Chronic obstructive pulmonary disease (COPD) is a smoking-induced lung disease that is the fourth leading cause of death in Australia. The immune system is highly likely to play an important role in the progression of this condition, because of the frequency of respiratory infections that occur. We will examine in detail the immune response of COPD patients, examining specific genes and proteins that are important in the defence against bacteria. Blood samples will be obtained from people with C ....Chronic obstructive pulmonary disease (COPD) is a smoking-induced lung disease that is the fourth leading cause of death in Australia. The immune system is highly likely to play an important role in the progression of this condition, because of the frequency of respiratory infections that occur. We will examine in detail the immune response of COPD patients, examining specific genes and proteins that are important in the defence against bacteria. Blood samples will be obtained from people with COPD who are stable. We will then obtain further blood samples when there is a flare-up of the lung condition, and during recovery. We will compare the results from the blood samples, with variations in the genes that people carry. Information about individual differences in the body's response to infection would help us to better understand how COPD develops, and to initiate research on new methods of diagnosis and treatment of COPD.Read moreRead less
Pathophysiological Correlates In Smokers And Smoking-related Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$283,500.00
Summary
Smoking-related chronic airway narrowing (COPD) is a common and major illness. Research on the characteristics of the actual pathological process in the airways in smokers and COPD using direct tissue sample is relatively new. Data is currently limited and rather contradictory. In this grant we will recruit a spectrum of smokers and COPD patients typical of those in the Australian community and will be undertaking a detailed analysis of the cellular and some vascular structural changes in the ai ....Smoking-related chronic airway narrowing (COPD) is a common and major illness. Research on the characteristics of the actual pathological process in the airways in smokers and COPD using direct tissue sample is relatively new. Data is currently limited and rather contradictory. In this grant we will recruit a spectrum of smokers and COPD patients typical of those in the Australian community and will be undertaking a detailed analysis of the cellular and some vascular structural changes in the airway wall. Both cellular and vascular changes will be related to the fixed and reversible component of airway obstruction. Reversible changes with smoking cessation will be studied. A very novel feature will be a preliminary assessment of the utility of proteomics for assessment of airway pathology.Read moreRead less
Restoring Skeletal Muscle In An Experimental Model Of COPD By Targeting The IGF-1-myostatin-macrophage Axis
Funder
National Health and Medical Research Council
Funding Amount
$508,183.00
Summary
Most people think that the serious disabilities of COPD (emphysema) patients follows damage to their lungs but wasted muscles may be even more important. We can not regrow lung but we have found a way that might help regrow muscle. We plan to use stem cells to make one of the body's own cells called 'macrophages' and genetically engineer these cells to help deliver healing proteins directly into the muscle. Making muscle stronger will help COPD patients live longer and improve quality of life.
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.
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
Asthma, Lung Function, Snoring And Passive Smoking In Busselton
Funder
National Health and Medical Research Council
Funding Amount
$115,110.00
Summary
Respiratory diseases such as asthma, chronic obstructive airway disease, and sleep apnoea are common in the community, and asthma is becoming more and more common. These diseases are a major cause of morbidity, lost time from work, use of health and community resources and death. Using information collected by the Busselton Health Studies between 1966 and 2000, we will investigate some new epidemiological aspects of respiratory diseases. Some of the questions we will examine are: * How much more ....Respiratory diseases such as asthma, chronic obstructive airway disease, and sleep apnoea are common in the community, and asthma is becoming more and more common. These diseases are a major cause of morbidity, lost time from work, use of health and community resources and death. Using information collected by the Busselton Health Studies between 1966 and 2000, we will investigate some new epidemiological aspects of respiratory diseases. Some of the questions we will examine are: * How much more common has asthma become in the Busselton population? Has the increase been more pronounced in some groups than in others (eg younger people)? Have other respiratory diseases also become more common? * Is decline in FEV1 over time a more useful measure of lung health than a single FEV1 measurement? How is decline in FEV1 related to age and other factors such as asthma, smoking, chronic respiratory diseases and hay fever? * Do the following put people at increased risk of sleep apnoea: overweight, recent weight gain, smoking, heavy alcohol intake, respiratory illness, cardiovascular disease and use of sedatives? * Do non-smoking spouses of smokers suffer more respiratory illness than spouses of non-smokers? We expect that results from this study will increase our understanding of the causes and progression of respiratory diseases, and may eventually point to ways of reducing the burden of these diseases in the community. Since all the information needed has already been collected in the course of earlier health surveys, this study will be particularly cost-effective.Read moreRead less
Alveolar Macrophage Zinc And Zinc Transporters And Their Role In Phagocytosis
Funder
National Health and Medical Research Council
Funding Amount
$288,975.00
Summary
Zinc is an essential dietary component that serves a number of functions in the lungs. It is both an anti-oxidant and anti-inflammatory agent. Some airway inflammatory diseases such as emphysema may involve a critical loss of lung zinc. We believe that cigarette smoke causes the loss of zinc and this prevents the lung macrophages from working properly to clear bacteria and dead cells. This will provide a foundation for our long term goals of better clinical management of emphysema.
Outcome Of Childhood Asthma In Adult Life And The Interaction With COPD
Funder
National Health and Medical Research Council
Funding Amount
$503,549.00
Summary
The Melbourne Study of Childhood Asthma (MESCA) is the longest, most comprehensive follow-up study of childhood asthma. The members were recruited in 1964 at the age of 7 and they have been reviewed at ages 10, 14, 21, 28, 35 and 42 years of age with a retention rate of 87% of survivors at the most recent follow-up. To date, the MESCA study has provided comprehensive data on the outcome of childhood asthma through to their adult years and has been particularly influential in establishing approac ....The Melbourne Study of Childhood Asthma (MESCA) is the longest, most comprehensive follow-up study of childhood asthma. The members were recruited in 1964 at the age of 7 and they have been reviewed at ages 10, 14, 21, 28, 35 and 42 years of age with a retention rate of 87% of survivors at the most recent follow-up. To date, the MESCA study has provided comprehensive data on the outcome of childhood asthma through to their adult years and has been particularly influential in establishing approaches to treatment of paediatric asthma nationally and internationally. The results of the study have been published widely over the years and cited extensively. The members of this cohort turn 50 in 2007 and will be invited to participate in a further review to reassess their clinical outcome to examine the relationship between long standing asthma and the development of COPD. Those members of the cohort who have had asthma persisting through their adult years have a degree of fixed obstruction on their tests of lung function and are potentially at risk of developing COPD. Some are at increased risk as approximately 30% of the members are regular smokers. In this review, at age 59 years, there is an excellent opportunity to examine the interaction of asthma and COPD and to compare the inflammatory processes between those who have continuing asthma, those whose asthma has resolved and in each group examine the effect of smoking. We will also look at a numbers of genetic markers associated with COPD to identify those who are more susceptible to the development of COPD. A second area of interest is the components of the immune system that influence asthma.. In an earlier study we identified one component of the immune system, known as the T cell system, that had returned to normal in those whose asthma had resolved. In this review, we plan to examine the T cell system in detail to understand what mechanisms may be responsible for resolution of childhood asthma.Read moreRead less
Hyperplasia And Hypertrophy Of Airway Smooth Muscle In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$286,250.00
Summary
Asthma is common in Australia with significant morbidity and it is the 6th Australian National Health Priority. Examination of the airways in asthma shows increased thickness of the airway wall (remodeling), and inflammation. Most long-term asthma treatment is currently focussed on treating inflammation. Since the contribution of smooth muscle to remodeling and excessive airway narrowing is crucial and may be largely independent of airway inflammation, new treatments aimed at the smooth muscle a ....Asthma is common in Australia with significant morbidity and it is the 6th Australian National Health Priority. Examination of the airways in asthma shows increased thickness of the airway wall (remodeling), and inflammation. Most long-term asthma treatment is currently focussed on treating inflammation. Since the contribution of smooth muscle to remodeling and excessive airway narrowing is crucial and may be largely independent of airway inflammation, new treatments aimed at the smooth muscle are needed. Treatments must be based on knowledge of the factors which result in more smooth muscle - hypertrophy (enlargement of cells), hyperplasia (more cells) or deposition of proteins (extracellular matrix) between the muscle cells. Matrix is produced by airway myofibroblasts which are more numerous in asthma. These various contributing factors have different signals that can be targeted for treatment, however, information regarding their relative importance is scant. We propose to examine cases of mild and severe asthma using archived tissue blocks in a multi-centre collaborative study using stereological techniques not previously applied to the airway in man. This study is important because it will: 1. Yield new data regarding the degree to which hyperplasia, hypertrophy and increased extracellular matrix vary in the airways; 2. Provide direction for the development of treatments of increased smooth muscle in asthma; 3. Provide relevance and direction to animal and tissue studies of airway smooth muscle; 4. Yield new information on the number of myofibroblasts in mild and severe asthma; 5. Yield new information on the effects of corticosteroids on smooth muscle, extracellular matrix and myofibroblasts in severe, fatal asthma, and 6. Relate increased smooth muscle to increased extracellular matrix, numbers of myofibroblasts and other airway wall dimensions including those close to the airway surface. These may be used to monitor airway pathology in asthma.Read moreRead less