Asthma is a common problem for women during pregnancy. There is concern about how asthma and its treatment may effect the baby, and also concern that asthma may deteriorate during pregnancy. Variable adherence to treatment compounds this situation. Current clinical measures are not very accurate in determining the correct dose of inhaled therapy to be used for asthma. However, there is now good evidence from clinical trials in nonpregnant adults and children that this situation can be improved b ....Asthma is a common problem for women during pregnancy. There is concern about how asthma and its treatment may effect the baby, and also concern that asthma may deteriorate during pregnancy. Variable adherence to treatment compounds this situation. Current clinical measures are not very accurate in determining the correct dose of inhaled therapy to be used for asthma. However, there is now good evidence from clinical trials in nonpregnant adults and children that this situation can be improved by using markers of inflammation to guide therapy. One of the promising tests of inflammation is exhaled nitric oxide. We wish to determine whether asthma can be better managed during pregnancy by using nitric oxide to guide therapy. We will examine whether this approach leads to fewer asthma exacerbations, lower doses of corticosteroid, better asthma control, and better outcomes for the baby. To do this we have put together a team with expertise across each of the important areas of asthma, pregnancy, and research methods. This will enable the study to provide a clear indication of which treatment approach is better, and this can then be offered to pregnant women and their health care team.Read moreRead less
Viral Infection And Exacerbations Of Asthma During Pregnancy: Characteristics, Mechanisms And Consequences
Funder
National Health and Medical Research Council
Funding Amount
$465,210.00
Summary
At least 12% of pregnant women in Australia have asthma and more than half of these women will experience an acute attack during pregnancy. This puts the fetus at risk of poor outcomes such as low birth weight or premature birth, which has a significant impact on their health in both the short term and long term. The mechanisms which lead to exacerbations of asthma during pregnancy are unknown, but have implications for the treatment of pregnant women with asthma. In non-pregnant adults, the maj ....At least 12% of pregnant women in Australia have asthma and more than half of these women will experience an acute attack during pregnancy. This puts the fetus at risk of poor outcomes such as low birth weight or premature birth, which has a significant impact on their health in both the short term and long term. The mechanisms which lead to exacerbations of asthma during pregnancy are unknown, but have implications for the treatment of pregnant women with asthma. In non-pregnant adults, the majority of asthma exacerbations are caused by viral infection and it is likely that a similar mechanism operates in pregnant women with asthma. No previous studies have identified the viruses responsible for exacerbations of asthma during pregnancy. We currently have a promising lead in this area, with data showing that one third of pregnant women with asthma have a severe exacerbation of their asthma requiring medical intervention during pregnancy, and a large proportion of these are likely to be due to viral infection. We propose that during pregnancy, pregnant women with asthma are more susceptible to viral infection than pregnant women without asthma. We also suggest that women with asthma will have more severe viral infections during pregnancy, and that these will contribute to the majority of acute asthma attacks during pregnancy. This project will determine the rate of infection among pregnant women with and without asthma and determine the viruses responsible for acute attacks of asthma during pregnancy. The study will also explore the inflammatory mechanisms which predispose women to viral infection. These results will contribute to a greater understanding of the mechanisms leading to exacerbations of asthma during pregnancy and will be used to develop more appropriate asthma monitoring and treatment strategies for pregnant women, which will have health benefits for both mother and baby.Read moreRead less
The AMAZES Study: Asthma And Macrolides: The AZithromycin Efficacy And Safety Study
Funder
National Health and Medical Research Council
Funding Amount
$3,157,566.00
Summary
Asthma is a health priority for Australia where better and new treatment approaches are needed. This project tests the benefit of a common antibiotic for use in asthma. We propose to conduct a large-scale, multicentre, double-blind, placebo controlled study comparing the efficacy (and safety) of the addition of oral low dose azithromycin to maintenance asthma therapy on the incidence of asthma exacerbations and clinical asthma status in participants with asthma.
Functional Significance Of Subcellular Localisation Of Viral 3C Protease In Rhinovirus Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$613,513.00
Summary
Rhinovirus (RV) infections are the major cause of virus induced asthma attacks and common colds, causing significant morbidity and mortality. The incidence of asthma is increasing worldwide with new strategies urgently needed to reduce RV-associated disease. We have observed RV 3C protease in the nuclear compartment of infected host cells and propose to determine its significance in RV pathogenesis with relevance to asthma therapies.
Chronic obstructive pulmonary disease (COPD) is a smoking-induced lung disease that is the fourth leading cause of death in Australia. The immune system is highly likely to play an important role in the progression of this condition, because of the frequency of respiratory infections that occur. We will examine in detail the immune response of COPD patients, examining specific genes and proteins that are important in the defence against bacteria. Blood samples will be obtained from people with C ....Chronic obstructive pulmonary disease (COPD) is a smoking-induced lung disease that is the fourth leading cause of death in Australia. The immune system is highly likely to play an important role in the progression of this condition, because of the frequency of respiratory infections that occur. We will examine in detail the immune response of COPD patients, examining specific genes and proteins that are important in the defence against bacteria. Blood samples will be obtained from people with COPD who are stable. We will then obtain further blood samples when there is a flare-up of the lung condition, and during recovery. We will compare the results from the blood samples, with variations in the genes that people carry. Information about individual differences in the body's response to infection would help us to better understand how COPD develops, and to initiate research on new methods of diagnosis and treatment of COPD.Read moreRead less
Respiratory Viral Infections As Triggers Of Acute Severe Asthma Exacerbations In Atopics: Mechanistic Studies In An Experimental Model
Funder
National Health and Medical Research Council
Funding Amount
$659,494.00
Summary
An important unresolved issue in asthma research is why almost all the children who present in hospital emergency with very severe asthma attacks are both allergic and virally infected. This project will seek to define how immune responses to viruses and aeroallergens interact to create very severe inflammation in the airways thus precipitating the severest type of asthma attacks. Understanding the underlying mechanisms will hopefully provide new clues towards better treatments.
Molecular Characterisation Of TRAIL-regulated Signal Transduction Pathways And Their Role In The Development, Persistence, And Exacerbation Of Allergic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$637,035.00
Summary
Molecules that promote the development, persistence, and exacerbation of asthma are only poorly defined. We have discovered a novel signalling pathway that is activated in the airway wall during asthma. Blocking a molecule that activates this pathway ameliorated asthma in mice. We now want to identify all the important components of this pathway and therapeutically modulate them to prevent the development, persistence, and exacerbation of asthma.
The Role Of Pulmonary Macrophages In The Pathogenesis Of An Acute Exacerbation Of Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$495,710.00
Summary
We will examine the role of lung defence cells, known as macrophages, in triggering the inflammation of acute severe asthma. The experimental work will use unique mouse models of mild chronic asthma and of an acute exacerbation of the illness, which have been developed in our laboratories. We will study the mechanisms of activation of the asthmatic response and assess whether treatment with drugs that suppress the function of macrophages can help to control steroid-resistant exacerbations.
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.
Macrophages, Sugars And Innate Immunity In Chronic Lung Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$413,150.00
Summary
This project is about a new idea to treat severe asthma, chronic obstructive lung disease (COPD) and sudden worsening of these diseases (exacerbations). Asthma and COPD are very common. Asthma afflicts approximately 10 % of all Australians and kills approximately 700 annually. COPD will be the third most common cause of death worldwide by 2010 (WHO) and costs more that $ AUS 10 Billion annually. The highest risk of death and greatest costs are associated with severe asthma and exacerbations. Our ....This project is about a new idea to treat severe asthma, chronic obstructive lung disease (COPD) and sudden worsening of these diseases (exacerbations). Asthma and COPD are very common. Asthma afflicts approximately 10 % of all Australians and kills approximately 700 annually. COPD will be the third most common cause of death worldwide by 2010 (WHO) and costs more that $ AUS 10 Billion annually. The highest risk of death and greatest costs are associated with severe asthma and exacerbations. Our idea, which is based on extensive animal data, is that these diseases can be treated by blocking the activity of proteins that allow a cell called the lung macrophage to grow, become activated, proliferate and survive. These proteins are called CSF-1 and GM-CSF and they belong to a larger class of proteins called colony stimulating factors (CSFs) Macrophages are important because they can rapidly respond to bacteria, viruses and fungi that can infect the lungs of asthma and COPD patients. Infections cause exacerbations. Normally, macrophages release a number of molecules called mediators that rouse a strong defensive reaction- a process called innate immunity. For example macrophages signal for a cell type called the neutrophil, which is a very efficient bacteria killer, to flood into the lung. However, these same cells can cause serious lung damage if the response is too strong or persistent. Macrophages and neutrophils need CSFs to work properly so blocking CSFs prevents lung damage. Although we now already know that blocking CSFs can prevent and reverse lung inflammation we still need to know a great deal more in order to know if this approach will be useful to treat people in the future. Our project is therefore all about understanding the fine detail of how CSFs can damage the lung. The importance of the project is that our work may lead to entirely new, and much more effective, treatments for people suffering from asthma and COPD.Read moreRead less