Search

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.

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 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

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.

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

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.

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.

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

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.

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

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 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

The outcomes and optimal management of cirrhotic patients who develop cryptococcosis before transplantation are not fully known.We conducted a multicenter study involving consecutive patients with cirrhosis and cryptococcosis between January 2000 and March 2014. Data collected were generated as standard of care.In all, 112 patients were followed until death or up to 9 years. Disseminated disease and fungemia were present in 76.8% (86/112) and 90-day mortality was 57.1% (64/112). Of the 39 patients listed for transplant, 20.5% (8) underwent liver transplantation, including 2 with active but unrecognized disease before transplantation. Median duration of pretransplant antifungal therapy and posttransplant therapy was 43 days (interquartile range, 8-130 days) and 272 days (interquartile range, 180-630 days), respectively. Transplantation was associated with lower mortality (P = 0.002). None of the transplant recipients developed disease progression during the median follow-up of 3.5 years with a survival rate of 87.5%.Cryptococcosis in patients with cirrhosis has grave prognosis. Our findings suggest that transplantation after recent cryptococcal disease may not be a categorical exclusion and may be cautiously undertaken in liver transplant candidates who are otherwise deemed clinically stable.

Objective To summarize and critically review the existing literature on the prevalence of posttraumatic stress disorder (PTSD) following organ transplantation, risk factors for posttransplantation PTSD and the relationship of posttransplant PTSD to other clinical outcomes including health-related quality of life (HRQOL) and mortality. Methods We conducted a systematic literature review using PubMed, CINAHL Plus, the Cochrane Library and PsycInfo and a search of the online contents of 18 journals. Results Twenty-three studies were included. Posttransplant, the point prevalence of clinician-ascertained PTSD ranged from 1% to 16% ( n =738), the point prevalence of questionnaire-assessed substantial PTSD symptoms ranged from 0% to 46% ( n =1024) and the cumulative incidence of clinician-ascertained transplant-specific PTSD ranged from 10% to 17% ( n =482). Consistent predictors of posttransplant PTSD included history of psychiatric illness prior to transplantation and poor social support posttransplantation. Posttransplant PTSD was consistently associated with worse mental HRQOL and potentially associated with worse physical HRQOL. Conclusions PTSD may impact a substantial proportion of organ transplant recipients. Future studies should focus on transplant-specific PTSD and clarify potential risk factors for, and adverse outcomes related to, posttransplant PTSD.

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.

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.

Summary of Objectives Bronchoalveolar lavage (BAL) is a key tool for clinical monitoring and research in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers, resulting in significant variability of practices. This ISHLT-supported consensus statement on BAL standardization aims to clarify definitions and propose common approaches to improve: a) clinical and research practice standards, b) comparison and validation of research data, and c) collaboration between centers. Methods After an open invitation to ISHLT members, an international workgroup of 68 LTx specialists from 10 countries (75% North America, 16% Europe, 9% Australia/Asia) was created and divided into 9 subgroups covering the following topics: 1) bronchoscopy procedure and BAL collection, 2) sample handling in the bronchoscopy department, 3) sample processing for clinical microbiology, 4) clinical cytology, 5) research and 6) microbiome, 7) sample inventory and tracking, 8) donor bronchoscopy and 9) pediatric considerations. The workgroup designed and administered an online survey to capture practices of BAL collection and processing in LTx, according to the 9 subgroup topics. Results from 112 of 159 invited LTx centers (response rate 70%) indicate significant inter-center discrepancies in the definitions and methodology of BAL collection and processing. A systematic literature analysis performed by the workgroup identified 525 relevant articles; a specifically designed questionnaire was used to a) identify relevant articles for each subgroup and b) assess the quality of published BAL methodology. Endpoints Based on the large-scale international survey and a systematic literature review, the ISHLT BAL Standardization Workgroup is currently preparing consensus statements relevant to the 9 subgroup topics above. The statements will be subjected to three rounds of voting by the workgroup according to the Delphi method (consensus goal >80% of responders within two integers of the median). This abstract will be updated in March 2019 with key excerpts from finalized statements, which will be presented at the ISHLT 2019 annual meeting and submitted for publication. This consensus document will be instrumental for the harmonization of clinical and research practices and will help improve the performance of the international LTx community in this regard.

Purpose On November 24, 2017, in an emergency action, the OPTN changed lung allocation policy by removing the donor service area (DSA) as the first unit of allocation for deceased donor lungs and replaced it with a 250 nautical mile (NM) circle around the donor hospital. Methods OPTN data on adult lung candidates and recipients was analyzed pre (11/25/2016- 8/24/2017) and post policy change (11/25/2017- 8/24/2018, 9 months). Comparisons were made to study the differences between cohorts. Results Comparison between the pre era (N=1,806) and the post era (N=1,843) cohorts revealed a significant increase in the match LAS at transplant (mean pre=47.24 vs. post=49.68, p Conclusion As expected, there was an increase in the distance traveled from transplant center to donor hospital to provide organs to candidates with a higher severity of illness. The waiting list mortality for LAS 60-70 decreased while transplant rate only decreased significantly for LAS 40-50. Lung utilization has not changed but an increase in the use of EVLP is noted. Continued evaluation is needed to understand the full effects of this policy change.

Purpose The OPTN/UNOS added fields to the deceased donor registration form on 3/31/2015 and the transplants recipient registration (TRR) form on 2/28/2018 to collect data on the utilization of ex vivo lung perfusion (EVLP) on donor lung. The steadily increasing use of EVLP, early outcomes, and new data collected on the TRR are summarized. Methods To determine trends in the use of EVLP, all deceased donor lungs recovered from 4/1/2015- 6/30/2018 were analyzed and divided into an EVLP and non-EVLP cohort. TRR data was available for recipients receiving a transplant between 2/28/2018- 6/30/2018. One year lung recipient survival was compared for the cohort spanning 4/1/2015- 6/30/2017. Results EVLP was utilized on 447 of 14,269 recovered lungs procured from 7,524 deceased donors. Of the 447 with EVLP utilized, 165 (34.6%) were DCD donors and 270 (56.6%) were transplanted. A total of 49 out of 58 (84%) OPOs perfused at least 1 lung. By examining the use of EVLP by annual quarters, the earliest quarter had 16 lungs perfused (1.7%) while the most recent quarter had 70 lungs perfused (5.8%). The discard rate for EVLP lungs was statistically higher than lungs that were not perfused (43.4% vs. 4.4%, p Conclusion Since April 2015, the use of EVLP has increased to the current reported level of almost 6% of deceased donor lungs recovered for transplant in the US. The majority of EVLP lungs are perfused at the recovery site by transplant programs and there is no evidence of a negative impact on one year recipient survival. Continued data collection on donor lung perfusion on both the DDR and TRR will allow the OPTN to better understand the utilization of this evolving technology.

Background Ganciclovir-resistant (ganR) cytomegalovirus (CMV) is an emerging and important problem in solid organ transplant (SOT) recipients. Only through direct comparison of ganR- and ganciclovir-sensitive (ganS) CMV infection can risk factors and outcomes attributable specifically to ganciclovir resistance appropriately be determined. Methods We performed a retrospective, case-control (1:3) study of SOT recipients with genotypically confirmed ganR-CMV (n = 37) and ganS-CMV infection (n = 109), matched by donor/recipient CMV serostatus, year and organ transplanted, and clinical manifestation. We used χ2 (categorical) and Mann-Whitney (continuous) tests to determine predisposing factors and morbidity attributable to resistance, and Kaplan-Meier plots to analyze survival differences. Results The rate of ganR-CMV was 1% (37/3467) overall and 4.1% (32/777) among CMV donor-positive, recipient-negative patients, and was stable over the study period. GanR-CMV was associated with increased prior exposure to ganciclovir (median, 153 vs 91 days, P < .001). Eighteen percent (3/17) of lung transplant recipients with ganR-CMV had received

Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers.

Purpose of review Lung transplantation is an important therapeutic treatment for many patients with life-threatening pulmonary diseases; however, long-term survival is still relatively limited compared with other solid organ transplants. Over the last year, several articles have been published helping to increase our knowledge of infections in lung transplant recipients. In particular, important new information has been published recently regarding cytomegalovirus (CMV) and fungal infections following lung transplantation. Recent findings Recent studies indicate prolonged (≥12 months) antiviral prophylaxis for CMV after lung transplant may be beneficial in high-risk transplant recipients. Epidemiologic studies show invasive fungal infections are increasingly being recognized following solid organ transplantation, particularly with Aspergillus and Candida species. Pulmonary infections with CMV and Aspergillus are likely contributors to the development of bronchiolitis obliterans syndrome (BOS). Summary Lung transplantation has many potential posttransplant complications with infection being a major contributor. More information has become available regarding CMV prophylaxis, CMV treatment, pulmonary fungal infection epidemiology, and the role of both CMV and Aspergillus on the development of BOS, which helps toward the goal of increasing long-term survival in lung transplant recipients.

BACKGROUND Chronic lung allograft dysfunction (CLAD) is a major cause of allograft loss post-lung transplantation. Prior studies have examined the association between respiratory virus infection (RVI) and CLAD were limited by older diagnostic techniques, study design, and case numbers. We examined the association between symptomatic RVI and CLAD using modern diagnostic techniques in a large contemporary cohort of lung transplant recipients (LTRs). METHODS We retrospectively assessed clinical variables including acute rejection, cytomegalovirus pneumonia, upper and lower RVI, and the primary endpoint of CLAD (determined by 2 independent reviewers) in 250 LTRs in a single university transplantation program. Univariate and multivariate Cox models were used to analyze the relationship between RVI and CLAD in a time-dependent manner, incorporating different periods of risk following RVI diagnosis. RESULTS Fifty patients (20%) were diagnosed with CLAD at a median of 95 weeks post-transplantation, and 79 (32%) had 114 episodes of RVI. In multivariate analysis, rejection and RVI were independently associated with CLAD (adjusted hazard ratio [95% confidence interval]) 2.2 (1.2-3.9), P = .01 and 1.9 (1.1-3.5), P = .03, respectively. The association of RVI with CLAD was stronger the more proximate the RVI episode: 4.8 (1.9-11.6), P < .01; 3.4 (1.5-7.5), P < .01; and 2.4 (1.2-5.0), P = .02 in multivariate analysis for 3, 6, and 12 months following RVI, respectively. CONCLUSIONS Symptomatic RVI is independently associated with development of CLAD, with increased risk at shorter time periods following RVI. Prospective studies to characterize the virologic determinants of CLAD and define the underlying mechanisms are warranted.