How Do Thick Airway Walls Affect Airway Hyperresponsiveness In Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$382,538.00
Summary
Asthmatic airways narrow too easily, a characteristic called airway hyperresponsiveness (AHR). To understand the cause of asthma we need to understand the cause of AHR. Thickened airway walls could amplify airway narrowing and increase AHR. However, thick airway walls are also stiff, and stiff walls could reduce narrowing and AHR. This project will examine the relationships between AHR and airway wall thickness and stiffness during and after treatment that reduces airway wall thickness.
Does The Pattern Of Ventilation Distribution Predict Airway Hyperresponsiveness?
Funder
National Health and Medical Research Council
Funding Amount
$256,973.00
Summary
The tendency for airways to narrow too easily when stimulated is called airway hyperresponsiveness (AHR). AHR is an important feature of asthma, but it also occurs in other diseases, such as chronic obstructive pulmonary disease (COPD) - an airway disease caused by smoking, and cystic fibrosis. People who have AHR have more severe respiratory disease, regardless of which disease they have, and are more likely to develop poor lung function in old age and to be hospitalised or die from their disea ....The tendency for airways to narrow too easily when stimulated is called airway hyperresponsiveness (AHR). AHR is an important feature of asthma, but it also occurs in other diseases, such as chronic obstructive pulmonary disease (COPD) - an airway disease caused by smoking, and cystic fibrosis. People who have AHR have more severe respiratory disease, regardless of which disease they have, and are more likely to develop poor lung function in old age and to be hospitalised or die from their disease. If we can understand the causes of AHR we will have a better understanding of why some people with respiratory disease have poor outcomes. We have recently discovered that, in asthma, there is a very close relationship between AHR and the uneven distribution of air within the lungs. We believe that structural changes in the airways that cause this uneven distribution make the airways prone to AHR. This raises the possibility that factors that cause uneven ventilation in other respiratory diseases might also predispose the airways to AHR. If this is true, it suggests that there is a single physiological basis for AHR in a range of different diseases, and would allow us to focus research more closely on the causes of uneven ventilation. In this project we will measure the relationship between AHR and uneven ventilation in people with asthma, COPD or cystic fibrosis. The study is important because older people with asthma, particularly those with permanently narrowed airways, are likely to have more structural changes in their airways than young asthmatics, whereas people with COPD and cystic fibrosis have a different pattern of both structural changes and airway inflammation from that in asthma. The study will tell us whether there is a consistent relationship between AHR and uneven ventilation. If so, this would be extremely strong evidence that the factors that cause uneven ventilation contribute to AHR, and will point the way to studies of new treatments.Read moreRead less
Circulatory Biomarkers For Idiopathic Pulmonary Fibrosis: Improving Patient Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$841,625.00
Summary
We are going to find molecules in the blood that would improve the diagnosis and treatment of a lung condition called Idiopathic Pulmonary Fibrosis (IPF). The project brings together well characterized patients from the Australian IPF registry, blood samples we have collected from them and cutting edge technologies to complete this project.
The Link Between Vitamin D Deficiency And Chronic Lung Disease Is Due To Increased Airway Smooth Muscle
Funder
National Health and Medical Research Council
Funding Amount
$644,067.00
Summary
Vitamin D deficiency is a global public health problem. It is becoming increasingly evident that vitamin D deficiency increases the severity of chronic lung disease. In this study we propose to examine a mechanism that we think clearly explains this association. These studies are critical to understanding how deficiencies in key nutrients can impact on chronic lung disease and will provide the data necessary to guide public health policy to reduce the burden of disease in the community.
Mechanical Mobility Of The Thorax For Continuous Determination Of Lung Gas Volume
Funder
National Health and Medical Research Council
Funding Amount
$165,000.00
Summary
Percussion is a valuable clinical method for physical examination of parts of the body. A sharp tap (impulsive force) is applied to the body wall and the sound radiated in response is observed. This sound may be dull (over liver) or stony dull (pleural effusion), or resonant (over normal lung) or hyper-resonant (over bowel). While the variation in radiated sound is not fully understood, it is apparent that the presence of gas, which is highly compliant, increases mobility of the overlying tissue ....Percussion is a valuable clinical method for physical examination of parts of the body. A sharp tap (impulsive force) is applied to the body wall and the sound radiated in response is observed. This sound may be dull (over liver) or stony dull (pleural effusion), or resonant (over normal lung) or hyper-resonant (over bowel). While the variation in radiated sound is not fully understood, it is apparent that the presence of gas, which is highly compliant, increases mobility of the overlying tissue and allows it to resonate; where the sub-tissue is largely fluid, tissue mobility is low and the percussive sound is dull. Percussion is useful for examining the adult chest and lung, but cannot for example be applied in infant intensive care as only limited impulsive force can be used, and the adult finger, which is both a coupling device and sounding board, is too large. As well, percussion requires skill and quiet conditions. Accordingly, we developed a device to measure mobility of the chest and other tissues in real time. The VibroPulse applies a known low-level force to the body surface and records the resultant velocity induced in the surface. The force is generated by a vibrating mass set in motion by an electromagnetic motor driven by pseudo-random noise. Tissue mobility, defined as velocity-force, is derived simultaneously across the frequency range, providing an easily interpreted quantitative output unaffected by ambient noise. This proposal has two aims we can achieve in 1 year: (1) to continue evaluating VibroPulse sensitivity to tissue composition, using symmetrical percussive sites on the human chest and abdomen that are dull on one side and resonant on the other, and the chest of anaesthetised animals with experimentally induced pneumothorax and lung collapse, two life-threatening conditions for which percussion is a key diagnostic method, and (2) to engineer a small device from our bulky prototype that is suitable for clinical use, in infants and adults.Read moreRead less
Array-based Comparative Genomic Hybridisation In Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$314,773.00
Summary
Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. W ....Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. With exposure to cancer-causing agents such as cigarette smoke, parts of the lung may suffer permanent damage that increases the risk of lung cancer. Many of these changes include the genes in air passages and lung tissue. In this study, we will use the latest technology in genetics called gene chips to study changes in genes that affect the spread of lung cancer. These gene chips can study a vast number of genes at once. In particular, we will whether there is an abnormal number of copies of genes in the lung cancer. We hope that this research study will provide new information about the diagnosis and treatment of lung cancer.Read moreRead less
Genomic Profiling To Predict Lung Cancer Metastases
Funder
National Health and Medical Research Council
Funding Amount
$323,500.00
Summary
Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. W ....Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. With exposure to cancer-causing agents such as cigarette smoke, parts of the lung may suffer permanent damage that increases the risk of lung cancer. Many of these changes include the genes in air passages and lung tissue. In this study, we will use the latest technology in genetics called gene chips to study changes in genes that affect the spread of lung cancer. These gene chips can study a vast number of genes at once. We hope that this research study will provide new information about the diagnosis and treatment of lung cancer.Read moreRead less
Determinants Of Circulating Surfactant Protein Levels In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$276,221.00
Summary
The lung allows the oxygenation of blood and clearance of carbon dioxide. To achieve this a large surface area (50-100 m2) interfaces with a complex microcirculation across a 0.1-0.2 ?m barrier - the alveolocapillary membrane. The alveolocapillary membrane is damaged under a variety of circumstances, of varying severity. Whereas severe impairment results in respiratory failure, often there is no clear delineation between OacceptableO and OpathologicalO changes. Therefore, we have coined the term ....The lung allows the oxygenation of blood and clearance of carbon dioxide. To achieve this a large surface area (50-100 m2) interfaces with a complex microcirculation across a 0.1-0.2 ?m barrier - the alveolocapillary membrane. The alveolocapillary membrane is damaged under a variety of circumstances, of varying severity. Whereas severe impairment results in respiratory failure, often there is no clear delineation between OacceptableO and OpathologicalO changes. Therefore, we have coined the term Olung healthO to encompass the broad spectrum. Generally speaking, lung health can be compromised by lifestyle or disease. Whereas lifestyle changes are typically progressive and chronic, those associated with disease tend to be severe and acute. Monitoring lung health clearly has important implications in terms of occupational health and lifestyle issues, including smoking. The need for a marker of lung permeability is also regarded as the Oholy grailO in the intensive care setting. Currently, there is no way of doing so. The alveolus is lined with a liquid layer into which is secreted a complex mixture of lipids and specific proteins known as alveolar surfactant. Surfactant reduces the work of breathing. Recently, we fortuitously discovered that surfactant proteins leak into the circulation and that changes in their levels are a sensitive and early generic index of the lung?s integrity. We discovered that lung damage from conditions as diverse as smoking to the acute respiratory distress syndrome elevate circulating surfactant proteins levels. To refine our discovery we aim to: Improve the techniques used to measure the proteins Study the rate at which they enter and clear the circulation Study the influence of storage, gender, age, circadian rhythm, and smoking on the levels Study the levels in acute lung injury and in radiotherapy and cytotoxic drug treatment where the ability to monitor lung damage has immediate benefit for the patients.Read moreRead less
The Scientific Basis For The Integration Of Surgery And Immunotherapy For Lung Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$516,394.00
Summary
The work in this grant focuses on the effects of cancer surgery (tumor resection and removal of lymph nodes) on the anti-cancer immune response. It also examines whether delivery of agents into the residual tumour bed following surgery can effectively boost the effects of surgery on the immune system. The results obtained will help guide the rational design of future combination surgery-immunotherapy treatment regimens.