Lung infections are the most frequent triggers of asthma exacerbations. While different infections cause exacerbations by they all result in the same type of lung inflammation. Using novel disease models, we have identified key molecules involved in a range of viral and bacterial induced asthma exacerbations. We will define these shared pathways that link viral and bacterial-mediated asthma exacerbations, thus these studies will pave the way for the development of unified treatments.
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.
Th17 Cell Cytokines In Airway Wall Remodelling In Chronic Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$295,983.00
Summary
In asthma, structural changes in the airway wall occur which thicken the muscle and epithelial layers, stiffen the airways and increase mucus production. This 'remodelling' makes breathing more difficult and is not effectively reversed with current treatments. We will study the cells and molecules involved in the development of these changes. This project will increase our understanding of the processes which drive these changes and may lead to the development of improved medications.
Monitoring Of Leucocyte Cytokine-chemokines To Improve Morbidity And Rejection Rates In Lung Transplant Patients
Funder
National Health and Medical Research Council
Funding Amount
$373,973.00
Summary
Lung transplantation has become established therapy for many serious lung diseases. The early success rate is now very good, but at five years after transplant the survival rate is only around 60%. This problem is largely due to chronic graft failue as a result of chronic rejection or bronchiolitis obliterans syndrome. This project will specifically investigate the causes of BOS and thereby provide new information on how we may best treat this problem. An improvement in this area is critical.
Airway Smooth Muscle Control Of Mast Cells In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$612,696.00
Summary
Around 12% of Australians are asthmatic, with up to 25% of children affected. Thus it is a significant burden for us and our healthcare system. Currently we treat asthma with corticosteroids to reduce airway inflammation, otherwise the inflammation leads to thickened airways with increased amounts of smooth muscle (ASM) that contracts too much and too easily. However more research is needed. Corticosteroids sometimes stop working or have unwanted side effects, especially for children, and we sti ....Around 12% of Australians are asthmatic, with up to 25% of children affected. Thus it is a significant burden for us and our healthcare system. Currently we treat asthma with corticosteroids to reduce airway inflammation, otherwise the inflammation leads to thickened airways with increased amounts of smooth muscle (ASM) that contracts too much and too easily. However more research is needed. Corticosteroids sometimes stop working or have unwanted side effects, especially for children, and we still cannot prevent asthma developing or cure it. We need to know more about the chemical signals which cause the pattern of inflammation that is specific for asthma in order to cure it and prevent it developing. Recently, inflammatory cells called mast cells (MC) have been found in increased numbers in the ASM layer of asthmatics compared with bronchitics or healthy people. MC release mediators that contract the airways, induce mucous secretion and promote further inflammation. We think the effects ASM cells and MC have on each other are central factors in causing physical changes to the airways of asthmatics. In asthmatics we have identified a chemical message (IP10) released in increased amounts by the ASM which attracts MC to it. We also have evidence that ASM from people without asthma release factors that prevent IP10 and similar chemical messages from working on MC. These two exciting findings demonstrate asthmatic ASM is different. We will investigate why asthmatic ASM produces more IP10 and try to prevent each of the steps we identify with drugs that have very specific actions. In addition, we will identify the factors released by non-asthmatic ASM that inhibit IP10 and similar chemical messages from working. The additional knowledge gained by this research may lead to the design of novel treatments to prevent asthma symptoms without side effects and lead to new strategies to prevent asthma developing, especially in children.Read moreRead less
Airway Smooth Muscle - Mast Cell Cross Talk In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$527,250.00
Summary
In Australia 1 in 4 children and 1 in 10 adults are asthmatic and so asthma is a significant burden to our community and our healthcare system. Currently we treat asthma with corticosteroids to reduce airway inflammation because, without them, chronic inflammation leads to thickened airways with increased amounts of smooth muscle that contracts too much and too easily. However, corticosteroids may have side effects , particularly in children. In order to design safer more specific treatments for ....In Australia 1 in 4 children and 1 in 10 adults are asthmatic and so asthma is a significant burden to our community and our healthcare system. Currently we treat asthma with corticosteroids to reduce airway inflammation because, without them, chronic inflammation leads to thickened airways with increased amounts of smooth muscle that contracts too much and too easily. However, corticosteroids may have side effects , particularly in children. In order to design safer more specific treatments for asthma, we need to know more about the pattern of inflammation that is specific for asthma and what chemical signals cause it. Then we will be able to target it more specifically. Recent research has demonstrated that in asthma, but not in bronchitis or in healthy people, inflammatory cells called mast cells are found in increased numbers down in the smooth muscle layer of the airways. Mast cells are key cells in all allergic reactions. In the airways they release mediators that contract the airways, induce mucous secretion and promote further inflammation. We think the effects airway smooth muscle cells and mast cells have on each other are central factors in causing the physical changes to the airways of asthmatics. We will identify what chemical messages released by the smooth muscle attract mast cells to it and once they are there, what the mast cells stick to on the smooth muscle. Then we will investigate how the two cell types interact with each other and affect each other. We will focus on how the functions of the smooth muscle cells are affected, especially those that would promote further inflammation and lead to increased amounts of more sensitive, more contractile smooth muscle. We will try to prevent each of the steps we identify with drugs that have very specific actions. This additional information may lead to the design of novel treatments for asthma that have fewer side effects.Read moreRead less