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Long-lasting Correction Of The Basic Defect In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$458,500.00
Summary
The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special ....The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special virus delivery-particles, after conditioning the airway to make it receptive to the particles. The method works in normal mice and in CF mice; it gives long lasting gene transfer from a single dose and seems to affect all airway cell types. The gene transfer may also be occurring in airway stem cells, i.e. the mother cells from which grow all the cells of the airway surface. Until now, no-one else has been able to produce prolonged gene transfer in this way, nor arrange gene transfer into stem cells in live airways. There are now a number of things that we must investigate before we could conduct safety and effectiveness trials in larger animals, or consider moving into clinical trials in humans. We need to understand exactly how our conditioning agent works and is it safe; measure how long the gene correction can last actually in our animals; decide if we can we re-dose animals (if needed) without losing effectiveness because of inflammation or immune responses that might occur; and decide how important the airway stem cells are in producing the length of the gene transfer. Because it has been difficult to measure gene correction in CF airways, we will also test new ways we have developed to measure how well the gene correction works in CF airways. The findings of this project will allow us to develop our method to where we can test it in larger animals, to provide a strong, long-lasting gene correction that will be safe for testing in human clinical trials.Read moreRead less
Circulatory Biomarkers For Idiopathic Pulmonary Fibrosis: Improving Patient Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$841,625.00
Summary
We are going to find molecules in the blood that would improve the diagnosis and treatment of a lung condition called Idiopathic Pulmonary Fibrosis (IPF). The project brings together well characterized patients from the Australian IPF registry, blood samples we have collected from them and cutting edge technologies to complete this project.
Mechanism/s Of Disease Caused By Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$479,517.00
Summary
A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract ill ....A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract illness similar to RSV, but with an unknown etiology, suggests that HMPV may mediate similar clinical pathology. Nothing is currently known about the immune response to HMPV, or the association of these responses with lung disease. The objectives of this proposal are to elucidate the mechanisms of immunity and disease pathogenesis associated with human metapneumovirus (HMPV) and to investigate the use of a novel vaccine to protect against HMPV infection. Once this data is obtained, the study will provide the foundation for further research in the development of vaccines or therapeutic protocols to treat HMPV. It will also provide valuable information for understanding the disease in humans. Also,it is likely that HMPV, like hRSV, may prove to be an agent associated with long-term decreased pulmonary function and airflow limitation perhaps developing to asthma.Read moreRead less
Chronic obstructive pulmonary disease (COPD) is a chronic lung condition caused by cigarette smoking. COPD consists of emphysema and chronic bronchitis, which lead to worsening breathlessness, cough and sputum production and need for oxygen. COPD is the third highest cause of burden of disease to the community in Australia and the fourth leading cause of death. People with COPD suffer many chest infections, which need antibiotics and offer need admission to hospital. However there is much variab ....Chronic obstructive pulmonary disease (COPD) is a chronic lung condition caused by cigarette smoking. COPD consists of emphysema and chronic bronchitis, which lead to worsening breathlessness, cough and sputum production and need for oxygen. COPD is the third highest cause of burden of disease to the community in Australia and the fourth leading cause of death. People with COPD suffer many chest infections, which need antibiotics and offer need admission to hospital. However there is much variability in the pattern of COPD related to infections. Natural chemicals produced by the body that fight infection are likely to be involved in this variability. Recently it has been discovered that there are variations in the genetic sequence of the genes that code for these chemicals. These genetic variations change the structure of the chemicals or the rate at which they are produced. Therefore it is highly likely that these genetic variations may influence the risk of developing COPD, and the risk of getting infections. In this study, we aim to systematically examine how these genetic variations alter the development of COPD and the risk of infections. At the start, we will collect a blood sample and phlegm (sputum) specimen from each person. The results of the genetic tests will then be compared to the risk of developing COPD, the chemicals produced and the risk of infection. We believe this study will improve our understanding of how COPD and its complications develop, leading to better treatment for this condition in the future.Read moreRead less
Active Lung Disease In Survivors Of Preterm Birth? Can We Treat It?
Funder
National Health and Medical Research Council
Funding Amount
$612,862.00
Summary
More than 15 million babies are born preterm each year. Those that survive face a lifetime of ongoing breathing problems and lung function that worsens through childhood. Our study will work out how inflammation in the lungs contributes to these ongoing breathing problems during childhood. We will also look at how the exhaled breath of preterm children is different to term children and test how treatment with an inhaled anti-inflammatory medicine changes the lung disease in preterm children.
Centre For Clinical Research Excellence In Respiratory And Sleep Medicine
Funder
National Health and Medical Research Council
Funding Amount
$2,200,000.00
Summary
The CCRE will enhance Australia's international research reputation in clinical respiratory and sleep medicine by enhancing links between hospital-based investigators. This will foster development of new clinical researchers in these fields. Major research projects will include reducing side effects of asthma therapy in the elderly, better and cheaper ways of diagnosing disorders such as sleep apnoea and blood clots in the lung, keeping patients with chronic lung diseases out of hospital and avo ....The CCRE will enhance Australia's international research reputation in clinical respiratory and sleep medicine by enhancing links between hospital-based investigators. This will foster development of new clinical researchers in these fields. Major research projects will include reducing side effects of asthma therapy in the elderly, better and cheaper ways of diagnosing disorders such as sleep apnoea and blood clots in the lung, keeping patients with chronic lung diseases out of hospital and avoiding accidents due to lack of sleep.Read moreRead less
Health, Economic, Psychological And Social Impact Of Educating Carers Of Patients With Advanced Pulmonary Disease (APD)
Funder
National Health and Medical Research Council
Funding Amount
$605,452.00
Summary
Our study aims to understand the health, economic and social costs associated with caring for patients with advanced pulmonary disease (APD) and to determine health, economic and social impact of improving the skills of caregivers of patients with APD has on patients and their carers. Patients with APD are a large population at high risk of health resource use, unnecessary medication use and emergency admission to hospital or residential care facilities. Although previous research has identified ....Our study aims to understand the health, economic and social costs associated with caring for patients with advanced pulmonary disease (APD) and to determine health, economic and social impact of improving the skills of caregivers of patients with APD has on patients and their carers. Patients with APD are a large population at high risk of health resource use, unnecessary medication use and emergency admission to hospital or residential care facilities. Although previous research has identified difficulties experienced by caregivers of the elderly in general, very little research has been undertaken with carers of patients with APD. The study will compare the usual practice of educating patients with APD who commence home oxygen therapy (HOT), and their carers, against a more detailed and individually targeted education program that increases the skills of patients and carers. This study has the potential to reduce hospital-residential care readmission, reduce carer distress, improve patient outcomes, reduce adverse effects of oxygen therapy and medication use, and minimize inappropriate presentation to tertiary care emergency departments.Read moreRead less
Improving Functional Capacity In Patients With Chronic Lung Disease With High Intensity Respiratory Muscle Training
Funder
National Health and Medical Research Council
Funding Amount
$340,880.00
Summary
Patients with chronic respiratory disease have limited exercise capacity, which severely impairs their quality of life. The mechanisms responsible for this impairment may relate to their lung disease, or to the long-term effects that inactivity has on the cardiovascular and musculoskeletal systems. Pulmonary rehabilitation programs involving whole-body exercise are now widely used as an addition to standard medical therapy as a way of decreasing symptoms and optimising function. While these gene ....Patients with chronic respiratory disease have limited exercise capacity, which severely impairs their quality of life. The mechanisms responsible for this impairment may relate to their lung disease, or to the long-term effects that inactivity has on the cardiovascular and musculoskeletal systems. Pulmonary rehabilitation programs involving whole-body exercise are now widely used as an addition to standard medical therapy as a way of decreasing symptoms and optimising function. While these generalised, broad-based programs result in modest improvements in peripheral muscle function, cardiovascular function, functional exercise capacity and quality of life, it is now apparent they have little or no effect on respiratory muscle function, which is also greatly impaired in COPD. The aims of this study are to answer two longstanding questions that are fundamental to rehabilitation programs in patients with COPD (i) does a program of specific respiratory muscle training alone improve whole-body exercise capacity, dyspnoea, and-or quality of life? and (ii) does the addition of a program of specific respiratory muscle training to a standard whole-body exercise rehabilitation program result in improvemed exercise capacity, dyspnoea and-or quality of life to a greater degree than a program of whole-body exercise training alone? The study is of importance to patients with COPD by investigating the mechanisms underlying the improvement in exercise capacity following a rehabilitation program and the role of respiratory muscle training in such a program. By more accurately defining the mechanisms of exercise limitation we may be able to maximise the benefits obtained during a rehabilitation program, including improved work capacity, reduction in the degree of breathlessness and improved quality of life.Read moreRead less
Investigatin The Causes Of Failed Efferocytosis In COPD-emphysema With A View To Identifying Novel Theraputic Targets
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
COPD is a leading cause of death. Smoking is the major cause of COPD and many sufferers are left with permanent damage and need ongoing treatment even after smoking cessation. Current treatments for COPD generally have limited efficacy. The project will identify the reason for the large number of dying cells and defective clearance of these cells that we have identified in the airways in COPD and study novel treatments that we hope will improve the health and well being of those with COPD.
A New Non-invasive Diagnostic Technique Based On Detection Of Exhaled Respiratory Pathogens.
Funder
National Health and Medical Research Council
Funding Amount
$179,300.00
Summary
We developed a special collection mask and showed that the breath of people with colds or flu contains a tiny amount of virus. Currently, diagnostic samples are collected by putting a tube into the airways - this is very uncomfortable. Our masks may provide a new and more comfortable way to diagnose lung infections. We want to build better masks and ways to detect viruses and bacteria to test out this method. This may create a new test that will improve diagnosis and treatment.