Australia has one of the highest asthma rates in the world. In this project we will study how natural regulatory T cells suppress asthma in a mouse model. We will determine where and when interactions between regulatory T cells and allergic T cells occur, and define the mechanisms used by regulatory cells to mediate their suppressive effects. Our findings will aid in understanding why asthma develops and how it may be controlled by the immune system itself.
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
Developmental Aspects Of Respiratory Inflammation, Allergy And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$7,169,609.00
Summary
Asthma develops as a complex series of interactions between genetic susceptibility and environmental exposures occurring in early life. While many children grow out of asthma others do not and develop the chronic form of the disease that persists into adult life. Our research involves understanding why some susceptible children develop asthma and why this becomes chronic in some. We will undertake studies in children to find out how and why this occurs. A major part of our studies involve longit ....Asthma develops as a complex series of interactions between genetic susceptibility and environmental exposures occurring in early life. While many children grow out of asthma others do not and develop the chronic form of the disease that persists into adult life. Our research involves understanding why some susceptible children develop asthma and why this becomes chronic in some. We will undertake studies in children to find out how and why this occurs. A major part of our studies involve longitudinal studies in cohorts of children recruited before birth. Having the ability to study children as they grow and develop conditions such as allergies and asthma allows us to understand why these conditions occur and allow us to predict which children are likely to develop them. Our research Program also has a solid focus on Translational Research, in which we will use the findings from our basic science studies to develop and test new methods of preventing and of treating asthma. These studies will include new methods for preventing the development of allergies, preventing the damage done to the lungs by severe viral respiratory infections in early life and better methods of treating established allergic asthma by improving immunotherapy techniques. By its very nature, primary prevention of disease in young children is controversial and raises some interesting questions. As part of this Program we intend to initiate consultation and debate in public, academic, regulatory and industry circles. An important role for our Program is shifting the current emphasis away from treatment of established disease towards preventing disease occurring. This is the best way to decrease the health, social and economic burden of chronic diseases such as asthma.Read moreRead less
Environmental Influences On Allergic Airways Disease From Birth To 8yrs: Long-term Outcomes Of A Randomised Trial (CAPS)
Funder
National Health and Medical Research Council
Funding Amount
$530,000.00
Summary
The prevalence of asthma in Australia is among 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, it will not be possible to give confident advice about how to prevent asthma. We are applying to continue follow up of the cohort of the ....The prevalence of asthma in Australia is among 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, it will not be possible to give confident advice about how to prevent asthma. We are applying to continue follow up of the cohort of 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. 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. The interventions are stopped at age 5 years. The continued follow up of the cohort to age 8 will enable us to test conclusively if 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
Allergen-sensitzation And Environmental Exposures In Early Life Interact Synergistically To Alter Lung Growth
Funder
National Health and Medical Research Council
Funding Amount
$425,088.00
Summary
Asthma develops as the result of complex interactions between genetic susceptibilities and environmental exposures. Approximately 40% of 6-year-old children in Perth are sensitized to inhaled allergens, however, only half of these have asthma. Allergic sensitization per se is therefore insufficient for the development of persistent asthma. A second hit, associated with lung inflammation in early life, increases this risk several fold. This second hit could come from viral infection or from other ....Asthma develops as the result of complex interactions between genetic susceptibilities and environmental exposures. Approximately 40% of 6-year-old children in Perth are sensitized to inhaled allergens, however, only half of these have asthma. Allergic sensitization per se is therefore insufficient for the development of persistent asthma. A second hit, associated with lung inflammation in early life, increases this risk several fold. This second hit could come from viral infection or from other inflammatory stimuli such as exposure to cigarette smoke, air pollutants and vehicle exhaust emissions. The timing of this second hit may well be important, particularly if it is early while the lungs are still growing and developing. The aim of this project is to examine interactions between allergen sensitization and exposure to environmental hazards in early life using a mouse model of allergic inflammation. We will test the hypothesis that the combination of allergic sensitization and viral infections in early life alter lung growth, airway function and airway hyperresponsiveness, however, exposure to air pollutants can not provide the 'second hit required to induce persistent asthma. Determining the role viral infection and environmental pollution have early in life may provide us with a strategy for intervention that could prevent life-long changes in respiratory function and airway hyperresponsiveness.Read moreRead less