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
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
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
MECHANISMS OF ABNORMAL EXPRESSION OF THE IGF2 GENE IN DISORDERS AFFECTING FOETAL GROWTH
Funder
National Health and Medical Research Council
Funding Amount
$560,434.00
Summary
The IGF2 gene is crucial for foetal growth. Only the copy inherited from the father is active, a phenomenon named parental imprinting. In some children with foetal overgrowth or growth retardation, the deregulation of imprinting of the IGF2 gene during the first days of foetal development will influence subsequent growth and will also have major implications in post-natal and adult life. We will investigate the mechanisms resulting in abnormal imprinting of the IGF2 early in development.
Mechanisms Of Abnormal Expression Of The IGF2 Gene In Disorders Affectin Foetal Growth
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
The IGF2 gene is crucial for foetal growth. Only the copy inherited from the father is active, a phenomenon named parental imprinting. In some children with foetal overgrowth or growth retardation, the deregulation of imprinting of the IGF2 gene during the first days of foetal development will influence subsequent growth and will also have major implications in post-natal and adult life. We will investigate the mechanisms resulting in abnormal imprinting of IGF2 early in development.
Understanding And Controlling Remodelling In Pulmonary Fibrosis And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$431,839.00
Summary
The development of scar tissue is a normal response to tissue injury. When airway and lung tissue is injured by exposure to irritants, scarring greatly diminishes the function of the lung to allow transfer of oxygen to the tissue. In severe disease, the scarring may be fatal. We discovered that two factors involved in formation of scar tissue neutralise each other's effects. We are examining this interaction in human lung to develop new treatments for scarring-related lung diseases.
The Early Life Origin Of Airway Smooth Muscle Thickening In Asthma Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$322,198.00
Summary
Previous studies have shown that fetal growth restriction (FGR) in the womb is associated with asthma in children; however the reason remains unknown. Thickening of the airway smooth muscle (ASM) is the primary structural abnormality in asthma. A model of FGR caused by low oxygen in the womb will be used to determine if associations between FGR and asthma involve an early life increase in ASM. That ASM may be increased from birth is a novel hypothesis which challenges conventional thinking.
The Central Role Of Connective Tissue Growth Factor In Remodelling Of Asthmatic Airways
Funder
National Health and Medical Research Council
Funding Amount
$689,019.00
Summary
In the asthmatic airway an increase in the number of blood vessels can affect an asthmatic's ability to breathe. We have recently found that growth factors which can promote vessel growth are increased in the airways of asthmatics. We want to understand how these growth factors act together to possibly control the blood vessels and how their behaviour is different in the asthmatic airways compared to the nonasthmatic airways.
Th17 Cell Cytokines In Airway Wall Remodelling In Chronic Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$295,983.00
Summary
In asthma, structural changes in the airway wall occur which thicken the muscle and epithelial layers, stiffen the airways and increase mucus production. This 'remodelling' makes breathing more difficult and is not effectively reversed with current treatments. We will study the cells and molecules involved in the development of these changes. This project will increase our understanding of the processes which drive these changes and may lead to the development of improved medications.
Teeth And Faces Of Australian Twins: A Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$647,226.00
Summary
We are seeking support from the NHMRC to complete a longitudinal study of 250 pairs of twins, both identical and non-identical, whom we have examined at around 4-6 years of age when all the baby teeth were present in the mouth, then again at around 8-10 years of age when both primary and permanent teeth were present. We now plan to examine these twins again at around the age of 11-13 years when all the permanent teeth, except the wisdom teeth, are normally present. Records to be obtained from th ....We are seeking support from the NHMRC to complete a longitudinal study of 250 pairs of twins, both identical and non-identical, whom we have examined at around 4-6 years of age when all the baby teeth were present in the mouth, then again at around 8-10 years of age when both primary and permanent teeth were present. We now plan to examine these twins again at around the age of 11-13 years when all the permanent teeth, except the wisdom teeth, are normally present. Records to be obtained from the twins over the next three years will include dental examinations, dental impressions from which casts can be made, shed primary teeth, and intra- and extra-oral photographs. We will apply modern methods of genetic analysis to determine the importance of genetic and environmental influences on observed variation in several dental and facial features. We will also study the fascinating phenomenon of mirror imaging in twins, where one twin mirrors the other for one or more features. Longitudinal studies of twins, in which a large sample of children is studied over several years, provide a powerful means of determining how genes influence growth and development. As far as we are aware, ours is the only large-scale longitudinal study of dental and facial growth in twins being undertaken in the world at present. Once we have collected all the data and carried out analyses, we will gain a much better understanding of the factors that can influence development of the teeth and face, and be in a much better position to be able to predict those children who are most likely to develop malocclusions in later life.Read moreRead less