I am a clinical scientist conducting translational and implementation research to improve diagnosis, management and understanding of airway diseases including asthma, COPD (chronic obstructive pulmonary disease), bronchiectasis and persistent cough.
Asthma causes a unique type of inflammation in the airways. Until recently, the cell responsible for this inflammation was thought to be the eosinophil. Eosinophils are evaluated in sputum samples from the airways and are commonly reported in increased levels from people with asthma. Recent work has identified that some people have symptoms of asthma but their eosinophil levels remain normal. Those with non-eosinophilic asthmatics may account for up to 50% of all asthma reported. Our study will ....Asthma causes a unique type of inflammation in the airways. Until recently, the cell responsible for this inflammation was thought to be the eosinophil. Eosinophils are evaluated in sputum samples from the airways and are commonly reported in increased levels from people with asthma. Recent work has identified that some people have symptoms of asthma but their eosinophil levels remain normal. Those with non-eosinophilic asthmatics may account for up to 50% of all asthma reported. Our study will investigate the cells present in the sputum of people that have non-eosinophilic asthma. It has been speculated that neutrophils (another cell causing inflammation in the lungs) may be responsible. Neutrophils are known to cause inflammation and release many chemical mediators, which are capable of destroying lung tissue. We will focus on the neutrophil and the chemicals that cause neutrophils to move into the lungs and then destroy tissue. By comparing the levels of neutrophils and its mediators between the eosinophilic and non-eosinophilic asthma populations it may be possible to understand the mechanism behind non-eosinophilic asthma. Current asthma treatments-preventers focus essentially on controlling the inflammation caused by eosinophils. By understanding what is causing the inflammation in people without eosinophils in their sputum, we can begin to investigate and design new treatments. One possible treatment is the use of macrolide antibiotics. These medicines have been shown to be useful in reducing inflammation in other chronic inflammatory diseases. We plan to investigate the usefulness of a macrolide antibiotic (erythromycin) in reducing inflammation in non-eosinophilic asthma by a randomised-controlled trial. Armed with more information about non-eosinophilic asthma we will be able to more effectively diagnose and treat this group in the community.Read moreRead less
Inhaled Mannitol For The Treatment Of Mucociliary Dysfunction- Its Effect And Mechanisms On The Clearance Of Mucus
Funder
National Health and Medical Research Council
Funding Amount
$324,100.00
Summary
Excessive secretion of mucus is a problem in asthma and bronchiectasis. Mucus is secreted from submucosal glands and goblet cells as a result of inflammation present in the airways. Excessive mucus is not easily transported by the cilia (hair like structures) in the airways and accumulation leads to productive cough and to recurrent infections. Cough is a secondary mechanism to clear mucus when the mucociliary system fails. Cough generates high airflow rates that can move mucus. However, patient ....Excessive secretion of mucus is a problem in asthma and bronchiectasis. Mucus is secreted from submucosal glands and goblet cells as a result of inflammation present in the airways. Excessive mucus is not easily transported by the cilia (hair like structures) in the airways and accumulation leads to productive cough and to recurrent infections. Cough is a secondary mechanism to clear mucus when the mucociliary system fails. Cough generates high airflow rates that can move mucus. However, patients with moderately to severely obstructed airways cannot generate high airflow rates. In addition, cough becomes very inefficient in moving mucus if it is sticky and viscous. As the cilia cannot transport large quantities of mucus the best approach is to alter the properties of mucus that would facilitate cough clearance. Increased hydration of mucus could change its surface and rheological properties. Increased hydration can be achieved by the osmotic movement of water into the airway lumen in response to inhaling an aerosol of salt or sugar. We have evidence using radioactive aerosols, that mannitol, a sugar, increases clearance of mucus acutely in patients with excessive secretions. We also have new evidence that mannitol taken daily over two weeks increases the health status in patients with bronchiectasis. Further we now have preliminary data demonstrating that mannitol changes the surface properties of mucus. We aim to study the properties of mucus in relation to its clearance in vivo in humans. This has not been done before. If we can demonstrate that changes in clearance in response to mannitol relate to the changes in mucus then we will be able to easily evaluate current treatments and doses for patients with excessive secretions and to identify new treatments. Mannitol is a potential treatment for diseases with excessive secretions and understanding of how it works will hopefully lead to better outcomes for patients.Read moreRead less
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.
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
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