While many cases of asthma are mild, severe cases require extensive health care resources and are virtually unresponsive to conventional treatment. This project will investigate whether specific compounds released from the airway are able to cause lung damage and airway abnormalities similar to that in severe asthma. We will investigate whether these changes are responsive to conventional therapy and investigate a potential treatment for regaining this responsiveness in severe asthma.
Intrinsic Response Of Airways To Cyclical Dilation And Elongation In Breathing
Funder
National Health and Medical Research Council
Funding Amount
$355,014.00
Summary
Variations in lung pressures during breathing produce cyclical expansion of the airway tubes. These respiratory movements provide one of the most powerful protective mechanisms for the lung. The protective mechanism fails in asthma so that cyclical expansion of the airway tubes can make breathing more difficult. Current belief is that protective and harmful effects of lung expansion occur by either relaxation or contraction of the muscles lining the airway tubes. Findings from this laboratory su ....Variations in lung pressures during breathing produce cyclical expansion of the airway tubes. These respiratory movements provide one of the most powerful protective mechanisms for the lung. The protective mechanism fails in asthma so that cyclical expansion of the airway tubes can make breathing more difficult. Current belief is that protective and harmful effects of lung expansion occur by either relaxation or contraction of the muscles lining the airway tubes. Findings from this laboratory suggest that the above dogma needs reconsideration. The project will utilize a novel model of the lung to enable us to determine the mechanisms producing both the protective effect, and in asthmatics the harmful effects of cyclical lung expansion. Once the part of the lung that 'fails' in this aspect of asthma has been detected then therapeutic strategies can be put in place to reverse the defect.Read moreRead less
Study Of The Functional Consequences Of Angiotensin II Induced Increases In Renal Innervation
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely imperv ....Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely impervious to preventative public health measures. While treatment of established high blood pressure can reduce the incidence of cardiovascular disease, preventing the development of hypertension in the first place is not possible at this time. A major impediment to the development of effective public health measure is our lack of knowledge of the pathological mechanisms involved, despite over 100 years of active research effort. The experiments planned in this study will probe below the surface of two important facts known about hypertension but not previously brought together - that the kidney's blood vessels and nerves are remodeled in hypertension, and that the kidney's control of the level of blood pressure must be changed in order for high blood pressure to develop in the first place. We hope that pursuit of this experimental line of enquiry will provide new clues on where to look for initiating factors in human hypertension.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.
Identification Of Heterogeneity In Vasodilator Function In Human And Rat Resistance Vessels: Potential Drug Targets?
Funder
National Health and Medical Research Council
Funding Amount
$595,330.00
Summary
The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not w ....The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not well understood. While current drugs for treating vascular disease either reduce vessel constriction or increase dilation, they are not specific for individual arteries; a situation that would allow us to control vascular diseases in a very specific manner. Recently, we have described differences between the ways that individual vessels are controlled. These changes relate to differences in the way that different vessels dilate. AIMS - To further understand normal blood vessel function and the changes that occur in blood vessels in cardiovascular disease, with a focus on the ways that blood vessels dilate in normal states and in obesity-related diseases, such as in hypertension and diabetes. - The eventual aim is to identify the specific ways that arteries function, so that artery-specific drug targets can be identified to treat disease-related changes in cardiovascular disease in a very specific manner. EXPECTED OUTCOMES This project will contribute to understanding blood vessel function in health and disease. The expected eventual outcome is the identification of the mechanisms that underlie the function of different arteries in different parts of the body, so that specific individual vessel function can be targeted to treat vascular disease. Additionally, this work will also verify the relevance of the diet-induced obesity animal model, in terms of the characteristics and causes of human obesity and related cardiovascular disease.Read moreRead less
THE EFFECT OF LONG ACTING BRONCHODILATORS ON VENTILATION IN COPD
Funder
National Health and Medical Research Council
Funding Amount
$143,676.00
Summary
COPD is a common and important smoking-related lung disease. Well-established treatments with inhaled medications including long-acting bronchodilators have a proven clinical track record. However the physiological basis for their effects is still under investigation. This research examines some of the physiological changes in lung function and the response to long-acting bronchodilators in patients with COPD, and may help explain why some patients respond to therapy while others do not, leading ....COPD is a common and important smoking-related lung disease. Well-established treatments with inhaled medications including long-acting bronchodilators have a proven clinical track record. However the physiological basis for their effects is still under investigation. This research examines some of the physiological changes in lung function and the response to long-acting bronchodilators in patients with COPD, and may help explain why some patients respond to therapy while others do not, leading to more targeted therapeuticsRead moreRead less