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Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students' t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients ( p = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR ( p = 0.03) and CLAD ( p = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kleid, Walter, Moehnle, Wichmann, Kovács, Humpe, Schneider, Michel, Kneidinger, Irlbeck, Fertmann, Dick and Kauke.)

Due to immunosuppression, transplant recipients are at higher risk of infections with SARS-CoV-2 and worse clinical outcomes than immunocompetent hosts. Furthermore, lung transplant patients represent a special group among solid organ recipients, since pneumonia is the main manifestation of COVID-19. However, data on the course of disease and the changes in morbidity and mortality during the course of the pandemic are limited. In our pulmonary rehabilitation clinic, we treat patients shortly after lung transplant as well as long-term transplant patients. Over the last almost 4 years of pandemic, we witnessed several COVID-19 infections in lung transplant patients in our clinic as well as patients who acquired an infection beforehand. In this paper, we aim at retrospectively describing a series of recent COVID-19 cases in our clinic, looking at the clinical course of disease and outcomes in lung transplant patients.

Lung transplantation is currently the gold standard treatment for end-stage lung diseases. Advances in the preservation of donor lungs, the surgical technique and immunosuppressive therapy have led to lung transplantation now being a routine procedure. Nevertheless, the shortage of donor organs, the acute and particularly chronic lung allograft dysfunction (CLAD) still represent major challenges even in experienced centers. Research in this area is still necessary to improve the long-term survival of lung recipients., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Lung transplant (LTx) recipients are at risk for poor outcomes from coronavirus disease 2019 (COVID-19). The aim of the study was to assess the outcome of patients receiving pre-exposure prophylaxis (PrEP) with tixagevimab and cilgavimab after LTx., Methods: All LTx recipients with outpatient visits from February 28th to October 31st, 2022 at two German centers were included. Baseline characteristics were recorded and patients followed until November 30rd, 2022. Infections with SARS-CoV-2, disease severity, and COVID-19-associated death were compared between patients with and without PrEP., Results: In total, 1438 patients were included in the analysis, and 419 (29%) received PrEP. Patients receiving PrEP were older and earlier after transplantation, had lower glomerular filtration rates, and lower levels of SARS-CoV-2-S antibodies. In total, 535 patients (37%) developed SARS-CoV-2 infection during a follow-up of median of 209 days. Fewer infections occurred in patients with PrEP during the study period (31% vs. 40%, p = 0.004). Breakthrough SARS-CoV-2 infections after PrEP occurred in 77 patients (19%). In total, 37 infections (8%) were severe or critical. No difference in severity of COVID-19 was observed between patients with and without PrEP. There were 15 COVID-19-associated deaths (n = 1 after PrEP). Compared to matched controls, there was a non-significant difference towards a lower risk for moderate to critical COVID-19 (p 0.184)., Conclusion: The number of SARS-CoV-2 infections was lower in LTx recipients with PrEP. Despite being at higher risk for worse outcome severity of COVID-19 and associated mortality were similar in patients with and without PrEP., (© 2023. The Author(s).)

Prolonged mechanical ventilation (PMV) after lung transplantation poses several risks, including higher tracheostomy rates and increased in-hospital mortality. Mechanical power (MP) of artificial ventilation unifies the ventilatory variables that determine gas exchange and may be related to allograft function following transplant, affecting ventilator weaning. We retrospectively analyzed consecutive double lung transplant recipients at a national transplant center, ventilated through endotracheal tubes upon ICU admission, excluding those receiving extracorporeal support. MP and derived indexes assessed up to 36 h after transplant were correlated with invasive ventilation duration using Spearman's coefficient, and we conducted receiver operating characteristic (ROC) curve analysis to evaluate the accuracy in predicting PMV (>72 h), expressed as area under the ROC curve (AUROC). PMV occurred in 82 (35%) out of 237 cases. MP was significantly correlated with invasive ventilation duration (Spearman's ρ = 0.252 [95% CI 0.129-0.369], p < 0.01), with power density (MP normalized to lung-thorax compliance) demonstrating the strongest correlation ( ρ = 0.452 [0.345-0.548], p < 0.01) and enhancing PMV prediction (AUROC 0.78 [95% CI 0.72-0.83], p < 0.01) compared to MP (AUROC 0.66 [0.60-0.72], p < 0.01). Mechanical power density may help identify patients at risk for PMV after double lung transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ghiani, Kneidinger, Neurohr, Frank, Hinske, Schneider, Michel and Irlbeck.)

Molecular matching is a new approach for virtual histocompatibility testing in organ transplantation. The aim of our study was to analyze whether the risk for de novo donor-specific HLA antibodies (dnDSA) after lung transplantation (LTX) can be predicted by molecular matching algorithms (MMA) and their combination. In this retrospective study we included 183 patients undergoing LTX at our center from 2012-2020. We monitored dnDSA development for 1 year. Eplet mismatches (epMM) using HLAMatchmaker were calculated and highly immunogenic eplets based on their ElliPro scores were identified. PIRCHE-II scores were calculated using PIRCHE-II algorithm (5- and 11-loci). We compared epMM and PIRCHE-II scores between patients with and without dnDSA using t-test and used ROC-curves to determine optimal cut-off values to categorize patients into four groups. We used logistic regression with AIC to compare the predictive value of PIRCHE-II, epMM, and their combination. In total 28.4% of patients developed dnDSA (n = 52), 12.5% class I dnDSA (n = 23), 24.6% class II dnDSA (n = 45), and 8.7% both class II and II dnDSA (n = 16). Mean epMMs (p-value = 0.005), mean highly immunogenic epMMs (p-value = 0.003), and PIRCHE-II (11-loci) (p = 0.01) were higher in patients with compared to without class II dnDSA. Patients with highly immunogenic epMMs above 30.5 and PIRCHE-II 11-loci above 560.0 were more likely to develop dnDSA (31.1% vs. 14.8%, p-value = 0.03). The logistic regression model including the grouping variable showed the best predictive value. MMA can support clinicians to identify patients at higher or lower risk for developing class II dnDSA and might be helpful tools for immunological risk assessment in LTX patients., (© 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)

Introduction: Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation., Methods: We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19)., Results: The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p < .0001) and having cystic fibrosis (CF) (OP = 10.1, p < .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES., Conclusion: Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection., (© 2022 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown., Methods: This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis., Results: A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the 'SSC' group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of 'SSC' patients was severely impaired compared to 'no SSC' patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004)., Conclusions: SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing., Competing Interests: Disclosure statement None of the authors have any relevant conflict of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Long-term outcome of lung transplantation (LTx) recipients is limited by chronic lung allograft dysfunction (CLAD). In this setting of new onset respiratory failure, the amount of oxygenated hemoglobin (OxyHem; hemoglobin (Hb) concentration × fractional oxygen saturation) may provide valuable information., Objective: We hypothesized that OxyHem predicts survival of LTx recipients at the onset of CLAD., Methods: Data from 292 LTx recipients with CLAD were analyzed. After excluding patients with missing data or supplemental oxygen, the final population comprised 218 patients. The relationship between survival upon CLAD and OxyHem was analyzed by Cox regression analyses and ROC curves., Results: Among the 218 patients (102 males, 116 females), 128 (58.7%) died, median survival time after CLAD onset being 1,156 days. Survival was significantly associated with type of transplantation, time to CLAD, CLAD stage at onset, and OxyHem, which was superior to Hb or oxygen saturation. The risk for death after CLAD increased by 14% per reduction of OxyHem by 1 g/dL, and values below 11 g/dL corresponded to an 80% increase in mortality risk., Conclusion: Thus, OxyHem was identified as an independent predictor of mortality after CLAD onset. Whether it is useful in supporting therapeutic decisions and potentially home monitoring in the surveillance of lung transplant recipients has to be studied further., (© 2022 S. Karger AG, Basel.)

Long-term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L-CsA-i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double-blind, placebo-controlled, multi-center Phase 3 study, 180 LT recipients in BOS grade 0 were planned to receive L-CsA-i or placebo in addition to triple-drug immunosuppression. L-CsA-i was administered twice daily via an Investigational eFlow nebulizer to recipients of single (SLT) and bilateral lung transplants (BLT) within 6-32 weeks posttransplant, and continued for 2 years. The primary endpoint was BOS-free survival. 130 patients were enrolled before the study was prematurely terminated for business reasons. Despite a 2-year actuarial difference in BOS-free survival of 14.1% in favor of L-CsA-i in the overall study population, the primary endpoint was not met (p = .243). The pre-defined per protocol analysis of SLT recipients (n = 24) resulted in a treatment difference of 58.2% (p = .053). No difference was observed in the BLT (n = 48) subpopulation (p = .973). L-CsA-i inhalation was well tolerated. Although this study failed to meet its primary endpoint, the results warrant additional investigation of L-CsA-i in lung transplant recipients., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: Chronic kidney disease (CKD) is associated with significant morbidity and mortality after lung transplantation (LTX). Calcineurin inhibitor (CNI) nephrotoxicity is the leading cause of CKD. After kidney transplantation, polyomavirus-associated nephropathy (PyVAN) is a well-recognized problem. This study aims to evaluate the role of polyomavirus in patients after LTX., Methods: From January 2017 to January 2020, all lung transplant recipients who performed follow-up visits in our center were included in the study and retrospectively assessed. We measured renal function (creatinine levels before and after transplantation), JCPyV, and BKPyV load by polymerase chain reaction (PCR) in serum and urine samples after transplantation., Results: In total, 104 consecutive patients (59 males, 56.7%) with a mean age of 49.6 ± 11.1 years were identified. JCPyV was found in urine of 36 patients (34.6%) and serum of 3 patients (2.9%). BKPyV was found in urine of 40 patients (38.5%) and serum of 4 patients (3.8%), respectively. Urine evidence for JCPyV (p < 0.001, coefficient: +21.44) and BKPyV (p < 0.001, coefficient: +29.65) correlated highly with further kidney function decline., Conclusion: Kidney function deterioration is associated with JCPyV and BKPyV viruria in patients after LTX. This might indicate a role of PyVAN in lung transplant recipients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to evaluate the benefits and potential of structured reports (SR) for chest computed tomography after lung transplantation., Methods: Free-text reports (FTR) and SR were generated for 49 computed tomography scans. Clinical routine reports were used as FTR. Two pulmonologists rated formal aspects, completeness, clinical utility, and overall quality. Wilcoxon and McNemar tests were used for statistical analysis., Results: Structured reports received significantly higher ratings for all formals aspects (P < 0.001, respectively). Completeness was higher in SR with regard to evaluation of bronchiectases, bronchial anastomoses, bronchiolitic and fibrotic changes (P < 0.001, respectively), and air trapping (P = 0.012), but not signs of pneumonia (P = 0.5). Clinical utility and overall quality were rated significantly higher for SR than FTR (P < 0.001, respectively). However, report type did not influence initiation of further diagnostic or therapeutic measures (P = 0.307 and 1.0)., Conclusions: Structured reports are superior to FTR with regard to formal aspects, completeness, clinical utility, and overall satisfaction of referring pulmonologists., Competing Interests: Wieland H. Sommer is a cofounder of the Smart Reporting GmbH, an online software company for structured reporting templates. Neither were the design, or implementation, or evaluation of our study influenced by Smart Reporting GmbH, nor did the company financially support the study. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Bronchiolitis obliterans syndrome (BOS) is a major complication after lung transplantation (LTx). BOS is characterised by massive peribronchial fibrosis, leading to air trapping-induced pulmonary dysfunction. Cathepsin B, a lysosomal cysteine protease, has been shown to enforce fibrotic pathways in several diseases. However, the relevance of cathepsin B in BOS progression has not yet been addressed. The aim of the study was to elucidate the function of cathepsin B in BOS pathogenesis.We determined cathepsin B levels in bronchoalveolar lavage fluid (BALF) and lung tissue from healthy donors (HD) and BOS LTx patients. Cathepsin B activity was assessed via a fluorescence resonance energy transfer-based assay and protein expression was determined using Western blotting, ELISA and immunostaining. To investigate the impact of cathepsin B in the pathophysiology of BOS, we used an in vivo orthotopic left LTx mouse model. Mechanistic studies were performed in vitro using macrophage and fibroblast cell lines.We found a significant increase of cathepsin B activity in BALF and lung tissue from BOS patients, as well as in our murine model of lymphocytic bronchiolitis. Moreover, cathepsin B activity was associated with increased biosynthesis of collagen and had a negative effect on lung function. We observed that cathepsin B was mainly expressed in macrophages that infiltrated areas characterised by a massive accumulation of collagen deposition. Mechanistically, macrophage-derived cathepsin B contributed to transforming growth factor-β1-dependent activation of fibroblasts, and its inhibition reversed the phenotype.Infiltrating macrophages release active cathepsin B, thereby promoting fibroblast activation and subsequent collagen deposition, which drive BOS. Cathepsin B represents a promising therapeutic target to prevent the progression of BOS., Competing Interests: Conflict of interest: C. Morrone has nothing to disclose. Conflict of interest: N.F. Smirnova has nothing to disclose. Conflict of interest: A. Jeridi has nothing to disclose. Conflict of interest: N. Kneidinger has nothing to disclose. Conflict of interest: C. Hollauer has nothing to disclose. Conflict of interest: J.C. Schupp has nothing to disclose. Conflict of interest: N. Kaminski reports personal fees for consultancy and/or advisory board work from Biogen Idec, Boehringer Ingelheim, Third Rock, Samumed, NuMedii, Indaloo, Theravance, LifeMax, Three Lake Partners, RohBar, Pliant and AstraZeneca; non-financial support from Miragen, equity with Pliant and miRagen, and a grant from Veracyte, all outside the submitted work; has patents on New Therapies in Pulmonary Fibrosis and on Peripheral Blood Gene Expression that have been licensed to Biotech; and serves as deputy editor of Thorax. Conflict of interest: D. Jenne has nothing to disclose. Conflict of interest: O. Eickelberg has nothing to disclose. Conflict of interest: A.Ö. Yildirim has nothing to disclose., (Copyright ©ERS 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Phenotyping chronic lung allograft dysfunction (CLAD) in single lung transplant (SLTX) recipients is challenging. The aim of this study was to assess the diagnostic and prognostic value of longitudinal lung function tests in SLTX recipients with CLAD., Methods: A total of 295 SLTX recipients were analyzed and stratified according to native lung physiology. In addition to spirometry, measurements of static lung volumes and lung capacities were used to phenotype patients and to assess their prognostic value. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n = 71)., Results: Of 224 lung transplant recipients, 105 (46.9%) developed CLAD. Time to CLAD onset (hazard ratio [HR]: 0.82, 95% CI: 0.74-0.90; p < 0.001), severity of CLAD at onset (HR: 0.97, 95% CI: 0.94-0.99; p = 0.009), and progression after onset of CLAD (HR: 1.03, 95% CI: 1.00-1.05; p = 0.023) were associated with outcome. Phenotypes at onset were bronchiolitis obliterans syndrome (BOS) (59.1%), restrictive allograft syndrome (RAS) (12.4%), mixed phenotype (6.7%), and undefined phenotype (21.9%). Survival estimates differed significantly between phenotypes (p = 0.004), with RAS and mixed phenotype being associated with the worst survival, followed by BOS and undefined phenotype. Finally, a higher hazard for mortality was noticed for RAS (HR: 2.34, 95% CI: 0.99-5.52; p = 0.054) and mixed phenotype (HR: 3.30, 95% CI: 1.20-9.11; p = 0.021) while controlling for time to CLAD onset and severity of CLAD at onset., Conclusions: Phenotyping CLAD in SLTX remains challenging with a high number of patients with an undefined phenotype despite comprehensive lung function testing. However, phenotyping is of prognostic value. Furthermore, early, severe, and progressive CLADs are associated with worse survival., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Tobacco use after lung transplantation is associated with adverse outcome. Therefore, active smoking is regarded as a contraindication for lung transplantation and should be excluded prior to placement on the waiting list. The aim of the study was to compare self-reporting with a systematic cotinine based screening approach to identify patients with active nicotine abuse. Nicotine use was systematically assessed by interviews and cotinine test in all lung transplant candidates at every visit in our center. Patients were classified according to the stage prior to transplantation and cotinine test results were compared to self-reports and retrospectively analyzed until June 2019. Of 620 lung transplant candidates, 92 patients (14.8%) had at least one positive cotinine test. COPD as underlying disease (OR 2.102, CI 1.110-3.981; p = 0.023), number of pack years (OR 1.014, CI 1.000-1.028; p = 0.047) and a time of cessation less than one year (OR 2.413, CI 1.410-4.128; p = 0.001) were associated with a positive cotinine test in multivariable regression analysis. The majority of non-COPD patients (n = 13, 72.2%) with a positive test had a cessation time of less than one year. 78 patients (84.7%) falsely declared not consuming any nicotine-based products prior to the test. Finally, all never smokers were test negative. In conclusion, our data demonstrate that active nicotine use is prevalent in transplant candidates with a high prevalence of falsely declaring nicotine abstinence. COPD was the main diagnosis in affected patients. Short cessation time and a high number of pack years are risk factors for continued nicotine abuse., Competing Interests: The authors have declared that no competing interests exist.

Background: Cytomegalovirus (CMV)-infection remains a major cause of morbidity and mortality after lung transplantation. Treatment with currently available drugs poses treatment difficulties in some patients due to drug resistance or intolerability., Methods: We report a series of 4 lung transplant recipients with CMV-infection and treatment failure upon standard care due to antiviral drug resistance and treatment-limiting side effects. As rescue therapy letermovir recently approved for the prophylaxis of CMV-infection in patients after hematopoietic stem cell transplantation was initiated. Patients received 480 mg/day for a follow up of 36.1 ± 12.9 weeks. Efficacy and tolerability were assessed retrospectively., Results: Mild nausea, vomiting, and diarrhea were the only side effects of letermovir reported by a single patient. A small adjustment of the tacrolimus dose was mandatory upon treatment initiation with letermovir. CMV viral load could be decreased and cleared subsequently in all patients. CMV clearance was observed after 17.7 ± 12.6 weeks despite lack of CMV-immunity., Conclusions: CMV-infection and -disease were successfully managed with letermovir. Letermovir was well tolerated and effective in treating CMV-infections in lung transplant recipients failing on currently available antiviral agents.

Background: The standard treatment of acute cellular rejection after lung transplantation (LTx) is a high-dose steroid pulse therapy. In our center, this therapy is also the standard of care for LTx recipients with acute loss of forced expiratory volume in 1 second (FEV 1 ), after excluding specific causes such as acute rejection on biopsy. The aim of this retrospective study was to evaluate the safety and efficacy of steroid pulse therapy., Methods: From 2015 to 2018, 33 consecutive patients (17 male patients, mean age ± SD, 50.5 ± 12.5 years) were included. All patients underwent routine examinations to exclude acute cellular rejection and other specific causes. FEV 1 was routinely measured after 5 days, and 1, 3, and 6 months. Positive response to steroid pulse therapy was defined by increase of FEV 1 > 10%., Results: The mean decrease ± SD from baseline in FEV 1 at the start of steroid pulse therapy was 380 ± 630 mL (P = .02). FEV 1 changed after 5 days by 170 ± 180 mL (P = .0007), and after 1 month by 140 ± 230 mL (P = .70), 3 months by -60 ± 240 mL (P = .15), and 6 months by -80 ± 290 mL (P = .73). A positive response was observed in 21% of patients after 3 months and 12% after 6 months. High bronchoalveolar lavage (BAL) eosinophil count correlated with a higher FEV 1 after steroid pulse therapy. Serious complications were observed in 4 out of 33 patients (12%) with 1 fatal event (pneumonia)., Conclusions: Only a minority of patients after LTx with loss of FEV 1 after exclusion of acute cellular rejection benefit from steroid pulse therapy. Patients with BAL eosinophilia are more likely to respond. However, severe complications were observed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pirfenidone demonstrated pleiotropic antiinflammatory effects in various experimental and clinical settings. The aim of this study was to assess the impact of previous treatment with pirfenidone on short-term outcomes after single lung transplantation (SLTx). Therefore, patients with idiopathic pulmonary fibrosis (IPF) who were undergoing SLTx were screened retrospectively for previous use of pirfenidone and compared to respective controls. Baseline parameters and short-term outcomes were recorded and analyzed. In total, 17 patients with pirfenidone were compared with 26 patients without antifibrotic treatment. Baseline characteristics and severity of disease did not differ between groups. Use of pirfenidone did not increase blood loss, wound-healing, or anastomotic complications. Severity of primary graft dysfunction at 72 hours was less (0.3 ± 0.6 vs 1.4 ± 1.3, P = .002), and length of mechanical ventilation (37.5 ± 34.8 vs 118.5 ± 151.0 hours, P = .016) and intensive care unit (ICU) stay (6.6 ± 7.1 vs 15.6 ± 20.3, P = .089) were shorter in patients with pirfenidone treatment. An independent beneficial effect of pirfenidone was confirmed by regression analysis while controlling for confounding variables (P = .016). Finally, incidence of acute cellular rejections within the first 30 days after SLTx was lower in patients with previous pirfenidone treatment (0.0% vs 19.2%; P = .040). Our data suggest a beneficial role of previous use of pirfenidone in patients with IPF who were undergoing SLTx., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: This study was meant to analyse the centre experience of the Munich Lung Transplant Group in lung transplantation of patients with severe pulmonary hypertension. Outcome data focus on survival and right heart remodelling., Methods: All patients receiving a lung transplant between 10/2010 and 08/2016 were retrospectively analysed (n = 343). Patients were categorised into individuals with or without severe pre-operative pulmonary hypertension (PH; mPAP ≥ 35 mm Hg or mPAP ≥ 25 mm Hg with cardiac index < 2.0 L/min/m 2 ). Among those, patients with severe PH secondary to lung disease (Nice Class III) were compared with patients with severe PH due to idiopathic PH (IPAH; Nice Class I). All surviving patients with severe PH were electively followed up by echocardiography., Results: Kaplan-Meier survival probabilities after lung transplantation of each group according to pre-operative mPAP values showed no statistically significant difference (P = 0.14 by log-rank test). Lung transplantation in severe PH patients led to marked right ventricular remodelling as indicated by significantly increased tricuspid annular plane systolic excursion (TAPSE) (P = 0.002), decreased right ventricular end-diastolic dimensions (P = 0.001) and overall reduction in tricuspid valvular regurgitation, when compared to pre-operative assessments., Conclusion: Sequential bilateral lung transplantation (BLTx) in patients with severe pulmonary hypertension is a feasible treatment option in this high-risk group in experienced high-volume centres. Lung transplantation allows for resolution of secondary right heart failure in these patients., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: There is a need for non-invasive parameters that are sensitive to the development of the bronchiolitis obliterans syndrome (BOS) in lung transplantation (LTx) patients. We studied whether the pulmonary diffusing capacity for inhaled nitric oxide is capable of detecting BOS stages., Methods: Sixty-one LTx patients were included into this cross-sectional study (19/29/7/3/3 in BOS stages 0/0-p/1/2/3). For analysis stages 0/0-p versus 1/2/3 ("BOS binary-early"), and stages 0/0-p/1 versus 2/3 ("BOS binary-late") were summarized. Measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) were compared with spirometry and bodyplethysmography, and their relative importance was evaluated by discriminant analysis., Results: Regarding the recognition of "BOS binary-early", among spirometric parameters forced expiratory volume in 1 s (FEV 1 ) was best, among bodyplethysmographic parameters airway resistance, and among diffusing parameters DLNO. Regarding "BOS binary-late", DLNO was inferior to bodyplethysmographic parameters., Conclusion: Although the study comprised only measurements at a single time point and no follow-up, DLNO outperformed FEV 1 , the time course of which is used in detecting BOS. Together with its pathophysiological plausibility, this result suggests that the measurement of DLNO, possibly over time, could be an easily applicable tool for the monitoring of LTx patients and should be evaluated in larger studies.

Introduction: Idiopathic pulmonary fibrosis (IPF) is considered a disease of older patients, being rare in patients ≤ 50 years. Still, IPF can occur in younger patients, but this particular patient group is not well characterised so far. The aim of this study was to compare the diagnostic certainty, clinical features, comorbidities and survival in young versus older IPF patients., Methods: We reviewed our medical records from February 2011 until February 2015, to identify IPF patients, who were then classified as young (≤ 50 years) or older IPF (> 50 years). Radiographic and histological findings, lung function parameters, comorbidities, disease progression and survival were analysed and compared between the two groups., Results: Of 440 patients with interstitial lung disease, 129 patients with IPF were identified, including 30 (23.3%) ≤50 years and 99 (76.7%) > 50 years. There were no differences between age groups in baseline demographics; younger patients were less likely to have a confirmed diagnosis by high-resolution computed tomography (p = 0.014), more likely to require a biopsy (p = 0.08) and less likely to have received antifibrotic therapy (p = 0.006). Despite an overall limited prognosis, younger patients had a significantly better median survival after diagnosis (p = 0.0375), with a significantly higher proportion of older patients dying due to respiratory failure (p = 0.0383)., Conclusion: IPF patients under the age of 50 years have similar features and clinical course compared to older IPF patients. These patients should be diagnosed by adopting a multidisciplinary team approach, potentially benefitting from earlier intervention with effective antifibrotic therapy.

Objectives: The Lung Allocation Score (LAS) was implemented in Germany on 10 December 2011 after demonstrating favourable outcomes in the USA since its introduction in 2005. There are only limited and short-term data on the effect of the LAS on lung transplantation programmes in Germany. The purpose of this study was to analyse our 5-year single-centre experience with the LAS within the influential area of the Eurotransplant Foundation (ET)., Methods: After implementation of the LAS until December 2016, 294 patients underwent a single-lung transplantation or a bilateral sequential lung transplantation for end-stage lung disease at our centre. Patients were divided into 4 groups according to their primary diagnosis. The Kaplan-Meier analyses of survival probabilities were performed to compare types of transplant procedures, underlying diagnoses and the LASs at the time of transplantation. Waitlist characteristics, transplant procedures and up to 5-year post-transplant outcomes were analysed., Results: The proportion of lung transplants performed for interstitial lung disease increased over time from 27% in 2012 to 54% in 2016 (P = 0.056). At the same time, the proportion of patients with chronic obstructive pulmonary disease undergoing lung transplantation declined over the 5-year period, i.e. from 29% in 2011 to 19% in 2016 (P = 0.029). Overall waiting times of transplanted patients were approximately 200 days and did not markedly change over time. There was an increasing proportion of chronic obstructive pulmonary disease patients on the waitlist from 41% in 2011 to 51% in 2016 (P = 0.51). Outcomes were independent of the underlying disease entity or the LAS. Bilateral sequential lung transplantation was associated with a better long-term survival probability when compared with a single-lung transplantation (P < 0.001)., Conclusions: Our centre-specific 5-year experience confirms previous findings demonstrating that the LAS is a well-established tool for the selection of lung transplant candidates, respecting urgency and prognostic transplant benefit in a disease-specific manner. However, the LAS did not shorten overall waiting times in transplanted patients. Further long-term and multicentre data with respect to differential transplant centre activities have to be gathered for further evaluation.

Posaconazole is an extended-spectrum triazole antifungal used in the treatment and prophylaxis of Aspergillus infections. It is available as oral suspension (POS-Liq) and delayed-release tablets (POS-Tab). The aim of this longitudinal, retrospective study was to compare the clinical effectiveness, toxicity and pharmacokinetics of POS-Liq vs POS-Tab in lung transplant recipients (LTx-recipients), who were treated with both formulations subsequently. Twenty-four consecutive LTx-recipients with 191 documented posaconazole trough levels (PTLs) for POS-Liq or POS-Tab were included. The administered daily doses were 300 mg for POS-Tab and 600 mg (prophylaxis) or 800 mg (therapy) for POS-Liq. Target PTLs were ≥700 ng/mL (prophylaxis) and ≥1250 ng/mL (therapy). The overall prophylactic and therapeutic response rates were 78% and 67%, respectively. No cases of hepatotoxicity or QT-prolongation were observed with either formulation. The achieved target PTLs were tripled under POS-Tab compared to POS-Liq with fewer risk factors for sub-therapeutic PTLs. Concomitant administration of POS-Tab significantly reduced the tacrolimus concentration-to-dose ratio (P = .001). We suggest the use of POS-Tab is appropriate for prophylaxis and therapy of Aspergillus infections in LTx-recipients, since POS-Tab displayed more reliable PTLs with no added adverse events. However, we recommend regular drug monitoring for POS-Liq and for therapy with POS-Tab and that immunosuppressant levels are monitored closely when the posaconazole formulation is switched., (© 2017 Blackwell Verlag GmbH.)

Objective: 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., Design: Retrospective data analysis., Setting: Single-center university hospital., Participants: A development data set of 170 consecutive patients and an independent validation cohort of 52 patients undergoing lung transplantation., Interventions: 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)., Measurements and Main Results: 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., Conclusions: 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.)

Identification of disease phenotypes might improve the understanding of patients with chronic lung allograft dysfunction (CLAD). The aim of the study was to assess the impact of pulmonary restriction and air trapping by lung volume measurements at the onset of CLAD.A total of 396 bilateral lung transplant recipients were analysed. At onset, CLAD was further categorised based on plethysmography. A restrictive CLAD (R-CLAD) was defined as a loss of total lung capacity from baseline. CLAD with air trapping (AT-CLAD) was defined as an increased ratio of residual volume to total lung capacity. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n=95).Of 301 lung transplant recipients, 94 (31.2%) developed CLAD. Patients with R-CLAD (n=20) and AT-CLAD (n=21), respectively, had a significantly worse survival (p<0.001) than patients with non-R/AT-CLAD. Both R-CLAD and AT-CLAD were associated with increased mortality when controlling for multiple confounding variables (hazard ratio (HR) 3.57, 95% CI 1.39-9.18; p=0.008; and HR 2.65, 95% CI 1.05-6.68; p=0.039). Furthermore, measurement of lung volumes was useful to identify patients with combined phenotypes.Measurement of lung volumes in the long-term follow-up of lung transplant recipients allows the identification of patients who are at risk for worse outcome and warrant special consideration., (Copyright ©ERS 2017.)

Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies.13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10 µm (PM 10 ) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway.After correction for macrolide use, we found associations between air pollution variables and CLAD/mortality. Given the important interaction with macrolides, we stratified according to macrolide use. No associations were observed in 2151 patients taking macrolides. However, in 3556 patients not taking macrolides, mortality was associated with PM 10 (hazard ratio 1.081, 95% CI 1.000-1.167); similarly, CLAD and mortality were associated with road lengths in buffers of 200-1000 and 100-500 m, respectively (hazard ratio 1.085- 1.130). Sensitivity analyses for various possible confounders confirmed the robustness of these associations.Long-term residential air pollution and traffic exposure were associated with CLAD and survival after lung transplantation, but only in patients not taking macrolides., (Copyright ©ERS 2017.)

Background: Careful patient selection is the prerequisite to raise transplant benefit. In lung transplant (LT) candidates, the effect of body mass index (BMI) on postoperative outcome remains controversial, possibly due to the inaccuracy of BMI in discriminating between fat and muscle mass. We therefore hypothesized that assessment of body composition by muscle mass measures is more accurate than by BMI regarding postoperative outcome., Methods: All LT recipients from 2011 to 2014 were included and retrospectively analyzed. Lean psoas area (LPA) was assessed from pretransplant computed tomography scans, and associations with postoperative outcomes were investigated., Results: Included were 103 consecutive LT recipients with a mean pre-LT BMI of 22.0 ± 4.0 kg/m(2) and a mean LPA of 22.3 ± 8.3 cm(2). LPA was inversely associated with length of mechanical ventilation (p = 0.03), requirement of tracheostomy (p = 0.035), and length of stay in the intensive care unit (p = 0.02), while controlling for underlying disease, BMI, sex, age, and procedure; in contrast, BMI was not (p = 0.25, p = 0.54, and p = 0.42, respectively.). Multiple regression analysis revealed that the 6-minute walk distance at the end of pulmonary rehabilitation was significantly associated with LPA (p = 0.02)., Conclusions: LPA can easily be assessed in LT candidates as part of pretransplant evaluation and was significantly associated with short-term outcome, whereas BMI was not. Assessment of LPA may provide additional information on body composition beyond BMI. However, the clinical utility has to be further evaluated., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Optimal rehabilitation programs are essential in the early phase after lung transplantation (LTx). Whole-body vibration (WBV) may be a novel approach in rehabilitation that has not yet been investigated in these patients., Patients and Methods: Ten patients in the early postoperative phase after LTx after discharge from the intensive care unit (ICU) were included in the study. WBV training was performed until transfer to a rehabilitation center. Six-minute walk distance (6-MWD), pulmonary function, maximal workload, and quality of life (SF-36) were assessed at the beginning and after completion of the training program., Results: Patients revealed a significant improvement of the 6-MWD, the vital capacity (VC), the maximal workload, and in quality of life. Peak cough flow (PCF), forced expiratory volume (FEV1), and parts of the quality of life questionnaire showed no significant changes. No adverse events occurred in these patients., Conclusion: WBV in lung transplant recipients after discharge from ICU is safe and feasible. WBV may effectively support rehabilitation programs improving pulmonary function and quality of life., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In December 2011, the Eurotransplant Foundation (Leiden, The Netherlands) changed the allocation system for donor lungs from a model based on urgency and waiting time to the lung allocation score (LAS)., Objective: The aim of the study was to investigate the effects of the LAS implementation on the early outcome after lung transplantation in Germany., Methods: We therefore retrospectively studied the outcome of the last 50 patients transplanted before and the first 50 patients transplanted after LAS implementation., Results: Both patient groups were comparable in baseline characteristics at the time of transplantation. Postoperative hospital stays were comparable between the groups, that is, 40.3 ± 26.8 and 40.3 ± 31.3 days (p = 0.992). Also, survival rates on intensive care, during entire hospital stay, at 90 days, 6 month, and 1 year after transplant were comparable between the groups. The retrospectively calculated LASs of the patients transplanted under the old allocation system were not statistically significantly different from those after LAS implementation, that is, 46.5 ± 14.2 and 51.2 ± 17.4 (p = 0.139)., Conclusion: We demonstrate, for the first time, that implementation of the LAS in Germany had no negative effect on the early outcome after lung transplantation. Our data indicate that patients transplanted before implementation of the LAS had a similar prospective transplant benefit., (Georg Thieme Verlag KG Stuttgart · New York.)

We report the case of a young female lung transplant recipient with difficult-to-treat cytomegalovirus (CMV) disease. While treatment with intravenous (IV) ganciclovir failed due to antiviral drug resistance, a trial with foscarnet resulted in severe side effects. In addition, the patient received IV CMV-specific immune globulins as adjunctive therapy and leflunomide as experimental therapy. In this context, CMV-specific immune monitoring was performed and was successfully implemented in management decisions. The patient was screened for acquisition of an adaptive immune response, and antiviral prophylaxis and therapy was tailored according to results. This report highlights the impact of CMV-specific immune monitoring on individualized therapy for appropriate prophylaxis and management of CMV infection and diseases.

Objective and Methods: The Eurotransplant Foundation introduced the lung allocation score (LAS) in Germany on December 10, 2011. We analyzed characteristics of the Munich Lung Transplant Group (MLTG) waiting list during the first 9 months after the introduction of the LAS., Results: A mean number of 39 ± 1 patients were constantly listed for lung transplantation and 60 transplants were performed by the MLTG during the observation period. While the majority (42 ± 0%) of patients waiting for transplant comprised chronic obstructive pulmonary disease (COPD)/emphysema patients, only 26% of transplanted patients suffered from COPD/emphysema. Instead, the majority (42%) of transplanted patients suffered from interstitial lung disease. Waiting times did not markedly change in the LAS era. Notably, patients with interstitial lung disease had shorter waiting times when compared with patients suffering from COPD/emphysema and cystic fibrosis, both on the waiting list and at the time of transplant., Conclusion: The MLTG lung transplant waiting list has not markedly changed during the first 9 months after the introduction of the LAS. Our data indicate that the LAS accommodates disease-specific patient statuses well. Although patients with interstitial lung disease are preferably transplanted, the LAS system provides a very reasonable basis to also list and transplant COPD/emphysema patients., (Georg Thieme Verlag KG Stuttgart · New York.)

The impact of de novo donor‐specific anti‐HLA‐antibodies (donor‐specific antibody [DSA]) on outcomes in lung transplantation is still a matter of debate. We hypothesize that differentiating DSA by persistent and transient appearance may offer an additional risk assessment. The clinical relevance of HLA‐antibodies was investigated prospectively in 72 recipients with a median follow‐up period of 21 months. The presence of HLA‐antibodies was analysed by a single antigen bead assay before and after (3 weeks, 3, 6, 12 and 18 months) transplantation. In 23 patients (32%), de novo DSAs were detected. In 10 of these patients (44%), DSA persisted throughout the follow‐up period, whereas 13 of these patients (56%) had transient DSA. There was a trend towards lower 1‐year‐survival in DSA‐positive compared with DSA‐negative patients (83% vs 94%; P = 0.199). Remarkably, patients with persistent DSA had significantly reduced survival (1‐year survival 60%) compared with both patients without DSA and those with transient DSA (P = 0.005). Persistent DSA represented as an independent prognostic factor for reduced overall survival in multivariate analysis (HR 8.3, 95% CI 1.8‐37.0; P = 0.006). Persistence of DSA during the first year after transplantation seems to be more harmful for lung allograft function than transiently detected DSA at an early stage. [ABSTRACT FROM AUTHOR]

Chronic lung allograft dysfunction ( CLAD) is a limiting factor for long-term survival in lung transplant recipients. Donor-specific human leukocyte antigen ( HLA)-antibodies ( DSA) have been suggested as potential risk factors for CLAD. However, their impact on clinical outcome following lung transplantation remains controversial. We performed a single-center study of 120 lung transplant recipients transplanted between 2006 and 2011. Patient sera were investigated before and after transplantation. The sera were screened by means of Luminex® technology (Luminex Inc., Austin, TX, USA) for IgG-HLA-class I and class II antibodies (ab). Using single antigen beads, DSA were identified and correlated retrospectively with clinical parameters. After transplantation 39 out of 120 patients (32.5%) were positive for HLA-ab. The incidence of de novo DSA formation was 27 of 120 patients (22.5%). Eleven of 27 (41%) of de novo DSA-positive patients developed BOS compared to 13 of 93 (14%) DSA-negative patients ( p = 0.002). Furthermore, the generation of de novo DSA was independently associated with the development of BOS in multivariable analysis [hazard ration ( HR) 2.5, 95% confidence interval ( CI) 1.0-6.08; p = 0.046). Our results indicate that de novo DSA are associated with the development of BOS after lung transplantation. Monitoring of HLA-ab after transplantation is useful for identifying high-risk patients and offers an opportunity for early therapeutic intervention. [ABSTRACT FROM AUTHOR]

Everolimus-based quadruple low calcineurin inhibitor (CNI) maintenance immunosuppression has been shown to be effective in preserving short-term renal function without compromising efficacy or safety after lung transplantation. However, long-term benefit remains unknown. An investigator-initiated 5-year follow-up analysis of the 4EVERLUNG study (NCT01404325), comparing everolimus-based quadruple low CNI with standard triple regimen was performed. Patients who remained on the randomized drug regimen until end of the 5-year observation were analysed as per protocol (PP) population. Patients in whom the assigned regimen was switched were analysed as intention to treat (ITT) population. In total, 123 patients (95%) from the core study were analysed. Over the observation period in 11 patients (19%) of the standard triple regimen and in 30 patients (46%) of the quadruple low CNI regimen the assigned immunosuppressive regimen was switched (p=0.002). Estimated glomerular filtration rate at 5-year follow-up did not differ between the groups in both the ITT (56 [48, 73] vs. 58 [48, 69] mL/min; p=0.951) and PP (59 [50, 73] vs. 59 [48, 69] mL/min; p=0.946) population. Thromboembolic events occurred more frequent in the quadruple low CNI regimen (ITT: 11% vs. 24%, p=0.048; PP 11% vs. 22%, p=0.162). There was a trend for a higher CLAD-free survival for the quadruple low CNI regimen in the PP population (p=0.082). No difference in the graft-survival was found between the groups. Initiation of an early everolimus-based quadruple low CNI regimen had no long-term benefit on renal function. The immunosuppressive efficacy and safety profile appears comparable to the standard triple regimen. [ABSTRACT FROM AUTHOR]

Bronchiolitis obliterans syndrome (BOS), the most common form of chronic lung allograft dysfunction (CLAD), and the major limitation to long-term survival after lung transplantation. BOS affects up to 50% of lung transplant recipients within 5 years after transplant, causing significant morbidity and mortality. BOS manifesting early after transplantation shows a poorer prognosis than late‐onset BOS. There are only few studies assessing treatment efficacy, but only a minority of patients respond to current treatment options. From trans‐bronchial surveillance biopsies and autopsies from diseased transplant recipients, the BOS lesions reveal interstitial fibrosis, which suggest the possible use of anti‐fibrotic agent like Pirfenidone. We hypothesized that there is a statistically significant difference between randomized study groups in the change in FEV1 from baseline to 6 months. This trial is investigator-initiated and including nine European expert lung transplant centers. Patients with new onset progressive BOS were randomized in a 1:1 ratio to receive either Pirfenidone or the matching placebo treatment for 6 months. Progressive BOS was defined by the following: at least 3 FEV1-measurements in the last 6 months, each at least 3 weeks apart, a total decline of at least 200ml in FEV1, and a mean decline of at least 50 ml in the last two measurements, as well as the exclusion of other reasons for FEV1 decline by an expert panel. All patients had to be on at least 250mg Azithromycin 3 times a week for at least 4 weeks prior to inclusion. A total of 80 patients were planned included in the study 40 in each group. The primary endpoint is to evaluate the effect of Pirfenidone on the change in FEV1 (ml) over 6 months in lung transplant recipients with BOS, who are treated with Azithromycin. Secondary endpoints are as follows; Categorical percentage change in FEV1, Change in FVC, Change in TLC, Change in FEV1/FVC ratio, Number of patients with treatment failure, Change in BOS grade, Change in percent predicted diffusion capacity (DLco), Change in functional level as assessed by 6MWT, Hospital admission for any reason, Death or re-transplantation rates, Change in quality of life assessed by EQ5D. [ABSTRACT FROM AUTHOR]