Outcome Of Childhood Asthma In Adult Life And The Interaction With COPD
Funder
National Health and Medical Research Council
Funding Amount
$503,549.00
Summary
The Melbourne Study of Childhood Asthma (MESCA) is the longest, most comprehensive follow-up study of childhood asthma. The members were recruited in 1964 at the age of 7 and they have been reviewed at ages 10, 14, 21, 28, 35 and 42 years of age with a retention rate of 87% of survivors at the most recent follow-up. To date, the MESCA study has provided comprehensive data on the outcome of childhood asthma through to their adult years and has been particularly influential in establishing approac ....The Melbourne Study of Childhood Asthma (MESCA) is the longest, most comprehensive follow-up study of childhood asthma. The members were recruited in 1964 at the age of 7 and they have been reviewed at ages 10, 14, 21, 28, 35 and 42 years of age with a retention rate of 87% of survivors at the most recent follow-up. To date, the MESCA study has provided comprehensive data on the outcome of childhood asthma through to their adult years and has been particularly influential in establishing approaches to treatment of paediatric asthma nationally and internationally. The results of the study have been published widely over the years and cited extensively. The members of this cohort turn 50 in 2007 and will be invited to participate in a further review to reassess their clinical outcome to examine the relationship between long standing asthma and the development of COPD. Those members of the cohort who have had asthma persisting through their adult years have a degree of fixed obstruction on their tests of lung function and are potentially at risk of developing COPD. Some are at increased risk as approximately 30% of the members are regular smokers. In this review, at age 59 years, there is an excellent opportunity to examine the interaction of asthma and COPD and to compare the inflammatory processes between those who have continuing asthma, those whose asthma has resolved and in each group examine the effect of smoking. We will also look at a numbers of genetic markers associated with COPD to identify those who are more susceptible to the development of COPD. A second area of interest is the components of the immune system that influence asthma.. In an earlier study we identified one component of the immune system, known as the T cell system, that had returned to normal in those whose asthma had resolved. In this review, we plan to examine the T cell system in detail to understand what mechanisms may be responsible for resolution of childhood asthma.Read moreRead less
The Effect Of Chronic Maternal Asthma And Acute Exacerbations On Placental Function And Fetal Development
Funder
National Health and Medical Research Council
Funding Amount
$224,623.00
Summary
Maternal asthma is the most common disease to complicate pregnancies in Australia. The data we have collected so far suggests that asthma represents a physiological maternal stress during pregnancy that influences placental function and fetal development. The purpose of this grant is to continue to determine what changes occur in the presence of maternal asthma that alter fetal growth. The findings of this work will be applicable to any psycho-social or physiological stressor during pregnancy.
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.
Developmental And Cellular Mechanisms Involved In The Pathological Changes To The Epithelium In Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$263,500.00
Summary
A consensus has developed in recent years that asthma involves chronic airway inflammation superimposed upon a background of airway remodelling. If untreated, these processes result in increased airway responsiveness, variable airflow obstruction and ultimately a progressive decline in lung function). Recently the role of the epithelium in the pathogenesis of asthma has been emphasised based upon observations indicating that the epithelium can play an important role in airway inflammation and re ....A consensus has developed in recent years that asthma involves chronic airway inflammation superimposed upon a background of airway remodelling. If untreated, these processes result in increased airway responsiveness, variable airflow obstruction and ultimately a progressive decline in lung function). Recently the role of the epithelium in the pathogenesis of asthma has been emphasised based upon observations indicating that the epithelium can play an important role in airway inflammation and remodelling. However, this paradigm has been developed using data accumulated almost exclusively from studies in adults. Epidemiological studies suggest that airway remodelling might play a less significant role in the majority of childhood asthma since most children with asthma have relatively minor symptoms, minimal disruption of lung function and tend not to have symptoms that persist into adulthood. Clearly the relative importance of inflammation and remodelling and the regulatory mechanisms involved are important factors to understand particularly if new, effective prevention and therapeutic strategies are to be developed. For the first time in children, the proposed project will allow the study of asthma mechanisms using target organ tissue (airway epithelium) from a large unselected population. Primary cell samples recovered by bronchial brushing will be analysed separately and also cultured in order to investigate critical elements of the pathogenesis of asthma. Data collected from symptomatic children can be easily compared with that from healthy controls and also with data from adults to determine age related factors that contribute to asthma. Furthermore, the establishment of a repository of cultured epithelial cells from these children will provide a unique resource that will allow future collaborations with scientists studying a variety of mechanisms in asthma and with the pharmaceutical industry.Read moreRead less
Is Lyn Tyrosine Kinase A Predictor Of Severe, Persistent Multi-trait Asthma And Allergy?
Funder
National Health and Medical Research Council
Funding Amount
$250,250.00
Summary
Asthma is a major health problem in Australia affecting over 10% of the population at any time, and more than 25% of the population at one stage in their lives. Although the public perception is that asthma treatments have improved management of the disease, more than 700 people die from severe asthma each year and hospitalisation from exacerbation (sudden worsening) is one of the most costly components of the health care burden in Australia and most developed countries. Currently there are no m ....Asthma is a major health problem in Australia affecting over 10% of the population at any time, and more than 25% of the population at one stage in their lives. Although the public perception is that asthma treatments have improved management of the disease, more than 700 people die from severe asthma each year and hospitalisation from exacerbation (sudden worsening) is one of the most costly components of the health care burden in Australia and most developed countries. Currently there are no molecular markers that can predict who will get severe asthma and there are no specific treatments to reverse severe exacerbations. This project will use advanced molecular biology methods to examine whether a molecule called Lyn may be important. The Lyn tyrosine kinase is a member of a family of genes that participate in transmitting information across the cell membrane. This enzyme is expressed in blood cells, and is involved in mechanisms pertaining to infection, immunity and allergic responses. To further our understanding of the role of this enzyme in the context of the whole animal, we have generated mice that are unable to make Lyn protein (Lyn-deficient mice). In animal models of asthma we know that if Lyn is not functioning, severe and persistent asthma develops. We have also made preliminary studies that suggest that Lyn does not work properly in people who have been admitted to the emergency ward with life threatenting asthma. In this study we will examine in detail the role that Lyn plays in asthma and allergy, and we intend to identify the pathways that give rise to asthma in Lyn-deficient mice. We will also investigate our hypothesis that Lyn activity may be reduced or disregulated in patients with asthma and allergy. This research should lead to better predictive markers for severe asthma and also to improved and specific treatments.Read moreRead less
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 prevalence of asthma in Australia is amongst the highest in the world yet no trials of primary prevention have been conducted which address the most common known causative agent (housedust mite allergens) and the most common known protective factor (dietary omega-3 fatty acids). Until the effectiveness of interventions which address these factors is certain, the value of the wide array of advice given to asthmatics by various health institutions will not be known. We are applying to continue ....The prevalence of asthma in Australia is amongst the highest in the world yet no trials of primary prevention have been conducted which address the most common known causative agent (housedust mite allergens) and the most common known protective factor (dietary omega-3 fatty acids). Until the effectiveness of interventions which address these factors is certain, the value of the wide array of advice given to asthmatics by various health institutions will not be known. We are applying to continue the Childhood Asthma Prevention Study (CAPS) which has been underway since mid-1997. CAPS is a randomised controlled trial in which 616 infants at high risk of developing asthma because of a family history have been enrolled. The interventions include allergen reduction and dietary supplementation with omega-3 fatty acids. The interventions are designed to have maximum effect but be simple to implement by parents. Several measures of compliance are being collected and regular contact is maintained though telephone calls and frequent home visits. Objective and subjective measurements of exposures, atopy, diet and asthmatic symptoms are being collected at 3 month intervals and at medical assessments when the children are 18 months, 3 and 5 years old. It is essential that we continue the study until all children are aged 5 and we will be able to test conclusively whether the interventions have had a positive effect. If so, CAPS will form the basis for a nationwide public health campaign which will have the potential to reduce the incidence of childhood asthma in Australia.Read moreRead less
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.
Targeting The Shared Beta-chain Of The IL-3, IL-5 And GM-CSF Receptors As Therapy For Allergic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$610,037.00
Summary
This research aims to develop new treatments for allergic diseases such as asthma and allergic rhinitis, which remain significant public health problems in Australia. We will develop therapies targeting a common receptor pathway with the potential to completely suppress acute and chronic disease whilst maintaining a single molecular target. We will perform preclinical testing of antibodies for treatment of allergic disorders using a novel mouse strain expressing the human form of this receptor
Role Of IL-3 In Allergic Inflammation: Modulation Of Basophils, Mast Cells, Eosinophils And Remodelling In Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$495,380.00
Summary
Asthma is an important disease in the Australian community. We will investigate how the underlying inflammation in this disease is controlled and will focus our studies on a hormone-like regulator of the immune system called interleukin-3. Our hypothesis is that interleukin-3 regulates basophils, mast cells and remodelling of the airways which are central features of asthma. This study will give a better understanding of how the inflammation is caused and information for new drug targets.