G-CSF: A Pathogenic Effector In Chronic Obstructive Pulmonary Disease And Its Comorbidities
Funder
National Health and Medical Research Council
Funding Amount
$1,241,551.00
Summary
Chronic Obstructive Pulmonary Disease (COPD) is an incurable lung disease that is a huge global health burden, and new therapies are urgently needed. We have recently discovered a possible cause of COPD. This single factor also appears to drive other associated medical problems that are the biggest contributors to patient deterioration. Using advanced genetics, biochemistry and molecular methods we are searching for ways to turn our discovery into effective treatments for this fatal disease.
Inflammometry In Stable COPD; A Randomised Controlled Trial (RCT)
Funder
National Health and Medical Research Council
Funding Amount
$743,351.00
Summary
COPD is a common condition associated with many clinical consequences that negatively impact on quality of life. The burden of illness from COPD remains high despite current treatment. There is an urgent need to improve management of COPD and we propose that individualized management targeted to airway and systemic inflammation will do this. This study will examine the effect of targeted anti-inflammatory treatment in patients with COPD and will examine the role of a simple blood test to assess ....COPD is a common condition associated with many clinical consequences that negatively impact on quality of life. The burden of illness from COPD remains high despite current treatment. There is an urgent need to improve management of COPD and we propose that individualized management targeted to airway and systemic inflammation will do this. This study will examine the effect of targeted anti-inflammatory treatment in patients with COPD and will examine the role of a simple blood test to assess and manage COPD.Read moreRead less
Scarring And Angiogenesis In The Airway Wall In Smoking And COPD: Links Between Inflammation And Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$361,614.00
Summary
Smoking damages airways to produce scarring and new blood vessel growth resulting in airway narrowing, so-called COPD. Details of these processes are poorly understood. We will analyse airway biopsies taken from smokers, to dissect out the linkages between airway damage, airway inflammation, structural remodelling, and clinical changes. We will investigate the effects on these processes of: 1) inhaled corticosteroid; and 2) smoking cessation over 3 and 12 months.
Chronic obstructive pulmonary disease (COPD) is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of COPD and accounts for more than 95% of cases in industrialized countries. Cigarette smoke triggers cells in the lung to release substances which cause inflammation and eat away lung tissue. In addition, these substances enter the blood and muscle where they eat away muscle resulting in signifi ....Chronic obstructive pulmonary disease (COPD) is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of COPD and accounts for more than 95% of cases in industrialized countries. Cigarette smoke triggers cells in the lung to release substances which cause inflammation and eat away lung tissue. In addition, these substances enter the blood and muscle where they eat away muscle resulting in significant weight loss. Patients with COPD have severe difficulty in breathing because the lungs are damaged and do not function properly. This process, once started, cannot be reversed and there is currently no satisfactory therapy to help treat individuals with this terrible disease. People with COPD are prone to viral and bacterial infections of the lungs. These infections cause further inflammation, lung damage and difficulty in breathing. These infections place a tremendous burden on health care resources, have a huge effect on the quality of life and are a common cause of death. The reason why respiratory infections are so serious for people with COPD is unclear. Preliminary results from our laboratory show that a substance called GM-CSF, released from cells in the lung, may be involved in the development of COPD. Thus, the aim of this project is to use our mouse models of COPD to determine whether GM-CSF is involved in the development of COPD. The insights gained may lead to the identification of potentially novel ways to prevent and treat COPD.Read moreRead less
Enhancing Innate Immune Responses To Influenza In Chronic Obstructive Pulmonary Disease
Funder
National Health and Medical Research Council
Funding Amount
$522,323.00
Summary
Infection with influenza is a serious health problem for all, but particularly those with chronic lung diseases such as chronic obstructive pulmonary disease (COPD). Current treatments are limited. We have previously shown that human COPD airway cells are more susceptible to infection with influenza and the virus is able to effectively block the early immune response. We propose to define the mechanism that underlie this and design novel inhibitors to enhance the early immune response of these c ....Infection with influenza is a serious health problem for all, but particularly those with chronic lung diseases such as chronic obstructive pulmonary disease (COPD). Current treatments are limited. We have previously shown that human COPD airway cells are more susceptible to infection with influenza and the virus is able to effectively block the early immune response. We propose to define the mechanism that underlie this and design novel inhibitors to enhance the early immune response of these cells and reduce the effects of infection.Read moreRead less
Characterisation And Treatment Of Innate Immune Dysfunction In Older People With Obstructive Airway Disease
Funder
National Health and Medical Research Council
Funding Amount
$434,083.00
Summary
Airway problems in older people are increasing. The two most common airway problems in people over the age of 60 are asthma and chronic obstructive pulmonary disease or COPD. These diseases have a major impact of the quality of life of older people. Airway inflammation is an important mediator of symptoms and exacerbations in younger people with airway disease, however little is understood about airway inflammation in the elderly. We will study airway inflammation in older people with airway dis ....Airway problems in older people are increasing. The two most common airway problems in people over the age of 60 are asthma and chronic obstructive pulmonary disease or COPD. These diseases have a major impact of the quality of life of older people. Airway inflammation is an important mediator of symptoms and exacerbations in younger people with airway disease, however little is understood about airway inflammation in the elderly. We will study airway inflammation in older people with airway disease and make comparisons with both younger and older healthy controls. While many changes occur in our bodies with age, we do not understand how ageing affects airway disease. Some of the changes which occur with ageing include increased inflammation and an increased susceptibility to infection. We do not understand how these changes affect people with respiratory disease or how they occur. Respiratory infections in older people with airway disease often result in hospitalisation, and some bacterial pathogens can survive in the airways for long periods of time without the typical symptoms of infection. This bacterial persistence can lead to an increased influx of inflammatory cells and chemicals which can cause destruction of the airways and lead to changes in the airway structure that are not reversible. We will investigate bacterial infection in older people with and without airway disease and investigate an important pathway of the immune system called innate immunity. We will assess the influence of ageing itself on these immune responses, and also the impact of associated airway disease. We will also trial an anti-inflammatory therapy in older people with airway disease who have persisting bacteria in their airways to see if this will help reduce inflammation and reduce the bacteria that persist in the airways. These are new and exciting approaches to a common and increasing problem for older Australians.Read moreRead less
Membrane TNF And Lymphotoxin Control Of Chemokine Induction And Inflammation In Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$457,500.00
Summary
Tuberculosis (TB) remains an enormous problem worldwide. Most TB is not due to disease at the time of infection, but is a reactivation of dormant disease in people who have never completely eradicated the organisms. Macrophages containing dormant TB organisms are located in lesions called granulomas. Granulomas consist of TB-infected macrophages surrounded by T lymphocytes that actively contain the infection. T lymphocytes prevent the growth of TB organisms in the macrophages and so prevent wide ....Tuberculosis (TB) remains an enormous problem worldwide. Most TB is not due to disease at the time of infection, but is a reactivation of dormant disease in people who have never completely eradicated the organisms. Macrophages containing dormant TB organisms are located in lesions called granulomas. Granulomas consist of TB-infected macrophages surrounded by T lymphocytes that actively contain the infection. T lymphocytes prevent the growth of TB organisms in the macrophages and so prevent widespread infection that would cause illness in the host. Activated T lymphocytes that recognise TB-infected macrophages circulate in blood, are recruited from blood capillaries into the lung, migrate through the tissue and co-localise with infected macrophages. Soluble molecules (cytokines and chemokines) are known to provide the signals that direct cell migration and activation events. This study will investigate in detail cytokines and chemokines that are involved, the cells that produce then and where these cells are located in the lung. We recently showed that tumour necrosis factor (TNF), and the related cytokine lymphotoxin (LT), are essential for lymphocyte migration through the lung. These belong to a family of related molecules that signal through the same panel of receptors and regulate chemokine expression and inflammation. In this study we will use genetically manipulated mice that lack TNF. LT or other family members or that express only membrane-bound TNF to study how each affects production of different chemokines, chemokine receptors and other molecules. Since there are at least 50 known chemokines and 17 chemokine receptors we will use microarray technology to simultaneously screen changes in expression of several thousand genes and laser microdissection to study cells from different location in infected lungs. Understanding signals necessary to direct T cells into granulomas may facilitate new treatments to prevent TB reactivation disease.Read moreRead less