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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
RNAi Therapeutic Intervention Of Human Viral Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$584,117.00
Summary
Human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. HMPV is emerging as a major cause of morbidity and life-threatening respiratory tract disease in infants, young children and the elderly worldwide. No treatment is currently available. The objectives of this proposal are to develop novel antiviral drugs that silence the expression of viral genes and to examine protection against the disease.
Postviral Wheezing In Childhood: Disregulation Of Airway Tone?
Funder
National Health and Medical Research Council
Funding Amount
$577,040.00
Summary
Asthma is a very common childhood condition that is becoming increasingly more common. Wheezing is common in infants and young children following viral infections and is often thought of as the first manifestation of asthma. However, many children and infants who wheeze with viral infections appear to grow out of asthma in their teenage years. Asthma that persists into adult life is usually associated with allergies to common environmental allergens, such as house dust mite and grass pollens. Ho ....Asthma is a very common childhood condition that is becoming increasingly more common. Wheezing is common in infants and young children following viral infections and is often thought of as the first manifestation of asthma. However, many children and infants who wheeze with viral infections appear to grow out of asthma in their teenage years. Asthma that persists into adult life is usually associated with allergies to common environmental allergens, such as house dust mite and grass pollens. However, many infants who wheeze with viral infections, especially in the first year of life, do not develop allergies in later life, raising the possibility that they did not have the same type of asthma as those whose symptoms persist. This project will study the effects of viral infections on lung function to determine whether particular types of virus can have detrimental effects of lung function lasting for years. We will also examine whether the age at which the infection occurs and the severity of the infection influence the long-term outcome. The project involves studying infants during the recovery phase of respiratory viral infections, older children years after documented infections and experimental animal models that have been infected under controlled conditions. By determining whether respiratory viral infections can have long-term effects on lung function that can mimic asthma, we will advance our understanding of how asthma develops. In addition, specific treatment and preventative strategies could then be developed to prevent these long-term abnormalities, instead of relying on asthma medication (especially inhaled corticosteroids) as is the current practice. Preventative strategies could include encouraging the development of specific vaccines.Read moreRead less
Mechanisms Of Induction And Progression Of Childhood Asthma: Investigations In A Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$517,586.00
Summary
This project investigates how certain respiratory viral infections in very young children might predispose to developing asthma, and how inflammation in the airways in asthma might then worsen. The experimental work, which will use unique mouse models developed in the laboratories of the chief investigators, will focus on changes in genes that control the pattern of immune response to allergens and that regulate the progression of inflammation.
Clinical Impact Of Clonal Pseudomonas Aeruginosa In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$547,238.00
Summary
In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on ....In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on the major bacterial problem, Pseudomonas aeruginosa. Several studies from Australia and the UK, including our own have shown that about 30% to 45% of patients share the same strain of Pseudomonas aeruginosa within a centre. We know that two dominant strains of Pseudomonas aeruginosa are found in CF centres on the eastern board of Australia. This is unexpected as this bacterium is usually acquired from the environment. The emergence of these clonal strains is causing increasing anxiety in the CF community. This study is designed to provide vitally needed information on the clinical implications of being infected by an clonal strain of Pseudomonas aeruginosa and the risk factors for the acquisition of an clonal strain. This new information will provide a rationale basis for the need for changes to infection control policies (including patient segregation), better outcome predictors for patients infected with clonal strain of Pseudomonas aeruginosa.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
Hypoxia-induced Suppression Of Respiratory Sensations And Reflexes
Funder
National Health and Medical Research Council
Funding Amount
$276,750.00
Summary
Many diseases that effect the respiratory system have their primary effect on the lungs and airway themselves but in some conditions, such as obstructive sleep apnea (OSA) and asthma, increased breathing load can induce periods of low blood oxygen which could further contribute to morbidity in these diseases. OSA is a disorder associated with snoring. Patients experience periods of sleep fragmentation and oxygen deprivation due to obstruction of the floppy portion of the upper airway (pharynx) d ....Many diseases that effect the respiratory system have their primary effect on the lungs and airway themselves but in some conditions, such as obstructive sleep apnea (OSA) and asthma, increased breathing load can induce periods of low blood oxygen which could further contribute to morbidity in these diseases. OSA is a disorder associated with snoring. Patients experience periods of sleep fragmentation and oxygen deprivation due to obstruction of the floppy portion of the upper airway (pharynx) during sleep. It affects 4% of men and 2% of women and causes excessive daytime sleepiness leading to increased risk of accidents, high blood pressure and premature cardiovascular disease. Asthma produces airway inflamation and narrowing and affects a wide range of people. Both OSA and asthma are associated with episodes of impaired breathing and reduced levels of oxygen in the blood. Low levels of oxygen in the blood (hypoxia) is well known to impair functioning of the central nervous system. We have recently found that hypoxia blunts sensations of increased breathing load in healthy people and in asthmatics. Hypoxia might therefore contribute to worsening of attacks in these diseases. This study aims to investigate how changes in blood oxygen levels affect brain processing of respiratory signals, how this translates to perception of sensations and the physiological adaptations that people make to cope with increased breathing load. We will also investigate whether the inhibitory effects of hypoxia on central nervous system function extend to other vital protective respiratory reflexes such as cough, awakening from sleep to increased breathing load and upper airway reflexes that are important for maintaining an open airway.Read moreRead less
How Do Thick Airway Walls Affect Airway Hyperresponsiveness In Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$382,538.00
Summary
Asthmatic airways narrow too easily, a characteristic called airway hyperresponsiveness (AHR). To understand the cause of asthma we need to understand the cause of AHR. Thickened airway walls could amplify airway narrowing and increase AHR. However, thick airway walls are also stiff, and stiff walls could reduce narrowing and AHR. This project will examine the relationships between AHR and airway wall thickness and stiffness during and after treatment that reduces airway wall thickness.
Randomised Double-blind Controlled Trial Of Oxygen Versus Air To Palliate Intractable End-of-life Dyspnoea When Pa02 >55
Funder
National Health and Medical Research Council
Funding Amount
$463,318.00
Summary
Shortness of breath at the end-of-life is one of the most feared symptoms. Unlike most other symptoms, it worsens as death approaches. Despite the fact that more than 50,000 Australian will die an expected death in the next year, of whom the majority will have breathlessness toward the end-of-life, we know little about how best to treat this symptom. Oxygen is frequently introduced but we have not identified whether it is more effective than medical air, and, if it is more effective, which patie ....Shortness of breath at the end-of-life is one of the most feared symptoms. Unlike most other symptoms, it worsens as death approaches. Despite the fact that more than 50,000 Australian will die an expected death in the next year, of whom the majority will have breathlessness toward the end-of-life, we know little about how best to treat this symptom. Oxygen is frequently introduced but we have not identified whether it is more effective than medical air, and, if it is more effective, which patients would most benefit from it. Because of this lack of evidence, oxygen is only funded in Australia in community settings for people who have severely low oxygen levels in their blood. Palliative oxygen is provided on a compassionate basis at times but this is on an ad hoc basis and does not ensure equitable access for people at the end of life who experience shortness of breath. This multi-centre study will compare oxygen and air, with neither the participant nor caring clinicians knowing which treatment they will receive. After careful explanation, volunteers who agree to participate will be asked to use the oxygen machine for at least 15 hours each day for 7 days and fill out a diary twice each day. Five centres across Australia are planning to enroll 240 participants in this study. Outcomes will include whether the sensation of breathlessness has improved, the overall quality of life while being treated, the ability to perform activities of daily living and any side effects experienced. This study is eagerly awaited by clinicians and health planners not only in Australia but in North America and Europe. This study will provide data in a long-standing international debate about the role of oxygen in people with relatively normal levels of oxygen in their blood who suffer from shortness of breath at the end-of-life.Read moreRead less