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
Assessment Of Airway Smooth Muscle Hypertrophy In Asthma And Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$298,055.00
Summary
Asthma and chronic obstructive pulmonary disease (COPD) are common in the Australian community. The cause of asthma is unknown and although COPD is most often due to smoking cigarettes it remains unknown why it develops only in some smokers and in some non-smokers. The pathology of asthma and COPD includes increased thickness of the airway smooth muscle layer. In asthma this is associated with relatively normal airway lumen size and intermittent, excessive airway narrowing whereas in COPD it is ....Asthma and chronic obstructive pulmonary disease (COPD) are common in the Australian community. The cause of asthma is unknown and although COPD is most often due to smoking cigarettes it remains unknown why it develops only in some smokers and in some non-smokers. The pathology of asthma and COPD includes increased thickness of the airway smooth muscle layer. In asthma this is associated with relatively normal airway lumen size and intermittent, excessive airway narrowing whereas in COPD it is associated with fixed narrowing of the airway lumens. The increased smooth muscle layer might result from more or bigger smooth muscle cells or from more connective tissue (matrix) between the muscle cells. This project aims to determine which of these 3 factors causes the increased thickness of the smooth muscle layer in asthma and COPD. We hypothesise that in asthma there are more muscle cells and more matrix, and that in COPD there is only more matrix. These differences would account for the different behaviour of the airways in asthma and COPD. Currently there is no useful or practical method to measure the amount of matrix in the airway wall, especially in the smooth muscle. This project will study the amount of matrix and muscle in very thin airway sections (< 1 m) from a large number of cases of asthma and COPD to allow, for the first time, accurate assessment of the fractions of matrix and muscle in the smooth muscle layer, since they barely overlap on these thin sections. The results of this study are important because they will: differentiate between mechanisms of increased thickness of the airway smooth muscle layer in asthma and COPD and therefore identify different prevention and treatment strategies; help to develop a method of monitoring airway remodeling in airway diseases that can be applied to bronchial biopsies.Read moreRead less
Airway Wall Thickness And Heterogeneity Are Key Determinants Of Asthmatic Airway Function.
Funder
National Health and Medical Research Council
Funding Amount
$207,509.00
Summary
Asthma is a common disease which is typified by excessive narrowing of the airways in response to stimuli that are trivial to non-asthmatic individuals. However, little is known about what causes asthmatic airways to be able to narrow so excessively. In this study, we will be looking at the importance of thickening of the airway walls in relation to excessive airway narrowing in asthmatics. We will also look to see how patchy the airway narrowing is in asthmatics and how this relates to excessiv ....Asthma is a common disease which is typified by excessive narrowing of the airways in response to stimuli that are trivial to non-asthmatic individuals. However, little is known about what causes asthmatic airways to be able to narrow so excessively. In this study, we will be looking at the importance of thickening of the airway walls in relation to excessive airway narrowing in asthmatics. We will also look to see how patchy the airway narrowing is in asthmatics and how this relates to excessive airway narrowing that occurs in severe asthmatic attacks. We will therefore be studying asthmatics of varying degrees of disease severity as well as those admitted to hospital because of acute severe attacks of asthma, and comparing them with a group of non-asthmatic subjects.Read moreRead less
The Relationship Between Vascular Remodelling And Mast Cells In Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$353,253.00
Summary
It is known that the airwalls of asthmatics have increased numbers of small blood vessels which can contribute to poor lung function in asthma. The proposed research uses a novel sheep model for chronic asthma to investigate the progressive changes to the blood vessels in the airway walls of asthmatic lungs. The information gained from our sheep model will assist the understanding of blood vessel growth and thus ulitmately help in devising new strategies to treat the effects of asthma.
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
Airway Smooth Muscle - Mast Cell Cross Talk In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$527,250.00
Summary
In Australia 1 in 4 children and 1 in 10 adults are asthmatic and so asthma is a significant burden to our community and our healthcare system. Currently we treat asthma with corticosteroids to reduce airway inflammation because, without them, chronic inflammation leads to thickened airways with increased amounts of smooth muscle that contracts too much and too easily. However, corticosteroids may have side effects , particularly in children. In order to design safer more specific treatments for ....In Australia 1 in 4 children and 1 in 10 adults are asthmatic and so asthma is a significant burden to our community and our healthcare system. Currently we treat asthma with corticosteroids to reduce airway inflammation because, without them, chronic inflammation leads to thickened airways with increased amounts of smooth muscle that contracts too much and too easily. However, corticosteroids may have side effects , particularly in children. In order to design safer more specific treatments for asthma, we need to know more about the pattern of inflammation that is specific for asthma and what chemical signals cause it. Then we will be able to target it more specifically. Recent research has demonstrated that in asthma, but not in bronchitis or in healthy people, inflammatory cells called mast cells are found in increased numbers down in the smooth muscle layer of the airways. Mast cells are key cells in all allergic reactions. In the airways they release mediators that contract the airways, induce mucous secretion and promote further inflammation. We think the effects airway smooth muscle cells and mast cells have on each other are central factors in causing the physical changes to the airways of asthmatics. We will identify what chemical messages released by the smooth muscle attract mast cells to it and once they are there, what the mast cells stick to on the smooth muscle. Then we will investigate how the two cell types interact with each other and affect each other. We will focus on how the functions of the smooth muscle cells are affected, especially those that would promote further inflammation and lead to increased amounts of more sensitive, more contractile smooth muscle. We will try to prevent each of the steps we identify with drugs that have very specific actions. This additional information may lead to the design of novel treatments for asthma that have fewer side effects.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
Clinical Outcomes, Safety And Incremental Cost Effectiveness Of Multi-level Airway Surgery In Patients With Moderate-severe Obstructive Sleep Apnea (OSA) Who Have Failed Medical Management
Funder
National Health and Medical Research Council
Funding Amount
$652,794.00
Summary
Obstructive sleep apnoea (OSA) is a serious medical disorder with a high public health cost. OSA can be effectively treated but poor treatment compliance is a major clinical problem. As a consequence many OSA patients remain untreated, with significant implications for their long term health. New effective and safe therapies are needed. We believe that we will demonstrate a relatively straightforward, safe and effective surgical procedure for OSA after primary treatments fail. This will lead to ....Obstructive sleep apnoea (OSA) is a serious medical disorder with a high public health cost. OSA can be effectively treated but poor treatment compliance is a major clinical problem. As a consequence many OSA patients remain untreated, with significant implications for their long term health. New effective and safe therapies are needed. We believe that we will demonstrate a relatively straightforward, safe and effective surgical procedure for OSA after primary treatments fail. This will lead to improved patient outcomes.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