Flinders Medical Centre Foundation
Flinders Medical Centre Foundation


Looking At The Changes In The Lung In Asthma And COPD

Unlocking The Key To Virus Entry

How Does Bronchiolitis Lead To Asthma?

Breathing A Sigh Of Relief For Lung Problems

Respiratory Syncytial Virus (RSV)

Looking At The Changes In The Lung In Asthma And COPD
First Published: Investigator - August 2009

Researchers at Flinders Medical Centre are exploring the enzymes that lead to the constriction of the airways in asthma and chronic obstructive pulmonary diseases (COPD) with the hope of creating better outcomes for sufferers.

Both asthma and COPD are characterised by inflammation in the lungs that is often a reaction to environmental factors or an infection which triggers ‘attacks’.

These conditions can cause breathing difficulties with symptoms like coughing, wheezing and shortness of breath as the airways constrict and limit airflow.

Unlike asthma, the damage caused by the inflammation in the lungs in COPD is irreversible and can get progressively worse over time.

“Asthma and COPD are also characterised by changes in the function and structure of the lungs,” said Associate Professor Rainer Haberberger from Anatomy and Histology at Flinders University.

Changes within the lungs’ blood vessels in these disorders can result in pulmonary hypertension - a reduction of blood flow in the lungs.

“There is some evidence that suggest these changes play an important role in the development of inflammatory airway disease, but we do not know exactly what role they take as this has not been extensively explored,” he said.

This is because the signalling pathways within cells that initiate this constriction of the lungs’ blood vessels are not fully understood.

Our cells use signalling pathways to pass messages along that activate certain functions within cells.

Assoc Prof Haberberger’s research points to the involvement of the sphingosine kinase 1 (SK1) pathway which triggers the creation of a lipid called sphingosine 1-phosphate (S1P), which is involved in controlling lung function.

“We predict that this SK1 and S1P pathway is involved in the vascular changes that accompany pulmonary inflammation in asthma and COPD,” said Assoc Prof Haberberger.

“If we are correct, this pathway could play a crucial role in the inflammation that characterise these diseases and create a promising target for better treatments for patients.”

Unlocking The Key To Virus Entry
First Published: Investigator - July 2008

Researchers at Flinders Medical Centre are trying to unlock the key to how one of the world’s most common respiratory viruses hitches a ride into human cells.

Human metapneumovirus (hMPV) is a major cause of respiratory tract infection in children, and also causes severe infection in the elderly and people with a compromised immune system.

Researchers hope that by working out how the virus attaches to human cells they can one day work on a method to block this first step in viral infection.

‘We’re looking at the mechanism hMPV uses to attach to cells. Once we discover that it will open the opportunity to block the action,’ said Professor David Gordon, the head of Microbiology and Infectious Diseases at Flinders Medical Centre.

The team also includes PhD student Anne Thammawat and Senior Scientist Dr Tania Sadlon and is particularly focusing its investigation on cellular glycosaminoglycans (GAGs).

‘GAGs are sugar structures present on all cells, and there is strong evidence that human metapneumonvirus use GAGs for cellular entry,’ said David.

The team is also studying the role played by the hMPV G protein, which is present on the surface of the virus and is thought to mediate attachment to cells.

‘We’ve been able to clone the G protein and are now testing its interaction with GAGs,’ David said. ‘The next step is to better understand the structure of G protein.’

‘This is important because the information will allow us to potentially design inhibitors to block infection.’

David said the research was important because respiratory tract infections are the most common infections in humans, and continue to be the leading cause of acute illness and mortality worldwide.

‘The impact on health in Australia is likely to be comparable to the United States, where respiratory tract infections are the sixth leading cause of death and account for more than half a million hospital admissions and 8-10 million outpatient visits each year,’ he said.

How Does Bronchiolitis Lead To Asthma?
First Published: Investigator - February 2007

How does infant Bronchiolitis caused by the Respiratory Syncytial Virus (RSV) lead to the development of asthma and persistent wheezing? Scientists at Flinders Medical Centre are attempting to unlock the answer to this question which has been of interest to researchers around the world for many years.

RSV Bronchiolitis is a very common illness usually contracted by infants during their first two years. It exhibits common cold like symptoms such as shortness of breath and coughing and in many infant cases the severity is such that hospitalisation is required.

Currently there is no specific treatment or vaccine for RSV Bronchiolitis. Those who develop this disease are generally cared for in a supportive manner similar to the treatment of a severe cold or flu with rest and oxygen supply if blood-oxygen levels drop too low.

“The natural course of this virus is normally only a week or two,” said Dr Dani-Louise Bryan, from the department of Critical Care Medicine. “However, there is a significant chance that children who contract RSV Bronchiolitis will go on to develop asthma or persistent wheezing.”

In past research Dr Bryan found an increase of a hormone like substance called prostaglandin (PGE2), which is triggered by the immune system to defend lung cells that have been exposed to the RSV virus by causing inflammation within the lung.

However, Dr Bryan has found that this defensive action can go too far, leading to the damage of healthy tissues and cells that aren’t infected. It is thought that this damage of healthy lung cells, to try and clear the virus, could be what leads to the development of asthma and persistent wheeze later in life.

“If the lungs are damaged when the patient is very young it seems that there is a predisposition to hyper-responsive lungs, causing breathing difficulties throughout their lives” said Dr Bryan. “With further investigation of PGE2 our team at Flinders hopes to pin point at what point this inflammatory response to RSV should be stopped.”

This research could lead to the development of a therapeutic agent that can modify the body’s responses to RSV where necessary and reduce healthy lung tissue damage.

Breathing A Sigh Of Relief For Lung Problems
First Published: Investigator - October 2003

A test to assist with the detection and management of Acute Respiratory Distress Syndrome (ARDS) and other lung problems in intensive care patients has been developed by doctors at Flinders.

The non-invasive test detects a protein (surfactant protein B) found in the bloodstream. This protein is normally confined to the air spaces of the lung, but when it leaks into the bloodstream its reveals not only lung damage but also levels of lung damage.

Surfactant is released with each breath or sigh, and lines the lungs allowing the surface tension to vary as you breathe.

Assessing lung health has previously been hindered by the fact that the lungs are inaccessible, particularly for patients with life threatening Acute Respiratory Distress Syndrome (ARDS).

This new blood test can therefore be used to predict who might develop severe lung problems.

ARDS is a worldwide problem affecting more than 1,500 Australian each year and more than 40% of those patients will die.

This lung test has been developed over many years with the help of funding from many sources including the FMC Foundation and more recently, a $250,000 Biocatalyst grant from the State Government development group, BioInnovationSA.

This funding will assist the test to be launched commercially by Lung Health Diagnostics P/L - a spin off company formed by Professor's Andrew Bersten from FMC's Critical Care Unit and Ian Doyle and Terry Nicholas from Flinders University's Department of Human Physiology.

Respiratory Syncytial Virus (RSV)
First Published: Investigator - April 2003

Respiratory Syncytial Virus (RSV) is the most common and dangerous virus in infants, effecting almost 100% of babies worldwide.

RSV lives inside the cells lining the respiratory system, causing swelling coupled with the production of large amounts of mucus.

Almost half of those infants affected by RSV will develop a severe chest infection commonly known as Bronchiolitis.

Bronchiolitis causes inflammation of the airways. It is not known what causes the inflammation. Without an understanding of this inflammation and how it occurs, it is not possible to develop effective treatments.

Professor Kevin Forsyth and his team in the Department of Paediatrics and Child Health at the Flinders Medical Centre have been investigating the mechanism of the disease process of RSV Bronchiolitis through a technique called Microarray Analysis, in an effort to create effective therapies.

Professor Forsyth explains, "When RSV infects the lungs, many cells release an array of substances known as cytokines. The Microarray Analysis allows the researchers to understand the response of thousands of genes expressed by these cells. Microarray analysis enable us to measure the response of thousands of genes which might be producing this lung inflammation.We are identifying which genes appear to be important in bronchiolitis. This will give us valuable clues in our search for understanding of the lung inflammation in bronchiolitis.

"The results obtained will lead us to identify several key substances important in the disease development of Bronchiolitis. If we can understand what happens then we can devise effective treatments. We are looking for a footprint if you like, to show us which genes are being switched on in this condition", said Professor Forsyth.

He added, "To date, our understanding on the range of these substances produced during acute bronchiolitis in children is limited. Lack of progess may have been caused by the difficulties in obtaining clinical material from babies and the lack of expertise and techniques. We now have access to fresh clinical material."

It is believed prevention of RSV bronchiolitis in babies will reduce the prevalence of childhood asthma in industrialised countries by 80%. With virtually 100% of newborn babies infected with RSV, this is welcome news.

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