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
Antiviral Defects Of The Airway Epithelium Associated With Wheeze And Atopy In Children
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Asthma affects 10-15% of Australian. Repeated respiratory viral infections increase the risk of developing asthma, and are also the principal cause of asthma attacks. Asthmatics may be more susceptible to respiratory viral infections due to a defect in the innate antiviral response to infection. Here we aim to identify defects in the antiviral response of children who are at risk of developing asthma, and understand how they occur so that future therapies may be developed.
Exploring The Role Of Respiratory Virus Infections In Childhood Asthma Exacerbations
Funder
National Health and Medical Research Council
Funding Amount
$596,649.00
Summary
The PEAK study will explore the reasons children get worse asthma symptoms when they get colds. These reasons examined include the asthma medications taken (or not taken), allergies and exposure to allergens and the type of virus involved. The study follows the children over the whole school term and uses a new way to sample virus by collecting it in the breath, this is more comfortable than old methods and can be done at home.
Asthma is a major health problem for the Australian community. Recent studies have shown increasing numbers of people of all ages are developing asthma. Despite extensive asthma research and the development of new asthma drugs, asthma remains a leading cause of ill- health, especially in children. In many cases the deterioration in asthma symptoms is related to a cold or flu like illness, Viruses are the leading cause of these infections and are known to make asthma symptoms worse. How they do t ....Asthma is a major health problem for the Australian community. Recent studies have shown increasing numbers of people of all ages are developing asthma. Despite extensive asthma research and the development of new asthma drugs, asthma remains a leading cause of ill- health, especially in children. In many cases the deterioration in asthma symptoms is related to a cold or flu like illness, Viruses are the leading cause of these infections and are known to make asthma symptoms worse. How they do this is not completely understood. Asthma causes a unique type of inflammation in the airways, which is present in even mild asthma and can be controlled by medication. Viruses also cause inflammation by infecting the lungs. Viruses can cause severe attacks of asthma even when asthma appears controlled on medication. The ways in which virus infections do this, are not established. By understanding how this happens we may be able to design effective treatment for this problem. Our initial results indicate that virus induced asthma is different to asthma that is triggered by allergens. We plan to investigate what effect certain viruses have on the lungs of people with asthma by measuring cells and chemicals that are present in sputum. We will use recently developed technologies to accurately see what viruses are infecting these people, and then evaluate the role of treatment of virus induced asthma. This study will shed important light on potential causes of unstable asthma and the role that viral infection plays in this. It may also lead to new opportunities to develop treatments that are more effective in preventing and controlling asthma.Read moreRead less
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.
I am a respiratory physician studying mechanisms of respiratory allergy and host defence against respiratory viruses. My research aims to develop new ways of treating airway inflammation in asthma and COPD.
Anti-viral Immune Dysfunction In Severe Asthma Varies Across Inflammatory Phenotypes.
Funder
National Health and Medical Research Council
Funding Amount
$997,153.00
Summary
Common cold viruses often trigger asthma flare-ups , but have relatively minor effects on healthy people. Why this happens is not clear. We have identified two different ways in which the immune system can react badly to a common cold virus in people with asthma. In this study we will find out more about why the immune system does not react normally in a large group of people with severe asthma. This study will help us discover improved treatments that can be targeted to people with asthma.
Exposure Of Bronchial Epithelial Cells To Inflammatory Stimuli Impairs Their Innate Immune Response To Rhinovirus.
Funder
National Health and Medical Research Council
Funding Amount
$325,966.00
Summary
Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory conditions in Australia, both of these conditions are characterised by acute attacks precipitated by respiratory virus infections. The most common trigger for these acute attacks is the usually innocuous common cold virus, rhinovirus. The reason for this susceptibility remains poorly understood. We have previously shown that the cells lining the airways of asthmatics are more susceptible to infection with rhi ....Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory conditions in Australia, both of these conditions are characterised by acute attacks precipitated by respiratory virus infections. The most common trigger for these acute attacks is the usually innocuous common cold virus, rhinovirus. The reason for this susceptibility remains poorly understood. We have previously shown that the cells lining the airways of asthmatics are more susceptible to infection with rhinovirus and fail to react to this infection effectively. We propose to further elucidate this defect and for the first time determine if it is also present in subjects with COPD. We will examine the airway cells of subjects with asthma and COPD and look for evidence of a defective immune response, relating this to the presence of persistent bacterial infection. We will then grow these and infect them with rhinovirus, carefully examining the mechanisms behind this impaired response to infection and then see if we can induce such impairment in these cells with chronic exposure to infection and inflammatory stimuli. Our laboratory is well placed to investigate these problems with an established track record in investigating patients with inflammatory airways disease and virus infection, unparalleled access to sufficient well characterised clinical samples and have demonstrated the ability to study virus epithelial cell interactions. This work will highlight those at risk of developing frequent debilitating exacerbations along with the reasons for this and identify areas to target novel therapeutic interventions.Read moreRead less
In the asthmatic lung structural changes or remodelling occur, which are thought to contribute to the abnormal functioning of the airways. These remodelling events which occur in the asthmatic airway include increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix ECM proteins), and an increased mass of bronchial smooth muscle cells. Many of these critical structural changes are not reversed or prevented with current asthma therapy. Remodelling is an i ....In the asthmatic lung structural changes or remodelling occur, which are thought to contribute to the abnormal functioning of the airways. These remodelling events which occur in the asthmatic airway include increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix ECM proteins), and an increased mass of bronchial smooth muscle cells. Many of these critical structural changes are not reversed or prevented with current asthma therapy. Remodelling is an important process in both the development and progression of asthma. The reason why remodelling occurs in the lungs of people with asthma is not known. It is thought that persistent inflammation drives the remodelling process; however remodelling can perpetuate inflammation, thereby creating a cyclic series of events. Furthermore we have shown that cells from non-asthmatic volunteers which are grown on asthmatic ECM change to become more like cells from asthmatic subjects. Viruses which infect the lungs may play a role in the development of asthma, and in the increased remodelling which is observed. Many common respiratory viruses are capable of infecting lung cells, eg epithelial cells, which evokes an inflammatory response. I will investigate if viral infection can alter the remodelling process, using lung cells isolated from asthmatic and non-asthmatic volunteers. Furthermore, I will assess if current and novel treatments are effective in reducing the remodelling process. We have preliminary evidence that infection of lung epithelial cells with rhinovirus (the common cold virus) alters the amount of ECM deposited by these cells. I hypothesise that this process will be increased in cells from volunteers with asthma compared to non-asthma. As current therapeutics are unlikely to be able to reverse these remodelling events these experiments will enable the development of new therapeutics which can target this important aspect of airway disease.Read moreRead less