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.
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.