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
Sex-related Changes In Asthma During The Transition Through Puberty In The CAPS Birth Cohort
Funder
National Health and Medical Research Council
Funding Amount
$831,581.00
Summary
Early adolescence is a critical period in the life of people with asthma. Some children grow out of their asthma and others acquire the disease for the first time. There are important sex differences in the pattern of change. We believe these changes are related to the passage through puberty. This study will examine changes in the features of asthma and allergy during this period and their relation to early life and current environmental exposures.
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
Exploration Of Exposures Associated With Bedding That Are Risks For Childhood Allergy And Asthma Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$263,500.00
Summary
Asthma prevalence in Australia has doubled in the last 20 years, with 1 in 4 children now affected. House dust mites are probably the single most important allergen associated with asthma. The prevalence of mite allergy is linked to exposure, and such allergy when combined with high exposure, is a potent risk factor for asthma exacerbations. The current international advice for managing mite-allergic asthma, strongly advocates the use of bedding encasings as the best way to reduce exposure. Howe ....Asthma prevalence in Australia has doubled in the last 20 years, with 1 in 4 children now affected. House dust mites are probably the single most important allergen associated with asthma. The prevalence of mite allergy is linked to exposure, and such allergy when combined with high exposure, is a potent risk factor for asthma exacerbations. The current international advice for managing mite-allergic asthma, strongly advocates the use of bedding encasings as the best way to reduce exposure. However, three recent major trials using encasings and a meta-analysis of earlier trials all fail to show a clinical benefit. One of the applicants (ET) recently showed, using expertise in measuring personal exposure, that these encasings, as used, fail to significantly reduce aeroallergen exposure. By contrast, 3 recent Australian studies, involving the applicants, AK, ALP and NG showed that feather bedding compared to synthetic bedding, was strongly protective for asthma - the opposite of public advice. The suggested mechanisms involve reduced exposure to mite allergens, or altered exposure to bacterial endotoxin, but persuasive experimental support is lacking. We also propose a novel hypothesis that feather exposure may induce allergic 'tolerance'. Currently there is a lack of certainty about valid approaches to prevent asthma, and the Global Initiative for Asthma has described the need to understand mechanisms and improve interventions as urgent. This project is an ideal opportunity to combine the expertise of the CIA (ET) in measuring airborne exposures (mite, endotoxin, proteins) with that of the others who have expertise in children's asthma, and who are already involved in two large clinical trails involving different bedding and allergen avoidance. Our measurements of these bedding exposures and their clinical outcomes will provide, for the first time, a quantitative basis to refine public health allergen-based interventions to prevent and manage asthma.Read moreRead less
We will conduct a survey of respiratory symptoms, lung function, smoking status, occupational exposures, and other risk factors among 3200 people aged 40 years and over living in five Australian communities: Melbourne, Sydney, Tasmania, Busselton (WA), and the Kimberley region (WA). In the Kimberley we will survey 400 Aboriginal people and 400 non-Aboriginal people. We will use a survey methodology that has been developed by an international expert panel and has been implemented in many other co ....We will conduct a survey of respiratory symptoms, lung function, smoking status, occupational exposures, and other risk factors among 3200 people aged 40 years and over living in five Australian communities: Melbourne, Sydney, Tasmania, Busselton (WA), and the Kimberley region (WA). In the Kimberley we will survey 400 Aboriginal people and 400 non-Aboriginal people. We will use a survey methodology that has been developed by an international expert panel and has been implemented in many other countries (in North and South America, Asia, and Europe). This study will provide the first nationally-representative information on the burden of chronic obstructive pulmonary disease (COPD) and the opportunities for health gain by improving the management of this illness. In Australia, COPD is a relatively silent and under-recognised disease but nevertheless is the third most important contributor to the burden of disease and the third leading cause of hospital admission as well as being the underlying cause of 4.2% of all deaths. The information we will collect is needed to form a basis for prevention and disease management interventions to reduce the burden of COPD, particularly among population sub-groups who are disproportionately affected, either due to greater exposure to risk factors (mainly tobacco smoking and occupation), greater susceptibility, under-recognition and under-diagnosis, or inadequate disease management. Importantly, the study will serve to raise awareness about the hazards of smoking for all Australians. By identifying target groups, prevalent exposures and management deficiencies, it will lead the way towards policy-relevant randomised controlled trials testing community-based interventions to prevent COPD and-or manage it more effectively. The information collected will help advance knowledge of the prevalence, burden and treatment of COPD that will be relevant to communities throughout the world.Read moreRead less
Does Caffeine Affect The Development Of The Very Immature Brain: Dose Response Relationship?
Funder
National Health and Medical Research Council
Funding Amount
$668,386.00
Summary
Premature birth is a major health problem worldwide. Preterm babies often develop apnoea of prematurity (AOP), which is commonly treated with caffeine. Trials indicate that preterm babies treated with low dose caffeine have less neurodevelopmental disabilities at 18 months. Higher doses of caffeine are often needed to reduce AOP but the risk of this is unknown. We will study the short and long-term effects of increasing doses of caffeine on the developing brain in a long-gestation species.
A Preclinical Model Of Relapse In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$573,515.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease. We also hope to identify markers that can be used to screen for patients at increased risk of relapse.