Impact of Extracorporeal Membrane Oxygenation Bridging Duration on Lung Transplant Outcomes.

BACKGROUND: We sought to characterize the association between venovenous extracorporeal membrane oxygenation (VV-ECMO) bridging duration and outcomes in patients listed for lung transplantation. METHODS: A retrospective observational study was conducted using the Organ Procurement and Transplantation Network (OPTN) database to identify adults (≥18 years old) who were listed for lung transplantation between 2016-2020 and who were bridged with VV-ECMO. Patients were then stratified into groups, determined by risk inflection points, depending on the amount of time spent on pre-transplant ECMO: Group 1 (≤5 days), Group 2 (6-10 days), Group 3 (11-20 days), and Group 4 (>20 days). Waitlist survival between groups was analyzed using Fine-Gray competing risk models. Post-transplant survival was compared using Cox regression. RESULTS: Of 566 eligible VV-ECMO bridge-to-lung-transplant patients (median age=54, 49% male), 174 (31%), 124 (22%), 130 (23%), and 138 (24%) were categorized as Groups 1, 2, 3, and 4, respectively. Overall, median duration of VV-ECMO was 10 days (range=1-211) and 178 patients (31%) died on the waitlist. In the Fine-Gray model, compared to Group 1, patients bridged with longer ECMO durations in Groups 2 (SHR=2.95, 95%CI: 1.63-5.35), 3 (SHR=3.96, 95%CI: 2.36-6.63), and 4 (SHR=4.33, 95%CI: 2.59-7.22, all p<0.001), were more likely to die on the waitlist. Of 388 patients receiving a transplant, pre-transplant ECMO duration was not associated with one-year survival in Cox regression. CONCLUSIONS: Prolonged ECMO bridging duration was associated with worse waitlist mortality but did not impact post-lung transplant survival. Prioritization of very early transplantation may improve waitlist outcomes in this population.

Debunking the July Effect in lung transplantation recipients.

Objective: The "July Effect" is a theory that the influx of trainees from July to September negatively impacts patient outcomes. We aimed to study this theoretical phenomenon in lung transplant recipients given the highly technical nature of thoracic procedures. Methods: Adult lung transplant hospitalizations were identified within the National Inpatient Sample (2005-2020). Recipients were categorized as academic Q1 (July to September) or Q2-Q4 (October to June). In-hospital mortality, operator-driven complications (pneumothorax, dehiscence including wound dehiscence, bronchial anastomosis, and others, and vocal cord/diaphragm paralysis, all 3 treated as a composite outcome), length of stay, and inflation-adjusted hospitalization charges were compared between both groups. Multivariable logistic regression was performed to assess the association between academic quarter and in-hospital mortality and operator-driven complications. The models were adjusted for recipient demographics and transplant characteristics. Subgroup analysis was performed between academic and nonacademic hospitals. Results: Of 30,788 lung transplants, 7838 occurred in Q1 and 22,950 occurred in Q2-Q4. Recipient demographic and clinical characteristics were similar between groups. Dehiscence (n = 922, 4% vs n = 236, 3%), post-transplant cardiac arrest (n = 532, 2% vs n = 113, 1%), and pulmonary embolism (n = 712, 3% vs n = 164, 2%) were more common in Q2-Q4 versus Q1 recipients (all P < .05). Other operator-driven complications, in-hospital mortality, and resource use were similar between groups (P > .05). These inferences remained unchanged in adjusted analyses and on subgroup analyses of academic versus nonacademic hospitals. Conclusions: The "July Effect" is not evident in US lung transplantation recipient outcomes during the transplant hospitalization. This suggests that current institutional monitoring systems for trainees across multiple specialties, including surgery, anesthesia, critical care, nursing, and others, are robust.

Bigger pies, bigger slices: Increased hospitalization costs for lung transplantation recipients in the non-donation service area allocation era.

OBJECTIVE: On November 24, 2017, lung transplant allocation switched from donation service area to a 250-nautical mile radius policy to improve equity in access to lung transplantation. Given the growing consideration of healthcare costs, we evaluated changes in hospitalization costs after this policy change. METHODS: Lung transplant hospitalizations were identified within the National Inpatient Sample from 2005 to 2020. Recipients were categorized as donation service area era (August 2015 to October 2017) or non-donation service area era (December 2017 to February 2020). Median total hospitalization costs (inflation adjusted) were compared by era nationally and regionally. Multivariable generalized linear regression was performed to determine if the removal of the donation service area was associated with total hospitalization costs. The model was adjusted for recipient demographics, Charlson Comorbidity Index, hospitalization region, transplant type (single, double), and use of extracorporeal membrane oxygenation, ex vivo lung perfusion, and mechanical ventilation. RESULTS: We analyzed 12,985 lung transplant recipients (median age of 61 years, 66% were male): 7070 in the donation service area era and 5915 in the non-donation service area era. Demographics were not different between recipients in both eras. Non-donation service area era recipients had greater extracorporeal membrane oxygenation use, mechanical ventilation (<24 hours), and longer length of stay than donation service area era recipients. Median total hospitalization costs for non-donation service area versus donation service area era recipients increased by $24,198 ($157,964 vs $182,162, percentage change = 15.32%, P < .001). Median costs increased in East North Central ($42,281) and Mountain ($35,521) regions (both P < .01). After adjustment, median costs for non-donation service area versus donation service area era recipients still increased ($19,168, 95% CI, 145-38,191, P = .048). CONCLUSIONS: Hospitalization costs for lung transplant hospitalizations have increased from 2015 to 2020. The transition from donation service area-based allocation to the non-donation service area system may have contributed to this increase after 2017 by increasing access to transplant for sicker recipients.

Age and associated outcomes among patients receiving venovenous extracorporeal membrane oxygenation for acute respiratory failure: analysis of the Extracorporeal Life Support Organization registry.

PURPOSE: Venovenous extracorporeal membrane oxygenation (VV-ECMO) can be used to support patients with refractory acute respiratory failure, though guidance on patient selection is lacking. While age is commonly utilized as a factor in establishing the potential VV-ECMO candidacy of these patients, little is known regarding its association with outcome. We studied the association between increasing patient age and outcomes among patients with acute respiratory failure receiving VV-ECMO. METHODS: In this registry-based cohort study, we used individual patient data from 144 centres. We included adult patients (≥ 18 years of age) receiving VV-ECMO from 2017 to 2022. The primary outcome was hospital mortality. Secondary outcomes included a composite of complications following initiation of VV-ECMO. We conducted Bayesian analyses to estimate the association between chronological age and outcomes. RESULTS: We included 27,811 patients receiving VV-ECMO. Of these, 11,533 (41.5%) died in hospital. For the analysis conducted using weakly informed priors, and as compared to the reference category of age 18-29, the age brackets of 30-39 (odds ratio [OR] 1.17, 95% credible interval [CrI] 1.06-1.31), 40-49 (OR 1.65, 95% CrI 1.49-1.82), 50-59 (OR 2.39, 95% CrI 2.16-2.61), 60-69 (OR 3.29, 95% CrI 2.97-3.67), 70-79 (OR 4.57, 95% CrI 3.90-5.37), and ≥ 80 (OR 8.08, 95% CrI 4.85-13.74) were independently associated with increasing hospital mortality. Similar results were found between increasing age and post-ECMO complications. CONCLUSIONS: Among patients receiving VV-ECMO for acute respiratory failure, increasing age is significantly associated with poorer outcomes, and this association emerges as early as 30 years of age.

Racial disparities among patients on venovenous extracorporeal membrane oxygenation in the pre-Coronavirus Disease 2019 and Coronavirus Disease 2019 eras: A retrospective registry review.

Objectives: Although many studies have addressed such disparities caused by COVID-19, to our knowledge, no study has focused on the association of race on outcomes for patients with COVID-19 requiring venovenous extracorporeal membrane oxygenation support. The goal of this study was to assess association of race on death and duration on venovenous extracorporeal membrane oxygenation in both the pre-COVID-19 and COVID-19 eras. Methods: We retrospectively reviewed the Extracorporeal Life Support Organization registry and included adults (≥18 years) who required venovenous extracorporeal membrane oxygenation between January 2019 and April 2021. We performed descriptive statistics and multivariable logistic regression. Our primary outcomes were death and extracorporeal membrane oxygenation duration. Results: A total of 7477 patients were included after excluding 340 patients (4.3%) who were missing race data. In the COVID-19 era, 1474 of 2777 COVID-19-positive patients (53.1%) died. Our regression model suggested somewhat of a protective effect on death for Black and multiple race patients. Additionally, a diagnosis of COVID-19 and patients in the COVID-19 era in general, irrespective of COVID-19 diagnosis, had higher odds of death. Hispanic patients had the longest average venovenous extracorporeal membrane oxygenation run times. Conclusions: Our study using data from the international Extracorporeal Life Support Organization Registry provides updated data on patients supported with venovenous extracorporeal membrane oxygenation in the pre-COVID-19 and COVID-19 eras between 2019 and 2021 with a focus on race. Patients in the COVID-19 era group also had higher mortality compared with those in the pre-COVID-19 era even after being adjusted for COVID-19 diagnosis. Black and multiple races appeared somewhat protective in terms of death. Hispanic race was associated with longer venovenous extracorporeal membrane oxygenation duration.

Outcomes of Recipients Aged 65 Years and Older Bridged to Lung Transplant With Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (BTT) has been used for critically ill candidates with excellent outcomes, but data on this strategy in older recipients remain limited. We compared outcomes of no BTT, mechanical ventilation (MV)-only BTT, and ECMO BTT in recipients of greater than or equal to 65 years. Lung-only recipients of greater than or equal to 65 years in the United Network for Organ Sharing database between 2008 and 2022 were included and stratified by bridging strategy. Of the 9,936 transplants included, 226 (2.3%) were MV-only BTT and 159 (1.6%) were ECMO BTT. Extracorporeal membrane oxygenation BTT recipients were more likely to have restrictive disease pathology, had higher median lung allocation score, and spent fewer days on the waitlist (all p < 0.001). Compared to no-BTT recipients, ECMO BTT recipients were more likely to be intubated or on ECMO at 72 hours posttransplant and had longer hospital lengths of stay (all p < 0.001). Extracorporeal membrane oxygenation BTT recipients had increased risk of 3 years mortality compared to both no-BTT (adjusted hazard ratio [aHR] = 1.48 [95% confidence interval {CI}: 1.14-1.91], p = 0.003) and MV-only recipients (aHR = 1.50 [95% CI: 1.08-2.07], p = 0.02). Overall, we found that ECMO BTT in older recipients is associated with inferior posttransplant outcomes compared to MV-only or no BTT, but over half of recipients remained alive at 3 years posttransplant.

Impact of recipient age on mortality among Cytomegalovirus (CMV)-seronegative lung transplant recipients with CMV-seropositive donors.

BACKGROUND: Cytomegalovirus (CMV)-seronegative lung transplant recipients (LTRs) with seropositive donors (CMV D+/R-) have the highest mortality of all CMV serostatuses. Due to immunosenescence and other factors, we hypothesized CMV D+/R- status might disproportionately impact older LTRs. Thus, we investigated whether recipient age modified the relationship between donor CMV status and mortality among CMV-seronegative LTRs. METHODS: Adult, CMV-seronegative first-time lung-only recipients were identified through the Scientific Registry of Transplant Recipients between May 2005 and December 2019. We used adjusted multivariable Cox regression to assess the relationship of donor CMV status and death. Interaction between recipient age and donor CMV was assessed via likelihood ratio testing of nested Cox models and by the relative excess risk due to interaction (RERI) and attributable proportion (AP) of joint effects. RESULTS: We identified 11,136 CMV-seronegative LTRs. The median age was 59 years; 65.2% were male, with leading transplant indication of idiopathic pulmonary fibrosis (35.6%); and 60.8% were CMV D+/R-. In multivariable modeling, CMV D+/R- status was associated with 27% increased hazard of death (adjusted hazard ratio: 1.27, 95% confidence interval: 1.21-1.34) compared to CMV D-/R-. Recipient age ≥60 years significantly modified the relationship between donor CMV-seropositive status and mortality on the additive scale, including RERI 0.24 and AP 11.4% (p = 0.001), that is, the interaction increased hazard of death by 0.24 and explained 11.4% of mortality in older CMV D+ recipients. CONCLUSIONS: Among CMV-seronegative LTRs, donor CMV-seropositive status confers higher risk of posttransplant mortality, which is amplified in older recipients. Future studies should define optimal strategies for CMV prevention and management in older D+/R- LTRs.

Uptake and 1-year outcomes of lung transplantation for COVID-19.

OBJECTIVE: End-stage lung disease from severe COVID-19 infection is an increasingly common indication for lung transplantation (LT), but there are limited data on outcomes. We evaluated 1-year COVID-19 LT outcomes. METHODS: We identified all adult US LT recipients January 2020 to October 2022 in the Scientific Registry for Transplant Recipients, using diagnosis codes to identify recipients transplanted for COVID-19. We used multivariable regression to compare in-hospital acute rejection, prolonged ventilator support, tracheostomy, dialysis, and 1-year mortality between COVID-19 and non-COVID-19 recipients, adjusting for donor, recipient, and transplant characteristics. RESULTS: LT for COVID-19 increased from 0.8% to 10.7% of total LT volume during 2020 to 2021. The number of centers performing LT for COVID-19 increased from 12 to 50. Recipients transplanted for COVID-19 were younger; were more likely to be male and Hispanic; were more likely to be on a ventilator, extracorporeal membrane oxygenation support, and dialysis pre-LT; were more likely to receive bilateral LT; and had higher lung allocation score and shorter waitlist time than other recipients (all P values < .001). COVID-19 LT had higher risk of prolonged ventilator support (adjusted odds ratio, 2.28; P < .001), tracheostomy (adjusted odds ratio 5.3; P < .001), and longer length of stay (median, 27 vs 19 days; P < .001). Risk of in-hospital acute rejection (adjusted odds ratio, 0.99; P = .95) and 1-year mortality (adjusted hazard ratio, 0.73; P = .12) were similar for COVID-19 LTs and LTs for other indications, even accounting for center-level differences. CONCLUSIONS: COVID-19 LT is associated with higher risk of immediate postoperative complications but similar risk of 1-year mortality despite more severe pre-LT illness. These encouraging results support the ongoing use of LT for COVID-19-related lung disease.

The effect of allograft ischemic time on outcomes following bilateral, single, and reoperative lung transplantation.

OBJECTIVE: To determine whether allograft ischemic times affect outcomes following bilateral, single, and redo lung transplantation. METHODS: A nationwide cohort of lung transplant recipients from 2005 through 2020 was examined using the Organ Procurement and Transplantation Network registry. The effects of standard (<6 hours) and extended (≥6 hours) ischemic times on outcomes following primary bilateral (n = 19,624), primary single (n = 688), redo bilateral (n = 8461), and redo single (n = 449) lung transplantation were analyzed. A priori subgroup analysis was performed in the primary and redo bilateral-lung transplant cohorts by further stratifying the extended ischemic time group into mild (≥6 and <8 hours), moderate (≥8 and <10 hours), and long (≥10 hours) subgroups. Primary outcomes included 30-day mortality, 1-year mortality, intubation at 72 hours' posttransplant, extracorporeal membrane oxygenation (ECMO) support at 72 hours' posttransplant, and a composite variable of intubation or ECMO at 72 hours' posttransplant. Secondary outcomes included acute rejection, postoperative dialysis, and hospital length of stay. RESULTS: Recipients of allografts with ischemic times ≥6 hours experienced increased 30-day and 1-year mortality following primary bilateral-lung transplantation, but increased mortality was not observed following primary single, redo bilateral, or redo single-lung transplants. Extended ischemic times correlated with prolonged intubation or increased postoperative ECMO support in the primary bilateral, primary single, and redo bilateral-lung transplant cohorts but did not affect these outcomes following redo single-lung transplantation. CONCLUSIONS: Since prolonged allograft ischemia correlates with worse transplant outcomes, the decision to use donor lungs with extended ischemic times must consider the specific benefits and risks associated with individual recipient factors and institutional expertise.

Extracorporeal membrane oxygenation as a bridge to lung transplantation: Practice patterns and patient outcomes.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly relied on to bridge patients with respiratory failure to lung transplantation despite limited evidence for its use in this setting. This study evaluated longitudinal trends in practice patterns, patient characteristics, and outcomes in patients bridged with ECMO to lung transplant. METHODS: A retrospective review of all adult isolated lung transplant patients in the United Network for Organ Sharing database between 2000 and 2019 was performed. Patients were classified as "ECMO" if supported with ECMO at the time of listing or transplantation and "non-ECMO" otherwise. Linear regression was used to evaluate trends in patient demographics during the study period. Trends in mortality were evaluated using Cox proportional hazards modeling, with time period as the primary covariate (2000-2004, 2005-2009, 2010-2014, or 2015-2019) and age, time on the waitlist, and underlying diagnosis as covariates. RESULTS: The number of patients included were 40,866, of whom 1,387 (3.4%) were classified as ECMO and 39,479 (96.6%) as no ECMO. Average age and initial Lung Allocation Score increased significantly during the study period in both cohorts, but occurred at a slower rate in the ECMO population. The hazard of death was significantly lower in more recent years (2015-2019) for both the ECMO and non-ECMO cohorts (aHR (adjusted hazards ratio) 0.59, 95% confidence interval (CI) 0.37-0.96 and aHR 0.74, 95% CI 0.70-0.79) when compared to the early years (2000-2004) of the study period. CONCLUSIONS: Post-transplantation survival for patients bridged to transplantation with ECMO demonstrates ongoing improvement despite cannulation of progressively older and sicker patients.

Outcomes of Lung Transplant Candidates Aged ≥70 Years During the Lung Allocation Score Era.

BACKGROUND: With the increasing age of lung transplant candidates, we studied waitlist and posttransplantation outcomes of candidates ≥70 years during the Lung Allocation Score era. METHODS: Adult lung transplant candidates from 2005 to 2020 in the United Network for Organ Sharing database were included and stratified on the basis of age at listing into 18 to 59 years old, 60 to 69 years old, and ≥70 years old. Baseline characteristics, waitlist outcomes, and posttransplantation outcomes were assessed. RESULTS: A total of 37,623 candidates were included (52.3% aged 18-59 years, 40.6% aged 60-69 years, 7.1% aged ≥70 years). Candidates ≥70 years were more likely than younger candidates to receive a transplant (81.9% vs 72.7% [aged 60-69 years] vs 61.6% [aged 18-59 years]) and less likely to die or to deteriorate on the waitlist within 1 year (9.1% vs 10.1% [aged 60-69 years] vs 12.2% [aged 18-59 years]; P < .001). Donors for older recipients were more likely to be extended criteria (75.7% vs 70.1% [aged 60-69 years] vs 65.7% [aged 18-59 years]; P < .001). Recipients ≥70 years were found to have lower rates of acute rejection (6.7% vs 7.4% [aged 60-69 years] vs 9.2% [aged 18-59 years]; P < .001) and prolonged intubation (21.7% vs 27.4% [aged 60-69 years] vs 34.5% [aged 18-59 years]; P < .001). Recipients aged ≥70 years had increased 1-year (adjusted hazard ratio [aHR], 1.19 [95% CI, 1.06-1.33]; P < .001), 3-year (aHR, 1.28 [95% CI, 1.18-1.39]; P < .001), and 5-year mortality (aHR, 1.29 [95% CI, 1.21-1.38]; P < .001) compared with recipients aged 60 to 69 years. CONCLUSIONS: Candidates ≥70 years had favorable waitlist and perioperative outcomes despite increased use of extended criteria donors. Careful selection of candidates and postoperative surveillance may improve posttransplantation survival in this population.

Racial Disparities in Waiting List Outcomes of Patients Listed for Lung Transplantation.

BACKGROUND: The Lung Allocation Score, implemented in 2005, prioritized lung transplant candidates by medical urgency rather than waiting list time and was expected to improve racial disparities in transplant allocation. We evaluated whether racial disparities in lung transplant persisted after 2005. METHODS: We identified all wait-listed adult lung transplant candidates in the United States from 2005 through 2021 using the Scientific Registry of Transplant Recipients. We evaluated the association between race and receipt of a transplant by using a multivariable competing risk regression model adjusted for demographics, socioeconomic status, Lung Allocation Score, clinical measures, and time. We evaluated interactions between race and age, sex, socioeconomic status, and Lung Allocation Score. RESULTS: We identified 33,158 candidates on the lung transplant waiting list between 2005 and 2021: 27,074 White (82%), 3350 African American (10%), and 2734 Hispanic (8%). White candidates were older, had higher education levels, and had lower Lung Allocation Scores (P < .001). After multivariable adjustment, African American and Hispanic candidates were less likely to receive lung transplants than White candidates (African American: adjusted subhazard ratio, 0.86; 95% CI, 0.82-0.91; Hispanic: adjusted subhazard ratio, 0.82; 95% CI, 0.78-0.87). Lung transplant was significantly less common among Hispanic candidates aged >65 years (P = .003) and non-White candidates from higher-poverty communities (African-American: P = .013; Hispanic: P =.0036). CONCLUSIONS: Despite implementation of the Lung Allocation Score, racial disparities persisted for wait-listed African American and Hispanic lung transplant candidates and differed by age and poverty status. Targeted interventions are needed to ensure equitable access to this life-saving intervention.

Incidence, risk factors, and outcomes of postoperative stroke in combined heart-lung transplantation: A retrospective cohort study of the UNOS registry.

Stroke is a well-characterized complication of isolated heart and lung transplantation, but has not been described in combined heart-lung transplantation (HLTx). We retrospectively reviewed national U.S. data to describe the incidence, risk factors, and impact of postoperative stroke in HLTx recipients. Of 871 heart-lung recipients between 1994-2022, 35 (4.0%) experienced stroke, and the incidence increased over time, trending toward significance (p-trend = .07). After adjustment, extracorporeal membrane oxygenation (ECMO) (Adjusted odds ratio [aOR] = 2.63, 95%CI = [1.13-6.11]) and pre-transplant implantable defibrillator (aOR = 2.86, 95%CI = [1.20-6.81]) were independent risk factors for stroke. Postoperative stroke is common and is increasing in an era where organ allocation is driven by mechanical circulatory support (MCS) bridging.

Cell-Free DNA Maps Tissue Injury and Correlates with Disease Severity in Lung Transplant Candidates.

Rationale: Plasma cell-free DNA levels correlate with disease severity in many conditions. Pretransplant cell-free DNA may risk stratify lung transplant candidates for post-transplant complications. Objectives: To evaluate if pretransplant cell-free DNA levels and tissue sources identify patients at high risk of primary graft dysfunction and other pre- and post-transplant outcomes. Methods: This multicenter, prospective cohort study recruited 186 lung transplant candidates. Pretransplant plasma samples were collected to measure cell-free DNA. Bisulfite sequencing was performed to identify the tissue sources of cell-free DNA. Multivariable regression models determined the association between cell-free DNA levels and the primary outcome of primary graft dysfunction and other transplant outcomes, including Lung Allocation Score, chronic lung allograft dysfunction, and death. Measurements and Main Results: Transplant candidates had twofold greater cell-free DNA levels than healthy control patients (median [interquartile range], 23.7 ng/ml [15.1-35.6] vs. 12.9 ng/ml [9.9-18.4]; P < 0.0001), primarily originating from inflammatory innate immune cells. Cell-free DNA levels and tissue sources differed by native lung disease category and correlated with the Lung Allocation Score (P < 0.001). High pretransplant cell-free DNA increased the risk of primary graft dysfunction (odds ratio, 1.60; 95% confidence interval [CI], 1.09-2.46; P = 0.0220), and death (hazard ratio, 1.43; 95% CI, 1.07-1.92; P = 0.0171) but not chronic lung allograft dysfunction (hazard ratio, 1.37; 95% CI, 0.97-1.94; P = 0.0767). Conclusions: Lung transplant candidates demonstrate a heightened degree of tissue injury with elevated cell-free DNA, primarily originating from innate immune cells. Pretransplant plasma cell-free DNA levels predict post-transplant complications.

National utilization, trends, and lung transplant outcomes of static versus portable ex vivo lung perfusion platforms.

BACKGROUND: This study compared utilization and outcomes of the 2 widely utilized ex vivo lung perfusion (EVLP) platforms in the United States: a static platform and a portable platform. METHODS: Adult (age 18 years or older) bilateral lung-only transplants utilizing EVLP between February 28, 2018, and December 31, 2022, in the United Network for Organ Sharing database were included. Predischarge acute rejection, intubation at 72 hours posttransplant, extracorporeal membrane oxygenation at 72 hours posttransplant, primary graft dysfunction grade 3 at 72 hours posttransplant, 30-day mortality, and 1-year mortality were evaluated using multivariable regressions. RESULTS: Overall, 607 (6.3%) lung transplants during the study period used EVLP (51.2% static, 48.8% portable). Static EVLP was primarily utilized in the eastern United States, whereas portable EVLP was primarily utilized in the western United States. Static EVLP donors were more likely to be donation after circulatory death (33.4% vs 26.0%; P = .005), have a >20 pack-year smoking history (13.5% vs 6.5%; P = .005), and be extended criteria donors (92.3% vs 85.0%; P = .013), whereas portable EVLP donors were more likely to be older than age 55 years (14.2% vs 8.0%; P = .02). Transplants utilizing the static and portable platforms had similar risk of acute rejection, intubation at 72 hours, extracorporeal membrane oxygenation at 72 hours, primary graft dysfunction grade 3 at 72 hours, and posttransplant mortality at 30 days and 1 year (all P values > .05). CONCLUSIONS: The static and portable platforms had significant differences in donor characteristics and geographic distributions of utilization. Despite this, posttransplant survival was similar between the 2 EVLP platforms.

To decline or not to decline: Consequences of decision-making regarding lung offers from donors with hepatitis C.

OBJECTIVE: Lung transplants from donors with hepatitis C (HCV D+) have excellent outcomes, but these organs continue to be declined. We evaluated whether (1) being listed to consider and (2) accepting versus declining HCV D+ offers provided a survival benefit to lung transplant candidates. METHODS: Using the Scientific Registry of Transplant Recipients, we identified all adult (≥18 years) lung transplant candidates 2016-2021 and compared waitlist mortality between those willing versus not willing to consider HCV D+ offers using competing risk regression. We identified all candidates offered an HCV D+ lung that was later accepted and followed them from offer decision until death or end-of-study. We estimated adjusted mortality risk of accepting versus declining an HCV D+ lung offer using propensity-weighted Cox regression. RESULTS: From 2016 to 2021, we identified 21,007 lung transplant candidates, 33.8% of whom were willing to consider HCV D+ offers. Candidates willing to consider HCV D+ offers had a 17% lower risk of waitlist mortality (subhazard ratio, 0.83; 95% confidence interval, 0.75-0.91, P < .001). Over the same period, 665 HCV D+ lung offers were accepted after being declined a total of 2562 times. HCV D+ offer acceptance versus decline was associated with a 20% lower risk of mortality (adjusted hazard ratio, 0.80; 95% confidence interval, 0.66-0.96, P = .02). CONCLUSIONS: Considering HCV D+ lung offers was associated with a 17% lower risk of waitlist mortality, whereas accepting versus declining an HCV D+ lung offer was associated with a 20% lower risk of mortality. Centers and candidates should consider accepting suitable HCV D+ lung offers to optimize outcomes.

Current status and future potential of ex vivo lung perfusion in clinical lung transplantation.

Lung transplantation is accepted as a well-established and effective treatment for patients with end-stage lung disease. While the number of candidates added to the waitlist continues to rise, the number of transplants performed remains limited by the number of suitable organ donors. Ex vivo lung perfusion (EVLP) emerged as a method of addressing the organ shortage by allowing the evaluation and potential reconditioning of marginal donor lungs or minimizing risks of prolonged ischemic time due to logistical challenges. The currently available FDA-approved EVLP systems have demonstrated excellent outcomes in clinical trials, and retrospective studies have demonstrated similar post-transplant survival between recipients who received marginal donor lungs perfused using EVLP and recipients who received standard criteria lungs stored using conventional methods. Despite this, widespread utilization has plateaued in the last few years, likely due to the significant costs associated with initiating EVLP programs. Centralized, dedicated EVLP perfusion centers are currently being investigated as a potential method of further expanding utilization of this technology. In the preclinical setting, potential applications of EVLP that are currently being studied include prolongation of organ preservation, reconditioning of unsuitable lungs, and further enhancement of already suitable lungs. As adoption of EVLP technology becomes more widespread, we may begin to see future implementation of these potential applications into the clinical setting.

Race-Specific Interpretation of Spirometry: Impact on the Lung Allocation Score.

Rationale: Interpretation of spirometry using race-specific reference equations may contribute to health disparities via underestimation of the degree of lung function impairment in Black patients. The use of race-specific equations may differentially affect patients with severe respiratory disease via the use of percentage predicted forced vital capacity (FVCpp) when included in the lung allocation score (LAS), the primary determinant of priority for lung transplantation. Objectives: To determine the impact of a race-specific versus a race-neutral approach to spirometry interpretation on the LAS among adults listed for lung transplantation in the United States. Methods: We developed a cohort from the United Network for Organ Sharing database including all White and Black adults listed for lung transplantation between January 7, 2009, and February 18, 2015. The LAS at listing was calculated for each patient under race-specific and race-neutral approaches, using the FVCpp generated from the Global Lung Function Initiative equation corresponding to each patient's race (race-specific) or from the Global Lung Function Initiative "other" (race-neutral) equation. Differences in LAS between approaches were compared by race, with positive values indicating a higher LAS under the race-neutral approach. Results: In this cohort of 8,982 patients, 90.3% were White and 9.7% were Black. The mean FVCpp was 4.4% higher versus 3.8% lower among White versus Black patients (P < 0.001) under a race-neutral compared with a race-specific approach. Compared with White patients, Black patients had a higher mean LAS under both a race-specific (41.9 vs. 43.9; P < 0.001) and a race-neutral (41.3 vs. 44.3; P < 0.001) approach. However, the mean difference in LAS under a race-neutral approach was -0.6 versus +0.6 for White versus Black patients (P < 0.001). Differences in LAS under a race-neutral approach were most pronounced for those in group B (pulmonary vascular disease) (-0.71 vs. +0.70; P < 0.001) and group D (restrictive lung disease) (-0.78 vs. +0.68; P < 0.001). Conclusions: A race-specific approach to spirometry interpretation has potential to adversely affect the care of Black patients with advanced respiratory disease. Compared with a race-neutral approach, a race-specific approach resulted in lower LASs for Black patients and higher LASs for White patients, which may have contributed to racially biased allocation of lung transplantation. The future use of race-specific equations must be carefully considered.

National Trends, Risk Factors, and Outcomes of Acute In-Hospital Stroke Following Lung Transplantation in the United States: Analysis of the United Network for Organ Sharing Registry.

BACKGROUND: Lung transplantation (LTx) is the definitive treatment for end-stage lung failure. However, there have been no large, long-term studies on the impact of acute in-hospital stroke in this population. RESEARCH QUESTION: What are the trends, risk factors, and outcomes of acute stroke in patients undergoing LTx in the United States? STUDY DESIGN AND METHODS: We identified adult first-time isolated LTx recipients from the United Network for Organ Sharing database, which comprehensively captures every transplant in the United States, between May 2005 and December 2020. Stroke was defined as occurring at any time after LTx but prior to discharge. Multivariable logistic regression with stepwise feature elimination was used to identify risk factors for stroke. Freedom from death in patients with a stroke vs those without a stroke was evaluated with Kaplan-Meier analysis. Cox proportional hazards analysis was used to identify predictors of death at 24 months. RESULTS: Of 28,564 patients (median age, 60 years; 60% male), 653 (2.3%) experienced an acute in-hospital stroke after LTx. Median follow-up was 1.2 (stroke) and 3.0 (non-stroke) years. Annual incidence of stroke increased (1.5% in 2005 to 2.4% in 2020; P for trend = .007), as did lung allocation score and utilization of post-LTx extracorporeal membrane oxygenation (P = .01 and P < .001, respectively). Compared with those without stroke, patients with stroke had lower survival at 1 month (84% vs 98%), 12 months (61% vs 88%), and 24 months (52% vs 80%) (log-rank test, P < .001 for all). In Cox analysis, acute stroke conferred a high hazard of mortality (hazard ratio, 3.01; 95% CI, 2.67-3.41). Post-LTx extracorporeal membrane oxygenation was the strongest risk factor for stroke (adjusted OR, 2.98; 95% CI, 2.19-4.06). INTERPRETATION: Acute in-hospital stroke post-LTx has been increasing over time and is associated with markedly worse short- and long-term survival. As increasingly sicker patients undergo LTx as well as experience stroke, further research on stroke characteristics, prevention, and management strategies is warranted.