K. Halloran

Outcomes of Lung Transplantation in Recipients with Hepatitis C Virus Infection

Hepatitis C virus (HCV) infection negatively impacts patient and graft survival following nonhepatic solid organ transplantation. Most data, however, are in kidney transplant, where despite modest impact on outcomes, transplantation is recommended for those with mild to moderate hepatic fibrosis given overall benefit compared to remaining on dialysis. In lung transplantation (LuTx), there is little data on outcomes and international guidelines are vague on the criteria under which transplant should be considered. The University of Alberta Lung Transplant Program routinely considers patients with HCV for lung transplant based on criteria extrapolated from the kidney transplant literature. Here we describe the outcomes of 27 HCV‐positive, compared to 443 HCV‐negative LuTx recipients. Prior to transplant, five patients were treated for HCV and cured. At the time of transplant, 14 patients remained HCV RNA positive. The 1‐, 3‐, and 5‐year survival were similar in HCV RNA–positive versus ‐negative recipients at 93%, 77%, and 77% versus 86%, 75%, and 66% (p = 0.93), respectively. Long‐term follow‐up in eight patients demonstrated no significant progression of fibrosis. In our cohort, HCV did not impact LuTx outcomes and in the era of interferon‐free HCV therapies this should not be a barrier to LuTx.

Case Report of Vertebral Osteomyelitis and Mycotic Abdominal Aortic Aneurysm Caused by Scedosporium apiospermum in a Lung Transplant Patient With Cystic Fibrosis

Cystic fibrosis patients are frequently plagued by infections, often with unusual or hardy organisms. Their infections are only complicated by transplantation. In this report, we review the case of a young woman who had a double lung transplant secondary to cystic fibrosis who developed a lumbar osteomyelitis/discitis several years after transplantation. After treatment, she went on to develop a mycotic abdominal aortic aneurysm. The patient underwent thoracic and abdominal aortic replacement, and histopathology revealed Scedosporium apiospermum infection. The patient recovered well from surgery and was discharged home on long-term antifungal therapy. This represents the first reported case of S apiospermum mycotic aneurysm in a lung transplant patient, and possibly the largest number and longest duration of S apiospermum infections reported in a single patient.

Lung Transplantation from Hepatitis C Viremic Donors to Uninfected Recipients

1. Königshoff M, Rojas M. Galectin-3: the bridge over troubled waters. Am J Respir Crit Care Med 2012;185:473–475. 2. Fenster BE, Lasalvia L, Schroeder JD, Smyser J, Silveira LJ, Buckner JK, et al. Galectin-3 levels are associated with right ventricular functional and morphologic changes in pulmonary arterial hypertension. Heart Vessels 2016;31:939–946. 3. Hao M, Li M, Li W. Galectin-3 inhibition ameliorates hypoxia-induced pulmonary artery hypertension. Mol Med Rep 2017;15:160–168. 4. Taraseviciene-Stewart L, Kasahara Y, Alger L, Hirth P, Mc Mahon G, Waltenberger J, et al. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J 2001; 15:427–438. 5. Gomez-Arroyo J, Voelkel NF, Bogaard HJ, Taraseviciene-Stewart L. Usefulness of a mousemodel of reversible pulmonary arterial hypertension: be cautious, choose carefully. Am J Respir Crit Care Med 2012;185:1326. 6. Harrison SA, Marri SR, Chalasani N, Kohli R, Aronstein W, Thompson GA, et al. Randomised clinical study: GR-MD-02, a galectin-3 inhibitor, vs. placebo in patients having non-alcoholic steatohepatitis with advanced fibrosis. Aliment Pharmacol Ther 2016;44:1183–1198. 7. Barman SA, Chen F, Su Y, Dimitropoulou C, Wang Y, Catravas JD, et al. NADPH oxidase 4 is expressed in pulmonary artery adventitia and contributes to hypertensive vascular remodeling. Arterioscler Thromb Vasc Biol 2014;34:1704–1715. 8. Mazurek JA, Horne BD, Saeed W, Sardar MR, Zolty R. Galectin-3 levels are elevated and predictive of mortality in pulmonary hypertension. Heart Lung Circ 2017;26:1208–1215. 9. Guo S, Feng Z. Galectin-3 mediates the effect of PDGF on pulmonary arterial hypertension. Int J Clin Exp Med 2015;8:15302–15307. 10. Wang X, Wang Y, Zhang J, Guan X, Chen M, Li Y, et al. Galectin-3 contributes to vascular fibrosis in monocrotaline-induced pulmonary arterial hypertension rat model. J Biochem Mol Toxicol 2017;31:e21879.

Mechanical Circulatory Support as a Bridge to Lung Transplantation: A Single Canadian Institution Review

Background Lung transplant (LTx) waitlists continue to grow internationally. Consequently, more patients are progressing to require mechanical circulatory support (MCS) as a bridge to transplantation (BTT). MCS strategies include interventional lung assist (iLA) and venovenous (VV) and venoarterial (VA) extracorporeal membrane oxygenation (ECMO). We review our series of patients bridged with MCS while listed for LTx. Methods All consecutive patients, listed for LTx requiring MCS as a BTT at the University of Alberta from 2004 to 2015, were included. Patient demographics and outcomes were compared for the 3 groups (iLA, VV-ECMO, and VA-ECMO). Results Of the 24 patients supported with MCS devices, 17 were successfully transplanted and 7 died waiting. In total, 25% (n = 6) were bridged with VA-ECMO, 54% (n = 13) with VV-ECMO, and 21% (n = 5) with iLA. Overall, 71% of patients were bridged successfully to LTx. The 1-year survival posttransplantation was 88%. Conclusion We have demonstrated the feasibility of utilizing the MCS modalities of VA-ECMO, VV-ECMO, and most recently iLA, as a BTT. MCS is a viable strategy for BTT, offering improved survival outcomes for decompensating adult patients awaiting LTx, resulting in excellent survival posttransplantation.

Baseline lung allograft dysfunction is associated with impaired survival after double-lung transplantation

BACKGROUND The prognostic value of defining normal vs abnormal baseline post-transplant lung function (or baseline lung allograft dysfunction [BLAD]) has not been studied using standardized reference values of percent predicted of the population. Our aim was to assess the association between BLAD and survival in double-lung transplant recipients and assess for potential pre-transplant donor and recipient risk factors for BLAD. METHODS We conducted a retrospective cohort study of double-lung transplant recipients in our program during the period 2004 to 2009. We defined normal baseline function as both forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) ≥80% predicted on at least 2 consecutive tests ≥3 weeks apart; we defined BLAD as failure to meet these criteria. We used a Cox regression model to assess the association between BLAD and survival. We used logistic regression to assess potential pre-transplant donor and recipient factors associated with BLAD. RESULTS Of 178 patients double-lung transplant recipients eligible for study, 75 (42%) met the criteria for BLAD. BLAD was associated with impaired survival (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.41 to 3.54]) via Cox regression compared to patients with normal baseline, and lower baseline was associated with greater risk of death in a dose-dependent fashion. Pre-transplant factors associated with BLAD included interstitial lung disease (ILD) as an indication for transplant (odds ratio [OR] 2.66, 95% CI 1.17 to 6.15) and heavy donor smoking history (OR 3.07, 95% CI 1.17 to 8.43). CONCLUSIONS BLAD is dynamic risk state associated with impaired survival after double-lung transplantation, and should be considered when physiologically phenotyping patients.

Banff Lung Report: Current knowledge and future research perspectives for diagnosis and treatment of pulmonary antibody-mediated rejection (AMR)

The Lung session of the 2017 14th Banff Foundation for Allograft Pathology Conference, Barcelona focused on the multiple aspects of antibody‐mediated rejection (AMR) in lung transplantation. Multidimensional approaches for AMR diagnosis, including classification, histological and immunohistochemical analysis, and donor‐ specific antibody (DSA) characterization with their current strengths and limitations were reviewed in view of recent research. The group also discussed the role of tissue gene expression analysis in the context of unmet needs in lung transplantation. The current best practice for monitoring of AMR and the therapeutic approach are summarized and highlighted in this report. The working group reached consensus of the major gaps in current knowledge and focused on the unanswered questions regarding pulmonary AMR. An important outcome of the meeting was agreement on the need for future collaborative research projects to address these gaps in the field of lung transplantation.

Extracorporeal Lung Support as a Bridge to Diagnosis of Pulmonary Tumor Embolism

Bridging to diagnosis is an emerging technique used in end-stage cardiorespiratory failure that prolongs a patients life using various modalities of extracorporeal lung support (ECLS) to achieve antemortem diagnosis. Pulmonary tumor embolism occurs when cell clusters travel from primary malignancies through venous circulation to the lungs, causing respiratory failure through inflammatory and venoocclusive pathways. Due to its nonspecific symptomatology, pulmonary tumor embolism remains an elusive diagnosis antemortem. Herein, we bridge a patient who presented in acute respiratory failure to the diagnosis of pulmonary tumor embolism from a gastric signet-ring cell carcinoma using ECLS modalities including venoarterial extracorporeal membrane oxygenation and centrally cannulated Novalung pumpless extracorporeal lung assist. We demonstrate the utility of this approach in diagnostically uncertain cases in unstable patients who are potentially acceptable ECLS and transplant candidates.