Extracorporeal photopheresis to attenuate decline in lung function due to refractory obstructive allograft dysfunction.

BACKGROUND: This study was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to attenuate the rate of decline of FEV1 in lung transplant recipients with refractory bronchiolitis obliterans. Due to an observed higher than expected early mortality, a preliminary analysis was performed. STUDY DESIGN AND METHODS: Subjects from 10 lung transplant centres were assigned to ECP treatment or to observation based on spirometric criteria, with potential crossover for those under observation. The primary endpoint of this study was to assess response to ECP (i.e., greater than a 50% decrease in the rate of FEV1 decline) before and 6 months after initiation of ECP. Mortality was also evaluated 6 and 12 months after enrolment as a secondary endpoint. RESULTS: Of 44 enrolled subjects, 31 were assigned to ECP treatment while 13 were initially assigned to observation on a non-random basis using specific spirometric inclusion criteria (seven of the observation patients subsequently crossed over to receive ECP). Of evaluable patients, 95% of patients initially assigned to treatment responded to ECP with rates of FEV1 decline that were reduced by 93% in evaluable ECP-treated patients. Mortality rates (percentages) at 6 and 12 months after enrolment was 32% and 41%, respectively. The most common (92%) primary cause of death was respiratory or graft failure. Significantly (p = 0.002) higher rates of FEV1 decline were observed in the non-survivors (-212 ± 177 ml/month) when compared to the survivors (-95 ± 117 ml/month) 12 months after enrolment. In addition, 18 patients with bronchiolitis obliterans syndrome (BOS) diagnosis within 6 months of enrolment had lost 38% of their baseline lung function at BOS diagnosis and 50% of their lung function at enrolment. CONCLUSIONS: These analyses suggest that earlier detection and treatment of BOS should be considered to appreciate improved outcomes with ECP.

Need for tracheostomy after lung transplant predicts decreased mid- and long-term survival.

BACKGROUND: Tracheostomy is an important adjunct for lung transplant patients requiring prolonged ventilation. We explored the effects of post-transplant tracheostomy on survival and bronchiolitis obliterans syndrome after lung transplant. METHODS: A retrospective, single center analysis was performed on all lung transplant recipients during the Lung Allocation Score (LAS) era. Risk factors for post-transplant tracheostomy or death within 30 days were assessed. Kaplan-Meier estimates and Cox proportional hazards models were used to examine the association between tracheostomy within 30 days after transplant and survival at 1 and 3 years. A total of 403 patients underwent single or bilateral lung transplant between May 2005 and February 2016 with complete data for 352 cases, and 35 patients (9.9%) underwent tracheostomy or died (N = 10, 2.8%) within 30 days. RESULTS: In adjusted analyses, primary graft dysfunction grade 3 (PGD3) was associated with a composite end point of tracheostomy or death within 30 days (HR 3.11 (1.69, 5.71), P-value < .001). Tracheostomy within 30 days was associated with decreased survival at 1(HR 4.25 [1.75, 10.35] P-value = .001) and 3 years (HR 2.74 [1.30, 5.76], P-value = .008), as well as decreased bronchiolitis obliterans (BOS)-free survival at 1 (HR 1.87 [1.02, 3.41] P-value = .042) and 3 years (HR 2.15 [1.33, 3.5], P-value = .002). CONCLUSION: Post-transplant tracheostomy is a marker for advanced lung allograft dysfunction with significant reduction in long-term overall and BOS-free survival.

Separate Effect of Perioperative Recombinant Human Factor VIIa Administration and Packed Red Blood Cell Transfusions on Midterm Survival in Lung Transplantation Recipients.

OBJECTIVE: The purpose of this study was to determine the relationship between blood product transfusion, with or without recombinant human activated factor VIIa, and survival after lung transplantation. DESIGN: Retrospective analysis of a single center with follow-up out to 6 years post-transplantation. SETTING: Single-center academic lung transplantation program. PARTICIPANTS: The study comprised 265 adult patients who underwent single or bilateral sequential lung transplantation from March 2011 to June 2017. INTERVENTIONS: Overall survival using Kaplan-Meier curves was compared among the following 3 cohorts: those not transfused with blood products, those transfused with blood products, and those given blood products and recombinant human activated factor VIIa. Cox proportional hazards regression was used to estimate hazard ratios (HRs), confidence intervals (CIs), and p values. MEASUREMENTS AND MAIN RESULTS: Seventy-eight patients received no packed red blood cell transfusions, 149 received packed red blood cell transfusions, and 38 received both packed red blood cell transfusions and recombinant human activated factor VII. Packed red blood cell transfusion was associated with an increased risk of mortality that did not reach statistical significance (HR 2.168, CI 0.978-4.805; p = 0.057). Additional packed red blood cells beyond 15 U were associated with worsened survival (HR 1.363, CI 1.137-1.633; p = 0.001), but recombinant human activated factor VIIa did not increase the risk of mortality. CONCLUSION: Blood product transfusion during and after lung transplantation is associated with decreased survival, especially with large-volume transfusions. Survival is not worse with recombinant human activated factor VIIa administration, but additional studies are needed to determine whether recombinant human activated factor VIIa administration reduces the need for blood product transfusions.

Single Versus Bilateral Lung Transplantation for Idiopathic Pulmonary Fibrosis in the Lung Allocation Score Era.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease. Lung transplantation is the only therapy associated with prolonged survival. The ideal transplant procedure for IPF is unclear. Outcomes after single transplantation (SLTx) versus bilateral lung transplantation (BLTx) in IPF patients after introduction of the Lung Allocation Score were examined. METHODS: Records of patients undergoing lung transplantation for IPF at our institution between May 2005 and March 2017 were reviewed to examine the effect of transplant laterality. Primary outcomes were overall, rejection-free, and bronchiolitis obliterans (BOS)-free survival at 1 and 5 years post-transplant. RESULTS: Lung transplantation was performed in 151 IPF patients post-Lung Allocation Score. Most recipients were male with average age 59 ± 8 years. SLTx was performed in 94 patients (62%). In the overall cohort, comparative survival between SLTx and BLTx was similar at 1 and 5 years before and after adjusting for age and pulmonary hypertension (PH). SLTx was associated with shorter ventilator time and intensive care unit stay and trended toward improved survival over BLTx in patients without PH. CONCLUSIONS: The use of SLTx versus BLTx in IPF did not correspond to significantly different survival adjusting for age and PH. BLTx was associated with prolonged postoperative ventilation and length of stay compared with SLTx. Patients without PH, all older patients, and patients with PH and advanced disease should be considered for SLTx for IPF.

Secondary pulmonary arterial hypertension: to treat or not to treat?

PURPOSE OF REVIEW: The purpose of this review is to review recent literature related to mechanisms and treatment options for 'secondary' (i.e., WHO Groups 3 and 5) pulmonary arterial hypertension (PAH). RECENT FINDINGS: Published randomized controlled trials, in general, do not support the use of approved therapies for 'primary' (i.e., WHO Group 1) PAH patients in patients with Group 3 PAH because of the small numbers of patients and inconsistent benefit. Therefore, we currently recommend against the use of these medications for Group 3 PAH. Similarly, there is limited evidence supporting the use of Group 1 PAH medications in Group 5 patients. In most patients with Group 5 PAH, treatment should be directed to the underlying disease. SUMMARY: The utility of PAH-specific therapy in WHO Group 3 PAH is unclear because of the small numbers of patients evaluated and inconsistent beneficial effects observed. There is limited evidence supporting the use of PAH medications in Group 5 patients, and they may be harmful in some cases.

Gender differences in long-term survival post-transplant: A single-institution analysis in the lung allocation score era.

The purpose of this study was to clarify the significance of recipient gender status on lung transplant outcomes in a large single-institution experience spanning three decades, we analyzed data from all lung transplants performed in our institution since 1986. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate the effect of recipient characteristics on survival and BOS score ≥1-free survival. Logistic regression analysis was used to explore the association of gender with short-term graft function. About 876 lung transplants were performed between 1986 and 2016. Kaplan-Meier survival estimates at 5 years post-transplant for females vs males in the LAS era were 71% vs 58%. In the LAS era, females showed greater unadjusted BOS≥1-free survival than males (35% vs 25%, P=.02) over 5 years. Female gender was the only factor in the LAS era significantly associated with improved adjusted 5-year survival [HR 0.56 (95% CI 0.33, 0.95) P=.03]. Conversely, in the pre-LAS era female gender was not associated with improved survival. Female recipients showed significantly improved survival over 5 years compared to males in the LAS era. A prospective analysis of biologic and immunologic differences is warranted.

Lung transplantation for pulmonary sarcoidosis. Twenty-five years of experience in the USA.

OBJECTIVE: Lung transplantation is the ultimate treatment for end-stage pulmonary sarcoidosis. Post-transplant survival outcomes remain unclear. METHODS: Survival models were used to assess survival and graft outcomes in patients with sarcoid among 20,896 lung transplants performed in the USA. RESULTS: 695 lung recipients were transplanted for pulmonary sarcoidosis. Sarcoid lung recipients had similar median survival rate (69.7 months (IQR 60.2-79.3)) compared with the non-sarcoid lung recipients (63.1 months (IQR 61.4-64.8), p=0.88). In multivariate Cox regression, sarcoidosis was not independently associated with worse mortality (HR 0.96 (95% CI 0.85 to 1.08), p=0.51). Among the sarcoid lung recipients, double lung transplantation (HR 0.76 (0.58 to 0.99), p=0.04) and lung allocation score era (HR 0.74 (0.56 to 0.97), p=0.03) were associated with improved survival. CONCLUSIONS: Recipients of lung transplants for pulmonary sarcoidosis had similar outcomes compared with non-sarcoid lung recipients.

Increasing fine particulate air pollution in China and the potential use of exposure and biomarker data in disease prevention.

Increased industrialization and urbanization have led to marked increases in air pollutants in China over the last decade. Pollutant levels in the north and eastern regions are often four times higher than current daily levels in the United States. Recent reports indicate a higher incidence of lung cancer and mortality in men and urban dwellers, but the contribution of air pollution to these findings remains unknown. Future studies that define individual exposures, combined with biomarkers linked to disease, will be essential to the understanding of risk posed by air pollution in China.

Impact of lung transplantation on diastolic dysfunction in recipients with pretransplant pulmonary hypertension.

OBJECTIVE: Pulmonary hypertension can cause left ventricular diastolic dysfunction through ventricular interdependence. Moreover, diastolic dysfunction has been linked to adverse outcomes after lung transplant. The impact of lung transplant on diastolic dysfunction in recipients with pretransplant pulmonary hypertension is not defined. In this cohort, we aimed to assess the prevalence of diastolic dysfunction, the change in diastolic dysfunction after lung transplant, and the impact of diastolic dysfunction on lung transplant outcomes. METHODS: In a large, single-center database from January 2011 to September 2021, single or bilateral lung transplant recipients with pulmonary hypertension (mean pulmonary artery pressure > 20 mm Hg) were retrospectively identified. Those without a pre- or post-transplant echocardiogram within 1 year were excluded. Diastolic dysfunction was diagnosed and graded according to the American Society of Echocardiography 2016 guideline on assessment of diastolic dysfunction (present, absent, indeterminate). McNemar's test was used to examine association between diastolic dysfunction pre- and post-transplant. Kaplan-Meier and Cox regression analysis were used to assess associations between pre-lung transplant diastolic dysfunction and post-lung transplant 1-year outcomes, including mortality, major adverse cardiac events, and bronchiolitis obliterans syndrome grade 1 or higher-free survival. RESULTS: Of 476 primary lung transplant recipients, 205 with pulmonary hypertension formed the study cohort (mean age, 56.6 ± 11.9 years, men 61.5%, mean pulmonary artery pressure 30.5 ± 9.8 mm Hg, left ventricular ejection fraction < 55% 9 [4.3%]). Pretransplant, diastolic dysfunction was present in 93 patients (45.4%) (grade I = 8, II = 84, III = 1), absent in 16 patients (7.8%), and indeterminate in 89 patients (43.4%), and 7 patients (3.4%) had missing data. Post-transplant, diastolic dysfunction was present in 7 patients (3.4%) (grade I = 2, II = 5, III = 0), absent in 164 patients (80.0%), and indeterminate in 15 patients (7.3%), and 19 patients (9.3%) had missing data. For those with diastolic dysfunction grades in both time periods (n = 180), there was a significant decrease in diastolic dysfunction post-transplant (148/169 patients with resolved diastolic dysfunction; McNemar's test P < .001). Pretransplant diastolic dysfunction was not associated with major adverse cardiac events (hazard ratio [HR], 1.08, 95% CI, 0.72-1.62; P = .71), bronchiolitis obliterans syndrome-free survival (HR, 0.67, 95% CI, 0.39-1.56; P = .15), or mortality (HR, 0.70, 95% CI, 0.33-1.46; P = .34) at 1 year. CONCLUSIONS: Diastolic dysfunction is highly prevalent in lung transplant candidates with normal left ventricular systolic function and pulmonary hypertension, and resolves in most patients after lung transplant regardless of patient characteristics. Pre-lung transplant diastolic dysfunction was not associated with adverse lung or cardiac outcomes after lung transplant. Collectively, these findings suggest that the presence of diastolic dysfunction in lung transplant recipients with pulmonary hypertension has no prognostic significance, and as such diastolic dysfunction and the associated clinical syndrome of heart failure with preserved ejection fraction should not be considered a relative contraindication to lung transplant in such patients.

Calcineurin inhibitors and Clostridium difficile infection in adult lung transplant recipients: the effect of cyclosporine versus tacrolimus.

BACKGROUND: Tacrolimus (FK506) has a superior immunosuppressive effect compared with cyclosporine (CSA) without a significant increase in generalized infectious complications. Differences in specific infections such as Clostridium difficile (CDI) have not been reported. We investigated the relationship between calcineurin inhibitors and CDI, hypothesizing that choice of calcineurin inhibitor (CSA or FK506) after lung transplantation would have no effect on the incidence of CDI. METHODS: We performed a retrospective chart review of lung transplant recipients between June 1, 2000, and December 31, 2005, at a single institution. Positive CDI assays through December 11, 2011, were also recorded. We used Student's t- and chi-squared tests (α = 0.05) to compare CSA and FK506 groups. We calculated adjusted hazard ratios for CDI using Cox proportional hazard models. RESULTS: We identified 217 lung transplant recipients: 106 patients in the CSA group and 111 patients in the FK506 group. A total of 31 patients (27.9%) in the FK506 group developed CDI postoperatively compared with 20 patients (18.9%) in the CSA group (P = 0.16). The adjusted hazard ratio for CDI in the FK506 group was not significantly higher (1.53; 95% confidence interval, 0.78-2.98). There was no significant difference in the intensive care unit or total length of stay, in-hospital incidence rate, time to first CDI episode, or recurrence rate between groups. CONCLUSIONS: The CDI rates were not significantly higher in the FK506 group than the CSA group in our study. These data are consistent with previous studies on FK506 that show no increase in infectious complications over CSA, and demonstrate its continued safety in lung transplantation.

The rise of Clostridium difficile infection in lung transplant recipients in the modern era.

PURPOSE: Clostridium difficile infection (CDI) rates have been rising in recent years. We aimed to characterize CDI in lung transplant recipients in the modern era and hypothesized that CDI would increase the mortality risk. METHODS: We performed a retrospective chart review of patients undergoing transplantation at our center from 1/2006 to 7/2011. Attributes of CDI+ and CDI- groups were compared using Student's t- and chi-square tests (α = 0.05). Multivariate Cox proportional hazard models were used to control for confounding factors. RESULTS: Overall CDI incidence was 22.5%. Seven of 151 patients (4.6%) developed CDI during the initial hospitalization after transplantation (mean time 10.6 ± 6 d) while 27 patients (19.7%) developed CDI after discharge (mean time 467 ± 471 d). Incidence rate was 224.6 cases/100 000 patient-days compared to 110 cases/100 000 patient-days (rate for entire hospital). CDI was not predictive of mortality (HR 2.06, 95% CI 0.94-4.52). CONCLUSION: CDI rates in lung transplant recipients are high in the modern era. No risk factors for CDI were identified. Although not statistically significant, CDI+ patients had a higher risk of death. The economic burden of CDI and trend toward worse outcomes for CDI patients have important implications for post-operative surveillance of CDI-related complications and need for CDI prophylaxis.

Automatic event detection in lung transplant recipients based on home monitoring of spirometry and symptoms.

OBJECTIVE: The goal of this study was to develop, implement, and test an automated decision system to provide early detection of clinically important bronchopulmonary events in a population of lung transplant recipients following a home monitoring protocol. SUBJECTS AND METHODS: Spirometry and other clinical data were collected daily at home by lung transplant recipients and transmitted weekly to the study data center. Decision rules were developed using wavelet analysis of declines in spirometry and increases in respiratory symptoms from a learning set of patient home data and validated with an independent patient set. RESULTS: Using forced expiratory volume in 1 s or symptoms, the detection captured the majority of events (sensitivity, 80-90%) at an acceptable level of false alarms. On average, detections occurred 6.6-10.8 days earlier than the known event records. CONCLUSIONS: This approach is useful for early discovery of pulmonary events and has the potential to decrease the time required for humans to review large amount of home monitoring data to discover relatively infrequent but clinically important events.

A randomized controlled trial comparing health and quality of life of lung transplant recipients following nurse and computer-based triage utilizing home spirometry monitoring.

BACKGROUND: Lung transplantation is now a standard intervention for patients with advanced lung disease. Home monitoring of pulmonary function and symptoms has been used to follow the progress of lung transplant recipients in an effort to improve care and clinical status. The study objective was to determine the relative performance of a computer-based Bayesian algorithm compared with a manual nurse decision process for triaging clinical intervention in lung transplant recipients participating in a home monitoring program. MATERIALS AND METHODS: This randomized controlled trial had 65 lung transplant recipients assigned to either the Bayesian or nurse triage study arm. Subjects monitored and transmitted spirometry and respiratory symptoms daily to the data center using an electronic spirometer/diary device. Subjects completed the Short Form-36 (SF-36) survey at baseline and after 1 year. End points were change from baseline after 1 year in forced expiratory volume at 1 s (FEV1) and quality of life (SF-36 scales) within and between each study arm. RESULTS: There were no statistically significant differences between groups in FEV1 or SF-36 scales at baseline or after 1 year.: Results were comparable between nurse and Bayesian system for detecting changes in spirometry and symptoms, providing support for using computer-based triage support systems as remote monitoring triage programs become more widely available. CONCLUSIONS: The feasibility of monitoring critical patient data with a computer-based decision system is especially important given the likely economic constraints on the growth in the nurse workforce capable of providing these early detection triage services.

Lung transplantation after hematopoietic stem cell transplantation.

INTRODUCTION: Pulmonary insufficiency following bone marrow transplant (BMT) is common and has significant associated mortality. Lung transplantation (LTX) is the only viable treatment for patients with end-stage pulmonary disease, but LTX after BMT is an uncommon event given the medical candidacy of the potential recipients. We sought to evaluate the short- and long-term outcomes of LTX in BMT recipients. METHODS: We performed a retrospective evaluation of our institution's longitudinal LTX and BMT databases. Demographic and outcomes variables were collected. RESULTS: We identified 639 LTX from January 1, 1988, through December 31, 2009, and 5525 BMT from program inception, March 21, 1974, through December 31, 2009. From the cross-referenced cohort, we identified four patients who had BMT followed by LTX. Our series was composed of two men and two women, with a mean age of 32.3 yr (range, 20-59 yr). Single LTX were performed in two recipients (50%). All patients had significant and expected morbidities related to their transplant immunosuppression. Three patients (75%) required cardiopulmonary bypass at the time of LTX. The two recipients who underwent bilateral LTX required open chest management and subsequent tracheostomy. All patients are still alive at follow-up (range, 19-119 months, median 39.5). CONCLUSION: Our study demonstrates that LTX in the setting of BMT is a high-risk operation with the potential for a tumultuous perioperative course. Despite this, good outcomes and survival are obtainable in carefully selected patients. Selection factors include clinically stable patients without active sepsis and preoperative optimization of nutrition in anticipation of a prolonged recovery. An experienced multidisciplinary team approach and a protocol-driven management plan are paramount for successful outcomes in this challenging population.

Lung Transplant Recipients With Prior Coronary Artery Bypass Grafting Are at Increased Risk of Death and Early Perioperative Hemorrhage.

Prior coronary artery bypass grafting (CABG) has been considered a relative contraindication to lung transplantation due to the atherosclerotic disease burden and technical challenges. We hypothesized that lung transplant recipients with prior CABG have increased mortality compared to recipients without prior CABG. Further, the causes of death are different for lung transplant recipients with prior CABG vs without CABG. The Scientific Registry of Transplant Recipients database was queried to define the survival and causes of death of lung transplant recipients with or without CABG during the Lung Allocation Score era from May 5, 2005 to December 31, 2015. The primary end-points were all-cause mortality at 1 year and 5 years, as well as mortality due to major causes of death. This retrospective study cohort included a total of 13,064 lung transplant recipients, of whom 319 patients had previously undergone CABG, representing 2.4% of all transplants. Patients without prior CABG were more likely to have undergone bilateral lung transplantation compared to those with prior CABG (61.2 % vs 15.7%, P < 0.001). Among patients with prior CABG, single right lung transplant was most common. Overall patient survival at 1 year was 76.8% for lung transplant recipients with prior CABG and 85.4% for patients without prior CABG. Freedom from death due to graft failure at 1 and 5 years in patients with a prior CABG was 93.1% and 76.2% respectively, cardiac and/or cerebrovascular disease 96.2% and 88.5% respectively, and hemorrhage 97.9% and 97.5% respectively. In a multivariate Cox regression model utilizing time-dependent coefficients for recipient age, prior CABG, among several other risk factors, was associated with increased mortality within 1 year. Prior CABG is associated with short- and long-term mortality in lung transplant recipients with history of CABG despite the majority of these patients undergoing single lung transplantation vs bilateral lung transplantation. Graft failure and/or pulmonary causes are the most common cause of death regardless of whether or not the lung transplant recipient had prior CABG, but patients with prior CABG are at increased risk of death due to graft failure, cardiac or cerebrovascular disease, and hemorrhage.

Time since primary transplant and poor functional status predict survival after redo lung transplant.

Background: In previous studies, lower functional status measured by Karnofsky Performance Status (KPS) correlated with worse survival after redo lung transplant. We hypothesize that combining reduced functional status and time from primary lung transplant will correlate with the etiology of lung allograft failure after primary lung transplant and more accurately predict survival after redo lung transplant. Methods: This retrospective study was approved by University of Minnesota Institutional Review Board. From the Scientific Registry of Transplant Recipients (SRTR) database, 739 patients underwent redo lung transplant (01/01/2005-8/30/2019). Pre-lung transplant characteristics, KPS, time between primary and redo lung transplant, outcomes, overall survival were evaluated. Paired comparisons were used to compare pre-transplant variables. A Cox regression model was fit to examine re-transplant survival. Due to non-proportional hazards, time between transplants was split into <1-year vs. 1+ years and analyzed with time-dependent coefficients, with follow-up time considered in three segments (0-6, 6-24, 24+ months). Results: After KPS grouping (10-40%, 50-70%, 80-100%), KPS 10-40% were less likely to be discharged after primary transplant and more likely required mechanical ventilation or extracorporeal membrane oxygenation (ECMO) bridging (P<0.001). Redo lung transplant survival was worse in the KPS 10-40% group who more likely underwent lung transplant <1 year after primary lung transplant. Mortality was significantly higher for patients who underwent redo lung transplant within one year of primary transplant when KPS was 10-40% (P<0.001). These patients were more likely to require redo lung transplant due to primary graft failure or acute cellular rejection. Conclusions: Functional status and time from primary lung transplant are strong predictors of outcome after redo lung transplant. We categorized redo lung transplant recipients in two distinct groups. One group has early allograft failure and poor functional status with a very poor prognosis after redo lung transplant. The other group has chronic allograft failure and overall better functional status with relatively better survival after redo lung transplant. Salvage redo lung transplant for primary allograft failure or acute rejection is associated with low one year survival.

A randomized, placebo-controlled trial of aprotinin to reduce primary graft dysfunction following lung transplantation.

PURPOSE: Severe primary graft dysfunction (PGD) is the major early problem following lung transplantation. Aprotinin, a serine protease inhibitor, has many anti-inflammatory properties that might reduce or prevent lung injury. Our hypothesis was that the incidence of PGD could be reduced by a combination of donor lung perfusion and systemic administration of aprotinin to recipients. METHODS AND MATERIALS: The study was randomized and placebo controlled. Donor lungs were perfused during procurement with 4 L Perfadex containing aprotinin (280 mg load + 70 mg/hL) or placebo. Aprotinin or placebo was also administered peri-operatively to the recipients. The study was powered to detect a 10% improvement in the primary endpoint of developing ISHLT grade III PGD anytime within 48 hr following the transplant procedure. RESULTS: There were 48 patients randomized. Diagnosis and the use of bypass were different between groups. The study was stopped prematurely at the planned interim analysis point because of published concerns about renal toxicity of aprotinin. There was no difference in the occurrence of the primary endpoint between groups of patients. The median change from the baseline creatinine level at 24, 48, 72 hr; 7 and 30 d following the transplant was not associated with the administration of aprotinin. CONCLUSIONS: There was no statistically significant difference in the incidence of the primary endpoint between groups in the study. Excess renal failure related to aprotinin administration in a patient population at high risk for the event was not observed.

Human neutrophil peptide in lung chronic allograft dysfunction.

CONTEXT: Our previous case-control study identified human neutrophil peptide (HNP) as a potential biomarker for bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. OBJECTIVE: To prospectively validate HNP as a biomarker for BOS. MATERIALS AND METHODS: HNP was measured by ELISA in bronchoalveolar lavage (BAL) fluid in lung transplant recipients. RESULTS: The first HNP measurement after reaching baseline pulmonary function was predictive of developing BOS ≥2 (p = 0.0419). HNP remained elevated in those that developed BOS. The effect of potential confounders did not significantly impact BOS-free survival time. CONCLUSION: HNP levels are elevated early and persistently in those that develop BOS.

Induction type and outcomes for kidney graft and patient survival in recipients with prior lung transplantation in the United States.

BACKGROUND: Induction immunosuppression regimens for kidney transplants in lung transplant recipients vary widely. We studied the impact of induction types for kidney after lung transplant recipients. METHODS: Using the Scientific Registry of Transplant Recipients database between 1994 and 2015, we studied outcomes of patients and kidney grafts for 330 kidney after lung transplant recipients for whom induction before kidney transplant included depletional (n = 115), non-depletional (n = 170), or no induction (steroids only; n = 45). We studied risk factors for recipient and graft survival using Cox proportional hazards model adjusted for kidney and lung induction, kidney donor type, dialysis status, recipient and donor ages, time from lung to kidney transplant, cause of lung disease, bilateral vs single lung transplant, diabetes, and human leukocyte antigen mismatches before kidney transplant, with transplant center as a random effect. RESULTS: There was no difference between groups in patient survival or death-censored kidney allograft survival. The 1-year kidney acute rejection rates were 15.5%, 7.14%, and 0% in depletional, non-depletional, and no induction groups, respectively. In the Cox model for patient survival, living kidney donor recipients and bilateral lung transplant recipients were favorable predictors. For death-censored graft survival, kidney induction type did not predict graft survival. Results did not change when models only included recipients on tacrolimus and mycophenolate based maintenance. CONCLUSIONS: The type of kidney induction did not influence patient or kidney graft survival following kidney transplants for those with previous lung transplants. No induction may be the preferred choice for kidney after lung transplant because of the lack of benefits from biologic induction in this large cohort.