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Background: Lung continuous distribution (CD), implemented on March 9, 2023, changed the calculation and relative importance of medical urgency and posttransplant survival in prioritizing candidates for transplant. We aimed to identify factors associated with waitlist clinical deterioration and change in expected posttransplant survival from listing to transplant in the current system., Methods: We used Organ Procurement and Transplantation Network (OPTN) data to conduct a retrospective study of 2,395 adult, lung-only transplant recipients added to the waiting list and transplanted between March 09, 2023, and March 08, 2024. We used multivariable linear regression to identify factors associated with change in waitlist area under the curve (WLAUC) and posttransplant area under the curve (PTAUC), representing expected survival (in days) without and with transplant, respectively., Results: In multivariable analysis, longer waiting time (β=-1.3 per 7 days; p<0.001), male birth sex (β=-11; p=0.006), diagnosis group D (β=-27; p<0.001), and blood type O (β=-13; p<0.001) were associated with greater clinical deterioration from listing to transplant. Older (β=3.2 per 10-year increase in age; p=0.023) and taller (β=3.0 per 5 cm increase in height; p=0.003) recipients were less likely to clinically deteriorate from listing to transplant. Diagnosis group D (β=-4.7, p=0.032) and blood type O (β=-4.2, p=0.025) recipients had lower expected posttransplant survival at transplant compared to listing., Conclusion: Our findings suggest the need to further investigate and address factors associated with waitlist clinical deterioration under CD. Future analysis of the effect of waitlist clinical deterioration on posttransplant outcomes under CD is needed., (Copyright © 2024. Published by Elsevier Inc.)

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor/tezacaftor/ivacaftor (ETI), significantly improve outcomes and quality of life for people with cystic fibrosis (CF). However, little is known about how lung transplant recipients (LTRs) perceive the use of ETI. We conducted a survey to assess perspectives on ETI among LTRs with CF at our lung transplant program. Of 81 CF LTRs, 46 participants (58 %) responded. The majority of respondents (88 %) were aware of ETI. Over 80 % considered treating non-lung symptoms of CF to be very important. Concerns regarding ETI included potential drug interactions with transplant medications (77 %), side effects (53 %), cost of medication (49 %), and lack of clinical trial data for LTRs (43 %). Half reported they would only consider taking ETI if their CF or transplant doctor recommended it. The findings suggest that CF LTRs seek informational support and shared decision-making about ETI from their clinicians., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Rationale: Lung transplantation can extend the lives of individuals with advanced cystic fibrosis (CF). Until March 2023, the Lung Allocation Score (LAS) was used in the United States to determine transplant priority. Certain clinical events or attributes ("risk events") that are not included in the LAS (e.g., massive hemoptysis) are relatively common and prognostically important in CF and may prompt an exception request to increase priority for donor lungs. The new Lung Composite Allocation Score (CAS) also allows for exceptions based on the same principles. Objectives: To evaluate the frequency of LAS exceptions in persons with CF (PwCFs) listed for lung transplantation and assess whether LAS exceptions are associated with improved waitlist outcomes for PwCFs compared with similarly "at-risk" individuals without LAS exceptions. Methods: A merged dataset combining data from the CF Foundation Patient Registry and the Organ Procurement and Transplantation Network (2005-2019) was used to identify PwCFs listed for lung transplantation. We compared waitlist outcomes between PwCFs with a LAS exception versus those without an exception despite having a risk event. Risk events were defined as an episode of massive hemoptysis, pneumothorax, at least three moderate/severe pulmonary exacerbations, and/or a decrease in forced expiratory volume in 1 second by ⩾30% predicted (absolute) in the prior 12 months. Analyses were performed using competing risk regression with time to transplantation as the primary outcome and death without a transplant as a competing risk. Results: Of 3,538 listings from 3,309 candidates, 2% of listings ( n  = 81) had at least one exception. Candidates with an exception and those with a risk event but no exception received lung transplants more slowly than people without an exception or risk event (subdistribution hazard ratio [95% confidence interval]: LAS exception cohort, 0.66 [0.52-0.85]; risk event cohort without exceptions, 0.79 [0.72-0.86]). There was no difference between those with LAS exceptions and those at risk without LAS exceptions: subdistribution hazard ratio, 0.84 (0.66-1.08). Conclusions: LAS exceptions are rare in PwCFs listed for lung transplantation. LAS exceptions resulted in a similar time to transplantation for PwCFs compared with similarly at-risk individuals. As we enter the CAS era, these LAS-based results are pertinent to improve risk stratification among PwCFs being considered for lung transplantation.

Objectives: Clinical practice guidelines (CPGs) are often created through collaboration among organizations. The use of inconsistent terminology may cause poor communication and delays. This study aimed to develop a glossary of terms related to collaboration in guideline development., Study Design and Setting: A literature review of collaborative guidelines was performed to develop an initial list of terms related to guideline collaboration. The list of terms was presented to the members of the Guideline International Network Guidelines Collaboration Working Group, who provided presumptive definitions for each term and proposed additional terms to be included. The revised list was subsequently reviewed by an international, multidisciplinary panel of expert stakeholders. Recommendations received during this pre-Delphi review were implemented to augment an initial draft glossary. The glossary was then critically evaluated and refined through two rounds of Delphi surveys and a virtual consensus meeting with all panel members as Delphi participants., Results: Forty-nine experts participated in the pre-Delphi survey, and 44 participated in the two-round Delphi process. Consensus was reached for 37 terms and definitions., Conclusion: Uptake and utilization of this guideline collaboration glossary by key organizations and stakeholder groups may facilitate collaboration among guideline-producing organizations by improving communication, minimizing conflicts, and increasing guideline development efficiency., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The first official donor lung allocation system in the United States was initiated by the United Network of Organ Sharing in 1990. The initial policy for lung allocation was simple with donor lungs allocated based on ABO match and the amount of time the candidates accrued on the waiting list. Donor offers were first given to candidates' donor service area. In March 2005, the implementation of the lung allocation score (LAS) was the major change in organ allocation. International adoption of the LAS-based allocation system can be seen worldwide., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Rationale: Hemoptysis is a common and important complication in persons with cystic fibrosis (PwCF). Despite this, there is limited literature on the impact of hemoptysis on contemporary cystic fibrosis (CF) outcomes. Objectives: Evaluate whether hemoptysis increases the risk of lung transplant or death without a transplant in PwCF. Methods: We reviewed a dataset of PwCF ages 12 years or older from the CFFPR (CF Foundation Patient Registry) that included 29,587 individuals. We identified hemoptysis as our predictor of interest and categorized PwCF as either no hemoptysis, any hemoptysis (submassive and/or massive), or massive hemoptysis. We subsequently evaluated whether hemoptysis, as defined above, was associated with death without transplant or receipt of lung transplant via logistic regression. We adjusted for age, sex, body mass index, forced expiratory volume in one second (FEV 1 ), number of exacerbations, supplemental oxygen use, CF-related diabetes, and Pseudomonas aeruginosa colonization status. Subgroup analyses were performed in advanced lung disease, defined as PwCF with an FEV 1  <40% predicted. Results: PwCF with any form of hemoptysis were more likely to progress to lung transplant or die without transplant than PwCF who did not have hemoptysis (odds ratio [OR], 1.3 [95% confidence interval (CI), 1.1-1.7]). The effect size of these associations was larger when hemoptysis events were classified as "massive" (massive hemoptysis OR, 2.2 [95% CI, 1.2-3.8]) or in PwCF with advanced lung disease (massive hemoptysis in advanced lung disease OR, 3.2 [95% CI 1.3-8.2]). Conclusions: Hemoptysis is associated with an increased risk of lung transplant and death without a transplant in PwCF, especially among those with massive hemoptysis or advanced lung disease. Our results suggest that hemoptysis functions as a useful predictor of serious outcomes in PwCF and may be important to incorporate into risk prediction models and/or transplant decisions in CF.

Background: 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., Methods: 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., Results: 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 (all <0.25). 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., Conclusions: 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., Competing Interests: Disclosure statement CHG, EDL, CAM, and KJR report additional grant support from the United States CFF. CAM reports grant support from the NIH Lung Transplant Outcomes Group. CHG reports grant support from the European Commission and NIH National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; and National Center for Research Resources. CHG reports personal or other fees from Gilead Sciences, Novartis, Boehringer Ingelheim, and Vertex Pharmaceuticals. KJR reports grant support from the NIH. None of these financial relationships influenced the interpretation or reporting of the current study. Grant/Research Support; Current/Ongoing - CHEST Foundation Grant in CF in partnership with Vertex Pharmaceuticals, Cystic Fibrosis Foundation (CFF), and the National Institutes of Health (NIH) (K23HL138154). A portion of the findings were presented during the 2022 ISHLT 42nd Annual Meeting and Scientific Sessions as a Mini Oral presentation by JMB., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of interest: A.R. Glanville has received an honorarium for an advisory role from Zambon and is chair of the Zambon DSMB for the Boston trials. Conflict of interest: G.M. Verleden has received an honorarium for an advisory role from Zambon. Conflict of interest: M. Perch has received an honorarium for an advisory role from Zambon, a research grant (institutional) from Roche, speaker fees from Novartis, GSK and Therakos, and other financial support from Boehringer. Conflict of interest: E.D. Lease has received an honorarium for an advisory role from Zambon. Conflict of interest: G-S. Cheng has received an honorarium for an advisory role from Zambon. Conflict of interest: A. Bergeron has received an honorarium for an advisory role from Zambon. Conflict of interest: C. Benden has received an honorarium for an advisory role from Zambon and speaker fees from Therakos. Conflict of interest: J. Gottlieb has received an honorarium for advisory roles from Zambon, research grants from Zambon and Deutsche Forschungsgemeinschaft, and advisory funding from Theravance, Merck and Altara. Conflict of interest: J.L. Todd has received an honorarium for an advisory role from Zambon, Altavant and Natera, and research grants (institutional) from Boehringer Ingelheim, AstraZeneca and CareDx. Conflict of interest: K.M. Williams has received an honorarium for an advisory role from Zambon., (Copyright ©The authors 2022.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Disclosure statement This work was conducted under the auspices of the Hennepin Healthcare Research Institute (HHRI), contractor for the SRTR, as a deliverable under contract no. HHSH75R60220C00011 (US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation). The US Government (and others acting on its behalf) retains a paid-up, nonexclusive, irrevocable, worldwide license for all works produced under the SRTR contract, and to reproduce them, prepare derivative works, distribute copies to the public, and perform publicly and display publicly, by or on behalf of the government. The data reported here have been supplied by HHRI as the contractor for SRTR. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by SRTR or the US Government. The authors thank SRTR colleagues Mary Van Beusekom, MS, ELS, and Anna Gillette for manuscript editing. No authors report a financial conflict of interest., (Copyright © 2022 International Society for Heart and Lung Transplantation. All rights reserved.)

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., Competing Interests: Disclosure The authors have no pertinent disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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 =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]., 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., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described., Methods: We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients., Results: Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P < .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, P = .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, P = .018], obesity [aOR 1.9, 95% CI 1.0-3.4, P = .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, P = .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, P = .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality., Conclusions: Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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 <18 years and adults with high lung allocation scores. Broader geographic distribution increased estimated organ procurement costs for a small percentage of lung transplants. Further analysis should elucidate the broad economic impact of such policies., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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 coronavirus disease 2019 (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, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p = .02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0-2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0-11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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., (© 2021 Special Care Dentistry Association and Wiley Periodicals LLC.)

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., (© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals, LLC. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

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: 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 to 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 = .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., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

The impact of Pseudomonas aeruginosa airway colonization on lung allografts is not entirely clear. In this issue of Cell Reports Medicine , Dugger et al. 1 identify distinct clinical outcomes and lung allograft biology in recipients with and without cystic fibrosis.

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: 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 < 17 kg/m 2 ) in the United States relative to normal-weight recipients with CF and other frequently transplanted patient cohorts., 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 < 17 kg/m 2 compared with recipients with COPD (reference)., 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 < 17 kg/m 2 , compared with those with CF and a BMI ≥ 17 kg/m 2 (7.0 years [4.5-7.9] vs 8.2 years [7.3-9.0]), Cox modeling found no increased mortality risk (adjusted hazard ratio, 1.09; 95% CI, 0.90-1.32; P = .38). There was no difference in posttransplant mortality between patients with CF and a BMI < 17 kg/m 2 and recipients with COPD and all BMIs (adjusted hazard ratio, 1.04; 95% CI, 0.86-1.25; P = .71)., Conclusions: Transplant recipients with CF and a BMI < 17 kg/m 2 had posttransplant survival rates comparable to those of other groups frequently undergoing transplantation. BMI < 17 kg/m 2 as a single risk factor in the CF population should not be treated as an absolute contraindication to LTx., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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.

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., (© 2019 Steunstichting ESOT.)

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., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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 <6 weeks of prior ganciclovir (current guideline-recommended resistance testing threshold), and all non-lung recipients had received ≥90 days (median, 160 [range, 90-284 days]) prior to diagnosis of ganR-CMV. GanR-CMV was associated with higher mortality (11% vs 1%, P = .004), fewer days alive and nonhospitalized (73 vs 81, P = .039), and decreased renal function (42% vs 19%, P = .008) by 3 months after diagnosis., Conclusions: GanR-CMV is associated with longer prior antiviral duration and higher attributable morbidity and mortality than ganS-CMV. Upcoming revised CMV guidelines should incorporate organ transplant-specific thresholds of prior drug exposure to guide rational ganR-CMV testing in SOT recipients. Improved strategies for prevention and treatment of ganR-CMV are warranted., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Lung transplantation (LTx) is frequently considered for patients with cystic fibrosis (CF) when the FEV 1 reaches < 30%. This study estimated transplant-free survival for patients with CF and an FEV 1  < 30% and identified predictors of death without LTx., 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  < 30% prior to LTx were included. We performed Kaplan-Meier survival estimates censored at LTx. Multivariable Cox proportional hazard regression identified predictors of mortality., Results: There were 3,340 patients with an FEV 1  < 30%. Death without LTx occurred in 1,250 patients (37.4%); 951 patients (28.5%) underwent LTx; 918 patients (27.5%) remained alive without LTx at the end of follow-up; and 221 patients (6.6%) were lost to follow-up. Median transplant-free survival after FEV 1  < 30% was 6.6 years (95% CI, 5.9-7.0). Adjusted predictors of death without LTx included supplemental oxygen use (hazard ratio [HR], 2.1; 95% CI, 1.7-2.6), Burkholderia cepacia infection (HR, 1.8; 95% CI, 1.3-2.6), BMI ≤ 18 (HR, 1.6; 95% CI, 1.3-1.9), female sex (HR, 1.6; 95% CI, 1.2-2.0), CF-related diabetes in patients receiving insulin (HR, 1.4; 95% CI, 1.2-1.8), and ≥ one exacerbation per year (HR, 1.7; 95% CI, 1.3-2.2 vs. 0 exacerbations)., Conclusions: Median survival was > 6.5 years for patients with CF and an FEV 1  < 30%, exceeding prior survival estimates. There was substantial heterogeneity in survival, with some patients with CF dying soon after reaching this lung function threshold and others living for many years. For this reason, we conclude that FEV 1  < 30% remains an important marker of disease severity for patients with CF. Patients with a supplemental oxygen requirement or frequent exacerbations should have prompt referral because of their increased risk of death., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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., (© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Prior studies reveal that a significant proportion of patients with cystic fibrosis (CF) and advanced lung disease are not referred for lung transplant (LTx) evaluation. We sought to assess expert CF physician perspectives on the timing of LTx referral and investigate their LTx knowledge., Methods: We developed an online anonymous survey that was distributed by the Cystic Fibrosis Foundation (CFF) to the medical directors of all CFF-accredited care centers in the United States in 2015. The survey addressed only adult patients (≥18 years old) and was sent to 119 adult CF physicians, 86 CFF-affiliated CF physicians (who see adults and children, but have smaller program sizes than adult or pediatric centers), and 127 pediatric CF physicians (who see some adults, but mostly children). The focus of the questions was on CFF-care center characteristics, physician experience and indications/contraindications to referral for LTx evaluation., Results: There were 114/332 (34%) total responses to the survey. The response rates were: 57/119 (48%) adult physicians, 12/86 (14%) affiliate physicians and 43/127 (34%) pediatric physicians; 2 physicians did not include their CFF center type. Despite the poor ability of FEV 1  < 30% to predict death within 2 years, 94% of responding CF physicians said they would refer an adult patient for LTx evaluation if the patient's lung function fell to FEV 1  < 30% predicted. Only 54% of respondents report that pulmonary hypertension would trigger referral. Pulmonary hypertension is an internationally recommended indication to list a patient for LTx (not just for referral for evaluation). Very few physicians (N = 17, 15%) employed components of the lung allocation score (LAS) to determine the timing of referral for LTx evaluation. Interestingly, patient preference not to undergo LTx was "often" or "always" the primary patient-related reason to defer referral for LTx evaluation for 41% (47/114) of respondents., Conclusions: Some potential barriers to timely LTx referral for patients with CF include physician knowledge regarding non-lung function-based recommendations related to timing of referral and listing for LTx, and patient preference not to undergo LTx. Further exploration of physician-level and CF patient-level barriers to timely LTx referral is warranted.

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<30% predicted in two consecutive years., 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., (Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

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., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)