Results of Lung Transplantation in Patients With Cystic Fibrosis

Lung transplantation (LT) is the only available option for patients with cystic fibrosis (CF) with end-stage lung disease. We reviewed our experience with LT in patients with end-stage CF (CFLT) to identify variables associated with survival and to compare the results with other indications for LT (OILT). Between October 1993 and October 2007, we performed 259 consecutive LTs in 250 patients for treatment of various end-stage pulmonary conditions. The indications for LT were CF in 78 patients idiopathic pulmonary fibrosis in 76, COPD in 64, bronchiectasis in 11, alfa-1-antitrypsin deficit in 5, primary pulmonary hypertension in 4, bronchiolitis obliterans syndrome in 4, and other indications in 11. Our study group comprised 78 patients with CF (30.11%) (CFLT). We observed significant differences in the actuarial survival between the CFLT and OILT groups. Perioperative mortality and the incidence of bronchiolitis obliterans syndrome were comparable in both groups. We found that in patients with CF, LT performed under urgency code (mechanical ventilation) showed no significant difference from LT performed electively insofar as long-term survival, early death, or perioperative death. The functional results in the CFLT group were excellent. We observed significant improvement in PaO₂, PaCO₂, forced vital capacity, and forced expiratory volume in the first second of expiration at 6, 12, and 36 months compared with the pretransplantation baseline values.     

Testicular Cancer in a Lung Transplant Patient With Cystic Fibrosis: A Case Report

BackgroundCystic fibrosis (CF) is one of the most common genetic disorders that develops from a mutation of the cystic fibrosis transmembrane regulator gene. Patients with CF are known to be at risk for malignancies, and lung transplantation–associated immunosuppression further increases this risk.Case ReportWe describe a case of a 29-year-old male patient with CF who developed testicular cancer 14 months after a lung transplantation. Immunosuppressive therapy included antithymocyte globulin induction and tacrolimus, mycophenolate, and prednisolone maintenance therapy as compared to standard alemtuzumab induction, followed by tacrolimus and prednisolone, as used in our center. He underwent semicastration and refused chemotherapy. Immunosuppressive treatment was changed to tacrolimus, everolimus, and prednisolone, which did not influence excellent graft function. This case report highlights the importance of uro-oncological observation of patients with CF following lung transplantations.     

National Healthcare Delivery Systems Influence Lung Transplant Outcomes for Cystic Fibrosis

Successful lung transplantation (LTx) depends on multiple components of healthcare delivery and performance. Therefore, we conducted an international registry analysis to compare post‐LTx outcomes for cystic fibrosis (CF) patients using the UNOS registry in the United States and the National Health Service (NHS) Transplant Registry in the United Kingdom. Patients with CF who underwent lung or heart–lung transplantation in the United States or United Kingdom between January 1, 2000 and December 31, 2011 were included. The primary outcome was all‐cause mortality. Kaplan–Meier analysis and Cox proportional hazards regression evaluated the effect of healthcare system and insurance on mortality after LTx. 2,307 US LTx recipients and 451 individuals in the United Kingdom were included. 894 (38.8%) US LTx recipients had publically funded Medicare/Medicaid insurance. US private insurance and UK patients had improved median predicted survival compared with US Medicare/Medicaid recipients (p < 0.001). In multivariable Cox regression, US Medicare/Medicaid insurance was associated with worse survival after LTx (US private: HR0.78,0.68–0.90,p = 0.001 and UK: HR0.63,0.41–0.97, p = 0.03). This study in CF patients is the largest comparison of LTx in two unique health systems. Both the United States and United Kingdom have similar early survival outcomes, suggesting important dissemination of best practices internationally. However, the performance of US public insurance is significantly worse and may put patients at risk.     

Lobar Lung Transplantation From Deceased Donors: A Valid Option for Small-Sized Patients With Cystic Fibrosis

BackgroundSmall-sized patients with cystic fibrosis usually face long waiting times for a suitable lung donor. Reduced-size lung transplantation (LTx) was promoted to shorten waiting times. We compared donor and recipient characteristics and outcome in lobar ([L]) versus full-size ([FS]) lung recipients.MethodsBetween July 1, 1991, and February 28, 2011, 535 isolated LTx were performed, including 74 in cystic fibrosis patients (8 L, 66 FS). Patients were followed up until September 2012.Results[L] recipients were younger, smaller, and lighter. Sex, waiting times, and donor data (age, sex, height, weight, PaO₂/FiO₂, and ventilation time) were comparable. Cardiopulmonary bypass was used more often in [L]; cold ischemia was comparable for first lung but longer in [L] for second lung; implantation times were comparable. In-hospital mortality rate was 0% in [L] versus 3% in [FS]. Both intensive care unit and hospital stay were longer in [L]. Grade 3 primary graft dysfunction was more pronounced in [L] at T0 and at T48. FEV₁ increased significantly in both groups from preoperative value. Bronchiolitis obliterans syndrome was absent in [L] and diagnosed in 18 patients in [FS], accounting for 6 of 15 late deaths. All [L] are still alive. No differences in survival were found between the groups.ConclusionsAlthough hindered by a higher incidence of primary graft dysfunction, L-LTx is a viable option with excellent survival and pulmonary function comparable to FS-LTx.     

Renal Histopathological Lesions After Lung Transplantation in Patients with Cystic Fibrosis

We have analyzed the evolution of renal status beyond the perioperative period in patients with cystic fibrosis (CF) undergoing lung transplantation and presented histological analysis of 15 patients biopsied for an episode of accelerated renal function loss (RFL).
Episodes of accelerated RFL after the perioperative period occurred in 32.5% of patients and significantly raised the risk of end-stage renal disease (ESRD) (p < 0.001). The histologic lesions associated with these episodes differed according to the time of onset. Early onset (10 cases) was associated with tubulointerstitial lesions in the form of oxalate nephropathy (50%) and/or a pigmented tubulopathy (80%). This latter was correlated with treatment with antiviral agents (p = 0.002) and aminoside and glycopeptide antibiotics (p = 0.03) administered in the month preceding biopsy. Lesions in late episodes of accelerated RFL (5 cases) were principally vascular: arteriosclerosis and arteriolosclerosis (p = 0.007, p = 0.00002), correlated with diabetic glomerulosclerosis or focal segmental glomerulosclerosis in the absence of prominent diabetic changes. Specific calcineurin-inhibitor nephrotoxicity was present in 93.3% of biopsies associated with thrombotic microangiopathy in 46.7% of cases.
The identification of specific etiologies of progressive kidney disease in patients with CF after lung transplantation should permit more effective post-transplant care of these patients.     

Phenotyping Established Chronic Lung Allograft Dysfunction Predicts Extracorporeal Photopheresis Response in Lung Transplant Patients

Chronic lung allograft dysfunction (CLAD) remains the leading cause of mortality in lung transplant recipients after the first year. Treatment remains limited and unpredictable. Existing data suggests extracorporeal photopheresis (ECP) may be beneficial. This study aimed to identify factors predicting treatment response and the prognostic implications. A single center retrospective analysis of all patients commencing ECP for CLAD between November 1, 2007 and September 1, 2011 was performed. In total 65 patients were included, 64 of whom had deteriorated under azithromycin. Median follow‐up after commencing ECP was 503 days. Upon commencing ECP, all patients were classified using proposed criteria for emerging clinical phenotypes, including “restrictive allograft syndrome (RAS)”, “neutrophilic CLAD (nCLAD)” and “rapid decliners”. At follow‐up, 8 patients demonstrated ≥10% improvement in FEV₁, 27 patients had stabilized and 30 patients exhibited ≥10% decline in FEV₁. Patients fulfilling criteria for “rapid decliners” (n = 21, p = 0.005), RAS (n = 22, p = 0.002) and those not exhibiting neutrophilia in bronchoalveolar lavage (n = 44, p = 0.01) exhibited poorer outcomes. ECP appears an effective second line treatment in CLAD patients progressing under azithromycin. ECP responders demonstrated improved progression‐free survival (median 401 vs. 133 days). Proposed CLAD phenotypes require refinement, but appear to predict the likelihood of ECP response.     

Combined Heart-Lung-Liver Transplantation for Patients With Cystic Fibrosis: The Australian Experience

BackgroundCombined multivisceral transplantation has emerged as a therapeutic option for a select patient cohort; however, clinical decision-making remains complex and controversial. The aim of this study was to examine patient characteristics, operative complications, and long-term outcomes of all patients who have undergone combined heart-lung-liver transplantation (HLLTx) in Australia.MethodsIn this study, we performed a retrospective analysis of all adult patients who have undergone combined HLLTx in Australia to date. Recipient clinical characteristics, waitlist, and transplant outcomes are described.ResultsEight adult patients have received HLLTx at a single Australian transplant center. Recipients of HLLTx have typically been young (median age, 30.1 years; range, 24-37), underweight (median body mass index, 19.8 kg/m²; range, 16.2-30.4) patients with cystic fibrosis (n = 8, 100%) with severe airflow obstruction (median forced expiratory volume in the first second of expiration, 24% predicted; range, 17%-48%) accompanied by liver cirrhosis confirmed on histopathology (n = 8, 100%). Despite relative preservation of synthetic function and low model for end-stage liver disease scores (median, 8; range, 6-17), all recipients had complications of portal hypertension prior to transplantation, with many patients having suffered life-threatening variceal hemorrhage. In this cohort, HLLTx was associated with overall posttransplant survival of 87.5% at 30 days, 71.4% at 1 year, and 42.9% at 5 years. Listing for combined HLLTx was associated with prolonged waitlist times relative to bilateral sequential single-lung transplantation (median 556 vs 56 days, respectively), however waitlist mortality and/or delisting was comparable between groups.ConclusionsTaken together, these findings highlight the opportunities and challenges facing combined (heart-) lung and liver transplantation in patients with multiorgan failure.