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Sintes H.,Hospital Of La Santa Creu I Sant Pau | Sibila O.,Hospital Of La Santa Creu I Sant Pau | Sibila O.,Biomedical Research Institute Sant Pau | Waterer G.W.,University of Western Australia | And 2 more authors.
European Respiratory Monograph | Year: 2014

Community-acquired pneumonia (CAP) remains a leading cause of death worldwide and a major burden on healthcare resources. CAP may vary in severity, from a mild disease managed in the community to a very severe illness requiring hospital or intensive care unit (ICU) admission. Illness severity is not always obvious at presentation and therefore a range of severity assessment tools have been developed to aid clinical decision making. Severity assessment toolshavebeenproventoaidthesiteofcaredecision,increasing the proportion of low-risk patients managed at home. Most severity tools were initially developed to predict mortality risk, and recent validation studies have demonstrated that risk of death is not always a good indicator for ICU care. Other severity scores have been developed recently with the aim to predict ICU admission or other clinical decisions. The introduction of biomarkers as prognostic indicators of severe CAP, whether used alone or in conjunction with other clinical severity of illness scores, is a promising area for future research. There remains no consensus on which is the best severity assessment tool in CAP. The most recent and relevant data regarding clinical prediction tools and biomarkers to predict severity in CAP are reviewed in this chapter. © 2014.


Strange G.,Monash University | Strange G.,Lung Institute of Western Australia | Playford D.,The University of Notre Dame Australia | Playford D.,University of Western Australia | And 10 more authors.
Heart | Year: 2012

Background: Pulmonary hypertension (PHT) lacks community prevalence and outcome data. Objective: To characterise minimum 'indicative'prevalences and mortality data for all forms of PHT in a selected population with an elevated estimated pulmonary artery systolic pressure (ePASP) on echocardiography. Design: Observational cohort study. Setting: Residents of Armadale and the surrounding region in Western Australia (population 165 450) referred to our unit for transthoracic echocardiography between January 2003 and December 2009. Results: Overall, 10 314 individuals (6.2% of the surrounding population) had 15 633 echo studies performed. Of these, 3320 patients (32%) had insufficient TR to ePASP and 936 individuals (9.1%, 95% CI 8.6% to 9.7%) had PHT, defined as, ePASP>40 mm Hg. The minimum 'indicative'prevalence for all forms of PHT is 326 cases/100 000 inhabitants of the local population, with left heart disease-associated PHT being the commonest cause (250 cases/100 000). 15 cases of pulmonary arterial hypertension/100 000 inhabitants were identified and an additional 144 individuals (15%) with no identified cause for their PHT. The mean time to death for those with ePASP >40 mm Hg, calculated from the first recorded ePASP, was 4.1 years (95% CI 3.9 to 4.3). PHT increased mortality whatever the underlying cause, but patients with PHT from left heart disease had the worst prognosis and those with idiopathic pulmonary arterial hypertension receiving disease-specific treatment the best prognosis. Risk of death increased with PHT severity: severe pulmonary hypertension shortened the lifespan by an average of 1.1 years compared with mild pulmonary hypertension. Conclusions: In this cohort, PHT was common and deadly. Left heart disease was the most common cause and had the worst prognosis and treated pulmonary arterial hypertension had the best prognosis.


Kolios G.,Democritus University of Thrace | Moodley Y.,University of Western Australia | Moodley Y.,Royal Perth Hospital | Moodley Y.,Lung Institute of Western Australia
Respiration | Year: 2013

Stem cells are a population of undifferentiated cells characterized by the ability to extensively proliferate (self-renewal), usually arise from a single cell (clonal), and differentiate into different types of cells and tissue (potent). There are several sources of stem cells with varying potencies. Pluripotent cells are embryonic stem cells derived from the inner cell mass of the embryo and induced pluripotent cells are formed following reprogramming of somatic cells. Pluripotent cells can differentiate into tissue from all 3 germ layers (endoderm, mesoderm, and ectoderm). Multipotent stem cells may differentiate into tissue derived from a single germ layer such as mesenchymal stem cells which form adipose tissue, bone, and cartilage. Tissue-resident stem cells are oligopotent since they can form terminally differentiated cells of a specific tissue. Stem cells can be used in cellular therapy to replace damaged cells or to regenerate organs. In addition, stem cells have expanded our understanding of development as well as the pathogenesis of disease. Disease-specific cell lines can also be propagated and used in drug development. Despite the significant advances in stem cell biology, issues such as ethical controversies with embryonic stem cells, tumor formation, and rejection limit their utility. However, many of these limitations are being bypassed and this could lead to major advances in the management of disease. This review is an introduction to the world of stem cells and discusses their definition, origin, and classification, as well as applications of these cells in regenerative medicine. Copyright © 2012 S. Karger AG, Basel.


Tobin C.L.,Sir Charles Gairdner Hospital | Lee Y.C.G.,Sir Charles Gairdner Hospital | Lee Y.C.G.,Lung Institute of Western Australia | Lee Y.C.G.,University of Western Australia
Current Opinion in Pulmonary Medicine | Year: 2012

PURPOSE OF REVIEW: Pleural infection remains a common and difficult problem to manage in the 21st century. Despite advances in modern healthcare, the rising incidence and mortality of empyema highlights a need for better understanding of the disease and more effective strategies in its diagnosis and treatment. RECENT FINDINGS: Recent studies have progressed our knowledge and understanding of the bacteriology and pathophysiology of pleural infection. However, rather than providing firm conclusions, examination of current literature provokes several unanswered questions on most aspects of the disease. SUMMARY: This review aims to challenge traditional current concepts and approaches to clinical practice in pleural infection, to stimulate debate and research into potential novel future therapies. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.


Chung L.P.,University of Western Australia | Chung L.P.,Lung Institute of Western Australia | Waterer G.W.,University of Western Australia | Waterer G.W.,Royal Perth Hospital Wellington Street Campus
Critical Reviews in Clinical Laboratory Sciences | Year: 2011

Genetic variations, in part, determine individual susceptibility to sepsis and pneumonia. Advances in genetic sequence analysis as well as high throughput platform analysis of gene expression has allowed for a better understanding of immunopathogenesis during sepsis. Differences in genes can also modulate immune and inflammatory response during sepsis thereby translating to differences in clinical outcomes. An increasing number of candidate genes have been implicated to play a role in sepsis susceptibility, most of which are controversial with few exceptions. This does not refute the significance of genetic polymorphisms in sepsis, but rather highlights the difficulties and pitfalls related to genetic association studies. These difficulties include differences in study design such as heterogeneous patient cohorts and differences in pathogenic organisms, linkage disequilibrium, and lack of power for detailed haplotype analysis or examination of gene-gene interactions. There is extensive diversity in the pathways of inflammation and immune response during sepsis making it even harder to prove the functional and clinical significance of one single genetic polymorphism which could be easily masqueraded or compensated by other upstream or downstream events of the pathway involved. The majority of studies have analysed candidate genes in isolation from other possible polymorphisms. It is likely that susceptibility to sepsis is the result of polymorphisms from multiple genes rather than one single mutation. Future studies should aim for multi-centered collaborative approach looking at genome wide association or gene profiling to provide a more complete appraisal of the key genetic players in determining genetic susceptibility to sepsis. This review paper will summarise the prominent candidate gene polymorphisms with known functional changes or those with haplotype data. In addition, a summary of the expanding research in the field of epigenetics and post-sepsis immunosuppression will be discussed. © 2011 Informa Healthcare USA, Inc.


Klingsberg R.C.,Tulane University | Mutsaers S.E.,PathWest Laboratory Medicine WA | Mutsaers S.E.,Lung Institute of Western Australia | Mutsaers S.E.,University of Western Australia | Lasky J.A.,Tulane University
Respirology | Year: 2010

Most pulmonary consultants are called upon to discuss IPF management with their patients. The gravity of IPF treatment discussion is immense in view of the data that 3- and 5-year mortality rates are approximately 50% and 80%, respectively. Although IPF occurs in older patients with comorbid diseases, most patients with IPF die as a direct consequence of their lung fibrosis. Here, the results of recently completed IPF trials and the rationale for ongoing studies are succinctly reviewed. There are a number of novel agents in clinical trials that are in the earlier stages of development, and there is new evidence supporting palliative therapies, which may help in managing symptoms of IPF, such as cough, without necessarily altering the course of the disease. The information provided herein should facilitate informed physician-patient dialogue. © 2010 Asian Pacific Society of Respirology.


Thomas R.,Sir Charles Gairdner Hospital | Thomas R.,University of Western Australia | Thomas R.,Lung Institute of Western Australia | Budgeon C.A.,Sir Charles Gairdner Hospital | And 9 more authors.
Chest | Year: 2014

BACKGROUND: Indwelling pleural catheters (IPCs) are commonly used to manage malignant effusions. Tumor spread along the catheter tract remains a clinical concern for which limited data exist. We report the largest series of IPC-related catheter tract metastases (CTMs) to date to our knowledge.METHODS: This is a single-center, retrospective review of IPCs inserted over a 44-month period. CTM was defined as a new, solid chest wall lesion over the IPC insertion site and/or the tunneled subcutaneous tract that was clinically compatible with a malignant tract metastasis.RESULTS: One hundred ten IPCs were placed in 107 patients (76.6% men; 60% with mesothelioma). CTM developed in 11 cases (10%): nine with malignant pleural mesothelioma and two with metastatic adenocarcinoma. CTM oft en developed late (median, 280 days; range, 56-693) post-IPC insertion. Seven cases had chest wall pain, and six received palliative radiotherapy to the CTM. Radiotherapy was well tolerated, with no major complications and causing no damage to the catheters. Longer interval aft er IPC insertion was the sole significant risk factor for development of CTM (OR, 2.495; 95% CI, 1.247-4.993; P = .0098) in the multivariate analyses.CONCLUSIONS: IPC-related CTM is uncommon but can complicate both mesothelioma and metastatic carcinomas. The duration of interval after IPC insertion is the key risk factor identified for development of CTM. Symptoms are generally mild and respond well to radiotherapy which can be administered safely without removal of the catheter. © 2014 AMERICAN COLLEGE OF CHEST PHYSICIANS.


Thomas R.,Sir Charles Gairdner Hospital | Thomas R.,University of Western Australia | Thomas R.,Lung Institute of Western Australia | Francis R.,University of Western Australia | And 5 more authors.
Respirology | Year: 2014

The approach to management of malignant pleural effusions (MPE) has changed over the past few decades. The key goals of MPE management are to relieve patient symptoms using the least invasive means and in the most cost-effective manner. There is now a realization that patient-reported outcome measures should be the primary goal of MPE treatment, and this now is the focus in most clinical trials. Efforts to minimize patient morbidity are complemented by development of less invasive treatments that have mostly replaced the more aggressive surgical approaches of the past. Therapeutic thoracentesis is simple, effective and generally safe, although its benefits may only be temporary. Pleurodesis is the conventional and for a long time the only definitive therapy available. However, the efficacy and safety of talc pleurodesis has been challenged. Indwelling pleural catheter (IPC) drainage is increasingly accepted worldwide and represents a new concept to improve symptoms without necessarily generating pleural symphysis. Recent studies support the effectiveness of IPC treatment and provide reassurance regarding its safety. An unprecedented number of clinical trials are now underway to improve various aspects of MPE care. However, choosing an optimal intervention for MPE in an individual patient remains a challenge due to our limited understanding of the underlying pathophysiology of breathlessness in MPE and a lack of predictors of survival and pleurodesis outcome. This review provides an overview of common pleural interventional procedures used for MPE management, controversies and limitations of current practice, and areas of research most needed to improve practice in future. © 2014 Asian Pacific Society of Respirology.


Fysh E.T.H.,University of Western Australia | Fysh E.T.H.,Sir Charles Gairdner Hospital | Smith N.A.,Sir Charles Gairdner Hospital | Lee Y.C.G.,University of Western Australia | And 2 more authors.
Seminars in Respiratory and Critical Care Medicine | Year: 2010

Drainage of the pleural space is not a modern concept, but the optimal size of chest drains to use remains debated. Conventional teaching advocates blunt dissection and large-bore tubes; but in recent years, small-bore catheters have gained popularity. In the absence of high-quality randomized data, this review summarizes the available literature on the choice of chest drains. The objective data supporting the use of large-bore tubes is scarce in most pleural diseases. Increasing evidence shows that small-bore catheters induce less pain and are of comparable efficacy to large-bore tubes, including in the management of pleural infection, malignant effusion, and pneumothoraces. The onus now is on those who favor large tubes to produce clinical data to justify the more invasive approach. Copyright © 2010 by Thieme Medical Publishers, Inc.


Bel E.H.,University of Amsterdam | Wenzel S.E.,University of Pittsburgh | Thompson P.J.,Lung Institute of Western Australia | Thompson P.J.,University of Western Australia | And 5 more authors.
New England Journal of Medicine | Year: 2014

Background: Many patients with severe asthma require regular treatment with oral glucocorticoids despite the use of high-dose inhaled therapy. However, the regular use of systemic glucocorticoids can result in serious and often irreversible adverse effects. Mepolizumab, a humanized monoclonal antibody that binds to and inactivates interleukin-5, has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma. Methods: In a randomized, double-blind trial involving 135 patients with severe eosinophilic asthma, we compared the glucocorticoid-sparing effect of mepolizumab (at a dose of 100 mg) with that of placebo administered subcutaneously every 4 weeks for 20 weeks. The primary outcome was the degree of reduction in the glucocorticoid dose (90 to 100% reduction, 75 to less than 90% reduction, 50 to less than 75% reduction, more than 0 to less than 50% reduction, or no decrease in oral glucocorticoid dose, a lack of asthma control during weeks 20 to 24, or withdrawal from treatment). Other outcomes included the rate of asthma exacerbations, asthma control, and safety. Results: The likelihood of a reduction in the glucocorticoid-dose stratum was 2.39 times greater in the mepolizumab group than in the placebo group (95% confidence interval, 1.25 to 4.56; P = 0.008). The median percentage reduction from baseline in the glucocorticoid dose was 50% in the mepolizumab group, as compared with no reduction in the placebo group (P = 0.007). Despite receiving a reduced glucocorticoid dose, patients in the mepolizumab group, as compared with those in the placebo group, had a relative reduction of 32% in the annualized rate of exacerbations (1.44 vs. 2.12, P = 0.04) and a reduction of 0.52 points with respect to asthma symptoms (P = 0.004), as measured on the Asthma Control Questionnaire 5 (in which the minimal clinically important difference is 0.5 points). The safety profile of mepolizumab was similar to that of placebo. Conclusions: In patients requiring daily oral glucocorticoid therapy to maintain asthma control, mepolizumab had a significant glucocorticoid-sparing effect, reduced exacerbations, and improved control of asthma symptoms. Copyright © 2014 Massachusetts Medical Society.

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