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Background: Chronic lung allograft dysfunction (CLAD) is the main factor limiting long-term survival after lung transplantation. Besides bronchiolitis obliterans syndrome, a restrictive phenotype of CLAD (rCLAD) exists, which is associated with poor prognosis after diagnosis. However, survival determinants for rCLAD remain to be elucidated. Our aim in this study was to establish parameters predicting survival in patients with rCLAD., Methods: All patients diagnosed with rCLAD in 2 lung transplant centers were assessed in a retrospective manner. Various clinical parameters [demography, pulmonary function, bronchoalveolar lavage (BAL), histopathology, radiology and blood differentials] at rCLAD diagnosis were correlated with graft survival using unadjusted and adjusted analysis., Results: A total of 53 patients with rCLAD were included with a median graft survival after diagnosis of 1.1 years. Univariate analysis demonstrated that lower-lobe-dominant or diffuse infiltrates on chest computed tomography, presence of an identifiable trigger before rCLAD onset, lymphocytic bronchiolitis, increased BAL neutrophilia, increased BAL eosinophilia and increased blood eosinophils were associated with inferior graft survival after rCLAD diagnosis. Multivariate analysis confirmed the association of location of infiltrates and blood eosinophilia on graft survival., Conclusion: In this study we have identified parameters associated with graft survival after rCLAD diagnosis that may be useful to predict prognosis., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

In this retrospective, single-center data analysis, we audited our clinical practice to treat Stenotrophomonas maltophilia in asymptomatic lung transplant recipients (LTRs). Eighteen LTRs with confirmed isolation of S. maltophilia were identified. Twelve of these LTRs have been treated with antibiotics, while 6 were managed without treatment. Treatment was based on antibiograms (trimethoprim/sulfamethoxazole [TMP/SMX] (8/12), levofloxacin (1/12), or both (3/12). Clearance (12/12 vs 6/6), eradication (10/12 vs 3/6, P=.27), and freedom from S. maltophilia recurrence (83%±11% vs 40%±22% after one year, log-rank P=.09) were not found to differ significantly between treated and untreated patients. None of the patient groups showed significant changes in lung function or biochemical variables. Creatinine levels at the end of the study period were found to be higher in treated patients compared to the untreated group (P=.049). De novo acquired TMP/SMX resistance in S. maltophilia strains was not observed. These results indicate no evidence that antibiotic treatment for S. maltophilia in asymptomatic LTRs alters lung function or the clinical outcome., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Brain death (BD) is associated with various systemic responses and a cascade of inflammatory reactions. It is still unknown how the time interval from BD to cold preservation (CP) affects outcome after lung transplantation (LTx). This report investigates the impact of the time interval from BD to CP on long-term outcome in LTx., Methods: We reviewed 250 consecutive recipients who underwent LTx at our institution between January 2000 and December 2011. In Group I (n = 212), the time interval from BD to CP was <24 h, and in Group II (n = 38) >24 h. Cox proportional hazard regression analysis was performed to determine the risk factors affecting survival., Results: The median time from BD to CP was 18.6 h (range 9-65). The rate of postoperative complications was comparable (P = 0.8). The 30-day mortality rate was 7.5% in Group I and 0% in Group II. The 5-year survival rate was better in Group II [70% (95% CI: 48.5-83.8%)] than in Group I [66% (95% CI: 58.3-72.5%)] without statistical significance (P = 0.3). Intraoperative extracorporeal membrane oxygenation (ECMO) use was identified as a significant risk factor for survival [HR = 1.7, (95% CI: 1.1-2.6), P = 0.01]., Conclusion: In our cohort, the time interval from BD to CP had no impact on long-term outcome after LTx., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

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

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.)

Objectives: Primary graft dysfunction (PGD) is a major cause of mortality within the first year following lung transplantation. Pulmonary hypertension, elevated body mass index (BMI), prolonged ischaemic time of the graft, intraoperative blood transfusions >1000 ml and the use of cardiopulmonary bypass or extracorporeal membrane oxygenation increase the risk for PGD. We aimed to evaluate whether dyslipidaemia is an additional risk factor for the development of PGD., Methods: We retrospectively analysed demographic and clinical data of 264 patients who received their first bilateral lung transplantation between March 2000 and October 2013 at our institution. The endpoint was PGD grade 3 at any time, defined according to the International Society for Heart and Lung Transplantation (ISHLT) criteria. Fasting lipid profiles at listing time or just before transplantation (baseline) were documented and dyslipidaemia was defined as any of the parameters being out of range. Comparisons of continuous variables between patients with PGD grade 3 and patients without were performed with the Mann-Whitney U-test, whereas proportions were compared with the χ(2) test. Continuous variables were presented as arithmetic means with standard deviation for ease of comparison, but levels of statistical significance were computed using the appropriate non-parametric statistical test. To identify PGD risk factors, a forward stepwise logistic regression model was used., Results: PGD occurred in 63 recipients (24%). Pretransplant dyslipidaemia was documented in 153 recipients (58%) and was significantly more prevalent among recipients developing PGD (45 vs 108, P < 0.013). Despite various underlying pulmonary pathologies, higher triglyceride (TG) levels (1.41 ± 0.78 vs 1.16 ± 0.78, P < 0.012), lower high-density lipoprotein-cholesterol (HDL-C) concentrations (1.24 ± 0.55 vs 1.57 ± 0.71, P < 0.0005) and higher cholesterol/HDL-C values (3.80 ± 2.02 vs 3.00 ± 0.92, P < 0.0005) were associated with a lower incidence of PGD. Patients with PGD had significantly longer ischaemic time (350 ± 89 vs 322 ± 91, P = 0.017) and higher BMI (23 ± 5 vs 21 ± 4.4, P < 0.007)., Conclusions: Dyslipidaemia seems to be an independent risk factor for PGD after lung transplantation: low circulating levels of HDL-C and hypertriglyceridaemia increase the incidence of PGD. Even if HDL-C levels are difficult to alter today, triglyceride and cholesterol levels can be addressed therapeutically and may have a positive influence on the development of PGD., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

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

Questions Under Study: To (1) assess distinct clusters of psychological distress and health-related quality of life during the first 6 months following lung transplantation; (2) identify patients with poor psychosocial outcomes; and (3) determine potential predictors regarding psychological distress and health-related quality (HRQoL) of life at 6 months post-transplant., Methods: A total of 40 patients were examined for psychological distress (Symptom Checklist short version-9) and quality of life (EuroQOL five-dimension health-related quality of life questionnaire) during their first 6 months post-transplant. Hierarchical cluster analyses were performed to identify specific types of post-transplant outcomes in terms of psychological distress and HRQoL over the first six post-transplant months. Correlational analyses examined medical and psychosocial predictors of the outcome at 6 months post-transplant., Results: Three distinctive clusters were identified, summarizing either groups of patients with (1) optimal (35%), (2) good (42%), and (3) poor outcome-clusters (23%). The latter tended to be older, to suffer from more severe disease, to have more co-morbidities, to have had a prolonged intensive care unit and/or hospital stay, to have more hospital admissions and were more frequently treated with antidepressants post-transplant. Disease severity, length of stay, quality of life two weeks post-transplant, hospital admissions and use of antidepressants were strong predictors of psychological distress and impaired health-related quality of life at six months of follow-up., Conclusion: Almost a quarter of the investigated patients suffered from elevated distress and substantially impaired HRQoL, with no improvements over time. Results underscore the psychosocial needs of patients with poor post-transplant outcomes.

Background: Lung transplant recipients (LTR) are at increased risk for squamous cell carcinoma of the skin (SCC), but risk factors (RF) are incompletely understood., Objective: To assess associations between exposure to certain medications and viral infections, and subsequent SCC development., Methods: Retrospective study examining incidence and potential RF for SCC in LTR transplanted from 1992 to 2010 followed up at one centre. Cumulative incidence and Cox proportional hazards regression models were used to evaluate RF in the first year post-transplant for SCC formation during the follow-up., Results: In 205 analysed LTR, 46 patients were diagnosed with SCC during a median follow-up of 4.9 years. The cumulative incidences of first SCC were 16.7% and 34.1%, for 5 and 10 years post-transplantation respectively. Multivariable analysis identified CMV replication (HR 7.69, 95% CI 2.93-20.2, P < 0.001) and moxifloxacin exposure (HR 2.35, 95% CI 1.15-4.81, P = 0.020) during the first year post-transplantation as independent RF for SCC development during follow-up., Conclusion: In our cohort, moxifloxacin use and CMV replication during the first year post-transplantation were associated with increased risk for SCC. These two factors could be indicators of over-immunosuppression. Their role in SCC development requires investigations in larger cohorts and prospective studies., (© 2015 European Academy of Dermatology and Venereology.)

Objectives: 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., Methods: 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., Results: 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., Conclusions: 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.)

Cardiothoracic transplantation has significantly impacted the lives of pediatric patients with advanced cardiopulmonary failure. The current state of lung transplantation in children as well as its ongoing and future challenges are discussed.

Multiplex PCR assays for respiratory viruses are widely used in routine diagnostics, as they are highly sensitive, rapid, and cost effective. However, depending on the assay system, cross-reactivity between viruses that share a high sequence homology as well as detection of rare virus isolates with sequence variations can be problematic. Virus sequence-independent metagenomic high-throughput sequencing allows for accurate detection of all virus species in a given sample, as we demonstrate here for human Enterovirus and Rhinovirus in a lung transplant patient. While early in infection a commercial PCR assay recorded Rhinovirus, high-throughput sequencing correctly identified human Enterovirus C104 as the source of infection, highlighting the potential of the technology and the benefit of applying open assay formats in complex diagnostic situations., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A 70-year-old lung transplant recipient patient was admitted with fever, nausea, abdominal pain, peripheral edema and pronounced weakness. An initial work-up for presumed infection revealed cholestatic hepatitis, leukocytosis and thrombocytopenia, but failed to detect a pathogen. An increased glucose uptake exclusively in the liver was demonstrated by positron emission tomography. Liver biopsy showed basophilic inclusions in the cytoplasm of hepatocytes. Broad- range 16S rRNA gene PCR followed by sequence analysis yielded Spiroplasma sp. in two independent blood samples and the liver biopsy, confirming Spiroplasma sp. as the causative agent. Antibiotic treatment with doxycycline and azithromycin led to complete recovery., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Extracorporeal life support (ECLS) as a bridge to lung transplantation (LuTx) is a promising option for patients with end-stage lung disease on the transplant waiting list. We investigated the outcome of patients bridged to lung transplantation on ECLS technologies, mainly extracorporeal membrane oxygenation (ECMO)., Methods: Between January 2007 and October 2013, ECLS was implanted in 30 patients with intention to bridge to LuTx. Twenty-six patients (26/30) were successfully bridged to LuTx on ECLS. The most common diagnosis was cystic fibrosis (N = 12). Venovenous ECMO was used in 10, venoarterial in 4, interventional lung assist in 5, and stepwise combination of them in 7 recipients., Results: Two patients weaned from ECMO, and 2 patients died on ECMO on the waiting list. Median duration of ECLS was 21 days (1-81 years). Six patients were awake and spontaneously breathing during ECLS support. Thirty-day, 1-year, and 2-year survivals were 89%, 68%, and 53%, respectively, for bridged patients and 96%, 85%, and 79%, respectively, for control group (P = 0.001). Three months conditional survivals were 89% and 69% at 1 and 2 years for ECLS group, compared to 92% and 86% for control group (P = 0.03). Cystic fibrosis recipients had 82% survival rate at 1 and 2 years. All recipients bridged to LuTx on awake ECLS (N = 6) are alive with a median follow-up of 10.8 months (range, 6-21 months)., Conclusions: Our data show significantly lower survival in this high-risk group compared to patients transplanted without preoperative ECLS. Awake and ambulatory ECLS provides the best prognosis for these high-risk patients.

Cystic fibrosis (CF) is one of the most common genetic disorders. Mutations of the cystic fibrosis transmembrane regulator causes dysfunction of epithelial membranes within the gastrointestinal and respiratory system. Patients with CF are known to be at risk for gastrointestinal malignancies, and lung transplantation further increases this risk. We report a case series of three CF patients who developed adenocarcinoma of the gastrointestinal tract in the posttransplant setting. One of these case histories describes a gastric cancer, which is a novel and to date unreported observation. These data emphasise the importance of checking CF patients for the development of abdominal complications following lung transplantation.

Background: Chronic lung allograft dysfunction (CLAD), predominantly manifest as bronchiolitis obliterans syndrome (BOS), is the primary cause of morbidity and death after lung transplantation. We assessed the efficacy and safety of 2 de novo immunosuppression protocols to prevent BOS., Methods: This was a multicenter, prospective, international, randomized (1:1) open-label superiority study of de novo enteric-coated mycophenolate sodium (MPS) vs delayed-onset everolimus (RAD), both arms in combination with cyclosporine (CsA) monitored by 2-hour post-dose (C2) levels, and corticosteroids. Target C2 levels were lower in the RAD group because RAD is known to potentiate CsA nephrotoxicity. Cytolytic induction therapy was not used. Patients were stratified at entry for cystic fibrosis. Confirmation of anastomotic healing was required for randomization. Primary efficacy was freedom from BOS Grade 1 on intention-to-treat (ITT) analysis. Secondary efficacy parameters were patient and graft survival and severity of rejection. Treatment failure was defined by graft loss, patient death, drug cessation, or need for other therapy., Results: The 3-year freedom from BOS Grade 1 was 70% for MPS (n = 80) vs 71% for RAD (n = 84; p = 0.95 by log-rank) in ITT but was lower in the RAD arm of the per-protocol population (p = 0.03). The 3-year survival was 84% (MPS) vs 76% (RAD; p = 0.19 by log-rank). Thirteen patients switched from MPS vs 31 from RAD (p < 0.01). Days on MPS were greater than days on RAD (p < 0.01). Rejection events proven by biopsy specimen were more common on MPS (p = 0.02), as were leucopenia (p < 0.01), diarrhea (p < 0.01), and cytomegalovirus infection (p = 0.04). Venous thromboembolism was more frequent on RAD (p = 0.02). Creatinine at 3 years was 160 ± 112 μmol/1iter in MPS patients vs 152 ± 98 μmol/1iter in RAD patients (p = 0.67)., Conclusions: This 3-year ITT analysis found no significant difference between arms but was underpowered to accept the null hypothesis that RAD and MPS have equivalent efficacy in preventing BOS or death after lung transplantation., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: An atherosclerotic disease burden sufficient to put lung transplant candidates at risk for end-organ disease after transplantation is considered to be a relative contraindication for lung transplantation., Objectives: The aim of this study was to assess our current practice of cardiac workup by coronary angiography in lung transplant candidates ≥50 years of age., Methods: We retrospectively analyzed 50 consecutive lung transplant candidates ≥50 years of age in which coronary angiography was performed at the University Hospital Zurich (2009-2013). For every patient, the risk of developing an acute coronary event was estimated by using a recalibrated version of the PROCAM study calculator for the Swiss population., Results: The median estimated risk of developing an acute coronary event within 10 years in the study cohort (n = 50) was 4.2% (interquartile range 1.9-7.6), which is considered to be a low risk. Sixteen percent of patients were considered to be at intermediate risk. In 66% of patients, coronary angiography showed no coronary artery disease (CAD). In 28% of patients, CAD without significant stenosis was diagnosed. In 6% of patients, significant coronary stenosis was detected requiring percutaneous coronary intervention. No correlation between the coronary status and the risk score or cardiovascular risk profile was found., Conclusions: The high prevalence of asymptomatic CAD in lung transplant candidates without correlation to a common clinical risk score supports the important role of coronary angiography for the assessment of coronary artery status. This approach might prevent cardiovascular events and improve long-term survival after transplantation., (© 2015 S. Karger AG, Basel.)

The appropriate selection of lung transplant recipients is an important determinant of outcomes. This consensus document is an update of the recipient selection guidelines published in 2006. The Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) organized a Writing Committee of international experts to provide consensus opinion regarding the appropriate timing of referral and listing of candidates for lung transplantation. A comprehensive search of the medical literature was conducted with the assistance of a medical librarian. Writing Committee members were assigned specific topics to research and discuss. The Chairs of the Writing Committee were responsible for evaluating the completeness of the literature search, providing editorial support for the manuscript, and organizing group discussions regarding its content. The consensus document makes specific recommendations regarding the timing of referral and of listing for lung transplantation. These recommendations include discussions not present in previous ISHLT guidelines, including lung allocation scores, bridging to transplant with mechanical circulatory and ventilator support, and expanded indications for lung transplantation. In the absence of high-grade evidence to support decision making, these consensus guidelines remain part of a continuum of expert opinion based on available studies and personal experience. Some positions are immutable. Although transplant is rightly a treatment of last resort for end-stage lung disease, early referral allows proper evaluation and thorough patient education. Subsequent waiting list activation implies a tacit agreement that transplant offers a significant individual survival advantage. It is both the challenge and the responsibility of the transplant community globally to ensure organ allocation maximizes the potential benefits of a scarce resource, thereby achieving that advantage., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Bronchiectasis is the term used for irreversibly dilated airways. Exact epidemiological information on the frequency of bronchiectasis is not available, but the morphological findings are increasingly detected and the associated syndrome is more frequently diagnosed due to improved imaging techniques and increased awareness among chest physicians. The workup of these patients includes a wide panel of investigations guided by patient history and clinical presentation. Despite thorough evaluation the aetiology frequently remains unclear. Chronic infection with Pseudomonas aeruginosa is associated with a severe course of the disease and its detection has impacts on the therapeutic management. Chest physiotherapy, mucoactive substances and antibiotics are the mainstay of therapy. In this review the evaluation of bronchiectasis and the recent therapeutic insights for non-cystic fibrosis bronchiectasis are discussed., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: For lung transplant recipients (LTRs) influenza infections pose a considerable risk for complications. These infections have mainly been described in hospitalized patients. The aim of this study was to describe characteristics of predominantly outpatient-treated influenza infections., Methods: We conducted a single-season (2010/2011) retrospective observational study using database information of our cohort. Patients with evidence for respiratory tract infection received empirical oseltamivir and an oral antibiotic, pending results from nasopharyngeal swab analysis. In laboratory-confirmed influenza infection, treatment was continued and serial weekly swabs were performed until virologic results were negative., Results: We identified 22 infections in 21 of 173 patients followed up; influenza A virus was diagnosed in 13 and influenza B virus in 9 infections. Leading presenting symptoms were cough and rhinorrhea. Oseltamivir was given within 48 h of symptom onset in 13 infections and within 72 h in 21 infections. Prolonged viral shedding (PVS) for ≥ 7 days was detected in 15 infections; median shedding duration for influenza A was 21 days. In univariable analysis, viral load (VL) at diagnosis was associated with extended duration of shedding (P = 0.006). Multivariable analysis confirmed this association. Bronchiolitis obliterans syndrome stage increased in 3 patients at 6-month follow-up., Conclusion: In this study, PVS of influenza virus was detected in the majority of LTRs and high VL at diagnosis was predictive for prolonged shedding, which occurred despite extended antiviral therapy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Fungal infections create a significant risk to pediatric lung transplant recipients. However, no international consensus guidelines exist for fungal infection prevention strategies. It was the aim to describe the current strategies of antifungal prophylaxis in pediatric lung transplant centers. A self-administered, web-based survey on current practices to prevent fungal infection was circulated to centers within the IPLTC. Twenty-one (88%) IPLTC centers participated, predominantly from Europe and the US. More than 50% of respondents perform adult and pediatric lung transplant operations. Twenty-four percent use universal prophylaxis, 28% give prophylaxis to all patients but stratify the antifungal coverage based on pretransplant risk, and 48% target prophylaxis to only the children with CF or pretransplantation fungal colonization. Commonly, centers aim to target Aspergillus and Candida infection. Monotherapy with either voriconazole or inhaled amphotericin B is used in the majority of centers. Institutions utilize prophylactic therapy for variable time periods (40% 3-6 months; 30% ≥12 months). Alternative drugs were prescribed for lack of tolerance, toxicity, or positive surveillance culture. TDM (itraconazole/voriconazole) was used in 86% of centers. The survey revealed a wide range of antifungal prophylaxis strategies as current international practice in pediatric lung transplant recipients., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

There is a lack of data regarding use of ECMO in children undergoing lung transplantation. We evaluated our experience of ECMO in pediatric lung transplant recipients. All patients (<18 yr) who underwent lung transplants between 1997 and 2011 were included (17 children; nine males; median age 16 yr), and the use of intra-operative ECMO evaluated. Transplant procedures were carried out with intra-operative ECMO in seven children (all bilateral lung transplants). Demographics of ECMO and non-ECMO patients were comparable. One child was already on ECMO pre-operative. Lung graft size reduction was undertaken in five ECMO and four non-ECMO cases, respectively. Five patients were taken off ECMO intra-operatively; the other patients were weaned off ECMO within 48 h post-operatively. Three-months survival was 100%. By 12 months post-transplantation, one patient each died in the ECMO and in the non-ECMO group. At the end of the study, six of seven ECMO cases were still alive (median survival 48.5 months); one patient required a retransplant at 53 months. Our small case series suggests that lung transplant procedures can be safely carried out in selected children on intra-operative ECMO support; however, our pediatric experience regarding this scenario is very limited but probably almost unique., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Severe mucosal tissue damage requiring efficient wound healing is a main feature of inflammatory bowel disease but excessive tissue repair promotes fibrosis. The clinical investigation of fibrosis is confined to the limited amount of biological material available from patients. This makes the establishment of a new animal model, a highly desirable goal. We investigated whether intestinal fibrosis occurs after heterotopic transplantation of small bowel resections in rats., Methods: Donor (Brown Norway or Lewis rats) small bowel resections were transplanted subcutaneously into the neck of recipients (Lewis rats). Grafts were explanted 2, 7, 14, and 21 days after transplantation., Results: Heterotopic intestinal transplants remained viable for 21 days. Rapid loss of crypt structures at day 2 after intestinal transplantation was followed by lymphocyte infiltration and obliteration of the intestinal lumen by fibrous tissue at day 21. Loss of the intestinal epithelium was confirmed by the lack of cytokeratin staining in immunohistochemistry. Collagen expression was increased with time after transplantation as confirmed by real-time PCRs, Elastica van Gieson, and Sirius Red staining. Lumen obliteration was connected with increased expression of potent mediators of fibrosis such as α5β6 integrin, interleukin (IL)-13, and transforming growth factor β. Myofibroblast phenotype was demonstrated by the presence of both α-smooth muscle actin and vimentin in the obliterated lumen., Conclusions: We established a method for heterotopic transplantation of small bowel resections. A variety of histologic and molecular features of fibrosis were observed in the heterotopic intestinal grafts which suggests, that this new in vivo model will be instrumental in studying pathogenesis and treatment of intestinal fibrosis.

Lung transplantation is an accepted therapy in selected patients with end-stage lung disease. However, there is a shortage of suitable donor organs, in particular for small or pediatric patients. Simultaneous bilateral lobar lung transplantation derived from one large donor into two small recipients is reported. The upper lobes were transplanted into the smaller female recipient, and the middle and right lower lobe and left lower lobe were transplanted into the male recipient., (Copyright © 2013. Published by Elsevier Inc.)

Allogenic BMT has been successfully performed as a treatment for hematologic diseases with an expected long-term survival. This survival is truncated by respiratory complications including airway obstruction especially BO. Chronic GVHD has been reported to precede almost all cases reported. LTx has become a therapeutic life-saving option for patients with end-stage lung disease that maybe offered for the treatment of GVHD. We report a multi-center experience of pediatric LTx following BMT in 11 patients age- and gender-matched with 11 controls who received LTx for end-stage lung disease secondary to CF. Overall death was 36.4% over a follow-up period of 19 months (range 3-36 months) for the cases and 27.3% for the control group followed for 17 months (range 8-32 months). Median FEV1 one yr post-transplant for the cases was 78% predicted compared with 67.3% predicted for the controls. The median for episodes of infection was comparable at a median of one episode per patient through the entire follow-up period among both groups. Acute rejection episodes were significantly higher in the control group with a median of one episode per patient in the control group compared to none within the cases. Our data suggest that LTx may be a valuable therapeutic option for children with end-stage lung disease post-BMT with comparable survival outcome to that after LTx in children for other indications such as CF. Hospital stay was significantly longer in our case group. Infection rate was comparable between groups albeit type of infection varied. Significantly and of interest is that acute rejection episodes were non-existent in these cases., (© 2012 John Wiley & Sons A/S.)

Meticulous attention to detail during the early postoperative period after lung transplantation is crucial for the overall success of the procedure. It starts in the intensive care unit with the initiation of immunosuppression, implementation of anti-infective strategies and stabilisation of respiratory function. The subsequent days and weeks on the regular ward focus on titration of immunosuppressive drugs, vigilant fluid management, early mobilisation and initiation of physiotherapy. In parallel, the lung transplant recipients are actively taught about self-monitoring and self-management strategies to allow for a smooth transition to outpatient follow-up care. This article intends to communicate the practical aspects and principles of the patient management used at the authors' centre on a daily basis by a multi-disciplinary transplant team, having at its core both a transplant pulmonologist and a thoracic surgeon. It focuses on the first month after lung transplantation, but does not cover surgical techniques, rare complications or long-term management issues of lung transplant recipients. The target audience of this practical guide are advanced trainees of pulmonology, thoracic surgery, intensive care, anaesthesiology and other clinicians involved in the early postoperative care of lung transplant recipients either in the intensive care unit or on the peripheral ward.

Background: Malnutrition is common in children undergoing lung transplantation, particularly among those with cystic fibrosis (CF). However, the effect of body habitus on outcome after pediatric lung transplantation is unknown. We studied body mass index (BMI) and its effect on outcome in pediatric lung transplantation., Methods: The International Society for Heart and Lung Transplantation Registry on Pediatric Lung Transplantation was queried for primary pediatric lung transplant recipients (aged<18 years) between 1990 and 2008. BMI cohorts were defined according to International Obesity Task Force cutoffs: thinness grade 3, BMI<16 kg/m(2); thinness grade 2, 16 to<17 kg/m(2); thinness grade 1, 17 to<18.5 kg/m(2); normal, 18.5 to<25 kg/m(2); overweight, 25 to<30 kg/m(2); and obese, ≥ 30 kg/m(2). Survival was compared among BMI cohorts within CF and non-CF recipient groups., Results: Included were 897 recipients. The median age at transplantation was 14 years (interquartile, 11, 16 years) and 63% had CF. The incidence of thinness was 59% in CF vs 39% in non-CF patients (p<0.001). A significant proportion of CF patients were underweight, whereas more non-CF patients were obese. Cox regression showed neither underweight nor overweight CF recipients differed in survival compared with recipients of normal-weight recipients. Grade of thinness was not related to outcome after transplantation. For non-CF recipients, being overweight/obese increased risk of death compared with normal-weight recipients (hazard ratio, 2.05; 95% confidence interval, 1.28-3.26; p = 0.002)., Conclusion: The incidence of underweight status amongst pediatric lung transplant recipients with CF is high. However, we did not find a significant negative effect of underweight body habitus on survival in CF children after lung transplantation. Overweight pediatric recipients appear to have poorer survival after transplant., (Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Lung transplantation (LTx) is a therapy for patients with cystic fibrosis (CF) end-stage lung disease. Pseudomonal airway colonization (PAC) is common in CF., Objectives: We investigated the influence of post-transplant sinus surgery and daily nasal douching on PAC after LTx and the influence of PAC on survival and bronchiolitis obliterans syndrome (BOS)., Methods: CF patients transplanted at our centre were included (November 1992 to December 2009). Clinical data, including microbiological data before and after LTx were collected. Survival and BOS following LTx were compared for CF recipients with and without PAC by Kaplan-Meier statistics and Cox regression analysis., Results: Ninety-four CF patients were transplanted, of whom 82 (87%) underwent sinus surgery after transplantation, and 65% of 66 patients with pre-transplant PAC had persistent PAC after transplantation. Upper and lower PAC is related. Patients without PAC after transplantation had a significantly better survival rate, and BOS was less frequent with a later onset. PAC was the only significant parameter for the development of BOS stage 2 in the multivariate analysis for cytomegalovirus infection, acute rejection and PAC., Conclusions: Sinus surgery and daily nasal douching reduced PAC in LTx recipients. Absence of post-transplant PAC had a positive impact on post-transplant survival and the development of BOS., (Copyright © 2012 S. Karger AG, Basel.)

Purpose of Review: Lung transplantation has evolved as an accepted therapy in carefully selected children with end-stage lung disease, offering a prolonged survival and improved quality of life. Presently, more than 100 lung transplant procedures are done in children annually worldwide. Specific aspects of children and adolescents undergoing lung transplantation will be reviewed and an update on most recent developments in the management of paediatric lung transplant recipients will be given., Recent Findings: Certain aspects are unique to children and adolescents undergoing lung transplantation such as a challenging surgical procedure, the effects of immunosuppressant therapy, and the impact of infections on the child's developing immune system and somatic growth. The underlying diagnoses leading to lung transplantation vary considerably by age group. Early referral, careful patient selection and appropriate timing of listing are crucial to achieve the maximal survival benefit. In particular, infectious complications are a common in children. Chronic lung allograft dysfunction remains the major obstacle for a better long-term survival., Summary: Lung transplantation has successfully been performed in infants, children and adolescents with outcomes similar to that in adults. Specific aspects of paediatric lung transplantation include donor shortage for smaller recipients, somatic growth, psychosocial aspects and adherence, and transition to adult care.