Involvement of IL-26 in bronchiolitis obliterans syndrome but not in acute rejection after lung transplantation.

BACKGROUND:  The main long-term complication after lung transplantation is bronchiolitis obliterans syndrome (BOS), a deadly condition in which neutrophils may play a critical pathophysiological role. Recent studies show that the cytokine interleukin IL-26 can facilitate neutrophil recruitment in response to pro-inflammatory stimuli in the airways. In this pilot study, we characterized the local involvement of IL-26 during BOS and acute rejection (AR) in human patients. METHOD:  From a biobank containing bronchoalveolar lavage (BAL) samples from 148 lung transplant recipients (LTR), clinically-matched patient pairs were identified to minimize the influence of clinical confounders. We identified ten pairs (BOS/non-BOS) with BAL samples harvested on three occasions for our longitudinal investigation and 12 pairs of patients with and without AR. The pairs were matched for age, gender, preoperative diagnosis, type of and time after surgery. Extracellular IL-26 protein was quantified in cell-free BAL samples using an enzyme-linked immunosorbent assay. Intracellular IL-26 protein in BAL cells was determined using immunocytochemistry (ICC) and flow cytometry. RESULTS:  The median extracellular concentration of IL-26 protein was markedly increased in BAL samples from patients with BOS (p < 0.0001) but not in samples from patients with AR. Intracellular IL-26 protein was confirmed in alveolar macrophages and lymphocytes (through ICC and flow cytometry) among BAL cells obtained from BOS patients. CONCLUSIONS:  Local IL-26 seems to be involved in BOS but not AR, and macrophages as well as lymphocytes constitute cellular sources in this clinical setting. The enhancement of extracellular IL-26 protein in LTRs with BOS warrants further investigation of its potential as a target for diagnosing, monitoring, and treating BOS.

Lung transplantation after allogeneic stem cell transplantation: a pan-European experience.

Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring subsequent 5-year survival of 50%. Lung transplantation is rarely performed in this setting due to concomitant extrapulmonary morbidity, excessive immunosuppression and concerns about recurring malignancy being considered contraindications. This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT.SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan-Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed.Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%), with prior mechanical ventilation (HR 6.9, 95% CI 1.0-46.7; p<0.001) the leading risk factor. No SCT-specific risk factors were identified. Recurring malignancy occurred in four patients (4%). Lung transplantation <2 years post-SCT increased all-cause 1-year mortality (HR 7.5, 95% CI 2.3-23.8; p=0.001).Lung transplantation outcomes following SCT were comparable to other end-stage diseases. Lung transplantation should be considered feasible in selected candidates. No SCT-specific factors influencing outcome were identified within this carefully selected patient cohort.

Microbiological findings in bronchoalveolar lavage fluid from lung transplant patients in Sweden.

BACKGROUND: Lung transplant patients experience a high risk of airway infections and microbial colonization of the lung due to constant exposure to the environment through inhaled microorganisms, denervation, reduced ciliary transport, and decreased cough. METHODS: In this nationwide prospective study on Swedish lung transplant patients, we evaluated the microbiological panorama of bacteria, fungi, and virus found in bronchoalveolar lavage fluid (BALF) obtained the first year after lung transplantation (LTx). Differences in microbiological findings depending of concomitant signs of infection and background factors were assessed. RESULTS: A total of 470 bronchoscopies from 126 patients were evaluated. Sixty-two percent (n = 293) of BALF samples had positive microbiological finding(s). Forty-six percent (n = 217) had bacterial growth, 29% (n = 137) fungal growth, and 9% (n = 43) were positive in viral PCR. In 38% of BALF samples (n = 181), a single microbe was found, whereas a combination of bacteria, fungi or virus was found in 24% (n = 112) of bronchoscopies. The most common microbiological findings were Candida albicans, Pseudomonas aeruginosa and coagulase negative Staphylococcus (in 42 (33%), 36 (29%), and 25 (20%) patients, respectively). Microbiological findings were similar in BALF from patients with and without signs of lung infection and the frequency of multidrug resistant (MDR) bacteria was low. No significant association was found between background factors and time to first lung infection. CONCLUSION: This study gives important epidemiologic insights and reinforces that microbiological findings have to be evaluated in the light of clinical symptoms and endobronchial appearance in the assessment of lung infections in lung transplant patients.

Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial.

The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3 ml/min) to last visit (51.4 ml/min) but decreased in controls (from 50.5 ml/min to 45.3 ml/min) and was significantly higher with everolimus at last follow-up (P = 0.004). The least squares mean (SE) change from randomization was -1.5 (1.7)ml/min with everolimus versus -7.2 (1.7)ml/min for controls (difference: 5.7 [95% CI 1.7; 9.6]ml/min; P = 0.006). The difference was accounted for by heart transplant patients (difference: 6.9 [95% 2.3; 11.5]ml/min; P = 0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death, and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% vs. 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least 5 years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained.

Lung transplantation in telomerase mutation carriers with pulmonary fibrosis.

Lung transplantation is the only intervention that prolongs survival in idiopathic pulmonary fibrosis (IPF). Telomerase mutations are the most common identifiable genetic cause of IPF, and at times, the telomere defect manifests in extrapulmonary disease such as bone marrow failure. The relevance of this genetic diagnosis for lung transplant management has not been examined. We gathered an international series of telomerase mutation carriers who underwent lung transplant in the U.S.A., Australia and Sweden. The median age at transplant was 52 years. Seven recipients are alive with a median follow-up of 1.9 years (range 6 months to 9 years); one died at 10 months. The most common complications were haematological, with recipients requiring platelet transfusion support (88%) and adjustment of immunosuppressives (100%). Four recipients (50%) required dialysis for tubular injury and calcineurin inhibitor toxicity. These complications occurred at significantly higher rates relative to historic series (p<0.0001). Our observations support the feasibility of lung transplantation in telomerase mutation carriers; however, severe post-transplant complications reflecting the syndromic nature of their disease appear to occur at higher rates. While these findings need to be expanded to other cohorts, caution should be exercised when approaching the transplant evaluation and management of this subset of pulmonary fibrosis patients.

Effect of once-per-day tacrolimus versus twice-per-day ciclosporin on 3-year incidence of chronic lung allograft dysfunction after lung transplantation in Scandinavia (ScanCLAD): a multicentre randomised controlled trial.

BACKGROUND: Evidence is low regarding the choice of calcineurin inhibitor for immunosuppression after lung transplantation. We aimed to compare the use of tacrolimus once per day with ciclosporin twice per day according to the current definition of chronic lung allograft dysfunction (CLAD) after lung transplantation. METHODS: ScanCLAD is an investigator-initiated, open-label, multicentre, randomised, controlled trial in Scandinavia evaluating whether an immunosuppressive protocol based on anti-thymocyte globulin induction followed by tacrolimus (once per day), mycophenolate mofetil, and corticosteroids reduces the incidence of CLAD after de novo lung transplantation compared with a protocol using ciclosporin (twice per day), mycophenolate mofetil, and corticosteroids. Patients aged 18-70 years who were scheduled to undergo double lung transplantation were randomly allocated (1:1) to receive either oral ciclosporin (2-3 mg/kg before transplantation and 3 mg/kg [twice per day] from postoperative day 1) or oral tacrolimus (0·05-0·1 mg/kg before transplantation and 0·1-0·2 mg/kg from postoperative day 1). The primary endpoint was CLAD at 36 months post transplantation, determined by repeated lung function tests and adjudicated by an independent committee, and was assessed with a competing-risks analysis with death and re-transplantation as competing events. The primary outcome was assessed in the modified intention-to-treat (mITT) population, defined as those who underwent transplantation and received at least one dose of study drug. This study is registered at ClinicalTrials.gov (NCT02936505) and EudraCT (2015-004137-27). FINDINGS: Between Oct 21, 2016, and July 10, 2019, 383 patients were screened for eligibility. 249 patients underwent double lung transplantation and received at least one dose of study drug, and were thus included in the mITT population: 125 (50%) in the ciclosporin group and 124 (50%) in the tacrolimus group. The mITT population consisted of 138 (55%) men and 111 (45%) women, with a mean age of 55·2 years (SD 10·2), and no patients were lost to follow-up. In the mITT population, CLAD occurred in 48 patients (cumulative incidence 39% [95% CI 31-48]) in the ciclosporin group and 16 patients (13% [8-21]) in the tacrolimus group at 36 months post transplantation (hazard ratio [HR] 0·28 [95% CI 0·15-0·52], log-rank p<0·0001). Overall survival did not differ between groups at 3 years in the mITT population (74% [65-81] for ciclosporin vs 79% [70-85] for tacrolimus; HR 0·72 [95% CI 0·41-1·27], log-rank p=0·25). However, in the per protocol CLAD population (those in the mITT population who also had at least one post-baseline lung function test allowing assessment of CLAD), allograft survival was significantly better in the tacrolimus group (HR 0·49 [95% CI 0·26-0·91], log-rank p=0·021). Adverse events totalled 1516 in the ciclosporin group and 1459 in the tacrolimus group. The most frequent adverse events were infection (453 events), acute rejection (165 events), and anaemia (129 events) in the ciclosporin group, and infection (568 events), anaemia (108 events), and acute rejection (98 events) in the tacrolimus group. 112 (90%) patients in the ciclosporin group and 108 (87%) in the tacrolimus group had at least one serious adverse event. INTERPRETATION: Immunosuppression based on use of tacrolimus once per day significantly reduced the incidence of CLAD compared with use of ciclosporin twice per day. These findings support the use of tacrolimus as the first choice of calcineurin inhibitor after lung transplantation. FUNDING: Astellas, the ALF-agreement, Scandiatransplant Organization, and Heart Centre Research Committee, Rigshospitalet, Denmark.

Long-term Extracorporeal Membrane Oxygenation Bridge to Lung Transplantation After COVID-19.

This report describes a patient with severe acute respiratory syndrome coronavirus 2 infection and irreversible lung destruction who underwent successful lung transplantation after 138 days of bridging with extracorporeal membrane oxygenation support. The case exemplifies that lung transplantation may be a possibility after very long-term coronavirus disease 2019 care, even if the patient is initially an unsuitable candidate.

Fungal Tracheobronchitis in Lung Transplant Recipients: Incidence and Utility of Diagnostic Markers.

Fungal tracheobronchitis caused by Aspergillus and Candida spp. is a recognized complication after lung transplantation, but knowledge of the incidence of Candida tracheobronchitis is lacking. The diagnosis relies on fungal cultures in bronchoalveolar lavage fluid (BALF), but cultures have low specificity. We aimed to evaluate the one-year incidence of fungal tracheobronchitis after lung transplantation and to assess the utility of diagnostic markers in serum and BALF to discriminate fungal tracheobronchitis from colonization. Ninety-seven consecutively included adult lung-transplant recipients were prospectively followed. BALF and serum samples were collected at 1, 3 and 12 months after transplantation and analyzed for betaglucan (serum and BALF), neutrophils (BALF) and galactomannan (BALF). Fungal tracheobronchitis was defined according to consensus criteria, modified to include Candida as a mycologic criterion. The cumulative one-year incidence of Candida and Aspergillus tracheobronchitis was 23% and 16%, respectively. Neutrophils of >75% of total leukocytes in BALF had 92% specificity for Candida tracheobronchitis. The area under the ROC curves for betaglucan and galactomannan in BALF to discriminate Aspergillus tracheobronchitis from colonization or no fungal infection were high (0.86 (p < 0.0001) and 0.93 (p < 0.0001), respectively). To conclude, the one-year incidence of fungal tracheobronchitis after lung transplantation was high and dominated by Candida spp. Diagnostic markers in BALF could be useful to discriminate fungal colonization from tracheobronchitis.

Effects of tobacco smoke on IL-16 in CD8+ cells from human airways and blood: a key role for oxygen free radicals?

Chronic exposure to tobacco smoke leads to an increase in the frequency of infections and in the number of CD8(+) and CD4(+) cells as well as the CD4(+) chemoattractant cytokine IL-16 in the airways. Here, we investigated whether tobacco smoke depletes intracellular IL-16 protein and inhibits de novo production of IL-16 in CD8(+) cells from human airways and blood while increasing extracellular IL-16 and whether oxygen free radicals (OFR) are involved. Intracellular IL-16 protein in CD8(+) cells and mRNA in all cells was decreased in bronchoalveolar lavage (BAL) samples from chronic smokers. This was also the case in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro, in which oxidized proteins were markedly increased. Extracellular IL-16 protein was increased in cell-free BAL fluid from chronic smokers and in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro. This was not observed in occasional smokers after short-term exposure to tobacco smoke. A marker of activation (CD69) was slightly increased, whereas other markers of key cellular functions (membrane integrity, apoptosis, and proliferation) in human blood CD8(+) cells in vitro were negatively affected by water-soluble tobacco smoke components. An OFR scavenger prevented these effects, whereas a protein synthesis inhibitor, a ß-adrenoceptor, a glucocorticoid receptor agonist, a phosphodiesterase, a calcineurin phosphatase, and a caspase-3 inhibitor did not. In conclusion, tobacco smoke depletes preformed intracellular IL-16 protein, inhibits its de novo synthesis, and distorts key cellular functions in human CD8(+) cells. OFR may play a key role in this context.

[Lungtransplantation in Sweden - over 1 200 patients transplanted since 1990]. / Lungtransplantationer i Sverige ­ över 1 200 patienter sedan 1990.

Lung transplantation is an accepted treatment for end stage lung diseases and performed at two national centers in Sweden - Gothenburg and Lund. Since the start in 1990 over 1 200 patients have been transplanted.  The indications are severe progressive lung diseases with short expected survival or severe negative effects on daily life. There are several contraindications among which severe other organ disease, recent malignancy or psychiatric disease are most important.  The most common causes for lung transplantation are chronic obstructive pulmonary disease (COPD), interstitial pulmonary disease, cystic fibrosis and pulmonary hypertension.  Long term survival after 5 years is 63 %, and after 10 years 48 %, which is better than the results reported in the international registry (57 % and 36 % respectively).   Lung transplantation is today a therapy for end stage pulmonary diseases with acceptable survival results. It is likely that the number of patients will increase in the future.

Extended use of extra corporeal membrane oxygenation as bridge to lung transplantation in two patients.

BACKGROUND: We have previously reported our outcome after extra-corporeal membrane oxygenation as bridge-to-lung transplantation, which initially was considered controversial, but over time have gained acceptance and now is performed in most high-volume institutions. CASE PRESENTATION: We now report two "extreme" extra-corporeal membrane oxygenation (ECMO) bridge-to-lung transplantation cases, on ECMO > 200 days prior to lung transplantation. One patient survived long-term and the other one did not, and clinical cause and morbidity is outlined in this case-report. CONCLUSION: We believe these two cases highlight the medical, ethical and resource allocation difficulties involved with saving patients in very dire circumstances. We have shown that a patient can survive extremely long duration of ECMO bridge to lung transplantation, but selection remains crucial to achieve a reasonable cost-benefit.

Design and Rationale of a Scandinavian Multicenter Randomized Study Evaluating if Once-Daily Tacrolimus Versus Twice-Daily Cyclosporine Reduces the 3-year Incidence of Chronic Lung Allograft Dysfunction After Lung Transplantation (ScanCLAD Study).

BACKGROUND: A low level of evidence exists regarding the choice of calcineurin inhibitor (CNI) for immunosuppression after lung transplantation (LTx). Therefore, we designed a randomized clinical trial according to good clinical practice rules to compare tacrolimus with cyclosporine after LTx. METHODS: The ScanCLAD study is an investigator-initiated, pragmatic, controlled, randomized, open-label, multicenter study evaluating if an immunosuppressive protocol based on anti-thymocyte globulin (ATG) induction, once-daily tacrolimus dose, mycophenolate mofetil, and corticosteroid reduces the incidence of chronic lung allograft dysfunction (CLAD) after LTx, compared to a cyclosporine-based protocol with all other immunosuppressive and prophylactic drugs being identical between groups. All patients will be followed for 3 years to determine the main endpoint of CLAD. The study is designed for superiority, and power calculations show that 242 patients are needed. Also, the study is designed with more than 10 substudies addressing other important and unresolved issues in LTx. In addition, the ScanCLAD study enabled the synchronization of the treatment and follow-up protocols of the lung transplantation programs of all five Scandinavian lung transplantation centers. PLANNED OUTCOMES: Recruitment started in 2016. At the end of April 2019, 227 patients were randomized. We anticipate the last patient to be randomized in autumn 2019, and thus the last patient visits will be in 2022. The ScanCLAD study is enrolling and investigates which CNI is to be preferred from a CLAD perspective after LTx. TRIAL REGISTRY NUMBER: ScanCLAD trial registered at ClinicalTrials.gov before patient enrollment (NCT02936505). EUDRACT number 2015-004137-27.

[Severe COPD can benefit from endobronchial valves]. / Svår KOL är en indikation för endobronkiella ventiler - Ger bättre livskvalitet, lungfunktion och prestationsförmåga enligt ny HTA-analys.

Lung volume reduction using endobronchial one-way valves (EBV) have been introduced as a new treatment for end-stage COPD and emphysema. They cause the lung parenchyma distal to the valve to collapse by causing an atelectasis. Nine randomized controlled trials (RCTs) studying the effects of insertion of EBVs in patients with severe emphysema were identified. In two of the RCTs both lungs were treated whereas in seven a unilateral approach was used. In comparison with optimal medical therapy, unilateral placement of EBVs resulted in clinically and statistically significant improvements in lung function, quality of life, and physical capacity in patients with heterogeneous or homogeneous emphysema. There were no significant differences in mortality. The frequency of serious complications and adverse events, especially pneumothorax, was higher. Bilateral EBV treatment did not show corresponding improvements in the outcome variables.

Outcomes and Long-term Survival After Pulmonary Retransplantation: A Single-Center Experience.

BACKGROUND: The median survival after lung retransplantation (ReLTx) reported to the International Society of Heart and Lung Transplantation is restricted to 2.5 years. We report the results after ReLTx from our center. METHODS: A retrospective data collection was performed for the 635 patients who underwent lung transplantation between 1991 and 2017 at our center. Recipient variables were compared between patients undergoing only primary lung transplantation (PLTx) and those undergoing PLTx and later ReLTx. Time to death was compared using the Kaplan-Meier method. The risk of ReLTx was analyzed in Cox regression models. Any interaction between type of transplantation, single/double, and PLTx/ReLTx was investigated. RESULTS: ReLTx was performed in 49 patients. Survival after ReLTx at 30 days and 1, 2, and 5 years was 90%, 76%, 71%, and 55%, respectively, and the corresponding survival after PLTx was 94%, 82%, 76%, and 61%, respectively. A hazard ratio of 1.73 for ReLTx was shown (95% confidence interval [CI], 1.14 to 2.63; P = .011). After adjustments for sex, age, diabetes, renal function, preoperative ventilator, and extracorporeal membrane oxygenation, the hazard ratio was 1.43 (95% CI, 0.90 to 2.26; P = .13). ReLTx was performed in 8 patients (16%) within the first year after PLTx. The 1-year survival for this group was 50% compared with 81% (P = .18) for patients who underwent ReLTx later than 1 year after the PLTx. One-year survival after double ReLTx was 60% (95% CI, 25% to 83%) compared with 79% (95% CI, 63% to 89%) for single ReLTx. CONCLUSIONS: ReLTx is a reasonable option for a selected group of patients. Ideally, a number of well-established risk factors are avoided and the ReLTx is performed more than 1 year after the PLTx.

Lung transplantation after ex vivo lung perfusion in two Scandinavian centres.

OBJECTIVES: We reviewed our combined clinical outcome in patients who underwent lung transplantation after ex vivo lung perfusion (EVLP) and compared it to the contemporary control group. METHODS: At 2 Scandinavian centres, lungs from brain-dead donors, not accepted for donation but with potential for improvement, were subjected to EVLP (n = 61) and were transplanted if predefined criteria were met. Transplantation outcome was compared with that of the contemporary control group consisting of patients (n = 271) who were transplanted with conventional donor lungs. RESULTS: Fifty-four recipients from the regular waiting list underwent transplantation with lungs subjected to EVLP (1 bilateral lobar, 7 single and 46 double). In the EVLP and control groups, arterial oxygen tension/inspired oxygen fraction ratio at arrival in the intensive care unit (ICU) was 30 ± 14 kPa compared to 36 ± 14 (P = 0.005); median time to extubation was 18 h (range 2-912) compared to 7 (range 0-2280) (P = 0.002); median ICU length of stay was 4 days (range 2-65) compared to 3 days (range 1-156) (P = 0.002); Percentage of expected forced expiratory volume at 1s (FEV1.0%) at 1 year was 75 ± 29 compared to 81 ± 26 (P = 0.18); and the 1-year survival rate was 87% [confidence interval (CI) 82-92%] compared to 83% (CI 81-85), respectively. Follow-up to a maximum of 5 years did not show any significant difference in survival between groups (log rank, P = 0.63). CONCLUSIONS: Patients transplanted with lungs after EVLP showed outcomes comparable to patients who received conventional organs at medium-term follow-up. Although early outcome immediately after transplantation showed worse lung function in the EVLP group, no differences were observed at a later stage, and we consider EVLP to be a safe method for increasing the number of transplantable organs.

Viral Respiratory Tract Infection During the First Postoperative Year Is a Risk Factor for Chronic Rejection After Lung Transplantation.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the major limiting factor for long-term survival in lung transplant recipients. Viral respiratory tract infection (VRTI) has been previously associated with CLAD development. The main purpose of this study was to evaluate the long-term effects of VRTI during the first year after lung transplantation in relation to CLAD development. METHOD: Ninety-eight patients undergoing lung transplantation were prospectively enrolled between 2009 and 2012. They were monitored for infections with predefined intervals and on extra visits during the first year, the total follow-up period ranged between 5 and 8 years. Nasopharyngeal swab and bronchoalveolar lavage samples were analyzed using a multiplex polymerase chain reaction panel for respiratory pathogens. Data regarding clinical characteristics and infectious events were recorded. RESULTS: Viral respiratory tract infection during the first year was identified as a risk factor for long-term CLAD development (P = 0.041, hazard ratio 1.94 [1.03-3.66]) in a time-dependent multivariate Cox regression analysis. We also found that coronavirus in particular was associated with increased risk for CLAD development. Other identified risk factors were acute rejection and cyclosporine treatment. CONCLUSIONS: This study suggests that VRTI during the first year after lung transplantation is associated with long-term CLAD development and that coronavirus infections in particular might be a risk factor.

Urgent lung allocation system in the Scandiatransplant countries.

BACKGROUND: Throughout the world, the scarcity of donor organs makes optimal allocation systems necessary. In the Scandiatransplant countries, organs for lung transplantation are allocated nationally. To ensure shorter wait time for critically ill patients, the Scandiatransplant urgent lung allocation system (ScULAS) was introduced in 2009, giving supranational priority to patients considered urgent. There were no pre-defined criteria for listing a patient as urgent, but each center was granted only 3 urgent calls per year. This study aims to explore the characteristics and outcome of patients listed as urgent, assess changes associated with the implementation of ScULAS, and describe how the system was utilized by the member centers. METHODS: All patients listed for lung transplantation at the 5 Scandiatransplant centers 5 years before and after implementation of ScULAS were included. RESULTS: After implementation, 8.3% of all listed patients received urgent status, of whom 81% were transplanted within 4 weeks. Patients listed as urgent were younger, more commonly had suppurative lung disease, and were more often on life support compared with patients without urgent status. For patients listed as urgent, post-transplant graft survival was inferior at 30 and 90 days. Although there were no pre-defined criteria for urgent listing, the system was not utilized at its maximum. CONCLUSIONS: ScULAS rapidly allocated organs to patients considered urgent. These patients were younger and more often had suppurative lung disease. Patients with urgent status had inferior short-term outcome, plausibly due to the higher proportion on life support before transplantation.

Quantification of Torque Teno Virus and Epstein-Barr Virus Is of Limited Value for Predicting the Net State of Immunosuppression After Lung Transplantation.

BACKGROUND: Major hurdles for survival after lung transplantation are rejections and infectious complications. Adequate methods for monitoring immune suppression status are lacking. Here, we evaluated quantification of torque teno virus (TTV) and Epstein-Barr virus (EBV) as biomarkers for defining the net state of immunosuppression in lung-transplanted patients. METHODS: This prospective single-center study included 98 patients followed for 2 years after transplantation. Bacterial infections, fungal infections, viral respiratory infections (VRTI), cytomegalovirus (CMV) viremia, and acute rejections, as well as TTV and EBV levels, were monitored. RESULTS: The levels of torque teno virus DNA increased rapidly after transplantation, likely due to immunosuppressive treatment. A modest increase in levels of Epstein-Barr virus DNA was also observed after transplantation. There were no associations between either TTV or EBV and infectious events or acute rejection, respectively, during follow-up. When Tacrolimus was the main immunosuppressive treatment, TTV DNA levels were significantly elevated 6-24 months after transplantation as compared with Cyclosporine treatment. CONCLUSIONS: Although replication of TTV, but not EBV, appears to reflect the functionality of the immune system, depending on the type of immunosuppressive treatment, quantification of TTV or EBV as biomarkers has limited potential for defining the net state of immune suppression.