Successful Lung Transplantation From Hepatitis C Positive Donor to Seronegative Recipient.

Lung transplantation using RNA+ hepatitis C (HCV+) donors to seronegative recipients is not currently performed due to the very high risk of transmission. Previous reports have shown poor survival when this practice was applied. The emergence of new direct-acting antiviral drugs (DAA) suggests a high chance of sustained virologic response in immunocompetent patients. We report here successful transplantation of lungs from HCV+ donor to HCV- recipient. The recipient was an HCV- patient with chronic lung allograft dysfunction. Viral transmission occurred early posttransplant but excellent clinical outcomes were observed including elimination of HCV after 12 weeks of treatment using DAAs.

Ex Vivo Perfusion Treatment of Infection in Human Donor Lungs.

Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were randomly assigned to two groups. In the antibiotic group (n = 8), lungs underwent EVLP for 12 h with high-dose antibiotics (ciprofloxacin 400 mg or azithromycin 500 mg, vancomycin 15 mg/kg, and meropenem 2 g). In the control group (n = 7), lungs underwent EVLP for 12 h without antibiotics. A quantitative decrease in bacterial counts in bronchoalveolar lavage (BAL) was found in all antibiotic-treated cases but in only two control cases. Perfusate endotoxin levels at 12 h were significantly lower in the antibiotic group compared with the control group. EVLP with broad-spectrum antibiotic therapy significantly improved pulmonary oxygenation and compliance and reduced pulmonary vascular resistance. Perfusate endotoxin levels at 12 h were strongly correlated with levels of perfusates tumor necrosis factor α, IL-1ß and macrophage inflammatory proteins 1α and 1ß at 12 h. In conclusion, EVLP treatment of infected donor lungs with broad-spectrum antibiotics significantly reduced BAL bacterial counts and endotoxin levels and improved donor lung function.

Impact of CLAD Phenotype on Survival After Lung Retransplantation: A Multicenter Study.

Chronic lung allograft dysfunction (CLAD) remains a major problem after lung transplantation with no definitive treatment except redo lung transplantation (re-LTx) in selected candidates. However, CLAD is not a homogeneous entity and different phenotypes exist. Therefore, we aimed to evaluate the effect of CLAD phenotypes on survival after re-LTx for CLAD. Patients who underwent re-LTx for respiratory failure secondary to CLAD in four LTx centers between 2003 and 2013 were included in this retrospective analysis. Bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD) were distinguished using pulmonary function, radiology and explant lung histopathology. Patient variables pre- and post-re-LTx were collected and analyzed. A total of 143 patients underwent re-LTx for CLAD resulting in 94 BOS (66%) and 49 rCLAD (34%) patients. Unadjusted and adjusted survival after re-LTx for rCLAD was worse compared to BOS (HR = 2.60, 1.59-4.24; p < 0.0001 and HR = 2.61, 1.51-4.51; p = 0.0006, respectively). Patients waiting at home prior to re-LTx experienced better survival compared to hospitalized patients (HR 0.40; 0.23-0.72; p = 0.0022). Patients with rCLAD redeveloped CLAD earlier and were more likely to redevelop rCLAD. Survival after re-LTx for rCLAD is worse compared to BOS. Consequently, re-LTx for rCLAD should be critically discussed, particularly when additional peri-operative risk factors are present.

Changes in neurocognitive functioning following lung transplantation.

Although neurocognitive impairment is relatively common among patients with advanced lung disease, little is known regarding changes in neurocognition following lung transplantation. We therefore administered 10 tests of neurocognitive functioning before and 6 months following lung transplantation and sought to identify predictors of change. Among the 49 study participants, native diseases included chronic obstructive pulmonary disease (n = 22), cystic fibrosis (n = 12), nonfibrotic diseases (n = 11) and other (n = 4). Although composite measures of executive function and verbal memory scores were generally within normal limits both before and after lung transplantation, verbal memory performance was slightly better posttransplant compared to baseline (p < 0.0001). Executive function scores improved in younger patients but worsened in older patients (p = 0.03). A minority subset of patients (29%) exhibited significant cognitive decline (i.e. >1 standard deviations on at least 20% of tests) from baseline to posttransplant. Patients who declined were older (p < 0.004) and tended to be less educated (p = 0.07). Lung transplantation, like cardiac revascularization procedures, appears to be associated with cognitive decline in a subset of older patients, which could impact daily functioning posttransplant.

Symptomatic pulmonary allograft Kaposi's sarcoma in two lung transplant recipients.

Kaposi's sarcoma (KS) is associated with solid-organ transplantation, but is extremely rare after lung transplantation. In this report, we describe two unique cases of lung transplant recipients who developed KS in the lung allograft and were treated with sirolimus and liposomal doxorubicin. One patient survived 12 months after the diagnosis of KS; the other survived 3 months after diagnosis and was found to have concomitant EBV-negative, HHV-8-positive B-cell lymphoma. We demonstrate a partial response of pulmonary KS to reduced immunosuppression and the initiation of sirolimus in one patient, as well as an association between increasing HHV-8 viremia and progression of pulmonary KS. Our report highlights the importance of secondary malignancies in patients with transplant-related KS and supports the association between HHV-8 infection and EBV-negative PTLD.

Baseline 6-min walk distance predicts survival in lung transplant candidates.

In a large, prospectively followed, two-center cohort of patients listed for lung transplantation (n = 376), we used Cox proportional hazards models to determine the importance of baseline 6-min walk distance (6MWD) in predicting patient survival. 6MWD used as a continuous variable was a significant predictor of survival after adjusting for other important covariates when transplant was considered as a time-varying covariate (HR for each 500 ft increase in 6MWD = 0.57, 95% CI: 0.43-0.77, p = 0.0002). 6MWD remained an important predictor of survival in models that considered only survival to transplant (HR for each 500 ft increase in 6MWD = 0.41, 95% CI: 0.27-0.62, p < 0.0001) or survival only after transplant (HR for each 500 ft increase in 6MWD = 0.40, 95% CI: 0.22-0.72, p = 0.002). Unadjusted Kaplan-Meier analysis demonstrates significantly different survival by 6MWD tertiles (<900, 900-1200, or >1200 ft, p-value = 0.0001). In the overall model, 6MWD prediction of survival was relatively homogeneous across disease category (6MWD by disease interaction term, p-value = 0.63). Our results demonstrate a significant relationship between baseline 6MWD and survival among patients listed for lung transplantation that exists across all native disease categories and extends through transplantation. The 6MWD is thus a useful measure of both urgency and utility among patients awaiting lung transplantation.