Innate Immune Factors Regulate Steroid-resistant Airways Hyperreactivity And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$524,456.00
Summary
Infection induced asthma is often difficult to manage because of lack of efficacy of steroid treatment. The innate immune system plays an important role in inflammation associated with infection. I have shown that two innate immune factors, IFN-gamma and lipopolysaccharide (LPS), induce airways hyperreactivity that is resistant to steroid therapy in a mouse model. Identification of how this pathway works may help in the treatment of infection induced steroid-resistant difficult to manage 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.
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
Mechanisms Of Airway Narrowing In Eosinophilic And Non-eosinophilic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$500,593.00
Summary
Asthma is associated with excessive airway narrowing, increased thickness of the airway wall and inflammation, most typically with eosinophils. However, 50% of cases have few eosinophils and respond less well to current treatments. This project will examine differences in airway structure between patients with or without eosinophils, using post-mortem tissue, as part of an international research collaboration.
Mannitol In The Assessment Of Bronchial Responsiveness In Airway Disease
Funder
National Health and Medical Research Council
Funding Amount
$365,250.00
Summary
The airways of people with asthma respond by narrowing too easily and too much to a wide range of stimuli. The tests most commonly used to measure airway responsiveness in asthma are the pharmacological agents methacholine and histamine. When inhaled, they act directly on bronchial muscle causing it to contract and hence the airways to narrow. We have developed a non-pharmacological test using a dry powder of a sugar - mannitol. When inhaled, mannitol causes narrowing of the airways in asthmatic ....The airways of people with asthma respond by narrowing too easily and too much to a wide range of stimuli. The tests most commonly used to measure airway responsiveness in asthma are the pharmacological agents methacholine and histamine. When inhaled, they act directly on bronchial muscle causing it to contract and hence the airways to narrow. We have developed a non-pharmacological test using a dry powder of a sugar - mannitol. When inhaled, mannitol causes narrowing of the airways in asthmatics but little or no effect in healthy subjects. Many asthmatics respond to mannitol even when they have few symptoms of asthma. Mannitol causes the airways to narrow 'indirectly' by causing the release of substances from inflammatory cells in the airways (e.g. histamine, leukotrienes and prostaglandins) that cause the muscle to contract. After the inflammation has cleared, either by treatment with inhaled steroids or spontaneously, the response to mannitol is close to healthy subjects. Thus the response to mannitol depends on the presence of inflammation and loss of responsiveness means resolution of inflammation. The significance of this is that the mannitol test may be used as an 'inflammometer'. It would be important if airway responsiveness to mannitol could be used to identify individuals with airway diseases other than asthma, (chronic bronchitis, and chronic obstructive lung disease) who could benefit from treatment with inhaled steroids. This would be significant as there is currently no test to identify those individuals and there are unwanted effects from using steroids. Further, it may be possible to use mannitol to identify individuals with other inflammatory diseases who may be at risk of developing asthma. Some people with asthma, chronic bronchitis and chronic obstructive lung disease have increased levels of oxidative stress. We wish to identify those people and to measure change after treatment with steroids.Read moreRead less
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.