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Mannitol In The Assessment Of Bronchial Responsiveness In Airway Disease
Funder
National Health and Medical Research Council
Funding Amount
$365,250.00
Summary
The airways of people with asthma respond by narrowing too easily and too much to a wide range of stimuli. The tests most commonly used to measure airway responsiveness in asthma are the pharmacological agents methacholine and histamine. When inhaled, they act directly on bronchial muscle causing it to contract and hence the airways to narrow. We have developed a non-pharmacological test using a dry powder of a sugar - mannitol. When inhaled, mannitol causes narrowing of the airways in asthmatic ....The airways of people with asthma respond by narrowing too easily and too much to a wide range of stimuli. The tests most commonly used to measure airway responsiveness in asthma are the pharmacological agents methacholine and histamine. When inhaled, they act directly on bronchial muscle causing it to contract and hence the airways to narrow. We have developed a non-pharmacological test using a dry powder of a sugar - mannitol. When inhaled, mannitol causes narrowing of the airways in asthmatics but little or no effect in healthy subjects. Many asthmatics respond to mannitol even when they have few symptoms of asthma. Mannitol causes the airways to narrow 'indirectly' by causing the release of substances from inflammatory cells in the airways (e.g. histamine, leukotrienes and prostaglandins) that cause the muscle to contract. After the inflammation has cleared, either by treatment with inhaled steroids or spontaneously, the response to mannitol is close to healthy subjects. Thus the response to mannitol depends on the presence of inflammation and loss of responsiveness means resolution of inflammation. The significance of this is that the mannitol test may be used as an 'inflammometer'. It would be important if airway responsiveness to mannitol could be used to identify individuals with airway diseases other than asthma, (chronic bronchitis, and chronic obstructive lung disease) who could benefit from treatment with inhaled steroids. This would be significant as there is currently no test to identify those individuals and there are unwanted effects from using steroids. Further, it may be possible to use mannitol to identify individuals with other inflammatory diseases who may be at risk of developing asthma. Some people with asthma, chronic bronchitis and chronic obstructive lung disease have increased levels of oxidative stress. We wish to identify those people and to measure change after treatment with steroids.Read moreRead less
Scarring And Angiogenesis In The Airway Wall In Smoking And COPD: Links Between Inflammation And Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$361,614.00
Summary
Smoking damages airways to produce scarring and new blood vessel growth resulting in airway narrowing, so-called COPD. Details of these processes are poorly understood. We will analyse airway biopsies taken from smokers, to dissect out the linkages between airway damage, airway inflammation, structural remodelling, and clinical changes. We will investigate the effects on these processes of: 1) inhaled corticosteroid; and 2) smoking cessation over 3 and 12 months.
Targeting IL-33 In Chronic Obstructive Pulmonary Disease (COPD), Chronic Asthma And Idiopathic Pulmonary Fibrosis (IPF)
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Lung diseases (emphysema, severe asthma & pulmonary fibrosis) are major burdens on Australian community and economy. Airway wounding is a key feature of all these diseases. Patients experience severe breathlessness seriously impacting quality of life and frequently leading to death. We will assess the potential of a new target (IL-33), & therapy (anti-IL-33) in suppressing wounding in experimental models and human tissues. This may lead to a new treatment to reverse and/or prevent lung diseases.
Targeting Remodelling In Chronic Obstructive Pulmonary Disease (COPD), Chronic Asthma And Idiopathic Pulmonary Fibrosis (IPF)
Funder
National Health and Medical Research Council
Funding Amount
$386,634.00
Summary
Lung diseases (emphysema, asthma & pulmonary fibrosis) are major burdens on Australian community and economy. Airway remodelling/wounding is a key feature of all these diseases. Patients experience severe breathlessness seriously impacting quality of life and frequently leading to death. We will assess the potential of new targets (including IL-33), & therapy in suppressing wounding in experimental models. This may lead to a new treatment to reverse or prevent lung diseases.
The Mechanisms Of Infection Of Bronchial Epithelial Cells By Human And Avian Influenza Viruses In Chronic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$395,559.00
Summary
Influenza is an important infection that causes disease every year in the Australian population. People with lung disease are at particular risk to its effects. The ability of the virus to grow in birds and change its appearance to our immune system allows this virus to cause severe disease every year. We will examine the immune response to this virus in human cells, comparing this response to human and bird strains of the virus and see why subjects with lung disease are more susceptible.
A-Prof Greg King is a respiratory physician researcher whose studies are to define the mechanisms by which diseases, such as asthma and COPD occur. He has developed novel tools to measure lung disease, particularly complex lung function testing and lung imaging.
Prediction Of Oral Appliance Treatment Outcome In Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$280,200.00
Summary
Obstructive sleep apnoea (OSA) is a very common disorder, affecting approximately 2% of women and 4% of men in the middle-aged workforce . It is characterised by repetitive, complete or partial closure of the throat passage during sleep, resulting in sleep disturbance and low oxygen levels. OSA is recognised as a serious public health problem. There is growing evidence supporting the use of oral appliances to treat OSA. It is thought that these work by enlarging the throat passage, but this rema ....Obstructive sleep apnoea (OSA) is a very common disorder, affecting approximately 2% of women and 4% of men in the middle-aged workforce . It is characterised by repetitive, complete or partial closure of the throat passage during sleep, resulting in sleep disturbance and low oxygen levels. OSA is recognised as a serious public health problem. There is growing evidence supporting the use of oral appliances to treat OSA. It is thought that these work by enlarging the throat passage, but this remains uncertain. The aim of this project is to gain a better understanding of how such appliances work, so as to be able to predict which patients will particularly benefit from this form of treatment.Read moreRead less
Does The Pattern Of Ventilation Distribution Predict Airway Hyperresponsiveness?
Funder
National Health and Medical Research Council
Funding Amount
$256,973.00
Summary
The tendency for airways to narrow too easily when stimulated is called airway hyperresponsiveness (AHR). AHR is an important feature of asthma, but it also occurs in other diseases, such as chronic obstructive pulmonary disease (COPD) - an airway disease caused by smoking, and cystic fibrosis. People who have AHR have more severe respiratory disease, regardless of which disease they have, and are more likely to develop poor lung function in old age and to be hospitalised or die from their disea ....The tendency for airways to narrow too easily when stimulated is called airway hyperresponsiveness (AHR). AHR is an important feature of asthma, but it also occurs in other diseases, such as chronic obstructive pulmonary disease (COPD) - an airway disease caused by smoking, and cystic fibrosis. People who have AHR have more severe respiratory disease, regardless of which disease they have, and are more likely to develop poor lung function in old age and to be hospitalised or die from their disease. If we can understand the causes of AHR we will have a better understanding of why some people with respiratory disease have poor outcomes. We have recently discovered that, in asthma, there is a very close relationship between AHR and the uneven distribution of air within the lungs. We believe that structural changes in the airways that cause this uneven distribution make the airways prone to AHR. This raises the possibility that factors that cause uneven ventilation in other respiratory diseases might also predispose the airways to AHR. If this is true, it suggests that there is a single physiological basis for AHR in a range of different diseases, and would allow us to focus research more closely on the causes of uneven ventilation. In this project we will measure the relationship between AHR and uneven ventilation in people with asthma, COPD or cystic fibrosis. The study is important because older people with asthma, particularly those with permanently narrowed airways, are likely to have more structural changes in their airways than young asthmatics, whereas people with COPD and cystic fibrosis have a different pattern of both structural changes and airway inflammation from that in asthma. The study will tell us whether there is a consistent relationship between AHR and uneven ventilation. If so, this would be extremely strong evidence that the factors that cause uneven ventilation contribute to AHR, and will point the way to studies of new treatments.Read moreRead less
Airway Extracellular Matrix And Smooth Muscle In Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$828,849.00
Summary
In asthma the layer of airway smooth muscle is thicker, due to more muscle cells. Airway narrowing is excessive but reversible. In chronic obstructive pulmonary disease (due mainly to smoking) the layer of airway smooth muscle is also thicker but the airways cannot be induced to open, or close. Our data suggest that this fixed airway narrowing is likely to be due to an excess of matrix between cells rather than muscle. This project will comprehensively test this new finding.