The Role Of Arousal And Respiratory Control Factors In The Pathogenesis Of Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$567,924.00
Summary
Sleep apnoea (OSA) is a very common breathing disorder in sleep characterized by repetitive closure of the collapsible portion of the throat with serious effects on sleep quality and health. Basic causes of OSA are still largely unknown. We will investigate waking responses to breathing load and related respiratory control factors that we believe may be fundamental causes of OSA, and potentially explain many features of OSA including worsening in light sleep and with increasing age.
Novel Neuromechanical Measurements Of The Human Upper Airway In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$543,728.00
Summary
Obstructive sleep apnea (OSA) is a common condition, in which the upper airway repeatedly collapses during sleep, causing the oxygen concentration in the blood to drop, carbon dioxide to rise, and the person to arouse in order to re-establish adequate oxygen supply. Consequences of OSA include increased daytime sleepiness, increased risk of accidents, and increased risk of cardiovascular diseases. It most commonly affects middle-aged males, but is also seen in the broader population. OSA is asso ....Obstructive sleep apnea (OSA) is a common condition, in which the upper airway repeatedly collapses during sleep, causing the oxygen concentration in the blood to drop, carbon dioxide to rise, and the person to arouse in order to re-establish adequate oxygen supply. Consequences of OSA include increased daytime sleepiness, increased risk of accidents, and increased risk of cardiovascular diseases. It most commonly affects middle-aged males, but is also seen in the broader population. OSA is associated with obesity and specific shapes of the upper airway and facial structure. These anatomical factors can be compensated for while awake but inadequate activity of the muscles surrounding the upper airway during sleep contributes to an increased predisposition of the airway to collapse. Airway collapse occurs when the muscles are unable to withstand the low pressures in the airway and collapse, obstructing the airway. This project will measure the stiffness and motion of the muscles surrounding the airway, in healthy people and those with OSA, to determine how these influence airway collapsibility. We will use two novel non-invasive Magnetic Resonance Imaging (MRI) techniques, MR Elastography, and MR tagging which will allow us to quantify the airway stiffness, or elasticity, and its motion (deformation). These will be the first direct measurements of the upper airway elasticity and deformation in humans. We will also measure how various treatments, such as CPAP therapy and mandibular advancement affect airway elasticity and deformation, so that their mechanisms can be better understood. This may also explain why some patients do not benefit from these therapies. These studies may lead to new diagnostic and treatment modalities, as well as gaining important insights into the basic mechanisms of airway collapse in humans.Read moreRead less
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
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
The Role Of Arousal And Diaphragm Displacement In The Pathogenesis Of Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$410,875.00
Summary
Obstructive sleep apnea (OSA) affects 4% of men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease e.g. heart attacks and strokes. OSA is characterized by repetitive obstructions of the floppy portion of the throat during sleep with adverse effects on oxygen levels and sleep quality. OSA is strongly associated with obesity and is 2-3 times more common in men than women. How obesity and male gender predispose to OSA is ....Obstructive sleep apnea (OSA) affects 4% of men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease e.g. heart attacks and strokes. OSA is characterized by repetitive obstructions of the floppy portion of the throat during sleep with adverse effects on oxygen levels and sleep quality. OSA is strongly associated with obesity and is 2-3 times more common in men than women. How obesity and male gender predispose to OSA is not known. We will investigate two factors that we believe are most likely involved in causing and explaining this gender difference in OSA. We will examine if breathing responses with brief awakening are sufficient to promote OSA patterns of breathing in snorers and if they are greater in male than female OSA patients. We have already shown that healthy men have greater breathing response to arousal compared to women. These brief arousals occur hundreds of times a night in OSA patients, and over-breathing on arousal may increase the probability of upper airway obstruction on falling back to sleep. We will also investigate why even healthy men show greater breathing responses compared to women. Men tend to accumulate fat centrally, particularly in the abdomen, whereas in women fat tends to be distributed more to the hips and thighs. This could be very important in OSA because downward pull exerted on the upper airway by the diaphragm is likely to be reduced in people with more abdominal obesity. This mechanisms has not yet been studied in humans. We will therefore investigate if increased forces placed on the diaphragm during sleep make the upper airway more prone to collapse. We will also investigate these effects during sleep onset, when there may well be important changes in diaphragm position as muscles relax.Read moreRead less
The Role Of Respiratory And Upper Airway Neural Control In Sleep Disordered Breathing
Funder
National Health and Medical Research Council
Funding Amount
$346,018.00
Summary
Obstructive Sleep Apnea (OSA) is a disorder associated with snoring. It affects 4% of adult men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease eg. heart attacks and strokes. Patients with OSA obstruct the floppy portion of the upper airway (UA) during sleep and consequently experience frequent episodes of oxygen deprivation as well as sleep fragmentation. OSA is at least 2-3 times more common in men than women. Whi ....Obstructive Sleep Apnea (OSA) is a disorder associated with snoring. It affects 4% of adult men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease eg. heart attacks and strokes. Patients with OSA obstruct the floppy portion of the upper airway (UA) during sleep and consequently experience frequent episodes of oxygen deprivation as well as sleep fragmentation. OSA is at least 2-3 times more common in men than women. While OSA patients seem, on average, to have smaller upper airways than normal subjects, the cause of OSA cannot be attributed to this factor alone. For example, a small UA cannot explain the male tendency for OSA. Abnormalities in breathing control or the control of upper airway muscles that normally hold the airway open might also be important in OSA. Men have previously been shown to have a greater increase in UA resistance during sleep than women, consistent with the idea that a gender difference in UA muscle control partly explains why more men than women have OSA. We aim to investigate how changes in breathing and UA dilator muscle control might lead to unstable patterns of breathing and to OSA. We propose that protective UA muscle reflexes are reduced during sleep more in men than women, and are reduced by low blood oxygen levels and alcohol (a known aggravator of sleep apnea). We further propose that low blood oxygen levels not only result from OSA but may also aggravate OSA by preferentially reducing the activity of UA dilating muscles, by making breathing patterns overall less stable and by depressing the ability of subjects to arouse from sleep to an airway blockage. We believe that this tendency to decrease UA activity may be exaggerated in OSA patients. We also propose that men are more vulnerable to the deleterious effects of low oxygen than women. We will also examine if men and snorers have exaggerated breathing responses on arousal from sleep.Read moreRead less
The Role Of Snoring Vibrations In The Pathogenesis Of Early Carotid Artery Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$593,833.00
Summary
Habitual snoring is a very common problem in the adult population, with a prevalence of between 20-40%. Increasingly it is now recognised that snoring may be an independent risk factor for the development of stroke. In this proposal, we will explore the hypothesis that chronic snoring transmits a pressure wave through the tissues of the neck to the carotid artery which may damage the artery wall and subsequently lead to stroke. This may lead to new strategies to treat habitual snoring.
Foetal Determinants Of Sleep Disordered Breathing In Infants
Funder
National Health and Medical Research Council
Funding Amount
$174,691.00
Summary
Obstructive sleep apnea (OSA) has been identified and recorded in infants, however the factors that lead to the development of OSA and its prevalence in infants is unknown. We have recorded OSA in some infants and we demonstrated that the severity of apnea was at its peak at approximately 2 months of age and then resolved by 1 year. We hypothesised that these infants possibly had a maturational delay of breathing control during sleep. This project is designed to examine the development and preva ....Obstructive sleep apnea (OSA) has been identified and recorded in infants, however the factors that lead to the development of OSA and its prevalence in infants is unknown. We have recorded OSA in some infants and we demonstrated that the severity of apnea was at its peak at approximately 2 months of age and then resolved by 1 year. We hypothesised that these infants possibly had a maturational delay of breathing control during sleep. This project is designed to examine the development and prevalence of sleep and breathing disorders in infants. The prenatal factors that possibly influence development of sleep and breathing disorders in infants, in particular, the effects of maternal smoking will be determined. Pregnant women will be recruited for the study during their third trimester. The foetal movements, foetal breathing movements, heart rate and sleep state will be monitored continuously overnight in the patients home between 32 and 36 weeks gestation using a newly developed foetal movement monitor. The infants will be subsequently studied using overnight polysomnography at 2 months of age to assess their breathing, sleep patterns, arousal behaviour, and the presence and severity of central and obstructive apnea. A group from these infants will be selected and studied longitudinally to examine the development of sleep and breathing disorders more closely. These infants will undergo overnight sleep studies during the first week of life, then at 2 and 6 months of age. A detailed medical history will also be collected regarding the pregnancy, the perinatal history of the infant, exposure to cigarette smoke during pregnancy and postnatally, and the medical history of other family members. We will examine the quality and quantity of foetal movements and its association with the development of OSA. The occurrence of sleep and breathing disorders in the infants will be correlated with the foetal behaviour and, the prenatal and postnatal factors.Read moreRead less
Alternatives To Polysomnography For Children With Suspected Obstructive Sleep Apnoea.
Funder
National Health and Medical Research Council
Funding Amount
$357,613.00
Summary
Snoring is the cardinal symptom of obstructive sleep apnoea (OSA), a major health issue in childhood with significant impacts on cognition, behaviour and cardiovascular health. Approximately 35% of children snore but only about 10% of those have OSA. Defining OSA in a snoring child requires polysomnography, a technically challenging and expensive test. In this study we will examine a number of simple tests for their predictive power for OSA, developing a tool that will enable clinicians to diagn ....Snoring is the cardinal symptom of obstructive sleep apnoea (OSA), a major health issue in childhood with significant impacts on cognition, behaviour and cardiovascular health. Approximately 35% of children snore but only about 10% of those have OSA. Defining OSA in a snoring child requires polysomnography, a technically challenging and expensive test. In this study we will examine a number of simple tests for their predictive power for OSA, developing a tool that will enable clinicians to diagnose OSA without the need for polysomnography.Read moreRead less
Pharyngeal Wall Folding: Role In Upper Airway Collapsibility
Funder
National Health and Medical Research Council
Funding Amount
$217,274.00
Summary
In obstructive sleep apnoea (OSA) the throat closes during sleep. In order for the throat to close the surface of the throat has to fold. Mathematical models predict that the more folds present, the more stable a structure will be. This research will examine how folding of the airway surface of the throat is achieved in subjects with and without OSA. It will also develop ways of changing the folding patterns using bench, animal and human studies. This will result in new treatments for OSA.