Imaging Lung Aeration And Lung Motion Following Very Premature Birth
Funder
National Health and Medical Research Council
Funding Amount
$517,631.00
Summary
Using a synchrotron as an X-ray source, we will image the lungs as they aerate at birth and optimise ventilation strategies that improve lung aeration while minimising the risk of ventilation-induced lung injury.
Does Increased Non-Linear Behavior Caused By Dynamic Variables Increase Ventilatory-Induced Lung Injury (VILI)?
Funder
National Health and Medical Research Council
Funding Amount
$109,625.00
Summary
Acute lung injury (ALI) is precipitated by a variety of different insults, either directly to the lung or elsewhere to the body. Approximately 50% of the patients die. ALI is characterized by an increase in the leakiness of the barrier that normally separates the blood from the airspaces. The fluid which consequently floods the airspaces not only makes it difficult for patients to adequately obtain oxygen, but also dramatically increases the work of breathing by changing the surface forces withi ....Acute lung injury (ALI) is precipitated by a variety of different insults, either directly to the lung or elsewhere to the body. Approximately 50% of the patients die. ALI is characterized by an increase in the leakiness of the barrier that normally separates the blood from the airspaces. The fluid which consequently floods the airspaces not only makes it difficult for patients to adequately obtain oxygen, but also dramatically increases the work of breathing by changing the surface forces within the lungs. As a result, the patients must be mechanically ventilated. However, the very act of using a positive pressure to inflate the lungs often creates further damage, either through repeated opening and closing of collapse tissue or through its over distension. Ventilatory-induced lung injury (VILI), in itself is estimated to contribute to ~30% of the mortality. The best way shown to minimize VILI is through the use of small programmed breaths so as not to overinflate the lungs while still allowing adequate gas exchanges, superimposed upon a background pressure, in order to pre-inflate the lungs and prevent them from repeatedly collapsing. A remaining problem is that just as a rubber band changes its elasticity as it is stretched, so too the lung changes its mechanical properties during distension. Moreover, the lung is considerably more complex since different regions have different elasticities, which change differentially as air flows in and out of them. Airflow in turn depends on regional differences in the location, size, and number of conducting airways. Indeed, we have recently shown for the first time that dynamic changes in lung mechanics may contribute to VILI in patients, despite the use of safe ventilation modalities. This application proposes to examine the extent to which dynamic changes in lung mechanic contribute to VILI in an animal model, as a prelude to more costly, large scale clinical trials aimed at improving mortality.Read moreRead less
Hyperpolarized Helium MRI To Quantify Regional Lung Damage And Ventilation For Improvement Of Recruitment Strategy.
Funder
National Health and Medical Research Council
Funding Amount
$455,160.00
Summary
Many lung injuries need mechanical ventilation to reopen collapsed lung airspaces and supply oxygen to the patient. This study uses two methods to monitor the lungs during ventilation: Hyperpolarised helium MRI to image the airspace, and electrical impedance tomography to measure lung volume. This information will allow adjustment of ventilator pressure to maximize oxygen transfer without increasing lung damage. Quicker repair of lung damage and patient recovery are the benefits of this study.
Optimising Lung Protective Resuscitation Using A Newborn Premature Lamb Model
Funder
National Health and Medical Research Council
Funding Amount
$392,218.00
Summary
Premature babies are at risk of severe, and potentially long-term, lung damage. These complications can be minimised if babies are optimally resuscitated at birth. This project will use promising new imaging technologies to examine the influence of different strategies, using mechanical ventilators, to help inflate the lung at birth, and their interactions with other therapies used to enhance lung maturity. It will provide new insights into resuscitating preterm babies.
Determinants Of Circulating Surfactant Protein Levels In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$276,221.00
Summary
The lung allows the oxygenation of blood and clearance of carbon dioxide. To achieve this a large surface area (50-100 m2) interfaces with a complex microcirculation across a 0.1-0.2 ?m barrier - the alveolocapillary membrane. The alveolocapillary membrane is damaged under a variety of circumstances, of varying severity. Whereas severe impairment results in respiratory failure, often there is no clear delineation between OacceptableO and OpathologicalO changes. Therefore, we have coined the term ....The lung allows the oxygenation of blood and clearance of carbon dioxide. To achieve this a large surface area (50-100 m2) interfaces with a complex microcirculation across a 0.1-0.2 ?m barrier - the alveolocapillary membrane. The alveolocapillary membrane is damaged under a variety of circumstances, of varying severity. Whereas severe impairment results in respiratory failure, often there is no clear delineation between OacceptableO and OpathologicalO changes. Therefore, we have coined the term Olung healthO to encompass the broad spectrum. Generally speaking, lung health can be compromised by lifestyle or disease. Whereas lifestyle changes are typically progressive and chronic, those associated with disease tend to be severe and acute. Monitoring lung health clearly has important implications in terms of occupational health and lifestyle issues, including smoking. The need for a marker of lung permeability is also regarded as the Oholy grailO in the intensive care setting. Currently, there is no way of doing so. The alveolus is lined with a liquid layer into which is secreted a complex mixture of lipids and specific proteins known as alveolar surfactant. Surfactant reduces the work of breathing. Recently, we fortuitously discovered that surfactant proteins leak into the circulation and that changes in their levels are a sensitive and early generic index of the lung?s integrity. We discovered that lung damage from conditions as diverse as smoking to the acute respiratory distress syndrome elevate circulating surfactant proteins levels. To refine our discovery we aim to: Improve the techniques used to measure the proteins Study the rate at which they enter and clear the circulation Study the influence of storage, gender, age, circadian rhythm, and smoking on the levels Study the levels in acute lung injury and in radiotherapy and cytotoxic drug treatment where the ability to monitor lung damage has immediate benefit for the patients.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.
Alveolar Epithelial Cell Differentiation And Apoptosis: Effects Of Preterm Birth, Corticosteroids And Stretch.
Funder
National Health and Medical Research Council
Funding Amount
$484,500.00
Summary
In the lung, gas exchange takes place in small terminal airsacs called alveoli. The internal surface of the alveoli are lined with 2 types of specialist cells, the type-I and type-II cells. Both cells are essential for the normal functioning of the lung; type-I cells provide a thin barrier for the gas exchange, whereas type-II cells produce the surface-active material, surfactant. In order to survive after birth, the lungs of the newborn must have appropriate numbers of each of these cell types. ....In the lung, gas exchange takes place in small terminal airsacs called alveoli. The internal surface of the alveoli are lined with 2 types of specialist cells, the type-I and type-II cells. Both cells are essential for the normal functioning of the lung; type-I cells provide a thin barrier for the gas exchange, whereas type-II cells produce the surface-active material, surfactant. In order to survive after birth, the lungs of the newborn must have appropriate numbers of each of these cell types. However, babies that are born very prematurely have few, if any, mature cells as most are non-specialised cells that possess none of the characteristics of mature type-I and type-II cells. Therefore, the lungs of very preterm babies have low levels of surfactant, are prone to injury and infection and are not efficient in the exchange of oxygen and carbon dioxide. As such, these infants are at high risk of developing chronic lung disease which is a serious debilitating disease that has long term health implications. We believe that the non-specialised cells are more prone to injury and cell death than mature cells which makes the very premature infant more susceptible to the development of chronic lung disease. As the survival and respiratory health of these infants depends upon most type-I and type-II cells maturing after birth, it is critical to understand the factors that regulate their maturation. This information will allow the development of treatments that can enhance the maturation of these cell types. This application is focused towards understanding the factors that control maturation of type-I and type-II cells, as well as the role of the non-specialised cells in the development of chronic lung disease in babies that are born very prematurely.Read moreRead less
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