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.
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
The survival of a baby at birth is crtically dependent upon the ability of the lungs to successfully take over the role of exchanging oxygen and carbon dioxide between the air and blood. To perform this task, during fetal life the lung must have grown properly and near the end of gestation it must mature both structurally and biochemically. Thus, babies that are born early, before the expected time of birth, are born before the lungs have had the opportunity to mature. It is not surprising, ther ....The survival of a baby at birth is crtically dependent upon the ability of the lungs to successfully take over the role of exchanging oxygen and carbon dioxide between the air and blood. To perform this task, during fetal life the lung must have grown properly and near the end of gestation it must mature both structurally and biochemically. Thus, babies that are born early, before the expected time of birth, are born before the lungs have had the opportunity to mature. It is not surprising, therefore, that an inability to breathe is one of the primary problems faced by a prematurely born infant. During late gestation the lung changes dramatically in order to increase its ability to exchange gases. There is an increase in surface area and a reduction in the barrier thickness between the airspace and the blood stream. The molecular mechanisms involved in this remodelling are unknown, but it is known that the administration of corticosteroids to women at risk of preterm labour causes a large decrease in this barrier thickness and increases the distensibility of the lung. This project seeks to understand how the structure of the lung matures in late gestation and to determine whether corticosteroids regulate these changes by altering the structure of a specialised molecule, called versican. Versican resides in the tissue space outside of cells and has special properties that allow it to retain water and help organise the surrounding matrix. We propose that alterations in the structure of versican will reduce its ability to retain water, thereby reducing the tissue volume and contributing to a reduction in the air-blood tissue barrier within the lung.Read moreRead less
Premature babies often need assistance to breathe but this can injure the lung and lead to abnormal lung development and long-term lung disease. We have recently identified 3 factors that we believe are fundamental to initiating this abnormal lung development. We will demonstrate that these 3 factors mediate abnormal lung development following lung injury at birth. This information can then be used to reduce the incidence and severity of chronic lung disease of the newborn.
My research is primarily aimed at understanding the physiology and pathophysiology of lung development; in particular, how lung development is affected by the fetal and neonatal environment such that adult lung function and respiratory health are impaired. In addition to the lung my research examines the effects of the prenatal environment on development of the brain and cardiovascular system.
Preventing Preterm Lung Disease - A Cell Therapy Approach.
Funder
National Health and Medical Research Council
Funding Amount
$460,610.00
Summary
Due to improvements in medical care, the survival of very premature babies has greatly improved over the past 20 years. However, many of these children are surviving with disability due to severe chronic lung disease of prematurity. Currently, there are no effective treatments for this lung disease. This project explores the use of placental stem cells as a lung repair and regeneration therapy - a therapy that can be given to the baby in the days immediately following its birth.
Fetal Responses To Intra-uterine Inflammation And The Postnatal Pulmonary Consequences
Funder
National Health and Medical Research Council
Funding Amount
$347,036.00
Summary
There is increasing evidence that exposure of the unborn baby to infection and inflammation may be the cause of several important and disabling illnesses in later life, including long-term lung injury and brain damage. Hospital-based studies have shown that infants who go on to develop these diseases have signs of inflammation before, and soon after, birth. These studies in humans, however, have only shown associations between inflammation and later disease. Carefully controlled scientific exper ....There is increasing evidence that exposure of the unborn baby to infection and inflammation may be the cause of several important and disabling illnesses in later life, including long-term lung injury and brain damage. Hospital-based studies have shown that infants who go on to develop these diseases have signs of inflammation before, and soon after, birth. These studies in humans, however, have only shown associations between inflammation and later disease. Carefully controlled scientific experiments are required to show that inflammation actually causes damage and to allow us to find ways to prevent or cure the diseases that result from such injury. In 1998, using sheep, our research group discovered a way to produce inflammation in the fetus without endangering its wellbeing or causing early labour. The inflammation is caused by injecting a sterile bacterial cell wall preparation (endotoxin) into the amniotic fluid surrounding the fetus. Using this model, we have found that an episode of inflammation before birth profoundly increases lung maturity, thus increasing the chances of survival if premature birth occurs. Based on our information from humans, we expect that if these lambs are allowed to survive past the first few days after birth, they will go on to develop chronic lung disease, and perhaps brain damage. This study will answer vital questions about the events that occur in the uterus and the fetus during periods of inflammation, and will then determine the long-term consequences in the weeks following birth. We expect that these lambs will have changes which at first will increase their chances of survival after birth, to be followed by chronic disability due to lung and brain damage. If confirmed, this finding will allow us to find treatments which can be applied before birth to ensure that children are less likely to be born with these disabling illnesses.Read moreRead less
Improved Respiratory Support And Outcomes For Very Preterm Babies
Funder
National Health and Medical Research Council
Funding Amount
$9,185,907.00
Summary
Premature babies are born with lungs that are not developed enough to sustain their breathing needs after birth. As a result, they need intensive care which is the most costly and challenging problem in newborn medicine as these infants can suffer life-long diseases because of their early birth. This programs study will help to understand the causes of lung disease in premature babies and develop better ways of caring for them to improve their chances of survival without ongoing illness and disa ....Premature babies are born with lungs that are not developed enough to sustain their breathing needs after birth. As a result, they need intensive care which is the most costly and challenging problem in newborn medicine as these infants can suffer life-long diseases because of their early birth. This programs study will help to understand the causes of lung disease in premature babies and develop better ways of caring for them to improve their chances of survival without ongoing illness and disabilityRead moreRead less