Understanding And Controlling Remodelling In Pulmonary Fibrosis And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$431,839.00
Summary
The development of scar tissue is a normal response to tissue injury. When airway and lung tissue is injured by exposure to irritants, scarring greatly diminishes the function of the lung to allow transfer of oxygen to the tissue. In severe disease, the scarring may be fatal. We discovered that two factors involved in formation of scar tissue neutralise each other's effects. We are examining this interaction in human lung to develop new treatments for scarring-related lung diseases.
Assessment Of Airway Smooth Muscle Hypertrophy In Asthma And Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$298,055.00
Summary
Asthma and chronic obstructive pulmonary disease (COPD) are common in the Australian community. The cause of asthma is unknown and although COPD is most often due to smoking cigarettes it remains unknown why it develops only in some smokers and in some non-smokers. The pathology of asthma and COPD includes increased thickness of the airway smooth muscle layer. In asthma this is associated with relatively normal airway lumen size and intermittent, excessive airway narrowing whereas in COPD it is ....Asthma and chronic obstructive pulmonary disease (COPD) are common in the Australian community. The cause of asthma is unknown and although COPD is most often due to smoking cigarettes it remains unknown why it develops only in some smokers and in some non-smokers. The pathology of asthma and COPD includes increased thickness of the airway smooth muscle layer. In asthma this is associated with relatively normal airway lumen size and intermittent, excessive airway narrowing whereas in COPD it is associated with fixed narrowing of the airway lumens. The increased smooth muscle layer might result from more or bigger smooth muscle cells or from more connective tissue (matrix) between the muscle cells. This project aims to determine which of these 3 factors causes the increased thickness of the smooth muscle layer in asthma and COPD. We hypothesise that in asthma there are more muscle cells and more matrix, and that in COPD there is only more matrix. These differences would account for the different behaviour of the airways in asthma and COPD. Currently there is no useful or practical method to measure the amount of matrix in the airway wall, especially in the smooth muscle. This project will study the amount of matrix and muscle in very thin airway sections (< 1 m) from a large number of cases of asthma and COPD to allow, for the first time, accurate assessment of the fractions of matrix and muscle in the smooth muscle layer, since they barely overlap on these thin sections. The results of this study are important because they will: differentiate between mechanisms of increased thickness of the airway smooth muscle layer in asthma and COPD and therefore identify different prevention and treatment strategies; help to develop a method of monitoring airway remodeling in airway diseases that can be applied to bronchial biopsies.Read moreRead less
Pathophysiological Correlates In Smokers And Smoking-related Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$283,500.00
Summary
Smoking-related chronic airway narrowing (COPD) is a common and major illness. Research on the characteristics of the actual pathological process in the airways in smokers and COPD using direct tissue sample is relatively new. Data is currently limited and rather contradictory. In this grant we will recruit a spectrum of smokers and COPD patients typical of those in the Australian community and will be undertaking a detailed analysis of the cellular and some vascular structural changes in the ai ....Smoking-related chronic airway narrowing (COPD) is a common and major illness. Research on the characteristics of the actual pathological process in the airways in smokers and COPD using direct tissue sample is relatively new. Data is currently limited and rather contradictory. In this grant we will recruit a spectrum of smokers and COPD patients typical of those in the Australian community and will be undertaking a detailed analysis of the cellular and some vascular structural changes in the airway wall. Both cellular and vascular changes will be related to the fixed and reversible component of airway obstruction. Reversible changes with smoking cessation will be studied. A very novel feature will be a preliminary assessment of the utility of proteomics for assessment of airway pathology.Read moreRead less
Response Of Human Airways To Deep Inflation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$281,037.00
Summary
The trachea and bronchi contain muscle that when it contracts narrows the air passages and makes it harder to breath. In healthy people taking a deep breath relaxes this airway muscle and improved breathing. However, in people who suffer from asthma and chronic airflow obstruction deep breaths do not have the normal relaxing actions on airway contraction. This study will use lung removed as part of surgery for lung cancer to study how the relaxing actions of deep breathing work in human airways.
Ventilation Heterogeneity And Airway Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$522,586.00
Summary
Asthma is a common and important as a cause of significant symptoms and even death. Associated with asthma is narrowing and stiffening of the arways which causes uneven ventilation of the lungs and reduced lung function. We have developed a new technique of imaging the lungs, as well as new lung function tests which measure uneven ventilation and stiffening of airways. This will help us design better medications, and help predict those who are at risk or severe asthma and death.
Chronic obstructive pulmonary disease (COPD) is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of COPD and accounts for more than 95% of cases in industrialized countries. Cigarette smoke triggers cells in the lung to release substances which cause inflammation and eat away lung tissue. In addition, these substances enter the blood and muscle where they eat away muscle resulting in signifi ....Chronic obstructive pulmonary disease (COPD) is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of COPD and accounts for more than 95% of cases in industrialized countries. Cigarette smoke triggers cells in the lung to release substances which cause inflammation and eat away lung tissue. In addition, these substances enter the blood and muscle where they eat away muscle resulting in significant weight loss. Patients with COPD have severe difficulty in breathing because the lungs are damaged and do not function properly. This process, once started, cannot be reversed and there is currently no satisfactory therapy to help treat individuals with this terrible disease. People with COPD are prone to viral and bacterial infections of the lungs. These infections cause further inflammation, lung damage and difficulty in breathing. These infections place a tremendous burden on health care resources, have a huge effect on the quality of life and are a common cause of death. The reason why respiratory infections are so serious for people with COPD is unclear. Preliminary results from our laboratory show that a substance called GM-CSF, released from cells in the lung, may be involved in the development of COPD. Thus, the aim of this project is to use our mouse models of COPD to determine whether GM-CSF is involved in the development of COPD. The insights gained may lead to the identification of potentially novel ways to prevent and treat COPD.Read moreRead less
Th17 Cell Cytokines In Airway Wall Remodelling In Chronic Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$295,983.00
Summary
In asthma, structural changes in the airway wall occur which thicken the muscle and epithelial layers, stiffen the airways and increase mucus production. This 'remodelling' makes breathing more difficult and is not effectively reversed with current treatments. We will study the cells and molecules involved in the development of these changes. This project will increase our understanding of the processes which drive these changes and may lead to the development of improved medications.
Long-lasting Correction Of The Basic Defect In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$458,500.00
Summary
The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special ....The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special virus delivery-particles, after conditioning the airway to make it receptive to the particles. The method works in normal mice and in CF mice; it gives long lasting gene transfer from a single dose and seems to affect all airway cell types. The gene transfer may also be occurring in airway stem cells, i.e. the mother cells from which grow all the cells of the airway surface. Until now, no-one else has been able to produce prolonged gene transfer in this way, nor arrange gene transfer into stem cells in live airways. There are now a number of things that we must investigate before we could conduct safety and effectiveness trials in larger animals, or consider moving into clinical trials in humans. We need to understand exactly how our conditioning agent works and is it safe; measure how long the gene correction can last actually in our animals; decide if we can we re-dose animals (if needed) without losing effectiveness because of inflammation or immune responses that might occur; and decide how important the airway stem cells are in producing the length of the gene transfer. Because it has been difficult to measure gene correction in CF airways, we will also test new ways we have developed to measure how well the gene correction works in CF airways. The findings of this project will allow us to develop our method to where we can test it in larger animals, to provide a strong, long-lasting gene correction that will be safe for testing in human clinical trials.Read moreRead less
Mechanisms Of Airway Narrowing In Eosinophilic And Non-eosinophilic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$500,593.00
Summary
Asthma is associated with excessive airway narrowing, increased thickness of the airway wall and inflammation, most typically with eosinophils. However, 50% of cases have few eosinophils and respond less well to current treatments. This project will examine differences in airway structure between patients with or without eosinophils, using post-mortem tissue, as part of an international research collaboration.