Survival Benefit Of Lung Transplantation Research Articles

Survival benefit of lung transplantation compared with medical management and pulmonary rehabilitation for patients with end-stage COPD.

BackgroundCOPD patients account for a large proportion of lung transplants; lung transplantation survival benefit for COPD patients is not well established.MethodsWe identified 4521 COPD patients in the United Network for Organ Sharing (UNOS) dataset transplanted from May 2005 to August 2016, and 604 patients assigned to receive pulmonary rehabilitation and medical management in the National Emphysema Treatment Trial (NETT). After trimming the populations for NETT eligibility criteria and data completeness, 1337 UNOS and 596 NETT patients remained. Kaplan–Meier estimates of transplant-free survival from transplantation for UNOS, and NETT randomisation, were compared between propensity score-matched UNOS (n=401) and NETT (n=262) patients.ResultsIn propensity-matched analyses, transplanted patients had better survival compared to medically managed patients in NETT (p=0.003). Stratifying on 6 min walk distance (6 MWD) and FEV1, UNOS patients with 6 MWD <1000 ft (∼300 m) or FEV1 <20% of predicted had better survival than NETT counterparts (median survival 5.0 years UNOS versus 3.4 years NETT; log-rank p<0.0001), while UNOS patients with 6 MWD ≥1000 ft (∼300 m) and FEV1 ≥20% had similar survival to NETT counterparts (median survival, 5.4 years UNOS versus 4.9 years NETT; log-rank p=0.73), interaction p=0.01.ConclusionsOverall survival is better for matched lung transplant patients compared with medical management alone. Patients who derive maximum benefit are those with 6 MWD <1000 ft (∼300 m) or FEV1 <20% of predicted, compared with pulmonary rehabilitation and medical management.

Lower Six Minute Walk distance or FEV1 Predict a Survival Benefit of Lung Transplantation compared to Medical Management for End Stage COPD

Although end stage COPD patients account for a large proportion of lung transplants, whether lung transplantation improves survival for COPD patients is not well documented.

Lung transplantation for chronic obstructive pulmonary disease: past, present, and future directions.

Lung transplantation offers an effective treatment modality for patients with end-stage chronic obstructive pulmonary disease (COPD). The exact determination of when to refer, list, and offer transplant as well as the preferred transplant procedure type remains unclear. Additionally, there are special considerations specific to patients with COPD being considered for lung transplantation, including the implications of single lung transplantation on lung cancer risk, native lung hyperinflation, and overall survival. The International Society for Heart and Lung Transplantation's most recent recommendations rely on an assessment of COPD severity based on BODE index. Despite the lack of evidence supporting a mortality benefit of bilateral over single lung transplantation for COPD patients, the majority of transplants performed in this population remain bilateral. Some of the concerns specific to single lung transplantation remain the possibility of de novo native lung cancer and the hemodynamic and physiologic implications of acute native lung hyperinflation. COPD remains the most common worldwide indication for lung transplantation. Ongoing study is still required to assess the overall survival benefit of lung transplantation and assess the overall quality of life impact on the COPD patient population.

Survival Benefit of Lung Transplantation in the Modern Era of Lung Allocation.

Lung transplantation is an accepted and increasingly employed treatment for advanced lung diseases, but the anticipated survival benefit of lung transplantation is poorly understood. To determine whether and for which patients lung transplantation confers a survival benefit in the modern era of U.S. lung allocation. Data on 13,040 adults listed for lung transplantation between May 2005 and September 2011 were obtained from the United Network for Organ Sharing. A structural nested accelerated failure time model was used to model the survival benefit of lung transplantation over time. The effects of patient, donor, and transplant center characteristics on the relative survival benefit of transplantation were examined. Overall, 73.8% of transplant recipients were predicted to achieve a 2-year survival benefit with lung transplantation. The survival benefit of transplantation varied by native disease group (P = 0.062), with 2-year expected benefit in 39.2 and 98.9% of transplants occurring in those with obstructive lung disease and cystic fibrosis, respectively, and by lung allocation score at the time of transplantation (P < 0.001), with net 2-year benefit in only 6.8% of transplants occurring for lung allocation score less than 32.5 and in 99.9% of transplants for lung allocation score exceeding 40. A majority of adults undergoing transplantation experience a survival benefit, with the greatest potential benefit in those with higher lung allocation scores or restrictive native lung disease or cystic fibrosis. These results provide novel information to assess the expected benefit of lung transplantation at an individual level and to enhance lung allocation policy.

Lung transplantation for cystic fibrosis: differential characteristics and outcomes between children and adults.

The survival benefit of lung transplantation (LTx) for cystic fibrosis (CF) patients is well demonstrated. We aim to compare children and adult CF recipients to assess whether there are differences in survival and clinical outcomes, and to identify risk factors for mortality. A retrospective analysis of 442 consecutive LTx performed at our institution in a 20-year period was conducted. CF patients were distributed into two groups: children (age <18 years) and adults (age ≥18 years). Donor and recipient general demographic data, perioperative and postoperative factors including 30-day mortality, survival, primary graft dysfunction (PGD), complications, acute rejection (AR) and chronic lung allograft dysfunction (CLAD) were analysed and compared between groups. Univariable, Kaplan-Meier and Cox regression analyses were performed. The study group included 120 consecutive CF patients: 50 children (13 ± 3 years) and 70 adults (25 ± 6 years) undergoing 111 bilateral, 4 lobar, 4 combined and 1 unilateral LTx. Comparative analysis (children versus adults): survival (overall; 5, 10 and 15 years) 57, 45, 35% vs 67, 55, 43% (P = 0.32); survival (1-year survivors; 5, 10 and 15 years): 75, 64, 46% vs 90, 75, 59% (P = 0.09); 30-day mortality: 14 vs 16% (P = 0.27); urgent LTx: 32 vs 17% (P = 0.04); use of cardiopulmonary bypass (CPB): 56 vs 28% (P = 0.002); intensive care unit stay: 20 ± 19 vs 10 ± 9 days (P = 0.006); AR episodes (n): 1.4 ± 0.7 vs 1.2 ± 0.8 (P = 0.004). Incidence of PGD and freedom from CLAD did not differ between groups. Predictors of mortality were: use of CPB (HR 3.12; 95% CI 1.33-7.35; P < 0.01), post-transplant diabetes mellitus (HR 2.49; 95% CI 1.13-5.43; P = 0.02) and pneumonia episodes within the first month post-transplant (HR 2.82; 95% CI 1.27-6.29; P = 0.01). Paediatric CF patients usually present with poorer pre-transplant status, require CPB more frequently and have a higher incidence of post-LTx diabetes and infections. This might explain the trend towards a better long-term survival observed in adult CF patients.

Survival Benefit of Lung Transplantation for Chronic Obstructive Pulmonary Disease in Sweden

Lung transplantation (LTx) is a therapeutic option for patients with life-threatening chronic obstructive pulmonary disease (COPD) that is refractory to conventional therapies. The survival benefit of LTx for COPD is difficult to assess. The aim of this study was to evaluate the Swedish series of LTx performed to treat COPD and to identify differences in outcome between COPD related to severe alpha-1-antitrypsin deficiency (AATD) and COPD with normal alpha-1-antitrypsin (AAT) levels. We retrospectively reviewed the data of 342 patients (128 AATD and 214 non-AATD) receiving lung transplants for end stage COPD from 1990 through2012. The majority (71%) of patients received a single lung transplant. The median survival time after LTx for all COPD patients was 9 years (95% confidence interval [CI]: 8 to 10). Non-AATD recipients had a shorter survival time than AATD recipients, 6 years (95% CI: 5.0 to 8.8) versus 12 years (95% CI: 9.6 to 13.5, p= 0.000). Mortality was higher among non-AATD recipients after adjusting for age, pack-years of smoking, body mass index, oxygen therapy use, exercise capacity, donor age, cytomegalovirus mismatch, and transplant type (hazard ratio 1.70, 95% CI: 1.02 to 2.82). The 5-year and 10-year survival rates for the AATD recipients were 75% and 59%, respectively, compared with 60% and 31% for the non-AATD recipients. Early deaths were mainly due to cardio/cerebrovascular accidents and sepsis, and late deaths to bronchiolitis obliterans syndrome and pulmonary infections. Survival after LTx is significantly better for patients with severe AATD and end stage COPD than for the patients with COPD related to cigarette smoking.

(58) - Outcomes and Survival Benefit of Lung Transplantation for Cystic Fibrosis: Single-Center Experience of 309 Consecutive Cases

(58) - Outcomes and Survival Benefit of Lung Transplantation for Cystic Fibrosis: Single-Center Experience of 309 Consecutive Cases

P203 Lung transplantation and survival in idiopathic pulmonary fibrosis - an Irish perspective

Introduction and ObjectivesIdiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial pneumonia of unknown aetiology. Its clinical course is unpredictable but invariably leads to progressive respiratory failure and death. Median...

Assessing the Causal Effect of Organ Transplantation on the Distribution of Residual Lifetime

Because the number of patients waiting for organ transplants exceeds the number of organs available, a better understanding of how transplantation affects the distribution of residual lifetime is needed to improve organ allocation. However, there has been little work to assess the survival benefit of transplantation from a causal perspective. Previous methods developed to estimate the causal effects of treatment in the presence of time-varying confounders have assumed that treatment assignment was independent across patients, which is not true for organ transplantation. We develop a version of G-estimation that accounts for the fact that treatment assignment is not independent across individuals to estimate the parameters of a structural nested failure time model. We derive the asymptotic properties of our estimator and confirm through simulation studies that our method leads to valid inference of the effect of transplantation on the distribution of residual lifetime. We demonstrate our method on the survival benefit of lung transplantation using data from the United Network for Organ Sharing.

Survival Benefit of Lung Transplant for Cystic Fibrosis since Lung Allocation Score Implementation

The survival benefit of lung transplantation (LT) in adult patients with cystic fibrosis (CF) is debated. We sought to assess the survival benefit of LT in adult patients with CF. We used data from the United Network for Organ Sharing Registry to identify adult patients with CF on a wait list for LT in the United States between 2005 and 2009. Survival times while on the wait list and after LT were modeled by use of a Cox model that incorporated transplantation status as a time-dependent covariate. Evolution in lung allocation score (LAS) while on the wait list was used as a surrogate for disease severity. We fitted a model for the joint distribution of survival and longitudinal disease process (LAS over time). A total of 704 adult patients with CF were registered on a wait list during the study period. The cumulative incidence of LT was 39.3% (95% confidence interval, 35.6-42.9%) at 3 months and 64.7% (61.0-68.4%) at 12 months, whereas the incidence of death while on the wait list at the same times was 8.5% (6.4-10.6%) and 12.9% (10.3-15.5%), respectively. Survival after LT was 96.5% (94.7-98.2%) at 3 months; 88.4% (85.1-91.8%) at 12 months; and 67.8% (59.9-76.8%) at 3 years. LT conferred a 69% reduction in the instantaneous risk of death (51-80%). The interaction between LAS and LT was significant: the higher the LAS, the greater the survival benefit of LT (P < 0.001). LT confers a survival benefit for adult patients with CF.

Survival Benefit of Lung Transplantation in Japan: Extreme Donor Shortage and the Potential Role of Living Transplantation

Purpose Cadaveric lung transplantation (LTx) in Japan has multiple limitations including 1) extreme donor shortage (only 44 cadaveric brain-death donors with 37 cadaveric LTx cases across Japan in 2011); 2) limited recipient age below 55 for bilateral and 60 for single LTx; 3) priority of LTx determined solely by waiting time on the list. Thus, living LTx could be the only life-saving option for those who cannot wait for cadaveric LTx. We examined the survival benefit of LTx (either cadaveric or living) among those who were listed for cadaveric LTx in Japan. Methods and Materials The relative risks of death on the waiting list and death after LTx were evaluated using multivariate Cox models. Reception of LTx was treated as censored on the list. Since the initiation of the current Japanese listing system in 1998, patients who were listed by July 31, 2012 were included in the study. Results 617 patients were listed and 174 received LTx (139 cadaveric, 35 living). Average waiting time for cadaveric LTx on the list was 966±676 (10-4507) days. In multivariate Cox regression models, idiopathic pulmonary fibrosis (IPF) showed the most significant risk of death on waiting list (n=115; hazard ratio (HR), 3.53; confidence interval (CI), 2.34-5.31; reference, PAH), while the risk of death after LTx (n=23, including cadaveric (n=15) and living (n=8)) was moderate (HR, 0.85; CI, 0.36-2.01; ref, PAH). Treating the conditions of being on cadacveric-LTx list and being post-LTx as time-dependent covariates, the estimated survival benefit of LTx was most significant in IPF (HR, 0.26; CI, 0.097-0.746). This trend persisted in subanalyses of living and cadaveric LTx. Conclusions IPF showed the most significant survival benefit by LTx. This is explained by their poor prognosis without LTx and reasonable outcome after LTx. Adult-to-adult living LTx, which appears suitable for relatively old IPF patients with small thorax, remains the only life-saving option for many IPF patients who cannot wait for cadaveric LTx.

Survival benefit of lung transplantation in individuals with severe α1-anti-trypsin deficiency (PiZZ) and emphysema

The objective of lung transplantation (LTx) is to prolong life, but the survival benefit for patients with severe α(1)-anti-trypsin deficiency (PiZZ) and emphysema is still unclear. The aim of this study was to assess whether PiZZ patients who have undergone lung transplantation (the lung transplant group, TxG) do better than patients who have continued on the usual medical therapy (the non-transplant group, NTxG). Between 1990, when the first patient received a lung transplant in Sweden, until June 2010, a total of 83 PiZZ patients with severe emphysema underwent transplantation. Seventy appropriate controls were identified from the Swedish National AAT Deficiency Registry. Each control was matched with a patient who had received a lung transplant, for age, gender, smoking history (number of pack-years) and lung function at the time of transplantation. Both controls and lung transplant patients had low spirometric values with a mean FEV(1) of 23 ± 6% and 22 ± 9% of predicted value, respectively (not a statistically significant difference). Of the 83 transplant patients, 62 (75%) underwent single-lung transplantation (SLTx). During follow-up, 37 (45%) deaths occurred in the TxG and 45 (64%) in the NTxG. In the TxG, the estimated median survival time was 11 years (95% confidence interval [CI] 9 to 14 years), compared with 5 years (95% CI 4 to 6 years) for the NTxG (p = 0.006). The most common cause of death was pulmonary infection among the transplant patients (38%) and respiratory failure (60%) among the controls. Lung transplantation significantly improves long-term survival of patients with severe α(1)-anti-trypsin deficiency (PiZZ) and emphysema.

Update on pediatric lung allocation in the United States

In May 2005, a system was established to allocate deceased donor lungs to adolescents and adults in the United States based on models of waiting list mortality and one-yr transplant survival benefit. The goal of the new system is to reduce the mortality of patients awaiting lung transplant and maximize the survival benefit of lung transplantation. This article discusses the considerations given to pediatric candidates during the development of the LAS, early outcome observations with emphasis on pediatric candidates and finally, future changes and impact on pediatric lung transplantation.

Disease-Specific Survival Benefit of Lung Transplantation in Adults: A National Cohort Study

The lung transplantation candidate population is heterogeneous and survival benefit has not been established for all patient groups. UK data from a cohort of 1997 adult (aged > or = 16), first lung transplant candidates (listed July 1995 to July 2006, follow-up to December 2007) were analyzed by diagnosis, to assess mortality relative to continued listing. Donor lungs were primarily allocated according to local criteria. Diagnosis groups studied were cystic fibrosis (430), bronchiectasis (123), pulmonary hypertension (74), diffuse parenchymal lung disease (564), chronic obstructive pulmonary disease (COPD, 647) and other (159). The proportion of patients in each group who died while listed varied significantly (respectively 37%, 48%, 41%, 49%, 19%, 38%). All groups had an increased risk of death at transplant, which fell below waiting list risk of death within 4.3 months. Thereafter, the hazard ratio for death relative to listing ranged from 0.34 for cystic fibrosis to 0.64 for COPD (p < 0.05 all groups except pulmonary hypertension). Mortality reduction was greater after bilateral lung transplantation in pulmonary fibrosis patients (p = 0.049), but not in COPD patients. Transplantation appeared to improve survival for all groups. Differential waiting list and posttransplant mortality by diagnosis suggest further use and development of algorithms to inform lung allocation.

Systemic Inhibition of NF-κB Activation Protects from Silicosis

BackgroundSilicosis is a complex lung disease for which no successful treatment is available and therefore lung transplantation is a potential alternative. Tumor necrosis factor alpha (TNFα) plays a central role in the pathogenesis of silicosis. TNFα signaling is mediated by the transcription factor, Nuclear Factor (NF)-κB, which regulates genes controlling several physiological processes including the innate immune responses, cell death, and inflammation. Therefore, inhibition of NF-κB activation represents a potential therapeutic strategy for silicosis.Methods/FindingsIn the present work we evaluated the lung transplant database (May 1986–July 2007) at the University of Pittsburgh to study the efficacy of lung transplantation in patients with silicosis (n = 11). We contrasted the overall survival and rate of graft rejection in these patients to that of patients with idiopathic pulmonary fibrosis (IPF, n = 79) that was selected as a control group because survival benefit of lung transplantation has been identified for these patients. At the time of lung transplantation, we found the lungs of silica-exposed subjects to contain multiple foci of inflammatory cells and silicotic nodules with proximal TNFα expressing macrophage and NF-κB activation in epithelial cells. Patients with silicosis had poor survival (median survival 2.4 yr; confidence interval (CI): 0.16–7.88 yr) compared to IPF patients (5.3 yr; CI: 2.8–15 yr; p = 0.07), and experienced early rejection of their lung grafts (0.9 yr; CI: 0.22–0.9 yr) following lung transplantation (2.4 yr; CI:1.5–3.6 yr; p<0.05). Using a mouse experimental model in which the endotracheal instillation of silica reproduces the silica-induced lung injury observed in humans we found that systemic inhibition of NF-κB activation with a pharmacologic inhibitor (BAY 11-7085) of IκBα phosphorylation decreased silica-induced inflammation and collagen deposition. In contrast, transgenic mice expressing a dominant negative IκBα mutant protein under the control of epithelial cell specific promoters demonstrate enhanced apoptosis and collagen deposition in their lungs in response to silica.ConclusionsAlthough limited by its size, our data support that patients with silicosis appear to have poor outcome following lung transplantation. Experimental data indicate that while the systemic inhibition of NF-κB protects from silica-induced lung injury, epithelial cell specific NF-κB inhibition appears to aggravate the outcome of experimental silicosis.

Determinants of the Survival Benefit of Lung Transplantation in Patients with Chronic Obstructive Pulmonary Disease

Although chronic obstructive pulmonary disease is the first indication for lung transplantation, the benefit of the procedure in terms of survival remains debated. To estimate the determinants of the survival benefit of lung transplantation in patients with chronic obstructive pulmonary disease. Using information from the United Network for Organ Sharing database on 8,182 patients, we developed an approach based on numerical simulations to estimate the survival effect of lung transplantation. The main outcome measure was the difference between median survival with transplantation and that without transplantation measured from time of transplant list registration. Survival benefit was greater with double than with single lung transplantation (mean difference, 307 d [95% confidence interval, 217-523]). With double lung transplantation, 44.6% of patients would gain 1 year or more, 29.4% would gain or lose less than 1 year, and 26% would lose 1 year or more. Major determinants of the survival effect of transplantation were systolic pulmonary artery pressure, FEV(1), body mass index, exercise capacity, functional status, and the need for continuous mechanical ventilation or oxygen. For instance, 79% of patients with an FEV(1) less than 16% of the predicted value would gain 1 year or more with double lung transplantation as compared with only 11% of patients with an FEV(1) of more than 25%. We identified several factors associated with the survival benefit of lung transplantation. External validation of our models is required before translating these results into clinical practice.

Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis

Objective Although lung transplantation is viewed as an acceptable option for patients with end-stage idiopathic pulmonary fibrosis, the survival benefit of this approach is still debated. This study examined whether there was a survival benefit of lung transplantation in a cohort of patients referred to our transplant center with a diagnosis of idiopathic pulmonary fibrosis according to American Thoracic Society criteria. Methods Forty-six patients accepted for lung transplantation during a 12-year period with a diagnosis of idiopathic pulmonary fibrosis form the basis of this study. Survival benefit offered by lung transplantation was assessed using Cox proportional-hazards modeling, with patients on a waiting list as the control group. Results Twenty-eight patients underwent lung transplantation (27 single and 1 double), 16 patients died while waiting, and 2 patients remained on the active waiting list. Diagnosis of idiopathic pulmonary fibrosis was made on histologic examination of the explanted lung or lung biopsy before lung transplantation. There was a pattern of usual interstitial pneumonia in 31 cases (67%). The 15 remaining patients fulfilled all American Thoracic Society criteria for idiopathic pulmonary fibrosis. The median waiting time for organs was 51 days. Survival after lung transplantation was 79.4% at 1 year, 63.5% at 2 years, and 39% at 5 years. The multivariable analysis showed that lung transplantation reduced the risk of death by 75% (95% confidence interval, 8%-86%; P = .03) after adjustment on potential confounding variables. Conclusions Lung transplantation is effective in improving the survival of selected patients affected by idiopathic pulmonary fibrosis.

Survival benefit of lung transplantation in cystic fibrosis patients infected with B. Cepacia

Survival benefit of lung transplantation in cystic fibrosis patients infected with B. Cepacia

Effect of Diagnosis on Survival Benefit of Lung Transplantation for End-Stage Lung Disease

Effect of Diagnosis on Survival Benefit of Lung Transplantation for End-Stage Lung Disease

Effect of diagnosis on survival benefit of lung transplantation for end-stage lung disease

Although certain forms of end-stage lung disease are debilitating, whether the associated mortality rate exceeds that of transplantation is unclear. We undertook analysis to clarify the survival benefit of lung transplantation for various types of end-stage lung disease. We analysed data for all patients listed for transplantation in the USA for emphysema, cystic fibrosis, or interstitial pulmonary fibrosis in the years 1992-94. The numbers of patients entered on the waiting list, post-transplantation, died waiting, and currently waiting were: emphysema group 1274, 843, 143, and 165; cystic fibrosis group 664, 318, 193, and 59; interstitial pulmonary fibrosis group 481, 230, 160, and 48. A time-dependent non-proportional hazard analysis was used to assess the risk of mortality after transplantation relative to that for patients on the waiting list. The clearest survival benefit from lung transplantation occurred in the cystic fibrosis group. The relative risks of transplantation compared with waiting were 0.87, 0.61, and 0.61 at 1 month, 6 months, and 1 year (p = 0.008), respectively. For interstitial pulmonary fibrosis, the corresponding relative risks were 2.09, 0.71, and 0.67 (p = 0.09). No survival benefit was apparent in the emphysema group. The risks of transplantation relative to waiting were 2.76, 1.12, and 1.10 at 1 month, 6 months, and 1 year, respectively, and the relative risk did not decrease to below 1.0 during 2 years of follow-up. These findings suggest that lung transplantation does not confer a survival benefit in patients with end-stage emphysema by 2 years of follow-up. Other benefits not accounted for in this analysis such as improved quality of life, however, may justify lung transplantation for these patients.