Dr Cheryl Salome
Dr Gregory King
To study people with and without airways disease, using both physiological and imaging techniques, to describe and measure the features that characterise the disease or reflect its severity, in order to understand the physiological mechanisms that cause the disease and its manifestations.
• PhD graduations by Sue Downie (2nd May 2008), Nathan Brown, Jessica Dame-Carroll and Ben Harris (19 December 2008).
• Claude Farah and Sophie Timmins were offered University of Sydney Postgraduate Awards to support their PhD research projects commencing in 2009.
• Sri Mahadev was awarded a postgraduate scholarship from Royal North Shore Medical Research Foundation to support his PhD research in 2009.
The move to Glebe, and availability of purpose-built laboratories, with adequate space and facilities, has signifi cantly enhanced our ability to undertake new studies and accommodate new students. Three new medically trained PhD students have joined the group in 2009, and we anticipate an increase in research activity and output in the coming year.
Ventilation heterogeneity and AHR in older asthma and COPD: We have discovered that ventilation heterogeneity, or uneven distribution of air throughout the lungs, is a strong predictor of airway hyperresponsiveness (AHR) in people with asthma. As a result of this observation we hypothesised that patchy ventilation may be the basis of AHR in other diseases. To test this we have examined the relationship ventilation heterogeneity and AHR in older people with asthma and in chronic obstructive pulmonary disease (COPD). The results do not support the hypothesis, but raise important questions about both the site of airway abnormalities that affect AHR in older asthmatics, and about the nature of the abnormalities that affect ventilation heterogeneity in COPD. Lead investigators: Sue Downie and Kate Hardaker
Ventilation heterogeneity and airway closure, measured by SPECT/CT in asthma: This study investigating the mechanisms or association between AHR and ventilation heterogeneity used direct lung imaging using SPECT/CT to measure the extent of airway closure that occurs after bronchial challenge. The findings provide important evidence to support our hypotheses and suggest that, rather than the widespread narrowing of airways, AHR is caused by the development of localised clusters of low ventilation and airway closure – representing a fundamental shift in our understanding of AHR in asthma.
Lead investigator: Catherine Walsh
Ventilation heterogeneity and airway closure in normal subjects: In normal subjects without asthma, simply avoiding taking deep breaths for twenty minutes increases the airway response to a bronchial challenge test. The aim of this study is to determine if avoiding deep breaths increases airway responsiveness by causing an increase in ventilation heterogeneity and airway closure. The finding show increased airway closure is indeed a contributing factor to AHR in asthmatics, and that the increase in airway responsiveness in non-asthmatics, after avoiding deep breaths, is due entirely to an increase in airway closure. Lead investigator: David Chapman
Normal values for ventilation heterogeneity: As our understanding of the importance of ventilation heterogeneity has grown, we have increasingly recognised the need to defi ne normal ranges for the important outcome variables. In a study of healthy subjects at RNSH, we have shown that ventilation heterogeneity in conducting and peripheral airways is affected by age, but not by sex, height or weight. Lead investigator: Samir Lahzami
Physiological markers of structural changes in the airways in asthma: Airway remodelling describes a range of structural changes in the airways that are presumed to be the result of damage inflicted by chronic inflammation in the airways. Nathan Brown’s studies are based on the premise that airway remodelling increases airway stiffness, measured by using the forced oscillation technique to detect the changes in airway calibre that occur as lung volume changes. These studies have shown that asthmatic airways are stiffer than those of non-asthmatics, a difference that is most likely due to changes in airway wall structure. Lead investigator: Nathan Brown
How do thick airway walls affect airway behaviour in asthma?: Airway remodelling in asthma thickens and stiffens the airway walls. This NHMRC funded project investigates the clinical relevance of airway remodelling, and determine the relationship between physical characteristics of the airway walls, such as their thickness and stiffness, and functional characteristics, such as AHR. Lead investigators: Jessica Kermode and Nathan Brown
Improved methods for imaging the structure of the airways: High-resolution Computed Tomography (HRCT) can be used to measure the thickening of airway walls in asthma, providing a non-invasive means to evaluate airway remodelling However, the potential for making objective measurements from these scans is limited by the availability of accurate software tools for making airway measurements. A programme has been developed that allows objective measurements to be made from three dimensional image data and takes into account errors due to different orientations of the airways. The measurements were validated against measurements made using an ultra-high resolution imaging method called Micro-CT, which were acquired at the Key Centre for Microscopy and Microanalysis, where the project is co-supervised by Dr Allan Jones. Lead investigator: Aneal Chandra
The effect of bronchodilator on airway caliber and airway closure in COPD: Data from a large population dataset, from the BOLD study in Sydney, have been used to defi ne the normal response to bronchodilator in people over the age of 50 years, and then compare them with fi ndings in subjects with COPD recruited from both clinic and general population samples. By using both spirometry and the forced oscillation technique we were able to separate the effects on airway caliber and airway closure. The findings suggest that the predominant effect of bronchodilator in COPD is to open up airways that were previously closed. Lead investigator: Chantale Diba, in collaboration with the BOLD team
Effects of bronchodilator on ventilation distribution in COPD: If the predominant action of bronchodilators in COPD is to open closed airspaces, then bronchodilatation is likely to have a substantial effect on the distribution of ventilation. In this study, broncho dilator had no overall effect on ventilation heterogeneity measuring either physiologically or by direct lung imaging. However, subjects who have an increase in the ventilated volume of their lungs appear to have a worsening of ventilation heterogeneity and a reduction in oxygen saturation. This implies that, in some subjects after bronchodilator, air may be redistributed from well ventilated and perfused to poorly ventilated and perfused areas of the lung. Lead investigator: Chantale Diba
Measuring airway hyperresponsiveness to mannitol using FOT: This study, completed as part of our research programme for the CRC for Asthma and Airways, has shown that the response to mannitol (Aridol) challenge can be measured reliably using FOT variables, with excellent repeatability, and a very high sensitivity and specificity for positive responses defi ned by traditional spirometric measurements. Lead investigators: Melissa McClean and Chris Htun
Using FOT for diagnosis of obstructive sleep apnoea: Diagnosis of obstructive sleep apnoea requires overnight study, usually during sleep in a Sleep Laboratory. This can be cumbersome and expensive and there is currently much work looking for an accurate diagnostic algorithm that can be used in a surgery. We found that measurements made by FOT in which we used a high oscillation frequency gave useful diagnostic information in a highprevalence group. This may be useful in future to help accurately predict the presence of sleep apnoea and in some may obviate the need for overnight studies. Lead investigators: Greg King, Don Lee, Richard Lee, Andrew Chan, Peter Cistulli
Dr Cheryl Salome, Research Leader, WIMR; Research Fellow, University of Sydney
Associate Professor Greg King, Research Leader, WIMR; Staff Specialist Royal North Shore Hospital; Associate Professor, University of Sydney
Dr Nathan Brown, Research Scientist, Laboratory Manager
Dr Sue Downie, Research Scientist
Dr Melissa McClean, Research Assistant
Ms Chantale Diba, Research Assistant
Ms Catherine Walsh, Research Assistant
Ms Kate Hardaker, Research Assistant
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