch combinations. B6D2F1/J (a cross between C57BL/6J and DBA/2J) (Haplotype H2b/d) lungs transplanted into DBA/2J (H2d) recipients were identified to show histopathology for bronchiolitis obliterans in all allogeneic grafts. Time course analysis showed an evolution from immune cell infiltration of the bronchioles and vessels at day 14, consistent with acute rejection and lymphocytic bronchitis, to subepithelial and intraluminal fibrotic lesions of bronchiolitis obliterans by day 28. Allografts at day 28 showed a significantly higher hydroxyproline content than the isografts (33.21 ± 1.89 versus 22.36 ± 2.33 μg/mL). At day 40 the hydroxyproline content had increased further (48.91 ± 7.09 μg/mL). Flow cytometric analysis was used to investigate the origin of mesenchymal cells in fibrotic allografts. Collagen I–positive cells (89.43% ± 6.53%) in day 28 allografts were H2Db positive, showing their donor origin. This novel murine model shows consistent and reproducible allograft fibrogenesis in the context of single-lung transplantation and represents a major step forward in investigating mechanisms of chronic graft failure. PMID:25848843

GMP-grade human fetal liver-derived mesenchymal stem cells for clinical transplantation.

PubMed

Larijani, Bagher; Aghayan, Hamid-Reza; Goodarzi, Parisa; Arjmand, Babak

2015-01-01

Stem cell therapy seems a promising avenue in regenerative medicine. Within various stem cells, mesenchymal stem cells have progressively used for cellular therapy. Because of the age-related decreasing in the frequency and differentiating capacity of adult MSCs, fetal tissues such as fetal liver, lung, pancreas, spleen, etc. have been introduced as an alternative source of MSCs for cellular therapy. On the other hand, using stem cells as advanced therapy medicinal products, must be performed in compliance with cGMP as a quality assurance system to ensure the safety, quality, and identity of cell products during translation from the basic stem cell sciences into clinical cell transplantation. In this chapter the authors have demonstrated the manufacturing of GMP-grade human fetal liver-derived mesenchymal stem cells.

The effect of donor treatment with hydrogen on lung allograft function in rats.

PubMed

Kawamura, Tomohiro; Huang, Chien-Sheng; Peng, Ximei; Masutani, Kosuke; Shigemura, Norihisa; Billiar, Timothy R; Okumura, Meinoshin; Toyoda, Yoshiya; Nakao, Atsunori

2011-08-01

Because inhaled hydrogen provides potent anti-inflammatory and antiapoptotic effects against acute lung injury, we hypothesized that treatment of organ donors with inhaled hydrogen during mechanical ventilation would decrease graft injury after lung transplantation. Orthotopic left lung transplants were performed using a fully allogeneic Lewis to Brown Norway rat model. The donors were exposed to mechanical ventilation with 98% oxygen plus 2% nitrogen or 2% hydrogen for 3 h prior to harvest, and the lung grafts underwent 4 h of cold storage in Perfadex (Vitrolife, Göteborg, Sweden). The graft function, histomorphologic changes, and inflammatory reactions were assessed. The combination of mechanical ventilation and prolonged cold ischemia resulted in marked deterioration of gas exchange when the donors were ventilated with 2% nitrogen/98% oxygen, which was accompanied by upregulation of proinflammatory cytokines and proapoptotic molecules. These lung injuries were attenuated significantly by ventilation with 2% hydrogen. Inhaled hydrogen induced heme oxygenase-1, an antioxidant enzyme, in the lung grafts prior to implantation, which might contribute to protective effects afforded by hydrogen. Preloaded hydrogen gas during ventilation prior to organ procurement protected lung grafts effectively from ischemia/reperfusion-induced injury in a rat lung transplantation model. Copyright © 2011 Mosby, Inc. All rights reserved.

Inhibition of the development of metastases by dietary vitamin C:K3 combination.

PubMed

Taper, Henryk S; Jamison, James M; Gilloteaux, Jacques; Summers, Jack L; Calderon, Pedro Buc

2004-07-09

The tumor growth-inhibiting and chemo-potentiating effects of vitamin C and K(3)combinations have been demonstrated both in vitro and in vivo. The purpose of this study was to investigate the influence of orally administered vitamin C and K(3) on the metastasis of mouse liver tumor (T.L.T.) cells implanted in C3H mice. Adult male C3H mice were given water containing vitamin C and K3 (15 g/0.15 g dissolved in 1000 ml) beginning 2 weeks before tumor transplantation until the end of the experiment. T.L.T. cells (106) were implanted intramuscularly in the right thigh of mice. All mice were sacrificed 42 days after tumor transplantation. Primary tumor, lungs, lymph nodes and other organs or tissues suspected of harboring metastases were macroscopically examined. Samples of primary tumors, their local lymph nodes, lungs and main organs such as liver, kidneys, spleen were taken for histological examination. Forty-two percent of control mice exhibited lung metastases and 27% possessed metastases in local lymph nodes whereas 24% of vitamin-treated mice exhibited lung metastases and 10% possessed local lymph nodes metastases. The total number of lung metastases was 19 in control group and 10 in vitamin C and K(3)-treated mice. Histopathological examination of the metastatic tumors from the vitamin-treated mice revealed the presence of many tumor cells undergoing autoschizic cell death. These results demonstrate that oral vitamin C and K(3) significantly inhibited the metastases of T.L.T. tumors in C3H mice. At least a portion of this inhibition was due to tumor cell death by autoschizis.

Utilization of the Organ Care System Lung for the assessment of lungs from a donor after cardiac death (DCD) before bilateral transplantation.

PubMed

Mohite, P N; Sabashnikov, A; García Sáez, D; Pates, B; Zeriouh, M; De Robertis, F; Simon, A R

2015-07-01

In this manuscript, we present the first experience of evaluating donation after circulatory death (DCD) lungs, using the normothermic preservation Organ Care System (OCS) and subsequent successful transplantation. The OCS could be a useful tool for the evaluation of marginal lungs from DCD donors as it allows a proper recruitment and bronchoscopy in such donations in addition to continuous ex-vivo perfusion and assessment and treatment during transport. The OCS could potentially be a standard of care in the evaluation of marginal lungs from DCD. © The Author(s) 2014.