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Morphometric Analysis Of Normal Airway Structure In Childhood And The Influence Of A History Of Asthma On This Structure
Funder
National Health and Medical Research Council
Funding Amount
$186,113.00
Summary
The architectural structure of the airways of the lung is thought to have profound effects on airway function. Changes in this structure are believed to be partly responsible for limiting the flow of air into the lung in conditions such as constant wheezing, bronchitis and asthma. Pathological studies carried out on adult lungs have shown that the structure of the airways is indeed altered in patients with lung disease when compared with patients with no history of breathing difficulties. For ex ....The architectural structure of the airways of the lung is thought to have profound effects on airway function. Changes in this structure are believed to be partly responsible for limiting the flow of air into the lung in conditions such as constant wheezing, bronchitis and asthma. Pathological studies carried out on adult lungs have shown that the structure of the airways is indeed altered in patients with lung disease when compared with patients with no history of breathing difficulties. For example, the walls of the airways are much thicker in patients with lung disease. This thickening means that the airways are much narrower and therefore not able to carry as much air as in people with healthy lungs. In addition, the muscle within the airway wall, which is normally very sparse, is much denser in people with asthma and bronchitis. Thus, the airways can be squeezed closed more easily. It is not known if these changes are present in children who have lung disease. X-rays and sophisticated breathing tests suggest that these children may also have thicker walls and more muscle in their airways. The major difficulties in assessing whether such changes are present in children, is the lack of information on the normal structure in infants; how this changes as they grow to adulthood; or if there are any gender differences. This project aims to obtain this information from the airways of male and female children from 0-18 years. This information can then be used as a basis for comparison with the structure found in children with lung disease, in particular asthma, and therefore assist in making assessments as to the cause of their breathing difficulties. With more knowledge about these causes, we will be in a better position to design new and better treatments and produce ways of preventing them ever occurring.Read moreRead less
Positive Feeding Practices And Food Preferences In Very Early Childhood - A Primary Care Obesity Prevention Program
Funder
National Health and Medical Research Council
Funding Amount
$1,459,238.00
Summary
The more than 1:5 and rapidly increasing number of overweight Australian children are at a substantially increased risk of becoming fat adults resulting in increased illness, mortality, health care burden and costs. Adult eating habits are influenced and formed by food preferences and capacity to self-regulate in response to behaviours developed in childhood. Thus parent feeding practices in very early childhood are critical. This study aims to show that a program of parent education and peer su ....The more than 1:5 and rapidly increasing number of overweight Australian children are at a substantially increased risk of becoming fat adults resulting in increased illness, mortality, health care burden and costs. Adult eating habits are influenced and formed by food preferences and capacity to self-regulate in response to behaviours developed in childhood. Thus parent feeding practices in very early childhood are critical. This study aims to show that a program of parent education and peer support to initiate and maintain positive feeding practices in very young children (6-10 months) will (1) promote healthy eating behaviours and (2) prevent excess weight gain and overweight in children. A successsful intervention will provide evidence for policies and programs that can be implemented within a large primary care service to equip and support mothers-carers in developing the confidence and skills to introduce positive feeding practices in very early childhood. This is consistent with current community interest in early childhood as the foundation for health and well-being.Read moreRead less
Regulation Of Inflammatory And Epithelial Responses In An Experimental Model Of Chronic Human Asthma
Funder
National Health and Medical Research Council
Funding Amount
$164,061.00
Summary
This project examines how chronic inflammation and scarring develop in the walls of the airways in asthma. The particular role of allergic mechanisms and of specific types of cells that are involved in allergic inflammation will be tested, using a much-improved mouse model of asthma. In this experimental model, which was developed by the investigators, sensitised mice are chronically exposed to low concentrations of aerosolised egg white protein. The proposed studies will involve comparisons wit ....This project examines how chronic inflammation and scarring develop in the walls of the airways in asthma. The particular role of allergic mechanisms and of specific types of cells that are involved in allergic inflammation will be tested, using a much-improved mouse model of asthma. In this experimental model, which was developed by the investigators, sensitised mice are chronically exposed to low concentrations of aerosolised egg white protein. The proposed studies will involve comparisons with animals that are genetically deficient in their ability to produce certain inflammation-related molecules, as well as with mice treated with antibodies to block the action of other such molecules.Read moreRead less
Integrin-growth Factor Interactions In The Development Of Airway Wall Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$405,300.00
Summary
Asthma is a clinically and socio-economically important disease with prevalence in the Australian population of approximately 13% for adults and approaching 25% for children. Currently, glucocorticoids (GCS) are first line prophylactic therapy for the disease. Despite a wide diversity of precipitating factors, the mechanisms underlying its pathogenesis remain unclear. A marked thickening of the airway wall bought about by excessive deposition of extracellular matrix is a prominent pathological f ....Asthma is a clinically and socio-economically important disease with prevalence in the Australian population of approximately 13% for adults and approaching 25% for children. Currently, glucocorticoids (GCS) are first line prophylactic therapy for the disease. Despite a wide diversity of precipitating factors, the mechanisms underlying its pathogenesis remain unclear. A marked thickening of the airway wall bought about by excessive deposition of extracellular matrix is a prominent pathological feature but why this occurs and how it can be prevented is equally unclear. Recent studies have suggested that interactions between cells and the extracellular matrix influence the airways response to inflammation and modulate the effectiveness of currently available therapies. Indeed, there is mounting evidence to suggest that GCS fail to modulate and indeed in some cases even contribute to structural changes in the remodeled airway wall. The aim of this study is to assess the mechanisms by which cells and the extracellular matrix interact to promote remodelling of the airway wall and to determine whether this association influences the responsiveness to traditional asthma therapies.Read moreRead less
Long-lasting Correction Of The Basic Defect In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$458,500.00
Summary
The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special ....The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special virus delivery-particles, after conditioning the airway to make it receptive to the particles. The method works in normal mice and in CF mice; it gives long lasting gene transfer from a single dose and seems to affect all airway cell types. The gene transfer may also be occurring in airway stem cells, i.e. the mother cells from which grow all the cells of the airway surface. Until now, no-one else has been able to produce prolonged gene transfer in this way, nor arrange gene transfer into stem cells in live airways. There are now a number of things that we must investigate before we could conduct safety and effectiveness trials in larger animals, or consider moving into clinical trials in humans. We need to understand exactly how our conditioning agent works and is it safe; measure how long the gene correction can last actually in our animals; decide if we can we re-dose animals (if needed) without losing effectiveness because of inflammation or immune responses that might occur; and decide how important the airway stem cells are in producing the length of the gene transfer. Because it has been difficult to measure gene correction in CF airways, we will also test new ways we have developed to measure how well the gene correction works in CF airways. The findings of this project will allow us to develop our method to where we can test it in larger animals, to provide a strong, long-lasting gene correction that will be safe for testing in human clinical trials.Read moreRead less