Elucidating Sub-clinical Pathways To Chronic Rejection In Lung Transplantation And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$416,587.00
Summary
Organ transplantation has become a feasible option for many end-stage clinical conditions, including advanced lung disease. However, despite often dramatic short term successful outcomes, late graft dysfunction due to chronic rejection remains a major obstacle to long-term success. This is particularly the case in lung transplantation despite the use of potent broad spectrum immunosuppressive agents. The three major risk factors that have been identified for chronic rejection following lung tran ....Organ transplantation has become a feasible option for many end-stage clinical conditions, including advanced lung disease. However, despite often dramatic short term successful outcomes, late graft dysfunction due to chronic rejection remains a major obstacle to long-term success. This is particularly the case in lung transplantation despite the use of potent broad spectrum immunosuppressive agents. The three major risk factors that have been identified for chronic rejection following lung transplantation are acute rejection episodes diagnosed on lung biopsy, reactivation of the ubiquitous human DNA virus CMV and persistent lymphocytosis in the transplanted lung suggesting that potent broad spectrum immunosuppression may have both beneficial and harmful effects in lung transplant recipients. This proposal will apply sensitive new immunological techniques to detect and quantitate each of these risk factors at a sub-clinical level with a view to delineating their relationship with each other and with the development of chronic rejection following lung transplantation. This information will help unravel the pathogenesis of chronic rejection in lung transplant recipients and improve clinical management decisions in these patients and therefore long term health outcomes.Read moreRead less
Randomised Controlled Trial Of Azithromycin To Reduce The Morbidity Of Severe Bronchiolitis In Indigenous Infants
Funder
National Health and Medical Research Council
Funding Amount
$1,456,802.00
Summary
Acute lower respiratory infections are the commonest cause of hospitalisations and retrievals from remote communities. Early severe respiratory infections likely impair lung growth. We will examine whether azithromycin (antibiotic with anti-inflammatory properties) should be used to treat infants hospitalised with bronchiolitis to reduce the severity of bronchiolitis and prevent rehospitalisation. The study potentially improves acute clinical care as well as prevents future respiratory illness.
Studies On The Effects Of RSV Infection During Infancy On Aeroallergen-specific T-cell Immunity And Lung Function
Funder
National Health and Medical Research Council
Funding Amount
$130,475.00
Summary
Many infants who develop transient severe wheezing in association with respiratory infections, go on to develop asthma which can persist throughout childhood and some times into adult life. It is not known whether the respiratory infections are a direct cause of later asthma, or whether they simply function as flag which identifies children who have a genetic predisposition to wheeze e.g. because they have abnormally narrow airways. This project will compare the effects of respiratory infection ....Many infants who develop transient severe wheezing in association with respiratory infections, go on to develop asthma which can persist throughout childhood and some times into adult life. It is not known whether the respiratory infections are a direct cause of later asthma, or whether they simply function as flag which identifies children who have a genetic predisposition to wheeze e.g. because they have abnormally narrow airways. This project will compare the effects of respiratory infection in infants with the RSV virus, who contract the disease at different ages, and who have varying levels of genetic risk for respiratory allergies. In particular, it will examine the possibility that in certain cases, infection of genetically susceptible individuals during early infancy will boost the development of allergies to airborne environmental allergens (such as house dust mite) which are known to trigger asthma attacks in older children and adults.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.
The Immunoregulatory Domains And Binding Interactions Of Human Respiratory Syncytial Virus Non-structural Proteins
Funder
National Health and Medical Research Council
Funding Amount
$484,051.00
Summary
Human respiratory syncytial virus (HRSV) is the leading cause of lower respiratory tract disease in infants and yet there are no vaccines available. HRSV exacerbates disease by interfering with the innate immune response. We aim to establish the mechanism by which this occurs by identifying the cellular-viral protein interactions involved, and by identifying the specific regions of the viral proteins responsible. This information will allow targeted vaccines and antivirals to be developed.
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
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.