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
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