Pharmacological Strategy For Blocking Lung Cell Damage By Toxic Smoke Constituents.
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
People retrieved from burning buildings or other hazardous situations involving fires are often at risk of death due to the effects of inhaled smoke. This reflects the presence of some very toxic substances in smoke that are products of the combustion of wood, vegetation and synthetic building materials. The most toxic substance present within smoke is acrolein, a very reactive chemical that attacks cells in the lining of the lung. This can result in a life-threatening condition known as oedema, ....People retrieved from burning buildings or other hazardous situations involving fires are often at risk of death due to the effects of inhaled smoke. This reflects the presence of some very toxic substances in smoke that are products of the combustion of wood, vegetation and synthetic building materials. The most toxic substance present within smoke is acrolein, a very reactive chemical that attacks cells in the lining of the lung. This can result in a life-threatening condition known as oedema, where the lung is flooded with fluids and is unable to perform its respiratory function. At present, the clinical approaches used to treat smoke inhalation victims are mostly directed against offsetting the symptoms of lung injury and do not take into account the role of lung cell injury by toxic substances in smoke such as acrolein. This project will provide a better understanding of the chemical events underlying the injury caused by smoke to lung cells, and also into possible drug strategies for treating victims of smoke inhalation. The work will explore the ability of a range of compounds that are chemically related to a blood pressure-lowering medicine (hydralazine) to protect lung cells against such smoke-induced damage. The work will employ a range of modern research techniques to understand the events occurring in lung cells exposed to smoke. Once this is understood, these approaches will be used to test the various drug compounds for their abilities to prevent the death of cells exposed to smoke or its toxic constutuent acrolein. This work will yield new information on a series of compounds concerning their ability to block the toxicity of smoke to lung cells. The goal is to identify one or two molecules that can be carried forward to testing in smoke-exposed animals.Read moreRead less
Mechanisms Of Epithelial Damage By The Noxious Smoke Constituent Acrolein
Funder
National Health and Medical Research Council
Funding Amount
$668,813.00
Summary
Due to increasing use of reactive chemicals by terrorists (e.g. chlorine gas), their effects on the lung are receiving increasing attention in the global toxicology community. This project focusses on acrolein, the major cytotoxic substance present in smoke produced on combustion of organic matter. We will explore the mechanisms whereby acrolein and high doses of smoke cause the lung to lose its watertight properties, and also test ways of preventing such damage with drugs.
Discrete Simulation Of Powder Dispersion In Pharmaceutical Aerosol Inhalers
Funder
National Health and Medical Research Council
Funding Amount
$35,085.00
Summary
This project seeks to develop fundamental understanding of the dispersion mechanisms of powders as aerosol for inhalation drug delivery. It couples computational simulations using computational fluid dynamics and discrete element method with experimental dispersion analysis. Successful development of this research will lead to a comprehensive understanding of factors controlling inhaler performance and thus maximizes the therapeutic benefits to the patients.
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.
Reducing Tobacco Harm During Pregnancy, Infancy And Early Childhood Among Groups With High Smoking Prevalence
Funder
National Health and Medical Research Council
Funding Amount
$346,449.00
Summary
This research will contribute to the evidence base for reducing harm from tobacco during pregnancy, infancy and early childhood, among groups with high smoking prevalence. It will: generate evidence on a program to help pregnant Indigenous women quit smoking; develop tools and evidence to support implementation of smoking cessation guidelines in public antenatal services; and explore people’s understanding regarding protecting children from harms of passive smoking at home.
Use Of Mouse Models To Study Mechanisms Of Pathology In Viral Exacerbations Of COPD
Funder
National Health and Medical Research Council
Funding Amount
$411,960.00
Summary
We want to understand why cigarette smoke exposure worsens respiratory virus infections. People who smoke, or who have smoked in the past, or who are exposed to environmental (passive) smoke, get sicker than nonsmokers when they get a respiratory virus infection, such as a common cold or the flu. This is true for people of all age groups, but we don't know why smoke has this effect. We think it may be because smoke interferes with some aspects of the immune response. A particular focus of our re ....We want to understand why cigarette smoke exposure worsens respiratory virus infections. People who smoke, or who have smoked in the past, or who are exposed to environmental (passive) smoke, get sicker than nonsmokers when they get a respiratory virus infection, such as a common cold or the flu. This is true for people of all age groups, but we don't know why smoke has this effect. We think it may be because smoke interferes with some aspects of the immune response. A particular focus of our research is chronic obstructive pulmonary disease. COPD is a serious lung disease which generally occurs in people who have smoked for many years. However, many COPD patients stopped smoking many years ago. COPD patients are especialy at risk of serious outcomes if they get a respiratory infection (known as an acute COPD exacerbation) and patients with COPD exacerbations use a lot of health care resources. There are no effective drugs to prevent or treat COPD exacerbations. We are currently using a mouse model of smoke exposure and virus infection to do this research, which is a much faster and more ethical approach than using humans in research. We believe that we will get a better understanding of how smoke affects the immune response to infection. This is likely to contribute to the development of better drugs for COPD exacerbations and other types of smoking related lung disease.Read moreRead less
Risk Factors For Asthma, Chronic Bronchitis And Emphysema In Older Adults
Funder
National Health and Medical Research Council
Funding Amount
$330,574.00
Summary
Chronic obstructive pulmonary disease (including chronic bronchitis and emphysema) is a major public health problem in Australia. The main known cause is cigarette smoking, which peaked among Australian men shortly after the second world war. Now that the consequences of this epidemic of smoking are passing, more attention needs to be paid to other causes of the condition. The proposed study will focus on occupational and domestic exposures and dietary factors in older people. Dusty jobs have lo ....Chronic obstructive pulmonary disease (including chronic bronchitis and emphysema) is a major public health problem in Australia. The main known cause is cigarette smoking, which peaked among Australian men shortly after the second world war. Now that the consequences of this epidemic of smoking are passing, more attention needs to be paid to other causes of the condition. The proposed study will focus on occupational and domestic exposures and dietary factors in older people. Dusty jobs have long been associated with COPD. However it is not known to what extent other occupational exposures to fumes and vapours are also responsible. Identifying such jobs would lead to better workplace conditions and prevention of further cases. Workers who have already developed COPD could be more fairly compensated. Similarly if indoor exposures to tobacco smoke and unvented gas appliances were found to play a role, further controls on smoking, flues and improved ventilation could also prevent cases of COPD. It is generally thought that emphysema develops from an imbalance between the oxidative stresses on the lungs and protective enzymes. A diet high in antioxidant vitamins and fish may protect against the development of COPD. If confirmed by this study, it would then be possible to conduct clinical trials of supplementation in smokers at risk of developing COPD. Public nutritional education could reduce the incidence of the condition in the future.Read moreRead less