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
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
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 Role Of Respiratory And Upper Airway Neural Control In Sleep Disordered Breathing
Funder
National Health and Medical Research Council
Funding Amount
$346,018.00
Summary
Obstructive Sleep Apnea (OSA) is a disorder associated with snoring. It affects 4% of adult men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease eg. heart attacks and strokes. Patients with OSA obstruct the floppy portion of the upper airway (UA) during sleep and consequently experience frequent episodes of oxygen deprivation as well as sleep fragmentation. OSA is at least 2-3 times more common in men than women. Whi ....Obstructive Sleep Apnea (OSA) is a disorder associated with snoring. It affects 4% of adult men and causes excessive daytime sleepiness leading to increased accidents, high blood pressure and premature cardiovascular disease eg. heart attacks and strokes. Patients with OSA obstruct the floppy portion of the upper airway (UA) during sleep and consequently experience frequent episodes of oxygen deprivation as well as sleep fragmentation. OSA is at least 2-3 times more common in men than women. While OSA patients seem, on average, to have smaller upper airways than normal subjects, the cause of OSA cannot be attributed to this factor alone. For example, a small UA cannot explain the male tendency for OSA. Abnormalities in breathing control or the control of upper airway muscles that normally hold the airway open might also be important in OSA. Men have previously been shown to have a greater increase in UA resistance during sleep than women, consistent with the idea that a gender difference in UA muscle control partly explains why more men than women have OSA. We aim to investigate how changes in breathing and UA dilator muscle control might lead to unstable patterns of breathing and to OSA. We propose that protective UA muscle reflexes are reduced during sleep more in men than women, and are reduced by low blood oxygen levels and alcohol (a known aggravator of sleep apnea). We further propose that low blood oxygen levels not only result from OSA but may also aggravate OSA by preferentially reducing the activity of UA dilating muscles, by making breathing patterns overall less stable and by depressing the ability of subjects to arouse from sleep to an airway blockage. We believe that this tendency to decrease UA activity may be exaggerated in OSA patients. We also propose that men are more vulnerable to the deleterious effects of low oxygen than women. We will also examine if men and snorers have exaggerated breathing responses on arousal from sleep.Read moreRead less
A Randomised Controlled Trial Of Non-invasive Ventilation In Stable, Hypercapnic Chronic Airflow Limitation
Funder
National Health and Medical Research Council
Funding Amount
$331,622.00
Summary
Chronic airflow limitation is a major cause of illness and death in Australia. Long term oxygen therapy is well established as one means of assisting people with chronic lung disease. Survival is still poor particularly when an individual is hypercapnic. Non-invasive ventilation used at night with a mask has been used in chronic hypercapnic respiratory failure from other causes with very good results. This study looks at whether non-invasive mask ventilation improves survival, improves clinical ....Chronic airflow limitation is a major cause of illness and death in Australia. Long term oxygen therapy is well established as one means of assisting people with chronic lung disease. Survival is still poor particularly when an individual is hypercapnic. Non-invasive ventilation used at night with a mask has been used in chronic hypercapnic respiratory failure from other causes with very good results. This study looks at whether non-invasive mask ventilation improves survival, improves clinical outcome measures and reduces health costs in people with chronic airflow limitation. The ventilatory support will be used at night during sleep and will be a bilevel positive airway pressure device. Apart from measuring the cost-benefit of home ventilatory support, this study will examine the relationship between the time of commencement of home ventilatory support and outcomes. In addition the relationships between daytime awake PaCO2, lung function, and body mass in CAL patients and the likely response to home ventilatory support will be examined.Read moreRead less
Assessment Of Physical Therapies To Improve Secretion Clearance In Patients With Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$302,310.00
Summary
People with cystic fibrosis (CF) produce thick mucus that is not cleared normally from the lungs. This retained mucus often becomes infected, which progressively damages the lungs. Various physical therapies which may help clear secretions are being used in CF. These include several types of devices which provide positive pressure to the airways. However, it is not known to what extent these devices, or other interventions such as manual chest physiotherapy and exercise, enhance mucus clearance. ....People with cystic fibrosis (CF) produce thick mucus that is not cleared normally from the lungs. This retained mucus often becomes infected, which progressively damages the lungs. Various physical therapies which may help clear secretions are being used in CF. These include several types of devices which provide positive pressure to the airways. However, it is not known to what extent these devices, or other interventions such as manual chest physiotherapy and exercise, enhance mucus clearance. As a result, it is not currently possible to scientifically prescribe intervention(s) to enhance mucus clearance in CF. This is partly because much of the research that has been performed in this area has been poorly-designed or has used inaccurate measures. Also, recent research has shown that these therapies may have significant effects beside their effect on mucus clearance. For instance, bacterial infection and the exchange of oxygen and carbon dioxide between the blood supply and air in the lung may all be affected by these interventions. Notably, the extent of benefit or detriment seen in these parameters does not always correlate with the effect on mucus clearance. We therefore believe a series of experiments is necessary to provide evidence upon which the scientific selection of mucus clearance therapies may be based. We have developed a new technique which allows clearance of mucus from the airways to be objectively measured in three-dimensions (3D). We intend to use the 3D technique to examine the effects of three different positive pressure devices, exercise, and manual chest physiotherapy on mucus clearance. Based on the outcomes of this research, we intend to compare the most appropriate therapy to performing no mucus clearance therapy in a short term trial. This trial will assess changes in the following: bacterial infection, mucus plugging in the airways, how well the lungs move air and exchange oxygen and carbon dioxide, and the patient's quality of life.Read moreRead less
RCT Of Headbox Oxygen Vs CPAP For Neonatal Respiratory Distress In Non-tertiary Hospitals
Funder
National Health and Medical Research Council
Funding Amount
$225,500.00
Summary
Each year in NSW hundreds of babies are transferred from local general hospital nurseries to a hospital with Neonatal Intensive Care Unit (NICU) because of breathing difficulties. Frequently, mothers are unable to accompany their babies at the time of transfer, leading to stress. When a mother is eventually transferred she is often separated from her partner and local supports causing further anxiety. In addition, if a baby has to be transferred, invasive procedures may be needed to ensure safet ....Each year in NSW hundreds of babies are transferred from local general hospital nurseries to a hospital with Neonatal Intensive Care Unit (NICU) because of breathing difficulties. Frequently, mothers are unable to accompany their babies at the time of transfer, leading to stress. When a mother is eventually transferred she is often separated from her partner and local supports causing further anxiety. In addition, if a baby has to be transferred, invasive procedures may be needed to ensure safety. Currently, babies who need oxygen in a local hospital are placed in a crib with a clear plastic box around their head and oxygen is run into the box (headbox oxygen). There is an alternative method of providing oxygen called CPAP (Continuous Positive Airway Pressure). This involves giving the oxygen directly into the baby's nose via soft rubber prongs. CPAP has been used since the 1970's. It is the main form of respiratory support for infants in many NICUs in Australia and the world. There is some evidence that death and lung disease may be reduced. However, the babies in these studies are sicker and smaller than babies in local hospital nurseries. CPAP is used in some local nurseries in New Zealand, however no studies have been done to see if CPAP reduces the need for inter-hospital transfer. The study will involve hospitals that have been selected because of their level of on site medical and nursing staff. These hospitals will have support and advice from two NICUs that use CPAP as their main form of respiratory support. Babies who need oxygen will be randomly allocated to either have headbox oxygen or CPAP. If the baby becomes so unwell such that certain preset criteria are met, the baby will be transferred to a NICU in the usual way. If CPAP safely reduces the need for inter-hospital transfer, many parents will be saved the anxiety associated with transfer, and the separation it often causes.Read moreRead less