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The Pathogenesis Of Distinct Endophenotypes Of Asthma Is Underpinned By The Collaborative Activation Of Specific PRRs.
Funder
National Health and Medical Research Council
Funding Amount
$678,754.00
Summary
Asthma is a chronic airway disease caused by inflammation. Although asthmatics can be sub-typed based on the type of inflammatory cells present in the lungs, medication specific for the treatment of these sub-types is not yet available. In this grant we will investigate the immune processes that orchestrate the development of the distinct inflammatory sub-types of asthma. This information will help us develop new therapies that will be tailored to target the appropriate type of inflammation.
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
Extending The MIS BAIR Randomised Trial Of BCG To Prevent Childhood Allergy And Infection
Funder
National Health and Medical Research Council
Funding Amount
$939,504.00
Summary
BCG (used till recently to prevent tuberculosis) is a potential low cost and readily available vaccine which could reduce the rates of allergy and infection in Australian children. We propose to extend our existing NHMRC-funded trial, which studies whether BCG vaccinatinon given at birth prevents the development food allergy, eczema and infection in the 1st year of life, to see if this effect continues until 5yrs of age. At this age, we can also see if BCG vaccination at birth prevents asthma.
Upper Bedding As A Prevention Measure In Childhood Asthma: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$198,075.00
Summary
Asthma has recently been identified as a National health Priority (1) by the Australian Government in view of the increasing prevalence of asthma and its great importance as a public health problem. The total health system costs of asthma are estimated to be in excess of $600 million (2). Recently, feather pillows have been shown to have more than five times less house dust mite allergen than other pillows. To date, several population-based studies have shown that children using feather upper be ....Asthma has recently been identified as a National health Priority (1) by the Australian Government in view of the increasing prevalence of asthma and its great importance as a public health problem. The total health system costs of asthma are estimated to be in excess of $600 million (2). Recently, feather pillows have been shown to have more than five times less house dust mite allergen than other pillows. To date, several population-based studies have shown that children using feather upper bedding are also reported by their parents to have less severe wheeze. These findings call into question the National Asthma Council recommendation that people with asthma who are allergic to house dust mite should use synthetic quilts rather than feather or down (3). However, concerns remain that these important findings may only have occurred because unmeasured factors, such as the socioeconomic status or child diet may be closely related to feather bedding use, and in themselves, protective against asthma. Alternatively, parents of a child with asthma symptoms may be more likely to have chosen non-feather bedding. The best way to address these concerns is to conduct a randomised controlled trial to evaluate whether the use of new feather upper bedding is associated with reduced asthma severity among house dust mite-sensitised children with severe asthma. This study is underway and has support in 2001-2002 from the Financial Markets Foundation for Children. The research will address the following NHMRC Primary Health Care project grant thematic research areas: Evidence based primary health care practice; Quality of primary care; and Illness prevention and health promotion as a primary health care strategy. (1) National Health Priority Areas: Asthma. http:--www.health.gov.au-hsdd-nhpq-asthma-index.htm (2) NH and MRC Evidence Based Clinical Practice Research Program Workshop - December 16-17, 1999. (3) National Asthma Campaign Asthma Management Handbook 1998Read 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
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
Providing Translatable Evidence To Advance Prevention And Management Of COPD: A Longitudinal Study From The 1st To 7th Decade Of Life
Funder
National Health and Medical Research Council
Funding Amount
$2,893,320.00
Summary
Chronic obstructive pulmonary disease (COPD) makes breathing difficult and reduces wellbeing. People are more likely to get COPD from the age of 60 years, but we do not know why and who. Our study will develop tools to identify early who will develop COPD by 60 years. We will also develop a tool to identify 60-year-old individuals whose lung function is declining faster than normal. These findings will help us to better prevent and manage COPD.
I am a research scientist measuring inhaled and exhaled bioaerosols, such as viruses and allergens, to determine their clinical role in human respiratory diseases, particularly asthma.
Inhibition Of Allergic Airway Inflammation By Nanoparticles
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Inhaled air pollution particulate matter causes asthma exacerbations, with 'ultrafine' nanoparticles thought to play a major role. Unexpectedly, we recently found that, by contrast, administration of inert ultrafine nanoparticles prevents allergic airway inflammation. We will identify the key particle physical and chemical properties associated with this novel type of disease inhibition, study particle effects in clinically-relevant disease models and identify mechanisms of action.