Physical Determinants Of Lung Development Before And After Birth
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Survival at birth is critically dependent upon the ability of the lungs to take on the role of exchanging gases; a role previously performed by the placenta. The lungs must, therefore, have grown and matured sufficiently during fetal life, before they are required at the time of birth. Inadequate development of the lungs during fetal life is the most common cause of death and disease in newborn babies. This may be due to premature birth, when the lungs have had insufficient time to develop, or i ....Survival at birth is critically dependent upon the ability of the lungs to take on the role of exchanging gases; a role previously performed by the placenta. The lungs must, therefore, have grown and matured sufficiently during fetal life, before they are required at the time of birth. Inadequate development of the lungs during fetal life is the most common cause of death and disease in newborn babies. This may be due to premature birth, when the lungs have had insufficient time to develop, or it may be due to inappropriate lung development during fetal life. It is important therefore, to understand the mechanisms that control growth and development of the lung both before and after birth. During fetal life the lungs are filled with liquid which expands the lungs and provides a stretch stimulus causing them to grow. Previously we have shown that a reduction in the degree of fetal lung expansion causes lung growth to cease. Likewise, if we increase the degree of lung expansion in the fetus, we induce a rapid increase in fetal lung growth and maturation. This stimulus is so potent that it can reverse an existing lung growth deficit, thus enabling survival of the newborn. In this application we will investigate the mechanisms by which alterations in lung expansion induce growth and maturation of the lung. Specifically we will investigate the role of calmodulin in fetal lung growth, because the genes that encode it are activated when the lung cells are growing most rapidly. In addition, we will identify other genes that are turned on or off during rapid growth of the lung because those genes are likely to play important roles in the regulation of fetal lung growth and development. We will also investigate the underlying differences in the control of lung growth at different stages of gestation, as well as investigate factors that regulate lung growth after birth, particularly in prematurely born animals.Read moreRead less
Respiratory failure at birth is a major cause of death and disease in newborn infants. At birth the airways must be cleared of liquid to allow the inhalation of air, but, little is known about the process of lung aeration, because it has not been possible to observe or measure it. We have developed imaging and analytical techniques to observed and measure lung aeration. We will determine ventilation procedures that promote uniform lung aeration and minimise lung injury in ventilated infants.
I am a developmental lung physiologist who specialises in understanding the factors regulating normal and abnormal lung development as well as the physiological transformation of the lung into an efficient gas-exchange organ at birth.
I am a developmental lung physiologist who specialises in understanding the factors regulating normal and abnormal lung development as well as the physiological transformation of the lung into an efficient gas-exchange organ at birth.
Defining Regional Lung Mechanics To Improve Lung Protective Ventilation Strategies In Newborn Infants
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
Over 3000 newly born infants require mechanical ventilation in Australia every year. The majority are very premature infants. About 30% of ventilated infants develop serious ventilator induced lung injury. Minimising such lung injury with improved techniques of ventilation which can protect the lung from injury will reduce the considerable short and long term health burden of this population.
Mechanical Mobility Of The Thorax For Continuous Determination Of Lung Gas Volume
Funder
National Health and Medical Research Council
Funding Amount
$165,000.00
Summary
Percussion is a valuable clinical method for physical examination of parts of the body. A sharp tap (impulsive force) is applied to the body wall and the sound radiated in response is observed. This sound may be dull (over liver) or stony dull (pleural effusion), or resonant (over normal lung) or hyper-resonant (over bowel). While the variation in radiated sound is not fully understood, it is apparent that the presence of gas, which is highly compliant, increases mobility of the overlying tissue ....Percussion is a valuable clinical method for physical examination of parts of the body. A sharp tap (impulsive force) is applied to the body wall and the sound radiated in response is observed. This sound may be dull (over liver) or stony dull (pleural effusion), or resonant (over normal lung) or hyper-resonant (over bowel). While the variation in radiated sound is not fully understood, it is apparent that the presence of gas, which is highly compliant, increases mobility of the overlying tissue and allows it to resonate; where the sub-tissue is largely fluid, tissue mobility is low and the percussive sound is dull. Percussion is useful for examining the adult chest and lung, but cannot for example be applied in infant intensive care as only limited impulsive force can be used, and the adult finger, which is both a coupling device and sounding board, is too large. As well, percussion requires skill and quiet conditions. Accordingly, we developed a device to measure mobility of the chest and other tissues in real time. The VibroPulse applies a known low-level force to the body surface and records the resultant velocity induced in the surface. The force is generated by a vibrating mass set in motion by an electromagnetic motor driven by pseudo-random noise. Tissue mobility, defined as velocity-force, is derived simultaneously across the frequency range, providing an easily interpreted quantitative output unaffected by ambient noise. This proposal has two aims we can achieve in 1 year: (1) to continue evaluating VibroPulse sensitivity to tissue composition, using symmetrical percussive sites on the human chest and abdomen that are dull on one side and resonant on the other, and the chest of anaesthetised animals with experimentally induced pneumothorax and lung collapse, two life-threatening conditions for which percussion is a key diagnostic method, and (2) to engineer a small device from our bulky prototype that is suitable for clinical use, in infants and adults.Read moreRead less
From The Synchrotron To The Clinic: Translation Of A Novel Functional Lung Imaging Technology
Funder
National Health and Medical Research Council
Funding Amount
$891,834.00
Summary
Our team has recently developed a synchrotron technology with a startling capacity for dynamic functional imaging that can act as a sensitive regional indicator of lung disease. We will demonstrate that this technology can be translated from the synchrotron to the lab and eventually the clinic. We will provide proof of this concept by the application of this technology to emphysema, asthma, lung cancer, cystic fibrosis lung disease and neonatal resuscitation.
Inter-hospital Variations In Outcomes Of Very Preterm Infants Admitted To Neonatal Intensive Care Units
Funder
National Health and Medical Research Council
Funding Amount
$130,440.00
Summary
Most babies who are born very preterm (less than 32 weeks' gestation; ie more than 2 months early) are admitted to a neonatal intensive care unit (NICU). These babies stay in hospital for 2 to 4 months and need lots of care (using vast amounts of the available health resources). When compared to babies born at term, these very preterm babies are much more likely to die or to suffer from a range of poor outcomes that impact on their long-term development and quality of life. The Australian and Ne ....Most babies who are born very preterm (less than 32 weeks' gestation; ie more than 2 months early) are admitted to a neonatal intensive care unit (NICU). These babies stay in hospital for 2 to 4 months and need lots of care (using vast amounts of the available health resources). When compared to babies born at term, these very preterm babies are much more likely to die or to suffer from a range of poor outcomes that impact on their long-term development and quality of life. The Australian and New Zealand Neonatal Network (ANZNN) is a collaboration of clinical staff in all 29 NICUs in the region, whose aim is to improve the care of high-risk newborn infants and their families in Australia and New Zealand through collaborative audit and research. This audit has reported considerable differences in the rates of death and poor outcomes between NICUs. Other networks have reported similar variations. Variations in outcomes could be due to 1) differences in the way the diagnosis is made in each unit, 2) differences in how small or ill the babies are when admitted, or 3) different quality of care in each NICU. We need to take account of the first two possibilities before we can compare NICUs fairly and allow them to work towards achieving the best outcomes for very premature babies. To do this, our project will use advanced statistical techniques to look at the risk factors associated with death and poor outcome in very preterm babies. We will then be able to 'predict' outcomes and see if the differences between NICUs are real or not. If the variation between units is explained by differences in clinical practices, then this has enormous potential for quality improvement within the NICUs and through the development of new policy guidelines for clinical practice. The statistical models developed during this project will be useful for clinicians in other health areas and in other countries.Read moreRead less
Randomised Controlled Trial Of Therapeutic Pulmonary Lavage In Meconium Aspiration Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$182,550.00
Summary
Meconium aspiration syndrome (MAS) is a serious respiratory disease of full term infants, which can lead to very severe respiratory failure. It is caused by the inhalation of meconium, the secretion of the fetal intestine, into the lung at or prior to delivery. As a result, the airways and air sacs within the lung are damaged, leading to difficulty with breathing and poor oxygen levels. About one-third of all infants with MAS require mechanical ventilation in the first days of life, and are ofte ....Meconium aspiration syndrome (MAS) is a serious respiratory disease of full term infants, which can lead to very severe respiratory failure. It is caused by the inhalation of meconium, the secretion of the fetal intestine, into the lung at or prior to delivery. As a result, the airways and air sacs within the lung are damaged, leading to difficulty with breathing and poor oxygen levels. About one-third of all infants with MAS require mechanical ventilation in the first days of life, and are often extremely difficult to manage. At present, the main treatments given to a ventilated infant with severe MAS are supportive, rather than curative. Lung cleansing procedures are not part of routine care in this condition, even though removal of meconium from the lung may reduce the amount of damage that occurs. This project is a randomised controlled trial of a lung cleansing procedure called lung lavage in ventilated infants with severe MAS. During the lung lavage, a quantity of cleansing fluid containing a natural substance called surfactant is introduced into the lung, and then removed by suctioning. This procedure cleanses the lung of some of the meconium, and in preliminary testing, appears to be safe and well-tolerated even in the sickest infants. In the proposed trial, we will randomly allocate ventilated infants with severe MAS to receive either a lung lavage procedure, or routine care. This will take place within 24 hours of birth. We are looking to see whether the lavage procedure shortens the duration of ventilation, oxygen therapy or hospitalisation. Because there are only a small number of ventilated infants with MAS at any one centre per year, we will involve as many Australian neonatal intensive care units as we can in the study. We aim to enrol 66 infants in the trial, of whom half will receive lavage therapy.Read moreRead less
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.