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The Central Role Of Connective Tissue Growth Factor In Remodelling Of Asthmatic Airways
Funder
National Health and Medical Research Council
Funding Amount
$689,019.00
Summary
In the asthmatic airway an increase in the number of blood vessels can affect an asthmatic's ability to breathe. We have recently found that growth factors which can promote vessel growth are increased in the airways of asthmatics. We want to understand how these growth factors act together to possibly control the blood vessels and how their behaviour is different in the asthmatic airways compared to the nonasthmatic airways.
The Role Of Reduced Lung Volume In The Pathogenesis Of Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$275,095.00
Summary
Asthma is a disease for which the cause is not understood. This project is designed to examine the possibilty that breathing at low volumes causes an abnormality in the smooth muscle of the airways that predisposes them to the airway hyperresponsiveness of asthma.
Ontogeny Of The Airway Smooth Muscle Layer In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$535,914.00
Summary
In asthmatic patients the thickness of the airway smooth muscle (ASM) layer is increased early in life and even before doctor-diagnosis. An intriguing possibility is our overarching hypothesis that the ASM layer is thickened from birth and represents an independent risk factor for the development of asthma. This project strives to understand better how the ASM layer matures from late gestation to adulthood and whether abnormal maturation contributes to disease susceptibility.
Regulation Of Pulmonary Responsiveness By Chronic Mechanical Strain And Its Role In Obstructive Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
The pressures required to breathe place a continuous but varying mechanical strain on airway passages and lung tissue. This mechanical strain may protect the airway from collapsing, however, this protection is deficient in lung diseases such as asthma. This project considers the possibility that abnormal mechanical strain occurring in lung disease predisposes the individual to debilitating and potentially life-threatening airflow obstruction.
Currently in Australia asthma prevalence is high compared with other countries, affecting 10%–12% of adults and 14%–16% of children. This project will determine the contribution of mast cells to the altered function of airway smooth muscle cells and identify how non asthmatic airway smooth muscle inhibits mast cell localisation to it. The findings will provide new targets for asthma therapies and a pathway for prevention strategies, which up until now have been unsuccessful.
Increased Airway Smooth Muscle Mass As An Independent Determinant Of Asthma Pathogenesis And Severity
Funder
National Health and Medical Research Council
Funding Amount
$409,966.00
Summary
Asthma is a major health burden to the community. The most common form of the disease is allergic asthma and it is thought that allergic inflammation drives associated airway abnormalities including increased airway smooth muscle (ASM) mass. This study tests a new hypothesis that airway abnormalities and allergy have separate origins but combine to produce allergic asthma, and it’s the individuals with the greatest amount of ASM who develop clinically severe asthma.
Heterogeneity Of Airway Smooth Muscle Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$623,078.00
Summary
Increased smooth muscle in the airways causes excessive narrowing and asthma symptoms. The distribution of the increased muscle in the lung varies between people with asthma and may determine how severe the asthma is and what treatments are best. This project will use tissues from many cases of asthma to map this distribution and will use laser scanning in the airways to develop a test to safely examine the smooth muscle in living people, in order to better treat or prevent asthma.
The Early Life Origin Of Airway Smooth Muscle Thickening In Asthma Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$322,198.00
Summary
Previous studies have shown that fetal growth restriction (FGR) in the womb is associated with asthma in children; however the reason remains unknown. Thickening of the airway smooth muscle (ASM) is the primary structural abnormality in asthma. A model of FGR caused by low oxygen in the womb will be used to determine if associations between FGR and asthma involve an early life increase in ASM. That ASM may be increased from birth is a novel hypothesis which challenges conventional thinking.
Abnormal Smooth Muscle Behaviour In Asthma: Toward An In Vivo Test
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
In order to understand asthma better, and to improve our ability both to prevent and to treat the disease, we need to understand why the airways of people with asthma narrow too easily and too much. Airway hyperresponsiveness is almost certainly a downstream consequence of several different abnormalities. Airway inflammation, resulting from an allergic reaction in the airways, probably plays a major role. It is also likely that the smooth muscle in the airways contributes to airway narrowing, bu ....In order to understand asthma better, and to improve our ability both to prevent and to treat the disease, we need to understand why the airways of people with asthma narrow too easily and too much. Airway hyperresponsiveness is almost certainly a downstream consequence of several different abnormalities. Airway inflammation, resulting from an allergic reaction in the airways, probably plays a major role. It is also likely that the smooth muscle in the airways contributes to airway narrowing, but at present we have no way to measure airway behaviour in the living human. In this project we will examine the response of the airways to a deep breath, to determine if this is an indicator of smooth muscle behaviour. When the airways are narrowed, taking a deep breath stretches them and helps to overcome the narrowing. It is well known that this stretching mechanism is impaired in asthma, probably as a result of inflammatory changes to the airway wall. What is less well known is that after the airway has been stretched by a deep breath, it re-narrows, and there is new evidence that the rate of re-narrowing is increased in asthma. Based on our knowledge of how the smooth muscle behaves in the organ bath, and of the types of abnormal behaviour found in muscle from allergic and some asthmatic people, it seems likely that the rate of airway re-narrowing following a deep breath is an indicator of smooth muscle behaviour. This hypothesis has not been tested before. If we can establish that the rate of re-narrowing is an indicator of smooth muscle behaviour, we can then determine if abnormal muscle behaviour occurs in asthma, and examine the factors associated with abnormal muscle behaviour. This will improve our understanding of the basic abnormalities in asthma, and facilitate studies to see if this test can predict who is at risk from developing asthma. Evidence that smooth muscle behaviour is abnormal in asthma may suggest new directions for drug therapy.Read moreRead less