Interview with Associate Professor Deborah Yates, UNSW conducted by
April Cashin-Garbutt, BA Hons (Cantab)
Please could you give us a brief explanation of what malignant mesothelioma is and who it affects?
Malignant mesothelioma is a rare tumor of the pleura which is the lining of the inside of the chest wall. It is highly linked with asbestos exposure. Typically, people are exposed to asbestos and then some 30 to 50 years later they develop this very nasty pleural tumor. It grows on the inside of the chest wall and eventually kills them.
Malignant mesothelioma is actually increasing in incidence in parallel with the exposure that occurred in many countries some 30 to 40 years ago.
What methods are currently used to diagnose malignant mesothelioma?
Currently we do a chest X-ray and then we do a CT scan of the chest. After this, we usually proceed to further tests. One of the most important tests we do is called a thoracoscopic biopsy. This is quite an invasive procedure involving an operation.
The chest wall is cut. The surgeon removes some tissue from the lining of the chest wall (the pleura) and then they try to stick the lining of the lungs to the chest wall .This is performed so that all the fluid that occurs with the tumor is removed, so that it does not come back again.
Why has malignant mesothelioma traditionally been difficult to diagnose in its early stages?
This is partly because the symptoms of malignant mesothelioma tend to present quite late. It is also because the pleura is a hidden cavity. Parts of the body that are deep inside are, of course, more difficult to access, and therefore present problems in that it is more difficult to find tumors in these cavities.
It is particularly problematic when people already have abnormal pleurae from asbestos exposure. Some people may already have pleural plaques, or a condition called diffuse pleural thickening. Trying to make a diagnosis of a malignant change in an already abnormal pleura can be very hard.
You have recently been testing an electronic nose (E-nose) to aid the diagnosis of malignant mesothelioma. Please could you describe what one of these is?
It's a device for measuring the chemical composition of the breath. It looks at the exhaled volatile organic compounds which are produced by the body's metabolic processes.
These analysers have been in use for some time. They have been applied in industrial settings. For example, they can detect whether sulphur dioxide has leaked from a particular factory.
The best analogy is breath detection of alcohol. However, it is not the exactly same technology.
The E-nose is a hand held device which needs training. You give the device the chemical, or, in our case, the complex chemical breath fingerprint. This tells the device what malignant mesothelioma smells like. Then the nose is meant to recognise the next time it smells it.
This is just a preliminary study, which means it is an early study. Our work does need to be substantiated by a much larger study, but so far it looks quite promising.
How does this device distinguish between benign and malignant disease?
The device picks up the breath fingerprint, which is different for benign and malignant disease.
This was in fact one of the reasons for doing our particular study. We wanted to check that the device did not get confused when someone had a benign pleural disease. We found that the E-nose did seem to be able to distinguish between the two.
Presumably the difference was in the volatile organic compound pattern that comes out of the patient in their breath fingerprint.
How do you think this device will transform the diagnosis of malignant mesothelioma?
It is early days yet, but we are really hoping that we will be able to put this into practice in a larger study where we will be able to pick up malignant disease early.
The advantages of the device are that it is totally non-invasive, it is relatively cheap and you can do it many times. It doesn't hurt the patient at all.
If the device proves successful in further trials, then we may be able to diagnose malignant mesothelioma at an early stage which means that there is a potential for being able to treat patients earlier and better.
This is because malignant mesothelioma is one of the diseases that doesn't metastasise until very late, if at all. Therefore, in theory it should be potentially removable; but we currently don't really understand enough about the mechanisms underlying why it occurs and by which it spreads.
Will this device be able to be used to aid the diagnosis of any other diseases?
This technology has been used for a variety of different diseases. People are using breath detection for example for detection of breast cancer.
We have also looked at breath detection in other types of diseases. We looked at whether the E-nose could be used to distinguish between asthma and chronic obstructive pulmonary disease (COPD). It could maybe be even used to distinguish between different types of asthma. The potential of this device is certainly there.
We're also hoping that we may be able to use the device for monitoring of treatment, in other words, seeing whether the trace changes from a positive test to a negative test after treatment.
What plans do you have for further research into this area?
What I'd like to do, but I haven't got the money at the moment, is a large prospective multi-center study, whereby we follow a cohort of people who are asbestos-exposed. We would follow them prospectively and see how this test compares to the other ones.
There are other blood tests around for example. There is one called serum mesothelin-related peptide (SMRP), which we evaluated previously in a screening study. We would like to do something similar to that.
The problem with a screening study in Australia is that we don't have a big enough population to do it quickly enough. We are trying to set up international collaborative links, as the more people we have in an international study, the more likely we would be to detect cases of malignant mesothelioma.
This is necessary as mesothelioma doesn't occur very often. In the SMRP study, we had a cohort of 528 people and we detected 15 abnormal results and 2 cases of malignancy after following the patients for a year. So, you do need to follow large numbers in order to see cases developing: the larger the study the better.
How do you think the future of malignant mesothelioma diagnosis will develop?
We are always looking for better therapy. If you know more about the disease, and if you diagnose it earlier, then your chances of being able to apply effective therapy are greater.
We are hoping that in the long run, the combination of different treatments – surgical with radiotherapy and chemotherapy – will lead to us being able to cure a few patients. The disease is almost a death sentence at the moment. It would be great to be able to cure the disease.
Would you like to make any further comments?
I would just like to emphasise that this test is not yet clinically available. We still have quite a few hoops to go through, there is the next step which is a screening study, and then following that there are all the regulatory approvals before you can put a test into clinical practice.
Where can readers find more information?
We summarised the different ways you can sample the breath after asbestos exposure in a paper that was published in the Journal of Breath Research: http://iopscience.iop.org/1752-7163/4/3/034001?fromSearchPage=true
For more information on the University of New South Wales, please visit: http://www.unsw.edu.au/
About Associate Professor Deborah Yates
Deborah Yates trained in Medicine at Cambridge University and developed her interest in asbestos and other dust diseases after working at the Pneumoconiosis Panel in London. She completed her higher degrees at the London School of Hygiene and Tropical Medicine and the National Heart & Lung Institute, London, and has been working in the field of occupational lung disease for many years.
She developed her interest in exhaled breath sampling during her research work into exhaled nitric oxide as part of her MD. This test is now used in the clinical management of asthma. Currently she is Senior Staff Specialist at St Vincent's Hospital, Sydney, NSW, and continues her clinical and research interests. Her primary concern is to develop techniques which are easy for patients to use and which eventually improve patient treatment.
