Exposure Of Bronchial Epithelial Cells To Inflammatory Stimuli Impairs Their Innate Immune Response To Rhinovirus.
Funder
National Health and Medical Research Council
Funding Amount
$325,966.00
Summary
Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory conditions in Australia, both of these conditions are characterised by acute attacks precipitated by respiratory virus infections. The most common trigger for these acute attacks is the usually innocuous common cold virus, rhinovirus. The reason for this susceptibility remains poorly understood. We have previously shown that the cells lining the airways of asthmatics are more susceptible to infection with rhi ....Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory conditions in Australia, both of these conditions are characterised by acute attacks precipitated by respiratory virus infections. The most common trigger for these acute attacks is the usually innocuous common cold virus, rhinovirus. The reason for this susceptibility remains poorly understood. We have previously shown that the cells lining the airways of asthmatics are more susceptible to infection with rhinovirus and fail to react to this infection effectively. We propose to further elucidate this defect and for the first time determine if it is also present in subjects with COPD. We will examine the airway cells of subjects with asthma and COPD and look for evidence of a defective immune response, relating this to the presence of persistent bacterial infection. We will then grow these and infect them with rhinovirus, carefully examining the mechanisms behind this impaired response to infection and then see if we can induce such impairment in these cells with chronic exposure to infection and inflammatory stimuli. Our laboratory is well placed to investigate these problems with an established track record in investigating patients with inflammatory airways disease and virus infection, unparalleled access to sufficient well characterised clinical samples and have demonstrated the ability to study virus epithelial cell interactions. This work will highlight those at risk of developing frequent debilitating exacerbations along with the reasons for this and identify areas to target novel therapeutic interventions.Read moreRead less
A Randomised Controlled Trial Investigating The Respiratory Effects Of Nitrogen Dioxide In Schoolchildren
Funder
National Health and Medical Research Council
Funding Amount
$212,189.00
Summary
Research has shown that exposures to air pollutants such as nitrogen dioxide (NO2), sulphur dioxide, ozone and respirable particulate matter less than 10 microns are associated with respiratory symptoms. Unlike the other air pollutants nitrogen dioxide is an indoor gas which occurs in higher concentrations than outdoors in households which cook or heat with gas. Recent research has demonstrated that NO2 at concentrations easily achieved indoors can increase respiratory illness, particularly in c ....Research has shown that exposures to air pollutants such as nitrogen dioxide (NO2), sulphur dioxide, ozone and respirable particulate matter less than 10 microns are associated with respiratory symptoms. Unlike the other air pollutants nitrogen dioxide is an indoor gas which occurs in higher concentrations than outdoors in households which cook or heat with gas. Recent research has demonstrated that NO2 at concentrations easily achieved indoors can increase respiratory illness, particularly in children and asthmatics. In South Australia we have the opportunity to demonstrate health effects of NO2 on children with asthma more conclusively, as a high number of schools heat their classrooms with unflued gas heaters which produce high NO2. In the proposed study, half of the primary schools with unflued gas heaters will have these heaters replaced with heaters which do not emit NO2. This process of selecting schools will be performed at random and in the school holidays, so as not to bias the children in regard to their exposure status. Additionally, only asthmatic children without gas appliances at home will be included. Asthma symptoms and lung function measurements will be collected in order to determine any differences in the health outcomes of both groups. The results of this study will be able to give conclusive information on health effects related to NO2, that will substantially contribute to the development of a recommended NO2 guideline. This is of worldwide interest.Read moreRead less
Airway Smooth Muscle Contribution To Remodelling In Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Asthma is an airway disease that affects more than 10% of adults and 25% of children in Australia and in 1998 caused 675 deaths. The cost to the community is in excess of $720 million a year. The abnormality in asthma is not fully understood, however inflammation, changes to the structure of the airways and excessive airway narrowing are key factors. Inflammation and the allergic reactions which accompany asthma cause fluid to leak from tiny blood vessels in the lung. This fluid and the inflamma ....Asthma is an airway disease that affects more than 10% of adults and 25% of children in Australia and in 1998 caused 675 deaths. The cost to the community is in excess of $720 million a year. The abnormality in asthma is not fully understood, however inflammation, changes to the structure of the airways and excessive airway narrowing are key factors. Inflammation and the allergic reactions which accompany asthma cause fluid to leak from tiny blood vessels in the lung. This fluid and the inflammation are linked to changes in the airway which include structural protein deposition - breakdown and an overgrowth of the smooth muscle that lines the walls of the airway. Our work is focussed on understanding the relationship between the structural protein deposition - breakdown and excess muscle growth. We also hope to gain a better understanding of the way asthma treatments combat these changes in the asthmatic airways.Read moreRead less
Intrinsic Response Of Airways To Cyclical Dilation And Elongation In Breathing
Funder
National Health and Medical Research Council
Funding Amount
$355,014.00
Summary
Variations in lung pressures during breathing produce cyclical expansion of the airway tubes. These respiratory movements provide one of the most powerful protective mechanisms for the lung. The protective mechanism fails in asthma so that cyclical expansion of the airway tubes can make breathing more difficult. Current belief is that protective and harmful effects of lung expansion occur by either relaxation or contraction of the muscles lining the airway tubes. Findings from this laboratory su ....Variations in lung pressures during breathing produce cyclical expansion of the airway tubes. These respiratory movements provide one of the most powerful protective mechanisms for the lung. The protective mechanism fails in asthma so that cyclical expansion of the airway tubes can make breathing more difficult. Current belief is that protective and harmful effects of lung expansion occur by either relaxation or contraction of the muscles lining the airway tubes. Findings from this laboratory suggest that the above dogma needs reconsideration. The project will utilize a novel model of the lung to enable us to determine the mechanisms producing both the protective effect, and in asthmatics the harmful effects of cyclical lung expansion. Once the part of the lung that 'fails' in this aspect of asthma has been detected then therapeutic strategies can be put in place to reverse the defect.Read moreRead less