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
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
Redesigning the transistor at the atomic-scale. Australian researchers have a world-wide leadership position in atomic-scale electronics. Through the development of powerful new fabrication technologies, Australian scientists are now poised to uncover the physical properties of electronic systems operating on the atomic-scale. This research will be internationally significant, providing ongoing international profile for Australian science. Perhaps more significantly, it will also lay the groundw ....Redesigning the transistor at the atomic-scale. Australian researchers have a world-wide leadership position in atomic-scale electronics. Through the development of powerful new fabrication technologies, Australian scientists are now poised to uncover the physical properties of electronic systems operating on the atomic-scale. This research will be internationally significant, providing ongoing international profile for Australian science. Perhaps more significantly, it will also lay the groundwork for future miniaturisation - and redesign - of the conventional transistor. Over the longer-term, it offers an opportunity for Australia to lift its involvement in the multi-trillion dollar global semiconductor industry.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0454224
Funder
Australian Research Council
Funding Amount
$1,234,800.00
Summary
Scanning probe facility for atomic-scale device fabrication in silicon and its integration with molecular electronics. This application will establish a unique scanning probe facility to launch two major new initiatives in electronic device fabrication in Australia: (i) atomic-scale device fabrication in silicon and (ii) the integration with molecular electronics. The revolutionary features of the Nanoprobe system exploits recent advances in scanning probe techniques to allow for the first time ....Scanning probe facility for atomic-scale device fabrication in silicon and its integration with molecular electronics. This application will establish a unique scanning probe facility to launch two major new initiatives in electronic device fabrication in Australia: (i) atomic-scale device fabrication in silicon and (ii) the integration with molecular electronics. The revolutionary features of the Nanoprobe system exploits recent advances in scanning probe techniques to allow for the first time fully functional silicon and hybrid silicon-molecular electronic devices to be fabricated and tested at the atomic-scale. Such a facility will draw together a host of experienced researchers in this emerging field enabling Australia to actively lead the development of this new technology at its early stages.Read moreRead less
Fundamental conduction mechanisms in atomic-scale silicon devices. This proposal will ensure that Australia remains at the forefront of worldwide research into atomic-scale electronics. It links leading nanotechnologists from Canada and Italy to a dynamic and growing Australian team, which already has strong collaborations with researchers in the UK, the US, Japan, and Taiwan. In the long-run, Australia stands to benefit indirectly from the research as it is a significant user of semiconductors ....Fundamental conduction mechanisms in atomic-scale silicon devices. This proposal will ensure that Australia remains at the forefront of worldwide research into atomic-scale electronics. It links leading nanotechnologists from Canada and Italy to a dynamic and growing Australian team, which already has strong collaborations with researchers in the UK, the US, Japan, and Taiwan. In the long-run, Australia stands to benefit indirectly from the research as it is a significant user of semiconductors across all major industries. More importantly, by anticipating the problems that electronic device manufacturers will face over their long-term horizons, the proposed research also seeks to provide Australia with a chance to lift its involvement in the multi-trillion dollar global semiconductor industry.Read moreRead less
Atomic-scale Devices in Silicon - the Ultimate Limit of Microelectronics. Miniaturisation is the driving force behind the microelectronics industry, but beyond 2015 there is no known route to reduce device sizes below 10nm. The Fellowship will launch a major new initiative for the fabrication of silicon electronic devices at the atomic-scale (0.1nm). The project will exploit recent advances in scanning probe techniques to develop smaller and faster conventional transistors, nanoscale integrated ....Atomic-scale Devices in Silicon - the Ultimate Limit of Microelectronics. Miniaturisation is the driving force behind the microelectronics industry, but beyond 2015 there is no known route to reduce device sizes below 10nm. The Fellowship will launch a major new initiative for the fabrication of silicon electronic devices at the atomic-scale (0.1nm). The project will exploit recent advances in scanning probe techniques to develop smaller and faster conventional transistors, nanoscale integrated circuits, and address device reproducibility at this scale. This will extend Australia's early lead in atomic-scale silicon electronics to the stage where interested industry partners can evaluate it commercially in a way that will maximise benefits to Australia.Read moreRead less