Clinical And Psychosocial Changes Over Late Childhood And Adolescence And Early Life Determinants Of Long Term Clinical Outcomes In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,135,570.00
Summary
Cystic fibrosis is the most common life shortening inherited disease in Caucasians. Lung damage starts in infancy and lung function falls most rapidly in adolescence although why and how this happens and early life determinants are not known. This study takes advantage of a previous study that monitored young children from 3 months to 5 years of life and follows them closely through early adolescence to investigate the protective and risk factors for falling lung function.
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
Role Of Zinc In The Respiratory Epithelium And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example ....This project will use a panel of Zinquin-derived Zn fluorophores developed in our laboratory, as well as probes for the mammalian family of vesicular ZnT transporters, to carry out a study of the normal physiology of Zn in the respiratory system and potential abnormalities of this in patients with chronic inflammatory respiratory disease (asthma, COPD, chronic smoking). Chronic inflammatory diseases of the respiratory tract affect a significant proportion of the Australian community. For example, asthma affects 12% of adults and amongst these, 15% waken weekly or more often with their asthma while 6% are hospitalized annually. There is a need to understand the basic mechanisms underlying these diseases so that new strategies can be developed to modify bronchocondtriction and inflammation. The project will provide new knowledge concerning the physiology of Zn in the respiratory epithelium and interactions between Zn deficiency and oxidants on injury in the respiratory tract. The usefulness of easily accessible nasal epithelial cells as a measure of Zn and Zn transporter levels deeper in the respiratory tract will be assessed. The project encompasses a number of fields and utilizes in vitro cellular and animal models, as well as tissues from human subjects.Read moreRead less
Airway Epithelial IAPs And Their Interaction With Zn Ions
Funder
National Health and Medical Research Council
Funding Amount
$260,779.00
Summary
The air we breathe contains a variety of harmful substances. Damage to the lining involves death of the ciliated cells that line the airways. We have shown that zinc protects these cells from premature death. This application focuses on a family of proteins called IAPs which bind zinc and regulate cell death in other tissues. This project focusses on how the IAPs and Zn may act together to mainitain healthy airways and how abnormalities of these may occur in people with asthma.
Common synaptic inputs to human upper airway muscles. Changes in the activity of upper airway muscles at sleep onset contribute to the development of Obstructive Sleep Apnoea. The aim of this project is to investigate how the brain controls upper airway muscles during wakefulness and sleep and to identify the pathological processes that lead to the development of Obstructive Sleep Apnoea.
From The Synchrotron To The Clinic: Translation Of A Novel Functional Lung Imaging Technology
Funder
National Health and Medical Research Council
Funding Amount
$891,834.00
Summary
Our team has recently developed a synchrotron technology with a startling capacity for dynamic functional imaging that can act as a sensitive regional indicator of lung disease. We will demonstrate that this technology can be translated from the synchrotron to the lab and eventually the clinic. We will provide proof of this concept by the application of this technology to emphysema, asthma, lung cancer, cystic fibrosis lung disease and neonatal resuscitation.
A new paradigm for surfactant composition and function - how do lungs cope with stress? Our research will increase the understanding of the scope of change and precise molecular interactions occurring in the surfactant lipids and proteins of animals under physiological stress. The novel insights will improve the treatment of lung diseases (such as chronic obstructive pulmonary disease and acute lung injury). We have formed a team of international surfactant researchers all experts in state-of-th ....A new paradigm for surfactant composition and function - how do lungs cope with stress? Our research will increase the understanding of the scope of change and precise molecular interactions occurring in the surfactant lipids and proteins of animals under physiological stress. The novel insights will improve the treatment of lung diseases (such as chronic obstructive pulmonary disease and acute lung injury). We have formed a team of international surfactant researchers all experts in state-of-the-art chemical and biophysical technologies relating to surfactant. These collaborations will bring new technological applications to Australia and provide outstanding cross-disciplinary training for postgraduate students and research staff at the interface between animal physiology, biophysical chemistry and respiratory medicine.Read moreRead less
Environmental control of genetic/phenotypic interactions in lung development: An evolutionary perspective. Vertebrate lungs all contain morphologically and functionally similar lung lining cells. However, the cellular arrangement (i.e. lung morphology) and the function of the surfactant these cells produce, differs dramatically between species. Hence, a subset of highly conserved lung-specific genes coincides with spectacular phenotypic diversity. How has this diversity evolved? Do environmental ....Environmental control of genetic/phenotypic interactions in lung development: An evolutionary perspective. Vertebrate lungs all contain morphologically and functionally similar lung lining cells. However, the cellular arrangement (i.e. lung morphology) and the function of the surfactant these cells produce, differs dramatically between species. Hence, a subset of highly conserved lung-specific genes coincides with spectacular phenotypic diversity. How has this diversity evolved? Do environmental conditions, birth strategy or phylogenetic relationships determine lung phenotype? We will experimentally manipulate developing lungs and cells to demonstrate how environmental conditions (temperature, oxygen, lung-fluid regulation and neuro-hormonal input) promote evolutionary processes by altering gene expression, protein/lipid synthesis, cellular differentiation and hence lung morphology/function in animals with different birth strategies.Read moreRead less
Towards early detection of upper airway obstruction in children: investigation of autonomic control. This project focuses on the investigation of new indicators for early detection of upper airway obstruction (UAO)-which is a common sleep disorder in children. Failure to treat UAO can result in serious adverse outcomes including failure to thrive, neurocognitive deficits, developmental delay, behavioural disorders and cardiovascular disease. Thus, early treatment of UAO will significantly improv ....Towards early detection of upper airway obstruction in children: investigation of autonomic control. This project focuses on the investigation of new indicators for early detection of upper airway obstruction (UAO)-which is a common sleep disorder in children. Failure to treat UAO can result in serious adverse outcomes including failure to thrive, neurocognitive deficits, developmental delay, behavioural disorders and cardiovascular disease. Thus, early treatment of UAO will significantly improve quality of life for the child. Direct benefits to community health via reduced costs for medical treatment will also be a key outcome. The establishment of new diagnostic indicators will form the basis of new tools for identifying child sleep disorders and contribute to advancing Australia's international leading position in health technology. Read moreRead less
Nanoparticle adsorption at air-water interfaces for foam stabilization. Pharmaceutical formulations and lightweight materials and processes such as mineral flotation and biocatalysis depend on the interactions between air bubbles and particles in water. This project will provide in-depth insight into how the physics and chemistry of the particle surfaces control the structure of the materials formed in those processes.