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.
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.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
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
Tapasin And Major Histocompatibility Complex Class I Antigen Presentation
Funder
National Health and Medical Research Council
Funding Amount
$226,650.00
Summary
An effective T cell response (cellular immune response) to infections is vital to a functional immune system. Normally, proteins are cleaved into small molecules called peptides and these peptides are in turn presented by Major Histocompatibility Complex molecules to T cells. However, we have only partial understanding of what determines the choice of peptides that are finally presented to T cells. Recent research suggests that a molecule called tapasin may also influence the choice of peptides. ....An effective T cell response (cellular immune response) to infections is vital to a functional immune system. Normally, proteins are cleaved into small molecules called peptides and these peptides are in turn presented by Major Histocompatibility Complex molecules to T cells. However, we have only partial understanding of what determines the choice of peptides that are finally presented to T cells. Recent research suggests that a molecule called tapasin may also influence the choice of peptides. This research proposal aims to examine the role of tapasin in this regard. A thorough understanding of the basic principles of peptide presentation to T cells is crucial to the design of effective vaccines. Furthermore it will also broaden our understanding of immunological responses to cancer, autoimmune diseases and infections.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
Systematic Expansion Of The Clinical Evidence Base In Opioid Prescribing For Refractory Dyspnoea At The End Of Life
Funder
National Health and Medical Research Council
Funding Amount
$414,535.00
Summary
Morphine can relieve breathlessness in the palliative setting. But many important questions remain. What is the best dose, should the dose change over time, do different medications provide the same relief, and how common is dyspnoea in the general population? This three part project will extend our knowledge to answer these questions. Population data will provide critical background to plan best care for future palliative patients distressed by breathlessness.