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
A Randomised Controlled Trial Investigating The Respiratory Effects Of Nitrogen Dioxide In Schoolchildren
Funder
National Health and Medical Research Council
Funding Amount
$212,189.00
Summary
Research has shown that exposures to air pollutants such as nitrogen dioxide (NO2), sulphur dioxide, ozone and respirable particulate matter less than 10 microns are associated with respiratory symptoms. Unlike the other air pollutants nitrogen dioxide is an indoor gas which occurs in higher concentrations than outdoors in households which cook or heat with gas. Recent research has demonstrated that NO2 at concentrations easily achieved indoors can increase respiratory illness, particularly in c ....Research has shown that exposures to air pollutants such as nitrogen dioxide (NO2), sulphur dioxide, ozone and respirable particulate matter less than 10 microns are associated with respiratory symptoms. Unlike the other air pollutants nitrogen dioxide is an indoor gas which occurs in higher concentrations than outdoors in households which cook or heat with gas. Recent research has demonstrated that NO2 at concentrations easily achieved indoors can increase respiratory illness, particularly in children and asthmatics. In South Australia we have the opportunity to demonstrate health effects of NO2 on children with asthma more conclusively, as a high number of schools heat their classrooms with unflued gas heaters which produce high NO2. In the proposed study, half of the primary schools with unflued gas heaters will have these heaters replaced with heaters which do not emit NO2. This process of selecting schools will be performed at random and in the school holidays, so as not to bias the children in regard to their exposure status. Additionally, only asthmatic children without gas appliances at home will be included. Asthma symptoms and lung function measurements will be collected in order to determine any differences in the health outcomes of both groups. The results of this study will be able to give conclusive information on health effects related to NO2, that will substantially contribute to the development of a recommended NO2 guideline. This is of worldwide interest.Read moreRead less
Influence Of Endothelin And Protease-activated Receptors On Eosinophil Trafficking In The Airways Of Allergic Mice
Funder
National Health and Medical Research Council
Funding Amount
$376,980.00
Summary
Asthma is a chronic inflammatory lung disease. This disease affects about 10% of the population, although its incidence in primary school-age children is as high as 30% in some cities. People suffering from asthma have very responsive (hyperresponsive) airways to substances which are usually innocuous. Many asthmatics are allergic to substances such as pollens, animal dander and house dust, which causes the airways of the asthma sufferer narrow, making breathing more difficult. The airways of as ....Asthma is a chronic inflammatory lung disease. This disease affects about 10% of the population, although its incidence in primary school-age children is as high as 30% in some cities. People suffering from asthma have very responsive (hyperresponsive) airways to substances which are usually innocuous. Many asthmatics are allergic to substances such as pollens, animal dander and house dust, which causes the airways of the asthma sufferer narrow, making breathing more difficult. The airways of asthma sufferers also become inflamed and the resulting swelling of the airways and excess formation of mucous makes breathing difficult. Inflamed asthmatic airways contain large numbers of cells called eosinophils, which move from the blood into the airways. Substances released from the eosinophils are thought to damage the airways and cause airways hyperresponsiveness. We have developed a mouse model of allergic inflammation which has many of the hallmark features of asthma, including high numbers of eosinophils and hyperresponsive airways. We have recently shown that these effects are inhibited by treatment of allergic mice with a drug called SB217242. SB217242 inhibits the actions of endothelin, a peptide that is produced in elevated amounts in the airways of asthma sufferers and which may produce many of the effects associated with asthma. We wish to investigate the mechanisms through which SB217242 and drugs which stimulate novel protease-activated receptors inhibits the increase in eosinophil numbers in the airways. We will investigate the possibility that these drugs inhibit the migration of eosinophils from the blood into the airways, using a unique microscope that allows us to visualize the movement of eosinophils into tissues such as the airways. These studies are likely to be of considerable strategic value in determining the potential usefulness of these drugs in the treatment of asthma.Read moreRead less
Airway Epithelial Barrier Function, Asthma And Aero-allergen Sensitization.
Funder
National Health and Medical Research Council
Funding Amount
$527,886.00
Summary
There is a strong association between allergy and asthma. This association been almost universally assumed to be causative. However, recent evidence suggests an alternative explanation ie., that the abnormal epithelium in asthma allows or facilitates sensitization to airborne allergens. This project will test this alternative hypothesis using human lung tissue and an animal model.
Reference Values For Spirometry, Lung Volumes, Diffusing Capacity, And Fractional Exhaled Nitric Oxide In First Nations Australians
Funder
National Health and Medical Research Council
Funding Amount
$83,832.00
Summary
Reference values in lung function tests allow respiratory doctors to accurately interpret results in order to effectively diagnose, treat and manage respiratory disease. Currently, reference values do not exist for First Nations adults. I will recruit 600 healthy First Nations adults from communities in Queensland and the Northern Territory for several lung function tests. Data collected will be submitted to the Global Lung Function Initiative to be incorporated into future guidelines.
This application will allow me to restructure my work to provide sufficient time to do full justice to the current and planned commitments of our Respiratory Research Group. Our research programme includes the immunopathology of chronic airway diseases; the epidemiology of respiratory disease (TAHS); clinical physiology technology to service these studies; respiratory clinical pharmacology; microbe-host interactions in CF and COPD; and EBM in chronic respiratory disease self-management .
Investigating The Effects Of Macrolides On Excessive Synthesis And Secretion Of Airway Mucins Using Novel Ex Vivo And In Vivo Approaches
Funder
National Health and Medical Research Council
Funding Amount
$520,821.00
Summary
Many people have difficulty breathing because the airway tubes that move air in and out of their lungs are blocked by excessive amounts of sticky mucus. Our project will use new techniques developed in our laboratories to investigate whether a group of medicines called “macrolides” can prevent the excessive production and release of mucus in the airways, and thus be beneficial in treating asthma, and potentially other lung diseases.
Disovery Of New Airway Epithelial Genes Regulating Allergic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$446,934.00
Summary
Asthma is an inflammatory disease of the lungs that affects over 10% of all Australians. A number of drugs are currently available for the treatment of asthma, but there are many people whose asthma does not respond well to treatment. We have identified 2 genes, aP2 and mal1, that may be important in the development of asthma. Drugs targeted against these genes may be useful in the treatment of asthma. In this project, we aim to understand how aP2 and mal1 contribute to disease development.