Functional Significance Of Subcellular Localisation Of Viral 3C Protease In Rhinovirus Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$613,513.00
Summary
Rhinovirus (RV) infections are the major cause of virus induced asthma attacks and common colds, causing significant morbidity and mortality. The incidence of asthma is increasing worldwide with new strategies urgently needed to reduce RV-associated disease. We have observed RV 3C protease in the nuclear compartment of infected host cells and propose to determine its significance in RV pathogenesis with relevance to asthma therapies.
Asthma is a major health problem for the Australian community. Recent studies have shown increasing numbers of people of all ages are developing asthma. Despite extensive asthma research and the development of new asthma drugs, asthma remains a leading cause of ill- health, especially in children. In many cases the deterioration in asthma symptoms is related to a cold or flu like illness, Viruses are the leading cause of these infections and are known to make asthma symptoms worse. How they do t ....Asthma is a major health problem for the Australian community. Recent studies have shown increasing numbers of people of all ages are developing asthma. Despite extensive asthma research and the development of new asthma drugs, asthma remains a leading cause of ill- health, especially in children. In many cases the deterioration in asthma symptoms is related to a cold or flu like illness, Viruses are the leading cause of these infections and are known to make asthma symptoms worse. How they do this is not completely understood. Asthma causes a unique type of inflammation in the airways, which is present in even mild asthma and can be controlled by medication. Viruses also cause inflammation by infecting the lungs. Viruses can cause severe attacks of asthma even when asthma appears controlled on medication. The ways in which virus infections do this, are not established. By understanding how this happens we may be able to design effective treatment for this problem. Our initial results indicate that virus induced asthma is different to asthma that is triggered by allergens. We plan to investigate what effect certain viruses have on the lungs of people with asthma by measuring cells and chemicals that are present in sputum. We will use recently developed technologies to accurately see what viruses are infecting these people, and then evaluate the role of treatment of virus induced asthma. This study will shed important light on potential causes of unstable asthma and the role that viral infection plays in this. It may also lead to new opportunities to develop treatments that are more effective in preventing and controlling 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
Effects Of Upper Versus Lower Respiratory Infections On The Induction Of Atopic Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$386,483.00
Summary
Asthma is more common now in developed countries than it was 20-30 years ago. Many fewer children have asthma in developing countries and there does not appear to have been the same increase in asthma in recent years. Children in developed countries tend to have fewer respiratory infections and recent studies suggest that this may be partly responsible for the increase in asthma. An understanding of why asthma has increased in developed countries may lead to strategies to prevent asthma. In orde ....Asthma is more common now in developed countries than it was 20-30 years ago. Many fewer children have asthma in developing countries and there does not appear to have been the same increase in asthma in recent years. Children in developed countries tend to have fewer respiratory infections and recent studies suggest that this may be partly responsible for the increase in asthma. An understanding of why asthma has increased in developed countries may lead to strategies to prevent asthma. In order to understand the role that respiratory infections may play in the induction of asthma, it is necessary to study babies from birth, documenting each respiratory inflection and monitoring their diet. In a recent large study we have shown that parental reports of common colds and chest infections do influence how many children have asthma at age 6. Also in this study, breast feeding for at least 4 months seemed to be protective against developing asthma. However, we were not able to verify how many infections the children in that study actually had. We are currently studying a population of 236 infants, all of whom are at high risk of developing asthma and allergies. At the end on November 1998, 163 of these infants had reached one year of age. During the first year of life, these infants had a total of 669 respiratory infections, with individual babies having between 0 and 11 infections. We now plan to monitor these children until they turn 5, when we will determine how many have asthma and allergies. In this way we will be able to determine whether children who have more respiratory infections early in life are more or less likely to have asthma and allergies at 5 years of age. We will also be able to tell whether breast-feeding is able to decrease the chance of developing asthma and allergies.Read moreRead less
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
Novel Interventions For The Diverse Population Of Australians With Bronchiectasis
Funder
National Health and Medical Research Council
Funding Amount
$726,822.00
Summary
Bronchiectasis is a chronic lung condition in which infection causes wheeze, breathlessness, fatigue and sputum production - markedly reducing quality of life and requiring repeated hospital admissions. Risk of hospitalisation due to the disease is up to 9-fold higher in Indigenous vs other Australians. This research will examine two new, low-cost therapies with excellent potential to treat bronchiectasis: a new antibiotic, Azithromycin, and a mucus-clearance agent, hypertonic saline.
Mechanisms Underlying Acute Changes In Lung Function And Airway Responsiveness Following Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$444,878.00
Summary
This study will investigate the mechanisms responsible for the increased airway responsiveness seen during respiratory viral infections to the common viruses of influenza (flu) and respiratory syncytial virus (RSV). Respiratory viral infections alter lung function and increase airway responsiveness in man. In addition, respiratory viral infections early in life are a risk factor for the subsequent development of asthma. The mechanisms responsible for this are unknown. Both the infecting virus an ....This study will investigate the mechanisms responsible for the increased airway responsiveness seen during respiratory viral infections to the common viruses of influenza (flu) and respiratory syncytial virus (RSV). Respiratory viral infections alter lung function and increase airway responsiveness in man. In addition, respiratory viral infections early in life are a risk factor for the subsequent development of asthma. The mechanisms responsible for this are unknown. Both the infecting virus and host factors, such as age of infection, gender and genetic predisposition, are likely to be important. OUTCOMES and SIGNIFICANCE: These studies will provide a comprehensive assessment of the effects of acute viral respiratory infections on lung function and airway responsiveness using cutting edge techniques developed in our labs. The results will provide new insights into how these infections cause lung disease and may provide clues for new approaches to prevent the adverse effects of these common respiratory viral infections.Read moreRead less
Pneumovirus Infection In Infancy Affects The Development Of Life-long Adaptive Immunity.
Funder
National Health and Medical Research Council
Funding Amount
$408,469.00
Summary
Respiratory syncytial virus is the most important cause of acute lower respiratory tract infection (RTI) in young children worldwide. Hospital admission rates in Western societies for RTIs are around 3% for children younger than 1 year. A vaccine to RSV is not yet available and repeat infections occur thoughout life, suggesting that the immune response does not develop correctly. In this project we are exploring the mechanisms that underpin disease development and promote incomplete immunity.