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
Stephen Stick Practitioner Fellowship In Paediatric Respiratory Medicine
Funder
National Health and Medical Research Council
Funding Amount
$542,272.00
Summary
Fellowship will facilitate the further study of mechanisms of chronic childhood respiratory disease and strategies for intervention to reduce morbidity and improve quality of life for patients and families.
Longitudinal Characterization Of Respiratory And Immune Development From Birth To Adulthood In The Perth Respiratory Birth Cohort
Funder
National Health and Medical Research Council
Funding Amount
$528,885.00
Summary
The Perth Respiratory Birth Cohort Study began in 1987 and has assessed 253 children before birth and at follow-up at 1, 6 & 12 months, and 6, 11 & 18 years of age. The study has resulted in 63 publications and achieved consistent international prominence. The proposed study of the cohort at 24 yrs aims to determine the respiratory and immunological status of the cohort as young adults. This follow-up is essential to determine how early risk factors affect respiratory outcome in young adults.
Improving Lung Health Of Indigenous Children, Through Identifying Interventional Targets From Long Term Follow-up Studies And Preventive Strategies
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Long term consequences of respiratory disease among Indigenous children are a public health issue. Studies included in this research program will provide new data and broaden our understanding on clinical predictors that significantly impact on lung health in Indigenous children. The studies will also direct future interventions and management pathways. This research will also contribute to improved asthma management, prevent uptake of smoking contributing to an overall improvement in health.
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
Mucous In Heterogeneous And Progressive Early Cystic Fibrosis Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$347,948.00
Summary
Cystic fibrosis (CF) is the most common genetically acquired, life-shortening chronic illness affecting young Australians today. Individuals with CF have a reduced ability to clear mucous from the airways resulting in respiratory infections and inflammation. This project will quantify the biochemical and biophysical properties of mucous in young children with CF to generate novel insights into the pathogenesis of early disease, biomarkers of disease progression and therapeutic targets.
Non-invasive Methods Of Measuring Work Of Breathing In Children
Funder
National Health and Medical Research Council
Funding Amount
$41,267.00
Summary
Sleep-disordered breathing such as obstructive sleep apnoea, is currently diagnosed if a child stops breathing more than once per hour. For children with asthma or cystic fibrosis, who may not stop breathing during the night, how hard their breathing muscles work can have a significant impact on their health. A non-invasive method of measuring respiratory effort, and incorporating this measurement into how sleep-disordered breathing is diagnosed, can revolutionize how sleep-disordered breathing ....Sleep-disordered breathing such as obstructive sleep apnoea, is currently diagnosed if a child stops breathing more than once per hour. For children with asthma or cystic fibrosis, who may not stop breathing during the night, how hard their breathing muscles work can have a significant impact on their health. A non-invasive method of measuring respiratory effort, and incorporating this measurement into how sleep-disordered breathing is diagnosed, can revolutionize how sleep-disordered breathing in children are managed world-wide.Read moreRead less
The Clinical Utility Of Small Airway Function Tests In Paediatric Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
Respiratory disease is an important child health issue with long term implications into adulthood. The evaluation of small airways involvement in disease processes, using an accurate sensitive measures of function, such as forced oscillation technique and multiple breath washout, potentially facilitates not only early detection of disease, but instigation of earlier treatment, better assessment of response to treatment, and ultimately better outcome.
Cervical Auscultation In The Diagnosis Of Aspiration In Children
Funder
National Health and Medical Research Council
Funding Amount
$96,183.00
Summary
Accurate assessment of aspiration risk is critical to prevent respiratory illness & recurrent hospitalisations in children.Current clinical tests have poor reliability in detecting aspiration.Cervical auscultation(CA) is a portable,low-cost instrumental technique that may improve the accuracy of clinical test.This research aims to determine accuracy & reliability of CA in detecting aspiration, compared to objective radiological evaluations.CA may improve aspiration detection & subsequently minim ....Accurate assessment of aspiration risk is critical to prevent respiratory illness & recurrent hospitalisations in children.Current clinical tests have poor reliability in detecting aspiration.Cervical auscultation(CA) is a portable,low-cost instrumental technique that may improve the accuracy of clinical test.This research aims to determine accuracy & reliability of CA in detecting aspiration, compared to objective radiological evaluations.CA may improve aspiration detection & subsequently minimise health system costs.Read moreRead less
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