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.
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
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
Correction And Measurement Of The Basic Defects In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$929,335.00
Summary
Airway disease caused by the genetic disease cystic fibrosis (CF) cannot currently be prevented or cured. Current treatments (other than lung transplant) can only slow the inevitable decline in lung health. Early death from lung failure occurs for many with CF. We have developed a gene transfer technique to introduce the corrective gene (CFTR) into CF-diseased airway cells. We have used airways in mice to test and develop this method, to determine if long-lasting genetic correction of the airway ....Airway disease caused by the genetic disease cystic fibrosis (CF) cannot currently be prevented or cured. Current treatments (other than lung transplant) can only slow the inevitable decline in lung health. Early death from lung failure occurs for many with CF. We have developed a gene transfer technique to introduce the corrective gene (CFTR) into CF-diseased airway cells. We have used airways in mice to test and develop this method, to determine if long-lasting genetic correction of the airway cells can be achieved. The gene is introduced into the airway as a single small dose of special delivery-particles (vector) that have been built using highly-modified components of the HIV-1 virus. If ultimately successful in humans with CF, the disease should be halted, or even cured. Our recent work indicates that we have been able to insert the gene into airway progenitor cells, confirming our hypothesis that long-lasting gene expression can be achieved this way. To know if the method would be safe and effective in humans, we must now test the technique in sheep (as a human-size lung) and in marmosets (as a human-like lung) before clinical trials could be considered. We will monitor animals for up to 3 years to be sure the effect of the gene is truly long-lasting, and we will document how the gene-transfer vector disappears from the body. We have also discovered a new way to examine the detail of the very thin fluid layer on the airway surface. This fluid is too shallow in CF airway (allowing bacteria to stick and start disease) and so a successful gene therapy should return the fluid to it's proper depth. This method uses X-ray light from a synchrotron, and we expect it will work without the need to sacrifice animals to measure the airway surface. If successful it also has potential to be used much like a normal X-ray in humans with CF, to test if a gene therapy has worked.Read moreRead less