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King G.G.,The Woolcock Institute of Medical Research | King G.G.,University of Sydney | King G.G.,Cooperative Research Center for Asthma and Airways
Pulmonary Pharmacology and Therapeutics | Year: 2011

Medical imaging has been increasingly used in respiratory research due to the rapid and ongoing development of medical technology. Current imaging is almost entirely 3-dimensional and allows the measurement of structure and function, often both simultaneously. The information complements other measurement methods in airway research because imaging's greatest contributions are those of topographical information, direct visualisation of functional or structural change, sampling of the whole organ (in contrast to for example bronchoscopy) and potential for in vivo imaging in a repeated, prospective nature. Medical imaging modalities of high-resolution computed tomography (HRCT), magnetic resonance imaging (MRI), ultra-high resolution imaging, positron emission computed tomography (PET) and single photon emission computed tomography (SPECT) are reviewed in relation to research in airways disease. © 2011 Elsevier Ltd. Source


King G.G.,Woolcock Institute of Medical Research | King G.G.,University of Sydney | King G.G.,Cooperative Research Center for Asthma and Airways | Harris B.,Woolcock Institute of Medical Research | And 3 more authors.
Seminars in Nuclear Medicine | Year: 2010

Single-photon emission computed tomography (SPECT) is being increasingly used as a tool in respiratory research, in particular ventilation SPECT. Much of the basic understanding of pulmonary physiology has been derived from inhaled radioactive inert gases because, as the lung behaves in an asymmetric manner, the nature of regional differences in ventilation is ideally studied with the use of imaging. It is well known to clinicians that ventilation is patchy in patients who have airways disease. However, the relevance to the disease mechanisms itself only started to be studied with the use of 3-dimensional imaging and with advances in quantitative image analysis. The measurements of both ventilation distribution and nonventilation (airway closure) have become very topical in the study of asthma, and accurate quantification of those parameters is of relevance to disease mechanisms. In chronic obstructive pulmonary disease, the drive is towards better characterization of disease groups ("phenotypes") and, again, description of ventilation patterns may prove to be useful. This is a review, therefore, on pulmonary SPECT imaging in respiratory research which includes a focus on methodology in relation to respiratory physiology. There has been relatively little published in this area but there is great potential for advances in the understanding of airways disease to be gained from SPECT imaging. © 2010 Elsevier Inc. All rights reserved. Source


King G.G.,University of Sydney | King G.G.,Cooperative Research Center for Asthma and Airways
Respirology | Year: 2011

Pulmonary function testing is part of routine clinical practice in respiratory medicine. It is based around spirometry, which will remain the central measurement of lung function given its prognostic significance and its integral role in defining severity of airways disease. However, there is an increasing body of evidence from studies using new methods of lung function measurement which are providing new insights into pathophysiology of disease. This body of data is forming a basis for their future clinical role, once the economics of producing the relevant devices becomes attractive. The forced oscillation technique and multiple breath nitrogen washout are currently the most commonly used of the newer lung function techniques, which are refinements of long-established techniques. Optical coherence tomography, optical reflection, electrical impedance and vibration response imaging have arisen by development of novel devices. The recent use of these techniques is reviewed. © 2011 Asian Pacific Society of Respirology. Source


Burgess J.K.,Woolcock Institute of Medical Research | Burgess J.K.,University of Sydney | Burgess J.K.,Cooperative Research Center for Asthma and Airways | Weckmann M.,Cooperative Research Center for Asthma and Airways | Weckmann M.,University of Lubeck
Pharmacology and Therapeutics | Year: 2012

The extracellular matrix is a complex network of fibrous and nonfibrous molecules that not only provide structure to the lung but also interact with and regulate the behaviour of the cells which it surrounds. Recently it has been recognised that components of the extracellular matrix proteins are released, often through the action of endogenous proteases, and these fragments are termed matrikines. Matrikines have biological activities, independent of their role within the extracellular matrix structure, which may play important roles in the lung in health and disease pathology. Integrins are the primary cell surface receptors, characterised to date, which are used by the matrikines to exert their effects on cells. However, evidence is emerging for the need for co-factors and other receptors for the matrikines to exert their effects on cells. The potential for matrikines, and peptides derived from these extracellular matrix protein fragments, as therapeutic agents has recently been recognised. The natural role of these matrikines (including inhibitors of angiogenesis and possibly inflammation) make them ideal targets to mimic as therapies. A number of these peptides have been taken forward into clinical trials. The focus of this review will be to summarise our current understanding of the role, and potential for highly relevant actions, of matrikines in lung health and disease. © 2012 Elsevier Inc. All rights reserved. Source


Thompson B.R.,Monash University | Thompson B.R.,Cooperative Research Center for Asthma and Airways | Douglass J.A.,Royal Melbourne Hospital | Ellis M.J.,Monash University | And 7 more authors.
Journal of Allergy and Clinical Immunology | Year: 2013

Background: Exacerbations of asthma are thought to be caused by airflow obstruction resulting from airway inflammation, bronchospasm, and mucus plugging. Histologic evidence suggests the small airways, including acinar air spaces, are involved; however, this has not been corroborated in vivo by measurements of peripheral small-airway function. Objective: We sought to determine whether asthma severity is linked to small-airway function, particularly in patients with acute severe asthma. Methods: Eighteen subjects admitted for an asthma exacerbation underwent lung function testing, including measures of acinar ventilation heterogeneity (Sacin) and conductive ventilation heterogeneity (Scond) using the multiple-breath nitrogen washout. Treatment requirement was defined according to Global Initiative for Asthma scores. Data were compared with those obtained in 19 patients with stable asthma. Results: For the asthma exacerbation group, the median FEV1 was 59% of predicted value (95% CI, 45% to 75% of predicted value), the median Scond value was 185% of predicted value (95% CI, 119% to 245% of predicted value), and the median Sacin value was 225% of predicted value (95% CI, 143% to 392% of predicted value). FEV1 (percent predicted) was correlated with Sacin (percent predicted) values (Spearman rho = -0.67, P =.006) but not with Scond (percent predicted) values (P >.1). The Global Initiative for Asthma score was significantly related to Sacin (percent predicted) (Spearman rho = 0.59, P =.016) but not to Scond (percent predicted) values (P >.1). The unstable group was characterized by considerably lower forced vital capacity (P <.001) and higher Scond (P =.001) values than the unstable group. In a subgroup of 11 unstable patients who could be reviewed after 4 weeks, FEV1, forced vital capacity, Sacin, and Scond values showed marked improvements. Conclusion: Our findings suggest that unstable asthma is characterized by a combined abnormality in the acinar and conductive lung zones, both of which are partly reversible. Functional abnormality in the acinar lung zone in particular showed a direct correlation with airflow obstruction and treatment requirement in patients with acute severe asthma. © 2012 American Academy of Allergy, Asthma & Immunology. Source

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