A5060644052- Asthma and respiratory diseases
- Transplantation: Methods and Outcomes
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neonatal Respiratory Health Research
- Immune Cell Function and Interaction
- Pediatric health and respiratory diseases
- Respiratory and Cough-Related Research
- Phagocytosis and Immune Regulation
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Inhalation and Respiratory Drug Delivery
- Renal Transplantation Outcomes and Treatments
- Immune cells in cancer
- Respiratory viral infections research
- Polyomavirus and related diseases
- Respiratory Support and Mechanisms
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Trace Elements in Health
- Inflammasome and immune disorders
- Galectins and Cancer Biology
- Sphingolipid Metabolism and Signaling
- Cytomegalovirus and herpesvirus research
- Heme Oxygenase-1 and Carbon Monoxide
- Smoking Behavior and Cessation
- Eosinophilic Esophagitis
Royal Adelaide Hospital
2015-2024
The University of Adelaide
2015-2024
Hanson Institute
2013-2024
Jichi Medical University
2019
Queen Elizabeth Hospital
2014
University of Missouri
2008
South Australia Pathology
2007
Novem (Netherlands)
2005
Women's and Children's Hospital
1998-2005
Child & Family Service
2003
Chronic obstructive pulmonary disease is a highly prevalent, complex disease, usually caused by cigarette smoke. It causes serious morbidity and mortality costs the global community billions of dollars per year. While chronic inflammation, extracellular matrix destruction increased airway epithelial cell apoptosis are reported in understanding basic pathogenesis limited there no effective treatments. We hypothesized that accumulation apoptotic cells could be due to defective phagocytic...
Chronic obstructive pulmonary disease (COPD) is associated with defective efferocytosis (apoptosis and alveolar macrophage [AM] phagocytic function) that may lead to secondary necrosis tissue damage. We investigated ex vivo AM ability recognition molecules (CD36, integrin alphaVbeta3, CD31, CD91, CD44) using flow cytometry. The transferrin receptor (CD71) was measured as an indicator of monocyte-macrophage differentiation in bronchoalveolar lavage (BAL). Proliferation assessed Ki-67. Based...
BackgroundAsthma pathophysiology and treatment responsiveness are predicted by inflammatory phenotype. However, the relationship between airway microbiology asthma phenotype is poorly understood.ObjectiveWe aimed to characterize microbiota in patients with symptomatic stable relate composition other phenotypic characteristics.MethodsThe microbial of induced sputum specimens collected from adult screened for a multicenter randomized controlled trial was determined using 16S rRNA gene...
Summary Background In asthma, the airway inflammatory phenotype influences clinical characteristics and treatment response. Although induced sputum is gold standard test for phenotyping a more accessible method needed practice. Objective To investigate whether white blood cell counts and/or their derived ratios can predict eosinophils or neutrophils in uncontrolled asthma. Methods This cross‐sectional study evaluated 164 treated but asthmatic patients with induction collection....
Asthma is a chronic inflammatory disorder of the airways where bacteria may act as protagonists inflammation. Little known about relation airway inflammation to presence specific bacterial taxa. We sought describe sputum microbiome in adults with poorly controlled asthma. DNA was extracted from induced and microbial communities were profiled using 16S rRNA pyrosequencing. Bacterial species characterised, relationship between populations, asthma subtypes other covariates explored. Real-time...
Rationale: The macrolide antibiotic azithromycin reduces exacerbations in adults with persistent symptomatic asthma. However, owing to the pleotropic properties of macrolides, unintended bacteriological consequences such as augmented pathogen colonization or dissemination antibiotic-resistant organisms can occur, calling into question long-term safety maintenance therapy.Objectives: To assess effects on airway microbiota, abundance, and carriage resistance genes.Methods: 16S rRNA sequencing...
Rationale: Defective efferocytosis (phagocytic clearance of apoptotic cells) in the airway may perpetuate inflammation via secondary necrosis chronic obstructive pulmonary disease (COPD). We have previously reported that low-dose azithromycin improved alveolar macrophage (AM) phagocytic function vitro.Objectives: investigated collectins (mannose-binding lectin [MBL] and surfactant protein [SP]-D) mannose receptor (MR) COPD their possible role azithromycin-mediated improvement...
There is heterogeneity in the propensity of smokers to develop chronic obstructive pulmonary disease (COPD), and improved treatment strategies are hindered by limited understanding COPD pathogenesis, especially as distinct from effects smoking per se . Although apoptosis essential for tissue homeostasis, increased may cause damage inflammation. This study addressed whether airway T-lymphocytes epithelial cells (AEC) show an likelihood undergoing if this was related smoking. Apoptosis...
Chronic obstructive pulmonary disease (COPD) is associated with increased apoptosis and defective phagocytosis in the airway. As uncleared cells can undergo secondary necrosis perpetuate inflammation, strategies to improve clearance would have therapeutic significance. There evidence that 15-member macrolide antibiotic azithromycin has anti-inflammatory properties. Its effects may be lung due its ability reach high concentrations alveolar macrophages (AMs). The present study investigated of...
The role of T cells in the pathophysiology chronic obstructive pulmonary disease (COPD) is not yet certain, although varying reports have shown increases helper 1 (Th1) and/or Th2 cytokines peripheral blood and bronchoalveolar lavage (BAL). No studies examined cytokine production by intraepithelial obtained bronchial brushing (BB). Intracellular analysis cell subsets from blood, BAL BB smoker ex-smoker COPD patients, patients receiving inhaled corticosteroids non-smoker control subjects was...
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Summary There is a limited understanding how of lung cancer cells evade cytotoxic attack. Previously, we have shown reduced production the mediator granzyme B by CD8+ T in tissue. We hypothesized that would be further associated with decreased B, perforin and proinflammatory cytokines other lymphocytes, natural killer (NK) T-like NK cells, this result from soluble mediators released cells. Lung non-cancer tissue five patients was identified experienced pathologists. Tumour necrosis factor...
Many patients with non-eosinophilic asthma have increased numbers of neutrophils in the airways. The explanation for this chronic inflammation remains unclear, but may result from an impaired ability alveolar macrophages to phagocytose apoptotic cells (a process termed 'efferocytosis'), as we shown obstructive pulmonary disease (COPD).To examine induced sputum a non-invasive technique characterize efferocytosis lung diseases and compare asthma, eosinophilic COPD.Participants stable (20 30...
Abstract Background Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission. Methods observational included 453 severe patients (41% male; mean age ± SD 55.7 14.7 years) from real‐world drug registries: Australian Mepolizumab Registry and Xolair Registry. The composite outcome clinical was defined zero exacerbations oral corticosteroids during previous 6 months assessed at 12...
Idiopathic pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular endothelial and smooth muscle cells causing increased resistance right heart failure. Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) are believed to cause familial form disease. Reduced expression BMPR2 also noted secondary PAH. Recent advances therapy PAH have improved quality life survival, but many patients continue do poorly. The possibility treating via improving signaling...
Our previous studies have shown that nutritional zinc restriction exacerbates airway inflammation accompanied by an increase in caspase-3 activation and accumulation of apoptotic epithelial cells the bronchioles mice. Normally, are rapidly cleared macrophage efferocytosis, limiting any secondary necrosis inflammation. We therefore hypothesized deficiency is not only pro-apoptotic but also impairs efferocytosis. Impaired efferocytic clearance alveolar macrophages occurs chronic obstructive...
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease; it leading cause of death and existing treatments have no proven disease-modifying effect. The mechanisms underlying this resistance are largely unknown, but suggest the presence some self-maintaining pathogenic process, possibly initiated by cigarette smoking, that prevents normal resolution inflammation. We previously reported increased production proinflammatory cytokines granzyme b CD8(+) T cells in...
Chronic inflammation and reduced airways integrity in chronic obstructive pulmonary disease (COPD) potentially results from secondary necrosis as a result of impaired phagocytosis apoptotic material by airway macrophages, increased bacterial colonization. We have previously shown that administration low-dose azithromycin to subjects with COPD improved macrophage epithelial cells, expression mannose receptor.We firstly investigated whether there were defects the ability both alveolar (AM)...
E-cigarettes are perceived as harmless; however, evidence of their safety is lacking. New data suggests discharge a range compounds capable physiological damage to users. We previously established that cigarette smoke caused defective alveolar macrophage phagocytosis. The present study compared the effect E-cigarette components; E-liquid flavors, nicotine, vegetable glycerine, and propylene glycol on phagocytosis, proinflammatory cytokine secretion, phagocytic recognition molecule expression...
Galectin-3 (gal-3), a member of the β-galactoside-binding animal lectins, is involved in recruitment, activation and removal neutrophils. Neutrophilic asthma characterized by persistent elevation airway neutrophils impaired efferocytosis. We hypothesized that sputum gal-3 would be reduced neutrophilic expression associated with other markers inflammation.Adults (n = 80) underwent induction following clinical assessment blood collection. Sputum was dispersed for differential cell count ELISA...
Periostin levels are associated with airway eosinophilia and suppressed by corticosteroid treatment in asthma. This study sought to determine the relationship between serum sputum periostin, inflammatory phenotype asthma control. Adults poorly-controlled (n = 83) underwent a clinical assessment, induction blood sampling. Dispersed was used for differential cell count periostin assessment (ELISA). Serum determined Elecsys® immunoassay. were significantly higher (median (IQR) of 51.6 (41.8,...
Abstract Background The AMAZES randomized controlled trial demonstrated that long‐term low‐dose azithromycin treatment reduces exacerbations of poorly asthma, but the therapeutic mechanisms remain unclear. Dysregulation inflammatory tumour necrosis factor (TNF) pathway is implicated in asthma and could be suppressed by azithromycin. We aimed to determine clinical associations soluble TNF signalling proteins (TNF receptors [TNFR] 1 2, TNF) sputum serum, test effect 48 weeks vs placebo on...