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Bronchiolitis obliterans syndrome (BOS) may develop after either lung or haematopoietic stem cell transplantation (HSCT), with similarities in histopathological features and clinical manifestations. However, there are differences in the contributory factors and clinical trajectories between the two conditions. BOS after HSCT occurs due to systemic graft-versus-host disease (GVHD), whereas BOS after lung transplantation is limited to the lung allograft. BOS diagnosis after HSCT is more challenging, as the lung function decline may occur due to extrapulmonary GVHD, causing sclerosis or inflammation in the fascia or muscles of the respiratory girdle. Treatment is generally empirical with no established effective therapies. This review provides rare insights and commonalities of both conditions, which are not well elaborated elsewhere in contemporary literature, and highlights the importance of cross disciplinary learning from experts in other transplant modalities. Treatment algorithms for each condition are presented, based on the published literature and consensus clinical opinion. Immunosuppression should be optimised, and other conditions or contributory factors treated where possible. When initial treatment fails, the ultimate therapeutic option is lung transplantation (or re-transplantation in the case of BOS after lung transplantation) in carefully selected candidates. Novel therapies under investigation include aerosolised liposomal cyclosporine, Janus kinase inhibitors, antifibrotic therapies and (in patients with BOS after lung transplantation) B-cell-directed therapies. Effective novel treatments that have a tangible impact on survival and thereby avoid the need for lung transplantation or re-transplantation are urgently required. ispartof: ERJ OPEN RESEARCH vol:8 issue:3 ispartof: location:England status: published

Infection remains a common cause of death throughout the lifespan of a lung transplant recipient. The increased susceptibility of lung transplant recipients is multifactorial including exposure of the graft to the external environment, impaired mucociliary clearance, and high levels of immunosuppression. Long-term outcomes in lung transplant recipients remain poor compared with other solid organ transplants largely due to deaths from infections and chronic allograft dysfunction. Antibacterial, antifungal, and antiviral prophylaxis may be used after lung transplantation to target a number of different opportunistic infections for varying durations of time. The first-month posttransplant is most commonly characterized by nosocomial infections and donor-derived infections. Following the first month to the first 6 months after transplant-a period of intense immunosuppression-is associated with opportunistic infections. While immunosuppression is reduced after the first year posttransplant, infection remains a risk with community-acquired and rarer infectious agents. Clinicians should be vigilant for infection at all time points after transplant. The use of patient-tailored prophylaxis and treatments help ensure graft and patient survival.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

On November 24, 2017, US lung transplant policy replaced donor service area with 250-nautical-mile radius as the first unit of allocation. Understanding this policy's economic impact is important, because the United States is poised to adopt the broadest feasible geographic organ distribution. All lung transplant recipients from January 1, 2015, to December 31, 2018, in the Scientific Registry of Transplant Recipients, were included. Recipients before and after November 24, 2017 were in the donor service area-first and 250-nautical-mile donor service area-free periods, respectively. Travel time was estimated using a Google application; mode was assigned as flying when driving time was longer than 60 min. Travel costs were estimated by mode and distance. Travel distance and time for organ procurement increased under the policy change. The estimated proportion of organs traveling by air increased from 61% to 76%. Estimated average costs increased by $14 051 if travel mode changed to flying, resulting in an average increase of $1264 for all transplants. Travel costs were highest for candidates

Patients with connective tissue disease (CTD) and advanced lung disease are often considered suboptimal candidates for lung transplantation (LTx) due to their underlying medical complexity and potential surgical risk. There is substantial variability across LTx centers regarding the evaluation and listing of these patients. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization aims to clarify definitions of each disease state included under the term CTD, to describe the extrapulmonary manifestations of each disease requiring consideration before transplantation, and to outline the absolute contraindications to transplantation allowing risk stratification during the evaluation and selection of candidates for LTx.

Efforts are underway to transition the current lung allocation system to a continuous distribution framework whereby multiple factors are simultaneously combined into a Composite Allocation Score (CAS) to prioritize candidates for lung transplant. The purpose of this study was to compare discrete CAS scenarios with the current concentric circle-based allocation system to assess their potential effects on the US lung transplantation system using the Scientific Registry of Transplant Recipients' thoracic simulated allocation model. Six alternative CAS scenarios were compared over 10 simulation runs using data from individuals on the lung transplant waiting list from January 1, 2018, through December 31, 2019. Outcome measures were transplant rate, count, waitlist deaths, posttransplant deaths within 2 years, donor-to-recipient distance, and percentage of organs predicted to have flown. Across scenarios, waitlist deaths decreased by 36% to 47%, with larger decreases in deaths at lower placement efficiency weight and higher weighting of the waitlist outcomes. When waitlist outcomes were equally weighted to posttransplant outcomes, more transplants occurred in individuals with the highest expected posttransplant survival. All CAS scenarios led to improved overall measures of equity compared with the current Lung Allocation Score system, including reduced waitlist deaths, and resulted in similar posttransplant survival.

Kaposi sarcoma (KS) can develop following organ transplantation through reactivation of recipient human herpesvirus 8 (HHV‐8) infection or through donor‐derived HHV‐8 transmission. We describe 6 cases of donor‐derived HHV‐8 infection and KS investigated from July 2018 to January 2020. Organs from 6 donors, retrospectively identified as HHV‐8‐positive, with a history of drug use disorder, were transplanted into 22 recipients. Four of 6 donors had risk factors for HHV‐8 infection reported in donor history questionnaires. Fourteen of 22 organ recipients (64%) had evidence of posttransplant HHV‐8 infection. Lung recipients were particularly susceptible to KS. Four of the 6 recipients who developed KS died from KS or associated complications. The US opioid crisis has resulted in an increasing number and proportion of organ donors with substance use disorder, and particularly injection drug use history, which may increase the risk of HHV‐8 transmission to recipients. Better awareness of the risk of posttransplant KS for recipients of organs from donors with HHV‐8 infection risk could be useful for recipient management. Testing donors and recipients for HHV‐8 is currently challenging with no validated commercial serology kits available. Limited HHV‐8 antibody testing is available through some US reference laboratories and the Centers for Disease Control and Prevention., The authors report a series of human herpesvirus 8 infections transmitted from deceased donors with drug use and/or sexual risk factors that led to Kaposi sarcoma in organ transplant recipients.

Background The patient ranking process for donor lung allocation in the United States is carried out by a classification-based, computerized algorithm, known as the match system. Experts have suggested that a continuous, points-based allocation framework would better serve waiting list candidates by removing hard boundaries and increasing transparency into the relative importance of factors used to prioritize candidates. We applied discrete choice modeling to match run data to determine the feasibility of approximating current lung allocation policy by one or more composite scores. Our study aimed to demystify the points-based approach to organ allocation policy; quantify the relative importance of factors used in current policy; and provide a viable policy option that adapts the current, classification-based system to the continuous allocation framework. Methods Rank ordered logistic regression models were estimated using 6466 match runs for 5913 adult donors and 534 match runs for 488 pediatric donors from 2018. Four primary attributes are used to rank candidates and were included in the models: (1) medical priority, (2) candidate age, (3) candidate’s transplant center proximity to the donor hospital, and (4) blood type compatibility with the donor. Results Two composite scores were developed, one for adult and one for pediatric donor allocation. Candidate rankings based on the composite scores were highly correlated with current policy rankings (Kendall’s Tau ~ 0.80, Spearman correlation > 90%), indicating both scores strongly reflect current policy. In both models, candidates are ranked higher if they have higher medical priority, are registered at a transplant center closer to the donor hospital, or have an identical blood type to the donor. Proximity was the most important attribute. Under a points-based scoring system, candidates in further away zones are sometimes ranked higher than more proximal candidates compared to current policy. Conclusions Revealed preference analysis of lung allocation match runs produced composite scores that capture the essence of current policy while removing rigid boundaries of the current classification-based system. A carefully crafted, continuous version of lung allocation policy has the potential to make better use of the limited supply of donor lungs in a manner consistent with the priorities of the transplant community.

Background Reduced BMI is an absolute contraindication for lung transplantation (LTx) at most centers in the United States. The objective of this study was to quantify post-LTx survival of moderate to severely underweight patients with cystic fibrosis (CF) (BMI Methods Using United Network for Organ Sharing Registry data (undergoing transplant from June 2005-November 2015), Kaplan-Meier estimates of median posttransplant survival were calculated for all patients with CF, COPD, and idiopathic pulmonary fibrosis (IPF), as well as low and normal weight CF subgroups. Cox regression modeling stratified according to transplant center assessed risk of posttransplant mortality in recipients with CF and a BMI Results Median posttransplant survival (95% CI) for CF, COPD, and IPF was 7.9 (7.2-8.6), 5.9 (5.6-6.2), and 5.5 (5.2-5.8) years, respectively. Although an absolute decrease was noted in posttransplant survival for recipients with CF and a BMI Conclusions Transplant recipients with CF and a BMI

Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International Society for Heart and Lung Transplantation-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:39 issue:11 pages:1171-1190 ispartof: location:United States status: published

Introduction Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined. Methods We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90. Results Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p = Conclusions In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment

Improved predictive models are needed in lung transplantation in the setting of a proposed allocation system that incorporates longer-term post-transplant survival in the United States. Allocation systems require accurate mortality predictions to justly allocate organs.Utilizing the United Network for Organ Sharing database (2005-2017), we fit models to predict 1-year mortality based on the Lung Allocation Score (LAS), the Chan, et al, 2019 model, a novel "clinician" model (a priori clinician selection of pre-transplant covariates), and two machine learning models (Least Absolute Shrinkage and Selection Operator; LASSO and Random Forests) for predicting 1-year and 3-year post-transplant mortality. We compared predictive accuracy among models. We evaluated the calibration of models by comparing average predicted probability vs observed outcome per decile. We repeated analyses fit for 3-year mortality, disease category, including donor covariates, and LAS era.The area under the cure for all models was low, ranging from 0.55 to 0.62. All exhibited reasonable negative predictive values (0.87-0.90), but the positive predictive value for was poor (all0.25). Evaluating LAS calibration found 1-year post-transplant estimates consistently overestimated risk of mortality, with greater differences in higher deciles. LASSO, Random Forests, and clinician models showed no improvement when evaluated by disease category or with the addition of donor covariates and performed worse for 3-year outcomes.The LAS overestimated patients' risk of post-transplant death, thus underestimating transplant benefit in the sickest candidates. Novel models based on pre-transplant recipient covariates failed to improve prediction. There should be wariness in post-transplant survival predictions from available models.

The lung allocation score prioritizes candidates for a lung transplant in the United States. As the country adopts the continuous distribution framework for organ allocation, we must reevaluate lung allocation score assumptions to maximize transplant benefit.We used Scientific Registry of Transplant Recipients data to study the impact of these changes: (1) updating cohorts; (2) transitioning from 1- to 5-year posttransplant survival; (3) using time-varying effects for non-proportional hazards; and (4) weighting waitlist and posttransplant area under the curve differently. Models were compared using Spearman correlations and C-statistics. The thoracic simulation allocation model characterized transplant rates and proportions of recipient subgroups under the current and new systems.Posttransplant areas under the curve models were estimated with recipients aged ≥12 from January 1, 2014, to December 31, 2018. All models had similar C-statistics and Spearman correlations, indicating similar predictive performance and posttransplant area under the curve rankings. Five-year posttransplant area under the curve across age and diagnosis groups varied more than 1-year groups. Using the thoracic simulation allocation model, 1- and 5-year posttransplant model under the curve models showed similar transplant rates and recipient characteristics under the current system, but under continuous distribution, 5-year posttransplant area under the curve resulted in increased transplant rates with more recipients younger and in diagnosis groups B and C.Incorporating equally weighted waitlist and posttransplant models using 5-year posttransplant survival detected the largest variability in survival under the continuous distribution system, which could improve long-term survival in the United States.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Lung transplant recipients (LTR) with Covid-19 may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with Covid-19 to compare mortality by 28-days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with Covid-19, 1,051 (65%) were hospitalized including 117/159 (74%) LTR and 934/1457 (64%) non-lung SOTR (p=0.02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p=0.035) and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0-2.6, p=0.05). Among LTR, independent risk factors for mortality included single lung transplant (aOR 2.8, 95% CI 1.0-7.7, p=0.04) and chronic lung allograft dysfunction (aOR 3.6, 95% CI 1.0-12.4, p=0.05), but not age >65 years, heart failure, or obesity. Among SOTR hospitalized for Covid-19, LTR had higher mortality than non-lung SOTR. In LTR, single lung transplant and chronic allograft dysfunction were independently associated with mortality.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

AIMS Dental clearance is typically part of the evaluation process prior to placement on the lung transplant waiting list. Individuals with cystic fibrosis (CF) are thought to be at low risk for dental disease. We hypothesized that individuals with CF in need of lung transplantation would have lower dental disease prevalence and shorter waitlist evaluation time than individuals with non-CF lung diseases. METHODS AND RESULTS We conducted a retrospective study of individuals who received a lung transplant between 2011 and 2017 at the University of Washington (Seattle, WA, USA) (N = 280). Untreated dental disease was assessed by the individual's dentist. Waitlist evaluation time was defined as the time, in days, from the initial evaluation by a transplant pulmonologist to placement on the lung transplant waiting list. We used logistic and linear regression models for hypothesis testing. The prevalence of untreated dental disease did not differ by CF status (p = 0.99). There was no difference in waitlist evaluation time for transplant recipients by CF status (p = 0.78) or by dental disease status (p = 0.93). CONCLUSIONS Our findings provide further evidence that individuals with CF are not at low risk for dental disease. Ensuring optimal oral health is important for all individuals with lung diseases.

Background Studies of solid organ transplant recipients (SOTr) hospitalized for Covid-19 have focused on short-term outcomes with approximately 30 days of follow-up time. Intermediate-term mortality and associated risk factors for intermediate-term death have not previously been reported. Methods Using data from a multi-center registry, we assessed mortality by 90 days among SOTr hospitalized for Covid-19 between 3/1/2020 and 12/31/2020. Multivariable Cox-proportional hazard models were used to compare risk factors for mortality by 28 and 90 days. Covariates were selected a priori based on known predictors of death in SOTr hospitalized for Covid-19. All patients were followed for 90 days or were censored at the time of death or last clinical contact, if this occurred prior to day 90 after diagnosis. Results Among SOTr hospitalized for Covid-19, 198/979 (20%) died within 90 days of diagnosis and 37/198 (19%) of deaths occurred between days 29 and 90. Risk factors for mortality by day 90 days included age >65 years (1.8, 95% CI 1.3-2.4, P< 0.001), lung transplant (compared to non-lung) (1.6, 95% CI 1.1-2.4, P=0.02), chronic lung disease (2.2, 95% CI 1.5-3.4, P=0.002) and heart failure (1.9, 95% CI 1.2-2.9), which were similar to risk factors reported for 28-day mortality (Table 1). Diagnosis during the second half of 2020 (6/20-12/31/20) was associated with lower mortality by 28 days (aHR 0.7, 95% CI 0.5-1.0, P=0.03) compared to diagnosis during the early half of 2020 (3/1-6/19/20); however, mortality by 90 days was similar in the late and early time periods (aHR 0.9, 95% CI 0.7-1.2, P=0.54). Obesity and mTOR inhibitor use were also associated with death by 28 but not 90 days. Kaplan-Meier survival curves by time period of diagnosis are shown in Figure 1. Table 1. Multivariable Cox-Proportional Hazard Model for Mortality at 28 and 90-days Among Solid Organ Transplant Recipients Hospitalized for Covid-19 (N=979) Figure 1. Survival among SOT recipients hospitalized for Covid-19 by diagnosis time period Vertical tick marks represent censored cases. Early 2020 refers to cases diagnosed between March 1 and June 19, 2020 and late 2020 refers to cases diagnosed between June 20 and December 31, 2020. Conclusion Approximately 20% of deaths among SOTr hospitalized for Covid-19 occurred between days 29 and 90. Future investigations are required to discern the mechanism(s) for the improvement in early, but not late, mortality among SOTr with Covid-19 during the course of the pandemic. Disclosures Madeleine R. Heldman, MD, Cigna Lifesource (Other Financial or Material Support, Speaking honoraria)Thermo Fisher Scientific (Other Financial or Material Support, Speaking honoraria) Olivia S. Kates, MD, Merk (Scientific Research Study Investigator) Ajit P. Limaye, MD, astellas (Scientific Research Study Investigator)CTI (Scientific Research Study Investigator)GSK (Consultant)Johnson&Johnson (Other Financial or Material Support, Adjudication Committee)merck (Consultant, Grant/Research Support, Scientific Research Study Investigator)moderna (Scientific Research Study Investigator)Novartis (Other Financial or Material Support, DMC member)Novo Nordisk (Consultant)

Lung transplantation can be lifesaving in end-stage cystic fibrosis (CF), but long-term survival is limited by chronic lung allograft dysfunction (CLAD). Persistent upper airway Pseudomonas aeruginosa (PsA) colonization can seed the allograft. While de novo PsA infection is associated with CLAD in non-CF recipients, this association is less clear for CF recipients experiencing PsA recolonization. Here, we evaluate host and pathogen contributions to this phenomenon. In the context of PsA infection, brushings from the airways of CF recipients demonstrate type 1 interferon gene suppression. Airway epithelial cell (AEC) cultures demonstrate similar findings in the absence of pathogens or immune cells, contrasting with the pre-transplant CF AEC phenotype. Type 1 interferon promoters are relatively hypermethylated in CF AECs. CF subjects in this cohort have more mucoid PsA, while non-CF PsA subjects have decreased microbiome α diversity. Peri-transplant protocols may benefit from consideration of this host and microbiome equilibrium.

Cystic fibrosis (CF) is the indication for transplantation in approximately 15% of recipients worldwide, and Cystic Fibrosis Lung Transplant Recipients (CFLTRs) have excellent long-term outcomes. Yet, CFLTRs have unique comorbidities that require specialized care. The objective of this document is to provide recommendations to CF and lung transplant clinicians for the management of perioperative and underlying comorbidities of CFLTRs and the impact of transplantation on these comorbidities. The Cystic Fibrosis Foundation (CFF) organized a multidisciplinary committee to develop CF Lung Transplant Clinical Care Recommendations. Three workgroups were formed to develop focused questions. Following a literature search, consensus recommendations were developed by the committee members based on literature review, committee experience and iterative revisions, and in response to public comment. The committee formulated 32 recommendation statements in the topics related to infectious disease, endocrine, gastroenterology, pharmacology, mental health and family planning. Broadly, the committee recommends close coordination of care between the lung transplant team, the cystic fibrosis care center, and specialists in other disciplines with experience in the care of CF and lung transplant recipients. These consensus statements will help lung transplant providers care for CFLTRs in order to improve post-transplant outcomes in this population.

BACKGROUND: Resilience represents the capacity to adapt to adversity. Resilience can improve following behavioral interventions. We examined lung transplant candidates’ resilience as a novel predictor using the Connor-Davidson Resilience Scale (RISC-10). METHODS: Waitlisted candidates at six centers were mailed questionnaires from 9/16/2015 – 10/1/2019. Follow-up surveys were collected annually and post-transplant. Outcomes were recorded through February 17, 2020. Primary outcome was pre-transplant death/delisting. Analyses included t-test or Chi-square for group comparisons, Pearson’s correlation coefficients for strength of relationships, and Cox proportional-hazard models to evaluate associations with outcomes, adjusting for age, sex, and mood. RESULTS: Participation was 55.3% (N=199). Baseline RISC-10 averaged 32.0±5.6 and did not differ by demographics, primary transplant diagnosis, or disease-severity markers. RISC-10 did not correlate to the commonly utilized Psychosocial Assessment of Candidates for Transplant [PACT] or Stanford Integrated Psychosocial Assessment for Transplantation [SIPAT] tools. Scores < 26.3 (representing >1 standard deviation below population average) occurred in 16% and were associated with pre-transplant death or delisting, adjusted Hazard Ratio of 2.60 (95% Confidence Interval 1.23 −5.77; p=0.01). CONCLUSION: One in six lung candidates had low resilience, predicting increased pre-transplant death / delisting. RISC-10 did not correlate with PACT or SIPAT; resilience may represent a novel risk factor.

With the rapidly expanding pandemic of SARS-CoV-2, there is concern that solid organ transplant recipients will be particularly vulnerable to infection and may experience a more severe clinical course. We report four cases of COVID-19 in solid organ transplant recipients including recipients of kidney, liver, lung, and heart transplants. We describe each patient's medical history including transplantation history, their clinical presentation and workup, and their course from diagnosis to either hospital discharge or to improvement in symptoms. These reports demonstrate a range of symptoms, clinical severity, and disease course in solid organ transplant recipients with COVID-19, including two hospitalized patients and two patients managed entirely in the outpatient setting.

Intensive care units (ICUs) are an appropriate focus of antibiotic stewardship program efforts because a large proportion of any hospital's use of parenteral antibiotics, especially broad-spectrum, occurs in the ICU. Given the importance of antibiotic stewardship for critically ill patients and the importance of critical care practitioners as the front line for antibiotic stewardship, a workshop was convened to specifically address barriers to antibiotic stewardship in the ICU and discuss tactics to overcome these. The working definition of antibiotic stewardship is "the right drug at the right time and the right dose for the right bug for the right duration." A major emphasis was that antibiotic stewardship should be a core competency of critical care clinicians. Fear of pathogens that are not covered by empirical antibiotics is a major driver of excessively broad-spectrum therapy in critically ill patients. Better diagnostics and outcome data can address this fear and expand efforts to narrow or shorten therapy. Greater awareness of the substantial adverse effects of antibiotics should be emphasized and is an important counterargument to broad-spectrum therapy in individual low-risk patients. Optimal antibiotic stewardship should not focus solely on reducing antibiotic use or ensuring compliance with guidelines. Instead, it should enhance care both for individual patients (by improving and individualizing their choice of antibiotic) and for the ICU population as a whole. Opportunities for antibiotic stewardship in common ICU infections, including community- and hospital-acquired pneumonia and sepsis, are discussed. Intensivists can partner with antibiotic stewardship programs to address barriers and improve patient care.

Lung transplantation has become an increasingly frequent treatment for patients with a variety of end-stage lung diseases. Survival after lung transplantation has improved over time but is still limited as compared to other solid organ transplant recipients. There are a myriad of pulmonary issues that may arise after a lung transplant as well as a large number of non-pulmonary complications frequently related to immunosuppressant effects and/or toxicities. Non-pulmonary complications include, but are not limited to, renal dysfunction, hematologic abnormalities, gastrointestinal complications, neurologic sequelae, oncologic manifestations, and metabolic derangements. For these reasons, following a lung transplant, recipients require intensive, life-long monitoring for the assessment, evaluation, and management of both allograft and non-allograft transplant-related complications.

Background: We examined the association of adult lung transplant candidates’ self-reported affect with transplant-related outcomes, evaluating whether a positive (vs negative) frame of mind might be protective. Method: Consenting waitlisted candidates from 6 centers completed the questionnaires including the Positive and Negative Affect Schedule annually and posttransplant. Univariate logistic regression analysis was performed to determine the association of baseline affect with outcomes of death or delisting. Models were subsequently adjusted for age, marital status, and education. Results: Questionnaires were completed by 169 candidates (77.9% participation). Mean positive affect, negative affect, and positive-to-negative affect ratio (positivity ratio) were similar to expected norms. The scores of the questionnaire did not change significantly over time. Fifteen (8.9%) waitlisted participants died. Candidates who died while waiting had lower positivity ratios compared to those who survived (1.82 vs 2.45; P = .02). A more negative affect was associated with increased death on the waiting list (adjusted odds ratio [OR] 1.10; P = .021). Conversely, a higher positivity ratio was associated with decreased death while waiting (adjusted OR: 0.45; P = .027). Conclusion: Negative affect may represent a novel risk factor for death on the waitlist. Enhancing positive affect may represent a useful target for psychological optimization in lung transplant candidates.

Background Lung transplantation (LTx) is frequently considered for patients with cystic fibrosis (CF) when the FEV 1 reaches 1 Methods We conducted a retrospective cohort study using the CF Foundation Patient Registry from January 1, 2003 to December 31, 2013. Adult patients (≥ 18 years) with FEV 1 Results There were 3,340 patients with an FEV 1 1 Conclusions Median survival was > 6.5 years for patients with CF and an FEV 1 1

While lung transplantation is a potentially life-saving therapeutic option for many patients with end-stage pulmonary disease, overall outcomes remain inferior to recipients of other solid organ transplants. The immediate post-operative period presents a particularly high risk time for this extremely vulnerable population with a wide array of possible early complications including infection, rejection, pulmonary edema, primary graft dysfunction, bleeding, wound and airway complications, and venous thromboembolism. This chapter reviews important diagnostic considerations for lung transplant recipients with pulmonary infiltrates in the immediate post-operative period, specifically pertaining to infection, rejection, and pulmonary edema.

Purpose The Organ Procurement and Transplantation Network (OPTN) US lung allocation policy was altered in 2017 by changing the first geographic unit of lung allocation from the donation service area (DSA) to a 250 nautical mile (NM) radius around the donor hospital. Methods OPTN data on lung candidates and recipients age gt; 11 was analyzed pre (11/26/2015- 11/24/2017) and post allocation policy change (11/25/2017- 11/24/2019). Cohorts were compared to study the differences. Results An increase was seen in the match lung allocation score (LAS) at transplant from pre to post era (mean pre=47.25 vs. post=49.79, p Conclusion Under the current system, lungs are being placed to sicker candidates with similar short-term post-transplant outcomes compared to the older allocation system. The next step for the lung allocation system in the US is a move to the Continuous Distribution framework to avoid hard boundaries in geography and other clinical classifications. The OPTN Lung Transplantation Committee is using these results and additional analyses to make evidence-based decisions for allocating lungs under the new framework.

Purpose Outcomes of lung transplant recipients (LTR) hospitalized for COVID-19 and comparisons to non-lung solid organ transplant recipients (SOTR) are incompletely described. Methods Using a multicenter prospective registry of SOTR, we examined 28-day outcomes (mortality [primary outcome], intensive care unit (ICU) admission, mechanical ventilation, and bacterial pneumonia) among both LTR and non-lung SOTR hospitalized with laboratory-confirmed COVID-19 diagnosed between March 1, 2020 and September 21, 2020. Data were analyzed using Stata (StataCorp, College Station, TX); chi-square tests were used to compare categorical variables and multivariable logistic regression was used to assess risk factors for mortality. Results The cohort included 72 LTR and 392 non-lung SOTR (Table 1). Overall, 28-day mortality trended higher in LTR vs. non-lung SOTR (27.8% vs. 19.9%, P=0.136). Other 28-day outcomes were similar between LTR and non-lung SOTR: ICU admission (45.8% vs. 39.1%, P=0.28), mechanical ventilation (32.9% vs. 31.1%, P=0.78), and bacterial pneumonia (15.3% vs. 8.2%, P=0.063). Congestive heart failure, diabetes, age >65 years, and obesity (BMI >= 30) were independently associated with mortality in non-lung SOTR, but not in LTR (Table 2). Conclusion In this large prospective cohort comparing lung and non-lung SOTR hospitalized for COVID-19, there were high but not significantly different rates of short-term morbidity and mortality. Baseline comorbidities appeared to drive mortality in non-lung SOTR but not LTR. Further studies are needed to identify risk factors for mortality among LTR.

Background Lung transplantation is an intervention that improves survival for adult patients with cystic fibrosis (CF). Some patients with CF are never referred for lung transplant evaluation despite meeting physiologic criteria for referral. Methods We performed a retrospective analysis of adult patients (≥18years of age) in the Cystic Fibrosis Foundation Patient Registry (CFFPR), eligible for their first evaluation for lung transplantation during the years 2001–2008 based on FEV1 Results Within the CFFPR, 1240 patients met eligibility criteria. Eight hundred and nine (65.2%) were referred for lung transplant evaluation, and 431 (34.8%) were not referred. In a multivariable model, Medicaid insurance (OR 1.79, 95% CI 1.29–2.47), older age (per 5year increase; OR 1.25, 95% CI 1.13–1.39), lack of high school graduate education (OR 2.27, 95% CI 1.42–3.64), and Burkholderia cepacia complex sputum culture positivity (OR 2.48, 95% CI 1.50–4.12) were associated with non-referral, while number of pulmonary exacerbations (OR 0.93, 95% CI 0.87–0.99) and supplemental oxygen use (OR 0.59, 95% CI 0.43–0.81) were associated with increased referral. Conclusions Despite meeting lung function criteria for lung transplant evaluation, 35% of patients with CF had not yet been referred to a lung transplant center. Predictors of non-referral included markers of low socioeconomic status, older age and B. cepacia complex sputum culture. Further work is needed to understand the outcomes for non-referred patients in order to refine referral recommendations in this population.

Background Pulmonary infection secondary to nontuberculous mycobacteria (NTM) is associated with significant morbidity and mortality, especially in individuals with underlying structural lung disease. Such infections are challenging to treat due to high virulence, antibiotic resistance, and the lack of effective and tolerable therapies. At many transplant centers, the isolation of NTM may be considered a contraindication for lung transplantation. Methods Institutional and referral medical records, microbiology, radiology and pathology databases were reviewed for patients who underwent lung transplantation at the University of Washington between 2006-2020. 8 patients with NTM disease were identified according to the American Thoracic Society (ATS) guidelines. 9 patients with sputum cultures positive for NTM, but not diagnosed with NTM disease were also evaluated. Results Patients with NTM disease continued antimycobacterial therapy pre- and post-operatively. NTM organisms isolated included M avium complex, M fortuitum, M abscessus, M kansasii, and M fortiutum. In the cohort with NTM-disease, one patient died within a year of transplantation (14%), three died within 1-5 years (43%), and four (51%) are still alive 1-9 years post-transplantation. Only one patient clearly died as a direct cause of the NTM infection, and this occurred early post-transplantation due to disseminated M abscessus infection. Of the other deceased patients with pre-existing NTM disease, one died due to graft rejection at 3 years, one died due to graft rejection with concomitant non-NTM pneumonia at 2 years, and one died due to cardiac arrest at 4 years. In the cohort without NTM disease, none died within 1 year of transplantation, 22% died within 1-5 years, 11% died more than 5 years post-transplant, and 66% are still alive 1-14 years post-transplant. The probability of survival more than 1 year and more than 5 years post-transplant and 38% in patients with NTM-disease, and 100% and 56% in patients without NTM disease. Conclusion NTM infection in the lung transplant candidate is uncommon and challenging, however successful treatment can occur, perhaps in the setting of certain subspecies and with prolonged combination antimicrobial therapy. Disclosures All Authors: No reported disclosures

Purpose The OPTN added fields to the deceased donor registration (DDR) form on 3/31/2015 and to the transplant recipient registration (TRR) form on 2/28/2018 to capture the utilization of ex vivo lung perfusion (EVLP) on donor lungs prior to transplantation (Tx) in the US. The aim is to examine the data fields currently being collected, summarize the use of EVLP over time, and to compare early transplant outcomes between EVLP lungs and lungs where EVLP was not considered. Methods All adult deceased donors with at least one lung recovered for Tx from 4/1/15- 6/30/19 were analyzed. The prevalence of EVLP was examined over time and by recovering OPO. Post-transplant 1-year recipient survival (Tx between 4/1/15-6/30/18) was compared between donors of lungs with EVLP vs. no EVLP. Results For adult deceased donors (N=10,167), 19,295 lungs were recovered for the purpose of Tx. EVLP was intended in of 785 lungs and 485 (61.8%) of EVLP donor lungs were Tx. Since data collection began the use of perfusion has increased from 1.7% (N=16) of lungs to 7.4% (N=97) in the most recent quarter (Figure 1). Approximately 65% of the lungs perfused were from non-DCD donors and 35% from DCD donors. 51 of the 58 OPOs have recovered at least one lung that has been perfused. Over time the discard rate for perfused lungs has decreased from approximately 50% in the earliest quarter to approximately 25% in the most recent quarter. 1-yr patient survival between groups (EVLP, n=136; non-EVLP, n=7,169) was not significantly different (p= 0.06). Conclusion The number of donor lungs perfused prior to Tx in the US has grown over the past 4 years to approximately 7% of all recovered donor lungs. Geographically, the use of EVLP varied greatly across OPOs. Early recipient outcomes did not differ statistically between EVLP intended donor lungs compared to conventional donation.

Purpose In 2016, the Organ Procurement and Transplantation Network (OPTN) developed a methodology to measure equity in access to deceased donor kidney transplantation that has since been applied to liver and, most recently, lung. The holistic approach is designed to measure disparities related to geographic, demographic, clinical, and socioeconomic factors while adjusting for factors used to prioritize candidates for allocation, as well as to quantify system-level equity by a single number that can be tracked over time. Methods For OPTN data on active lung candidates we fit 36 separate Poisson rate models over rolling 6-month periods examined quarterly from 1/2010 to 6/2019, adjusting for 15 candidates covariates. Disparity was quantified as the Winsorized standard deviation (SD) of of predicted transplant rates (on log scale) among lung registrations, after “discounting” for desired, policy-induced disparities such as the lung allocation score by holding these factors constant. Risk-adjusted, factor-specific disparities were calculated as the SD of the log(transplant rate), holding all other factors constant. Results Despite 3 policy modifications over the time period, the overall disparity metric has remained very stable (fig1). Donation service area (DSA) was the factor most independently associated with disparities in access to lung transplant in each period. Other factors that rose to the top, but well below DSA, include gender, ethnicity, diagnosis group, and age. Conclusion Even after removing DSA as a unit of allocation for lung in 2017, DSA still is the factor contributing the most to inequities. This methodology will be used for monitoring the impact on equity of future policy changes, such as the anticipated transition to “Continuous Distribution” for lungs.

Purpose Resilience can be defined as a patient's capacity to adapt to or recover from adverse experiences. We hypothesize that resilience may be an important factor associated with lung transplant outcomes. Our objective was to describe resilience in lung transplant candidates and examine resilience as a potential predictor of lung transplant outcomes. Methods Adult lung transplant candidates on the waiting list between 9/16/2015 to 10/1/2019 at six transplant centers were mailed prospective questionnaires which included the validated Connor-Davidson Resilience Scale (RISC-10). Non-responders were declared non-participators after three recruitment attempts by mail. Demographics and transplant-related outcomes were recorded. Results Survey metrics were excellent with 56.9% participation (N = 199) and Conclusion In lung transplant candidates, resilience was comparable to population norms. However, one in six lung transplant candidates had low resilience. Addressing stress may be a potential target for improving resilience in future studies.

Atrial fibrillation and flutter (AF/AFL) are common following lung transplant surgery although risk factors for AF/AFL development are controversial. We reevaluated risk factors and the effects of prophylactic beta blocker use on incident AF/AFL. We performed a single-center retrospective study of

Airway complications remain a major cause of morbidity and mortality after cardiothoracic transplantation. The reported incidence of airway ischemic complications varies widely, contributed to by the lack of a universally accepted grading system and standardized definitions. Furthermore, the majority of the existing classification systems fail to integrate the wide range of possible bronchial complications that may develop after lung transplant. Hence, a Working Group was created by the International Society for Heart and Lung Transplantation with the aim of elaborating a universal definition of adult and pediatric airway complications and grading system. One such area of focus is to understand the problem in the context of a more standardized consensus of classifying airway ischemia. This consensus definition will have major clinical, therapeutics, and research implications.

Following transplantation, medical management of the lung transplant recipient is vital for maintaining the health of the allograft and to promote an overall successful outcome after a lung transplant surgery. This includes vigilant and meticulous monitoring for all lung transplant-related issues, including administering appropriate immunosuppression with antirejection medications while monitoring for associated toxicities and drug interactions as well as prompt detection of infection and lung allograft rejection. In addition, there must be full awareness of the many non-pulmonary complications that may arise following lung transplantation, a large number of which are related to immunosuppressant effects or toxicities. Non-pulmonary complications include but are not limited to renal dysfunction, hematologic abnormalities, gastrointestinal complications, neurologic sequelae, oncologic manifestations, and metabolic derangements. While monitoring lung allograft function following transplantation is critical to overall survival, monitoring of the subsequent non-pulmonary complications is also important to avoid increased morbidity and mortality in lung transplant recipients. The lung transplant pulmonologist must assume the role of a very thorough internist for the lung transplant recipient in order to monitor and address the many complications occurring after lung transplantation. This chapter focuses on the medical management of non-pulmonary issues in the lung transplant recipient.

Acute cellular and antibody-mediated (humoral) rejections are two forms of acute rejection seen following lung transplantation. The management of acute cellular and antibody-mediated rejection is complex and may be individualized based on the unique situation of each patient. The prevention of acute cellular rejection starts with induction immunosuppression and frequent clinical monitoring as well as through the management of potential risk factors such as gastroesophageal reflux disease and various infections. Antibody-mediated rejection is less understood and requires further study. The mainstay of treatment for acute cellular rejection as well as antibody-mediated rejection is through the augmentation of immunosuppression through a variety of medical strategies. The management of acute cellular rejection and antibody-mediated rejection is important due to the associations with the development of chronic lung allograft dysfunction, the primary cause of mortality following lung transplantation. With optimal management and further study, the goal is for improved survival and quality of life for all lung transplant recipients.