Post-lung Transplant Survival Research Articles

(631) - Invasive Mechanical Ventilation Status at 72 Hours May be a Pragmatic and Valid Early Outcome Associated with Post-Lung Transplant Survival

(631) - Invasive Mechanical Ventilation Status at 72 Hours May be a Pragmatic and Valid Early Outcome Associated with Post-Lung Transplant Survival

Association of Pulmonary Artery Pressure Change With Post-Lung Transplantation Survival: Retrospective Analysis of China Registry.

Extracorporeal membrane oxygenation (ECMO) has been used as intraoperative hemodynamic support in patients with end-stage lung diseases and pulmonary hypertension undergoing lung transplantation (LT). The aim of this study was to identify the association of pulmonary artery pressure change during ECMO and post-LT survival. The study investigators collected and analyzed the data from Chinese Lung Transplantation Registry. Patients who have severe pulmonary hypertension with intraoperative ECMO support were enrolled. Post-LT mortality and morbidity were further collected and compared. A total of 208 recipients were included in the study, during which 53 deaths occurred post-LT. All the patients had severe pulmonary hypertension and were supported by intraoperative ECMO. Using eXtreme Gradient Boosting, or XGboost, model method, 20 variables were selected and ranked. Changes of mean pulmonary artery pressure at the time of ECMO support and ECMO wean-off (ΔmPAP) were related to post-LT survival, after adjusting for potential confounders (recipient age, New York Heart Association functional class status before LT, body mass index, pre-LT hypertension, pre-LT steroids, and pre-LT ECMO bridging). A nonlinear relationship was detected between ΔmPAP and post-LT survival, which had an inflection point of 35mmHg. Recipients with ΔmPAP ≦35 mmHg had higher mortality rate calculated through the Kaplan-Meier estimator (P = 0.041). Interaction analysis showed that recipients admitted in LT center with high case volume (≥50 cases/year) and ΔmPAP >35mmHg had better long-term survival. The trend was reversed in recipients who were admitted in LT center with low case volume (<50 cases/year). The relationship between ΔmPAP and post-LT survival was nonlinear. Optimal perioperative ECMO management strategy with experienced team is further warranted.

The U-shaped association of post-lung transplant mortality with pretransplant eGFR underscores possible limitations of creatinine-based estimation equations for risk stratification.

Pre-existing chronic kidney disease (CKD) may have an impact on post-lung transplant survival and the development of end stage kidney disease (ESKD). We analyzed the US transplant database from 2006 to 2020. Adult patients who received their first lung transplant and were not on dialysis were included. Multivariable Cox regression was used to assess the effect of pretransplant eGFR on mortality and cumulative incidence competing risk was used to explore the effect on ESKD. The adjusted hazard ratio (aHR) for mortality showed a "U" shaped association with eGFR with a rising mortality at <60 and >100 ml/min/1.73m2. The increase in mortality with higher eGFR was only seen in those <30 year and were primarily in whites with a lower body mass index and in patients with cystic fibrosis (CF). The aHR for ESKD increased below an eGFR of 100 rising to 1.74 at an eGFR of 60. Any decrease in eGFR between listing and transplant >10% was associated with higher risk of ESKD. The U-shaped association of pretransplant eGFR with post-transplant mortality correlated with younger age, lower BMI and a diagnosis of CF. The aHR for ESKD following lung transplantation increased exponentially with worsening eGFR pretransplant.

The lung allocation score and other available models lack predictive accuracy for post-lung transplant survival.

Improved predictive models are needed in lung transplantation in the setting of a proposed allocation system that incorporates longer-term post-transplant survival in the United States. Allocation systems require accurate mortality predictions to justly allocate organs. Utilizing the United Network for Organ Sharing database (2005-2017), we fit models to predict 1-year mortality based on the Lung Allocation Score (LAS), the Chan, etal, 2019 model, a novel "clinician" model (a priori clinician selection of pre-transplant covariates), and two machine learning models (Least Absolute Shrinkage and Selection Operator; LASSO and Random Forests) for predicting 1-year and 3-year post-transplant mortality. We compared predictive accuracy among models. We evaluated the calibration of models by comparing average predicted probability vs observed outcome per decile. We repeated analyses fit for 3-year mortality, disease category, including donor covariates, and LAS era. The area under the cure for all models was low, ranging from 0.55 to 0.62. All exhibited reasonable negative predictive values (0.87-0.90), but the positive predictive value for was poor (all <0.25). Evaluating LAS calibration found 1-year post-transplant estimates consistently overestimated risk of mortality, with greater differences in higher deciles. LASSO, Random Forests, and clinician models showed no improvement when evaluated by disease category or with the addition of donor covariates and performed worse for 3-year outcomes. The LAS overestimated patients' risk of post-transplant death, thus underestimating transplant benefit in the sickest candidates. Novel models based on pre-transplant recipient covariates failed to improve prediction. There should be wariness in post-transplant survival predictions from available models.

Influence of mycophenolate mofetil dosage and plasma levels on the occurrence of chronic lung allograft dysfunction in lung transplants: a retrospective cohort analysis.

Development of chronic lung allograft dysfunction is a limiting factor for post-lung transplant survival. We evaluated whether the dose of the immunosuppressant mycophenolate mofetil or plasma concentrations of the active metabolite mycophenolic acid affect the development of chronic lung allograft dysfunction. In this retrospective cohort study we recruited 71 patients with a lung transplant between 2010 and 2014 which survived the first year after transplantation up to 1 July 2021. An event-time-analytical Cox proportional-hazards regression model with time-varying-covariates (18,431 measurements for MPA, mycophenolate mofetil dosage, lymphocytes) was used to predict chronic lung allograft dysfunction, with adjustment for sociodemographic factors and lung function at baseline. 37 patients did not develop chronic lung allograft dysfunction (age 41.3 ± 15.6 years, baseline FEV1 95.5 ± 19.1% predicted) and 34 patients developed chronic lung allograft dysfunction (age 50.9 ± 13.3 years, baseline FEV1 102.2 ± 25.4% predicted). Mean mycophenolic acid did not differ significantly between the groups (2.8 ± 1.7 and 3.0 ± 2.3 mg/l; p = 0.724). In the first 4 post-transplant years the death rate was 25%. A total of 50% of the patients died by the ninth post-transplant year. There was a dose-effect relationship between mycophenolate mofetil dosage, mycophenolic acid (r2 = 0.02, p <0.001), as well as lymphocyte levels (r2 = -0.007, p <0.001), but only the traditional risk factor age predicted chronic lung allograft dysfunction. Continuously measured mycophenolic acid did not predict chronic lung allograft dysfunction (hazard ratio 0.98, 95% confidence interval 0.90-1.06, p = 0.64 over a period of 382.97 patient-years). Mycophenolate mofetil dosage and mycophenolic acid were not associated with chronic lung allograft dysfunction development. Thus, the mycophenolate mofetil dose or mycophenolic acid plasma concentration are not a primary factor related to organ rejection, but chronic lung allograft dysfunction may be influenced by other components of immunosuppression or other factors.

Survival After Lung Transplantation in Europe - Clad as Major Cause of Death

<h3>Purpose</h3> Lung transplantation (LTX) outcomes are poor in comparison to other solid organ transplantations. Our aim was to review survival, leading chronic complications, and major causes of death in Europe. A particular focus is put on Chronic Lung Allograft Dysfunction (CLAD) and its trends. <h3>Methods</h3> There is no dedicated European registry on lung transplantation, outcomes, and complications. Therefore, accessible data from ISHLT registry with focus on the European continent, European Registries and German Quality report were screened for lung transplantation survival data. Furthermore, a dedicated literature research on chronic complications following LTX and particularly CLAD was performed with focus on Europe. In a further step, clinical trial registries were screened for advanced trials addressing the leading form of CLAD - obstructive phenotype - Bronchiolitis Obliterans Syndrome (CLAD-BOS). <h3>Results</h3> Survival rate for LTX reaches 83.2% and 71% at 1 and 3 years, based on 3502 cases included between 2013 and 2016 in the ISHLT registry - European Continent, under exclusion of retransplant. Eurotransplant data from 2012 to 2016 comprising 3053 LTX from Austria, Belgium, Germany, and the Netherlands state survival rates of 83.5%, 76.8% and 62.5% at year 1, 2 and 5. Yet, pan-European data are lacking. Some large monocentric European studies report CLAD rates ranging from 38% at 3 years to 44% at longer follow-up. These findings are in line with US data. CLAD-BOS represented consistently the most prevalent phenotype, up to 80% of all CLAD cases. Although no dedicated European registry data are available, monocentric studies pinpoint CLAD as the single largest cause of death post-LTX. Within CLAD, BOS phenotype accounts for two-thirds of deaths based on reported autopsy analysis. Currently, two substances targeting CLAD-BOS are in phase 3 clinical investigation in Europe. <h3>Conclusion</h3> In Europe, 3-year post-lung transplantation survival is around 70% and 5-year survival at 63%. CLAD is consistently the most prevalent and fatal complication in lung transplant recipients. CLAD-BOS is the most frequent phenotype. New treatments to address chronic graft failure and primary cause of death in LTX, namely CLAD-BOS, are needed. Currently two therapeutic approaches are under investigation in phase 3 clinical trials aiming at CLAD-BOS in Europe.

Comparison of dynamic updating strategies for clinical prediction models

BackgroundPrediction models inform many medical decisions, but their performance often deteriorates over time. Several discrete-time update strategies have been proposed in the literature, including model recalibration and revision. However, these strategies have not been compared in the dynamic updating setting.MethodsWe used post-lung transplant survival data during 2010-2015 and compared the Brier Score (BS), discrimination, and calibration of the following update strategies: (1) never update, (2) update using the closed testing procedure proposed in the literature, (3) always recalibrate the intercept, (4) always recalibrate the intercept and slope, and (5) always refit/revise the model. In each case, we explored update intervals of every 1, 2, 4, and 8 quarters. We also examined how the performance of the update strategies changed as the amount of old data included in the update (i.e., sliding window length) increased.ResultsAll methods of updating the model led to meaningful improvement in BS relative to never updating. More frequent updating yielded better BS, discrimination, and calibration, regardless of update strategy. Recalibration strategies led to more consistent improvements and less variability over time compared to the other updating strategies. Using longer sliding windows did not substantially impact the recalibration strategies, but did improve the discrimination and calibration of the closed testing procedure and model revision strategies.ConclusionsModel updating leads to improved BS, with more frequent updating performing better than less frequent updating. Model recalibration strategies appeared to be the least sensitive to the update interval and sliding window length.

Outcomes after lung transplantation among Chinese patients with connective tissue disease-associated interstitial lung disease and pulmonary hypertension: a retrospective cohort study.

The present study aimed to compare the post-lung transplant survival and complications of connective tissue disease (CTD)-related interstitial lung disease (ILD) and/or pulmonary arterial hypertension with idiopathic pulmonary fibrosis (IPF). The clinical data of patients with CTD-ILD or IPF who received lung transplantation between 2015 and 2020 were retrospectively reviewed. Cumulative survival rates after transplantation were estimated using the Kaplan-Meier method. The study included 31 patients with confirmed CTD-ILD and 98 with IPF. Patients with CTD-ILD were significantly younger (53.2 ± 13.7 vs. 62.3 ± 7.2 years, p=0.001) and more likely female (61.3% vs. 7.1%, p<0.001) than patients with IPF. No significant difference was noticed in the 1-year and 5-year survival rates between CTD-ILD and IPF patients (1-year, 73.2% vs 71.4%, p=0.76; 5-year, 69.1% vs. 39.5%, p=0.21). The incidence of primary graft dysfunction was significantly higher in CTD-ILD patients (90.3% vs. 70.4%, p=0.03), while there was no significant difference in primary graft dysfunction-related mortality (6.5% vs. 6.1%, p=0.95) between the two groups. There was no significant difference in post-lung transplant survival and complications between CTD-ILD and IPF.

Induction of Epithelial-Mesenchymal Transition (EMT) by Neutrophil Extracellular Traps (NETs) as Possible Molecular Mechanism in CLAD

Purpose Chronic Lung Allograft Dysfunction (CLAD) is the main limitation to long term post lung transplant survival and is characterized by interstitial or airway fibrosis. Recruitment and activation of Neutrophils in the graft has been described in CLAD. Neutrophils are an essential component of the innate immune system which can undergo different activation processes, among which NETosis. NETs can drive epithelial cell injury and induce endothelial mesenchymal transition or epithelial mesenchymal transition (EMT) of breast cancer cells. We here aim to investigate whether NETs can induce EMT on a human alveolar basal epithelial cell line (A549) as possible mechanism of fibrosis in CLAD. Methods NETosis was induced on healthy donor-derived neutrophils (Neu) with PMA. EMT was studied on A549 cells in three conditions (PMA-activated Neu (PMA-Neu), purified NETs from PMA-Neu and TGF-β). To study the induction of EMT, we evaluate the expression of two main proteins representative of EMT mechanism (α-SMA and E-cadherin) by western blot of cell lysates. Since it is known that neutrophils activated against NETosis can induce cell damage, we decided to evaluate cell toxicity after treatments with PMA-Neu or NETs by flow cytometry. Results Confocal microscope images confirmed that PMA treatment leads to release NETs by neutrophils. NETs changed the typical epithelial morphology of A549 cells into a mesenchymal phenotype. These morphological changes are also visible after treatment with TGF-β, the best known EMT effector. Morphological changes were confirmed by western blot analysis of EMT markers expression. Both PMA-Neu and purified NETs induced EMT in A549 after 24h, increasing α-SMA (1.21±0.025 and 1.34±0.025, respectively) and decreasing E-Cadherin expression (0.245±0.10 and 0.08±0.002, respectively). Moreover we observed that NETs activate EMT without toxic effects rather than PMA-Neu which induced 33.70 ± 4.37 % cell death compared to control cells. Conclusion This study highlights the contribution NETs as trigger of lung fibrosis, and suggest this mechanism might contribute to CLAD pathogenesis.

Advances in lung transplantation for interstitial lung diseases.

Lung transplantation (LTx) is increasingly used as ultimate treatment modality in end-stage interstitial lung diseases (ILDs). This review aims to give an overview of the latest evolutions in this field. In the last two years, important new findings regarding LTx outcomes in specific ILD entities have been reported. More data are available on optimization of pre-LTx management of ILD patients especially with regard to pretransplant antifibrotic treatment. LTx is the only treatment option with curative intent for ILDs and is increasingly used for this indication. Several studies have now reported adequate outcomes in different ILD entities, although outcome is shown to be affected by underlying telomeropathies. As new studies could not replicate inferior survival with single compared with double LTx, both options remain acceptable. ILD specialists can beneficially impact on post-LTx outcome by optimizing pre-LTx management: corticosteroids should be avoided, antifibrotics should be initiated whenever possible and BMI and nutritional status optimized, rehabilitation and depression-screening strategies should be implemented in all LTx candidates, as these interventions may all improve postlung transplant survival.

Patient Travel Distance and Post Lung Transplant Survival in the United States: A Cohort Study.

In response to a longstanding Federal mandate to minimize the role of geography in access to transplant in the United States, we assessed whether patient travel distance was associated with lung transplant outcomes. We focused on the posttransplant time period, when the majority of patient visits to a transplant center occur. We present a cohort study of lung transplants in the United States between January 1, 2006, and May 31, 2017. Travel distance was measured from the patient's permanent home zip code to the transplant center using SAS URL access to GoogleMaps. We leveraged data from the US Census, US Department of Agriculture, and the Economic Innovations Group to assess socioeconomic status. Multivariable Cox models were used to assess graft survival. We included 18 128 patients who met the inclusion criteria. Median distance was 69.6 miles. Among patients who traveled >60 miles to reach a transplant center, 41.8% bypassed a closer center and sought care at a more distant center. Patients traveling longer distances sought care at centers with a higher annual transplant volume. In the adjusted Cox Model, patients who traveled >360 miles had a slightly higher risk for posttransplant graft failure than patients traveling ≤60 miles (hazard ratio 1.09; 95% CI, 1.01-1.18), and a higher risk for treated acute rejection (hazard ratio, 1.63; 95% CI, 1.43-1.86). Travel distance was significantly associated with post lung transplant survival. However, this effect was relatively modest. Patient travel distance is an important component of access to lung transplant care.

Impact of Donor Diabetes on Outcomes of Lung Transplantation in the United States

BackgroundDiabetes mellitus is among several factors considered when assessing the suitability of donated organs for transplantation. Lungs from diabetic donors (LDD) are not contraindicated for use as allografts, despite established evidence of diabetes-mediated parenchymal damage. The present study used a national database to assess the impact of donor diabetes on the longevity of lung transplant recipients. MethodsThis retrospective study of the United Network for Organ Sharing database analyzed all adult lung transplant recipients from June 2005 through September 2016. Donor and recipient demographics including the presence of diabetes were used to create a multivariable model. The primary outcome was 5-y mortality, with hazard ratios (HRs) assessed using multivariable Cox regression analysis. Survival curves were calculated using the Kaplan–Meier method. ResultsOf the 17,839 lung transplant recipients analyzed, 1203 (6.7%) received LDD. Recipients of LDD were more likely to be female (44.1% versus 40.2%, P < 0.01) and have mismatched race (47.5% versus 42.2%, P < 0.01). Diabetic donors were more likely to have hypertension (74.6% versus 19.0%, P < 0.01). Multivariable analysis revealed LDD to be an independent predictor of mortality at 5 y (HR 1.16 [1.04-1.29], P < 0.01). However, among the subgroup of diabetic recipients, transplantation of LDD showed no independent association with 5-y mortality (HR 0.81 [0.63-1.06], P = 0.12). ConclusionsRecipients of LDD had a lower 5-y post lung transplantation survival compared with recipients of lungs from nondiabetic donors. LDD allografts did not influence the survival of diabetic recipients.

Factors Associated with Prolonged Survival (>15 Years) after Lung Transplantation: Analysis of the ISHLT Registry

Purpose Long- term outcomes after lung transplantation remain suboptimal with the median survival of 6 years. There is a paucity of data about lung transplant recipients with prolonged (>15 years) survival (pLTS). The aim of this study was to examine the prevalence of pLTS and identify their perioperative and post-operative features compared to a contemporary group with shorter survival. Methods The ISHLT Transplant Registry was queried for adult(>=18 years) patients transplanted from 1990-2001 who survived more than 15 years and patients with post-lung transplant survival between 1 and 5 years. We excluded re-transplants, and multiorgan transplants. To understand the prevalence of pLTS, Kaplan Meier method was used to estimate the 15 year post-transplant survival probability. To identify potential predictors of pLTS, peri-transplant characteristics of the two groups were compared using Fisher's Exact Test and Wilcoxon Rank Sum Test. Variables with more than 25% of the data missing were excluded from this analysis. Results A total of 5346 patients were included in the study, 1848 in the pLTS cohort and 3498 in the 1-to-5 year survival cohort. The 15year post-transplant survival probability was 19.5%. Recipient younger age, lower body mass index (BMI), female gender, bilateral transplant as well as donor female gender were associated with pLTS. Blood type and donor age were not associated with pLTS. While overall, most lung transplants were performed in lower volume centers, a higher number pLTS were transplanted in centers performing >25 transplants/year. A higher proportion of cystic fibrosis patients tended to be pLTS. Conclusion Age, BMI, gender, transplant type, transplant center volume, and primary lung disease were associated with long term survival after lung transplant suggesting that these pre-transplant characteristics may be used to build prognostic model for predicting the occurrence of pLTS at the time of transplant.

Association of Chest CT-Based Quantitative Measures of Muscle and Fat with Post-Lung Transplant Survival and Morbidity: A Single Institutional Retrospective Cohort Study in Korean Population.

Abnormal body composition is an important modifiable risk factor in lung transplantation. Therefore, precise quantification of different body components, including muscle and fat, may play an important role in optimizing outcomes in lung transplant patients. The purpose of the study was to investigate the prognostic significance of muscle and subcutaneous fat mass measured on chest CT with regard to lung transplantation survival and other post-transplant outcomes. The study population included 45 consecutive adult lung transplant recipients (mean age of 47.9 ± 12.1 years; 31 males and 14 females) between 2011 and 2017. Preoperative cross-sectional areas of muscle and subcutaneous fat were semi-automatically measured on axial CT images at the level of the 12th thoracic vertebra (T12). Additional normalized indexed parameters, adjusted for either height or weight, were obtained. Associations of quantitative parameters with survival and various other post-transplant outcomes were evaluated. Of the 45 patients included in the present study, 10 mortalities were observed during the follow-up period. Patients with relative sarcopenia (RS) classified based on height-adjusted muscle area with a cut-off value of 28.07 cm²/m² demonstrated worse postoperative survival (log-rank test, p = 0.007; hazard ratio [HR], 6.39:1) despite being adjusted for age, sex, and body mass index (HR, 8.58:1; p = 0.022). Weight-adjusted parameters of muscle area were negatively correlated with duration of ventilator support (R = -0.54, p < 0.001) and intensive care unit (ICU) stay (R = -0.33, p = 0.021). Patients with RS demonstrate worse survival after lung transplantation that those without RS. Additionally, quantitative parameters of muscles measured at the T12 level on chest CT were associated with the duration of post-lung transplant ventilator support and duration of stay in the ICU.

Objective Donor Scoring System for Lung Transplantation

There is no objective method to estimate post-lung transplant survival solely on the basis of cumulative donor risk factors. The United Network Organ Sharing thoracic transplant database was queried to identify patients who underwent lung transplantation between 2005 and 2015. A Cox proportional hazard model was generated using a training set to identify donor risk factors significantly associated with posttransplant survival. Significant donor risk factors were assigned a score on the basis of their hazard ratio. Donor risk score was calculated for each patient by adding the individual donor risk factor scores. Donors in the validation set were then categorized into low-risk (score= 0), intermediate-risk (score= 1), and high-risk (score >1) categories on the basis of the cumulative risk score. The Lung Allocation Score was used as a surrogate for recipient risk. Survival for each risk group was calculated using Kaplan-Meier curves. The donor risk groups' respective survival at 1 year was 85%, 81%, and 77%, and at 5 years it was 53%, 50%, and 42% (p < 0.001). The combination of low-risk recipients and low-risk donors had 1- and 5-year survival of 89% and 59%, respectively. The combination of high-risk recipients and high-risk donors had 1- and 5-year survival of 70% and 30%, respectively. The proposed lung donor scoring system is a simple, easy to use method that can aid transplant surgeons in the selection of a potential lung transplant donor. Using the lung donor score in conjunction with the Lung Allocation Score can allow for matching of recipients and donors, to optimize posttransplant outcomes.

Malignancies after lung transplantation.

Lung transplantation has become an efficient life-saving treatment for patients with end stage respiratory disease. The increasing good outcome following lung transplantation may be explained by growing experience of transplant teams and availability of potent immunosuppressive drugs. Nevertheless, the latter carries an inherent risk for malignancy besides other common side effects such as systemic hypertension, diabetes and renal dysfunction. Malignancies occur in a smaller proportion of patients but explain for a large proportion of deaths following transplantation. From the first year post-transplantation they will represent the third cause of death with an increasing incidence along post lung transplant survival. In this chapter, we will browse the different types of malignancies arising following lung transplantation. According to the different techniques for lung transplantation, specific types of bronchogenic carcinoma will be described in the explanted lung, in the native lung, and in the graft. Risk factors associated to immunosuppressive therapy, but also to occupational and environmental factors, especially smoking, will be discussed. Eventually, we will strive at integrating recommendations for the treatment of malignancies following lung transplantation.

Use of drug intoxicated donors for lung transplant: Impact on survival outcomes.

The number of increasing deaths due to the opioid epidemic has led to a potential greater supply of organ donors. There is hesitancy to use drug intoxicated donors, and we evaluated their impact on post-transplant survival. Patients ≥18years of age undergoing lung transplantation and donors from whom at least one organ was donated between January 2005 and March 2015 were selected from the United Network of Organ Sharing database. Baseline characteristics and post-transplant survival were compared between drug intoxicated and all other donors. The utilization of drug intoxicated donors increased from 1.86% in 2005 to 6.23% in 2014. The 2 study groups had similar characteristics including age, gender, and Lung Allocation Score. As compared to all other donors, drug intoxicated donors were younger (29.1±9.4 vs 34.6±13.4years, P<.0001), less likely to be male (52% vs 61%, P<.0001), and had a greater smoking history (14% vs 11%, P .04). There was no difference in post-lung transplant survival at 1, 3, and 5years between drug intoxicated donors (85%, 64%, and 47%) and non-drug intoxicated donors (83%, 65%, and 51%). Transplantation utilizing drug intoxicated donor lungs has significantly increased over the past decade without significantly impacting post-transplant survival.

Impact of Carbon Dioxide Tension on Survival After Lung Transplantation for Pulmonary Fibrosis

Low forced vital capacity (FVC), decreased carbon monoxide diffusing capacity, and hypoxemia have been linked to poor prognosis in pulmonary fibrosis. The restrictive physiology may result in an increased respiratory rate, lower carbon dioxide tension (PaCO2), and less functional transplanted lung volume. We hypothesize that a low recipient PaCO2 at the time of listing negatively impacts post-lung transplant survival in patients with pulmonary fibrosis.

Clinical characteristics of cystic fibrosis patients prior to lung transplantation: An international comparison between Canada and the United States

Cystic fibrosis (CF) patients from Canada have better-reported post-lung transplant survival compared to patients from the United States. We hypothesized the clinical characteristics of CF patients prior to lung transplant differ between the two countries. Population-based cohort study utilizing combined Canadian CF Registry and US CF Foundation Patient Registry data from 1986 to 2013. Demographic and clinical variables were analyzed prior to lung transplant. Between 1986 and 2013, 607 (10.2%) CF patients underwent lung transplantation in Canada and 3428 (7.5%) in the United States. A lower proportion of recipients had growth of B. cepacia complex prior to transplant in the United States compared to Canada (0.8% vs 4.3%). Lung function was similar between recipients from the two countries. The proportion of patients classified as underweight was significantly higher in the United States compared to Canada (39.8% vs 28.0%; SD 26.1) despite higher rates of feeding tube use (42.5% vs 28.6%; SD 29.0). CF lung transplant recipients from the United States have similar lung function, lower rates of B. cepacia complex, and worse nutritional parameters prior to transplant compared to counterparts in Canada. Future studies are necessary to evaluate the impact of these differences on post-transplant survival.

A clinical tool to calculate post-transplant survival using pre-transplant clinical characteristics in adults with cystic fibrosis.

We previously identified factors associated with a greater risk of death post-transplant. The purpose of this study was to develop a clinical tool to estimate the risk of death after transplant based on pre-transplant variables. We utilized the Canadian CF registry to develop a nomogram that incorporates pre-transplant clinical measures to assess post-lung transplant survival. The 1-, 3-, and 5-year survival estimates were calculated using Cox proportional hazards models. Between 1988 and 2012, 539 adult Canadians with CF received a lung transplant with 208 deaths in the study period. Four pre-transplant factors most predictive of poor post-transplant survival were older age at transplantation, infection with B. cepacia complex, low FEV1 percent predicted, and pancreatic sufficiency. A nonlinear relationship was found between risk of death and FEV1 percent predicted, age at transplant, and BMI. We constructed a risk calculator based on our model to estimate the 1-, 3-, and 5-year probability of survival after transplant which is available online. Our risk calculator quantifies the risk of death associated with lung transplant using pre-transplant factors. This tool could aid clinicians and patients in the decision-making process and provide information regarding the timing of lung transplantation.