Long-term Outcome Of Lung Transplantation Research Articles

How safe is lung transplantation in patients of 65 years or older? A single-center retrospective cohort

IntroductionWith increasing experience in high-volume centers, age alone should not be an absolute contra-indication to lung transplantation (LT) but be considered as part of the patient's initial characteristics. The objective of this study is to provide early and long-term outcomes of LT in recipients aged 65 or older, compared with their younger counterparts. MethodsThis is a retrospective study, including all patients undergoing LT in Bichat Hospital (Paris, France) from January 2014 to March 2019. Two groups were defined depending on the patients’ age when they were transplanted: patients older than 65 were defined as the “elderly group” and patients younger than 65 years old were defined as the « younger group ». Primary endpoint was 90-day mortality. Secondary endpoints included 1-year mortality, 1-year FEV1 (forced expiratory volume in one second), and 5-year overall survival. ResultsFrom September 2014 to March 2019, 22 patients were included in the “elderly group” and 213 were included in the « younger group ». The elderly group had more single LT (SLT) (82% vs. 29%, p < 0.001), with a shorter cold ischemic time (243 min vs. 310 min, p = 0.001) and a lower rate of early humoral rejection (9% vs. 30%, p = 0.045) compared to the younger group. Ninety-day mortality was not significantly different between elderly and younger group (9% vs. 14%, p = 0.95, respectively), nor were 1-year mortality (23% vs. 25%, p = 0.9, respectively) and 5-year overall survival. Six months after LT, FEV1 was significantly better in the elderly group compared to the younger group (77.0% vs. 65.5%, p = 0.037 respectively), but the difference did not reach statistical significance after one year (78.5 vs. 68.3%, p = 0.18 respectively). ConclusionElderly patients underwent more frequently single LT, and achieved similar short and long term postoperative outcomes compared to their younger counterparts. LT for patients 65 years or older should be routinely considered when carefully selected.

Long-term outcomes of lung transplantation with ex vivo lung perfusion technique.

Ex vivo lung perfusion (EVLP) has demonstrated encouraging short- and medium-term outcomes with limited data available on its long-term outcomes. This study assesses (1) EVLP long-term outcomes and (2) EVLP era-based sub-analysis in addition to secondary outcomes of recipients with EVLP-treated donor lungs compared with recipients of conventionally preserved donor lungs in unmatched and propensity score-matched cohorts. Double lung transplants performed between 1st January 2012 and 31st December 2021 were included. A total of 57 recipients received EVLP-treated lungs compared to 202 unmatched and 57 matched recipients who were subjected to non-EVLP-treated lungs. The EVLP group had a significantly lower mean PaO2/FiO2 ratio and significantly higher mean BMI than the non-EVLP group in the unmatched and matched cohorts. The proportion of smoking history in the unmatched cohort was significantly higher in the EVLP group, while a similar smoking history was demonstrated in the matched cohorts. No difference was demonstrated in overall freedom from death and retransplantation between the groups in the unmatched and matched cohorts (unmatched: hazard ratio (HR) 1.28, 95% confidence interval (CI) 0.79-2.07, P = 0.32; matched: HR 1.06, 95% CI 0.59-1.89). P = 0.89). In the unmatched cohort, overall freedom from chronic allograft dysfunction (CLAD) was significantly different between the groups (HR 1.64, 95% CI 1.07-2.52, P = 0.02); however, the cumulative CLAD incidence was similar (HR 0.72, 95% CI 0.48-1.1, P = 0.13). In the matched cohort, the overall freedom from CLAD (HR 1.69, 95% CI 0.97-2.95, P = 0.06) and cumulative CLAD incidence (HR 0.91, 95% CI 0.37-2.215, P = 0.83) were similar between the groups. The EVLP era sub-analysis of the unmatched cohort in 2012-2014 had a significantly higher cumulative CLAD incidence in the EVLP group; however, this was not demonstrated in the matched cohort. All secondary outcomes were similar between the groups in the unmatched and matched cohorts. In conclusion, transplantation of marginal donor lungs after EVLP evaluation is non-detrimental compared to conventionally preserved donor lungs in terms of mortality, retransplantation, cumulative CLAD incidence, and secondary outcomes. Although the unmatched EVLP era of 2012-2014 had a significantly higher cumulative CLAD incidence, no such finding was demonstrated in the matched cohort of the same era.

Long-term outcomes of lung transplantation requiring renal replacement therapy: A single-center experience

BackgroundLife-long immunosuppressive therapy after lung transplantation (LT) may lead to end-stage renal disease (ESRD), requiring renal replacement therapy (RRT). We aimed to investigate the characteristics and long-term outcomes of patients undergoing LT and requiring RRT. MethodsThis study was a single-center, retrospective cohort study. The patients were divided into the RRT (n = 15) and non-RRT (n = 170) groups. We summarized the clinical features of patients in the RRT group and compared patient characteristics, overall survival, and chronic lung allograft dysfunction (CLAD)-free survival between the two groups. ResultsThe cumulative incidences of ESRD requiring RRT after LT at 5, 10, and 15 years were 0.8 %, 7.6 %, and 25.2 %, respectively. In the RRT group, all 15 patients underwent hemodialysis but not peritoneal dialysis, and two patients underwent living-donor kidney transplantation. The median follow-up period was longer in the RRT group than in the non-RRT group (P < 0.001). The CLAD-free survival and overall survival did not differ between the two groups. The 5-year survival rate even after the initiation of hemodialysis was 53.3 %, and the leading cause of death in the RRT group was infection. ConclusionsFavorable long-term outcomes can be achieved by RRT for ESRD after LT.

Oxygenated Hemoglobin Predicts Outcome in Patients with Chronic Lung Allograft Dysfunction

Background: Long-term outcome of lung transplantation (LTx) recipients is limited by chronic lung allograft dysfunction (CLAD). In this setting of new onset respiratory failure, the amount of oxygenated hemoglobin (OxyHem; hemoglobin (Hb) concentration × fractional oxygen saturation) may provide valuable information. Objective: We hypothesized that OxyHem predicts survival of LTx recipients at the onset of CLAD. Methods: Data from 292 LTx recipients with CLAD were analyzed. After excluding patients with missing data or supplemental oxygen, the final population comprised 218 patients. The relationship between survival upon CLAD and OxyHem was analyzed by Cox regression analyses and ROC curves. Results: Among the 218 patients (102 males, 116 females), 128 (58.7%) died, median survival time after CLAD onset being 1,156 days. Survival was significantly associated with type of transplantation, time to CLAD, CLAD stage at onset, and OxyHem, which was superior to Hb or oxygen saturation. The risk for death after CLAD increased by 14% per reduction of OxyHem by 1 g/dL, and values below 11 g/dL corresponded to an 80% increase in mortality risk. Conclusion: Thus, OxyHem was identified as an independent predictor of mortality after CLAD onset. Whether it is useful in supporting therapeutic decisions and potentially home monitoring in the surveillance of lung transplant recipients has to be studied further.

Impact of extended-criteria donor lungs according to preoperative recipient status and age in lung transplantation.

BackgroundOrgan donor shortage remains as one of the limiting factors for lung transplantation. Given the increase in waiting time, preoperative condition has worsened and affects surgical outcomes. This study aimed to evaluate the immediate postoperative and long-term outcomes of lung transplantation in extended-criteria donor (ECD) lungs compared with standard-criteria donor (SCD) lungs.MethodsA total of 246 patients who had undergone double-lung transplantation during the study period were enrolled. SCD was defined based on the following characteristics age <55 years, <20 pack-years smoking history, and PaO2/fraction of O2 ratio >300 mmHg. Organ donors who do not fulfill these criteria were classified as ECD. Pre- and postoperative data for outcomes and survival data were analyzed.ResultsECD showed significant association with extracorporeal membrane oxygenation weaning in the operating room (hazard ratio [HR], 0.531; 95% confidence interval [CI], 0.291–0.970; P=0.039) considering recipient’s age and status at operation. The ECD group showed comparable survival rate with the SCD group (HR, 1.413; 95% CI, 0.885–2.255; P=0.148), with adjustment of other factors. However, when the recipient had Korean Network for Organ Sharing (KONOS) status 0 at the time of transplantation (HR, 1.662; 95% CI, 1.025–2.568; P=0.039), G3 primary graft dysfunction at 72 hours after surgery (HR, 2.508; 95% CI, 1.416–4.440; P=0.002) was a risk factor that decreased survival.ConclusionsThe outcome of ECD is not inferior to that of SCD. Therefore, ECD lung should be considered a potential donor organ following active donor management rather than a contraindication of transplantation in highly selected recipients.

Antithymocyte Globulin is Associated with a Lower Incidence of De Novo Donor-Specific Antibody Detection in Lung Transplant Recipients: A Single-Center Experience

De novo donor-specific anti-HLA antibodies (DSA) have been associated with significantly increased risk for antibody-mediated rejection (AMR) and lung allograft dysfunction. Induction immunosuppression has improved the long-term outcome of lung transplantation. However, the impact of Induction immunosuppression on the development of de novo DSA in lung transplant recipients is not well defined METHODS: We assessed the relationship between using rabbit Antithymocyte Globulin (rATG) for induction immunosuppression and the development of de novo DSA in a cohort of consecutive lung transplant recipients (n = 67) that were followed for 12 months post-transplant. All recipients had negative flow cytometry crossmatch on the day of transplant. Anti-HLA antibodies in the serum were assessed at 1, 3, 6, 12 months post-transplant. DSA were defined as having a Mean Fluorescence Intensity (MFI) > 1000 RESULTS: 41/67 lung transplant recipients (LTR) received a single dose rATG (1.5 mg/kg) within 24 hours of transplant. De novo DSA were detected in 10/41 (24.3%) compared to 13/26 (50%) ATG and no ATG groups respectively at 12 months post-transplant. However, de novo DSA were detected within 1 month post-transplant in 5/10 (50%) compared to 3/13 (23.3%) rATG and no rATG groups respectively. There was no significant difference in the de novo DSA MFI levels between the rATG group (median MFI = 1379 & 2124 for class I & II respectively) compared to the no rATG group (median MFI = 2186 & 2388 for class I & II respectively) at 12 months post-transplant. De novo DSA prevalence is shown in Table 1. Induction with a single dose of rATG is associated with a significant decrease in the prevalence of HLA de novo DSA in LTR at 12 months post-transplant. De novo DSA were detected earlier in the rATG group compared to no rATG group. These findings warrant investigating in a larger study the impact of rATG induction on de novo DSA levels and lung allograft dysfunction.

The role of innate immunity in the long-term outcome of lung transplantation.

Long-term survival after lung transplantation remains suboptimal due to chronic lung allograft dysfunction (CLAD), a progressive scarring process affecting the graft. Although anti-donor alloimmunity is central to the pathogenesis of CLAD, its underlying mechanisms are not fully elucidated and it is neither preventable nor treatable using currently available immunosuppression. Recent evidence has shown that innate immune stimuli are fundamental to the development of CLAD. Here, we examine long-standing assumptions and new concepts linking innate immune activation to late lung allograft fibrosis.

Extracorporeal Photopheresis as Treatment Option of Chronic Lung Allograft Dysfunction. Is ECP the Therapy of the Future?

Long-term outcomes of lung transplantation are severely affected by the development of chronic lung allograft dysfunction (CLAD), which unfortunately has few efficient therapeutic options. In the last 10 years, extracorporeal photopheresis has been increasingly used in our center as second-line therapy and we present herein our experience.

Apoptosis of the Tracheal Epithelium Can Increase the Number of Recipient Bone Marrow-Derived Myofibroblasts in Allografts and Exacerbate Obliterative Bronchiolitis After Tracheal Transplantation in Mice.

The long-term outcome of lung transplantation is impeded by the development of obliterative bronchiolitis (OB). We sought to investigate the relationship between the apoptosis of tracheal epithelial cells and bone marrow-derived myofibroblasts in the process of OB. The mouse orthotopic tracheal transplant model was established. The allografts and syngrafts were harvested at 1, 2, 3, and 4 weeks after tracheal transplant. The percentage of tracheal lumen occlusion was assayed via histology and morphometry. Immunofluorescence staining was used to detect the apoptotic epithelial cells and recipient-derived myofibroblasts. The expression of SDF-1α and TGF-β and the infiltrations of CD4 and CD8 T cells in the grafts were detected using immunohistochemical staining. We found that there were more apoptotic epithelia in the allograft group than in the syngraft group and that the level of tracheal lumen occlusion was higher at different time points. Moreover, the increase in the apoptosis of the tracheal epithelium occurred earlier than that of occlusion of the tracheal lumen. There were more myofibroblasts derived from the recipient's bone marrow and more CD4 and CD8 T cells in the allografts. The expression of SDF-1α and TGF-β was higher in the epithelium from allografts than in those of the syngrafts. Our study indicated that the apoptotic tracheal epithelia in the OB model might increase the amount of myofibroblasts derived from the recipient's bone marrow. Therapeutic methods aimed at preventing apoptosis of the tracheal epithelium may improve the outcome of lung transplantation.

Sa1619 Long-Term Outcomes of Lung Transplantation in Patients With Hepatitis C Infection: The Data from the U.S. Transplant Registry

Sa1619 Long-Term Outcomes of Lung Transplantation in Patients With Hepatitis C Infection: The Data from the U.S. Transplant Registry

Molecular Profiling in Lung Biopsies of Human Pulmonary Allografts to Predict Chronic Lung Allograft Dysfunction

Chronic lung allograft dysfunction (CLAD) is the main reason for poor long-term outcome of lung transplantation, with bronchiolitis obliterans (BO) representing the predominant pathological feature. BO is defined as a progressive fibrous obliteration of the small airways, thought to be triggered by a combination of nonimmune bronchial injury and alloimmune and autoimmune mechanisms. Because biopsy samples are too insensitive to reliably detect BO and a decline in lung function test results, which is clinically used to define CLAD, does not detect early stages, there is need for alternative biomarkers for early diagnosis. Herein, we analyzed the cellular composition and differential expression of 45 tissue remodeling-associated genes in transbronchial lung biopsy specimens from two cohorts with 18 patients each: patients who did not develop CLAD within 3 years after transplantation (48 biopsy specimens) and patients rapidly developing CLAD within the first 3 postoperative years (57 biopsy specimens). Integrating the mRNA expression levels of the five most significantly dysregulated genes from the transforming growth factor-β axis (BMP4, IL6, MMP1, SMAD1, and THBS1) into a score, patient groups could be confidently separated and the outcome predicted (P < 0.001). We conclude that overexpression of fibrosis-associated genes may be valuable as a tissue-based molecular biomarker to more accurately diagnose or predict the development of CLAD.

Lung Transplantation in a Patient with Pre-transplant Colonization of Extensively Drug-resistant Acinetobacter baumannii

Colonization of the pre-transplant lung by multidrug-resistant bacteria affects short- and long-term outcomes of lung transplantation. However, there are no case reports on the colonization of a pre-transplant lung by drug-resistant Acinetobacter baumannii. We report a case of extensively drug resistant (XDR) A. baumannii colonization in the tracheobronchial tree that caused severe infectious complications after bilateral lung transplantation. A 23-year-old man diagnosed with bronchiolitis obliterans syndrome (BOS) 4 years earlier with a history of allogenic bone marrow transplantation for acute lymphoblastic leukemia was admitted to the hospital with dyspnea. Due to progressive hypercapnic respiratory failure, long-term mechanical ventilation was started after a tracheostomy was performed, and the patient underwent a bilateral lung transplantation to treat end-stage BOS. After the transplantation, the colonization of XDR A. baumannii caused severe bacterial pneumonia in the early postoperative period. Combined treatment with colistin and meropenem led to recovery from the pneumonia but caused drug-induced renal failure. Because many centers are willing to transplant candidates who are on mechanical ventilation or extracorporeal life support, the incidence of XDR A. baumannii colonization of pretransplant lungs is expected to increase. Further studies are needed to examine pre-transplant management strategies in patients colonized with XDR A. baumannii.

Preoperative Mild-to-Moderate Coronary Artery Disease Does Not Affect Long-Term Outcomes of Lung Transplantation

Preoperative Mild-to-Moderate Coronary Artery Disease Does Not Affect Long-Term Outcomes of Lung Transplantation

Preoperative Mild-to-Moderate Coronary Artery Disease Does Not Affect Long-Term Outcomes of Lung Transplantation

Coronary artery disease has a high prevalence among lung transplant recipients and has historically been a contraindication to transplant at many institutions. In patients with mild-to-moderate coronary artery disease (Mod-CAD) undergoing lung transplant, outcomes are not well defined. All patients who underwent pulmonary transplantation from January 1996 through November 2010 with pretransplant coronary angiogram were included in our study. Recipients of multivisceral, redo, and lobar lung transplants and those who underwent pretransplant coronary revascularization were excluded. Patients were grouped into Mod-CAD or no-coronary artery disease group (No-CAD). Primary end point was overall survival. Secondary end points were 30-day events and the need for posttransplant coronary revascularization. Approximately 539 patients were included in the study: 362 in the No-CAD, 177 in the Mod-CAD group. Patients with Mod-CAD were predominantly male, older, and had a higher body mass index. No difference in either perioperative morbidity and mortality (Mod-CAD, 4.2% vs. No-CAD 3.3%, P=0.705) or late overall mortality was shown between groups. Mod-CAD patients had a shorter hospitalization (median: 12 days vs. 14 days, P=0.009) and required a higher rate of late coronary revascularization procedures (PCI: Mod-CAD vs. No-CAD, 0.3% vs. 4.0%, P=0.0035; CABG: Mod-CAD vs. No-CAD, 0.3% vs. 2.3%, P=0.0411). Mod-CAD does not appear to be associated with increased perioperative morbidity or decreased survival after transplant. Coronary artery disease may worsen and require coronary revascularization in patients with risk factors for disease progression. In these patients, close follow-up and screening for progression of coronary artery disease may help prevent late cardiac morbidity.

Long-term Outcome of Lung Transplantation in Previous Intravenous Drug Users With Talc Lung Granulomatosis

Talc lung granulomatosis results from the intravenous use of medication intended for oral use. Talc (magnesium silicate) acts as filler in some oral medications; when injected intravenously, it deposits in the lungs leading to airflow obstruction and impaired gas exchange. Allocation of donor lungs to previous intravenous drug users is controversial. After a careful selection process, 19 patients with talc lung granulomatosis have received lung allografts inour program. Long-term survival for these patients is excellent and our results suggest the previous use of intravenous drugs should not necessarily preclude lung transplantation.

86 Preoperative Mild or Moderate Coronary Artery Disease (CAD) Does Not Affect Long-Term Outcomes of Lung Transplantation

86 Preoperative Mild or Moderate Coronary Artery Disease (CAD) Does Not Affect Long-Term Outcomes of Lung Transplantation

Viral Infections in Lung Transplant Recipients

Viral infections, including beta-herpes viruses and community respiratory viruses, are frequent pathogens in lung transplant recipients. These pathogens have become increasingly recognized as having a significant role in long-term outcomes of lung transplantation, which has been limited by the frequent development of infections, and chronic allograft dysfunction. Community respiratory viruses, such as influenza and respiratory syncytial virus have been associated with both acute rejection and chronic allograft dysfunction, particularly if early treatment was not administered. beta-herpes viruses, particularly cytomegalovirus (CMV), have long been associated with increased mortality in lung transplant recipients, although the advent of effective antiviral strategies has led to improved morbidity and mortality. Because these pathogens have been associated with altered immune responses against the allograft, a better understanding of immunopathogenesis of viral infections may lead to a broader approach to limit the morbidity from these pathogens.

63: The Influence of HLA-DR Mismatching on Long-Term Outcome of Lung Transplantation Is Masked by a New Immunosuppressive Protocol

63: The Influence of HLA-DR Mismatching on Long-Term Outcome of Lung Transplantation Is Masked by a New Immunosuppressive Protocol

Posttransplant monitoring of pediatric lung transplant recipients

This article reviews current trends in pediatric lung posttransplant management, reveals pitfalls that exist, and introduces additional parameters that may have an impact on long-term survival. A number of parameters are monitored after transplantation to prevent or identify early complications related to lung transplantation in hope of reducing morbidity and mortality. These include routine laboratory studies, imaging, and monitoring of drug levels and lung function. Drug monitoring allows individualization of a patient's immunosuppressive therapy; however, drug levels alone may not reflect the patient's immune status. ImmuKnow is a general immune-monitoring assay that may help guide therapy. Two major complications are rejection and infection, and bronchoscopy is used to differentiate these two entities. Silent rejection may occur and increase the chance of developing bronchiolitis obliterans; therefore, many centers perform surveillance bronchoscopies. Recently, de-novo anti-histocompatibility locus antigen antibodies and gastroesophageal reflux have been associated with poor outcomes, and many centers are monitoring these entities as part of care following lung transplant. There has been little improvement in long-term outcomes of lung transplantation. Current monitoring methods are utilized to maintain or improve outcomes and recently additional monitoring parameters have been identified which hopefully will improve long-term outcomes.

Influence of Donor Characteristics on Outcome After Lung Transplantation: A Multicenter Study

The liberalization of lung-donor criteria and the use of marginal donors have been advocated to face the current shortage of donors in lung transplantation. However, the impact of donor characteristics on the outcome of lung transplantation is still largely unknown. We aimed to determine, on a large cohort of patients, the effect of donors characteristics on short- and long-term outcome of lung transplantation Between 1988 and 1998, a total of 785 adult patients underwent single-lung transplantation (n = 270), bilateral-lung transplantation (n = 251), and heart-lung transplantation (n = 264) in 7 centers in France. We constructed several multivariate models to assess the relationship between donor characteristics and early gas exchange, duration of mechanical ventilation, and long-term survival after lung transplantation. Among donor characteristics, donor gas exchange before harvest was found to be significantly associated with recipient early gas exchange, duration of mechanical ventilation, and long-term survival after adjustment for potential confounding variables. Moreover, nonlinear modeling showed a steep increase in the relative risk of death when donor PaO2/FiO2 before harvest was below 350 (hazard ratio 1.43; 95% confidence interval 1.10-1.85; p = 0.01). Donor and recipient sex mismatch were also found to be significantly associated with long-term survival. Although liberalization of lung-donor criteria may be considered to overcome the shortage of lung donors, our data suggest that the violation of the gas-exchange criterion should be avoided.