Does Adenotonsillectomy Change Vascular Function In Children With Sleep Breathing Disorders?
Funder
National Health and Medical Research Council
Funding Amount
$522,105.00
Summary
Sleep breathing disorders affect 10% of all children and when severe, obstruction in the upper airways causes serious deficits in growth, development, brain function and heart health. But even mild snoring (without obstruction) may also cause poor health in the arteries that supply blood to the brain and heart, as well as the smaller arteries in the arms and legs. In both adults and children with conditions like diabetes and obesity, poor blood vessel health has been shown to greatly increase th ....Sleep breathing disorders affect 10% of all children and when severe, obstruction in the upper airways causes serious deficits in growth, development, brain function and heart health. But even mild snoring (without obstruction) may also cause poor health in the arteries that supply blood to the brain and heart, as well as the smaller arteries in the arms and legs. In both adults and children with conditions like diabetes and obesity, poor blood vessel health has been shown to greatly increase the future risk of heart attacks, angina and strokes. Children with severe sleep breathing disorders (such as sleep apnoea syndrome) are currently treated by removal of the tonsils and adenoids, which typically resolves snoring and improves sleep, but it is not yet known whether there are any benefits for blood vessel health. The earliest signs of blood vessel disease in children are abnormal function of the lining of the blood vessels (endothelial dysfunction) and thickening of the lining of blood vessels (intima media thickness). They precede the adult diseases of atherosclerosis - which causes heart attacks and strokes, and diabetic kidney and eye disease. These changes can be measured accurately and non-invasively using ultrasound imaging of arteries in the neck and arm. Our primary aim is to assess whether changes in blood vessel health occur in children with sleep breathing disorders across the range of severity, with a secondary aim to measure any changes in cardiovascular control during both sleep (when snoring occurs). Most importantly, by assessing children before and after surgery, we will be able to see for the first time whether treatment of childhood snoring improves blood vessel health. This study may have major implications for the clinical management of snoring children, who may require treatment at an earlier age to prevent poor blood vessel health and an increased risk of cardiovascular diseases later in life.Read moreRead less
Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms c ....Mucopolysaccharidoses (MPS) are a related group of 11 debilitating genetic disorders affecting children. They result from a reduction or total deficiency of an enzyme required for the removal of carbohydrate structures called glycosaminoglycans (gags). Gag degradation occurs inside the cell in specific organelles termed lysosomes and in the absence of the appropriate enzyme, undegraded gag accumulates in the cell. This leads to a range of clinical symptoms and multiple tissue failure. Symptoms common to more than one MPS type include mental deterioration, blindness, abdominal organ enlargement and bone growth problems leading to short stature and bone loss. My laboratory has had a long-term interest in developing treatment for MPS and our research led to the clinical implementation of enzyme replacement therapy (ERT) for MPS VI in 2005. While providing the first effective, multi-tissue treatment for MPS, our research showed that several tissues were not responsive to ERT. These are the brain, cartilage and cornea, thus children on ERT regimens will still suffer from mental retardation, arthritis and blindness. With the goal of treating these particular tissues we have developed a new approach to MPS therapy called substrate deprivation therapy (SDT). Instead of adding back the missing enzyme, SDT acts by decreasing gag production which in turn reduces the level of accumulated gag in cells. SDT results in the correction of MPS cells in culture and reduces several key clinical symptoms in the mouse model of MPS IIIA. In this proposal we will extend our research to evaluate the effect of SDT on brain and bone-joint pathology. Evaluation of efficacy will take place in the MPS VII mouse which exhibits both brain and bone disease and in a new model of MPS IVA developed specifically for this study which exhibits a joint pathology unique amongst the MPS disorders.Read moreRead less
The Effect Of Adenotonsillectomy On Neurocognitive Functioning In Children With Upper Airway Obstruction
Funder
National Health and Medical Research Council
Funding Amount
$185,850.00
Summary
Upper airway obstruction during sleep affects up to 3% of all children and is very frequently unrecognised. If severe it causes growth failure, developmental delay and heart failure. However, there is little information on the effects of less severe degrees of upper airway obstruction in children but recent work suggests that reduced academic performance may also be present in children with relatively mild degrees of upper airway obstruction. In particular, the areas most affected appear to be i ....Upper airway obstruction during sleep affects up to 3% of all children and is very frequently unrecognised. If severe it causes growth failure, developmental delay and heart failure. However, there is little information on the effects of less severe degrees of upper airway obstruction in children but recent work suggests that reduced academic performance may also be present in children with relatively mild degrees of upper airway obstruction. In particular, the areas most affected appear to be intelligence, memory, behaviour and attentional capacity . Currently it is unclear whether these deficits are due to sleep disruption or reduced nocturnal oxygen levels. The treatment of upper airway obstruction is the removal of adenoids and tonsils, however, it is unknown whether or not this improves the child's intellectual capacity. This study aims to be one of the first to critically evaluate the impact of upper airway obstruction during sleep on children's intelligence, memory, behaviour and attentional capacity, and the improvements wrought by the removal of the child's tonsils and adenoids.Read moreRead less
Therapy For CNS Degeneration In MPS Disorders That Targets Both Glycosaminoglycan And Ganglioside Storage.
Funder
National Health and Medical Research Council
Funding Amount
$368,043.00
Summary
Children with seven of the eleven types of mucopolysaccharidosis (MPS) disorders exhibit a profound, irreversible neurological deterioration that manifests in infancy. This results from the continual buildup of undegraded sugar and fat in brain cells. The goal of this proposal is to prevent the accumulation of lipid alone or both lipid and sugar in the brain in order to alter the progression of neurological disease. Treatment will be assessed in mouse models of MPS.
Sleep Disordered Breathing And Neurocognitive Function In Children Post-adenotonsillectomy: Three Year Follow-up
Funder
National Health and Medical Research Council
Funding Amount
$266,536.00
Summary
Snoring is very common and affects at least 10% of children, or an estimated 0.25 million children in Australia. It is associated with deficits in a wide range of neurocognitive areas including intelligence, memory, reasoning, learning and behaviour. We have recently studied a group of 53 snoring children both before and six months after removal of their tonsils and adenoids, to treat suspected upper airway obstruction associated with their snoring. We found that prior to surgery, intelligence, ....Snoring is very common and affects at least 10% of children, or an estimated 0.25 million children in Australia. It is associated with deficits in a wide range of neurocognitive areas including intelligence, memory, reasoning, learning and behaviour. We have recently studied a group of 53 snoring children both before and six months after removal of their tonsils and adenoids, to treat suspected upper airway obstruction associated with their snoring. We found that prior to surgery, intelligence, memory, reasoning, language and behaviour were significantly reduced, by up to 10% compared to 53 non-snoring control children matched by age, gender, social class and area of residence. To our great surprise, at six months after surgery we found that although sleep and behaviour improves, intelligence, memory, reasoning and language development do not. We now wish to study these same children at 3 years after tonsils and adenoids removal, as we believe that if the deficits that we described at 6 months are still present, they are likely now to be permanent. Given the degree of deficit that we have found in snoring compared to non-snoring children, even 6 months after the snoring group of children have been treated, if still present at 3 years post-surgery then it is likely that these deficits will affect the children's future learning potential and academic success. In turn, this would suggest that early identification and treatment of sleep-related upper airway obstruction is critical in preventing long-term deficits in children's daytime functioning and behaviour.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
Factor V Leiden Mutation: A Contributory Factor For Cerebral Palsy?
Funder
National Health and Medical Research Council
Funding Amount
$72,595.00
Summary
Cerebral palsy is the commonest physical disability in childhood. It has a major impact on individuals and families. In a significant proportion of cases, the cause is unknown so further research is essential to define the reasons for this condition, and thereby develop preventative strategies. Two mutations have been identified that predispose carriers to develop blood clots (called thrombosis). These mutations are the Factor V Leiden mutation and the coagulation gene for prothrombin (also know ....Cerebral palsy is the commonest physical disability in childhood. It has a major impact on individuals and families. In a significant proportion of cases, the cause is unknown so further research is essential to define the reasons for this condition, and thereby develop preventative strategies. Two mutations have been identified that predispose carriers to develop blood clots (called thrombosis). These mutations are the Factor V Leiden mutation and the coagulation gene for prothrombin (also known as the G20210A mutation). If blood clots form in, or travel to the brain (embolism), they can obstruct the blood supply causing damage that may result in cerebral palsy in young children. Our research will investigate both mothers of children with cerebral palsy, and the children themselves. The study of the mothers will determine whether those that are carriers of these mutations are at an increased risk of having children with cerebral palsy. Factors that may precipitate the development of blood clots, such as smoking during pregnancy, will be investigated. The children with cerebral palsy will be studied to determine whether they carry the mutations, and if so, whether they have brain scan evidence of previous blood clots. Children will be tested for the mutation using the blood spot taken routinely early in life. These blood spots are stored on cards (Guthrie cards) and are available for research following parental consent. The mothers will be tested for the mutation by using a saliva sample and will also be interviewed to obtain details of their pregnancies. As a result of this project, useful information will be provided for families and health care providers. It will be established whether these mutations play a role in the genesis of cerebral palsy. In addition, data about possible factors which may increase the risk in carrier mothers, such as smoking, will be provided.Read moreRead less
Previous research has shown that SIDS victims have a number of subtle abnormalities that set them apart from the normal population. These include the occurrence of upper airway obstruction in sleep, a reduced ability to awaken from sleep and abnormalities of the automatic control of heart rate and blood pressure in sleep. These body functions are controlled by a component of the brain called the autonomic nervous system which controls the heart and other internal functions by means of nerves cal ....Previous research has shown that SIDS victims have a number of subtle abnormalities that set them apart from the normal population. These include the occurrence of upper airway obstruction in sleep, a reduced ability to awaken from sleep and abnormalities of the automatic control of heart rate and blood pressure in sleep. These body functions are controlled by a component of the brain called the autonomic nervous system which controls the heart and other internal functions by means of nerves called the parasymmpathetic and sympathetic systems. The purpose of this project is to undertake studies of the autonomic system in normal infants and in those infants who are considered to be at risk for SIDS. As SIDS occurs almost exclusively in sleep it is important to study the infant?s heart rate and blood pressure responses to various challenges whilst asleep. All infants (both controls and subjects) enrolled in the protocol will therefore undergo overnight sleep studies during which their automatic responses to a variety of stimuli will be measured. Once we have established the normal response to these stimuli we can then compare them to the results of the at risk group. If, as we anticipate, there is a difference between our at risk group and the normal controls in automatic function then we will measure some of the stress hormones in the body which reflect the function of the autonomic nervous system. If there is a difference in the levels of these hormones between the normal and the at risk groups which correlates with the expected subtle abnormalities in function we may be able to devise an accessible and quantifiable measure for those infants at risk of SIDSRead moreRead less