Influence Of Endothelin And Protease-activated Receptors On Eosinophil Trafficking In The Airways Of Allergic Mice
Funder
National Health and Medical Research Council
Funding Amount
$376,980.00
Summary
Asthma is a chronic inflammatory lung disease. This disease affects about 10% of the population, although its incidence in primary school-age children is as high as 30% in some cities. People suffering from asthma have very responsive (hyperresponsive) airways to substances which are usually innocuous. Many asthmatics are allergic to substances such as pollens, animal dander and house dust, which causes the airways of the asthma sufferer narrow, making breathing more difficult. The airways of as ....Asthma is a chronic inflammatory lung disease. This disease affects about 10% of the population, although its incidence in primary school-age children is as high as 30% in some cities. People suffering from asthma have very responsive (hyperresponsive) airways to substances which are usually innocuous. Many asthmatics are allergic to substances such as pollens, animal dander and house dust, which causes the airways of the asthma sufferer narrow, making breathing more difficult. The airways of asthma sufferers also become inflamed and the resulting swelling of the airways and excess formation of mucous makes breathing difficult. Inflamed asthmatic airways contain large numbers of cells called eosinophils, which move from the blood into the airways. Substances released from the eosinophils are thought to damage the airways and cause airways hyperresponsiveness. We have developed a mouse model of allergic inflammation which has many of the hallmark features of asthma, including high numbers of eosinophils and hyperresponsive airways. We have recently shown that these effects are inhibited by treatment of allergic mice with a drug called SB217242. SB217242 inhibits the actions of endothelin, a peptide that is produced in elevated amounts in the airways of asthma sufferers and which may produce many of the effects associated with asthma. We wish to investigate the mechanisms through which SB217242 and drugs which stimulate novel protease-activated receptors inhibits the increase in eosinophil numbers in the airways. We will investigate the possibility that these drugs inhibit the migration of eosinophils from the blood into the airways, using a unique microscope that allows us to visualize the movement of eosinophils into tissues such as the airways. These studies are likely to be of considerable strategic value in determining the potential usefulness of these drugs in the treatment of asthma.Read moreRead less
Dysfunction of the nervous system plays an important role in the symptoms of many respiratory diseases. For example, excessive non-productive coughing, elevated mucous secretion, reduced airway patency and hyperreactivity are all characteristic symptoms of diseases such as asthma and all involve over-activity of the nervous system. This research aims to understand the neural circuitry that is involved in controlling the airways and the mechanisms that underlie how this circuitry can become dysfu ....Dysfunction of the nervous system plays an important role in the symptoms of many respiratory diseases. For example, excessive non-productive coughing, elevated mucous secretion, reduced airway patency and hyperreactivity are all characteristic symptoms of diseases such as asthma and all involve over-activity of the nervous system. This research aims to understand the neural circuitry that is involved in controlling the airways and the mechanisms that underlie how this circuitry can become dysfunctional.Read moreRead less
Predictors And Consequences Of Allergies That Impact On Children Getting A Healthy Start To Life:a Prospective Study
Funder
National Health and Medical Research Council
Funding Amount
$893,559.00
Summary
Allergic diseases prevent Australian children getting a healthy start to life by causing long term illnesses. This group of diseases includes asthma, hay fever, eczema and food allergies. Half of all Australian children are born into families with a history of these conditions and these children are at increased risk. Some of these children develop allergies while the others do not. It is also known that allergic conditions change over time, but we have no information on causes of these changes. ....Allergic diseases prevent Australian children getting a healthy start to life by causing long term illnesses. This group of diseases includes asthma, hay fever, eczema and food allergies. Half of all Australian children are born into families with a history of these conditions and these children are at increased risk. Some of these children develop allergies while the others do not. It is also known that allergic conditions change over time, but we have no information on causes of these changes. For example some infants with eczema continue to have eczema or develop hay fever and asthma, while others do not. The aim of this study is to determine what factors cause allergies and what factors influence these changes. This will provide evidence to guide health policy and clinical practice. Looking at the different conditions in family members over time is a good way to answer these types of questions, because parents and siblings share similar exposures, but not all the same genes. This helps to disentangle the effects of the environment and genes. The Melbourne Atopic Cohort Study (MACS) is amongst the world�s major studies on the development of allergies. MACS commenced in 1991-94 by recruiting 620 babies prior to birth. Only infants born into families with a history of allergic disease were included. MACS is unique because all family members and the home environment were assessed at the time of birth of the child. These children have been followed regularly over the first ten years of their life. The MACS now provides a unique opportunity to conduct a family study that can examine genes, childhood environment and individual risk factors for allergies. This will also allow exploration of the impact of allergies on families and the health care system, and how we can reduce that impact. Such information will provide evidence to guide health care policy and clinical practice. Also, the current study will provide a platform for future studies to investigate the progression of allergies in this family cohort. This will be the world's only longitudinal family follow-up of allergies that spans all of childhood. It will assist in reducing the impact of these common conditions, and the findings will be original and significant not only in Australia but also internationally.Read moreRead less
An Investigation Of Care Planning Decisions In Advanced Pulmonary And Cardiac Illness In The Bayside Health Care Region
Funder
National Health and Medical Research Council
Funding Amount
$47,726.00
Summary
There has been little Australian research to develop interventions that facilitate end of life decision making. This project will provide a framework for understanding the issues in the planning of end of life care for people with chronic and life limiting illness and the relationship of this planning to organizational policy. The care decisions in hospital records of people with advanced lung and heart disease will be reviewed and people with those diseases interviewed about the issues they exp ....There has been little Australian research to develop interventions that facilitate end of life decision making. This project will provide a framework for understanding the issues in the planning of end of life care for people with chronic and life limiting illness and the relationship of this planning to organizational policy. The care decisions in hospital records of people with advanced lung and heart disease will be reviewed and people with those diseases interviewed about the issues they experience in planning their future care. Professionals from a range of health organisations will be interviewed about their experiences of care planning for people with life limiting lung and heart disease. As a pilot, this project will be used to contribute to the development of a model for a coordinated multidisciplinary process that brings together the health care services in a region and contributes to the systematic, ongoing development of infrastructure to improve end of life care.Read moreRead less
Low-yield Cigarettes And Diminution Of Small Airways Lung Function In Long-term Smokers
Funder
National Health and Medical Research Council
Funding Amount
$209,500.00
Summary
The modern cigarette has been designed to produce low yields of tar when the tobacco in the cigarette is burnt. The tar contains human carcinogens, and monitoring and regulating yields of tar has long been part of the comprehensive tobacco control strategy in Australia. This focus on tar has given an implicit endorsement of the low-yield cigarette as a safer cigarette. Recently, however, controversy has emerged about whether smoking low-yield cigarettes has reduced the harm done by smoking. The ....The modern cigarette has been designed to produce low yields of tar when the tobacco in the cigarette is burnt. The tar contains human carcinogens, and monitoring and regulating yields of tar has long been part of the comprehensive tobacco control strategy in Australia. This focus on tar has given an implicit endorsement of the low-yield cigarette as a safer cigarette. Recently, however, controversy has emerged about whether smoking low-yield cigarettes has reduced the harm done by smoking. The concern is that adenocarcinoma of the lung, a type of lung cancer that is most common in the small peripheral airways, has increased in frequency. This could be because the low-yield cigarette, with reduced yields of nicotine as well as tar, is smoked more intensely by smokers to compensate for the low nicotine. By smoking more intensely, we mean taking larger and more frequent puffs, inhaling the smoke deeply into the lungs, and holding the breath before expiring. This method of smoking would result in more tar particles being deposited in the peripheries of the lung where adenocarcinoma is most common. Because cigarette smoking has been linked also with other structural changes in the small airways of the lung, resulting in obstruction of airflow, we will test whether smoking low-yield cigarettes is associated with greater obstruction of the small airways than is smoking higher-yield cigarettes. To test whether the mechanism is the method of smoking, we will carefully describe and quantify each subject's pattern of smoking including the deposition of smoke-like Technegas particles in the peripheral lung.Read moreRead less
Airway Epithelial Barrier Function, Asthma And Aero-allergen Sensitization.
Funder
National Health and Medical Research Council
Funding Amount
$527,886.00
Summary
There is a strong association between allergy and asthma. This association been almost universally assumed to be causative. However, recent evidence suggests an alternative explanation ie., that the abnormal epithelium in asthma allows or facilitates sensitization to airborne allergens. This project will test this alternative hypothesis using human lung tissue and an animal model.
Reference Values For Spirometry, Lung Volumes, Diffusing Capacity, And Fractional Exhaled Nitric Oxide In First Nations Australians
Funder
National Health and Medical Research Council
Funding Amount
$83,832.00
Summary
Reference values in lung function tests allow respiratory doctors to accurately interpret results in order to effectively diagnose, treat and manage respiratory disease. Currently, reference values do not exist for First Nations adults. I will recruit 600 healthy First Nations adults from communities in Queensland and the Northern Territory for several lung function tests. Data collected will be submitted to the Global Lung Function Initiative to be incorporated into future guidelines.