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
A Novel Strategy Targeting Quorum Sensing Molecules And Catalase Function To Block Pseudomonas Aeruginosa Lung Infection
Funder
National Health and Medical Research Council
Funding Amount
$451,118.00
Summary
Pseudomonas aeruginosa causes serious infections, particularly in those with Cystic Fibrosis, immunocompromise, serious burns or long term catheters. We will use a unique strategy to target virulence factors that will assist in clearing acute infection, prevent establishment of new chronic infections, and potentially reduce severity of established chronic infections. It has the potential to make antibiotic therapy more effective and lessen the extent of antibiotic therapy required.
Array-based Comparative Genomic Hybridisation In Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$314,773.00
Summary
Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. W ....Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. With exposure to cancer-causing agents such as cigarette smoke, parts of the lung may suffer permanent damage that increases the risk of lung cancer. Many of these changes include the genes in air passages and lung tissue. In this study, we will use the latest technology in genetics called gene chips to study changes in genes that affect the spread of lung cancer. These gene chips can study a vast number of genes at once. In particular, we will whether there is an abnormal number of copies of genes in the lung cancer. We hope that this research study will provide new information about the diagnosis and treatment of lung cancer.Read moreRead less
The Role Of Pulmonary Macrophages In The Pathogenesis Of An Acute Exacerbation Of Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$495,710.00
Summary
We will examine the role of lung defence cells, known as macrophages, in triggering the inflammation of acute severe asthma. The experimental work will use unique mouse models of mild chronic asthma and of an acute exacerbation of the illness, which have been developed in our laboratories. We will study the mechanisms of activation of the asthmatic response and assess whether treatment with drugs that suppress the function of macrophages can help to control steroid-resistant exacerbations.
The Impact Of CPAP Treatment On Carotid Artery Atherosclerosis In Heavy Snoring And Mild Sleep Disordered Breathing
Funder
National Health and Medical Research Council
Funding Amount
$697,512.00
Summary
Mild sleep disordered breathing, including habitual snoring, is a very common problem in the adult population, with a prevalence of between 20-40%. Increasingly it is now recognised that habitual snoring may be an independent risk factor for the development of stroke. In this proposal we will explore the hypothesis that treatment for snoring will slow or stop the development of carotid artery atherosclerosis.
Response Of Human Airways To Deep Inflation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$281,037.00
Summary
The trachea and bronchi contain muscle that when it contracts narrows the air passages and makes it harder to breath. In healthy people taking a deep breath relaxes this airway muscle and improved breathing. However, in people who suffer from asthma and chronic airflow obstruction deep breaths do not have the normal relaxing actions on airway contraction. This study will use lung removed as part of surgery for lung cancer to study how the relaxing actions of deep breathing work in human airways.
Surfactant Protein D As A Candidate Therapy In COPD
Funder
National Health and Medical Research Council
Funding Amount
$405,749.00
Summary
Smoking -related chronic bronchitis and emphysema, otherwise known COPD, costs the healthcare system over $800 million per year. People continue to suffer even after they have given up smoking, and the treatments available result in only modest improvements. COPD is associated with a a defect of the scavenging cells in the lung, which normally clear away dying cells, and some of the proteins ivolved in this process. We will investigate whether supplementing these proteins will help.
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
THE CHANGING PREVALENCE OF ASTHMA AND CHRONIC OBSTRUCTIVE AIRWAY DISEASE IN AUSTRALIA
Funder
National Health and Medical Research Council
Funding Amount
$737,817.00
Summary
Respiratory illnesses are common with asthma symptoms affecting up to 15% of adults and 30% of children in the Australian community. Chronic obstructive pulmonary disease (COPD) is also common. The term encompasses emphysema and bronchitis and is mainly due to cigarette smoking. Although COPD is less common than asthma it causes more persistent disability especially in older people. Asthma is associated with faster decline in lung function with age and may also ultimately cause COPD. A diagnosis ....Respiratory illnesses are common with asthma symptoms affecting up to 15% of adults and 30% of children in the Australian community. Chronic obstructive pulmonary disease (COPD) is also common. The term encompasses emphysema and bronchitis and is mainly due to cigarette smoking. Although COPD is less common than asthma it causes more persistent disability especially in older people. Asthma is associated with faster decline in lung function with age and may also ultimately cause COPD. A diagnosis of asthma has become more common especially in children although this may be due to increased awareness and available treatments. Less is known about changes in the prevalence of asthma and COPD in adults over the last 10 years. These airway diseases are associated with inflammation in the airways and changes in airway structure. Tests of lung function and airway responsiveness have been used repeatedly in Busselton a coastal town in the south west of Western Australia since 1966 to provide information on changes in airway structure (calibre). Recently non invasive tests that can provide evidence of inflammation have been developed. Although treatment of asthma can control symptoms and improve lung function, airway inflammation tends to persist. The extent to which inflammation and abnormal structure are present in the airways of people in the community who do not complain of respiratory symptoms is not known. This study will determine if the frequency of asthma and COPD are actually increasing in the population of Busselton in comparison to previous estimates over the past 35 years. It will determine the degree to which unrecognised airway inflammation is present in the community and the best ways of detecting it. The results of the study will help to look for causes of asthma, determine how big a problem airway inflammation is in the community, and how it relates to abnormal airway structure, lung function, airway responsiveness and respiratory symptoms.Read moreRead less
Airway Inflammation In Asthma And Chronic Obstructive Pulmonary Disease
Funder
National Health and Medical Research Council
Funding Amount
$390,509.00
Summary
In chronic diseases of the airway such as asthma and airway narrowing due to cigarette smoking - chronic obstructive pulmonary disease (COPD), the airways show inflammation (increased numbers of cells and their products) and remodelling (increased thickness and scarring) which persist for many years, possibly indefinitely. The exact mechanisms by which inflammation persists in the airway wall in asthma and COPD are unknown. We and others have shown that greater numbers of memory T-lymphocytes (T ....In chronic diseases of the airway such as asthma and airway narrowing due to cigarette smoking - chronic obstructive pulmonary disease (COPD), the airways show inflammation (increased numbers of cells and their products) and remodelling (increased thickness and scarring) which persist for many years, possibly indefinitely. The exact mechanisms by which inflammation persists in the airway wall in asthma and COPD are unknown. We and others have shown that greater numbers of memory T-lymphocytes (T-cells) are present in the airway wall in asthma and COPD. T-cells orchestrate the processes involved in inflammation. We have hypothesised that the persistence of airway inflammation in asthma and COPD results from the proliferation of memory T-cells within the airway wall. Unlike na ve T-cells, memory T-cells have previously been stimulated and can easily be activated to proliferate and promote inflammation by other cells which are fixed in the airway. Data from our current work examining this process suggests that, although cells fixed in the airway such as fibroblasts and macrophages are activated in asthma and COPD and may activate T-cells, they do not seem to be causing T-cell proliferation. We now wish to extend these studies by determinimg if memory T- lymphocytes are proliferating in the airway wall within aggregations of lymphoid cells which act like lymph nodes and promote T-cell growth. To do this we will compare the number of these aggregations and the types of T-cells they contain in mild and severe cases of asthma and COPD with those in normal subjects. This work will provide new knowledge to help understand the mechanisms for the persistance of airway inflammation in asthma and COPD and may thereby also provide a focus for effective treatments of these condition.Read moreRead less