Publications by authors named "Bronwyn Levvey"

Background: Although the demand for allografts continuously surpasses the supply, the majority of lungs offered for transplant are declined based on various factors, including donor age. This in turn sustains the wait-list mortality of patients with end-stage pulmonary disease.

Methods: In this single-center, observational cohort study, we investigated the impact of donor age on graft survival.

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The use of extracorporeal life support (ECLS) throughout the perioperative phase of lung transplantation requires nuanced planning and execution by an integrated team of multidisciplinary experts. To date, no multidisciplinary consensus document has examined the perioperative considerations of how to best manage these patients. To address this challenge, this perioperative utilization of ECLS in lung transplantation consensus statement was approved for development by the International Society for Heart and Lung Transplantation Standards and Guidelines Committee.

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HLA (HLA) are a major barrier to transplant success, as HLA-A and -B molecules are principal ligands for T-cells, and HLA-C for Killer cell Immunoglobulin-like Receptors (KIR), directing Natural Killer (NK) cell function. HLA-C molecules are designated "C1" or "C2" ligands based on residues 77 and 80, which determine the NK cell responses. Here, we investigated donor/recipient HLA-C mismatch associations with the development of chronic lung allograft dysfunction (CLAD) following lung transplantation (LTx).

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Purpose Of Review: Lung transplantation activity continues to be limited by the availability of timely quality donor lungs. It is apparent though that progress has been made. The steady evolution of clinical practice, combined with painstaking scientific discovery and innovation are described.

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Article Synopsis
  • COVID-19 has significantly affected lung transplant recipients (LTR), who were previously at high risk for severe outcomes, but recent data shows improved results thanks to vaccinations and new treatments.
  • A study of 279 LTR at Alfred Health revealed that only a small percentage experienced severe disease or mortality, with effective antiviral treatments and vaccinations providing considerable protection.
  • Post-infection lung function also showed minimal decline, with only 17% of patients experiencing a significant drop, suggesting that prior rejection issues were the main factor influencing lung function post-COVID.
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Article Synopsis
  • - The study investigates the impact of non-HLA antibodies in the development of chronic lung allograft dysfunction (CLAD), a major issue for lung transplant recipients, by analyzing data from 226 patients.
  • - Researchers identified a specific group of 18 non-HLA antibodies that were more prevalent in CLAD patients compared to those who were stable, with the presence of both non-HLA and donor-specific HLA antibodies creating an even higher risk for developing CLAD.
  • - Findings suggest that the presence of these antibodies contributes significantly to the risk of CLAD and graft loss, highlighting the importance of monitoring humoral immunity in lung transplant patients.
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Peak spirometry after single lung transplantation (SLTx) for interstitial lung disease (ILD) is lower than after double lung transplantation (DLTx), however the pathophysiologic mechanisms are unclear. We aim to assess respiratory mechanics in SLTx and DLTx for ILD using oscillometry. Spirometry and oscillometry (tremoflo C-100) were performed in stable SLTx and DLTx recipients in a multi-center study.

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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.

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Outcomes after lung transplantation (LTx) remain poor, despite advances in sequencing technology and development of algorithms defining immunologic compatibility. Presently, there is no consensus regarding the best approach to define human leukocyte antigen (HLA) compatibility in LTx. In this study, we compared 5 different HLA compatibility tools in a high-resolution HLA-typed, clinically characterized cohort, to determine which approach predicts outcomes after LTx.

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Unlabelled: Cytomegalovirus (CMV) infection causes significant morbidity and mortality in lung transplant recipients. Current guidelines use pretransplant donor and recipient CMV serostatus to predict the risk of subsequent CMV replication and length of antiviral prophylaxis. Immunological monitoring may better inform the risk of CMV infection in patients, thereby allowing for improved tailoring of antiviral prophylaxis.

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Article Synopsis
  • Recent technological and supportive changes in Australian transplantation are significant and numerous.
  • These advancements are often implemented without comprehensive understanding from the broader clinical community about their origins and impacts.
  • The aim is to clarify these changes and explore future efforts to enhance patient outcomes.
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Background: Baseline lung allograft dysfunction (BLAD), the failure to achieve ≥80%-predicted spirometry after lung transplant (LTx), is associated with impaired survival. Physiologic abnormalities in BLAD are poorly understood. Airway oscillometry measures respiratory system mechanics and may provide insight into understanding the mechanisms of BLAD.

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Unlabelled: Currently, the assessment of immunological risk in lung transplantation (LTx) does not completely consider HLA compatibility at the molecular level. We have previously demonstrated the association of HLA eplets in predicting chronic lung allograft dysfunction following LTx; however, the associations between HLA eplet mismatch (epMM) loads and overall survival are unknown.

Methods: In this retrospective, single-center study, 277 LTx donor-recipient pairs were high resolution HLA typed and analyzed for HLA epMMs using HLAMatchmaker (version 3.

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Lung transplantation is limited by a lack of suitable lung donors. In Australia, the national donation organisation (DonateLife) has taken a major role in optimising organ donor identification. However, the potential outside the DonateLife network hospitals remains uncertain.

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The continuing shortage of pulmonary grafts from donors after brain death has led to a resurgence of interest in lung transplantation from donors after circulatory death (DCD). Most lungs from donors after withdrawal from life-sustaining therapy can be recovered rapidly and transplanted directly without ex-vivo assessment in case functional warm ischemic time is limited to 30 to 60 min. The potential of the DCD lung pool is still underutilized and should be maximized in countries with existing legislation.

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Immune sensitization, defined as the presence of alloreactive donor-specific antibodies (DSA), is associated with increased wait-times and inferior transplant outcomes. Identifying pretransplant DSA with a physical cell-based assay is critical in defining immunological risk. However, improved solid phase antibody detection has provided the potential to forgo this physical assay.

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Background: Problematic mitral regurgitation (MR) may develop following lung transplantation (LTx). There is limited information on the management of MR in LTx patients, as such we sought to evaluate our centre's experience.

Methods: From 2000 to 2019, 1,054 patients underwent LTx at our centre (896 bilateral, 158 single).

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Background: In Australia, increased organ donation and subsequent lung transplantation (LTx) rates have followed enhanced donor identification, referral and management, as well as the introduction of a donation after circulatory death (DCD) pathway. However, the number of patients waiting for LTx still continues to exceed the number of lung donors and the search for further suitable donors is critical.

Methods: All 2014-2018 Victorian DonateLife hospital deaths after intensive care unit (ICU) admission were analysed retrospectively to quantify unrecognised lung donors using current criteria, as well as novel time-extended (90 mins-24 hrs post-withdrawal) DCD lung donors.

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Background: Access to lung transplantation (LTx) and rates of waiting list and posttransplant mortality for patients with interstitial lung disease (ILD) remain problematic. We evaluated the outcomes of ILD patients listed for LTx at our institution.

Methods: Between 2012 and 2018, adult patients with ILD were listed and transplanted from a donor-pool that included extended criteria and donation after circulatory-determined death donors.

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Unlabelled: Chronic lung allograft dysfunction (CLAD) is the major factor limiting survival post lung transplantation (LTx) with limited effective therapeutic options. We report our 12-y experience of antithymocyte globulin (ATG) as second-line CLAD therapy.

Methods: Clinical and lung function data were collected on LTx patients receiving ATG.

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Although the use of donation after circulatory death (DCD) donors has increased lung transplant activity, 25-40% of intended DCD donors do not convert to actual donation because of no progression to asystole in the required time frame after withdrawal of cardiorespiratory support (WCRS). No studies have specifically focussed on DCD lung donor progression. This retrospective study reviewed intended DCD lung donors to make a prediction model of the likelihood of progression to death using logistic regression and classification and regression tree (CART).

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Background: Optimizing immunosuppression in lung transplant recipients (LTR) is crucially important in minimizing the risk of infection and rejection. Quantiferon®-Monitor (QFM) is a candidate immune function biomarker which has not yet been rigorously evaluated in the lung transplant setting. The aim of this prospective cohort study was to explore relationships between QFM results, immunosuppression, and infection/rejection in LTR.

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Background: Even in the extended-criteria era, the reasons for declining lung donors are not always clear. Furthermore, it has not been determined how many actual declined lungs would be retrieved by ex vivo lung perfusion (EVLP) beyond that already achieved in centers with an existing high utilization rate.

Methods: This retrospective study reviewed all lung donor referrals between 2014 and 2018, including detailed formal referrals and preliminary notifications.

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Background: Anti-viral treatments to control cytomegalovirus (CMV) after lung transplantation (LTx) are associated with toxicity and anti-viral resistance. Cellular immunotherapy with virus-specific cytotoxic T cells has yielded promising results but requires donor/recipient matching. γδ T cells are involved in anti-viral immunity and can recognize antigens independently of major histocompatibility complex molecules and may not require the same level of matching.

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