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Controlled donation after circulatory death (cDCD) has become a standard in liver, kidney, and lung transplantation (LTx). Based on recent innovations in ex vivo heart preservation, heart transplant centers have started to accept cDCD heart allografts. Because the heart has very limited tolerance to warm ischemia, changes to the cDCD organ procurement procedures are needed. These changes entail delayed ventilation and prolonged warm ischemia for the lungs. Whether this negatively impacts lung allograft function is unclear.A retrospective analysis of cDCD lungs transplanted between 2012 and February 2022 at the Medical University of Vienna was performed. The heart + lung group consisted of cases in which the heart was procured by a cardiac team for subsequent normothermic ex vivo perfusion. A control group (lung group) was formed by cases where only the lungs were explanted. In heart + lung group cases, the heart procurement team placed cannulas after circulatory death and a hands-off time, collected donor blood for ex vivo perfusion, and performed rapid organ perfusion with Custodiol solution, after which the heart was explanted. Up to this point, the lung procurement team did not interfere. No concurrent lung ventilation or pulmonary artery perfusion was performed. After the cardiac procurement team left the table, ventilation was initiated, and lung perfusion was performed directly through both stumps of the pulmonary arteries using 2 large-bore Foley catheters. This study analyzed procedural explant times, postoperative outcomes, primary graft dysfunction (PGD), duration of mechanical ventilation, length of intensive care unit (ICU) stay, and early survival after LTx.A total of 56 cDCD lungs were transplanted during the study period. In 7 cases (12.5%), the heart was also procured (heart + lung group); in 49 cases (87.5%), only the lungs were explanted (lung group). Basic donor parameters were comparable in the 2 groups. The median times from circulatory arrest to lung perfusion (24 minutes vs 13.5 minutes;Although prioritized cDCD heart explantation is associated with delayed ventilation and significantly longer warm ischemic time to the lungs, post-LTx outcomes within the first year are unchanged. Prioritizing heart perfusion and explantation in the setting of cDCD procurement can be considered acceptable.

Many lung transplants fail due to chronic lung allograft dysfunction (CLAD). We recently showed that transbronchial biopsies (TBBs) from CLAD patients manifest severe parenchymal injury and dedifferentiation, distinct from time-dependent changes. The present study explored time-selective and CLAD-selective transcripts in mucosal biopsies from the third bronchial bifurcation (3BMBs), compared to those in TBBs.We used genome-wide microarray measurements in 324 3BMBs to identify CLAD-selective changes as well as time-dependent changes and develop a CLAD classifier. CLAD-selective transcripts were identified with linear models for microarray data (limma) and were used to build an ensemble of 12 classifiers to predict CLAD. Hazard models and random forests were then used to predict the risk of graft loss using the CLAD classifier, transcript sets associated with rejection, injury, and time.T cell-mediated rejection and donor-specific antibody were increased in CLAD 3BMBs but most had no rejection. Like TBBs, 3BMBs showed a time-dependent increase in transcripts expressed in inflammatory cells that was not associated with CLAD or survival. Also like TBBs, the CLAD-selective transcripts in 3BMBs reflected severe parenchymal injury and dedifferentiation, not inflammation or rejection. While 3BMBs and TBBs did not overlap in their top 20 CLAD-selective transcripts, many CLAD-selective transcripts were significantly increased in both for example LOXL1, an enzyme controlling matrix remodeling. In Cox models for one-year survival, the 3BMB CLAD-selective transcripts and CLAD classifier predicted graft loss and correlated with CLAD stage. Many 3BMB CLAD-selective transcripts were also increased by injury in kidney transplants and correlated with decreased kidney survival, including LOXL1.Mucosal and transbronchial biopsies from CLAD patients reveal a diffuse molecular injury and dedifferentiation state that impacts prognosis and correlates with the physiologic disturbances. CLAD state in lung transplants shares features with failing kidney transplants, indicating elements shared by the injury responses of distressed organs.

Izhodišča: Presaditev pljuč je zahtevna metoda zdravljenja za izbrane bolnike z napredovalo pljučno boleznijo. Naraščanje števila primernih kandidatov in standarizacija posega sta v letu 2018 omogočila vzpostavitev transplantacijskega centra v UKC Ljubljana. Prispevek poroča o prvih rezultatih. Metode: Opravili smo analizo lastnega registra bolnikov. Rezultate smo primerjali s skupino bolnikov, ki so jim pred tem opravili presaditev v AKH Dunaj. Rezultati: Med 15. 9. 2018 in 15. 9. 2021 smo opravili 37 presaditev pljuč (od tega pri 13 ženskah). Indikacije so bile KOPB (n = 13, 35 %), pljučne fibroze (n = 7, 19 %), cistična fibroza (n = 5, 14 %), kovidna pljučnica (n = 4, 11 %), bronhiektazije (n = 3, 8 %), pljučna hipertenzija (n = 2, 5 %), limfangioleiomiomatoza (n = 1, 3 %), pomanjkanje alfa-1-antitripsina (n = 1, 3 %) in bronhiolitis (n = 1, 3 %). V primerjavi s prejšnjo skupino bolnikov, napotenih v AKH Dunaj (71 bolnikov, od tega 35 žensk), je bil delež bolnikov s KOPB višji (35 % in 16 %, p = 0,019), bolniki pa so bili starejši (mediana [razpon], 59 [14–68] in 43 [4–58] let, p = 0,001). 76 % darovanih pljuč ni ustrezalo standardnim merilom (30 % darovalcev je bilo starejših od 55 let, 22 % jih je imelo infiltrate na rentgenogramu pljuč, 24 % pa ni izpolnjevalo enega od ostalih meril), v 43 % pa je bila potrebna redukcija velikosti, kar pa ni vplivalo na primarno odpoved presadka. Kratkoročno preživetje je bili podobno v obeh skupinah (1-letno preživetje v UKC Ljubljana 89 % [95 % CI 78–99 %] in v AKH Dunaj 83 % [95 % CI 74–92 %]). Zaključek: Prvi rezultati kažejo, da so zgodnji izidi po presaditvi pljuč primerljivi pri bolnikih, ki so imeli presaditev v UKC Ljubljana ali v AKH Dunaj.

Potent immunosuppressive drugs have been introduced into clinical care for solid organ transplant recipients. It is now time to guide these drugs on an individual level to optimize their efficacy. An ideal tool simultaneously detects overimmunosuppression and underimmunosuppression, is highly standardized, and is straightforward to implement into routine. Randomized controlled interventional trials are crucial to demonstrate clinical value. To date, proposed assays have mainly focused on the prediction of rejection and were based on the assessment of few immune compartments. Recently, novel tools have been introduced based on a more integrated approach to characterize the immune function and cover a broader spectrum of the immune system. In this respect, the quantification of the plasma load of a highly prevalent and apathogenic virus that might reflect the immune function of its host has been proposed: the torque teno virus (TTV). Although TTV control is driven by T cells, other major immune compartments might contribute to the hosts' response. A standardized in-house polymerase chain reaction and a conformité européenne-certified commercially available polymerase chain reaction are available for TTV quantification. TTV load is associated with rejection and infection in solid organ transplant recipients, and cutoff values for risk stratification of such events have been proposed for lung and kidney transplantation. Test performance of TTV load does not allow for the diagnosis of rejection and infection but is able to define at-risk patients. Hitherto TTV load has not been used in interventional settings, but two interventional randomized controlled trials are currently testing the safety and efficacy of TTV-guided immunosuppression.

Transplanted lungs suffer worse outcomes than other organ transplants with many developing chronic lung allograft dysfunction (CLAD), diagnosed by physiologic changes. Histology of transbronchial biopsies (TBB) yields little insight, and the molecular basis of CLAD is not defined. We hypothesized that gene expression in TBBs would reveal the nature of CLAD and distinguish CLAD from changes due simply to time posttransplant. Whole-genome mRNA profiling was performed with microarrays in 498 prospectively collected TBBs from the INTERLUNG study, 90 diagnosed as CLAD. Time was associated with increased expression of inflammation genes e.g. CD1E and immunoglobulins. After correcting for time, CLAD manifested not as inflammation but as parenchymal response-to-wounding, with increased expression of genes such as HIF1A, SERPINE2, and IGF1 that are increased in many injury and disease states and cancers, associated with development, angiogenesis, and epithelial response-to-wounding in pathway analysis. Fibrillar collagen genes were increased in CLAD, indicating matrix changes, and normal transcripts were decreased - dedifferentiation. Gene-based classifiers predicted CLAD with AUC 0.70 (no time-correction) and 0.87 (time-corrected). CLAD related gene sets and classifiers were strongly prognostic for graft failure and correlated with CLAD stage. Thus, in TBBs molecular changes indicate that CLAD primarily reflects severe parenchymal injury-induced changes and dedifferentiation.

Objective A small but relevant proportion of patients with cystic fibrosis develop severely asymmetric chest cavities during the course of their disease. For these patients, the best surgical approach for lung transplantation (LTx) and optimal size matching strategies are controversial. Methods All cystic fibrosis patients with asymmetric chest cavities who underwent LTx at the Medical University of Vienna between 2003 and 2017 were identified (n = 13). Patients were grouped according to different surgical strategies: unilateral full-size and contralateral lobar transplantation (n = 4), standard double LTx after mobilization/repositioning of the mediastinum (n = 3), oversized single LTx followed by pneumonectomy on the smaller contralateral side (n = 4), and single LTx after a remote contralateral pneumonectomy (n = 2). Results Compared with cystic fibrosis patients with symmetric chests (n = 276, control group), the perioperative management of patients with asymmetric chests was often more complicated. Consequently, 90-day mortality was heightened (23.1% vs 6.5%). Despite this, long-term survival was good with a 5-year survival rate of 69% compared with 78%. Of note, outcome seemed superior for patients who surgery was undertaken with a bilateral compared with a unilateral approach. Conclusions Severely asymmetric chest cavities present challenges in regard to the surgical strategy, size matching, and postoperative management. However, in carefully selected patients, LTx provides an adequate long-term outcome.

Summary Purpose There is reason to believe that the favorable measurement properties of the 6‑minute walk test (6MWT) reported for retest reliability and its capability to detect a true change in healthy individuals or persons with chronic respiratory disease may not apply to lung transplant recipients (LuTXr). We therefore investigated retest reliability of the 6MWT and, in addition, made an attempt to explore whether the 6MWT was sensitive enough to detect important changes that occur with postacute rehabilitation in LuTXr after first time LuTX. Methods Immediately before postacute rehabilitation, 50 LuTXr completed 6MWT testing twice, separated by 1–2 workdays (retest reliability), and were reassessed after completion of rehabilitation 2 months later (sensitivity to changes). Body function measures and health-related quality of life (HRQoL) assessments were collected at baseline. Results Baseline retest 6‑minute walk distance (6MWD) and the age-related predicted walking distance (6MWD%pred) scores significantly increased before postacute rehabilitation. The intraclass coefficient of correlation ICC of the 6MWD was 0.93 (95% confidence interval, CI: 0.88–0.96) and its smallest real difference (SRD) 79 m (95% CI: 52;107). Receiver operating curve analyses revealed the rehabilitation associated changes in 6MWD/6MWD%pred to exceed the SRD/SRD% values in a highly accurate way. Conclusion The 6MWT overall represents a reliable functional performance tool in LuTXr that is sensitive to detect changes in physical performance as a result of medical postacute rehabilitation.

OBJECTIVES Only a small proportion of lung transplant recipients achieve a physical status comparable to healthy individuals in the long term. It is reasonable to hypothesize that the necessary cardiopulmonary adaptation required for strenuous physical exercise may be impaired. Exposure to high altitude provides an optimal platform to study the physiological cardiopulmonary adaptation in lung transplant recipients under aerobic conditions. To gain a deeper understanding, 14 healthy lung transplant recipients and healthcare professionals climbed the highest peak in North Africa (Mount Jebel Toubkal; 4167 m) in September 2019. METHODS Monitoring included daily assessment of vital signs, repeated transthoracic echocardiography, pulmonary function tests, and capillary blood sampling throughout the expedition. RESULTS Eleven out of fourteen lung transplant recipients reached the summit. All recipients showed a stable lung function and vital parameters and physiological adaptation of blood gases. Similar results were found in healthy controls. Lung transplant recipients showed worse results in the 6-minute walk test at low and high altitude compared to controls (day 1: 662 m vs. 725 m, p

OBJECTIVES Traditionally, patients on bridge-to-transplant extracorporeal membrane oxygenation were kept sedated and intubated. However, awake bridging strategies have evolved during recent years. This study aims to elaborate differences in physical activity and postoperative outcomes after lung transplantation (LTx), depending on bridging strategy and duration. METHODS Bridged patients receiving LTx between March 2013 and April 2021 were analysed. Awake bridging was defined as a Richmond Agitation-Sedation Scale score of ≥−1 until 24 h before transplantation. Patients were grouped in awake and sedated cohorts. RESULTS A total of 88 patients (35 awake, 53 sedated bridging) were included. After LTx, mobilization to standing position was achieved earlier in awake bridged patients (7 vs 15 days, P < 0.001). Postoperative ventilation time (247 vs 88 h, P = 0.005) and intensive care unit stay (30 vs 16 days, P = 0.004) were longer in the sedated cohort. Awake patients with bridging duration >6 days showed shorter postoperative ventilation time (108 vs 383 h, P = 0.003), less intensive care unit days (23 vs 36, P = 0.003) and earlier mobilization to standing position (9 vs 17 days, P < 0.001). In contrast, postoperative ventilation time and days in intensive care unit in patients with bridge-to-transplant duration ≤6 days were comparable between cohorts. Mobilization to standing position was achieved faster in the awake (≤6 days) bridged cohort (5 vs 9 days, P = 0.024). CONCLUSIONS Despite the complex management of bridged patients, excellent survival rates after LTx can be achieved. Especially in patients with more than 1 week on extracorporeal membrane oxygenation, awake bridging concepts are associated with significantly faster recovery.

ZusammenfassungAsthma und COPD sind die häufigsten obstruktiven Atemwegserkrankungen. Die chronische Inflammation bedingt eine Induktion von proinflammatorischen Zytokinkaskaden. Neben der systemischen Inflammation tragen Hypoxämie, Hyperkapnie, eine katabole Stoffwechsellage, eine gonadale oder eine Schilddrüsendysfunktion, eine muskuloskelettale Dysfunktion und Inaktivität sowie Vitamin D‑Mangel zu einem erhöhten Knochenbruchrisiko bei. Iatrogene Ursachen der Osteoporose sind die zum Teil langjährigen Anwendungen von inhalativen oder systemischen Glukokortikoiden (GC). Die inhalative GC Applikation bei Asthma ist oft schon im Kindes- und Jugendalter indiziert, aber auch interstitielle Lungenerkrankungen wie die chronisch organisierende Pneumonie, die Sarkoidose oder rheumatische Erkrankungen mit Lungenbeteiligung werden mit inhalativen oder oralen GC behandelt. Bei PatientInnen mit zystischer Fibrose kommt es durch die Malabsorption im Rahmen der Pankreasinsuffizienz, durch Hypogonadismus und chronische Inflammation mit erhöhter Knochenresorption zu einer Abnahme der Knochenstruktur. Nach Lungentransplantation ist die Immunsuppression mit GC ein Risikofaktor.Die pneumologischen Grunderkrankungen führen zu einer Veränderung der trabekulären und kortikalen Mikroarchitektur des Knochens und zu einer Verminderung von osteologischen Formations- und Resorptionsmarkern. Hyperkapnie, Azidose und Vitamin D‑Mangel können diesen Prozess beschleunigen und somit das individuelle Risiko für osteoporotische Fragilitätsfrakturen erhöhen.Eine Knochendichtemessung mit einem T‑Score −2,5 auf. Eine niedrig-traumatische Fraktur in der Anamnese indiziert eine osteologische Therapie.Neben der Optimierung des Vitamin D‑Spiegels sind sämtliche in Österreich zur Behandlung der Osteoporose zugelassenen antiresorptiv oder anabol wirksamen Medikamente auch bei pneumologischen PatientInnen mit einem erhöhten Knochenbruchrisiko entsprechend der nationalen Erstattungskriterien indiziert.

Chronic inflammation induces proinflammatory cytokine cascades. In addition to systemic inflammation, hypoxemia, hypercapnia, a catabolic metabolism, gonadal or thyroid dysfunction, musculoskeletal dysfunction and inactivity as well as vitamin D deficiency contribute to an increased risk of fragility fractures. Iatrogenic causes of osteoporosis are long-term use of inhaled or systemic glucocorticoids (GC). Inhalative GC application in asthma is often indicated in childhood and adolescence, but interstitial lung diseases such as chronic organizing pneumonia, COPD, sarcoid or rheumatic diseases with lung involvement are also treated with inhalative or oral GC. In patients with cystic fibrosis, malabsorption in the context of pancreatic insufficiency, hypogonadism and chronic inflammation with increased bone resorption lead to a decrease in bone structure. After lung transplantation, immunosuppression with GC is a risk factor.The underlying pneumological diseases lead to a change in the trabecular and cortical bone microarchitecture and to a reduction in osteological formation and resorption markers. Hypercapnia, acidosis and vitamin D deficiency can accelerate this process and thus increase the individual risk of osteoporotic fragility fractures.A bone mineral density measurement with a T‑Score -2.5 is a threshold value for the diagnosis of osteoporosis; in contrast the vast majority of all osteoporotic fractures occur with a T‑Score -2.5. A history of low-trauma fracture indicates osteological therapy.All antiresorptive or anabolic drugs approved in Austria for the treatment of osteoporosis are also indicated for pneumological patients with an increased fragility fracture risk of bone fractures in accordance with the national reimbursement criteria.Asthma und COPD sind die häufigsten obstruktiven Atemwegserkrankungen. Die chronische Inflammation bedingt eine Induktion von proinflammatorischen Zytokinkaskaden. Neben der systemischen Inflammation tragen Hypoxämie, Hyperkapnie, eine katabole Stoffwechsellage, eine gonadale oder eine Schilddrüsendysfunktion, eine muskuloskelettale Dysfunktion und Inaktivität sowie Vitamin D‑Mangel zu einem erhöhten Knochenbruchrisiko bei. Iatrogene Ursachen der Osteoporose sind die zum Teil langjährigen Anwendungen von inhalativen oder systemischen Glukokortikoiden (GC). Die inhalative GC Applikation bei Asthma ist oft schon im Kindes- und Jugendalter indiziert, aber auch interstitielle Lungenerkrankungen wie die chronisch organisierende Pneumonie, die Sarkoidose oder rheumatische Erkrankungen mit Lungenbeteiligung werden mit inhalativen oder oralen GC behandelt. Bei PatientInnen mit zystischer Fibrose kommt es durch die Malabsorption im Rahmen der Pankreasinsuffizienz, durch Hypogonadismus und chronische Inflammation mit erhöhter Knochenresorption zu einer Abnahme der Knochenstruktur. Nach Lungentransplantation ist die Immunsuppression mit GC ein Risikofaktor.Die pneumologischen Grunderkrankungen führen zu einer Veränderung der trabekulären und kortikalen Mikroarchitektur des Knochens und zu einer Verminderung von osteologischen Formations- und Resorptionsmarkern. Hyperkapnie, Azidose und Vitamin D‑Mangel können diesen Prozess beschleunigen und somit das individuelle Risiko für osteoporotische Fragilitätsfrakturen erhöhen.Eine Knochendichtemessung mit einem T‑Score −2,5 ist ein Schwellenwert zur Diagnose der Osteoporose, die überwiegende Mehrzahl aller osteoporotischen Frakturen tritt bei einem T‑Score von −2,5 auf. Eine niedrig-traumatische Fraktur in der Anamnese indiziert eine osteologische Therapie.Neben der Optimierung des Vitamin D‑Spiegels sind sämtliche in Österreich zur Behandlung der Osteoporose zugelassenen antiresorptiv oder anabol wirksamen Medikamente auch bei pneumologischen PatientInnen mit einem erhöhten Knochenbruchrisiko entsprechend der nationalen Erstattungskriterien indiziert.

Objectifying donor lung quality is difficult and currently there is no consensus. Several donor scoring systems have been proposed in recent years. They all lack large‐scale external validation and widespread acceptance. A retrospective evaluation of 2201 donor lungs offered to the lung transplant program at the Medical University of Vienna between January 2010 and June 2018 was performed. Five different lung donor scores were calculated for each offer (Oto, ET, MALT, UMN‐DLQI, and ODSS). Prediction of organ utilization, 1‐year graft survival, and long‐term outcome were analyzed for each score. 1049 organs were rejected at the initial offer (group I), 209 lungs declined after procurement (group II), and 841 lungs accepted and transplanted (group III). The Oto score was superior in predicting acceptance of the initial offer (AUC: 0.795; CI: 0.776–0.815) and actual donor utilization (AUC: 0.660; CI: 0.618–0.701). Prediction of 1‐year graft survival was best using the MALT score, Oto score, and UMN‐DLQI. Stratification of early outcome by MALT was significant for length of mechanical ventilation (LMV), PGD3 rates, ICU stay and hospital stay, and in‐hospital‐mortality, respectively. To the best of our knowledge, this study is the largest validation analysis comparing currently available donor scores. The Oto score was superior in predicting organ utilization, and MALT score and UMN‐DLQI for predicting outcome after lung transplantation., In this large retrospective analysis, the authors compare several available donor scores and their utility in predicting lung offer acceptance, lung utilization, and postoperative outcomes.

Severe chest wall deformities are considered an absolute contraindication for lung transplantation. The significantly impaired chest compliance associated with pectus excavatum is thought to result in a high risk of postoperative respiratory complications and significant morbidity and mortality. We herein report our pooled institutional experience consisting of 3 patients who underwent bilateral lung transplantation and simultaneous correction of a pectus excavatum. Two of the patients were children and 1 patient had severe asymmetric pectus. All patients received a size‐reduced double lung transplant and the deformity was corrected by a Nuss or modified Ravitch procedure. The perioperative course was complicated by prolonged weaning requiring tracheostomy in 2 of the 3 patients. However, long‐term results were good and all 3 patients are alive in excellent clinical condition 72, 60, and 12 months after the transplantation. This case series demonstrates that patients with severe chest wall deformities should not a priori be excluded from lung transplantation, and a combined approach is feasible for selected patients., This case series suggests that, for selected cases, lung transplantation with simultaneous correction of severe chest wall deformity may be feasible.

BACKGROUND Currently, the primary graft dysfunction (PGD) score is used to measure allograft function in the early post–lung transplant period. Although PGD grades at later time points (T48 hours and T72 hours) are useful to predict mid- and long-term outcomes, their predictive value is less relevant within the first 24 hours after transplantation. This study aimed to evaluate the capability of PGD grades to predict prolonged mechanical ventilation (MV) and compare it with a model derived from ventilation parameters measured on arrival at the intensive care unit (ICU). METHODS A retrospective single-center analysis of 422 double lung transplantations (LTxs) was performed. PGD was assessed 2 hours after arrival at ICU, and grades were associated with length of MV (LMV). In addition, peak inspiratory pressure (PIP), ratio of the arterial partial pressure of oxygen to fraction of inspired oxygen (P/F ratio), and dynamic compliance (cDyn) were collected, and a logistic regression model was created. The predictive capability for prolonged MV was calculated for both (the PGD score and the model). In a second step, the created model was externally validated using a prospective, international multicenter cohort including 102 patients from the lung transplant centers of Vienna, Toronto, and Budapest. RESULTS In the retrospective cohort, a high percentage of extubated patients was reported at 24 hours (35.1%), 48 hours (68.0%), and 72 hours (80.3%) after transplantation. At T0 (time point defined as 2 hours after arrival at the ICU), patients with PGD grade 0 had a shorter LMV with a median of 26 hours (interquartile range [IQR]: 16–47 hours) than those with PGD grade 1 (median: 42 hours, IQR: 27–50 hours), PGD grade 2 (median: 37.5 hours, IQR: 15.5–78.5 hours), and PGD grade 3 (median: 46 hours, IQR: 27–86 hours). However, IQRs largely overlapped for all grades, and the value of PGD to predict prolonged MV was poor. A total of 3 ventilation parameters (PIP, cDyn, and P/F ratio), determined at T0, were chosen on the basis of clinical reasoning. A logistic regression model including these parameters predicted prolonged MV (>72 hours) with an optimism-corrected area under the curve (AUC) of 0.727. In the prospective validation cohort, the model proved to be stable and achieved an AUC of 0.679. CONCLUSIONS The prediction model reported in this study combines 3 easily obtainable variables. It can be employed immediately after LTx to quantify the risk of prolonged MV, an important early outcome parameter.

Alemtuzumab is a monoclonal antibody targeting CD52, used as induction therapy after lung transplantation (LTx). Its engagement produces a long-lasting immunodepletion; however, the mechanisms driving cell reconstitution are poorly defined. We hypothesized that miRNAs are involved in this process. The expression of a set of miRNAs, cytokines and co-signaling molecules was measured with RT-qPCR and flow cytometry in prospectively collected serum samples of LTx recipients, after alemtuzumab or no induction therapy. Twenty-six LTx recipients who received alemtuzumab and twenty-seven matched LTx recipients without induction therapy were included in the analysis. One year after transplantation four miRNAs were differentially regulated: miR-23b (p = 0.05) miR-146 (p = 0.04), miR-155 (p p p p p

Objective: The impact of previous lung volume reduction surgery (LVRS) or endoscopic lung volume reduction (ELVR) on lung transplantation (LuTX) remains unclear. This study assesses the risk of previous lung volume reduction on the outcome of a later LuTX. Methods: Patients suffering from emphysema who underwent bilateral LuTX were included in this multicenter analysis. Study groups were defined as: previous LVRS, previous ELVR, controls. Imbalances were corrected by coarsened exact matching for center, gender, age, diagnosis, and BMI. A comparative analysis of intraoperative characteristics, perioperative outcome and long-term survival was performed. Results: 615 patients were included (LVRS = 26; ELVR = 60). Compared to controls, LVRS patients had a higher rate of postoperative ECMO (15.4 vs. 3.9%; p = 0.006), whereas ELVR patients suffered more often from wound infections (8.9% vs. 2.5%; p = 0.018). Perioperative outcome, duration of ventilation, ICU stay, and hospital stay were comparable between groups. Bacterial colonization of the airway differed significantly between both LVR groups and controls in pre- and post-LuTX cultures. Survival was not impacted (1-/3-/5-year survival for LVRS: 92.3%/85.7%/77.1%; controls: 91.3%/82.4%/76.3%; p = 0.58 | ELVR: 93.1%/91%/91%; controls 91.2%/81.7%/75.3%; p = 0.17). Conclusion: Lung volume reduction does not impact short and long-time survival after bilateral LuTX. Due to differences in airway colonization after LVR, caution to prevent infectious complications is warranted. ispartof: Transpl Int vol:35 pages:10048-10048 ispartof: location:Switzerland status: Published online

BACKGROUND We previously developed molecular assessment systems for lung transplant transbronchial biopsies (TBBs) with high surfactant and bronchial mucosal biopsies, identifying T-cell‒mediated rejection (TCMR) on the basis of the expression of rejection-associated transcripts, but the relationship of rejection to graft loss is unknown. This study aimed to develop molecular assessments for TBBs and mucosal biopsies and to establish the impact of molecular TCMR on graft survival. METHODS We used microarrays and machine learning to assign TCMR scores to an expanded cohort of 457 TBBs (367 high surfactant plus 90 low surfactant) and 314 mucosal biopsies. We tested the score agreement between TBB–TBB, mucosal–mucosal, and TBB–mucosal biopsy pairs in the same patient. We also assessed the association of molecular TCMR scores with graft loss (death or retransplantation) and compared it with the prognostic associations for histology and donor-specific antibodies. RESULTS The molecular TCMR scores assigned in all the TBBs performed similarly to those in high-surfactant TBBs, indicating that variation in alveolation in TBBs does not prevent the detection of TCMR. Mucosal biopsy pieces showed less piece-to-piece variation than TBBs. TCMR scores in TBBs agreed with those in mucosal biopsies. In both TBBs and mucosal biopsies, molecular TCMR was associated with graft loss, whereas histologic rejection and donor-specific antibodies were not. CONCLUSIONS Molecular TCMR can be detected in TBBs regardless of surfactant and in mucosal biopsies, which show less variability in the sampled tissue than TBBs. On the basis of these findings, molecular TCMR appears to be an important predictor of the risk of future graft failure. Trial registration ClinicalTrials.gov NCT02812290.

ZusammenfassungMitglieder der Österreichischen Gesellschaft für Pneumologie (ÖGP) beschreiben die erwartete Entwicklung der respiratorischen Gesundheit und zeigen Wege einer patientenorientierten und kosteneffizienten Versorgung für Österreich auf.Methoden: Im November 2017 trifft sich eine Gruppe von respiratorisch tätigen Ärzten, Pflegekräften und Physiotherapeuten, gemeinsam mit Vertretern von Selbsthilfe-Gruppen und Experten für Gesundheitsentwicklung, um die Themen Rahmenbedingungen für Lungengesundheit, Asthma und Allergie, COPD, Mukoviszidose und andere Krankheitsbilder der pädiatrischen Pneumologie, Infektionen in der Pneumologie, Schlafbezogene Atemstörungen, Interventionelle Pneumologie, Thorakale Onkologie, und Orphan Diseases zu bearbeiten.Ergebnisse: Respiratorische Erkrankungen sind extrem häufig und werden sehr oft durch individuelles Fehlverhalten (Zigarettenrauchen, Überernährung, körperliche Inaktivität) verursacht. Zudem wird für respiratorische Erkrankungen eine Zunahme der Prävalenz, aber eine Abnahme der Hospitalisierungen erwartet. Folgende Maßnahmen sind erforderlich, um den Herausforderungen der Zukunft zu begegnen.1. Maßnahmen des Screenings und der Fallfindung sollen für Lungenkarzinom und COPD umgesetzt werden.2. E-Health (Telemedizin, personalisierte Apps) soll vermehrt eingesetzt werden mit dem Ziel das Patientenmanagement zu erleichtern.3. Regionale Unterschiede der medizinischen Versorgung können durch E‑Health und Harmonisierung der Angebote der Gesundheitskassen reduziert werden.4. Patientenschulung und Awareness für respiratorische Erkrankungen soll verbessert werden (essentiell für Schlafstörungen, aber auch für andere respiratorische Erkrankungen)5. Die angebotene Versorgung soll interprofessionell, und auf der Grundlage erkrankungsspezifischer Boards wie bei Tumorboards (z. B. für interstitielle Lungenerkrankungen, Schlaf und Allergie) erfolgen.6. Die ambulante Rehabilitation im niedergelassenen Bereich kann einen großen Beitrag zur respiratorischen Gesundheit leisten.7. Das vermehrte Verständnis der Molekularbiologie wird die personalisierte Medizin und zielgerichtete Therapien (z. B. für Asthma, Lungenkarzinom) ermöglichen, aber auch Gesundheitskosten verändern.

ZusammenfassungDie Lungentransplantation (LuTX) ist eine etablierte Option bei chronischen Lungenerkrankungen, wenn alle anderen therapeutischen Möglichkeiten ausgeschöpft sind. Die häufigsten Indikationen stellen weiterhin das Lungenemphysem (30 %), die idiopathische Lungenfibrose (26 %) sowie die zystische Fibrose (15 %) dar. Zurzeit erfolgt in den meisten Fällen eine doppelseitige Operation. Mögliche Kandidaten für eine LuTX werden sorgfältig voruntersucht, um Komorbiditäten zu erfassen, die eine absolute oder relative Kontraindikation darstellen würden. Die Überlebenszahlen verbesserten sich in den letzten Jahren weiter. In großen Zentren betragen das 1‑Jahres-Überleben >90 % und das 5‑Jahres-Überleben 75–80 %. Zu den Problemen im Langzeit-Follow-up gehört die Entwicklung einer sog. chronischen Abstoßung (CLAD [„chronic lung allograft dysfunction“]). Sie stellt die häufigste Todesursache ab dem 2. Jahr nach LuTX dar, und die Therapiemöglichkeiten sind, trotz intensiver Bemühungen, noch gering.

Background Aneurysm of the main pulmonary artery trunk (PAA) is a rare but severe complicating factor in patients suffering from pulmonary arterial hypertension (PAH). Many centers consider PAA an indication for a heart-lung transplantation. We aimed to summarize our institutional experience with a lung-only strategy in this complex group of patients. Methods We performed a retrospective single-center analysis of patients with PAH and a severe PAA who underwent lung transplantation between January 1996 and November 2018. Results A total of 127 patients with PAH underwent lung transplantation during the study period. Seven patients presented with severe PAA (mean diameter, 70.4 mm). Donor lungs were procured together with the main pulmonary artery (PA). In the recipient, cardiopulmonary bypass with bicaval cannulation was established, and bilateral pneumonectomy together with resection of the entire PA trunk was performed. The right donor lung was implanted, and the attached PA trunk was pulled through behind the superior vena cava and ascending aorta. Anastomosis was performed just above the level of the pulmonary valve. Thereafter, the left lung was implanted by reconnecting the left PA to the main PA trunk. All but 1 patient, who died from sepsis on postoperative day 13, were successfully discharged. Conclusions To the best of our knowledge, this is the largest published experience of patients with PAH and severe PAA who underwent lung transplantation. We show that these patients are eligible for double lung transplantation and do not require heart-lung transplantation.

ZusammenfassungDie COVID-19-Pandemie stellt derzeit weltweit eine Herausforderung dar. In Österreich konnte eine Krise innerhalb des medizinischen Versorgungssystems bisher verhindert werden. Die Behandlung von Patienten mit ambulant erworbener Pneumonie („community acquired pneumonia“, CAP), inklusive durch SARS-CoV-2-Infektionen, sollte sich auch während der Pandemie weiterhin an evidenzbasierten CAP-Leitlinien orientieren. COVID-19-spezifische Anpassungen sind jedoch sinnvoll. Die Behandlung von Patienten mit chronischen Lungenerkrankungen muss während der Pandemie angepasst werden, ist aber weiterhin zu gewährleisten.

Diagnosing lung transplant rejection currently depends on histologic assessment of transbronchial biopsies (TBB) with limited reproducibility and considerable risk of complications. Mucosal biopsies are safer but not histologically interpretable. Microarray-based diagnostic systems for TBBs and other transplants suggest such systems could assess mucosal biopsies as well. We studied 243 mucosal biopsies from the third bronchial bifurcation (3BMBs) collected from seven centers and classified them using unsupervised machine learning algorithms. Using the expression of a set of rejection-associated transcripts annotated in kidneys and validated in hearts and lung transplant TBBs, the algorithms identified and scored major rejection and injury-related phenotypes in 3BMBs without need for labeled training data. No rejection or injury, rejection, late inflammation, and recent injury phenotypes were thus scored in new 3BMBs. The rejection phenotype correlated with IFNG-inducible transcripts, the hallmarks of rejection. Progressive atrophy-related changes reflected by the late inflammation phenotype in 3BMBs suggest widespread time-dependent airway deterioration, which was especially pronounced after two years posttransplant. Thus molecular assessment of 3BMBs can detect rejection in a previously unusable biopsy format with potential utility in patients with severe lung dysfunction where TBB is not possible and provide unique insights into airway deterioration. ClinicalTrials.gov NCT02812290.

Introduction: The diagnosis and treatment of antibody-mediated rejection (AMR) after lung transplantation has recently gained recognition within the transplant community. Extracorporeal photopheresis (ECP), currently used to treat chronic lung allograft dysfunction, modulates various pathways of the immune system known to be involved in AMR. We hypothesize that adding ECP to established AMR treatments could prevent the rebound of donor-specific antibodies (DSA). Objectives: This study aimed to analyze the role of ECP as an add-on therapy to prevent the rebound of DSA. Methods: Lung transplant recipients who received ECP as an add-on therapy for pulmonary AMR between January 2010 and January 2019 were included in this single-center retrospective analysis. Baseline demographics of the patients, as well as their immunological characteristics and long-term transplant outcomes, were analyzed. Results: A total of 41 patients developed clinical AMR during the study period. Sixteen patients received ECP as an add-on therapy after first-line AMR treatment. Among the 16 patients, 2 (13%) had pretransplant DSA, both against human leukocyte antigen (HLA) class I (B38, B13, and C06). Fifteen patients (94%) developed de novo DSA (dnDSA), i.e., 10 (63%) against class I and 14 (88%) against class II. The median time to dnDSA after lung transplantation was 361 days (range 25–2,548). According to the most recent International Society of Heart and Lung Transplantation (ISHLT) consensus report, 2 (13%) patients had definite clinical AMR, 6 (38%) had probable AMR, and 7 (44%) had possible AMR. The median mean fluorescence intensity (MFI) of dnDSA at the time of clinical diagnosis was 4,220 (range 1,319–10,552) for anti-HLA class I and 10,953 (range 1,969–27,501) for anti-HLA class II antibodies. ECP was performed for a median of 14 cycles (range 1–64). MFI values of dnDSA against HLA classes I and II were significantly reduced over the treatment period (for anti-class I: 752; range 70–2,066; for anti-class II: 5,612; range 1,689–21,858). The 1-year survival rate was 55%. No adverse events related to ECP were reported in any of the patients. Conclusions: ECP is associated with a reduction of dnDSA in lung transplant recipients affected by AMR. Prospective studies are warranted to confirm the beneficial effects of ECP in the setting of AMR.

CD16We included 30 DSAOur study revealed that the VMAPRTLIL and VMTPRTLVL UL40 variants were significantly overrepresented in DSADistinct UL40 peptide variants of the infecting HCMV-strain are associated with the development of ABMR after lung transplantation, due to a shift towards a highly cytotoxic CD16