Changing patterns in lung transplant for respiratory failure due to COVID-19 in the U.S.

Many patients with severe COVID-19 have been affected by acute respiratory distress syndrome, which has been associated with increased mortality, and up to 31% of these survivors had persistent interstitial lung abnormalities with impaired lung function and quality of life even after 6 to 24 months after initial disease. Lung transplantation quickly emerged as a viable therapy for select patients with respiratory failure due to COVID-19 by mid-2020. In this report, we identified 477 patients who underwent lung transplantation for COVID-19 in the U.S. between March 2020 and December 2022. The number of patients waitlisted and undergoing lung transplantation for COVID-19 increased steadily in the early part of the pandemic with a peak of 97 patients waitlisted between October and December 2021, before steadily decreasing since. Notably, the procedure is now increasingly being done for survivors of COVID-19 with pulmonary fibrosis, rather than for refractory ARDS patients. The 1-year post-transplant mortality was 13.7%.

Development of the Lung Transplant Frailty Scale (LT-FS).

BACKGROUND: Existing measures of frailty developed in community dwelling older adults may misclassify frailty in lung transplant candidates. We aimed to develop a novel frailty scale for lung transplantation with improved performance characteristics. METHODS: We measured the short physical performance battery (SPPB), fried frailty phenotype (FFP), Body Composition, and serum Biomarkers representative of putative frailty mechanisms. We applied a 4-step established approach (identify frailty domain variable bivariate associations with the outcome of waitlist delisting or death; build models sequentially incorporating variables from each frailty domain cluster; retain variables that improved model performance ability by c-statistic or AIC) to develop 3 candidate "Lung Transplant Frailty Scale (LT-FS)" measures: 1 incorporating readily available clinical data; 1 adding muscle mass, and 1 adding muscle mass and research-grade Biomarkers. We compared construct and predictive validity of LT-FS models to the SPPB and FFP by ANOVA, ANCOVA, and Cox proportional-hazard modeling. RESULTS: In 342 lung transplant candidates, LT-FS models exhibited superior construct and predictive validity compared to the SPPB and FFP. The addition of muscle mass and Biomarkers improved model performance. Frailty by all measures was associated with waitlist disability, poorer HRQL, and waitlist delisting/death. LT-FS models exhibited stronger associations with waitlist delisting/death than SPPB or FFP (C-statistic range: 0.73-0.78 vs. 0.57 and 0.55 for SPPB and FFP, respectively). Compared to SPPB and FFP, LT-FS models were generally more strongly associated with delisting/death and improved delisting/death net reclassification, with greater improvements with increasing LT-FS model complexity (range: 0.11-0.34). For example, LT-FS-Body Composition hazard ratio for delisting/death: 6.0 (95%CI: 2.5, 14.2), SPPB HR: 2.5 (95%CI: 1.1, 5.8), FFP HR: 4.3 (95%CI: 1.8, 10.1). Pre-transplant LT-FS frailty, but not SPPB or FFP, was associated with mortality after transplant. CONCLUSIONS: The LT-FS is a disease-specific physical frailty measure with face and construct validity that has superior predictive validity over established measures.

Subphenotypes of frailty in lung transplant candidates.

Heterogeneous frailty pathobiology might explain the inconsistent associations observed between frailty and lung transplant outcomes. A Subphenotype analysis could refine frailty measurement. In a 3-center pilot cohort study, we measured frailty by the Short Physical Performance Battery, body composition, and serum biomarkers reflecting causes of frailty. We applied latent class modeling for these baseline data. Next, we tested class construct validity with disability, waitlist delisting/death, and early postoperative complications. Among 422 lung transplant candidates, 2 class model fit the best (P = .01). Compared with Subphenotype 1 (n = 333), Subphenotype 2 (n = 89) was characterized by systemic and innate inflammation (higher IL-6, CRP, PTX3, TNF-R1, and IL-1RA); mitochondrial stress (higher GDF-15 and FGF-21); sarcopenia; malnutrition; and lower hemoglobin and walk distance. Subphenotype 2 had a worse disability and higher risk of waitlist delisting or death (hazards ratio: 4.0; 95% confidence interval: 1.8-9.1). Of the total cohort, 257 underwent transplant (Subphenotype 1: 196; Subphenotype 2: 61). Subphenotype 2 had a higher need for take back to the operating room (48% vs 28%; P = .005) and longer posttransplant hospital length of stay (21 days [interquartile range: 14-33] vs 18 days [14-28]; P = .04). Subphenotype 2 trended toward fewer ventilator-free days, needing more postoperative extracorporeal membrane oxygenation and dialysis, and higher need for discharge to rehabilitation facilities (P ≤ .20). In this early phase study, we identified biological frailty Subphenotypes in lung transplant candidates. A hyperinflammatory, sarcopenic Subphenotype seems to be associated with worse clinical outcomes.

Common Noninfectious Complications Following Lung Transplantation.

According to the Scientific Registry of Transplant Recipients, both transplant volume and survival among lung transplant recipients are improving over time. However, the outcomes of lung transplantation remain challenged by multiple thoracic and extrathoracic complications. With improving lung transplant survival, patients experience prolonged exposure to chronic immunosuppressive agents that can lead to multiple infectious and noninfectious complications. This article focuses on most common noninfectious complications with significant clinical impact.

BK DNAemia and native kidney polyomavirus nephropathy following lung transplantation.

BK virus DNAemia (BKPyV) and nephropathy are common after kidney transplant; however, there are limited data on BK infections in nonrenal solid organ transplant recipients. We examined the frequency, clinical and pathologic features, and kidney and lung outcomes of BKPyV and BK virus native kidney nephropathy (BKVN) in lung transplant recipients at our center. Among 878 recipients transplanted from 2003 to 2019, 56 (6%) developed BKPyV at a median of 30.1 months after transplant (range, 0.6-213) and 11 (1.3%) developed BKVN at a median of 46 months after transplant (range, 9-213). The incidence of end-stage kidney disease was significantly higher in patients with peak viral load ≥10 000 copies/mL (39% vs 8%, P < .001). All cases of BKVN were in patients with peak viral load of ≥10 000 copies/mL, and 55% of these patients developed end-stage kidney disease. Despite the reduction of immunosuppression to treat BKVN, only 1 patient developed acute rejection, and lung function was stable >1 year. BKPyV and nephropathy are more common after lung transplantation than previously reported. Routine screening for BKPyV should be considered in all lung transplant recipients.

Lung transplant waitlist outcomes among ABO blood groups vary based on disease severity.

BACKGROUND: Blood group O candidates have lower lung transplantation rates despite having the most common blood group. We postulated that waitlist outcomes among these candidates and those with other blood types vary with disease severity and lung allocation score (LAS). METHODS: We performed a retrospective cohort study of 32,772 waitlist candidates using the United Network of Organ Sharing registry from May 2005 to 2020. After identifying an interaction between blood group and LAS, we evaluated the association between blood group and waitlist outcomes within LAS quartiles using unadjusted and adjusted competing risk models. RESULTS: In the lowest LAS quartile, blood group O had a 20% reduced transplantation rate (SHR: 0.80, 95%CI: 0.75-0.85) and higher waitlist death/removal (1.33, 95%CI: 1.15-1.55) compared with group A. Blood group AB had a 52% higher transplantation rate (SHR: 1.52, 95%CI: 1.34-1.73) in the lowest LAS quartile compared with group A. In the highest LAS quartile, there was no difference in transplantation rates between groups O and A. In contrast, group B had a 19% reduced transplantation rate (SHR, 0.81 95%CI: 0.73-0.89) and AB had a 28% reduced transplantation rate (SHR: 0.72, 95%CI: 0.61-0.86) in the highest LAS quartile. Additionally, groups B and AB had increased risk of waitlist death/removal in the highest LAS quartile compared with A (SHR: 1.27, 95%CI: 1.08-1.48; SHR: 1.31, 95%CI: 1.00-1.72). CONCLUSIONS: Waitlist outcomes among ABO blood groups vary depending on illness severity, which is represented by LAS. Blood group O has lower transplantation rates at low LAS while groups B and AB have lower transplantation rates at high LAS.

Quality of Life Outcomes and Associated Symptoms Reported by Lung Transplant Recipients Amidst COVID-19 Pandemic: Applying a Novel Assessment Tool.

BACKGROUND: There are 2 main aims of lung transplantation for people with end-stage lung disease: (1) to extend life and (2) to improve its quality. Much consideration is given to how to support the longevity and functioning of the allograft, though less robust studies have been done on the quality of the recipients' lives. With an interest in providing compassionate and holistic patient-centered care, it is vital that the treatment providers accurately understand their patients' lived experience. This study aimed to describe the health-related quality of life experiences of lung transplant recipients. An interest was held for where patients may struggle, thus informing where support might be needed to achieve the best possible outcomes. METHODS: This single-center study used a validated Lung Transplant Quality of Life questionnaire, which was sent in autumn of 2020 to all of the lung transplant recipients (n = 581) under the care of Columbia University Irving Medical Center (New York, NY). RESULTS: "Anxiety/Depression" had the highest concentration of struggle responses, followed closely by "Pulmonary Symptoms" and "Neuromuscular Symptoms." "Neuromuscular Problems" and "Sexual Problems" had the highest percentage of struggle responses. As the struggles increased, the overall quality of life rating dropped proportionately. There was no correlation between the overall quality of life and graft dysfunction, age, or time out from transplant date. All of the domains held an average rating of "Satisfactory," except "Treatment Burden," which was rated as "Favorable." Those ratings dropped for the cohort of patients who died during the study period. CONCLUSIONS: With the goal of providing comprehensive care at the forefront of transplant priorities, we found the newly developed questionnaire invaluable in targeting areas for quality improvements, mostly notably respecting recipient mental health.

Nonallograft Complications of Lung Transplantation.

Long-term exposure to immunosuppressive therapy may exacerbate pre-existing medical comorbidities or result in the development of new chronic medical conditions after lung transplantation. This article focuses on common nonallograft complications with the highest impact on short- and long-term outcomes after transplantation. These include diabetes mellitus, hypertension, dyslipidemia, kidney disease (acute and chronic), and malignancy. We discuss evidence-based strategies for the prevention, diagnosis, and management of these nonallograft complications in this article.

One Year Into the Pandemic: Evolving COVID-19 Outcomes in Lung Transplant Recipients, a Single-center Experience.

In the early months of the coronavirus disease 2019 (COVID-19) pandemic, our center reported a mortality rate of 34% in a cohort of 32 lung transplant recipients with COVID-19 between March and May 2020. Since then, there has been evolving knowledge in prevention and treatments of COVID-19. To evaluate the impact of these changes, we describe the clinical presentation, management, and outcomes of a more recent cohort of lung transplant recipients during the second surge and provide a comparison with our first cohort. Methods: We conducted a retrospective cohort study that included all consecutive lung transplant recipients who tested positive for severe acute respiratory syndrome coronavirus 2 between November 2020 and February 28, 2021. We compared baseline demographics and major outcomes between the first- and second-surge cohorts. Results: We identified 47 lung transplant recipients (median age, 60; 51% female) who tested positive for severe acute respiratory syndrome coronavirus 2 between November 2020 and February 28, 2021. The current cohort had a higher proportion of patients with mild disease (34% versus 16%) and fewer patients with a history of obesity (4% versus 25%). Sixty-six percent (n = 31) required hospitalization and were treated with remdesivir (90%) and dexamethasone (84%). Among those hospitalized, 77% (n = 24) required supplemental oxygen, and 22% (n = 7) required invasive mechanical ventilation. The overall 90-d mortality decreased from 34% to 17% from the first cohort to the second (adjusted odds ratio, 0.26; 95% confidence interval, 0.08-0.85; P = 0.026). Conclusions: Although COVID-19-associated mortality rate in lung transplant recipients at our center has decreased over time, COVID-19 continues to be associated with significant morbidity and mortality.

Lung Transplantation for Pulmonary Fibrosis Associated With Hermansky-Pudlak Syndrome. A Single-center Experience.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet storage defect with resultant bleeding diathesis, and pulmonary fibrosis. The bleeding diathesis associated with HPS had long been considered a contraindication to lung transplantation; consequently, few reports of successful lung transplantation for HPS exist. Methods: In the largest case series on lung transplant for HPS, we describe the characteristics of 11 lung transplant candidates with HPS-related pulmonary fibrosis, and the management and outcomes of 7 patients who underwent lung transplantation. Results: Of the 7 patients transplanted, 30-d survival was 85.7% (6/7). Six patients had at least 2 y of follow-up available with a 1-y survival of 83.3% and a 2-y survival of 83.3% (5/6). The median age at referral was 48 y (range 29-62 y). Eight patients (72.7%) were of Puerto Rican ancestry with confirmed type 1 HPS mutation. Six out of 7 patients received prophylaxis for bleeding diathesis, with a majority receiving desmopressin; 1 patient was administered aminocaproic acid infusion, and another received 2 units of platelets before surgery. Estimated blood loss and the amount of intraoperative blood product administered was highly variable with or without prophylaxis. Median blood loss was 400 mL (range 125-750) and estimated blood products administered was 700 mL (range 490-4043). Conclusions: HPS should not be considered a contraindication for lung transplantation. Although patients with HPS seem to have an increased risk of massive hemorrhage, the risk is unpredictable. Transplant teams should prepare a preoperative plan in consultation with hematology and consider the use of prophylactic platelet transfusion and desmopressin.

Malakoplakia Presenting as a Lung Mass in a Lung Transplant Recipient: Case Report.

Lung nodules or masses due to a variety of malignant or benign conditions such as opportunistic infections are observed after lung transplant. Malakoplakia is a rare complication in immunocompromised patients. Here we describe the clinical course and management of a lung transplant recipient with pulmonary malakoplakia and provide a review of the literature. To our knowledge, this is the first report of a case of pulmonary malakoplakia due to Escherichia coli infection in a lung allograft.

Bronchoscopic Lobar Lavage in the Treatment of a Single Lung Transplant Recipient With Pulmonary Alveolar Proteinosis: A Case Report.

Pulmonary alveolar proteinosis is a rare disorder that results from impaired clearance of surfactant. There are few case reports in lung transplant recipients. We report the case of a 57-year-old man with chronic hypersensitivity pneumonitis who underwent left single lung transplantation. Approximately 1 year after transplant, he was diagnosed as having pulmonary alveolar proteinosis by surgical lung biopsy. He was successfully treated with bronchoscopic lobar lavage of his allograft but later was diagnosed as having peritoneal mesothelioma. We highlight the challenges in the diagnosis, discuss potential etiologies, and describe a unique therapy of this rare disorder in lung transplant recipients.

Risk Factors and Outcomes for Gastroparesis After Lung Transplantation.

BACKGROUND: Gastroparesis is common after lung transplantation and is associated with worse transplant outcomes, including the development of chronic lung allograft dysfunction (CLAD). This study sought to identify the prevalence, risk factors, and outcomes associated with a new diagnosis of gastroparesis after lung transplantation. METHODS: This was a single-center retrospective study of patients who underwent lung transplantation in 2008-2018. The primary outcome was a new diagnosis of gastroparesis within 3 years of transplant. Secondary outcomes included a new diagnosis of gastroesophageal reflux and the association between gastroparesis and both post-transplant survival and CLAD-free survival. Multivariable logistic regression was used to compare diagnosis of gastroparesis and gastroesophageal reflux, while multivariable Cox proportional hazards models were used to analyze gastroparesis and post-transplant outcomes. RESULTS: Of 616 patients with no prior history of gastroparesis, 107 (17.4%) were diagnosed with delayed gastric emptying within 3 years of transplant. On multivariable logistic regression, black race (OR 2.16, 95% CI 1.18-3.98, p = 0.013) was significantly associated with a new diagnosis of gastroparesis. Age, sex, history of diabetes, connective tissue disease, type of transplant, diagnosis group, renal function, and body mass index were not predictive of gastroparesis post-transplant. Gastroparesis was significantly associated with CLAD (HR 1.76, 95% CI 1.20-2.59, p = 0.004), but not with overall mortality (HR 1.16, p = 0.43). CONCLUSION: While gastroparesis is common after lung transplantation, it remains difficult to predict which patients will develop these complications post-transplant. Black patients were more likely to be diagnosed with gastroparesis after adjusting for relevant confounders. Gastroparesis is associated with increased risk of CLAD, and further studies are needed to assess whether early detection and treatment can reduce the incidence of CLAD.

Early Mobilization during Extracorporeal Membrane Oxygenation for Cardiopulmonary Failure in Adults: Factors Associated with Intensity of Treatment.

Rationale: Early mobilization of extracorporeal membrane oxygenation (ECMO)-supported patients is increasingly common, but it remains unknown whether there are factors predictive of achieving higher intensity mobilization among those able to participate in physical therapy. Additionally, data regarding the safety and feasibility of early mobilization with femoral cannulation, particularly ambulation, are sparse. Objectives: To determine whether there are factors associated with achieving out-of-bed versus in-bed physical therapy in ECMO-supported patients participating in physical therapy, and whether mobilization with femoral cannulation is safe and feasible. Methods: This large, single-center, retrospective study evaluated adult patients who performed active physical therapy while receiving ECMO. Mixed effects modeling was used to identify predictors of out-of-bed versus in-bed activity. Rates of mobilization with femoral cannulation and adverse events were also reported. Results: Between April 2009 and January 2020, 511 patients were supported with ECMO in a single medical intensive care unit, of whom 177 (35%) underwent active physical therapy and were included in the analysis, including 124 of 141 (88%) bridge to lung transplantation and 53 of 370 (14%) bridge to recovery. These 177 patients accounted for 2,706 active physical therapy sessions, with 138 patients (78%) achieving out-of-bed activity. In total, 108 (61%) patients ambulated (1,284 sessions), 34 of whom had femoral cannulae (250 sessions). Bridge-to-transplant (odds ratio [OR], 17.2; 95% confidence interval [CI], 4.12-72.1), venovenous ECMO (OR, 2.83; 95% CI, 1.29-6.22), later cannulation year (OR, 1.65; 95% CI, 1.37-1.98) and higher Charlson comorbidity index (OR, 1.53; 95% CI, 1.07-2.19) were associated with increased odds of achieving out-of-bed versus in-bed physical therapy, whereas invasive mechanical ventilation (OR, 0.11; 95% CI, 0.05-0.25) and femoral cannulation (OR, 0.19; 95% CI, 0.04-0.92) were associated with decreased odds of performing out-of-bed activities. Adverse events occurred in 2% of sessions. Conclusions: Several patient- and ECMO-related factors were associated with achieving higher intensity of early mobilization in patients participating in rehabilitation. Physical therapy with femoral cannulation was safe and feasible, and complications related to mobilization were uncommon.

Identification of Lung Transplant Recipients With a Survival Benefit After Fundoplication.

BACKGROUND: Gastroesophageal reflux disease (GERD) and aspiration of enteric contents are associated with worse outcomes after lung transplantation. The purpose of this study was to elucidate populations of patients who benefit the most from fundoplication after lung transplantation. METHODS: Lung transplantations from 2001 to 2019 (n = 971) were retrospectively reviewed and stratified by fundoplication before (n = 128) or after (n = 24) chronic lung allograft dysfunction (CLAD) development vs patients who did not undergo fundoplication. Patients with a fundoplication before CLAD were propensity matched to patients without a fundoplication. The primary outcome of interest was posttransplant survival. Time-to-event rates were calculated using a multivariable Cox proportional hazards model and Kaplan-Meier functions. RESULTS: Fundoplication before CLAD improved posttransplant survival before and after propensity matching, and it remained a significant predictor after adjusting for baseline characteristics (hazard ratio [HR],0.57; 95 % confidence interval [CI], 0.4 to 0.8; P = .001). Transplant recipients with a restrictive disorder (HR, 0.46; 95 % CI, 0.3 to 0.73; P = .001), age younger than 65 years (HR, 0.48; 95 % CI, 0.32 to 0.71; P < ;0.001), and with both single (HR, 0.47; 95 % CI, 0.28 to 0.79; P = .005) and double (HR, 0.55; 95 % CI, 0.32 to 0.93; P = .027) lung transplants had a significant decrease in mortality after fundoplication. The effect was present after excluding early deaths and CLAD diagnoses. Gastroesophageal reflux disease diagnosed by pH, impedance, or esophagogastroduodenoscopy was not associated with worse outcomes. Among patients with CLAD, a fundoplication was an independent predictor of post-CLAD survival (HR, 0.27; 95 % CI; 0.12 to 0.61; P = .002). CONCLUSIONS: Fundoplication before or after CLAD development is an independent predictor of survival. Younger patients with restrictive disease, independent of the type of transplant, have a survival benefit. Gastroesophageal reflux disease diagnosed by conventional methods was not associated with worse survival.

Geographic disparities in lung transplantation in the United States before and after the November 2017 allocation change.

BACKGROUND: The primary lung allocation unit was expanded from the donation service area to a 250-mile radius in 2017. Prior to the change, geographic disparities in donor lung availability impacted waitlist outcomes. We sought to determine if the new allocation system improved these disparities. METHODS: We conducted a retrospective cohort study comparing the 2-year period before and after the change. Donor lung availability was defined as the ratio of donor lungs to waitlist candidates in the primary allocation unit. Transplant centers were divided into quartiles by donor lung availability. Multivariable competing risk models were used to determine the association between lung availability and waitlist outcomes. Multivariable Cox proportional hazards models compared post-transplant survival. RESULTS: Prior to the allocation change, the unadjusted transplant rate at centers in the lowest and highest quartiles was 132 and 607 transplants per 100 waitlist years. Candidates in the lowest quartile of donor lung availability had a 61% adjusted lower transplantation rate compared to candidates in highest quartile (sub-hazard ratio [sHR]: 0.39, 95% confidence interval [CI]: 0.34-0.44). After the allocation change, the disparity decreased resulting in an unadjusted transplant rate of 141 and 309 among centers in the lowest and highest quartiles. Candidates in the lowest quartile had a 38% adjusted lower transplantation rate compared to those in the highest (sHR: 0.62, 95% CI: 0.57-0.68). There was no significant difference in 1-year post-transplant survival. CONCLUSIONS: Although the expansion of the primary allocation unit improved disparities in waitlist outcomes without any change in post-transplant survival, there still remain significant differences due to geography.

Lung transplantation disparities based on diagnosis for patients bridging to transplant on extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized as a bridge to lung transplantation, but ECMO status is not explicitly accounted for in the Lung Allocation Score (LAS). We hypothesized that among waitlist patients on ECMO, patients with pulmonary arterial hypertension (PAH) would have lower transplantation rates. METHODS: Using United Network for Organ Sharing data, we conducted a retrospective cohort study of patients who were ≥12 years old, active on the lung transplant waitlist, and required ECMO support from June 1, 2015 through June 12, 2020. Multivariable competing risk analysis was used to examine waitlist outcomes. RESULTS: 1064 waitlist subjects required ECMO support; 40 (3.8%) had obstructive lung disease (OLD), 97 (9.1%) had PAH,138 (13.0%) had cystic fibrosis (CF), and 789 (74.1%) had interstitial lung disease (ILD). Ultimately, 671 (63.1%) underwent transplant, while 334 (31.4%) died or were delisted. The transplant rate per person-years on the waitlist on ECMO was 15.41 for OLD, 6.05 for PAH, 15.66 for CF, and 15.62 for ILD. Compared to PAH patients, OLD, CF, and ILD patients were 78%, 69%, and 62% more likely to undergo transplant throughout the study period, respectively (adjusted SHRs 1.78 p = 0.007, 1.69 p = 0.002, and 1.62 p = 0.001). The median LAS at waitlist removal for transplantation, death, or delisting were 75.1 for OLD, 79.6 for PAH, 91.0 for CF, and 88.3 for ILD (p < 0.001). CONCLUSIONS: Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD.

Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation.

Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation.