Chronic obstructive pulmonary disease (COPD) is a smoking-induced lung disease that is the fourth leading cause of death in Australia. The immune system is highly likely to play an important role in the progression of this condition, because of the frequency of respiratory infections that occur. We will examine in detail the immune response of COPD patients, examining specific genes and proteins that are important in the defence against bacteria. Blood samples will be obtained from people with C ....Chronic obstructive pulmonary disease (COPD) is a smoking-induced lung disease that is the fourth leading cause of death in Australia. The immune system is highly likely to play an important role in the progression of this condition, because of the frequency of respiratory infections that occur. We will examine in detail the immune response of COPD patients, examining specific genes and proteins that are important in the defence against bacteria. Blood samples will be obtained from people with COPD who are stable. We will then obtain further blood samples when there is a flare-up of the lung condition, and during recovery. We will compare the results from the blood samples, with variations in the genes that people carry. Information about individual differences in the body's response to infection would help us to better understand how COPD develops, and to initiate research on new methods of diagnosis and treatment of COPD.Read moreRead less
Mechanisms Of Protease-activated Receptor-2-mediated Bronchoprotection
Funder
National Health and Medical Research Council
Funding Amount
$354,758.00
Summary
The incidence of asthma continues to increase globally, yet there have been few real therapeutic advances. Our research, however, has recently uncovered a novel mechanism that protects the airways from inflammatory diseases like asthma. We have found that the layer of cells that line the airways - the epithelium - acts as a detector of early inflammatory events and releases anti-inflammatory substances. The lungs achieve this level of protection via 'sensor' molecules called receptors which are ....The incidence of asthma continues to increase globally, yet there have been few real therapeutic advances. Our research, however, has recently uncovered a novel mechanism that protects the airways from inflammatory diseases like asthma. We have found that the layer of cells that line the airways - the epithelium - acts as a detector of early inflammatory events and releases anti-inflammatory substances. The lungs achieve this level of protection via 'sensor' molecules called receptors which are located in the epithelium. In the case of our discovery, these receptors are called protease-activated receptors (PARs) to highlight the unique manner in which they are turned on or activated by enzymes called proteases. We have discovered that the epithelium of the lungs stores these enzymes and probably releases them during the inital stages of infection. Once released, these enzymes are detected by PARs on epithelial cells which then release substances that inhibit multiple inflammatory pathways. This mechanism protects the airways from effects that make breathing difficult, as in asthma. We have confirmed that this system provides protection in the airways of intact animals. The purpose of this projects outlined in this application is to examine the effects of activating one PAR, PAR2, on several processes in the lung, in order to characterise the individual events and processes that underlie the protective response. These studies will enable us to determine whether synthetic compounds that activate PAR2 are potential novel compounds for the treatment of diseases like asthma.Read moreRead less
Risk Factors For Asthma, Chronic Bronchitis And Emphysema In Older Adults
Funder
National Health and Medical Research Council
Funding Amount
$330,574.00
Summary
Chronic obstructive pulmonary disease (including chronic bronchitis and emphysema) is a major public health problem in Australia. The main known cause is cigarette smoking, which peaked among Australian men shortly after the second world war. Now that the consequences of this epidemic of smoking are passing, more attention needs to be paid to other causes of the condition. The proposed study will focus on occupational and domestic exposures and dietary factors in older people. Dusty jobs have lo ....Chronic obstructive pulmonary disease (including chronic bronchitis and emphysema) is a major public health problem in Australia. The main known cause is cigarette smoking, which peaked among Australian men shortly after the second world war. Now that the consequences of this epidemic of smoking are passing, more attention needs to be paid to other causes of the condition. The proposed study will focus on occupational and domestic exposures and dietary factors in older people. Dusty jobs have long been associated with COPD. However it is not known to what extent other occupational exposures to fumes and vapours are also responsible. Identifying such jobs would lead to better workplace conditions and prevention of further cases. Workers who have already developed COPD could be more fairly compensated. Similarly if indoor exposures to tobacco smoke and unvented gas appliances were found to play a role, further controls on smoking, flues and improved ventilation could also prevent cases of COPD. It is generally thought that emphysema develops from an imbalance between the oxidative stresses on the lungs and protective enzymes. A diet high in antioxidant vitamins and fish may protect against the development of COPD. If confirmed by this study, it would then be possible to conduct clinical trials of supplementation in smokers at risk of developing COPD. Public nutritional education could reduce the incidence of the condition in the future.Read moreRead less
Acute Bronchitis In General Practice: What Factors Predict A Poor Outcome And Can Antibiotics Help?
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
In Australia acute bronchitis is one of the commonest reasons for patients to attend their general practitioner. It can have considerable impact on patients lives with patients coughing on average for two weeks, with a third spending some time in bed and a quarter not returning to their usual activities for many weeks. If they attend a general practitioner (GP) it is likely they will receive antibiotics. But researchers believe that antibiotics are over prescribed for this condition and the emer ....In Australia acute bronchitis is one of the commonest reasons for patients to attend their general practitioner. It can have considerable impact on patients lives with patients coughing on average for two weeks, with a third spending some time in bed and a quarter not returning to their usual activities for many weeks. If they attend a general practitioner (GP) it is likely they will receive antibiotics. But researchers believe that antibiotics are over prescribed for this condition and the emergence of bacterial resistance is a real concern to health authorities. GPs are therefore being urged to reduce the prescription of antibioics for this common condition. But surveys by the National Prescribing Service (NPS) indicate that this is one area where GPs find it difficult to meet national recommendations. In part this may be because GPs do not wish to undertreat or miss a serious respiratory illness. Also results from randomised controlled trials examining the effectiveness of antibiotics for acute bronchitis suggest some benefit from treatment, at least in some patients. However it is not clear who these patients are and how much benefit they would get from receiving antibiotics. This creates a great deal of uncertainity for GPs who then opt for a 'just in case prescription' for everyone presenting with acute bronchitis. Our study will re-examine the symptoms, and clinical findings of patients presenting to their GP with acute cough and explore the impact of this common illness on patients lives. We will determine who does and does not benefit from antibiotics, and give guidance to GPs about the symptoms, clinical findings and investigations that predict a poorer outcome. Evidence from this study will be incorporated into treatment guidelines for acute bronchitis leading to more rational and effective management of this common problem.Read moreRead less
Modulation Of Asthmatic Airway Inflammation By Activation Of Epithelial Proteinase Activated Receptors
Funder
National Health and Medical Research Council
Funding Amount
$188,912.00
Summary
Children and adults feel the symptoms of asthma because their airways close up too easily. We have discovered a new mechanism that the healthy lung uses to keep airways open. The epithelial cells which line the airway release an enzyme that cuts of a small part of another protein, called a PAR receptor, that sits on the same cell. When this happens the epithelial cell releases relaxing substances from their lower surface. The relaxing substances keep the airways open. This grant application is d ....Children and adults feel the symptoms of asthma because their airways close up too easily. We have discovered a new mechanism that the healthy lung uses to keep airways open. The epithelial cells which line the airway release an enzyme that cuts of a small part of another protein, called a PAR receptor, that sits on the same cell. When this happens the epithelial cell releases relaxing substances from their lower surface. The relaxing substances keep the airways open. This grant application is designed to test whether the relaxing system also stops the airways from developing inflammation. If the relaxing system does this we will be able to use the knowlege we have that lets us activate the PAR receptors artificially to design new types of drugs. These drugs would be better than existing asthma drugs because they would prevent inflammation and relax the airways at the same time. These drugs could also be useful in other lung diseases such as chronic bronchitis.Read moreRead less