High Field Magnetic Resonance Evaluation Of Cerebral And Brainstem Dysfunction In Obstructive Sleep Apnea.
Funder
National Health and Medical Research Council
Funding Amount
$335,175.00
Summary
BACKGROUND: Obstructive Sleep Apnea (OSA) is a condition where repetitive obstruction of the upper airway occurs during sleep. This occurs in susceptible patients when the muscles which normally hold the upper airway open relax with sleep onset. During these interruptions to breathing (apneas) oxygen levels can fall significantly and repetitive awakenings from sleep result. Patients with sleep apnea are often sleepy during the day and experience difficulties with concentration on complex or bori ....BACKGROUND: Obstructive Sleep Apnea (OSA) is a condition where repetitive obstruction of the upper airway occurs during sleep. This occurs in susceptible patients when the muscles which normally hold the upper airway open relax with sleep onset. During these interruptions to breathing (apneas) oxygen levels can fall significantly and repetitive awakenings from sleep result. Patients with sleep apnea are often sleepy during the day and experience difficulties with concentration on complex or boring tasks. Recent improvements in magnetic resonance imaging (MRI) technology allow targeting very small areas of the brain, such as the brainstem, the region of the brain which contols the upper airway muscles. MRI can detect subtle signs of damage to brain cells, and can assess brain activation induced by a task, such as moving the tongue . AIM 1. To identify the presence and patterns of damage to brain cells in patients with OSA by MRI scanning. 2. To examine whether patients with the most severe patterns of injury are also those with the greatest difficulties with sleepiness and concentration. 3. To determine whether these brain abnormalities improve after 6 months of treatment of OSA. 4. To assess activity of the brainstem in wakefulness in OSA patients and compare this to the activity in subjects without OSA. SIGNIFICANCE: This project will advance our understanding of the causes of obstructive sleep apnea. We anticipate it will provide a new method for investigating injury to brain cells in this disease. It will also provide a new means for investigating the causes of OSA and for evaluating novel therapies aimed at enhancing the activity of upper airway muscles and preventing obstruction during sleep.Read moreRead less
Functional Characterisation Of Novel Metabolites In Asthma And Identification Of New Biomarkers
Funder
National Health and Medical Research Council
Funding Amount
$829,922.00
Summary
Asthma is a chronic inflammatory disease of the airways that represents a major health burden. Severe asthma represents 10% of those suffering the disease and poses an urgent problem due to exacerbations and resistance to current therapies. We have conducted the first study of the metabolites that are altered in the airways of patients with severe asthma and identified functional metabolites and disease biomarkers. We now aim to assess the function of these molecules in asthma disease models.
We will conduct a survey of respiratory symptoms, lung function, smoking status, occupational exposures, and other risk factors among 3200 people aged 40 years and over living in five Australian communities: Melbourne, Sydney, Tasmania, Busselton (WA), and the Kimberley region (WA). In the Kimberley we will survey 400 Aboriginal people and 400 non-Aboriginal people. We will use a survey methodology that has been developed by an international expert panel and has been implemented in many other co ....We will conduct a survey of respiratory symptoms, lung function, smoking status, occupational exposures, and other risk factors among 3200 people aged 40 years and over living in five Australian communities: Melbourne, Sydney, Tasmania, Busselton (WA), and the Kimberley region (WA). In the Kimberley we will survey 400 Aboriginal people and 400 non-Aboriginal people. We will use a survey methodology that has been developed by an international expert panel and has been implemented in many other countries (in North and South America, Asia, and Europe). This study will provide the first nationally-representative information on the burden of chronic obstructive pulmonary disease (COPD) and the opportunities for health gain by improving the management of this illness. In Australia, COPD is a relatively silent and under-recognised disease but nevertheless is the third most important contributor to the burden of disease and the third leading cause of hospital admission as well as being the underlying cause of 4.2% of all deaths. The information we will collect is needed to form a basis for prevention and disease management interventions to reduce the burden of COPD, particularly among population sub-groups who are disproportionately affected, either due to greater exposure to risk factors (mainly tobacco smoking and occupation), greater susceptibility, under-recognition and under-diagnosis, or inadequate disease management. Importantly, the study will serve to raise awareness about the hazards of smoking for all Australians. By identifying target groups, prevalent exposures and management deficiencies, it will lead the way towards policy-relevant randomised controlled trials testing community-based interventions to prevent COPD and-or manage it more effectively. The information collected will help advance knowledge of the prevalence, burden and treatment of COPD that will be relevant to communities throughout the world.Read moreRead less
The Emerging Problem Of Non-tuberculous Mycobacteria Infection: Understanding Aetiology, Geospatial Epidemiology And Developing Interventions
Funder
National Health and Medical Research Council
Funding Amount
$988,791.00
Summary
This project will be largest study of non-tuberculous mycobacterial (NTM) infection in cystic fibrosis. By combining growing the bacteria with detailed information from the CF patient data registry, geographical location and environmental conditions, this study will provide novel insights into factors associated with NTM. Gene sequencing and airway infection profiling will extend understanding and has the potential to identify novel risk factors and biomarkers for NTM-related airways disease.
The health effects of electronic cigarette use are virtually unknown. They have only recently been introduced into widespread use, and as such their effects on human health will not be known for many years. We will use our expertise in exposure models and health outcome measurement to provide timely hard-data on their potential to impact health – data that are urgently required to guide policy makers in this area.
The Link Between Vitamin D Deficiency And Chronic Lung Disease Is Due To Increased Airway Smooth Muscle
Funder
National Health and Medical Research Council
Funding Amount
$644,067.00
Summary
Vitamin D deficiency is a global public health problem. It is becoming increasingly evident that vitamin D deficiency increases the severity of chronic lung disease. In this study we propose to examine a mechanism that we think clearly explains this association. These studies are critical to understanding how deficiencies in key nutrients can impact on chronic lung disease and will provide the data necessary to guide public health policy to reduce the burden of disease in the community.
Examining The Early Origins Of Asthma And Chronic Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$384,768.00
Summary
Asthma is the most common chronic lung disease of childhood. Birth cohort studies show that early life environmental stressors may increase asthma risk. This study will examine the impact of multiple early-life stressors using a novel ‘exposome’ model in international birth cohort studies, to identify the most significant factors. This will allow for interventions in a planned Australian birth cohort study, leading to improved health for Australians.
Functional And Structural Relationships Of The Peripheral Airways In Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$318,917.00
Summary
It is now considered that airway wall thickening (airway remodeling), a consequence of persistent airway inflammation in asthmatics, significantly contributes to the symptoms and risk of death from asthma. Despite recent advances in the field, there are still many clinically relevant questions that have not been addressed. Some important issues still to be elucidated are: What is the precise sequence of tissue changes in remodeling? Which components of remodeling are reversible in the absence of ....It is now considered that airway wall thickening (airway remodeling), a consequence of persistent airway inflammation in asthmatics, significantly contributes to the symptoms and risk of death from asthma. Despite recent advances in the field, there are still many clinically relevant questions that have not been addressed. Some important issues still to be elucidated are: What is the precise sequence of tissue changes in remodeling? Which components of remodeling are reversible in the absence of allergen provocation? At what point does airway remodeling become irreversible? Does early intervention with anti-inflammatory medication have long term benefits in terms of reducing long-term remodeling? As there have been few appropriate models for addressing these types of remodeling issues, we propose to utilise a large animal model for chronic asthma to address these questions. One of the main focuses of this proposal is to identify biomarkers or functional indices of the different stages of remodelling. The sheep model is well placed to achieve these objectives given that the structure, physiology and asthma pathophysiology of sheep airways is similar to human airways. The novel experimental design is to expose four spatially separate lung regions (segments) in individual sheep with different durations of repeated weekly doses of HDM. The strength of the proposal is that lung function and structure of challenged segments from successive stages of remodeling can be assessed in one sheep. A separate experiment will examine how lung structure and function return to normal in chronically HDM-treated lung segments over successive months after exposure to HDM ceases. It is expected that information gained from this research will lead to a greater fundamental understanding of disease mechanisms in chronic asthma. This will increase the chances of improving current treatments, and allows for new strategies to be devised for treating asthma more effectively.Read moreRead less