Pregabalin And Speech Pathology Treatment For Refractory Chronic Cough With Laryngeal Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$155,747.00
Summary
Persistent cough that does not respond to medical treatment is debilitating and frustrating for the sufferer and very expensive for the Australian government. This research will provide a new and effective treatment option and extend our current reputation as the world leader in the identification and treatment of refractory chronic cough. This treatment strategy has not been trialled before and the findings will change current medical practice and significantly reduce community health costs.
The Effect Of CPAP On Erectile And Endothelial Dysfunction In Impotent Men With Obstructive Sleep Apnea
Funder
National Health and Medical Research Council
Funding Amount
$609,559.00
Summary
Erectile dysfunction is common in men with obstructive sleep apnea, due to vascular damage, which leads to heart attack. CPAP is the preferred treatment for patients with OSA because of its well-proven ability to decrease sleepiness and improve blood pressure control. This study will establish if CPAP can also improve erectile and vascular endothelial dysfunction. These results will shed light on the mechanisms that underpin the relationship between OSA and Erectile Dysfunction.
Protecting The Endothelial Glycocalyx To Improve Transplant Rates And Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$725,180.00
Summary
A tiny, previously overlooked, structure called the endothelial glycocalyx (EG) is now known to ‘waterproof’ blood vessels. This grant extends our exciting preliminary data in the field of lung transplantation, where we have shown that EG loss is the main cause of a poorly functioning organ, to develop new tests of lung and kidney function, as well as treatments to resuscitate marginal organs outside the body, so improving access to and the safety of transplantation.
Dynamic In Vivo Size & Shape Measurement Of The Human Upper Airway Using Endoscopic Long-range Optical Coherence Tomogra
Funder
National Health and Medical Research Council
Funding Amount
$184,250.00
Summary
This project will fund the construction of a clinically deployable prototype device to measure changes in upper airway size and shape in patients with obstructive sleep apnoea. We have recently developed and validated a technique based on endoscopic optical coherence tomography (OCT). Preliminary in vivo studies have been performed in the human upper airway and the results published. To our knowledge, this is the only such system world-wide capable of making these important measurements. The tec ....This project will fund the construction of a clinically deployable prototype device to measure changes in upper airway size and shape in patients with obstructive sleep apnoea. We have recently developed and validated a technique based on endoscopic optical coherence tomography (OCT). Preliminary in vivo studies have been performed in the human upper airway and the results published. To our knowledge, this is the only such system world-wide capable of making these important measurements. The technique has wide commercially applicability as it can be used to measure the internal dimensions of any hollow organ system.Read moreRead less
Pulmonary hypertension is a disease affecting the blood vessels in the lungs that causes severe shortness of breath and early death. Genetic mutations are known to cause this disease but the precise link between these mutations and the changes in the lungs are poorly understood. If we could understand this process better, we could design better treatments. This project will look at how the cells in the lungs communicate with each other and how this process is disturbed in pulmonary hypertension.
Novel Pharmacological Strategies To Treat Cognitive Dysfunction In COPD
Funder
National Health and Medical Research Council
Funding Amount
$872,455.00
Summary
Chronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and is the 4th largest cause of death worldwide. Up to 60% of COPD patients suffer from cognitive dysfunction (i.e. a brain disorder which affects learning, memory, attention) which often leads to dementia. The reason for this is unknown so the aim of this study is to determine why people with COPD suffer from mental disorders then develop novel treatments to treat these disorders in COPD patients.
Endothelial Development From Pluripotent Stem Cells As A Means To Study Pathology In Pulmonary Artery Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Pulmonary artery hypertension (PAH) is a fatal disease primarily affecting young adults. It is caused by a defect in cells that form the vessel that carries blood from the heart to the lungs. We will use stem cells made from the skin of PAH patients to examine why the blood vessel cells from these patients fail to function normally.
Determining The Cellular Mechanisms Involved In The Airway Response To Topical Citrate
Funder
National Health and Medical Research Council
Funding Amount
$444,491.00
Summary
The air passages of the lungs are lined by mucous membranes. These membranes are covered by a thin layer of fluid to protect the airways from drying. This fluid allows the cilia, the hair like projections on top of the airway cells to beat more effectively to remove mucous and inhaled particles from the lungs. The volume and composition of this fluid is determined by the salt and water movement across the mucous membranes of the airways. These processes are abnormal in cystic fibrosis (CF), the ....The air passages of the lungs are lined by mucous membranes. These membranes are covered by a thin layer of fluid to protect the airways from drying. This fluid allows the cilia, the hair like projections on top of the airway cells to beat more effectively to remove mucous and inhaled particles from the lungs. The volume and composition of this fluid is determined by the salt and water movement across the mucous membranes of the airways. These processes are abnormal in cystic fibrosis (CF), the most common lethal inherited disease affecting Australians. In CF, an abnormal gene disrupts one of the major mechanisms for salt and water movement in the air passages. This abnormal salt transport causes drying of the airway surface which impairs the working of the cilia. This leads to retention of mucous in the airways with repeated bacterial infections damaging the lungs. Over the last 10 years, we have developed a series of simple tests to measure the abnormalities in the CF airway of human subjects. We have isolated an exciting new clinical application for sodium citrate, a substance used in blood transfusions. Citrate appears to alter both the salt transport abnormalities found in CF. This research proposal seeks to better understand the dual effects of citrate and to test similar compounds that may have stronger effects. The ultimate aim of our research is to have sufficient knowledge to work out the best way to develop a new treatment for CF.Read moreRead less
Neurons And Neurotransmitters That Control Phasic Laryngeal Motoneuron Activity
Funder
National Health and Medical Research Council
Funding Amount
$278,736.00
Summary
Opening and closing of the vocal cords with breathing is an automatic function that is present before birth and is essential for life. Opening the vocal cords allows inspired air to enter the lungs and closure serves to protect the lungs from food and drink. Failure of coordination is associated with a range of life-threatening airway disorders, particularly in newborns. Nerves in the brain and the chemicals they release transmit the rhythm of breathing to the nerves that control the vocal cords ....Opening and closing of the vocal cords with breathing is an automatic function that is present before birth and is essential for life. Opening the vocal cords allows inspired air to enter the lungs and closure serves to protect the lungs from food and drink. Failure of coordination is associated with a range of life-threatening airway disorders, particularly in newborns. Nerves in the brain and the chemicals they release transmit the rhythm of breathing to the nerves that control the vocal cords. However, the specific neurons and chemicals involved are not known. This information is crucial in understanding the chemical disorder in the brain responsible for the loss of coordination between breathing and vocal cord activity, and in formulating strategies to treat these conditions using drugs that correct the chemical disorder. By way of example, we have used our animal studies to develop the first ever drug trial to treat children with congenital vocal cord paralysis, whose vocal cords fail to open with inspiration and require a tracheostomy. We have selected a drug that corrects the proposed disorder of brain chemistry responsible for this condition. This approach will serve as a template for the management of a variety of other life-threatening airway disorders in newborns using drugs that act on the brain. We will now carry out further experiments to identify the nerves and their chemicals that control the motoneurons that drive the vocal cords. The key experiment involves recording from inside an individual vocal cord motoneuron in the brain while simultaneously applying a range of chemicals to its external surface. By recording the response of the nerve, we can determine which chemicals control its activity. Using our knowledge of the pattern of chemicals released by respiratory neurons, we will identify neurons for further study, and establish chemical and anatomical relationships between the respiratory nerve and the vocal cord nerve.Read moreRead less
Factors Determining Collapsibility Of The Human Upper Airway During Sleep And General Anaesthesia
Funder
National Health and Medical Research Council
Funding Amount
$259,625.00
Summary
Obstructive sleep apnoea (OSA) is common, affecting between 2-4% of middle-aged adults. It is characterised by repetitive partial or complete collapse of the upper airway during sleep. Each episode is accompanied by transient hypoxemia, hypertension and arousal. The repetitive arousals disrupt sleep resulting in excessive daytime tiredness and lethargy, which have major consequences for social well-being and productivity in our community. OSA is an independent risk factor for vascular disease. C ....Obstructive sleep apnoea (OSA) is common, affecting between 2-4% of middle-aged adults. It is characterised by repetitive partial or complete collapse of the upper airway during sleep. Each episode is accompanied by transient hypoxemia, hypertension and arousal. The repetitive arousals disrupt sleep resulting in excessive daytime tiredness and lethargy, which have major consequences for social well-being and productivity in our community. OSA is an independent risk factor for vascular disease. Central to understanding OSA is knowledge of the mechanisms responsible for vulnerability to upper airway collapse. It remains unclear to what extent this vulnerability relates to abnormalities in the underlying structure and passive physical characteristics of the upper airway, versus abnormalities in activity of upper airway muscles. Making this distinction has been problematic because current methods of testing upper airway collapsibility in sleeping humans tend to result in changes in muscle activity and-or sleep state, affecting the measurements. It is, however, possible to suppress upper airway muscle activity and eliminate measurement-related changes in muscle activity and state with general anaesthesia, while maintaining normal spontaneous breathing. We have developed and refined this method and propose to use it in novel investigations to (a) relate the behaviour of the flaccid airway (no muscle activity) under anaesthesia to its behaviour during sleep (when muscle activity is variable but quantifiable), and (b) determine the effect of changes in body habitus (posture and lung volume) on airway collapsibility. These studies will allow examination of the exciting possibility that measurements made under brief general anaesthesia could be used to define propensity to obstruction during sleep. They will also allow examination of the contribution of common changes in body habitus toward vulnerability to upper airway collapse.Read moreRead less