Upper Airway Dilator Muscle Activity During Sleep Onset.
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Disorders of breathing during sleep are recognised as a major health problem. Of these, Obstructive Sleep Apnoea is the most prevalent, occurring in approximately 4% of the male and 2% of the female population. In this disorder the upper airway collapses during sleep causing cessation of airflow and subsequent oxygen desaturation. The airway is thought to occlude because dilator muscles are unable to sustain patency in the face of the negative pressures generated by inspiratory effort. In order ....Disorders of breathing during sleep are recognised as a major health problem. Of these, Obstructive Sleep Apnoea is the most prevalent, occurring in approximately 4% of the male and 2% of the female population. In this disorder the upper airway collapses during sleep causing cessation of airflow and subsequent oxygen desaturation. The airway is thought to occlude because dilator muscles are unable to sustain patency in the face of the negative pressures generated by inspiratory effort. In order for patency of the airway to be re-established some form of arousal from sleep must occur . As the UA is likely to collapse on the resumption of sleep, the cycle becomes repetitive, causing significant sleep disruption. OSA is a significant health risk, being associated with increased risk of cardiovascular disorders, increased mortality, excessive daytime sleepiness, reduced daytime performance and increased risk of accidents. In previous work we have demonstrated that normal sleep related changes in the activity of upper airway dilator muscles result in a reduction in the calibre of the airway at sleep onset. This exposes some individuals, such as those with narrow airways, to airway obstruction during sleep. We have also reported that elderly men have larger reductions in upper airway muscle activity at sleep onset than younger men, suggesting one reason why they may have a higher prevalence for Obstructive Sleep Apnea. The aim of the present project is to determine what causes the larger reductions in upper airway muscle activity in older males. The answer to this question will contribute to understanding why this group is so susceptible to Obstructive Sleep Apnea and will elucidate the mechanisms leading to the disorder.Read moreRead less
The Influence Of Sleep On The Behaviour Of The Upper Airway Muscles, Genioglossus And Tensor Palatini
Funder
National Health and Medical Research Council
Funding Amount
$295,880.00
Summary
The human airway has limited bone or cartilage support and muscular activity is required to keep the airway open. Central activation of these muscles is reduced during sleep, resulting in the disorder Obstructive Sleep Apnoea. Potential treatments include pharmocological or electrical stimulation of upper airway muscles. However, this is hampered by a lack of understanding of the control of upper airway muscles. This project will study two critical muscles, genioglossus and tensor palatini.
Regulatory Control Of The Upper Airway Muscle Genioglossus During Sleep
Funder
National Health and Medical Research Council
Funding Amount
$329,855.00
Summary
Difficulty breathing during sleep is a major health problem. Obstructive Sleep Apnoea (OSA) is the most frequently occurring of these disorders, being found in approximately 4% of males and 2% of females. In OSA the upper airway (UA) collapses during sleep preventing airflow and causing a fall in oxygen levels in the blood. The airway collapses because during sleep muscles in the UA are unable to offset the negative pressure generated within the airway by the effort of inspiring. If the negative ....Difficulty breathing during sleep is a major health problem. Obstructive Sleep Apnoea (OSA) is the most frequently occurring of these disorders, being found in approximately 4% of males and 2% of females. In OSA the upper airway (UA) collapses during sleep preventing airflow and causing a fall in oxygen levels in the blood. The airway collapses because during sleep muscles in the UA are unable to offset the negative pressure generated within the airway by the effort of inspiring. If the negative pressure is too great and the airway collapses the person has to wake up to reopen the airway. As the UA collapses again on the return of sleep, the cycle becomes repetitive, causing sleep disruption. OSA is a significant health risk causing heart disorders, increased mortality, daytime sleepiness, reduced daytime performance and increased risk of accidents. OSA is due to two interacting factors. First, people with a narrow airway have to generate a greater negative pressure during inspiration. Second, and critically, sleep reduces activity in the UA muscles. The importance of this sleep effect is indicated by the observation that OSA patients do not obstruct while awake. Thus, a respiratory abnormality during sleep is a necessary component of the disorder. However, progress in understanding motor control of UA muscles has been slow. We argue that this is in part because research has concentrated on analysing the activity of the UA muscles, rather than measuring the individual motor units that make up the muscles. In this project we propose to investigate the sleep related activity of individual motor units in the UA muscle, genioglossus (GG). GG plays a critical role in the UA as it keeps the tongue from collapsing backwards into the airway. We anticipate that this approach will provide insights into motor control of the tongue and the role of GG in the development of OSA.Read moreRead less
Interaction Between Sleep Apnea And Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$423,650.00
Summary
In this proposal, we will study possible ways in which sleep disordered breathing (snoring sickness or sleep apnea) may cause or worsen metabolic syndrome. Sleep apnea is a common disorder frequently linked to metabolic syndrome. Metabolic syndrome is a cluster of health risk factors including increased risk of diabetes, high cholesterol, high blood pressure and excess fat around the abdomen. Metabolic syndrome is an important cause of increased death from cardiovascular disease and affects abou ....In this proposal, we will study possible ways in which sleep disordered breathing (snoring sickness or sleep apnea) may cause or worsen metabolic syndrome. Sleep apnea is a common disorder frequently linked to metabolic syndrome. Metabolic syndrome is a cluster of health risk factors including increased risk of diabetes, high cholesterol, high blood pressure and excess fat around the abdomen. Metabolic syndrome is an important cause of increased death from cardiovascular disease and affects about 3 million Australians. Our theory is that lack of oxygen during sleep and disruption of normal sleep patterns leads to increased activity of the body stress handling systems and damage to the lining of the body's blood vessels. In turn, this may promote high blood fat levels and cause excess fat deposits in muscle and liver. We will measure blood, muscle and liver fat changes with treatment of sleep apnea. We believe that by damaging the lining of blood vessels, sleep apnea will also cause an inability of the body's arteries to relax properly. We will measure sleep apnea and the ability of the body's arteries to expand using novel techniques before and after treatment of sleep apnea. We will also take people off treatment to see if these changes get worse. Part of the proposal includes investigating whether snoring and lack of oxygen during sleep leads to increased blood fat levels. Finally, in another study, we will measure the change in metabolic syndrome related disorders in people with sleep apnea losing weight.Read moreRead less
A Functional Autoantibody In Human Narcolepsy: Direct Evidence For The Autoimmune Hypothesis
Funder
National Health and Medical Research Council
Funding Amount
$444,928.00
Summary
Narcolepsy is a chronic disabling sleep disorder causing irresistible sleepiness and, in most cases, brief attacks of weakness on emotional arousal (cataplexy). Other symptoms include a transient paralysis at the beginning or end of sleep and vivid hallucinations at the start of sleep. Symptoms usually appear during adolescence or early adulthood. It affects between one in 1,000 and one in 2,000 people, yet the diagnosis is often delayed for several years because of the lack of a simple diagnost ....Narcolepsy is a chronic disabling sleep disorder causing irresistible sleepiness and, in most cases, brief attacks of weakness on emotional arousal (cataplexy). Other symptoms include a transient paralysis at the beginning or end of sleep and vivid hallucinations at the start of sleep. Symptoms usually appear during adolescence or early adulthood. It affects between one in 1,000 and one in 2,000 people, yet the diagnosis is often delayed for several years because of the lack of a simple diagnostic marker. It has been suspected for some time that narcolepsy is caused by a malfunctioning immune system, but direct evidence for the so-called autoimmune hypothesis has been lacking. We have recently discovered the smoking gun in the form of an autoantibody that circulates in the bloodstream and produces some of the features of narcolepsy on transfer to experimental animals. The identification of the autoantibody, which we term a functional autoantibody because it directly alters the function of nerves thought to be involved in narcolepsy and cataplexy, opens a new chapter in narcolepsy research that has important diagnostic and therapeutic implications. Testing for the autoantibody in subjects recruited from national and international centres for sleep research will determine its value in the diagnosis of narcolepsy and may help distinguish narcolepsy from other sleep disorders. Preliminary findings are encouraging and suggest that the autoantibody is a sensitive and specific marker for human narcolepsy and might lead to a clinically useful diagnostic test. In another part of the project, experimental approaches willl be used to identify an antibody called an antiidiotype that can neutralise the narcolepsy autoantibody and therefore be developed as a therapeutic agent. Finally, experiments have been designed to examine the effect of the autoantibody on neurotransmitters in the brain that are believed to result in cataplexy.Read moreRead less
Impact Of Sleep Disordered Breathing On Cardiovascular, Behavioural And Neurocognitive Function In Preschool Children
Funder
National Health and Medical Research Council
Funding Amount
$425,703.00
Summary
Studies in school age children have shown that disruption to normal sleep patterns resulting from sleep disordered breathing (SDB) has severe consequences for both the cardiovascular system and neurocognition. To date there have been limited investigations of the effects of SDB in pre-school children despite the knowledge that disruptions to breathing during sleep are maximal at this age and the central nervous system which is immature and developing at this time, is most vulnerable to injury.
Cardiovascular, Neurophysiological And Neurocognitive Assessments To Define Sleep Disordered Breathing In Children
Funder
National Health and Medical Research Council
Funding Amount
$324,008.00
Summary
Disruptions to breathing during sleep (snoring), known as sleep disordered breathing occurs in up to 27% of children and forms a continuum of symptoms ranging from mild to severe. It has previously been thought that only severe disruptions to breathing, as occurs in obstructive sleep apnoea (OSA), were of clinical significance requiring intervention, however recent studies have shown that even snoring with no currently used signs of altered blood oxygenation levels or sleep disruption can have a ....Disruptions to breathing during sleep (snoring), known as sleep disordered breathing occurs in up to 27% of children and forms a continuum of symptoms ranging from mild to severe. It has previously been thought that only severe disruptions to breathing, as occurs in obstructive sleep apnoea (OSA), were of clinical significance requiring intervention, however recent studies have shown that even snoring with no currently used signs of altered blood oxygenation levels or sleep disruption can have a significant impact on daytime functioning and school performance. It is also known that cardiovascular disease is a long-term consequence of untreated sleep disordered breathing in adults, however the long-term effects on the cardiovascular system in children are unknown. This study will examine both the neurocognitive and cardiovascular effects of a range of severities of sleep disordered breathing in children and will identify new more sensitive markers of sleep disruption in order to predict neurocognitive dysfunction. In order to address this most important issue, this project will combine the expertise of scientists and clinicians in the fields of paediatric sleep, cardiovascular control and neuropsychological assessment from Monash and Melbourne Universities, and the Monash Medical Centre and Royal Children's Hospital.Read moreRead less