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
Response Of Human Airways To Deep Inflation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$281,037.00
Summary
The trachea and bronchi contain muscle that when it contracts narrows the air passages and makes it harder to breath. In healthy people taking a deep breath relaxes this airway muscle and improved breathing. However, in people who suffer from asthma and chronic airflow obstruction deep breaths do not have the normal relaxing actions on airway contraction. This study will use lung removed as part of surgery for lung cancer to study how the relaxing actions of deep breathing work in human airways.
In the asthmatic lung structural changes, such as increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix proteins), and an increased mass of bronchial smooth muscle cells occur. Many of these critical structural changes are not reversed or prevented with current asthma therapy, thus we need to investigate, by using lung cells and tissues , why they happen and how we can prevent them.
Molecular Mechanisms Of Wasting In Experimental COPD
Funder
National Health and Medical Research Council
Funding Amount
$389,521.00
Summary
Chronic obstructive pulmonary disease (COPD) is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of COPD and accounts for more than 95% of cases in industrialized countries. Currently no therapies exist to halt the inevitable progression of the disease. To date most of the research has focused on the aspects of this disease which result in destruction of the lung however it is becoming incre ....Chronic obstructive pulmonary disease (COPD) is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of COPD and accounts for more than 95% of cases in industrialized countries. Currently no therapies exist to halt the inevitable progression of the disease. To date most of the research has focused on the aspects of this disease which result in destruction of the lung however it is becoming increasingly evident that COPD is a disease of multiple organs. Until recently it had been widely believed that the profound loss of exercise tolerance observed in COPD patients was due to impaired gas exchange secondary to lung structural damage. Loss of lean body mass (muscle) is now recognised as a major co-morbidity of COPD and a direct cause of functional impairment with patients suffering marked deteriorations in quality of life, increased mortality, breathlessness and decreased exercise tolerance. Skeletal muscle wasting is a powerful predictor of mortality in COPD, independent of the lung function impairment. Despite the clinical seriousness of muscle wasting and suggestive evidence that it may be reversible, little is known about the pathogenic mechanisms. Therefore the goal of this project is to use experimental models of COPD to identify the molecular basis of wasting, in order to restore skeletal muscle homeostasis. The insights gained from this research proposal may lead to the identification of potentially novel targets for the prevention and reversal of the debilitating and life threatening effects of skeletal muscle wasting in COPD. For the COPD patient this has the potential to increase quality of life, functional ability and life expectancy.Read moreRead less
Restoring Skeletal Muscle In An Experimental Model Of COPD By Targeting The IGF-1-myostatin-macrophage Axis
Funder
National Health and Medical Research Council
Funding Amount
$508,183.00
Summary
Most people think that the serious disabilities of COPD (emphysema) patients follows damage to their lungs but wasted muscles may be even more important. We can not regrow lung but we have found a way that might help regrow muscle. We plan to use stem cells to make one of the body's own cells called 'macrophages' and genetically engineer these cells to help deliver healing proteins directly into the muscle. Making muscle stronger will help COPD patients live longer and improve quality of life.
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.