Distribution Of Monodisperse Aerosols Inhaled By Children For Determination Of Optimal Therapeutic Inhaler Formulations
Funder
National Health and Medical Research Council
Funding Amount
$326,000.00
Summary
Inhalers are the primary form of treatment for asthma, allowing the delivery of lower doses of medication directly to the lungs. Consistent daily use of these inhalers is often necessary to effectively control the symptoms of asthma. Inhalers are now increasingly used to treat infants with lung problems. Many of these inhalers are not designed for use by such young children, who may be unable to perform the breathing techniques necessary for effective use of these inhalers. Not all the drug inha ....Inhalers are the primary form of treatment for asthma, allowing the delivery of lower doses of medication directly to the lungs. Consistent daily use of these inhalers is often necessary to effectively control the symptoms of asthma. Inhalers are now increasingly used to treat infants with lung problems. Many of these inhalers are not designed for use by such young children, who may be unable to perform the breathing techniques necessary for effective use of these inhalers. Not all the drug inhaled by patients will end up in the lungs where it is needed; a large proportion is left in the mouth, throat and stomach. Our earlier studies have shown that there is a large amount of variability in the amount of drug received by children using inhalers. We intend to assess the important factors involved in improving the efficiency of inhaler therapy for children, such as the size of the inhaled particles and the breathing pattern of the child. The results obtained from this study will enable us to determine the best method of delivering these drugs to children so that they only receive the lowest effective dose for treatment of the symptoms of asthma while minimising unwanted effects.Read moreRead less
Determining The Cellular Mechanisms Involved In The Airway Response To Topical Citrate
Funder
National Health and Medical Research Council
Funding Amount
$444,491.00
Summary
The air passages of the lungs are lined by mucous membranes. These membranes are covered by a thin layer of fluid to protect the airways from drying. This fluid allows the cilia, the hair like projections on top of the airway cells to beat more effectively to remove mucous and inhaled particles from the lungs. The volume and composition of this fluid is determined by the salt and water movement across the mucous membranes of the airways. These processes are abnormal in cystic fibrosis (CF), the ....The air passages of the lungs are lined by mucous membranes. These membranes are covered by a thin layer of fluid to protect the airways from drying. This fluid allows the cilia, the hair like projections on top of the airway cells to beat more effectively to remove mucous and inhaled particles from the lungs. The volume and composition of this fluid is determined by the salt and water movement across the mucous membranes of the airways. These processes are abnormal in cystic fibrosis (CF), the most common lethal inherited disease affecting Australians. In CF, an abnormal gene disrupts one of the major mechanisms for salt and water movement in the air passages. This abnormal salt transport causes drying of the airway surface which impairs the working of the cilia. This leads to retention of mucous in the airways with repeated bacterial infections damaging the lungs. Over the last 10 years, we have developed a series of simple tests to measure the abnormalities in the CF airway of human subjects. We have isolated an exciting new clinical application for sodium citrate, a substance used in blood transfusions. Citrate appears to alter both the salt transport abnormalities found in CF. This research proposal seeks to better understand the dual effects of citrate and to test similar compounds that may have stronger effects. The ultimate aim of our research is to have sufficient knowledge to work out the best way to develop a new treatment for CF.Read moreRead less
Engineered Cell And Exosome Therapy For Pulmonary Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$838,490.00
Summary
Diseases affecting the blood vessels in the lungs cause early death and the currently available treatments are not curative. We will take advantage of the latest developments in the understanding of the molecular basis of these diseases to design and test a new treatment approach using cells and cell-derived products as a therapy.
This program of work focuses on smoking related lung diseases including chronic bronchitis and emphysema, and lung cancer, as well as diseases affecting the blood vessels in the lungs. The work includes basic cell biology and human clinical trials.There is a high likelihood that new approaches to treating lung disease will emerge.
A Randomised Controlled Trial Of Non-invasive Ventilation In Stable, Hypercapnic Chronic Airflow Limitation
Funder
National Health and Medical Research Council
Funding Amount
$331,622.00
Summary
Chronic airflow limitation is a major cause of illness and death in Australia. Long term oxygen therapy is well established as one means of assisting people with chronic lung disease. Survival is still poor particularly when an individual is hypercapnic. Non-invasive ventilation used at night with a mask has been used in chronic hypercapnic respiratory failure from other causes with very good results. This study looks at whether non-invasive mask ventilation improves survival, improves clinical ....Chronic airflow limitation is a major cause of illness and death in Australia. Long term oxygen therapy is well established as one means of assisting people with chronic lung disease. Survival is still poor particularly when an individual is hypercapnic. Non-invasive ventilation used at night with a mask has been used in chronic hypercapnic respiratory failure from other causes with very good results. This study looks at whether non-invasive mask ventilation improves survival, improves clinical outcome measures and reduces health costs in people with chronic airflow limitation. The ventilatory support will be used at night during sleep and will be a bilevel positive airway pressure device. Apart from measuring the cost-benefit of home ventilatory support, this study will examine the relationship between the time of commencement of home ventilatory support and outcomes. In addition the relationships between daytime awake PaCO2, lung function, and body mass in CAL patients and the likely response to home ventilatory support will be examined.Read moreRead less
Assessment Of Physical Therapies To Improve Secretion Clearance In Patients With Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$302,310.00
Summary
People with cystic fibrosis (CF) produce thick mucus that is not cleared normally from the lungs. This retained mucus often becomes infected, which progressively damages the lungs. Various physical therapies which may help clear secretions are being used in CF. These include several types of devices which provide positive pressure to the airways. However, it is not known to what extent these devices, or other interventions such as manual chest physiotherapy and exercise, enhance mucus clearance. ....People with cystic fibrosis (CF) produce thick mucus that is not cleared normally from the lungs. This retained mucus often becomes infected, which progressively damages the lungs. Various physical therapies which may help clear secretions are being used in CF. These include several types of devices which provide positive pressure to the airways. However, it is not known to what extent these devices, or other interventions such as manual chest physiotherapy and exercise, enhance mucus clearance. As a result, it is not currently possible to scientifically prescribe intervention(s) to enhance mucus clearance in CF. This is partly because much of the research that has been performed in this area has been poorly-designed or has used inaccurate measures. Also, recent research has shown that these therapies may have significant effects beside their effect on mucus clearance. For instance, bacterial infection and the exchange of oxygen and carbon dioxide between the blood supply and air in the lung may all be affected by these interventions. Notably, the extent of benefit or detriment seen in these parameters does not always correlate with the effect on mucus clearance. We therefore believe a series of experiments is necessary to provide evidence upon which the scientific selection of mucus clearance therapies may be based. We have developed a new technique which allows clearance of mucus from the airways to be objectively measured in three-dimensions (3D). We intend to use the 3D technique to examine the effects of three different positive pressure devices, exercise, and manual chest physiotherapy on mucus clearance. Based on the outcomes of this research, we intend to compare the most appropriate therapy to performing no mucus clearance therapy in a short term trial. This trial will assess changes in the following: bacterial infection, mucus plugging in the airways, how well the lungs move air and exchange oxygen and carbon dioxide, and the patient's quality of life.Read moreRead less
Elucidating The Roles And Mechanisms Of Activation Of NLRP3 Inflammasomes And Developing Therapeutic Interventions For Severe Steroid-resistant Asthma
Funder
National Health and Medical Research Council
Funding Amount
$961,929.00
Summary
Severe asthma is a major clinical issue. There are no effective treatments because we don’t understand how it occurs. We have identified a factor called an “inflammasome” that we think causes severe asthma. We have produced a new inhibitor of this factor, and shown experimentally that it may suppress important symptoms of severe asthma. We now aim to work out precisely how this inflammasome causes severe asthma and progress our new inhibitor towards therapeutic development.
Targeting Neutrophil Extracellular Traps To Reduce Inflammation In Severe Asthma
Funder
National Health and Medical Research Council
Funding Amount
$585,240.00
Summary
People with severe asthma, a chronic disease of the lungs, often have many inflammatory cells in the airways called neutrophils. Neutrophils release a meshwork of fibers in a web like trap called NETs, which are made of the cells DNA and other proteins that fight infection. These NETs can promote inflammation in the persons airways. Current asthma treatments have no effect on NETs. This project will measure NETs in the airways and test a new treatment to reduce NETs, and relieve asthma symptoms.
Predicting The Successful Resolution Of Obstructive Sleep Apnoea Following Weight-loss Surgery
Funder
National Health and Medical Research Council
Funding Amount
$729,284.00
Summary
The current project aims to determine how obesity causes obstructive sleep apnoea (OSA), a disorder associated with significant cardiovascular morbidity & mortality. This research is a burgeoning area given that obesity is one of the western world’s leading health care concerns. Our findings may ultimately offer a refinement of weight-loss interventions to maximise their effects on OSA as well as offering novel treatment strategies in the management of this disorder that is desperately needed.
Elucidating The Mechanisms Of Infection-induced, Steroid-resistant Asthma
Funder
National Health and Medical Research Council
Funding Amount
$348,070.00
Summary
Steroid-resistant asthma is an important clinical problem and effective therapies are urgently required. Substantial evidence links bacterial and viral respiratory infections with steroid-resistant asthma, however, how infections are associated with steroid-resistant asthma is not known. This project will investigate the role of specific immune factors, that we have identified, in infection-induced steroid-resistant asthma. Our project may identify new therapeutic targets for this severe form of ....Steroid-resistant asthma is an important clinical problem and effective therapies are urgently required. Substantial evidence links bacterial and viral respiratory infections with steroid-resistant asthma, however, how infections are associated with steroid-resistant asthma is not known. This project will investigate the role of specific immune factors, that we have identified, in infection-induced steroid-resistant asthma. Our project may identify new therapeutic targets for this severe form of asthma.Read moreRead less