The risk of tuberculosis is increased after solid organ transplantation (SOT) and associated with morbidity and mortality. Pre-transplantation screening and treatment for tuberculosis infection (TBI) is recommended. Aims of this prospective cohort study were determining the prevalence of positive pre-transplantation interferon-gamma release assays (IGRAs), risk factors for a positive result, and describe TBI management. We included SOT candidates from 2020 to 2023 at Rigshospitalet, Denmark with a pre-transplantation IGRA. Data were collected from records and the Danish Microbiology Database. Of 586 patients, 564 (96%) had a pre-transplantation IGRA. Twenty-two (4%) had positive, 537 (95%) negative, and 5 (1%) indeterminate results. Risk factors for a positive IGRA were diabetes (14/480 (3%) without diabetes, 8/84 (10%) with diabetes, aOR 3.07, 95% CI 1.14-7.78), birth in other low-incidence countries (4/24 (17%) vs. 8/463 (2%), aOR 10.14, CI 2.48-35.95) or medium-/high-incidence countries (10/77 (13%), aOR 8.22, CI 3.11-22.43), and alcohol use (aOR 2.75, CI 1.04-7.15). Seventeen patients had TBI; 16 (94%) treated with isoniazid for 6 months, one (6%) with rifampicin for 4 months; treatment discontinued in one case. In conclusion, IGRA screening coverage was high. Positive IGRAs were associated with birth in other low- or medium-/high-incidence countries, diabetes, alcohol use. TBI treatment was well tolerated.

Loss of elastic recoil in emphysema causes hyperinflation of the lung tissue, stretching the respiratory muscles. Maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) decline in severe emphysema. We hypothesized that treating hyperinflation with lung volume reduction surgery (LVRS) or via bronchoscopic lung volume reduction (BLVR) with valves could lead to improved MIP or MEP. Consecutive emphysema patients referred for treatment with LVRS or BLVR from October 2020 to June 2023 were included. We applied a mixed linear model with the different treatments as independent variables to compare MIP/MEP prior to treatment, with values at 3-month follow-up. A total of 61 patients had preoperative MIP/MEP done prior to LVRS (42) or BLVR (19) treatment. Thirty-nine also had MIP/MEP measurements at 3 months follow-up, 31 after LVRS and 8 after BLVR, respectively. There was no significant increase in MIP from baseline to follow-up in the LVRS (p = 0.37) and BLVR (p = 0.32) groups. Nor was there any difference between the BLVR and LVRS group at baseline (p = 0.12) or at follow-up (p = 0.19). Similarly, MEP values were unchanged in the BLVR and LVRS groups from preoperative level to 3-month follow-up for BLVR (p = 0.59) and for LVRS (p = 0.11).

Cytomegalovirus (CMV) disease in solid organ transplant recipients (SOTr) can be prevented by antiviral prophylaxis or pre-emptive therapy (PET). The optimal CMV monitoring frequency remains unclear, and it is debated whether CMV surveillance after prophylaxis (SAP) is needed. CMV IgG donor (D)+/recipient (R)- or R+ SOTr in Zürich, Lausanne, and Copenhagen (2008-2021) were followed up for 6 months after the stoppage of CMV prophylaxis or transplantation if no prophylaxis was given. Associations between monitoring intervals and CMV disease were analyzed by Cox regression. Numbers needed to test (NNTs) with monitoring intervals of ≤7 vs >7 days were calculated. Among 3411 SOTr, CMV monitoring interval of 8 to 14 or >14 days vs ≤7 days were associated with higher risk of CMV disease (adjusted hazard ratio, 4.74; 95% confidence interval [CI], 2.17-10.36; and adjusted hazard ratio, 3.98; 95% CI, 1.92-8.26, respectively). The increased risk of CMV disease associated with monitoring intervals >7 days was consistent across subgroups. For the first 3 months of PET/SAP, the NNT was 11 (95% CI, 8-19) for D+/R- vs 71 (95% CI, 35-218) for R+ SOTr and did not differ between PET and SAP. Our findings support weekly CMV monitoring during first 3 months for recipients at risk, regardless of CMV preventative strategy. Close monitoring is more efficient in D+/R- SOTr, reflected by lower NNTs.

BACKGROUND/AIM:This investigator-initiated, open-labelled study describes safety and extrapulmonary outcomes of elexacaftor/tezacaftor/ivacaftor (ETI) treatment in people with cystic fibrosis after lung transplantation (pwCF + LTX), with particular focus on sino-nasal symptoms. ETI has not been systematically administered to people with cystic fibrosis after lunge transplantation (pwCF + LTX) due to lack of data from this subgroup and concerns about potential interactions with immunosuppressive therapy. METHODS:All pwCF + LTX in Denmark were screened for eligibility and included participants were treated with ETI in standard dosages for 24 weeks, with examinations before and after ETI initiation. Eligibility criteria were at least one F508del mutation, estimated glomerular filtration rate (eGFR) above 30 ml/min/1,73m2, ≤Child-Pugh class B, did not already receive ETI, contraception usage for women, life expectancy exceeding study duration, and considered able to adhere to safety protocol. Safety was determined by calcineurin inhibitor (CNI) trough levels, biochemical markers of organ failure, adverse events, and hospital admissions. Examinations included blood samples (including trough levels of immunosuppressants), Sino-nasal Outcome Test 22 (SNOT-22), smell test, nasal endoscopy score and sinus CT scan, sweat test and spirometry. RESULTS:Of the 36 pwCF + LTX screened, 24 were eligible and 17 accepted to participate. Five participants ended ETI treatment before study completion because of side effects, most commonly dizziness, flu-like symptoms, sleep problems, and gastrointestinal symptoms. The study showed striking effects on sino-nasal symptoms based on a significantly reduced sinonasal symptom score (SNOT-22) and CT scores; further, the ability to smell improved objectively and nasal endoscopy showed reductions in polyp size, edema and discharge. No effects were found on weight, HbA1C, and FEV1 % predicted. Most participants required reduction in CNI dose, but management of immunosuppression was uncomplicated. CONCLUSION:ETI has a dramatic effect on sino-nasal symptoms and can safely be co-administered with CNI with careful monitoring of trough levels.

BACKGROUND:Sex-based differences may affect recipient profiles, donor selection, support, and outcomes after heart transplantation. Using the International Society for Heart and Lung Transplantation Registry, we evaluated trends by recipient sex. METHODS:Adults undergoing primary heart-alone transplantation from 2005 through 2023 were analyzed. Recipient and donor characteristics, support strategies, donor utilization, 1-year survival, and 5-year conditional survival among 1-year survivors were compared by recipient sex. Multivariable Cox models were adjusted for clinical covariates and predicted heart mass difference. RESULTS:Among 50,614 recipients, 13,248 (26.2%) were female. Compared with male recipients, female recipients were younger and more often had nonischemic cardiomyopathy, hypertrophic cardiomyopathy, or congenital heart disease. They also had higher rates of allosensitization, were less often bridged with durable left ventricular assist devices, and were more often transplanted without mechanical circulatory support. Expanded donor use increased in both sexes, while durable left ventricular assist device use declined and temporary support increased. One-year survival improved over time and was similar by recipient sex within eras. After adjustment, most donor-recipient sex-pairing associations were attenuated. Female donor-female recipient transplantation remained associated with higher 1-year mortality versus male donor-male recipient transplantation (hazard ratio, 1.12; 95% confidence interval, 1.02-1.22), and male donor-female recipient transplantation was associated with higher 5-year conditional mortality (hazard ratio, 1.17; 95% confidence interval, 1.04-1.31). CONCLUSIONS:Recipient sex is associated with distinct case mix, support strategies, donor utilization, and outcome patterns. These findings support matching strategies that incorporate size, immunologic, and clinical risk.

IntroductionIn the general population elevated circulating inflammatory markers have been associated with impaired lung function in cross-sectional and longitudinal studies. No studies have investigated this association in liver transplant recipients, and we aimed to investigate if elevated inflammatory markers were associated with impaired lung function in this population.MethodsAdult liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study, with available spirometry, high sensitivity (hs)-CRP, interleukin (IL)-1β, IL-2, IL-6, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were included. Outcomes were forced expiratory volume in one second (FEV1), forced vital capacity (FVC), airflow limitation, and preserved ratio impaired spirometry (PRISm).ResultsWe included 335 liver transplant recipients. The prevalence of airflow limitation and PRISm was 11.6% and 24.5%, respectively. The median FEV1 was 2790 mL (IQR 2230–3505 mL) and the median FVC was 3680 mL (IQR 2980–3755 mL). When adjusted for age and sex, hs-CRP >3 mg/L was associated with increased odds of PRISm (aOR 2.08, 95% CI: 1.1; 3.9, p=0.02), lower FEV1 (-209 mL 95% CI -340; -77 mL, p<0.01), and lower FVC (-290 mL 95% CI -448 mL; -132 mL, p<0.01). For FEV1 and FVC, the associations were consistent when additionally adjusted for ethnicity, BMI, and smoking status. None of the remaining inflammatory markers were significantly associated with any of the outcomes across statistical models.ConclusionElevated hs-CRP was associated with impaired lung function indicating that systemic inflammation may be part of the pathophysiology of impaired lung function in liver transplant recipients.

IntroductionLiver transplant recipients have an increased risk of pulmonary complications, yet the pathogenesis remains poorly elucidated. The pulmonary endothelium is central in maintaining lung function, and endothelial dysfunction may contribute to airflow obstruction. Soluble thrombomodulin (TM) and syndecan-1 (SDC-1) are markers of endothelial damage, but whether TM and SDC-1 are related to lung function in liver transplant recipients remain unknown. This study investigated whether TM and SDC-1 are associated with forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and airflow obstruction in liver transplant recipients.MethodsWe included liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study. Airflow obstruction was defined as FEV1/FVC <0.7. TM and SDC-1 were dichotomized, and an elevated concentration was defined as above the 3rd quartile. Outcomes were analyzed using linear and logistic regression.Results340 liver transplant recipients were included. Liver transplant recipients with elevated TM had 39.5 mL lower FEV1 than liver transplant recipients with low TM (95% CI: -173.7;94.7, p=0.564), and 72.2 mL lower FVC (95% CI: -227.2;82.8, p=0.362), adjusted for confounders. The odds ratio (OR) for airflow obstruction was 1.01 (95% CI: 0.43;2.38, p=0.984). Liver transplant recipients with elevated SDC-1 had 93.4 mL lower FEV1 than liver transplant recipients with low SDC-1 (95% CI: -223.1;36.3, p=0.159) and 31.2 mL lower FVC (95% CI: -181.6;119.2, p=0.684), adjusted for confounders. The OR for airflow obstruction was 0.97 (95% CI: 0.42;2.27, p=0.950).ConclusionIn this study, we found no significant associations between TM or SDC-1 and FEV1, FVC, and airflow obstruction in liver transplant recipients. Further research is warranted to elucidate the mechanisms underlying pulmonary complications in liver transplant recipients.

Solid organ transplant (SOT) recipients are due to their immunosuppressed state susceptible to serious disease caused by respiratory tract infections with influenza or respiratory syncytial virus (RSV). While there is extensive knowledge on influenza among SOT recipients, data on how RSV affect this population remain limited and inconsistent. It is unknown whether severity and outcomes differ between influenza and RSV. All SOT recipients at Copenhagen University Hospital, Denmark, aged >18 years and transplanted in the study period 1st January 2010 to 28th February 2021 were included. The cumulative incidence rate of tests and positive tests were analyzed from date of transplantation until death, re-transplantation, emigration, or end of study. To examine associations between influenza/RSV and mortality we estimated mortality rates (MR) in time periods before infection (including patients who never tested positive), 0-180 days and > 180 after infection. MR ratios were estimated using Poisson regression analyses, adjusted for age, gender, time after transplant, and transplantation type. A total of 1862 SOT recipients were included (Table 1), of whom 693 (37.2%) and 202 (10.8%) were tested for influenza and RSV, respectively (Figure 1); test positive rates were 17.7% for influenza and 15,8% for RSV. There was a tendency towards more severe outcomes for lung versus for non-lung SOT recipients in the first 30 days after infection, but most comparisons did not reach statistical significance (Table 2). Influenza and RSV were associated with an approximately 3-5 fold increased mortality the first 6 months following infection (Table 3). Testing was more frequent for influenza than RSV, but test-positive rates were similar suggesting underdiagnosis of RSV. Both influenza and RSV were associated with significantly increased mortality the first 6 months following infection. These findings suggest importance of broader testing for RSV and prevention efforts. All Authors: No reported disclosures

BACKGROUND:Chronic lung allograft dysfunction (CLAD) is a major obstacle to improving outcomes after lung transplantation. Bronchiolitis obliterans syndrome (BOS), characterised by progressive decline in forced expiratory volume in 1 s (FEV1) due to fibrotic scarring of the small airways, accounts for most CLAD cases. Pirfenidone, an antifibrotic agent used for idiopathic pulmonary fibrosis, was assessed for treating progressive BOS. METHODS:An investigator-initiated, international, multicentre, randomised, double-blind, placebo-controlled phase II trial was conducted in nine European lung transplant centres. Adults with bilateral lung transplants and progressive BOS were randomised (1:1) to receive pirfenidone 2403 mg·day-1 or placebo with standard care for 26 weeks. The primary end-point was change in FEV1 from baseline to week 26, with imputation for missing values. FINDINGS:From 1 May 2015 to 1 December 2019, 477 patients were screened, and 90 were randomised to pirfenidone (n=48) or placebo (n=42). Both groups showed continued decline in FEV1 from baseline to week 26, with no significant difference in intention to treat (ITT), ITT with imputation, or per-protocol analyses. Secondary end-points (graft loss, death, re-transplantation) were similar between groups. Treatment-related serious adverse events were distributed equally. INTERPRETATION:Pirfenidone did not show superiority over placebo and standard care in this exploratory trial. It cannot be recommended for treating BOS. Further research is needed to explore other treatments for CLAD to improve long-term outcomes after lung transplantation.

Background:Literature on pregnancy after heart and/or lung transplantation (heart transplantation (HTx), lung transplantation (LTx), heart lung transplantation (HLTx)) remains sparse. This study assessed short- and long-term outcomes of pregnancies post-thoracic organ transplantation across Europe and analyzed center management of these patients. Methods:European centers provided retrospective data on post-HTx/LTx pregnancies and center strategies for handling transplant recipients with a pregnancy wish. Descriptive statistics and linear regression analysis were used. Results:Forty-two females had 50 pregnancies across 12 European centers. Pregnancy-induced hypertension occurred in 50% (HTx), 28% (LTx), and 20% (HLTx), and preeclampsia in 19%, 16%, and 20%, respectively. Preterm birth (<37 weeks) occurred in 23% (HTx) and 68% (LTx), and birth weight <2,500 g in 8% and 58%, respectively. Live birth rate was 98%. In multivariable analysis, a trend for higher birth weight with higher pre-pregnancy estimated glomerular filtration rate was observed (B 13.3, 95% CI -1.7-28.4, p = 0.08). Graft function remained stable in most patients during and after pregnancy. During follow-up (mean 15 years, range 5-31 post-transplantation), 6/40 mothers (15%) died (1 HTx, 2 LTx, 3 HLTx), with their children aged 0-11 years. No specific physical health problems were mentioned in 29/30 children (age 0-22 years). Physician opinions towards pregnancy differed from reluctant (31%) to positive (69%), with numerous management variations. Conclusions:We show reassuring pregnancy outcomes for post-HTx, LTx, and HLTx patients in an exclusive European cohort, despite high pregnancy complication rates. Graft function and overall maternal survival appear unaffected. We highlight differences in pregnancy management between centers and suggest development of a uniform approach.

Background The efficacy of endobronchial valve (EBV) treatment has been demonstrated in randomized controlled trials. However, real-life nationwide data from more heterogeneous patient populations remains limited. Therefore, this study aims to evaluate the one-year outcome of EBV treatment in a nationwide cohort study. Method In this nationwide cohort study, Danish patients treated with endobronchial valves from 2017-2024 were included. Outcomes, such as lung function, exercise capacity, and dyspnea, were assessed at 3 and 12 months, together with data on complications and mortality. Data was obtained from electronic medical records. Results A total of 232 patients were included in the study. Follow-up visits at 3 (1-5) and 12 (9-18) months were available for 189 and 165 patients, respectively. Nine patients died within the first year, and 37 patients underwent valve removal. Significant improvements from baseline were observed at both follow-up points in lung function (forced expiratory volume in 1 second +4.75%points & +3.43 %points, residual volume -30.5%points & -27.7 %points, total lung capacity -7.0%points & -5.7%points), physical ability (6-minute walk distance +30.6 m & +20.8 m), and dyspnea (Medical Research Council dyspnea scale -0.73 & -0.47). Responder rates declined over time, but 40-50% of patients maintained a clinically meaningful benefit at the 12-month visit. Revision bronchoscopies were performed in 44% of the patients. Conclusions Endobronchial valve treatment is associated with statistically significant improvements in lung function, exercise capacity, and dyspnea at both 3 and 12 months, with considerable inter-individual variability.

BACKGROUND:Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplant and hematopoietic stem cell transplant recipients, and is often associated with Epstein-Barr virus (EBV) reactivation. The sZEBRA protein, a soluble form of the EBV nuclear immediate-early antigen BZLF1 (also called Zta), plays a crucial role in EBV reactivation and immune evasion. This study aimed to externally validate an association between sZEBRA and the diagnosis of PTLD. METHODS:In this retrospective case-control study, the relative odds of having PTLD according to sZEBRA plasma levels at diagnosis of PTLD and comparable follow-up for controls was analyzed using logistic regression adjusting for demographics, transplant information, and sample timing. The model was further adjusted for corresponding EBV PCR plasma levels. The level of sZEBRA was fitted in the model either as present/absent or in quartiles. RESULTS:Thirty-three (17%) PTLD cases and 161 (83%) controls were included. The adjusted odds ratio (aOR) of a positive versus negative sZEBRA test for PTLD diagnosis was 2.82 (95% confidence interval [CI], 1.37-7.68); after additional adjustment for EBV PCR levels, the aOR was 4.15 (95% CI, 1.31-13.14). Separating sZEBRA levels into quartiles, aOR of sZEBRA in the fourth quartile was 12.43 (95% CI, 1.99-77.55) compared to a negative result in the fully adjusted model. CONCLUSIONS:Elevated sZEBRA levels, especially those in the highest quartile and when combined with EBV PCR, were associated with PTLD and may serve as a complementary biomarker to EBV PCR to identify patients with PTLD.

BACKGROUND:Invasive fungal infections (IFIs) are of major concern in lung transplant recipients. Although Aspergillus fumigatus is the predominant pathogen, non-A fumigatus mould infections (NAFMIs) also account for a substantial proportion of IFIs. We aimed to describe the epidemiology, clinical spectrum, risk factors, and outcomes of NAFMIs after lung transplantation. METHODS:We performed a retrospective, international, multicentre, case-control study across nine tertiary care centres in Canada and Europe. We included adult (aged ≥18 years) lung transplant recipients. Cases were defined as individuals with proven or probable IFIs caused by a mould other than A fumigatus (NAFMI group). Exclusion criteria were a concomitant infection with A fumigatus and a non-A-fumigatus mould and isolated positivity of galactomannan in serum or bronchoalveolar lavage. Two controls per case were included: one with IFI due to A fumigatus (A fumigatus control group) and one free of any IFI (IFI-free control group). 1:1:1 matching was done according to centre and time after transplantation (for IFI-free controls). We reviewed medical records to assess the clinical and radiological presentation and clinical outcomes (including 12-week therapeutic response, 12-month survival, development of chronic lung allograft dysfunction [CLAD] and post-transplant lymphoroliferative disorder) and used logistic regression models to assess risk factors for IFIs. The primary outcomes were the description of the microbial aetiologies of NAFMI, survival and CLAD 12-month post-IFI, and identification of factors associated with NAFMI. FINDINGS:Between Jan 1, 2010, and Jan 1, 2020, we included 120 individuals in the NAFMI group and 240 individuals in the control groups (n=120 in each control group). Median age at transplantation was 56 years (IQR 44-63); 170 (47%) of 360 participants were female and 190 (53%) were male. Only eight (7%) of 120 individuals in the NAFMI group had a polyfungal or mixed infection. Aspergillus flavus (26 [22%] of 120) and Aspergillus niger (24 [20%]) were the most common pathogens in the NAFMI group, followed by Scedosporium apiospermum (9[8%]). Respiratory symptoms predominated in individuals with IFI, and clinical presentations were similar in individuals with NAFMI and A fumigatus IFI. 12-month mortality was comparable across groups (NAFMI: 37/118 [31%], A fumigatus: 36/117 [31%], p=1; IFI-free controls: 25/120 [21%], p=0·11 compared with NAFMI). CLAD at 12-month post-IFI occurred at similar frequencies in cases and controls (NAFMI: 13/108 [12%], A fumigatus 17/111 [15%], p=0·69; IFI-free controls: 8/110 [7%], p=0·36 compared with NAFMI). Pre-transplant immunosuppression (adjusted odds ratio 3·82, 95% CI 1·55-9·38; p=0·0039) and pre-transplant intensive care unit stay (3·07, 1·01-9·34; p=0·048) were independently associated with NAFMI occurrence, when compared with IFI-free controls. INTERPRETATION:NAFMIs mostly involve non-fumigatus Aspergillus spp. Diagnostic features of NAFMIs are similar to those of A fumigatus infections; pre-transplant immunosuppression can increase the risk of NAFMI onset. These findings reinforce the importance of a thorough investigation when a mould is isolated from the airways after lung transplantation. FUNDING:None.

Cytomegalovirus (CMV) is a major cause of morbidity among solid organ transplant recipients (SOTr). The risk of CMV disease during the first post-transplant year can be reduced by antiviral prophylaxis or pre-emptive therapy (PET), i.e. monitoring for early CMV replication in patients not receiving prophylaxis. For patients completing prophylaxis, surveillance after prophylaxis (SAP), may be used. However, the optimal frequency of CMV monitoring for PET/SAP remains unclear, and it is debated whether SAP is needed at all.Table 1:Interval between CMV PCR monitoring during PET/SAP follow-up and risk of CMV disease at time of diagnosis of CMV infection.Table 2:Incidence rates and adjusted hazard rates of CMV disease associated with CMV PCR monitoring of > 7 vs. ≤ 7 days for prevention of CMV disease during the first 3 months of PET/SAP. All adults who received a SOT in Zürich/Lausanne (2010-2022) or Copenhagen (2012-2021), CMV IgG donor (D) and/or recipient (R) positive were included and followed for 6 months after stop of CMV prophylaxis or 6 months after transplantation if no prophylaxis was given. Cumulative incidences of CMV disease at time of diagnosis of CMV infection (i.e. failure of applying a PET/SAP strategy) were examined in analyses including death and re-transplantation as competing risks. Multivariable Cox regression investigated associations between CMV PCR monitoring intervals and risk of CMV disease. Cox model-derived number needed to test (NNT) to prevent CMV disease with monitoring intervals of ≤ 7 vs > 7 days were calculated.Table 3:Number Needed to Test for interval between CMV PCR monitoring of ≤ 7 vs. > 7 days for prevention of CMV disease during the first 3 months of PET/SAP. Of 3,424 SOTr, median age 54 years (interquartile range 43-62), 72 (2.1%) were diagnosed with CMV disease concurrently with CMV infection within the first 3 months of PET/SAP, whereas only 17 (0.5%) cases were seen in month 4-6 (Table 1). A CMV monitoring interval of ≤ 7 vs. 7-14 days within the first 3 months of PET/SAP was associated with significantly lower risk of CMV disease, while the risk did not differ between > 14 vs. 7-14 days (Table1). The increased risk of CMV disease associated with CMV monitoring intervals > 7 days was consistent across all subgroups of SOTr (Table 2). The NNT to prevent one event of CMV disease was 11 (95%-CI: 8-20) for the D+/R- vs. 70 (95%-CI: 27-235) for the R+ SOTr but did not differ according to prior use of prophylaxis (Table 3). Our finding of significant lower risk of CMV disease associated with frequent CMV monitoring for PET/SAP, supports close monitoring and a hybrid CMV prevention strategy with SAP. Frequent monitoring is more efficient in D+/R- SOTr, as reflected by the lower NNTs for this group. All Authors: No reported disclosures

Cardiovascular control during exercise is impaired in chronic obstructive pulmonary disease (COPD). The central cardiopulmonary pathologies in COPD might drive the local muscle vascular abnormalities. We hypothesised that contracting muscle perfusion and O2 utilisation improve after lung transplantation (LTx) in COPD. Ten patients with end-stage COPD were tested on the LTx waiting list (pre-LTx) and again 6 months after LTx (post-LTx). We measured leg blood flow ( Q ̇ leg , main outcome) during submaximal one-leg knee-extensor exercise (KEE), and femoral arterial-venous blood samples were obtained for the determination of O2 kinetics across the leg and vasoactive compounds. Cardiac output and stroke volume in response to KEE peak workload (WLpeak), walking distance and physical activity (triaxial accelerometry) were also assessed. Lung function (one single and nine double LTx), walking distance and physical activity increased post-LTx, whereas leg lean mass and WLpeak remained unchanged. Arterial oxygen partial pressure decreased in response to KEE pre-LTx but was maintained at resting levels post-LTx. Working muscle capillary O2 tension and saturation were also higher post-LTx, with no difference in muscle O2 conductance or extraction. We found no changes in Q ̇ leg during submaximal KEE (pre-LTx: 1026 ± 278 vs. post-LTx: 941 ± 186 mL min-1, P = 0.49); mean arterial pressure and circulating pro-brain natriuretic peptide levels were lower post-LTx and cardiac output higher. Cardiac output (pre-LTx: 6.1 ± 0.4 vs. post-LTx: 8.3 ± 0.5 L min-1, P = 0.0001) and stroke volume responses to WLpeak were also higher post-LTx. LTx did not affect muscle blood flow regulation during moderate-intensity KEE in end-stage COPD and seemed to be disconnected from the augmented cardiac output responses to exercise.

Antibody-mediated rejection (AMR) is an increasingly recognized form of rejection and cause of graft failure after lung transplantation. AMR has been the focus of extensive research over the past decade. Despite growing awareness and recent advances in our understanding of AMR, outcomes remain dismal with a 2-year survival of only 20%. The International Society for Heart and Lung Transplantation convened a multidisciplinary workgroup of experts in AMR to review the most up-to-date research and clinical experience and to update the 2016 definition. The workgroup was divided into 9 subgroups covering a broad range of topics pertaining to AMR and used the modified Delphi method to synthesize a cohesive summary of the literature. A multidimensional definition was developed to enhance precision by reporting the specific presenting features. This Graft, Antibody, and Pathology (GAP) definition is based on the presence of Graft dysfunction, the presence and characteristics of Antibodies, and Pathological findings. The workgroup emphasized that identifying better treatments for AMR is a critical unmet need and proposed that a more precise definition might allow better management by providing a platform for testing and developing new therapies.