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
Does Increased Non-Linear Behavior Caused By Dynamic Variables Increase Ventilatory-Induced Lung Injury (VILI)?
Funder
National Health and Medical Research Council
Funding Amount
$109,625.00
Summary
Acute lung injury (ALI) is precipitated by a variety of different insults, either directly to the lung or elsewhere to the body. Approximately 50% of the patients die. ALI is characterized by an increase in the leakiness of the barrier that normally separates the blood from the airspaces. The fluid which consequently floods the airspaces not only makes it difficult for patients to adequately obtain oxygen, but also dramatically increases the work of breathing by changing the surface forces withi ....Acute lung injury (ALI) is precipitated by a variety of different insults, either directly to the lung or elsewhere to the body. Approximately 50% of the patients die. ALI is characterized by an increase in the leakiness of the barrier that normally separates the blood from the airspaces. The fluid which consequently floods the airspaces not only makes it difficult for patients to adequately obtain oxygen, but also dramatically increases the work of breathing by changing the surface forces within the lungs. As a result, the patients must be mechanically ventilated. However, the very act of using a positive pressure to inflate the lungs often creates further damage, either through repeated opening and closing of collapse tissue or through its over distension. Ventilatory-induced lung injury (VILI), in itself is estimated to contribute to ~30% of the mortality. The best way shown to minimize VILI is through the use of small programmed breaths so as not to overinflate the lungs while still allowing adequate gas exchanges, superimposed upon a background pressure, in order to pre-inflate the lungs and prevent them from repeatedly collapsing. A remaining problem is that just as a rubber band changes its elasticity as it is stretched, so too the lung changes its mechanical properties during distension. Moreover, the lung is considerably more complex since different regions have different elasticities, which change differentially as air flows in and out of them. Airflow in turn depends on regional differences in the location, size, and number of conducting airways. Indeed, we have recently shown for the first time that dynamic changes in lung mechanics may contribute to VILI in patients, despite the use of safe ventilation modalities. This application proposes to examine the extent to which dynamic changes in lung mechanic contribute to VILI in an animal model, as a prelude to more costly, large scale clinical trials aimed at improving mortality.Read moreRead less
Preventing Adverse Outcomes Of Neonatal Hypoxic Ischaemic Encephalopathy With Erythropoietin: A Randomised Controlled Multicentre Australian Trial
Funder
National Health and Medical Research Council
Funding Amount
$2,103,844.00
Summary
One in five babies die worldwide from Hypoxic Ischaemic Encephalopathy caused by low oxygen or blood supply to the brain around birth. Survivors often have low IQ, cerebral palsy, epilepsy or autism. Cooling the baby after birth (hypothermia) reduces the severity of brain damage, but half still die or are disabled. This randomised, controlled trial will test whether Erythropoietin (a natural hormone) can further protect and repair these babies' brains, saving lives and preventing disability.
Stem Cell Treatment For Neonatal Hypoxic Ischaemic Encephalopathy
Funder
National Health and Medical Research Council
Funding Amount
$954,195.00
Summary
Hypoxic-ischaemic encephalopathy occurs when the fetus receives inadequate oxygen in labour and many babies die or have brain damage. Stem cell therapy might save these babies from brain damage but there are many unknowns, such as which stem cells to use and how many. Through our skills in stem cells and measuring the rescued brain following injury, we will determine the necessary details for the most effective stem cell therapy to be ready to immediately test the treatment in a RCT in babies.
Protecting Newborn Brains Via Innovative Monitoring Technology
Funder
National Health and Medical Research Council
Funding Amount
$394,460.00
Summary
This project aims to develop innovative brain monitoring technology which could help minimise brain damage in newborn babies with brain injuries, thereby delivering a healthier start to life. Such novel technology may automatically analyse babies’ brain activity and deliver instant detection of critical abnormalities, which could enable more effective treatment of brain injuries. Babies with reduced oxygen or blood supply to the brain and premature babies could benefit from such innovations.
Lung Volume Recruitment In Neuromuscular Disease: Can Breath-stacking Improve Lung Function, Respiratory Symptoms And Quality Of Life In People With Neuromuscular Disorders?
Funder
National Health and Medical Research Council
Funding Amount
$108,845.00
Summary
Difficulty taking deep breaths or coughing are two of the breathing complications people with a neuromuscular disease can face. Lung volume recruitment, also known as breath-stacking, is a simple and inexpensive therapy that may help. This research will look at the short and medium-term effects of breath-stacking exercises on the breathing system. If lung volume, chest stiffness and cough effectiveness improve then symptoms, quality of life and potentially survival are likely to be better.
The Potential Of Cord Blood Stem Cells To Reduce Neuroinflammation
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Cerebral palsy (CP) is the most common cause of physical disability in children and it is well recognised that the brain injury that underlies CP occurs during pregnancy or around the time of birth. Stem cells isolated from umbilical cord blood offer a promising new therapy for children with CP. This proposal will explore the mechanism of how cord blood stem cells can reduce brain inflammation and damage caused by hypoxia-ischemia, an event known to lead to cerebral palsy.
A Randomised Controlled Trial Of Whole Body Cooling On The Outcome Of Term Infants With Hypoxic Ischaemic Encephalopathy
Funder
National Health and Medical Research Council
Funding Amount
$386,732.00
Summary
The aim of this project is to investigate whether the brain damage caused by a serious lack of oxygen around the time of birth can be prevented or reduced by cooling the baby's temperature to 34C for 72 hours. The consequences, of a lack of oxygen, to the brain, around the time of birth can be devastating. Over 30% of those babies with abnormal brain function soon after birth either die or survive with severe permanent brain damage. There is no specific treatment for these infants. Evidence from ....The aim of this project is to investigate whether the brain damage caused by a serious lack of oxygen around the time of birth can be prevented or reduced by cooling the baby's temperature to 34C for 72 hours. The consequences, of a lack of oxygen, to the brain, around the time of birth can be devastating. Over 30% of those babies with abnormal brain function soon after birth either die or survive with severe permanent brain damage. There is no specific treatment for these infants. Evidence from studies in animals, as well as human adults and a small number of newborn infants, suggests that moderate body cooling started soon after birth in babies with serious abnormal brain function might prevent or reduce brain damage. This project is a multicentre trial, where infants who have suffered from a severe lack of oxygen around birth, are randomised to body cooling to 34C for 72 hours. This will be started as soon as possible after birth at their hospital of birth. If the baby needs to be transported this will be started when the newborn transport team collects the baby for transfer to a newborn intensive care unit. This new treatment will be compared with maintaining the baby's temperature at 37C. This project will investigate a new, simple and pragmatic treatment that might reduce brain damage. If it finds that cooling infants who have been severely deprived of oxygen is an effective and safe treatment, the information will be applicable to any of the very large number of babies around the world who suffer from a serious lack of oxygen around the time of birth.Read moreRead less