Utility of the Stanford Integrated Psychosocial Assessment for Transplant in predicting outcomes before and after lung transplantation.

Background: Optimizing donor use and achieving maximal survival following lung transplantation (LTx) require a pretransplant assessment that identifies clinical, physiological, and psychosocial patient factors associated with both poor and optimal post-LTx survival. We examined the utility of a psychosocial tool, the Stanford Integrated Psychosocial Assessment for Transplant (SIPAT), to identify patient suitability for LTx, as well as its association with clinical outcomes before and after LTx.

Methods: This was a retrospective single-center study analyzing LTx assessment clinical variables (age, gender, diagnosis, functional capacity, nutrition, renal function), with a particular focus on the utility of the SIPAT score, to predict patient suitability for LTx.

The molecular features of chronic lung allograft dysfunction in lung transplant airway mucosa.

Background: Many lung transplants fail due to chronic lung allograft dysfunction (CLAD). We recently showed that transbronchial biopsies (TBBs) from CLAD patients manifest severe parenchymal injury and dedifferentiation, distinct from time-dependent changes. The present study explored time-selective and CLAD-selective transcripts in mucosal biopsies from the third bronchial bifurcation (3BMBs), compared to those in TBBs.

Transcripts associated with chronic lung allograft dysfunction in transbronchial biopsies of lung transplants.

Transplanted lungs suffer worse outcomes than other organ transplants with many developing chronic lung allograft dysfunction (CLAD), diagnosed by physiologic changes. Histology of transbronchial biopsies (TBB) yields little insight, and the molecular basis of CLAD is not defined. We hypothesized that gene expression in TBBs would reveal the nature of CLAD and distinguish CLAD from changes due simply to time posttransplant.

Outcomes Following Extracorporeal Photopheresis for Chronic Lung Allograft Dysfunction Following Lung Transplantation: A Single-Center Experience.

Introduction: Survival following lung transplantation (LTx) is limited by the development of chronic lung allograft dysfunction (CLAD), for which there are few effective therapies and no standardized management. Several small studies have demonstrated the effectiveness of extracorporeal photopheresis (ECP) as a therapeutic option for CLAD.

Methods: A retrospective descriptive audit of 12 LTx recipients who received rescue ECP for CLAD over 5 years (2013-2018) at the Alfred Hospital, Melbourne, Australia, was completed.

A donor PaO/FiO < 300 mm Hg does not determine graft function or survival after lung transplantation.

Background: A donor arterial PO/FiO (P/F ratio) of less than the 300 threshold would frequently result in either exclusion of the donor or placement of the lungs on ex vivo lung perfusion (EVLP). The aim was to investigate the veracity of the P/F ratio threshold of 300 for donor lung acceptability.

Methods: In 93 brain dead lung donors, arterial blood gases were drawn in the intensive care unit (ICU) just before procurement and each of the 4 donor pulmonary veins in the operating room (OR).

Enrichment of Cytomegalovirus-induced NKG2C+ Natural Killer Cells in the Lung Allograft.

Background: In lung transplant recipients, immunosuppressive medications result in impaired antiviral immunity and a propensity for cytomegalovirus (CMV) reactivation within the lung allograft. Natural killer (NK) cells play a key role in immunity to CMV, with an increase in the proportion of NK cells expressing activating CD94-NKG2C receptors in the blood being a strong correlate of CMV infection. Whether a similar increase in NKG2C NK cells occurs in lung transplant recipients following CMV reactivation in the allograft and if such cells contribute to viral control remains unclear.

HLA class II Eplet mismatch predicts De Novo DSA formation post lung transplant.

The use of algorithms such as HLAMatchmaker to redefine donor-recipient HLA matching is gaining increasing attention. Our research has previously demonstrated that higher HLA class II eplet mismatches correlated with the development of chronic lung allograft dysfunction (CLAD). In this study of lung transplant recipients we prospectively examined the association between donor-recipient HLA eplet mismatches as defined by HLAMatchmaker (version 2.

A successful aggressive surgical and medical approach to pulmonary artery obstruction due to Mycobacterium abscessus infection post lung transplantation.

Mycobacterium abscessus infection following lung transplantation has historically been associated with poor outcomes. We report a case of bilateral lung retransplantation complicated by obstruction of the right pulmonary artery secondary to M. abscessus mycotic aneurysm.

Donor-Derived Mycoplasma hominis and an Apparent Cluster of M. hominis Cases in Solid Organ Transplant Recipients.

Background: Invasive and disseminated Mycoplasma hominis infections are well recognized but uncommon complications in solid organ transplant recipients. In a single center, a cluster of M. hominis infections were identified in lung transplant recipients from the same thoracic intensive care unit (ICU).

Clinical effectiveness of early posaconazole suspension pre-emptive therapy in lung transplant recipients: The Alfred's experience.

Objectives: This study describes the clinical outcomes and therapeutic drug monitoring (TDM) following posaconazole suspension pre-emptive therapy in lung transplant (LTx) recipients.

Methods: This was a single-centre, retrospective cohort study evaluating posaconazole suspension pre-emptive therapy in LTx recipients between January 2009 and December 2015.

Results: Forty-two LTx recipients were prescribed posaconazole suspension pre-emptively.

Outcomes of adolescent recipients after lung transplantation: An analysis of the International Society for Heart and Lung Transplantation Registry.

Background: Recipient adolescent age for non-lung solid-organ transplantation is associated with higher rates of rejection, graft loss and mortality. Although there have been no studies specifically examining adolescent outcomes after lung transplantation (LTx), limited data from the International Society of Heart and Lung Transplantation (ISHLT) Registry suggest that a similar association may exist. Recently, adolescence has been defined as 10 to 24 years of age, taking into account the biologic and sociologic transitions that occur during this age interval.

Substantial Increases Occur in Serum Activins and Follistatin during Lung Transplantation.

Background: Lung transplantation exposes the donated lung to a period of anoxia. Re-establishing the circulation after ischemia stimulates inflammation causing organ damage. Since our published data established that activin A is a key pro-inflammatory cytokine, we assessed the roles of activin A and B, and their binding protein, follistatin, in patients undergoing lung transplantation.

Antibody-mediated rejection.

Purpose Of Review: Pulmonary antibody-mediated rejection (AMR) while contributing to acute and chronic allograft dysfunction remains a diagnostic and therapeutic challenge. The diagnostic tenets upon which AMR is defined will be reviewed in the light of recent studies.

Recent Findings: The introduction of solid phase assays such as the Luminex platform has provided a wealth of quantitative data on the presence of anti-human leukocyte antigen (HLA) donor-specific antibodies (DSA).

Early bronchiolitis obliterans syndrome shows an abnormality of perfusion not ventilation in lung transplant recipients.

Long-term survival of lung transplant patients is limited, principally because of Bronchiolitis Obliterans Syndrome (BOS). BOS is primarily classified based on airflow obstruction however there is recent data to suggest that the rejection process can lead to a restrictive ventilatory defect with involvement of the pulmonary vasculature. This study evaluates perfusion heterogeneity in different BOS stages by measuring the relative dispersion (RD) of an arterial spin labelling MRI blood flow image.

Antibody-mediated rejection in lung transplantation: fable, spin, or fact?

The lung transplant community continues to struggle with the diagnosis and management of antibody-mediated rejection. The four diagnostic tenets of donor-specific antibodies, C4d staining, histopathologic changes, and allograft dysfunction, which were largely derived from the early Banff meetings on renal transplantation, have somewhat arbitrarily been applied to lung transplantation. With the passage of time, it is increasingly apparent that merits of these diagnostic pillars are less robust in lung transplantation.

A consensus document for the selection of lung transplant candidates: 2014--an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation.

The appropriate selection of lung transplant recipients is an important determinant of outcomes. This consensus document is an update of the recipient selection guidelines published in 2006. The Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) organized a Writing Committee of international experts to provide consensus opinion regarding the appropriate timing of referral and listing of candidates for lung transplantation.

Evolving experience of treating antibody-mediated rejection following lung transplantation.

Background: The importance of antibody-mediated rejection (AMR) following lung transplantation remains contentious. In particular, the diagnostic criteria suggested to define AMR, namely the presence of donor-specific antibodies (DSA), C4d immunoreactivity, histological features and allograft dysfunction are not always readily applicable or confirmatory in lung transplantation.

Methods: In a retrospective single-center study of 255 lung transplant recipients (LTR), we identified 9 patients in whom a clinical diagnosis of AMR was made within 12months of transplant, and define the immunological, histological, clinical features, as well as the therapeutic response of this cohort.

Sustained function of genetically modified porcine lungs in an ex vivo model of pulmonary xenotransplantation.

Background: Xenotransplantation could provide a solution to the donor shortage that is currently the major barrier to solid-organ transplantation. The ability to breed pigs with multiple genetic modifications provides a unique opportunity to explore the immunologic challenges of pulmonary xenotransplantation.

Methods: Explanted lungs from wild-type and 3 groups of genetically modified pigs were studied: (i) α1,3-galactosyltransferase gene knockout (GTKO); (ii) GTKO pigs expressing the human complementary regulatory proteins CD55 and CD59 (GTKO/CD55-59); and (iii) GTKO pigs expressing both CD55-59 and CD39 (GTKO/CD55-59/CD39).

Impact of commonly used transplant immunosuppressive drugs on human NK cell function is dependent upon stimulation condition.

Lung transplantation is a recognised treatment for patients with end stage pulmonary disease. Transplant recipients receive life-long administration of immunosuppressive drugs that target T cell mediated graft rejection. However little is known of the impact on NK cells, which have the potential to be alloreactive in response to HLA-mismatched ligands on the lung allograft and in doing so, may impact negatively on allograft survival.

Proliferating bronchial webs after lung transplantation.

This case details the decline in lung function due to bronchial webs in a lung transplant recipient. The decline occurred 2 years after transplantation and, despite therapy, the webs, which had an inflammatory component, became treatment resistant. We outline the pathological findings and management strategies used, discuss the evidence in the literature, and offer possible causes for these unusual clinical findings.

High levels of mannose-binding lectin are associated with poor outcomes after lung transplantation.

Background: Mannose-binding lectin (MBL) is a key molecule of the innate immune system and, in addition to the classical and alternative pathways, a principle driver of complement activation. Genetic mutations of MBL are common, result in low serum levels of MBL, and are associated with increased infection risk in solid-organ transplant recipients.

Methods: We performed a retrospective study of MBL2 genotype and plasma and bronchoalveolar lavage (BAL) MBL levels in 37 lung transplant recipients (LTR).

Long-term outcomes from bronchoscopic lung volume reduction using a bronchial prosthesis.

Background And Objective: We evaluated long-term safety and lung function outcomes in a cohort of patients with severe upper-zone heterogeneous emphysema who underwent bronchoscopic lung volume reduction (BLVR) performed with the Emphasys one-way valve.

Methods: A retrospective cohort study was undertaken to assess long-term outcomes in 23 consecutive patients who underwent upper lobe BLVR between July 2001 and November 2003 as part of a first-in-humans study. Long-term follow up (>12 months) was available in 16/23 patients (median duration of follow up 64 months (range 15-90 months)).

Lung transplant survival despite unexpected pulmonary metastatic thyroid cancer in the explant.

A recent history of malignancy is considered by most transplant units as an absolute contraindication to transplantation. This particularly applies to the adult population, where the higher incidence of malignancy is related to age and exposure to relevant risk factors (e.g.