What Happens to Frailty in the First Year After Lung Transplantation?

BACKGROUND: Frailty is prevalent in lung transplant (LTx) candidates, but the impact and subsequent frailty trajectory is unclear. This study aimed to investigate frailty over the first year after LTx. METHOD: Post-LTx recipients completed a thrice weekly 12-week directly supervised exercise rehabilitation program. Edmonton Frail Scale (EFS) was used to assess frailty. Primary outcome was 6-Minute Walk Distance (6MWD) measured at pre-LTx, prerehabilitation, postrehabilitation, and 1 year post-LTx. RESULTS: 106 of 139 recruited participants underwent LTx: mean age 58 years, 48% male, 52% with chronic obstructive pulmonary disease. Mean (± SD) frailty scores pre-LTx and 1 year post-LTx were 5.54 ± 2.4 and 3.28 ±1.5. Mean 6MWD improved significantly for all: prerehabilitation 326 m (SD 116), versus postrehabilitation 523 m (SD 101) (p < 0.001) versus 1 year 512 m (SD 120) (p < 0.001). There were significant differences between an EFS > 7 (frail) and EFS ≤ 7 (not frail) for 6MWD, grip strength (GS), anxiety, and depression. Postrehabilitation, there were no significant differences in 6MWD, GS, anxiety, or depression while comparing EFS > 7 versus ≤ 7. At 1 year, there was a significant difference in depression but not 6MWD, GS, or anxiety between those EFS ≤ 7 and > 7 (p = 0.017). CONCLUSION: Participants in a structured post-LTx rehabilitation program improved in functional exercise capacity (6MWD), GS, depression, and anxiety. For frail participants exercise capacity, depression, anxiety, and GS were well managed in rehabilitation with no significant differences between those who were not frail. Pre-LTx frailty may be reversible post-LTx and should not be an absolute contraindication to LTx.

Trimethoprim-sulfamethoxazole acute respiratory distress syndrome requiring lung transplantation.

Trimethoprim-sulfamethoxazole (TMP-SMX) acute respiratory distress syndrome (ARDS) is a rare, but severe complication of a commonly prescribed antibiotic. TMP-SMX typically affects young, otherwise well patients with a specific human leukocyte antigen type (HLA-B*07:02 and HLA-C*07:02). The condition is poorly understood with a unique pathological appearance and mechanism that remains unclear. Mortality rate is greater than one third. We describe the case of a previously well 18-year-old woman treated with a prolonged course of TMP-SMX for a complex urinary tract infection who developed rapidly progressive respiratory failure requiring prolonged intensive care admission, extra-corporeal membranous oxygenation, and eventual lung transplantation. No targeted treatment exists, further research is required to better understand disease pathogenetic mechanisms and potential therapeutic interventions.

Utility of the Stanford Integrated Psychosocial Assessment for Transplant in predicting outcomes before and after lung transplantation.

BACKGROUND: Optimizing donor use and achieving maximal survival following lung transplantation (LTx) require a pretransplant assessment that identifies clinical, physiological, and psychosocial patient factors associated with both poor and optimal post-LTx survival. We examined the utility of a psychosocial tool, the Stanford Integrated Psychosocial Assessment for Transplant (SIPAT), to identify patient suitability for LTx, as well as its association with clinical outcomes before and after LTx. METHODS: This was a retrospective single-center study analyzing LTx assessment clinical variables (age, gender, diagnosis, functional capacity, nutrition, renal function), with a particular focus on the utility of the SIPAT score, to predict patient suitability for LTx. The same variables were analyzed against LTx waitlist mortality, as well as post-LTx survival. RESULTS: Over an 8-year period dating from December 2012, 914 patients (male 54.4%, mean age 55.2 years) underwent LTx assessment. Patients declined for LTx (n = 152, 16.6%) were older and had reduced functional capacity, nutritional markers, and renal function but had a higher SIPAT score. Once listed for LTx, a higher SIPAT score was not associated with waitlist mortality or reduced post-LTx survival. CONCLUSIONS: The SIPAT tool measures psychosocial suitability for transplantation that can be incorporated into a standardized assessment of LTx suitability. While patients with higher SIPAT score were more likely to be declined for LTx, the SIPAT score did not predict outcome in transplanted patients. A subgroup of patients with high SIPAT scores were successfully transplanted, suggesting that unfavorable psychosocial variables are potentially modifiable with a well-resourced multidisciplinary LTx team.

Impulse Oscillometry Versus Spirometry to Detect Bronchiolitis Obliterans Syndrome in Bilateral Lung Transplant Recipients: A Prospective Diagnostic Study.

BACKGROUND: Chronic lung allograft dysfunction (CLAD), and especially bronchiolitis obliterans syndrome (BOS), remain dominant causes of morbidity and mortality after lung transplantation. Interest is growing in the forced oscillation technique, of which impulse oscillometry (IOS) is a form, as a tool to improve our understanding of these disorders. However, data remain limited and no longitudinal studies have been published, meaning there is no information regarding any capacity IOS may have for the early detection of CLAD. METHODS: We conducted a prospective longitudinal study enrolling a consecutive sample of adult bilateral lung transplant recipients with healthy lung allografts or CLAD and performed ongoing paired IOS and spirometry tests on a clinically determined basis. We assessed for correlations between IOS and spirometry and examined any predictive value either modality may hold for the early detection of BOS. RESULTS: We enrolled 91 patients and conducted testing for 43 mo, collecting 558 analyzable paired IOS and spirometry tests, with a median of 9 tests per subject (interquartile range, 5-12) and a median testing interval of 92 d (interquartile range, 62-161). Statistically significant moderate-to-strong correlations were demonstrated between all IOS parameters and spirometry, except resistance at 20 Hz, which is a proximal airway measure. No predictive value for the early detection of BOS was found for IOS or spirometry. CONCLUSIONS: This study presents the first longitudinal data from IOS after lung transplantation and adds considerably to the growing literature, showing unequivocal correlations with spirometry but failing to demonstrate a predictive value for BOS.

Clinical outcomes following cessation of parenteral immunoglobulin therapy following lung transplantation.

Broad use of parenteral immunoglobulin (IgG) therapy in lung transplant (LTx) patients occurs without robust clinical evidence or guidelines. Main indications include secondary hypogammaglobulinemia, antibody-mediated rejection (AMR), and treatment or prevention of graft rejection where the use of conventional immunosuppressive therapies is contraindicated. As part of routine auditing of IgG use in our LTx service, we assessed for adverse clinical outcomes related to IgG therapy cessation between November 2017 and February 2022. Of 220 LTx recipients receiving IgG therapy at our center during this period (approximately 20% of our total LTx cohort), 48 patients ceased therapy. No adverse outcomes were experienced in 83.3% patients. About 10.4% recommenced therapy for the same indication within 6 months with no longer term sequelae. One AMR patient developed progressive Chronic lung allograft dysfunction and died within 12 months, where therapy cessation was patient-initiated and associated with general noncompliance. These data provide reassurance that physician-directed cessation of IgG therapy is safe when based on sound clinical information and part of a robust clinical auditing process.

Defining a natural killer cell-enriched molecular rejection-like state in lung transplant transbronchial biopsies.

In lung transplantation, antibody-mediated rejection (AMR) diagnosed using the International Society for Heart and Lung Transplantation criteria is uncommon compared with other organs, and previous studies failed to find molecular AMR (ABMR) in lung biopsies. However, understanding of ABMR has changed with the recognition that ABMR in kidney transplants is often donor-specific antibody (DSA)-negative and associated with natural killer (NK) cell transcripts. We therefore searched for a similar molecular ABMR-like state in transbronchial biopsies using gene expression microarray results from the INTERLUNG study (#NCT02812290). After optimizing rejection-selective transcript sets in a training set (N = 488), the resulting algorithms separated an NK cell-enriched molecular rejection-like state (NKRL) from T cell-mediated rejection (TCMR)/Mixed in a test set (N = 488). Applying this approach to all 896 transbronchial biopsies distinguished 3 groups: no rejection, TCMR/Mixed, and NKRL. Like TCMR/Mixed, NKRL had increased expression of all-rejection transcripts, but NKRL had increased expression of NK cell transcripts, whereas TCMR/Mixed had increased effector T cell and activated macrophage transcripts. NKRL was usually DSA-negative and not recognized as AMR clinically. TCMR/Mixed was associated with chronic lung allograft dysfunction, reduced one-second forced expiratory volume at the time of biopsy, and short-term graft failure, but NKRL was not. Thus, some lung transplants manifest a molecular state similar to DSA-negative ABMR in kidney and heart transplants, but its clinical significance must be established.

Everolimus Based Immunosuppression Strategies in Adult Lung Transplant Recipients: Calcineurin Inhibitor Minimization Versus Calcineurin Inhibitor Elimination.

Everolimus (EVE) provides an alternative to maintenance immunosuppression when conventional immunosuppression cannot be tolerated. EVE can be utilized with a calcineurin inhibitor (CNI) minimization or elimination strategy. To date, clinical studies investigating EVE after lung transplant (LTx) have primarily focused on the minimization strategy to preserve renal function. The primary aim was to determine the preferred method of EVE utilization for lung transplant recipients (LTR). To undertake this aim, we compared the safety and efficacy outcomes of EVE as part of minimization and elimination immunosuppressant regimens. Single center retrospective study of 217 LTR initiated on EVE (120 CNI minimization and 97 CNI elimination). Survival outcomes were calculated from the date of EVE commencement. On multivariate analysis, LTR who received EVE as part of the CNI elimination strategy had poorer survival outcomes compared to the CNI minimization strategy [HR 1.61, 95% CI: 1.11-2.32, p=0.010]. Utilization of EVE for renal preservation was associated with improved survival compared to other indications [HR 0.64, 95% CI: 0.42-0.97, p=0.032]. EVE can be successfully utilized for maintenance immunosuppression post LTx, particularly for renal preservation. However, immunosuppressive regimens containing low dose CNI had superior survival outcomes, highlighting the importance of retaining a CNI wherever possible.

Major technological advances will enhance Australian donor-recipient matching and improve transplant outcomes.

In recent times, numerous and significant technological and supportive changes have taken place in Australian transplantation. These changes are often deployed without the wider clinical community having a full understanding of what has brought about these changes and the impacts they have. Here, we aim to clarify the reasoning behind these changes and shed light on potential future endeavours to improve patient outcomes.

Post-operative, inpatient rehabilitation after lung transplant evaluation (PIRATE): A feasibility randomized controlled trial.

BACKGROUND: Postoperative rehabilitation is crucial following lung transplantation (LTx); however, it is unclear whether intensive rehabilitation is feasible to deliver in the acute setting. We aimed to establish the feasibility and safety of intensive acute physiotherapy post-LTx. METHODS: This feasibility trial randomized 40 adults following bilateral sequential LTx to either standard (once-daily) or intensive (twice-daily) physiotherapy. Primary outcomes were feasibility (recruitment and delivery of intensive intervention) and safety. Secondary outcomes included six-minute walk test; 60-second sit-to-stand; grip strength; physical activity; pain; EQ-5D-5L; length of stay; and readmissions. Data were collected at baseline, week 3, and week 10 post-LTx. ClinicalTrials.gov #NCT03095859. RESULTS: Of 83 LTx completed during the trial, 49% were eligible and 48% provided consent. Median age was 61 years {range 18-70}; waitlist time 85 days [IQR 35-187]. Median time to first mobilization was 2 days [2-3]. Both groups received a median of 10 [7-14] standard interventions post-randomization. A median of 9 [6-18] individual intensive interventions were attempted (86% successful), the most common barrier being medical procedures/investigations (67%). No intervention-related adverse events or between-group differences in secondary outcomes were observed. CONCLUSIONS: Acute, intensive physiotherapy was feasible and safe post-LTx. This trial provides data to underpin definitive trials to establish efficacy.

The molecular features of chronic lung allograft dysfunction in lung transplant airway mucosa.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Can we HALT obesity following lung transplant? A Dietitian- and Physiotherapy-directed pilot intervention.

INTRODUCTION: Unintentional weight gain, overweight and obesity following solid organ transplantation (SOT) are well-established and linked to morbidity and mortality risk factors. No interventional studies aimed at prevention have been undertaken among lung transplant (LTx) recipients. The combination of group education and telephone coaching is effective in the general population but is untested among SOT cohorts. METHODS: A non-randomized, interventional pilot study was conducted among new LTx recipients. The control group received standard care. In addition to standard care, the intervention involved four group education and four individual, telephone coaching sessions over 12-months. Data collection occurred at 2 weeks, 3- and 12 months post-LTx. Measurements included weight, BMI, fat mass (FM), fat mass index (FMI), fat-free mass (FFM), fat-free mass index (FFMI), waist circumference (WC), visceral adipose tissue (VAT), nutrition knowledge, diet, physical activity, lipid profile, HbA1C , FEV1 , six-minute walk distance and patient satisfaction. RESULTS: Fifteen LTx recipients were recruited into each group. One control participant died 120 days post-LTx, unrelated to the study. There were trends towards lower increases in weight (6.7±7.2 kg vs. 9.8±11.3 kg), BMI (9.6% of baseline vs. 13%), FM (19.7% vs. 40%), FMI, VAT (7.1% vs. 30.8%) and WC (5.5% vs. 9.5%), and greater increases in FFM and FFMI (all P > .05), among the intervention group by 12 months. The intervention was well-accepted by participants. CONCLUSION: This feasible intervention demonstrated non-significant, but clinically meaningful, favorable weight and body composition trends among LTx recipients over 12 months compared to standard care.

Surgical management of giant pulmonary artery aneurysms in patients with severe pulmonary arterial hypertension.

BACKGROUND AND AIM: Giant aneurysm of the pulmonary artery (PAA) is an extremely rare condition that may develop in patients with pulmonary arterial hypertension (PAH) which may be complicated by rupture, dissection or intravascular thrombus formation. The aim of this study was to examine available literature with regard to surgical strategies in patients undergoing transplantation for PAH with PAA. RESULTS: These patients were traditionally considered for heart-lung transplantation but more recently, there have been reports of successful lung transplantation with reconstruction of the pulmonary artery. CONCLUSIONS: Unless there is a mandatory indication for heart-lung transplantation, patients with PAH and PAA can undergo lung transplantation and reconstruction of the pulmonary artery without compromising the outcome.

Transcripts associated with chronic lung allograft dysfunction in transbronchial biopsies of lung transplants.

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, for example, 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.

Outcomes Following Extracorporeal Photopheresis for Chronic Lung Allograft Dysfunction Following Lung Transplantation: A Single-Center Experience.

INTRODUCTION: Survival following lung transplantation (LTx) is limited by the development of chronic lung allograft dysfunction (CLAD), for which there are few effective therapies and no standardized management. Several small studies have demonstrated the effectiveness of extracorporeal photopheresis (ECP) as a therapeutic option for CLAD. METHODS: A retrospective descriptive audit of 12 LTx recipients who received rescue ECP for CLAD over 5 years (2013-2018) at the Alfred Hospital, Melbourne, Australia, was completed. Nonresponders to ECP were defined as patients who experienced a 20% decrease in forced expiratory volume (FEV1) within 6 weeks of commencing therapy. RESULTS: Mean time since LTx was 849 days and mean time since diagnosis of CLAD was 131 days. Fifty-eight percent of patients were male (n = 7) and 67% responded to ECP therapy (n = 8). Among responders, the mean (95% confidence interval) decline in FEV1 pre-ECP was 9.0 mL/day (5-12 mL/day), compared to 1.4 mL/day (0-4 mL/day) post-ECP (P = .01). Among nonresponders, mean (95% confidence interval) decline in FEV1 was 7.2 mL/day (4-10 mL/day) pre-ECP and 5.0 mL/day (3-7 mL/day) post ECP (P = .2). Nonresponders were more likely to be female (P = .01) and neutropenic (P = .005). Patients with prior exposure to anti-thymocyte globulin had a lowered response to ECP. CONCLUSION: Rescue ECP arrested the decline of lung function in 67% of patients with CLAD. Sex, pre-ECP neutrophil count, and exposure to anti-thymocyte globulin may help determine response to ECP. Future clinical trials are needed to confirm this effect, help predict response to therapy, and ultimately guide the placement of ECP in the treatment algorithm for CLAD.

The Utility of the Sit-to-Stand Test for Inpatients in the Acute Hospital Setting After Lung Transplantation.

OBJECTIVE: Measurement of physical function is important to guide physical therapy for patients post-lung transplantation (LTx). The Sit-to-Stand (STS) test has proven utility in chronic disease, but psychometric properties post-LTx are unknown. The study aimed to assess reliability, validity, responsiveness, and feasibility of the 60-second STS post-LTx. METHODS: This was a measurement study in 62 inpatients post-LTx (31 acute postoperative; 31 medical readmissions). Interrater reliability was assessed with 2 STS tests undertaken by different assessors at baseline. Known group validity was assessed by comparing STS repetitions in postoperative and medical groups. Content validity was assessed using comparisons to knee extensor and grip strength, measured with hand-held dynamometry. Criterion validity was assessed by comparison of STS repetitions and 6-minute walk distance postoperatively. Responsiveness was assessed using effect sizes over inpatient admission. RESULTS: Median (interquartile range) age was 62 (56-67) years; time post-LTx was 5 (5-7) days postoperative and 696 (244-1849) days for medical readmissions. Interrater reliability was excellent (intraclass correlation coefficient type 2,1 = 0.96), with a mean learning effect of 2 repetitions. Repetitions were greater for medical at baseline (mean 18 vs 8). More STS repetitions were associated with greater knee extensor strength (postoperative r = 0.57; medical r = 0.47) and 6-minute walk distance (postoperative r = 0.68). Effect sizes were 0.94 and 0.09, with a floor effect of 23% and 3% at baseline (postoperative/medical) improving to 10% at discharge. Patients incapable of attempting a STS test were excluded, reducing generalizability to critical care. Physical rehabilitation was not standardized, possibly reducing responsiveness. CONCLUSIONS: The 60-second STS demonstrated excellent interrater reliability and moderate validity and was responsive to change postoperatively. IMPACT: The 60-second STS represents a safe, feasible functional performance tool for inpatients post-LTx. Two tests should be completed at each time point.

Cost-effectiveness of transplanting lungs and kidneys from donors with potential hepatitis C exposure or infection.

Organ transplant guidelines in many settings recommend that people with potential hepatitis C virus (HCV) exposure or infection are deemed ineligible to donate. The recent availability of highly-effective treatments for HCV means that this may no longer be necessary. We used a mathematical model to estimate the expected difference in healthcare costs, difference in disability-adjusted life years (DALYs) and cost-effectiveness of removing HCV restrictions for lung and kidney donations in Australia. Our model suggests that allowing organ donations from people who inject drugs, people with a history of incarceration and people who are HCV antibody-positive could lead to an estimated 10% increase in organ supply, population-level improvements in health (reduction in DALYs), and on average save AU$2,399 (95%CI AU$1,155-3,352) and AU$2,611 (95%CI AU$1,835-3,869) per person requiring a lung and kidney transplant respectively. These findings are likely to hold for international settings, since this policy change remained cost saving with positive health gains regardless of HCV prevalence, HCV treatment cost and waiting list survival probabilities. This study suggests that guidelines on organ donation should be revisited in light of recent changes to clinical outcomes for people with HCV.

A donor PaO2/FiO2 < 300 mm Hg does not determine graft function or survival after lung transplantation.

BACKGROUND: A donor arterial PO2/FiO2 (P/F ratio) of less than the 300 threshold would frequently result in either exclusion of the donor or placement of the lungs on ex vivo lung perfusion (EVLP). The aim was to investigate the veracity of the P/F ratio threshold of 300 for donor lung acceptability. METHODS: In 93 brain dead lung donors, arterial blood gases were drawn in the intensive care unit (ICU) just before procurement and each of the 4 donor pulmonary veins in the operating room (OR). No donor lungs were rejected for transplantation based on the last ICU or OR P/F ratio, and EVLP was not used. The recipients were followed up 6 and 12 months following transplantation. RESULTS: There were 93 recipients of bilateral lung transplantation. An arterial P/F ratio of < 300 was largely driven by a low P/F ratio in the lower lobes. There were no differences between the recipients receiving donor lungs where the ICU P/F ratio was < 300 compared with ≥ 300 in the time to extubation, grade of primary graft dysfunction, pulmonary function at 6 and 12 months, and 12-month survival. CONCLUSIONS: From this study:(1) If a donor P/F threshold of 300 was adhered to, 36% would have been rejected, and (2) The donor P/F ratio threshold of 300 is excessively conservative and results in the wastage of donor lungs and the application of unnecessary EVLP.

Atrial Flutter and Fibrillation Following Lung Transplantation: Incidence, Associations and a Suggested Therapeutic Algorithm.

BACKGROUND: Atrial arrhythmias are relatively common following lung transplantation and confer considerable perioperative risk, specifically haemodynamic instability, pulmonary congestion, dyspnoea, and can mask other post-transplant complications such as infection or acute rejection. However, for most patients, arrhythmias are limited to the short-term perioperative period. METHODS: We present a retrospective case-control analysis of 200 lung transplant recipients and using multivariate regression analysis, document the present incidence, risk factors, and outcomes between the two groups. RESULTS: Twenty-five per cent (25%) of lung transplantation patients developed atrial flutter or fibrillation, most frequently at day 5-7 post lung transplantation, and more commonly present in older recipients and those with underlying chronic obstructive pulmonary disease (COPD), but not in those with previously noted structural heart disease, or in those undergoing single rather than double lung transplants. Atrial arrhythmias were associated with increased intensive care unit and overall length of stay, but were not associated with increased risk of in-hospital stroke, or mortality. Based on our experience, we propose a suggested management algorithm for pharmacological and mechanical rate/rhythm control strategies, for anticoagulation, and discuss the appropriate duration of treatment. CONCLUSIONS: Atrial arrhythmias are relatively common post lung transplantation. Carefully managed, the associated risk of perioperative morbidity and mortality can be mitigated. Further prospective studies are required to validate these strategies.

Donation after circulatory death in lung transplantation-five-year follow-up from ISHLT Registry.

BACKGROUND: This study aimed to examine intermediate-term outcomes of lung transplantation (LTx) recipients from donors after circulatory death (DCD). METHODS: We examined the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry data for patients transplanted between January 2003 and June 2017 at 22 centers in North America, Europe, and Australia participating in the DCD Registry. The distribution of continuous variables was summarized as median and interquartile range (IQR) values. Wilcoxon rank sum test was used to compare distribution of continuous variables and chi-square or Fisher's exact test for categorical variables. Kaplan-Meier survival rates after LTx from January 2003 to June 2016 were compared between DCD-III (Maastricht category III withdrawal of life-sustaining therapy [WLST]) only and donors after brain death (DBD) using the log-rank test. Risk factors for 5-year mortality were investigated using Cox multivariate proportional-hazards model. RESULTS: The study cohort included 11,516 lung transplants, of which 1,090 (9.5%) were DCD lung transplants with complete data. DCD-III comprised 94.1% of the DCD cohort. Among the participating centers, the proportion of DCD-LTx performed each year increased from 0.6% in 2003 to 13.5% in 2016. DCD donor management included extubation in 91%, intravenous heparin in 53% and pre-transplant normothermic ex vivo donor lung perfusion in 15%. The median time interval from WLST to cardiac arrest was 15 minutes (IQR: 11-22 minutes) and to cold flush 32 minutes (IQR: 26-41minutes). Compared with DBD, donor age was higher in DCD-III donors (46 years [IQR: 34-55] vs 40 years [IQR: 24-52]), bilateral LTx was performed more often (88.3% vs 76.6%), and more recipients had chronic obstructive pulmonary disease and emphysema as their transplant indication. Five-year survival rates were comparable (63% vs 61%, p = 0.72). In multivariable analysis, recipient and donor ages, indication diagnosis, procedure type (single vs bilateral and double LTx), and transplant era (2003-2009 vs 2010-2016) were independently associated with survival (p < 0.001), but donor type was not (DCD-III vs DBD; hazard ratio, 1.04 [0.90-1.19], p = 0.61). CONCLUSION: This ISHLT DCD Registry report with 5-year follow-up demonstrated similar favorable long-term survival in DCD-III and DBD lung donor recipients at 22 experienced centers globally. These data indicate that more extensive use of DCD-LTx would increase donor organ availability and may reduce waiting list mortality.