Antiviral Defects Of The Airway Epithelium Associated With Wheeze And Atopy In Children
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Asthma affects 10-15% of Australian. Repeated respiratory viral infections increase the risk of developing asthma, and are also the principal cause of asthma attacks. Asthmatics may be more susceptible to respiratory viral infections due to a defect in the innate antiviral response to infection. Here we aim to identify defects in the antiviral response of children who are at risk of developing asthma, and understand how they occur so that future therapies may be developed.
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
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.
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
An Education Intervention For Childhood Asthma By Local Aboriginal And Torres Strait Islander Health Workers
Funder
National Health and Medical Research Council
Funding Amount
$97,500.00
Summary
There are only a few studies on asthma in Aboriginal and Torres Strait Islander children, and those are restricted to prevalence and hospitalisation data. We have previously shown that the prevalence of childhood asthma in the Torres is similar to that of mainstream Australia and that children of this region generally have more severe asthma than children seen in urban areas. Using a model of care appropriate for Aboriginal and Torres Strait Islander people, with the involvement of local Indigen ....There are only a few studies on asthma in Aboriginal and Torres Strait Islander children, and those are restricted to prevalence and hospitalisation data. We have previously shown that the prevalence of childhood asthma in the Torres is similar to that of mainstream Australia and that children of this region generally have more severe asthma than children seen in urban areas. Using a model of care appropriate for Aboriginal and Torres Strait Islander people, with the involvement of local Indigenous health care workers, we have adapted an asthma information package. With Study 1, we will examine the effect of local health care workers using this education package to educate children about their asthma. Our hypotheses is that children who receive additional asthma education by health worker have better asthma control. So we propose a randomized controlled trial of a culturally appropriate education intervention with children diagnosed with asthma. Enrolled children will be allocated by chance to one of the two regimes: (1) additional asthma education intervention: children will receive a personalised booklet (containing individual data eg. growth, photo of the child, health worker visits etc) that will be used during the medical consultation. They will also have 3 visits from the health worker for their asthma. (2) no additional intervention (they will receive usual information about asthma at the consultation and no health worker visit). With Study 2 we will examine the natural history of children with asthma and asthma-like symptoms and with symptoms suggestive of sleep breathing problems. Two groups of children previously seen by this team (5 years ago) will be clinically reassessed. Our hypothesis is that short to medium term history of asthma in Indigenous children in the Torres Strait is similar to non-Indigenous Australian children where there is a general improvement with age.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