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Background: The prognostic value of evaluating spirometry at a fixed time point using standardized population reference has not previously been evaluated. Our aim was to assess the association between spirometric phenotype at 12 months (Spiro 12M ), survival and incidence of chronic lung allograft dysfunction (CLAD) in bilateral lung transplant recipients., Methods: We conducted a retrospective cohort study of bilateral lung transplant recipients transplanted between January 2003 and September 2012. We defined Spiro 12M as the mean of the 2 prebronchodilator FEV 1 measurements 12-month post-transplant. Normal spirometry was defined as FEV 1 /FVC ≥0.7 and FEV1≥80% and FVC≥80% predicted population-based values for that recipient. Abnormal spirometry was defined as failure to attain normal function by 12-months. We used a Cox regression model to assess the association between Spiro 12M , survival, and CLAD. We used logistic regression to assess potential pretransplant donor and recipient factors associated with abnormal Spiro 12M RESULTS: One hundred and eleven (51%) lung transplant recipients normalized their Spiro 12M . Normal Spiro 12M was associated improved survival (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.41-0.88], p = 0.009. Each 10% decrement in FEV 1 increased the risk of death in a stepwise fashion. Additionally, CLAD was reduced in those with normal Spiro 12M (HR:0.65, 95%CI:0.46-0.92, p = 0.016). Donor smoking history (OR:2.93, 95% CI:1.21-7.09; p = 0.018) and mechanical ventilation time in hours (OR:1.03, 95% CI:1.004-1.05; p = 0.02) were identified as independent predictors of abnormal Spiro 12M ., Conclusions: Abnormal Spiro 12M is associated with increased mortality and the development of CLAD. The effect is dose dependent with increased dysfunction corresponding to increased risk. This assessment of phenotype at 12-months can easily be incorporated into standard of care., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Activin A, a member of the transforming growth factor β super-family, is a key regulator of multiple biological pathways including the physiological processes of organ development and homeostasis; as well as the pathological processes of inflammation, remodelling and fibrosis. Dysregulation of activin A and its naturally occurring antagonist follistatin, contribute to the development of disease in multiple organ systems. In this review, we summarize the regulation of activin A, its dysregulated expression in a number of respiratory diseases and postulate its potential role in contributing to allograft dysfunction following lung transplantation.

The number of lung transplants performed globally continues to increase year after year. Despite this growing experience, long-term outcomes following lung transplantation continue to fall far short of that described in other solid-organ transplant settings. Chronic lung allograft dysfunction (CLAD) remains common and is the end result of exposure to a multitude of potentially injurious insults that include alloreactivity and infection among others. Central to any description of the clinical performance of the transplanted lung is an assessment of its physiology by pulmonary function testing. Spirometry and the evaluation of forced expiratory volume in 1 s and forced vital capacity, remain core indices that are measured as part of routine clinical follow-up. Spirometry, while reproducible in detecting lung allograft dysfunction, lacks specificity in differentiating the different complications of lung transplantation such as rejection, infection and bronchiolitis obliterans. However, interpretation of spirometry is central to defining the different 'chronic rejection' phenotypes. It is becoming apparent that the maximal lung function achieved following transplantation, as measured by spirometry, is influenced by a number of donor and recipient factors as well as the type of surgery performed (single vs double vs lobar lung transplant). In this review, we discuss the wide range of variables that need to be considered when interpreting lung function testing in lung transplant recipients. Finally, we review a number of novel measurements of pulmonary function that may in the future serve as better biomarkers to detect and diagnose the cause of the failing lung allograft., (© 2014 Asian Pacific Society of Respirology.)

To describe our experience to date of four children with end-stage lung disease who have been bridged with ECMO to successful lung transplantation in our institution. Between March 2006 and June 2012, a total of 21 pediatric patients successfully underwent lung transplantation within The Alfred's lung transplantation program. This included four children who were bridged on ECMO prior to transplantation according to the "ECMO bridge to transplant" protocol and whose clinical notes and outcomes were reviewed. Lung transplantation is an established life-saving treatment for patients with severe lung disease, but remains limited due to scarcity of suitable donor organs. This is a particular issue in the pediatric setting, where the smaller child waits disproportionately longer compared with adult patients for size-matched donor lungs. As ECMO has become more widely accepted, its use as a bridge to lung transplantation in pediatric patients with severe acute lung injury or end-stage chronic lung disease has been considered. The medical notes from the four pediatric patients were retrospectively reviewed. Our report describes excellent short- and medium-term outcomes in a small number of children who have been bridged to transplant on ECMO., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The plasminogen activation system (PAS) and the plasmin it forms have dual roles in chronic respiratory diseases including asthma, chronic obstructive pulmonary disease and interstitial lung disease. Whilst plasmin-mediated airspace fibrinolysis is beneficial, interstitial plasmin contributes to lung dysfunction because of its pro-inflammatory and tissue remodeling activities. Recent studies highlight the potential of fibrinolytic agents, including small molecule inhibitors of plasminogen activator inhibitor-1 (PAI-1), as treatments for chronic respiratory disease. Current data also suggest that interstitial urokinase plasminogen activator is an important mediator of lung inflammation and remodeling. However, further preclinical characterization of uPA as a drug target for lung disease is required. Here we review the concept of selectively targeting the contributions of PAS to treat chronic respiratory disease., (Copyright © 2013. Published by Elsevier Ltd.)

Aspergillus fumigatus can cause different clinical manifestations/phenotypes in lung transplant (LTx) recipients and patients with chronic respiratory diseases. It can also precipitate chronic lung allograft dysfunction (CLAD) in LTx recipients. Many host factors have been linked with the severity of A. fumigatus infection, but little is known about the contribution of different A. fumigatus strains to the development of different phenotypes and CLAD. We used multi-locus microsatellite typing (MLMT) to determine if there is a relationship between strain (i.e., genotype) and phenotype in 60 patients post LTx or with chronic respiratory disease across two time periods (1 November 2006–31 March 2009 and 1 November 2015–30 June 2017). The MLMT (STRAf) assay was highly discriminatory (Simpson's diversity index of 0.9819–0.9942) with no dominant strain detected. No specific genotype–phenotype link was detected, but several clusters and related strains were associated with invasive aspergillosis (IA) and colonisation in the absence of CLAD. Host factors were linked to clinical phenotypes, with prior lymphopenia significantly more common in IA cases as compared with A. fumigatus-colonised patients (12/16 [75%] vs. 13/36 [36.1%]; p = 0.01), and prior Staphylococcus aureus infection was a significant risk factor for the development of IA (odds ratio 13.8; 95% confidence interval [2.01–279.23]). A trend toward a greater incidence of CMV reactivation post-A. fumigatus isolation was observed (0 vs. 5; p = 0.06) in LTx recipients. Further research is required to determine the pathogenicity and immunogenicity of specific A. fumigatus strains. [ABSTRACT FROM AUTHOR]

Background and objectives Little is known about the prevalence of anxiety in interstitial lung disease ( ILD), and the contributors to depression are not clear. The aim of this study was to determine the prevalence and predictors of anxiety and depression in people with ILD. Methods One hundred and twenty-four individuals with ILD (age 64 years (standard deviation 12), 48 idiopathic pulmonary fibrosis) participated. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale to determine likely cases and borderline cases. Associations with demographic data, respiratory function, 6-min walk and Modified Medical Research Council Dyspnoea Scale ( MMRC) were examined. Results The prevalence of anxiety was 31%, with clinically significant anxiety in 12%. Depression was present in 23% of individuals, with 7% having clinically significant depression. Independent predictors of anxiety were a higher MMRC score ( P = 0.005, odds ratio ( OR) for case 2.60, 95% confidence interval 1.37 to 4.92) and higher nadir SpO2 during walking ( P = 0.003, OR for case 1.16, 1.04-1.30). Independent predictors of depression were a higher MMRC score ( P = 0.006, case OR 3.84, 1.25-11.78, borderline case OR 2.44, 1.14-5.19) and a greater number of comorbidities ( P = 0.003, case OR 2.02, 0.97-4.21, borderline case OR 2.26, 1.30-3.93). Conclusions Anxiety and depression are present in a significant minority of individuals with ILD. Dyspnoea and comorbidities are important contributors that may be amenable to intervention. [ABSTRACT FROM AUTHOR]

Purpose: This study reports the feasibility and safety of novel second-generation bronchoscopic lung volume reduction (LVR) technology, independent of collateral ventilation. Description: Eleven patients with severe heterogeneous emphysema underwent unilateral bronchoscopic application of vapor thermal energy (mean 4.9 cal/g alveolar tissue; range, 3 to 7.5) with bronchial thermal vapor ablation (BTVA) aiming to induce a controlled inflammatory airway and parenchymal response with resultant LVR. Evaluation: Nine women and 2 men, with a mean age of 61 years, forced expiratory volume in 1 second (FEV1) of 0.77 ± 0.17 L (32% predicted), residual volume (RV) of 4.1 ± 0.9 L (219% predicted), and gas transfer of 7.8 ± 2.2 (34% predicted), underwent unilateral upper lobe treatments. Serious adverse events in 5 included probable bacterial pneumonia and exacerbations of airways disease in 2. Although no important FEV1 or RV changes occurred during 6 months of follow-up, gas transfer improved, 16% to 9.0% ± 2.1% (38% predicted), the Medical Research Council Dyspnoea Score improved from 2.6 to 2.1, and the St. George Respiratory Questionnaire Total Score improved from 64.4 at baseline to 49.1. Conclusions: These preliminary data on unilateral BTVA therapy confirm feasibility, an acceptable safety profile, and the potential for efficacy. [Copyright &y& Elsevier]

With the introduction of ciclosporin (cyclosporine) into routine clinical practice 20 years ago, lung transplantation has become an established treatment for patients with advanced lung disease. Most lung transplant recipients routinely continue to receive a triple-drug maintenance immunosuppressive regimen consisting of a calcineurin inhibitor, an antimetabolite and corticosteroids. The use of antibody-based induction therapy remains common, although there has been a shift away from T cell-depleting agents, such as antithymocyte globulin, towards anti-interleukin-2 receptor monoclonal antibodies. Recent years have seen the introduction of sirolimus and everolimus, immunosuppressive drugs that act by blocking growth factor-driven cell proliferation. While the newer immunosuppressive drugs have been rigorously evaluated in large randomised trials in kidney, liver and cardiac transplantation, such studies are lacking in lung transplantation. Despite a shift towards more potent immunosuppressive regimens that incorporate tacrolimus and mycophenolate mofetil, the development of chronic allograft rejection, as manifested by the bronchiolitis obliterans syndrome continues to negatively impact on the long-term survival of lung transplant recipients. This article reviews the evidence for the immunosuppressive regimens used during induction and maintenance of patients undergoing lung transplantation, and discusses current strategies in the management of chronic rejection. [ABSTRACT FROM AUTHOR]

See article, page 524 [ABSTRACT FROM AUTHOR]

Access to timely suitably size-matched quality organs remains a challenge for pediatric (pLTx) and adult (aLTx) lung transplantation. The outcomes of donation after circulatory death (DCD) donor lungs from pediatric or adult donors are rarely reported. This report describes the controlled DCD and pLTx activity (≤ age 18 years) and outcomes since 2006 when DCD LTx started at our center at the Alfred Hospital. Forty pLTx have been performed since 2006, 9 utilizing DCD and 31 donation after brain death (DBD) donors. A total of 22 pLTX have been conducted since 2012 (when DCD pLTx started); 9 DCD LTx (median age 15 years), including 4 pediatric DCD donors (mean age 8 years) and 5 adult (including 2 cutdown bilobar) DCD LTx donors (mean age 43 years). The other 13 pLTx utilized DBD donors — 8 pediatric (mean age 9 years) and 5 adult (including 2 cutdown bilobar) DBD LTx donors (mean age 44 years). One hundred percent survived 1 year, and 7 of 9 DCD pLTx (78%) are alive (median of 1,316 days), with one Chronic Lung Allograft Dysfunction (CLAD) death at 531 days and one renal failure death at 1,813 days. Three waiting list pediatric deaths occurred at 166 and 320 days. Since 2006, 77 pediatric donors have been used for LTx. Fifteen of these were DCD donors (median age 16 years), 11 of 15 have been used for aLTx (73%). Ten of 11 aLTx are alive at a median 1,992 days (91%) with 1 death at Day 2,444 from CLAD. Controlled DCD provide a significant and quality donor lung pool to increase LTx opportunities for pediatric patients (and adults) with terminal lung disease. [ABSTRACT FROM AUTHOR]