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.
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
Invasive Cardiopulmonary Exercise Testing For The Evaluation Of Unexplained And Complex Multifactorial BREATHlessnEss (i-BREATHE)
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Breathlessness is a common symptom that can be caused by diseases of the heart, lungs or muscles. It is not uncommon that the cause is undiagnosed either because conventional tests do not yield a diagnosis, or because an individual suffers from multiple diseases. This research aims to use invasive cardiopulmonary exercise testing, a highly specialised test which simultaneously measures breathing, heart and muscle function, to improve the diagnosis and treatment of patients with breathlessness.
Central, Reflex And Mechanical Factors In The Control Of Human Breathing Muscles.
Funder
National Health and Medical Research Council
Funding Amount
$497,968.00
Summary
We will study the neural output to human inspiratory muscles and how it is related to mechanical effectiveness for breathing and then how this relationship can change with respiratory disorders such as chronic obstructive pulmonary disease and obstructive sleep apnoea. We will also examine the spinal reflex connections of human breathing muscles in people with spinal cord injury. This work promises new understanding of the basic control of respiration and how it changes with disease.
Pulmonary Artery Pulsatility As A Predictor Of Survival Following Hospitalized Exacerbation Of Chronic Obstructive Pulmonary Disease
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Many patients with Chronic Obstructive Pulmonary Disease (COPD) also have elevated lung blood pressures, or pulmonary hypertension (PH). Having both conditions increases the risk of death. It is difficult to diagnose PH in COPD. We will be using a new Computed Tomography (X-ray imaging) technique to investigate a marker of PH called ‘pulmonary artery pulsatility’. If PH can be diagnosed easily and accurately new treatments can be devised and researched potentially improving outcomes in COPD.
NOVEL NON-INVASIVE METHODS FOR THE EARLY DETECTION OF PULMONARY VASCULAR DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$320,463.00
Summary
Pulmonary arterial hypertension (PAH) is a severe, progressive disorder. Current non-invasive diagnostic modalities are insensitive for detecting early disease, thus preventing early intervention with therapy. We aim to develop novel and reproducible ways to assess the pulmonary circulation, which will ultimately allow for the early diagnosis of PAH and in turn facilitate early initiation of treatment and improved patient outcomes.
Pulmonary Hypertension In Chronic Obstructive Pulmonary Disease: Pulmonary Hyperinflation, Gas Trapping And Disproportionate Pulmonary Hypertension.
Funder
National Health and Medical Research Council
Funding Amount
$103,583.00
Summary
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in Australia. Raised blood pressure in the lungs (pulmonary hypertension, PH) predicts a worse prognosis in patients with COPD. The mechanisms contributing to PH are incompletely understood. We aim to determine the role of lung hyperinflation in contributing to the development of PH in COPD. We also aim to identify a sub-group of patients that develop severe PH which may benefit from specific therapy.
Targeting IL-33 In Chronic Obstructive Pulmonary Disease (COPD), Chronic Asthma And Idiopathic Pulmonary Fibrosis (IPF)
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Lung diseases (emphysema, severe asthma & pulmonary fibrosis) are major burdens on Australian community and economy. Airway wounding is a key feature of all these diseases. Patients experience severe breathlessness seriously impacting quality of life and frequently leading to death. We will assess the potential of a new target (IL-33), & therapy (anti-IL-33) in suppressing wounding in experimental models and human tissues. This may lead to a new treatment to reverse and/or prevent lung diseases.