Mast Cells - Bystanders Or Instigators Of Airway Remodelling In Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$623,764.00
Summary
Current asthma treatments have little effect on changes to the breathing tubes in our lungs. The tubes are thickened and stiffer, with more muscle, blood vessels, matrix and mucus. We propose that a particular inflammatory cell, called a mast cell, causes these changes to the breathing tubes and we will find out how it does that. Thus this project will establish why and how the changes to the breathing tubes happen in asthma and reveal how best to target and reverse-prevent them in the future.
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.
The Relationship Between Vascular Remodelling And Mast Cells In Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$353,253.00
Summary
It is known that the airwalls of asthmatics have increased numbers of small blood vessels which can contribute to poor lung function in asthma. The proposed research uses a novel sheep model for chronic asthma to investigate the progressive changes to the blood vessels in the airway walls of asthmatic lungs. The information gained from our sheep model will assist the understanding of blood vessel growth and thus ulitmately help in devising new strategies to treat the effects of asthma.
It has recently become apparent that we all make a substance in the lungs called nitric oxide. The amount that we make is increased in diseases such as allergic asthma. This project will study the connection between the allergen being inhaled and the excess nitric oxide being made by cells in the lung. From this research we will have a better understanding of the processess involved and develop better therapies for asthma.
Currently in Australia asthma prevalence is high compared with other countries, affecting 10%–12% of adults and 14%–16% of children. This project will determine the contribution of mast cells to the altered function of airway smooth muscle cells and identify how non asthmatic airway smooth muscle inhibits mast cell localisation to it. The findings will provide new targets for asthma therapies and a pathway for prevention strategies, which up until now have been unsuccessful.
Airway Inflammation In Asthma And Chronic Obstructive Pulmonary Disease
Funder
National Health and Medical Research Council
Funding Amount
$390,509.00
Summary
In chronic diseases of the airway such as asthma and airway narrowing due to cigarette smoking - chronic obstructive pulmonary disease (COPD), the airways show inflammation (increased numbers of cells and their products) and remodelling (increased thickness and scarring) which persist for many years, possibly indefinitely. The exact mechanisms by which inflammation persists in the airway wall in asthma and COPD are unknown. We and others have shown that greater numbers of memory T-lymphocytes (T ....In chronic diseases of the airway such as asthma and airway narrowing due to cigarette smoking - chronic obstructive pulmonary disease (COPD), the airways show inflammation (increased numbers of cells and their products) and remodelling (increased thickness and scarring) which persist for many years, possibly indefinitely. The exact mechanisms by which inflammation persists in the airway wall in asthma and COPD are unknown. We and others have shown that greater numbers of memory T-lymphocytes (T-cells) are present in the airway wall in asthma and COPD. T-cells orchestrate the processes involved in inflammation. We have hypothesised that the persistence of airway inflammation in asthma and COPD results from the proliferation of memory T-cells within the airway wall. Unlike na ve T-cells, memory T-cells have previously been stimulated and can easily be activated to proliferate and promote inflammation by other cells which are fixed in the airway. Data from our current work examining this process suggests that, although cells fixed in the airway such as fibroblasts and macrophages are activated in asthma and COPD and may activate T-cells, they do not seem to be causing T-cell proliferation. We now wish to extend these studies by determinimg if memory T- lymphocytes are proliferating in the airway wall within aggregations of lymphoid cells which act like lymph nodes and promote T-cell growth. To do this we will compare the number of these aggregations and the types of T-cells they contain in mild and severe cases of asthma and COPD with those in normal subjects. This work will provide new knowledge to help understand the mechanisms for the persistance of airway inflammation in asthma and COPD and may thereby also provide a focus for effective treatments of these condition.Read moreRead less
In the asthmatic lung structural changes, such as increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix proteins), and an increased mass of bronchial smooth muscle cells occur. Many of these critical structural changes are not reversed or prevented with current asthma therapy, thus we need to investigate, by using lung cells and tissues , why they happen and how we can prevent them.