Respiratory-control Deficits In A Model Of Sleep Apnoea During Early Development: Mechanisms And Associations
Funder
National Health and Medical Research Council
Funding Amount
$206,717.00
Summary
A recent study showed that it is possible to induce changes in the respiratory control system of piglets after birth. This new study will examine the mechanism of that change, and develop diagnostic tools that can detect whether similar changes have occurred in babies. The results will help to diagnose the complications of respiratory problems in young babies, and will guide research regarding the potential site of the abnormalities that predispose to SIDS. Piglets have very similar development ....A recent study showed that it is possible to induce changes in the respiratory control system of piglets after birth. This new study will examine the mechanism of that change, and develop diagnostic tools that can detect whether similar changes have occurred in babies. The results will help to diagnose the complications of respiratory problems in young babies, and will guide research regarding the potential site of the abnormalities that predispose to SIDS. Piglets have very similar development of the brain and respiratory system to human infants during early development after birth. This study uses piglets to model exposure to factors that occur during infancy, and thus model some of the common respiratory diseases, including risk factors for the sudden infant death syndrome (SIDS). For example, infants may have upper-airway obstruction during sleep, or may get their face trapped in bed clothes so that they breath a mixture of lower oxygen and higher carbon-dioxide than that found in fresh air. We recently found that, during early development of piglets, repeated exposure to these types of gas mixes depressed respiratory responses tested later. Thus, respiratory responses become less vigorous over time, and this finding could explain how the exposures complicate infants' respiratory problems, or increase their risk for SIDS: Less vigorous responses mean the infant does not wake or move, the exposure becomes more severe, and may finally cause death. This study will examine piglets after such repeated exposure to: 1. find out whether heart-rate variability is reduced, in the same way as babies who later died from SIDS 2. develop a new diagnostic tool, to show the site where the abnormality is located 3. determine whether brain chemical alterations could explain the change in breathing 3. find out if exposure to cigarette smoke, known to increase respiratory problems in babies, causes even more severe disturbance of respiratory control in piglets.Read moreRead less
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
Lung Volume Recruitment In Neuromuscular Disease: Can Breath-stacking Improve Lung Function, Respiratory Symptoms And Quality Of Life In People With Neuromuscular Disorders?
Funder
National Health and Medical Research Council
Funding Amount
$108,845.00
Summary
Difficulty taking deep breaths or coughing are two of the breathing complications people with a neuromuscular disease can face. Lung volume recruitment, also known as breath-stacking, is a simple and inexpensive therapy that may help. This research will look at the short and medium-term effects of breath-stacking exercises on the breathing system. If lung volume, chest stiffness and cough effectiveness improve then symptoms, quality of life and potentially survival are likely to be better.
The aim of this project is to develop mathematical models and computer software capable of predicting immune responses to infection and disease. This “artificial immune system” should lead to improved vaccine design and better understanding of what causes the immune system to attack its own body, causing autoimmune disease, or fail to respond, causing immunodeficiency. This enabling science could then lead to improvements in treatment for a range of conditions of clinical importance.