EPITHELIAL ION TRANSPORT DEFECTS IN CYSTIC FIBROSIS: PATHOPHYSIOLOGY AND TREATMENT
Funder
National Health and Medical Research Council
Funding Amount
$290,440.00
Summary
The thin layer of fluid covering the surface of the air passages acts to protect the airway surface from drying. This fluid also allows the hair-like projections, or cilia, on the top of the airway cells to beat more effectively. The volume and composition of this fluid is determined by the movement of salt and water across the mucous membranes of the air passages. The importance of this fluid is shown by the problems that occur in Cystic Fibrosis (CF), the most common lethal inherited disease a ....The thin layer of fluid covering the surface of the air passages acts to protect the airway surface from drying. This fluid also allows the hair-like projections, or cilia, on the top of the airway cells to beat more effectively. The volume and composition of this fluid is determined by the movement of salt and water across the mucous membranes of the air passages. The importance of this fluid is shown by the problems that occur in Cystic Fibrosis (CF), the most common lethal inherited disease affecting Australians. In CF, altered salt transport causes drying of the airway surface which impairs the working of the cilia. This leads to retention of mucous in the airway with repeated bacterial infections damaging the lungs. Simple tests have been designed to directly measure the movement of salt across the surface of the nasal passage using a fine soft rubber tube. Movement of mucous in the nose is measured using other simple techniques that are currently used diagnostically. Together, these tests in the nose provide vital information about how the surface of normal human airway moves salt, water and mucous. Any differences found in CF patients will then give us a good idea of the problems found in the CF lung. We will study the interactions between calcium, sodium and chloride in the fluid lining the airways, measuring changes in salt and mucous movement. A range of testing procedures will be used in human volunteers, anaesthetised mice and isolated tissues from sheep. We have already demonstrated important links between the fluid lining the airways and salt movement, and we expect that this may lead to the development of new treatments for Cystic Fibrosis. This therapy will focus on treating the lung problems of CF patients, the major cause of disability. We anticipate that this preventative therapy may offer real benefits in the fight to cure CF.Read moreRead less
Inhaled Mannitol For The Treatment Of Mucociliary Dysfunction- Its Effect And Mechanisms On The Clearance Of Mucus
Funder
National Health and Medical Research Council
Funding Amount
$324,100.00
Summary
Excessive secretion of mucus is a problem in asthma and bronchiectasis. Mucus is secreted from submucosal glands and goblet cells as a result of inflammation present in the airways. Excessive mucus is not easily transported by the cilia (hair like structures) in the airways and accumulation leads to productive cough and to recurrent infections. Cough is a secondary mechanism to clear mucus when the mucociliary system fails. Cough generates high airflow rates that can move mucus. However, patient ....Excessive secretion of mucus is a problem in asthma and bronchiectasis. Mucus is secreted from submucosal glands and goblet cells as a result of inflammation present in the airways. Excessive mucus is not easily transported by the cilia (hair like structures) in the airways and accumulation leads to productive cough and to recurrent infections. Cough is a secondary mechanism to clear mucus when the mucociliary system fails. Cough generates high airflow rates that can move mucus. However, patients with moderately to severely obstructed airways cannot generate high airflow rates. In addition, cough becomes very inefficient in moving mucus if it is sticky and viscous. As the cilia cannot transport large quantities of mucus the best approach is to alter the properties of mucus that would facilitate cough clearance. Increased hydration of mucus could change its surface and rheological properties. Increased hydration can be achieved by the osmotic movement of water into the airway lumen in response to inhaling an aerosol of salt or sugar. We have evidence using radioactive aerosols, that mannitol, a sugar, increases clearance of mucus acutely in patients with excessive secretions. We also have new evidence that mannitol taken daily over two weeks increases the health status in patients with bronchiectasis. Further we now have preliminary data demonstrating that mannitol changes the surface properties of mucus. We aim to study the properties of mucus in relation to its clearance in vivo in humans. This has not been done before. If we can demonstrate that changes in clearance in response to mannitol relate to the changes in mucus then we will be able to easily evaluate current treatments and doses for patients with excessive secretions and to identify new treatments. Mannitol is a potential treatment for diseases with excessive secretions and understanding of how it works will hopefully lead to better outcomes for patients.Read moreRead less
Bronchoscopic Applications Of Anatomical Optical Coherence Tomography.
Funder
National Health and Medical Research Council
Funding Amount
$408,366.00
Summary
This research proposal aims to investigate the potential utility of a novel, Australian designed dianostic laser system. A tube positioned in the lungs takes real-time images of the shape and size inside the airways. This can have both clinical and research benefits. It may help doctors choose the right size hardware when opening up cancerous airways and it will help us understand disease mechanisms of lung diseases by studying parts of the airways not previously able to be measured.