How Do Thick Airway Walls Affect Airway Hyperresponsiveness In Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$382,538.00
Summary
Asthmatic airways narrow too easily, a characteristic called airway hyperresponsiveness (AHR). To understand the cause of asthma we need to understand the cause of AHR. Thickened airway walls could amplify airway narrowing and increase AHR. However, thick airway walls are also stiff, and stiff walls could reduce narrowing and AHR. This project will examine the relationships between AHR and airway wall thickness and stiffness during and after treatment that reduces airway wall thickness.
Does The Pattern Of Ventilation Distribution Predict Airway Hyperresponsiveness?
Funder
National Health and Medical Research Council
Funding Amount
$256,973.00
Summary
The tendency for airways to narrow too easily when stimulated is called airway hyperresponsiveness (AHR). AHR is an important feature of asthma, but it also occurs in other diseases, such as chronic obstructive pulmonary disease (COPD) - an airway disease caused by smoking, and cystic fibrosis. People who have AHR have more severe respiratory disease, regardless of which disease they have, and are more likely to develop poor lung function in old age and to be hospitalised or die from their disea ....The tendency for airways to narrow too easily when stimulated is called airway hyperresponsiveness (AHR). AHR is an important feature of asthma, but it also occurs in other diseases, such as chronic obstructive pulmonary disease (COPD) - an airway disease caused by smoking, and cystic fibrosis. People who have AHR have more severe respiratory disease, regardless of which disease they have, and are more likely to develop poor lung function in old age and to be hospitalised or die from their disease. If we can understand the causes of AHR we will have a better understanding of why some people with respiratory disease have poor outcomes. We have recently discovered that, in asthma, there is a very close relationship between AHR and the uneven distribution of air within the lungs. We believe that structural changes in the airways that cause this uneven distribution make the airways prone to AHR. This raises the possibility that factors that cause uneven ventilation in other respiratory diseases might also predispose the airways to AHR. If this is true, it suggests that there is a single physiological basis for AHR in a range of different diseases, and would allow us to focus research more closely on the causes of uneven ventilation. In this project we will measure the relationship between AHR and uneven ventilation in people with asthma, COPD or cystic fibrosis. The study is important because older people with asthma, particularly those with permanently narrowed airways, are likely to have more structural changes in their airways than young asthmatics, whereas people with COPD and cystic fibrosis have a different pattern of both structural changes and airway inflammation from that in asthma. The study will tell us whether there is a consistent relationship between AHR and uneven ventilation. If so, this would be extremely strong evidence that the factors that cause uneven ventilation contribute to AHR, and will point the way to studies of new treatments.Read moreRead less
Novel Neuromechanical Measurements Of The Human Upper Airway In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$543,728.00
Summary
Obstructive sleep apnea (OSA) is a common condition, in which the upper airway repeatedly collapses during sleep, causing the oxygen concentration in the blood to drop, carbon dioxide to rise, and the person to arouse in order to re-establish adequate oxygen supply. Consequences of OSA include increased daytime sleepiness, increased risk of accidents, and increased risk of cardiovascular diseases. It most commonly affects middle-aged males, but is also seen in the broader population. OSA is asso ....Obstructive sleep apnea (OSA) is a common condition, in which the upper airway repeatedly collapses during sleep, causing the oxygen concentration in the blood to drop, carbon dioxide to rise, and the person to arouse in order to re-establish adequate oxygen supply. Consequences of OSA include increased daytime sleepiness, increased risk of accidents, and increased risk of cardiovascular diseases. It most commonly affects middle-aged males, but is also seen in the broader population. OSA is associated with obesity and specific shapes of the upper airway and facial structure. These anatomical factors can be compensated for while awake but inadequate activity of the muscles surrounding the upper airway during sleep contributes to an increased predisposition of the airway to collapse. Airway collapse occurs when the muscles are unable to withstand the low pressures in the airway and collapse, obstructing the airway. This project will measure the stiffness and motion of the muscles surrounding the airway, in healthy people and those with OSA, to determine how these influence airway collapsibility. We will use two novel non-invasive Magnetic Resonance Imaging (MRI) techniques, MR Elastography, and MR tagging which will allow us to quantify the airway stiffness, or elasticity, and its motion (deformation). These will be the first direct measurements of the upper airway elasticity and deformation in humans. We will also measure how various treatments, such as CPAP therapy and mandibular advancement affect airway elasticity and deformation, so that their mechanisms can be better understood. This may also explain why some patients do not benefit from these therapies. These studies may lead to new diagnostic and treatment modalities, as well as gaining important insights into the basic mechanisms of airway collapse in humans.Read moreRead less
Structural And Mechanical Determinants Of Airway Hyperresponsiveness
Funder
National Health and Medical Research Council
Funding Amount
$415,219.00
Summary
In asthma and chronic obstructive pulmonary disease, the capacity for airway passages to narrow is increased which limits airflow in and out of the lung and contributes to disease severity. The aim of this project is to identify the underlying physiological abnormalities producing the increased narrowing capacity. The investigations will focus on the role of the airway smooth muscle and epithelial layers that are widely implicated in driving the increased narrowing response, but for which the ev ....In asthma and chronic obstructive pulmonary disease, the capacity for airway passages to narrow is increased which limits airflow in and out of the lung and contributes to disease severity. The aim of this project is to identify the underlying physiological abnormalities producing the increased narrowing capacity. The investigations will focus on the role of the airway smooth muscle and epithelial layers that are widely implicated in driving the increased narrowing response, but for which the evidence remains circumstantial.Read moreRead less
Prediction Of Oral Appliance Treatment Outcome In Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$280,200.00
Summary
Obstructive sleep apnoea (OSA) is a very common disorder, affecting approximately 2% of women and 4% of men in the middle-aged workforce . It is characterised by repetitive, complete or partial closure of the throat passage during sleep, resulting in sleep disturbance and low oxygen levels. OSA is recognised as a serious public health problem. There is growing evidence supporting the use of oral appliances to treat OSA. It is thought that these work by enlarging the throat passage, but this rema ....Obstructive sleep apnoea (OSA) is a very common disorder, affecting approximately 2% of women and 4% of men in the middle-aged workforce . It is characterised by repetitive, complete or partial closure of the throat passage during sleep, resulting in sleep disturbance and low oxygen levels. OSA is recognised as a serious public health problem. There is growing evidence supporting the use of oral appliances to treat OSA. It is thought that these work by enlarging the throat passage, but this remains uncertain. The aim of this project is to gain a better understanding of how such appliances work, so as to be able to predict which patients will particularly benefit from this form of treatment.Read moreRead less
Morphometric Analysis Of Normal Airway Structure In Childhood And The Influence Of A History Of Asthma On This Structure
Funder
National Health and Medical Research Council
Funding Amount
$186,113.00
Summary
The architectural structure of the airways of the lung is thought to have profound effects on airway function. Changes in this structure are believed to be partly responsible for limiting the flow of air into the lung in conditions such as constant wheezing, bronchitis and asthma. Pathological studies carried out on adult lungs have shown that the structure of the airways is indeed altered in patients with lung disease when compared with patients with no history of breathing difficulties. For ex ....The architectural structure of the airways of the lung is thought to have profound effects on airway function. Changes in this structure are believed to be partly responsible for limiting the flow of air into the lung in conditions such as constant wheezing, bronchitis and asthma. Pathological studies carried out on adult lungs have shown that the structure of the airways is indeed altered in patients with lung disease when compared with patients with no history of breathing difficulties. For example, the walls of the airways are much thicker in patients with lung disease. This thickening means that the airways are much narrower and therefore not able to carry as much air as in people with healthy lungs. In addition, the muscle within the airway wall, which is normally very sparse, is much denser in people with asthma and bronchitis. Thus, the airways can be squeezed closed more easily. It is not known if these changes are present in children who have lung disease. X-rays and sophisticated breathing tests suggest that these children may also have thicker walls and more muscle in their airways. The major difficulties in assessing whether such changes are present in children, is the lack of information on the normal structure in infants; how this changes as they grow to adulthood; or if there are any gender differences. This project aims to obtain this information from the airways of male and female children from 0-18 years. This information can then be used as a basis for comparison with the structure found in children with lung disease, in particular asthma, and therefore assist in making assessments as to the cause of their breathing difficulties. With more knowledge about these causes, we will be in a better position to design new and better treatments and produce ways of preventing them ever occurring.Read moreRead less
Functional Characterisation Of Novel Metabolites In Asthma And Identification Of New Biomarkers
Funder
National Health and Medical Research Council
Funding Amount
$829,922.00
Summary
Asthma is a chronic inflammatory disease of the airways that represents a major health burden. Severe asthma represents 10% of those suffering the disease and poses an urgent problem due to exacerbations and resistance to current therapies. We have conducted the first study of the metabolites that are altered in the airways of patients with severe asthma and identified functional metabolites and disease biomarkers. We now aim to assess the function of these molecules in asthma disease models.
We will conduct a survey of respiratory symptoms, lung function, smoking status, occupational exposures, and other risk factors among 3200 people aged 40 years and over living in five Australian communities: Melbourne, Sydney, Tasmania, Busselton (WA), and the Kimberley region (WA). In the Kimberley we will survey 400 Aboriginal people and 400 non-Aboriginal people. We will use a survey methodology that has been developed by an international expert panel and has been implemented in many other co ....We will conduct a survey of respiratory symptoms, lung function, smoking status, occupational exposures, and other risk factors among 3200 people aged 40 years and over living in five Australian communities: Melbourne, Sydney, Tasmania, Busselton (WA), and the Kimberley region (WA). In the Kimberley we will survey 400 Aboriginal people and 400 non-Aboriginal people. We will use a survey methodology that has been developed by an international expert panel and has been implemented in many other countries (in North and South America, Asia, and Europe). This study will provide the first nationally-representative information on the burden of chronic obstructive pulmonary disease (COPD) and the opportunities for health gain by improving the management of this illness. In Australia, COPD is a relatively silent and under-recognised disease but nevertheless is the third most important contributor to the burden of disease and the third leading cause of hospital admission as well as being the underlying cause of 4.2% of all deaths. The information we will collect is needed to form a basis for prevention and disease management interventions to reduce the burden of COPD, particularly among population sub-groups who are disproportionately affected, either due to greater exposure to risk factors (mainly tobacco smoking and occupation), greater susceptibility, under-recognition and under-diagnosis, or inadequate disease management. Importantly, the study will serve to raise awareness about the hazards of smoking for all Australians. By identifying target groups, prevalent exposures and management deficiencies, it will lead the way towards policy-relevant randomised controlled trials testing community-based interventions to prevent COPD and-or manage it more effectively. The information collected will help advance knowledge of the prevalence, burden and treatment of COPD that will be relevant to communities throughout the world.Read moreRead less