Mechanisms Of Impaired Bronchodilator Response Associated With Fatty Acid Intake In Obese Asthma
Funder
National Health and Medical Research Council
Funding Amount
$694,365.00
Summary
Obese asthmatics typically have a high dietary fat intake, which reduces the efficacy of their asthma medications. We will determine which types of dietary fat affect asthma medications. We will also determine which asthma medications are affected by a high fat load. Finally, we will examine the mechanisms by which fatty acids affect the efficacy of asthma medications. This is will inform new treatment options for managing the many obese asthmatics who are not able to achieve weight loss.
Asthma causes wheeze and shortness of breath via airway narrowing, with asthma attacks commonly caused by virus infections. We plan to investigate how airway narrowing during an asthma attack decreases the body’s ability to fight off a viral infection, causing prolonged infection, worse asthma symptoms, more airway inflammation and long-term damage within the airways. We will attempt to use current and novel treatments to reverse these problems, and improve treatment for asthma.
The breathing difficulty experienced by asthmatics occurs because of excessive narrowing in the bronchial tubes or airways. These airways are normally held open by the pressures in the chest during breathing. It is possible that the excessive airway narrowing in asthma occurs because these pressures are no longer effective. This may be due to changes in the airway stiffness which occurs during asthma. The project will involve experts Canada and Australia who have developed new techniques which a ....The breathing difficulty experienced by asthmatics occurs because of excessive narrowing in the bronchial tubes or airways. These airways are normally held open by the pressures in the chest during breathing. It is possible that the excessive airway narrowing in asthma occurs because these pressures are no longer effective. This may be due to changes in the airway stiffness which occurs during asthma. The project will involve experts Canada and Australia who have developed new techniques which allow the airways to be seen so that these changes can be measured.Read moreRead less
ORIGIN AND REGULATION OF VAGAL PREGANGLIONIC NEURON SUBTYPES CONTROLLING AIRWAY SMOOTH MUSCLE TONE
Funder
National Health and Medical Research Council
Funding Amount
$438,700.00
Summary
The primary role of the airways is to allow the exchange of oxygen and carbon dioxide between the environment and the lungs. However, the airways are not merely a series of static tubes, but rather their size (or caliber) is subject to breath-by-breath alterations, thereby regulating gas exchange to match the body's demands. Regulation of airway caliber is achieved largely by subconscious changes in the tone of the muscle lining the airway wall. Airway muscle tone is primarily under the control ....The primary role of the airways is to allow the exchange of oxygen and carbon dioxide between the environment and the lungs. However, the airways are not merely a series of static tubes, but rather their size (or caliber) is subject to breath-by-breath alterations, thereby regulating gas exchange to match the body's demands. Regulation of airway caliber is achieved largely by subconscious changes in the tone of the muscle lining the airway wall. Airway muscle tone is primarily under the control of the parasympathetic division of the autonomic nervous system. Two distinct types of parasympathetic nerves innervate the airways: One type employs the neurotransmitter acetylcholine which causes airway muscle to contract and the airways to constrict, while the other type employs nitric oxide which evokes airway dilatation. The normal regulation of airway caliber is altered in a variety of inflammatory airways diseases. In asthma and chronic obstructive pulmonary disease (COPD) there is an increase in airway muscle tone (airway constriction) which compromises the normal movement of gasses and contributes to the morbidity and mortality of the diseases. There is a growing body of evidence to suggest that exaggerated airway muscle tone may in part result from dysfunction of either the contractile or relaxant parasympathetic nerves innervating the airways. However, at present very little is known about the parasympathetic pathways regulating airway caliber. A complete understanding of the mechanisms controlling airway smooth muscle tone is therefore essential to fully understanding possible role of autonomic dysfunction in the pathogenesis of obstructive airways diseases. The aim of this grant is to better define the physiological and anatomical properties of airway parasympathetic nerves in the brain stem.Read moreRead less
Functional Analysis Of The Ym2 Chitinase-like Lectin In Allergic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$283,767.00
Summary
The prevalence of asthma is widespread and nationally affects over two million Australians. Consequently, one of the Country s National Health Priorities is to improve our understanding of this condition. Analyses of the asthmatic lung reveal an airway wall that is thickened, an airway lumen that is obstructed and abnormal spasmogenicity of the airway smooth muscle: processes that collectively contribute to both acute and chronic respiratory dysfunction. Asthmatics develop an immune response tha ....The prevalence of asthma is widespread and nationally affects over two million Australians. Consequently, one of the Country s National Health Priorities is to improve our understanding of this condition. Analyses of the asthmatic lung reveal an airway wall that is thickened, an airway lumen that is obstructed and abnormal spasmogenicity of the airway smooth muscle: processes that collectively contribute to both acute and chronic respiratory dysfunction. Asthmatics develop an immune response that is biased toward production of allergy-related T helper 2 cytokines of which interleukin (IL)-13 is a potent mediator of disease. However, the molecular processes linking IL-13 with abnormal airway wall changes are unclear. To identify previously uncharacterised IL-13-related molecules, we used a protein profiling approach that identified a novel lectin (carbohydrate-binding protein) termed Ym2, which is secreted abundantly into the airway fluid of mice in which allergic airways disease has been induced. Preliminary studies suggest that Ym2 is an intermediary of IL-13 that is involved in respiratory dysfunction. This project aims to work out how Ym2 interacts with the molecules and cells of the respiratory tract to regulate allergic disease. Specific inhibitors of Ym2 will be developed to examine what happens to allergic responses when Ym2 can t function; transgenic mice will be developed to determine if we see features of allergy when Ym2 is over-expressed in the normal lung, and human samples will be screened to identify the human counterpart of Ym2 and whether this counterpart is secreted into the lung fluid of asthmatics. Defining the mechanism by which Ym2 regulates the pathogenesis of allergic disease will not only contribute to our basic understanding of the processes underlying asthma pathology, but also generate new information for better design of therapeutics directed against specific mediators of this debilitating and widespread disease.Read moreRead less
Targeting Small Airways To Overcome Resistance To Therapy In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$531,045.00
Summary
There is a pressing need to overcome resistance to current therapies for severe asthma. Targetting inflammation-induced changes in small airway contraction offers an alternative strategy. We have identified a novel bronchodilator that relaxes maximally contracted mouse small airways when current treatment is ineffective. We will demonstrate its efficacy in animal models mimicking key features of human asthma, and define new ways to improve outcomes in poorly-controlled asthma.