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.
While many cases of asthma are mild, severe cases require extensive health care resources and are virtually unresponsive to conventional treatment. This project will investigate whether specific compounds released from the airway are able to cause lung damage and airway abnormalities similar to that in severe asthma. We will investigate whether these changes are responsive to conventional therapy and investigate a potential treatment for regaining this responsiveness in severe 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.
Fetal Growth Restriction, Low Birth Weight And The Development Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$397,003.00
Summary
Asthma is a common disease in Australia that causes breathing difficulties. Studies have shown that restricted growth in the womb may be linked to developing asthma in childhood and adulthood. The reason for this isn't clear but we believe that restricted growth may alter the normal development of the baby's airway and lungs. Changes to the normal structure of the lungs leads to a higher risk of developing asthma.
Structural And Mechanical Determinants Of Airway Hyperresponsiveness
Funder
National Health and Medical Research Council
Funding Amount
$415,219.00
Summary
In asthma and chronic obstructive pulmonary disease, the capacity for airway passages to narrow is increased which limits airflow in and out of the lung and contributes to disease severity. The aim of this project is to identify the underlying physiological abnormalities producing the increased narrowing capacity. The investigations will focus on the role of the airway smooth muscle and epithelial layers that are widely implicated in driving the increased narrowing response, but for which the ev ....In asthma and chronic obstructive pulmonary disease, the capacity for airway passages to narrow is increased which limits airflow in and out of the lung and contributes to disease severity. The aim of this project is to identify the underlying physiological abnormalities producing the increased narrowing capacity. The investigations will focus on the role of the airway smooth muscle and epithelial layers that are widely implicated in driving the increased narrowing response, but for which the evidence remains circumstantial.Read moreRead less
Understanding The Impact Of Preterm Birth On Development: Improving Outcomes For Preterm Infants.
Funder
National Health and Medical Research Council
Funding Amount
$823,008.00
Summary
Approximately 10% of babies are born prematurely and many suffer long-term health problems. Our aim is to understand how premature birth affects the development of the cardiovascular, respiratory and central nervous systems. This understanding will help to improve the long-term health outcomes for premature infants. By working with medical practitioners treating premature babies we are well placed to translate our findings on preventing and treating developmental injury into clinical practice.
Regulation Of Inflammatory And Epithelial Responses In An Experimental Model Of Chronic Human Asthma
Funder
National Health and Medical Research Council
Funding Amount
$164,061.00
Summary
This project examines how chronic inflammation and scarring develop in the walls of the airways in asthma. The particular role of allergic mechanisms and of specific types of cells that are involved in allergic inflammation will be tested, using a much-improved mouse model of asthma. In this experimental model, which was developed by the investigators, sensitised mice are chronically exposed to low concentrations of aerosolised egg white protein. The proposed studies will involve comparisons wit ....This project examines how chronic inflammation and scarring develop in the walls of the airways in asthma. The particular role of allergic mechanisms and of specific types of cells that are involved in allergic inflammation will be tested, using a much-improved mouse model of asthma. In this experimental model, which was developed by the investigators, sensitised mice are chronically exposed to low concentrations of aerosolised egg white protein. The proposed studies will involve comparisons with animals that are genetically deficient in their ability to produce certain inflammation-related molecules, as well as with mice treated with antibodies to block the action of other such molecules.Read moreRead less
Pathophysiological Correlates In Smokers And Smoking-related Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$283,500.00
Summary
Smoking-related chronic airway narrowing (COPD) is a common and major illness. Research on the characteristics of the actual pathological process in the airways in smokers and COPD using direct tissue sample is relatively new. Data is currently limited and rather contradictory. In this grant we will recruit a spectrum of smokers and COPD patients typical of those in the Australian community and will be undertaking a detailed analysis of the cellular and some vascular structural changes in the ai ....Smoking-related chronic airway narrowing (COPD) is a common and major illness. Research on the characteristics of the actual pathological process in the airways in smokers and COPD using direct tissue sample is relatively new. Data is currently limited and rather contradictory. In this grant we will recruit a spectrum of smokers and COPD patients typical of those in the Australian community and will be undertaking a detailed analysis of the cellular and some vascular structural changes in the airway wall. Both cellular and vascular changes will be related to the fixed and reversible component of airway obstruction. Reversible changes with smoking cessation will be studied. A very novel feature will be a preliminary assessment of the utility of proteomics for assessment of airway pathology.Read moreRead less