Survival Tree Provides Individualized Estimates of Survival After Lung Transplant.

INTRODUCTION: Identifying contributors to lung transplant survival is vital in mitigating mortality. To enhance individualized mortality estimation and determine variable interaction, we employed a survival tree algorithm utilizing recipient and donor data. METHODS: United Network Organ Sharing data (2000-2021) were queried for single and double lung transplants in adult patients. Graft survival time <7 d was excluded. Sixty preoperative and immediate postoperative factors were evaluated with stepwise logistic regression on mortality; final model variables were included in survival tree modeling. Data were split into training and testing sets and additionally validated with 10-fold cross validation. Survival tree pruning and model selection was based on Akaike information criteria and log-likelihood values. Estimated survival probabilities and log-rank pairwise comparisons between subgroups were calculated. RESULTS: A total of 27,296 lung transplant patients (8175 single; 19,121 double lung) were included. Stepwise logistic regression yielded 47 significant variables associated with mortality. Survival tree modeling returned six significant factors: recipient age, length of stay from transplant to discharge, recipient ventilator duration post-transplant, double lung transplant, recipient reintubation post-transplant, and donor cytomegalovirus status. Eight subgroups consisting of combinations of these factors were identified with distinct Kaplan-Meier survival curves. CONCLUSIONS: Survival trees provide the ability to understand the effects and interactions of covariates on survival after lung transplantation. Individualized survival probability with this technique found that preoperative and postoperative factors influence survival after lung transplantation. Thus, preoperative patient counseling should acknowledge a degree of uncertainty given the influence of postoperative factors.

Early Extubation: Who Qualifies Postoperatively in Lung Transplantation?

INTRODUCTION: Early extubation has been adopted in many settings within cardiothoracic surgery, with several advantages for patients. We sought to determine the association of timing of extubation in lung transplant recipients' short- and long-term outcomes. METHODS: Adult, primary lung transplants were identified from the United Network for Organ Sharing database. Recipients were stratified based on the duration of postoperative ventilation: 1) None (NV); 2) <5 Days (<5D); and 3) 5+ Days (5+D). Comparative statistics were performed, and both unadjusted and adjusted survival were analyzed with Kaplan-Meier Methods and a Cox proportional hazard model. A multivariable model including recipient, donor, and transplant characteristics was created to examine factors associated with NV. RESULTS: 28,575 recipients were identified (NV = 960, <5D = 21,959, 5+D = 5656). The NV group had shorter median length of stay (P < 0.01) and lower incidence of postoperative dialysis (P < 0.01). The NV and <5D groups had similar survival, while 5+D recipients had decreased survival (P < 0.01). The multivariable model demonstrated increased donor BMI, center volume, ischemic time, single lung transplant, and transplantation between 2011 and 2015 were associated with NV (P < 0.01 for all). Use of donation after cardiac death donors and transplantation between 2016 and 2021 was associated with postoperative ventilator use. CONCLUSIONS: Patients extubated early after lung transplantation have a shorter median length of stay without an associated increase in mortality. While not all patients are appropriate for earlier extubation, it is possible to extubate patients early following lung transplant. Further efforts are necessary to help expand this practice and ensure its' success for recipients.

Management of immunosuppression in lung transplant recipients and COVID-19 outcomes: an observational retrospective cohort-study.

BACKGROUND: The aim of this study was to assess the impact of immunosuppression management on coronavirus disease 2019 (COVID-19) outcomes. METHODS: We performed a single-center retrospective study in a cohort of 358 lung transplant recipients (LTx) over the period from March 2020 to April 2022. All included symptomatic patients had at least one positive SARS-CoV-2 rt-PCR. We used a composite primary outcome for COVID-19 including increased need for oxygen since the hospital admission, ICU transfer, and in-hospital mortality. We assessed by univariate and multivariate analyses the risk factors for poor outcomes. RESULTS: Overall, we included 91 LTx who contracted COVID-19. The COVID-19 in-hospital mortality rate reached 4.4%. By hierarchical clustering, we found a strong and independent association between the composite poor outcome and the discontinuation of at least one immunosuppressive molecule among tacrolimus, cyclosporine, mycophenolate mofetil, and everolimus. Obesity (OR = 16, 95%CI (1.96; 167), p = 0.01) and chronic renal failure (OR = 4.6, 95%CI (1.4; 18), p = 0.01) were also independently associated with the composite poor outcome. Conversely, full vaccination was protective (OR = 0.23, 95%CI (0.046; 0.89), p = 0.047). CONCLUSION: The administration of immunosuppressive drugs such as tacrolimus, cyclocporine or everolimus can have a protective effect in LTx with COVID-19, probably related to their intrinsic antiviral capacity.

A Framework for Using Real-World Data and Health Outcomes Modeling to Evaluate Machine Learning-Based Risk Prediction Models.

OBJECTIVES: We propose a framework of health outcomes modeling with dynamic decision making and real-world data (RWD) to evaluate the potential utility of novel risk prediction models in clinical practice. Lung transplant (LTx) referral decisions in cystic fibrosis offer a complex case study. METHODS: We used longitudinal RWD for a cohort of adults (n = 4247) from the Cystic Fibrosis Foundation Patient Registry to compare outcomes of an LTx referral policy based on machine learning (ML) mortality risk predictions to referral based on (1) forced expiratory volume in 1 second (FEV1) alone and (2) heterogenous usual care (UC). We then developed a patient-level simulation model to project number of patients referred for LTx and 5-year survival, accounting for transplant availability, organ allocation policy, and heterogenous treatment effects. RESULTS: Only 12% of patients (95% confidence interval 11%-13%) were referred for LTx over 5 years under UC, compared with 19% (18%-20%) under FEV1 and 20% (19%-22%) under ML. Of 309 patients who died before LTx referral under UC, 31% (27%-36%) would have been referred under FEV1 and 40% (35%-45%) would have been referred under ML. Given a fixed supply of organs, differences in referral time did not lead to significant differences in transplants, pretransplant or post-transplant deaths, or overall survival in 5 years. CONCLUSIONS: Health outcomes modeling with RWD may help to identify novel ML risk prediction models with high potential real-world clinical utility and rule out further investment in models that are unlikely to offer meaningful real-world benefits.

Clinical Characteristics and Outcomes of Patients With COVID-19-Associated Acute Respiratory Distress Syndrome Who Underwent Lung Transplant.

Importance: Lung transplantation is a potentially lifesaving treatment for patients who are critically ill due to COVID-19-associated acute respiratory distress syndrome (ARDS), but there is limited information about the long-term outcome. Objective: To report the clinical characteristics and outcomes of patients who had COVID-19-associated ARDS and underwent a lung transplant at a single US hospital. Design, Setting, and Participants: Retrospective case series of 102 consecutive patients who underwent a lung transplant at Northwestern University Medical Center in Chicago, Illinois, between January 21, 2020, and September 30, 2021, including 30 patients who had COVID-19-associated ARDS. The date of final follow-up was November 15, 2021. Exposures: Lung transplant. Main Outcomes and Measures: Demographic, clinical, laboratory, and treatment data were collected and analyzed. Outcomes of lung transplant, including postoperative complications, intensive care unit and hospital length of stay, and survival, were recorded. Results: Among the 102 lung transplant recipients, 30 patients (median age, 53 years [range, 27 to 62]; 13 women [43%]) had COVID-19-associated ARDS and 72 patients (median age, 62 years [range, 22 to 74]; 32 women [44%]) had chronic end-stage lung disease without COVID-19. For lung transplant recipients with COVID-19 compared with those without COVID-19, the median lung allocation scores were 85.8 vs 46.7, the median time on the lung transplant waitlist was 11.5 vs 15 days, and preoperative venovenous extracorporeal membrane oxygenation (ECMO) was used in 56.7% vs 1.4%, respectively. During transplant, patients who had COVID-19-associated ARDS received transfusion of a median of 6.5 units of packed red blood cells vs 0 in those without COVID-19, 96.7% vs 62.5% underwent intraoperative venoarterial ECMO, and the median operative time was 8.5 vs 7.4 hours, respectively. Postoperatively, the rates of primary graft dysfunction (grades 1 to 3) within 72 hours were 70% in the COVID-19 cohort vs 20.8% in those without COVID-19, the median time receiving invasive mechanical ventilation was 6.5 vs 2.0 days, the median duration of intensive care unit stay was 18 vs 9 days, the median post-lung transplant hospitalization duration was 28.5 vs 16 days, and 13.3% vs 5.5% required permanent hemodialysis, respectively. None of the lung transplant recipients who had COVID-19-associated ARDS demonstrated antibody-mediated rejection compared with 12.5% in those without COVID-19. At follow-up, all 30 lung transplant recipients who had COVID-19-associated ARDS were alive (median follow-up, 351 days [IQR, 176-555] after transplant) vs 60 patients (83%) who were alive in the non-COVID-19 cohort (median follow-up, 488 days [IQR, 368-570] after lung transplant). Conclusions and Relevance: In this single-center case series of 102 consecutive patients who underwent a lung transplant between January 21, 2020, and September 30, 2021, survival was 100% in the 30 patients who had COVID-19-associated ARDS as of November 15, 2021.

A shifting landscape: Practice patterns and outcomes of cystic fibrosis and non-cystic fibrosis pediatric lung transplantation.

BACKGROUND: New drugs may further decrease the need for lung transplant (LTx) in pediatric patients with cystic fibrosis (CF), but few studies highlight pediatric non-CF LTx characteristics and outcomes. METHODS: The ISHLT registry was used to report morbidity, graft failure, and survival for primary pediatric (<18 years) LTx performed 1990-2017. Recipient/donor characteristics and long-term outcomes were analyzed for CF and non-CF recipients. Survival was assessed using Kaplan-Meier curves. RESULTS: Of 2232 primary LTx, (43% in males), 918 (41%) were performed for non-CF indications; most commonly pulmonary hypertension (43%). Non-CF patients were younger (median age 11 vs. 15, p < .001), and more frequently on inotropes and/or extracorporeal membrane oxygenation (15% vs. 2.4%, p < .001) at transplant, compared to CF recipients. In-hospital major complications more commonly affected CF LTx recipients (57% vs. 48%, p = .003), but 30-day mortality was higher in the non-CF group (9% non-CF vs. 5% CF, p < .001). One-, five-, and ten-year mortality was 18%, 50%, and 65% for CF recipients, respectively, and 21%, 45%, and 58% for non-CF recipients (p = .01 at 10 years). Five-year survival was significantly better for non-CF females versus CF females (56% vs. 48%, p = .013), but was similar between groups for males (55% vs. 54%, p = .305). While age was a late outcomes risk factor, pulmonary hypertension and later transplants eras were protective. CONCLUSIONS: Early mortality is higher and late mortality is lower in non-CF LTx. Current non-CF LTx outcomes leave room for improvement. Further study is needed to evaluate the effects of center volume and pediatric-specific experience on outcomes.

Pediatric lung transplant: Correlation of pretransplant condition with post-transplant outcomes.

BACKGROUND: It is generally accepted that patients who have greater functional capacity are better candidates for lung transplantation. Accurate assessment of physical condition is important in identifying appropriate candidates for transplant. The focus of this study was to determine which measures of pretransplant physical condition correlate with positive post-transplant outcomes in children undergoing lung transplant. METHODS: A retrospective chart review was done on 44 patients, ages 5 to 21 years. The pretransplant data collected included functional status, 6MWT, ambulatory status, and mechanical support. Post-transplant outcome data included time on the ventilator, days in the ICU, length of hospitalization, and 12-month survival. RESULTS: Results were analyzed using Fisher exact and Kruskal-Wallis tests. Patients with limited ambulation had more days in the ICU compared to the most ambulatory group (P = .043). Patients independent or needing some help with ADL had less time on the ventilator compared to patients needing total help. (P = .014). Patients with 6MWT result greater than 500' had fewer ICU days (P = .044) and marginally better 12-month survival (P = .057). The 12-month survival of children needing invasive ventilatory support pretransplant was not significantly worse than those who did not; however, they required significantly more time on the ventilator (P = .004), days in ICU (P = .013), and longer hospitalization. DISCUSSION: This study demonstrated that pretransplant physical condition affects post-transplant outcomes in children. Measures associated with positive post-transplant outcomes were identified and could be beneficial in determining which patients are optimal candidates for lung transplant.

Effect of Lung-Protective Ventilation in Organ Donors on Lung Procurement and Recipient Survival.

Rationale: Previous studies have shown that a lung-protective strategy, which aims at minimizing ventilator-induced lung injury (with low Vt/high positive end-expiratory pressure as the main pillars), in selected potential organ donors after brain death increased lung eligibility and procurement.Objectives: This prospective nationwide cohort study aimed to evaluate the impact of lung-protective ventilation (PV) in nonselected donors on lung procurement and recipient survival after lung transplantation.Methods: We included all reported donors aged 18-70 years after brain death without a lung recovery contraindication and with at least one organ recovered between January 2016 and December 2017. PV was defined as Vt ≤8 ml/kg predicted body weight and positive end-expiratory pressure ≥8 cm H2O. The association between PV at the time of lung proposal (T1) and lung procurement was determined by multivariable logistic regression stratified by propensity score quintile to account for PV and non-PV group differences in baseline characteristics. We studied 1-year survival of recipients from donors with or without PV at T1.Measurements and Main Results: Of 1,626 included lung donors, 1,109 (68%) had at least one lung proposed; 678 (61%) of these had at least one lung recovered. At T1, only 25.6% of donors with at least one lung proposed for lung transplantation were ventilated with a protective strategy. For donors with a lung proposal, the probability of lung procurement was increased with PV at T1 (odds ratio, 1.43; 95% confidence interval [CI], 1.03-1.98; P = 0.03). One-year survival did not differ between recipients of lungs from donors with and without PV (82.7%, 95% CI 76.0-87.8% vs. 82.3%, 95% CI 78.5-85.4%; P = 0.94).Conclusions: The use of lung PV in nonselected donors may increase lung procurement. One-year survival did not differ between recipients of lungs from donors with PV or from those without PV.

The prognostic nutritional index is correlated negatively with the lung allocation score and predicts survival after both cadaveric and living-donor lobar lung transplantation.

PURPOSE: The prognostic nutritional index (PNI), calculated based on the serum albumin levels and the total lymphocyte count, has been identified as a predictor of clinical outcomes in various fields of surgery. In this study, we investigated the relationship between the PNI and the lung allocation score (LAS) as well as the impact of the PNI on the outcomes of both cadaveric lung transplantation (CLT) and living-donor lobar lung transplantation (LDLLT). METHODS: We reviewed retrospective data for 127 recipients of lung transplantation (LT), including 71 recipients of CLT and 56 recipients of LDLLT. RESULTS: The PNI was correlated significantly and negatively with the LAS (r = - 0.40, P = 0.0000037). Multivariate analysis revealed that age (P = 0.00093), BMI (P = 0.00087), and PNI (P = 0.0046) were independent prognostic factors of a worse outcome after LT. In a subgroup analysis, survival after both CLT (P = 0.015) and LDLLT (P = 0.041) was significantly worse in the low PNI group than in the high PNI group. CONCLUSION: Preoperative nutritional evaluations using the PNI can assist with the assessment of disease severity in LT recipients and may predict survival after both CLT and LDLLT.

Importance of the preoperative prognostic nutritional index score as a predictor of chronic lung allograft dysfunction after lung transplantation: a Japanese single-institution study.

PURPOSES: Numerous indicators have been discussed as predictive markers for the incidence of chronic allograft dysfunction (CLAD) after lung transplantation (LTX). The aim of this study was to evaluate whether or not the preoperative prognostic nutrition index (PNI) correlated with the development of CLAD. METHOD: This study is a single-center and retrospective cohort study. Forty-six patients underwent cadaveric lung transplantation between 2000 and 2016 at our institution. The primary endpoint of this study was the CLAD-free survival of the patients. RESULT: CLAD was diagnosed in 11 patients (23%) during the follow-up period. Potential risk factors included recipient factors, donor factors, number of HLA mismatches, operation-related factors, and preoperative blood test results, including the preoperative PNI. The patients with a higher PNI showed a longer CLAD-free survival after LTX than those with lower values according to univariate and multivariate analyses (p = 0.01, 0.04, respectively). The 5-year CLAD-free survival rates in the higher-PNI patients and lower-PNI patients were 94% and 62%, respectively. CONCLUSION: We found that a lower preoperative PNI of the recipient was significantly associated with a higher incidence rate of CLAD. The preoperative PNI may, therefore, be useful as a predictor of the development of CLAD.

Combined lung and liver procurement in controlled donation after circulatory death using normothermic abdominal perfusion. Initial experience in two Spanish centers.

Combining simultaneously lung and liver procurement in controlled donation after circulatory death (cDCD) using normothermic abdominal perfusion (NRP) for abdominal grafts and cooling and rapid recovery technique (RR) for the lungs increases the complexity of the procurement procedure and might injure the grafts. A total of 19 cDCDs from two centers using this combined procedure were evaluated, and 16 liver and 21 lung transplantations were performed. As controls, 34 donors after brain death (DBDs) were included (29 liver and 41 lung transplantations were performed). Two cDCD liver recipients developed primary nonfunction (12.5%). No cases of ischemic cholangiopathy were observed among cDCD recipients. The 1-year and 2-year liver recipients survival was 87.5% and 87.5% for the cDCD group, and 96% and 84.5% for the DBD group, respectively (P = .496). The 1-year and 2-year lung recipients survival was 84% and 84% for the cDCD group and 90% and 90% for the DBD group, respectively (P = .577). This is the largest experience ever reported in cDCD with the use of NRP combined with RR of the lungs. This combined method offers an outstanding recovery rate and liver and lung recipients survival comparable with those transplanted with DBDs. Further studies are needed to confirm our findings.

The impact of first untreated subclinical minimal acute rejection on risk for chronic lung allograft dysfunction or death after lung transplantation.

Acute cellular rejection (ACR) is a significant risk factor for chronic lung allograft dysfunction (CLAD). Although clinically manifest and higher grade (≥A2) ACR is generally treated with augmented immunosuppression, management of minimal (grade A1) ACR remains controversial. In our program, patients with subclinical and spirometrically stable A1 rejection (StA1R) are routinely not treated with augmented immunosuppression. We hypothesized that an untreated first StA1R does not increase the risk of CLAD or death compared to episodes of spirometrically stable no ACR (StNAR). The cohort was drawn from all consecutive adult, first, bilateral lung transplantations performed between 1999 and 2017. Biopsies obtained in the first-year posttransplant were paired with (forced expiratory volume in 1 second FEV1 ). The first occurrence of StA1R was compared to a time-matched StNAR. The risk of CLAD or death was assessed using univariable and multivariable Cox proportional hazards models. The analyses demonstrated no significant difference in risk of CLAD or death in patients with a first StA1R compared to StNAR. This largest study to date shows that, in clinically stable patients, an untreated first A1 ACR in the first-year posttransplant is not significantly associated with an increased risk for CLAD or death. Watchful-waiting approach may be an acceptable tactic for stable A1 episodes in lung transplant recipients.

Lung transplant outcomes are influenced by severity of neutropenia and granulocyte colony-stimulating factor treatment.

Although neutropenia is a common complication after lung transplant, its relationship with recipient outcomes remains understudied. We evaluated a retrospective cohort of 228 adult lung transplant recipients between 2008 and 2013 to assess the association of neutropenia and granulocyte colony-stimulating factor (GCSF) treatment with outcomes. Neutropenia was categorized as mild (absolute neutrophil count 1000-1499), moderate (500-999), or severe (<500) and as a time-varying continuous variable. Associations with survival, acute rejection, and chronic lung allograft dysfunction (CLAD) were assessed with the use of Cox proportional hazards regression. GCSF therapy impact on survival, CLAD, and acute rejection development was analyzed by propensity score matching. Of 228 patients, 101 (42.1%) developed neutropenia. Recipients with severe neutropenia had higher mortality rates than those of recipients with no (adjusted hazard ratio [aHR] 2.97, 95% confidence interval [CI] 1.05-8.41, P = .040), mild (aHR 14.508, 95% CI 1.58-13.34, P = .018), or moderate (aHR 3.27, 95% CI 0.89-12.01, P = .074) neutropenia. Surprisingly, GCSF treatment was associated with a higher risk for CLAD in mildly neutropenic patients (aHR 3.49, 95% CI 0.93-13.04, P = .063), although it did decrease death risk in severely neutropenic patients (aHR 0.24, 95% CI 0.07-0.88, P = .031). Taken together, our data point to an important relationship between neutropenia severity and GCSF treatment in lung transplant outcomes.

Acute Kidney Injury in Patients Undergoing Cardiopulmonary Bypass for Lung Transplantation.

BACKGROUND: Cardiopulmonary bypass (CPB) is often used to support patients undergoing lung transplantation who are intolerant of anatomic manipulation or single lung ventilation during the procedure. However, CPB may be associated with adverse outcomes. We evaluated the hypothesis that CPB is associated with increased acute kidney injury (AKI) and postoperative mortality after lung transplantation. MATERIALS AND METHODS: This was a retrospective review of our institutional lung transplant database at the University of Texas Southwestern Medical Center from 2012 to 2018. Patients were grouped based on their need for CPB. The primary outcome was AKI within 48 h of transplantation, which was defined as Kidney Disease Improving Global Outcomes stage 1 or greater. Secondary outcomes included all-cause mortality. RESULTS: A total of 426 patients underwent lung transplantation with 39.0% (n = 166) requiring CPB. There were no differences in demographics and comorbidities, including baseline renal function, between CPB and no CPB. CPB use was higher in recipients with interstitial lung diseases and primary pulmonary hypertension. Median lung allocation score was higher in those needing CPB (47 [interquartile range, 40-59] versus 39 [interquartile range, 35-47]). Patients requiring CPB were significantly more likely to experience AKI (61.44% versus 36.5.3%, P < 0.01) and postoperative hemodialysis (6.6% versus 0.4%, P < 0.01). On multivariable analysis, CPB was significantly associated with postoperative AKI (odds ratio, 1.66; 95% CI, 1.01-2.75; P = 0.04). Thirty-day mortality was higher in patients undergoing CPB (4.2% versus 0.8%, P = 0.03). CONCLUSIONS: CPB for lung transplantation is associated with a higher incidence of AKI, renal failure requiring hemodialysis, and 30-d mortality. CPB should be used selectively for lung transplantation.

Mortality after lung transplantation: a single-centre cohort analysis.

Detailed data on postoperative death in lung transplant (LTx) recipients are lacking. Therefore, we investigated all deaths after LTx in a large, single-centre, 25-year follow-up cohort. Prevalence, time, place and cause of death (COD) were retrospectively analysed for all patients undergoing primary LTx between July 1991 and December 2015 in our centre. Over subsequent years, postoperative survival significantly improved, with proportionally more patients surviving to 1-year post-LTx (P < 0.0001). A total of 347 (38.9%) LTx recipients died, of which 53.6% expired within 3 years post-LTx [median time to death 910 (236-2447) days]. Autopsy was performed in 34.8% of deaths. COD included CLAD in 27.1% (BOS 63.8% vs. RAS 36.2%); infection (26.5%); malignancy (15.6%); postoperative complication (11.2%); cardiovascular disease (4.6%) or other causes (6.9%). In 8.1%, no clear COD could be determined. COD significantly differed between the various LTx indications (P = 0.047). With longer follow-up, infection becomes a less prevalent COD, but CLAD and malignancies a more important COD. The majority of patients died on the intensive care unit (40.6%) or hospital ward (29.1%), but place of death varied depending on the underlying COD. The current study provides insights into the postoperative deaths of LTx recipients.

Pediatric lung transplantation: Results of volume reduction in smaller children.

Pediatric LTX is challenged by the scarcity of suitable donor organs. To alleviate the problem of size matching, volume reduction of the donor is a possible option. Previous reports address mostly older teenagers, and data about younger patients are lacking. The purpose of this study was to investigate whether trimming had influence on the morbidity and mortality in slightly younger recipients, operated in a single center. Between 2015 and 2018, 20 patients were transplanted at the GOSH London. The mean age was 11.5 (±4.6) years. Nine patients underwent volume reduction prior to transplantation (T group). The other patients received classical bilateral LTX (NT group). Ischemia times were longer in the T group, but this difference was not statistically significant. We observed no 30-day mortality. Hospital survival in the T group was 78% vs 90% in the NT group. After almost 3 years, mortality in the T group was 22% vs 28% in the NT group. None of these differences was statistically significant. The mean duration of MV, intensive care stay, and hospital stay were 11.5, 19.9, and 44.8 days, respectively. Results were equal in terms of morbidity, defined as respiratory and neurological complications or the need for ECMO. Results show that volume reduction prior to LTX is a feasible option, even in smaller children. While awaiting long-term results, accepting larger donor organs could be a strategy to further reduce waiting list time and subsequently lower the mortality on the waiting list.

Chronic Obstructive Pulmonary Disease and Lung Transplantation.

Lung transplantation (LTx) has been a viable option for patients with end-stage chronic obstructive pulmonary disease (COPD), with more than 20,000 procedures performed worldwide. Survival after LTx lags behind most other forms of solid-organ transplantation, with median survival for COPD recipients being a sobering 6.0 years. Given the limited supply of suitable donor organs, not all patients with end-stage COPD are candidates for LTx. We discuss appropriate criteria for accepting patients for LTx, as well as contraindications and exclusionary criteria. In the first year post-LTx, infection and graft failure are the leading causes of death. Beyond this chronic graft rejection-currently referred to as chronic lung allograft dysfunction-represents the leading cause of death at all time points, with infection and over time malignancy also limiting survival. Referral of COPD patients to a lung transplant center should be considered in the presence of progressing disease despite maximal medical therapy. As a rule of thumb, a forced expiratory volume in 1 second < 25% predicted in the absence of exacerbation, hypoxia (PaO2 < 60 mm Hg/8 kPa), and/or hypercapnia (PaCO2 > 50 mm Hg/6.6 kPa) and satisfactory general clinical condition should be considered the basic prerequisites for timely referral. We also discuss salient issues post-LTx and factors that impact posttransplant survival and morbidity such as infections, malignancy, renal insufficiency, and complications associated with long-term immunosuppression.

Clinical outcomes and survival following lung transplantation in patients with pulmonary Langerhans cell histiocytosis.

BACKGROUND AND OBJECTIVE: Disease-specific outcomes following lung transplantation (LT) in patients with pulmonary Langerhans cell histiocytosis (PLCH) are not well established. We queried the Organ Procurement and Transplantation Network database to identify adult PLCH patients who had undergone LT in the United States. METHODS: Overall survival data were analysed with Kaplan-Meier curves. Cox proportional hazard model was used to determine the effect of demographic, clinical and physiological variables on post-transplant survival. RESULTS: A total of 87 patients with PLCH underwent LT in the United States between October 1987 and June 2017, accounting for 0.25% of the total LT during this period. The mean age at LT for PLCH patients was 49 years (range: 19-67 years), with a near equal gender distribution. Bilateral sequential LT was performed in 71 patients (82%). Pulmonary hypertension was present in 85% of patients, with a mean pulmonary artery pressure of 38.5 ± 14.1 mm Hg. The mean pre-transplant forced expiratory volume in 1 s (FEV1 ) was 41 ± 21% predicted and the mean 6-min walk distance was 221 ± 111 m. Median post-LT survival for PLCH patients was comparable to patients with other lung diseases (5.1 vs 5.5 years, P = 0.76). The actuarial Kaplan-Meier post-LT survival for PLCH patients was 85%, 65%, 49% and 22% at 1, 3, 5 and 10 years, respectively. Female sex (hazard ratio (HR): 0.40, 95% CI: 0.22-0.72), pre-transplant serum bilirubin (HR: 1.66, 95% CI: 1.23-2.26) and serum creatinine (HR: 4.03, 95% CI: 1.01-14.76) were independently associated with post-LT mortality in our cohort. CONCLUSION: Post-LT survival in patients with PLCH is similar to patients with other lung diseases and is significantly affected by patient gender.

Impact of allograft ischemic time on long-term survival in lung transplantation: a Swedish monocentric study.

Purpose: The influence of allograft ischemic time (IT) on short- and long-term mortality remains under debate in lung transplantation (LTx). Due to a scarcity in donors, better understanding of IT might improve the outcome after LTx. Methods: Between January 1990 and June 2016; 307 patients underwent LTx at Lund university hospital, Sweden. The end-point used was death/Re-LTx assessed by Cox regression and Kaplan-Meier survival. Results: Kaplan-Meier survival for mean IT (min) between subgroups ≤120, 121-240, 241-360 and 361+ showed significant difference for pairwise-comparisons with superior outcome for IT between ≤120 and 240 min. Cox regression analyses for each hour of IT in patients with a limited survival up to 1- and 5-year had a hazard ratio (HR) of 1.119 and 1.063 respectively (p < .05). Conclusions: In LTx, every 2-hour increase of IT is equivalent to an increased mortality of up to 24% within 5 years. LTx with an IT of ≤120 min had a superior survival in both 1- and 5 years in comparison to an IT of up to 360 min. Better application of IT provides a key role in improving LTx outcome.