Disease detection at your fingertips with Professor Alaina Ammit

So, I’m Alaina Ammit and I’m here to talk about some of the work we’re doing here at UTS, but also at the Woolcock Institute. So yes, this is who I am, professor of respiratory pharmacology, so I work on pharmacology, so the mechanism of action of drugs, here at the Faculty of Science, and also I’m the Director the Woolcock Emphysema Centre. So I just want to point this out, because this is where UTS is really doing very interesting things. We’re not just in one institution; we’re across a lot of different institutions, and like Jen, I really respect and really think it is so valuable to collaborate to answer very important questions. Okay. Let’s just take a moment now and let’s just breathe. Everybody have a few breaths. Think about your breathing. We breathe 22,000 times a day. We breathe all the time. If we don’t breathe, nothing else matters. We really, life does not go on. Breath is at the central part of our lives. But in so many cases, we don’t really think about it – we think about breath as just, yeah, we do it, it’s easy, it’s done. But in some cases, it’s not so easy, and this is the – there are a number of different chronic conditions that I’m involved in researching, and the one that I’m mostly involved in is COPD. So, COPD, we’ll look at its causes and consequences throughout this lecture, but I just want to say that it’s a very highly prevalent disease. The disease really affects, if you’re over 40, about one in seven Australians. If you’re older, when you get to about 75, the data is that maybe about one in three people. It is a disease that’s highly prevalent in Australia and across the world. So, what is it? COPD stands for chronic obstructive pulmonary disease, but it’s really an umbrella term that encapsulates diseases such as emphysema or bronchitis, and really, and the bottom line of this, there’s damage within the lungs, so the small airways of the lungs become damaged, and the symptoms that are very characteristic are breathlessness, so the inability to really capture your breath, go about your daily business and you’re breathless, or a repetitive cough with phlegm and mucus most days. Now, I have to tell some bad news, that it’s a long-term disease that gets worse over time, and even though it’s preventable and treatable, there is no cure, which is why we need research. What causes it? So, in the western world, predominantly cigarette smoking is the single largest cause of COPD, but really, we’re not – 20 per cent of people who have COPD are never smokers, and there are a lot of other causes as well, such as exposure to environmental agents, so you know, we all work in Australia in very safe places where there’s good work health and safety; this is because the chronic inspiration of noxious materials may have some effect on your lungs, of course. So, indoor and outdoor pollutants in Australia, we’re pretty good at controlling those occupational dust and chemicals, but across the world, this is not as well defined, and we really need to make sure the pollution is kept at a minimum. There is also a genetic basis to COPD, [inaudible] antitripsyn disease. Okay, now let’s think about lung function. Think about your lung function right now. Now, this graph is a very classic graph where there is, on the x axis here, is age. So, as we age, the bad news is, our lung function decreases. So, here up on the top there, the green line is lung function decline if you’re not susceptible or have COPD. On the y axis is a measure called FEV1 – forced expiratory volume in one second. I’m going to talk about some of the tests that we use to detect lung function throughout this measure. So, basically, when you’re born your lungs develop to a stage that you’re an adult, and you have – when you’re an adult, you have a set lung function. So, say at about age 25, if you take that as a percentage that your peak of lung function, it starts to decline over time. If you have COPD or if you smoke, the decline is at a really rapid rate. And there is an impact if you stop smoking, so that’s the good news, but what we want to do is to stop this lung function decline in COPD. So, I’ll come back to this graph, because it’s very important in what we’re trying to do in disease detection. And a lot of the figures that I’m going to talk about and a lot of the data I’m going to talk about is from our partners, the Lung Foundation of Australia. I recommended their website to you – they’re very good in terms of information for patients and health professionals alike, and particularly their program, Check in with your lungs, which I’ll come back to. So let’s think about lungs. We all know we have lungs in our chest, and we have the left and the right lung, but what are they? They’re basically tubes through which we breathe in air, and if we take a little close up, there are a whole lot of tubes that become smaller and smaller and smaller and smaller. And at the end of those tubes are these things called alveola ducts, and they’re basically surrounded by veins and arteries and they do that because, as you take oxygen in, then it has to pass to the bloodstream to allow everything to occur in your body. So oxygen comes in and carbon dioxide comes out. In disease, in chronic obstructive pulmonary disease, chronic bronchitis, those tubes become damaged. The tubes as shown here, there’s a thickening of the tube, it becomes, if you think – if a tube becomes more thickened from the middle, then it’s really hard for air to get through; the tube becomes very narrow. So chronic bronchitis is a thickening of the tube, there’s mucus, and the air becomes difficult to breathe in. And in emphysema, the alveola duct that is so important for this exchange of gas to your blood, becomes damaged and broken down, so emphysema is a damage of the lung as well. So, thinking about that, what do we need to do? These are the effects that we see – we see chronic bronchitis or we see emphysema, so our list of things that we need to do, and how our research can help, is shown here. Firstly, we need to detect COPD earlier, and that’s what I’m going to talk about the most today, because we really want to get it before there’s major lung destruction occurs. Then secondly, if we can detect it, we need to slow that progression, so if we’ve got lung function decline, we really just want to slow that just to a normal, healthy individual. We need to understand the causes of COPD so that we can develop more effective medicines, and I’ll touch on that briefly at the end. And from this, we’ll develop innovative therapies to not only treat but reverse that disease. So this is our goal. So, as I’ve said, I’m going to focus mostly on detecting disease early. Now, the title of this whole lecture series, as Jen says, is Disease Detection at your Fingertips. Actually, in this case, it’s at your lips, or through your breath. The way in which we detect disease in COPD and in respiratory is through breath. So now you’re going to become lung physiologists and I’m going to describe to you some of the techniques in which we detect your lung function. Spirometry – first term. Spirometry measures the amount of air that you can breathe in, and how hard and fast you can blow it out. So, when we do FEV1, so what that means is it’s, you basically ask someone to breathe in really deeply, and then really rapidly push it out. And so, it, spirometry will detect how hard and fast you can breathe out. What that means is that if you had disease, your lungs are really not so – they’re not as elastic as they normally are. They might be a little more floppy because of emphysema. So, it’s harder for you to really rapidly push that air out. So, spirometry is a thing that we test in the lab to, in a lung physiology lab, to test your overall lung function. So, this is a picture of a, spirometry in a real clinical setting where there’s a mouthpiece, the patient breathes, takes a deep breath, and then blows on the mouthpiece, and it’s detected through the series of tubes here and then there’s an analysis on a computer. And this is a picture from the lung physiology lab at the Woolcock Institute of Medical Research, led by doctors Greg King and Cindy Thamrin. Greg King is a clinician and Cindy Thamrin is a biomedical engineer, and they are, they’re in the emphysema centre and at the forefront of technology in this area. So that’s how you detect lung function – you know, big box that we only have in labs, but it’s a clinic and everyone’s able to be referred there. We can also use some smaller tools, so little tools like this one, called the Piko-6, that we use in collaboration with our partners, Lung Foundation of Australia, to do screenings. So this is a picture of my student Gina, from Germany, and we did this big lung function screening day – healthy lung testing at Martin Place. We took lung function of about 600 or 700 people in a lunch time and we used these screening tools, and Lung Health Awareness Month is right now, and last week was World COPD day. So these little tools will allow us to get a bit of a measure of your lung function, and now of course, everything has to be in an app and there’s also a company that has apps so that you can connect it to your iPhone and measure all your data as well. Okay, so detecting disease early – can we detect disease early? I’ve told you about spirometry – what we need to do is to detect, at this really early part. Now, currently that’s a challenge. This is where the technology is currently at. We want to detect early so that we can get people on the best patient management plans possible, or to allow them to really have really good pulmonary abilitation and exercise so they can really stop this decline. Now, how is that done formally? Well, there is an organisation, global organisation, called global initiative for chronic obstructive lung disease, referred to as GOLD, that we use classically spirometry to stage people into different ages, different phases of disease, at mild stage, all the way down to severe. Now, we need to detect disease early, because even though it’s severe stage is stage 4 when lung function becomes quite disabling and people have to be on oxygen, the rate of decline – oops, sorry, the rate of decline of lung function is actually greater at the early parts of the disease. So, if we can detect early, we can stop [inaudible] decline at a really important stage. So, how can we do that? This is the challenge. Now, back to this, what does the lung look like? The lung, this is the bronchus and then it branches out into bronchioles and it’s like a tree and we get smaller and smaller. So, in anatomy, thinking about you as a physiologist and an anatomist now, we have the tube, which is the trachea, go smaller and smaller to bronchi, bronchioles, [inaudible] bronchioles and down here, alveolar sacs at the end of those trees. What’s the problem? The problem is, there is a quiet zone. If you go and have spirometry, the spirometry basically detects up here, the higher level of that bronchial tube. It’s written here: terminal airways contribute little to what we detect in spirometry. So if you’ve got disease in the most peripheral part of your lungs, it’s very hard to detect that through spirometry. So this quiet zone is something that developed and was first known in 1970s, and this has always been the challenge, and how are we addressing this challenge? We’ve detected ways in which to listen to the quiet zone – again, the work of Cindy Thamrin and Greg King. We have some sensitive techniques, and these techniques are growing and they’re going to become smaller and smaller over the next couple of years. The first one is a nitrogen – it’s called the multiple breath nitrogen washout. Basically, people have – also use the breath; people have a tube that has nitrogen and they do tidal breathing, normal breathing, and they breathe nitrogen in so that it goes all around the lungs, and then they wash it out, so it’s washed out with oxygen, and all it does is detect the evenness of gas distribution. So, say if you had emphysema in your peripheral lungs, the evenness would not be there; it would be more central or around this area. So, that’s one test that we do. The other one is called forced oscillation technique, and this one is now becoming smaller and smaller – this is a device, you can just have it in the home, and you basically breathe normally and it sends a wave, so an oscillatory wave, to provide information on respiratory resistance and elasticity. So, these two techniques can allow us to listen to the quiet zone. What is the quiet zone telling us? This is really early work that we’re now doing, and there’s another paper coming and a clinical trial currently underway. It, listening to the quiet zone has allowed us to detect disease that’s not detectable via spirometry, so the standard spirometry shows it’s fine, but in people who have enrolled in this trial, there’s abnormal airway function that’s not detectable by spirometry but is detectable by these sensitive techniques, and what’s shown here on this graph is that it correlates with pack years – in that case, it correlates with how much people have smoked. So, these new techniques will allow us to detect early disease, and these are clinical trials that are going on to see whether we can then reduce lung function decline. Alright. So, if we can detect disease early with these techniques, these two techniques or other techniques, what do we do then? What’s the use? We have to do a couple of things, and the main thing is to detect and prevent flare-ups. So flare-ups are exacerbations of disease, so the technology I’ve described – the forced oscillation technique – can actually be used in the home. It’s a smaller device now, and you can just, you know, every morning go and breathe into it for a while. The information can be uploaded through the internet, straight to medical doctors, straight to a database, and that data can be measured. Measuring the data can allow you to predict when will you have an exacerbation – an exacerbation’s a flare up. So just like you can analyse stock data – when will that stock data go up? – the same technology’s used here, so monitoring of these studies will allow the doctor to say, or just the algorithm to say, ‘You need to take more of your medicines now or perhaps even go to hospital.’ With technology, when we design detect early, we can design and develop more effective medicines. This is the research that we do in my lab. We work on inflammation, so this whole lung function decline is driven by inflammation, and the medicines that we currently have, because the disease don’t allow – don’t really affect this lung function decline, they’re symptomatic and help relieve breathlessness but don’t address the lung function decline. So, we’re working on a particular protein that I’m not going to go into today, but it’s basically, TTP is its acronym; it’s called tristetraprolin. It’s an anti-inflammatory mechanism that is, we can use like a molecular switch. We’re doing drug discovery where this molecule is normally turned off in inflammation; we can turn it on and reduce inflammation, and that’s currently going on in my lab, funded by National Health and Medical Research Council, in collaboration with people across the globe. What else can we do if we detect early is to look after your lungs, so this is the message I’m going to leave you with, is that always check in with your lungs. Always be very mindful of your own physical health, and then check-in with your lung program is just listed here, so say if you looked at this questionnaire, have you got a new cough or have you coughed up mucus, do you get breathless more easily than others your age, have you experienced chest tightness or wheeze, or have you had frequent chest infections? Experienced chest pain or fatigue or sudden weight loss? If you’ve answered yes to any of these, or you’ve also smoked or worked in an industry that exposed you to dust and fumes, this is something that you should probably start to talk to your doctor about. So, this is a program that’s rolled out across the country, through pharmacies, through screening programs such as the one in Martin Place, and I really recommend it to everyone to check in with their lungs and be aware of this disease called chronic obstructive pulmonary disease. Thank you very much.

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