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BRITISH BROADCASTING CORPORATION
RADIO SCIENCE UNIT
CASE NOTES
Programme 10. - Asthma
RADIO 4
TUESDAY 14/03/06 2100-2100
PRESENTER:
MARK PORTER
CONTRIBUTORS:
STEPHEN HOLGATE
CLIVE PAGE
MIKE THOMAS
ANN BRUTON
DENISE GIBSON
PRODUCER:
ERIKA WRIGHT
NOT CHECKED AS BROADCAST
ASTHMA PATIENT
I was born three months early, so my lungs didn't develop very well. My father had asthma and it sort of got passed on to me. I think I've not known any different because I've always had breathing problems but it does mean every time I have an attack it's still frightens the life out of me because it kind of feels like you're trying to breathe through a straw and your nose is all blocked up, it's really hard to get your breath and your chest feels tight and sore, it is really scary. It's hard to - and people say oh try and relax, it's like well you try and relax when you can't breathe - it's a nightmare. I can go through phases where I can go months and have no problems and then I'll just get one thing that'll trigger it off like a cold or a chest infection then I'm ill for months on end, I'll be in and out of hospital for like four to six weeks. I think with every attack it takes a lot out of you and it takes longer to recover from.
EILEEN
My name is Eileen. I've had asthma now since the early '90s. I have three inhalers every day plus tablets at night time plus I have ventolin as well, which I have to have on a daily basis, I also take steroids. It's not very nice not being able to breathe properly and it makes it very difficult to walk. Uphill is impossible, carrying things isn't very easy and also getting backwards and forwards to work is also very difficult.
PORTER
An insight into what it's like to live with severe asthma for two of our listeners.
Fortunately most of the five million people affected in the UK have far milder symptoms that should be easy to control with medication. Even so asthma has a huge impact on the health - and the wealth - of the nation. Around 1 in 10 of the population is currently on some form of treatment for the condition, and it costs the NHS nearly a billion pounds a year.
I'll be finding out about a new test that could confirm the diagnosis more accurately, and help your GP ensure that you are on the right dose of medication - and not taking too little, or too much.
And I'll be meeting a physiotherapist involved in research to find out whether teaching people with asthma to breathe differently can help relieve their symptoms.
But first why has asthma become so common? Stephen Holgate, Professor of Medicine at the University Southampton, is one of the UK's foremost experts on the condition.
HOLGATE
For the last three decades asthma's been increasing but the last five years has seen a plateauing off of asthma prevalence. We're still talking about 22% of British children carrying an inhaler, so we're talking about still a very high prevalence. But whatever's happening out there it clearly is beginning to slow down now. As far as explaining all of this there's been so many theories, the most popular of course is this hygiene hypothesis.
PORTER
And this is the theory that our clean modern lifestyles make asthma more likely?
HOLGATE
Yes, and that if we wallow around in dirt and put our children through it a little bit when they're younger then maybe they'll be protected against allergy and asthma. I think it's a nice starting point but it hasn't really explained, in the different countries, the changing trends. For example, if we go to New Zealand what obviously is a very country lifestyle there and compare that say with Sweden, or compare it with the United Kingdom, we've got huge differences in the way that people bring up their families and the way they interface with the environment. Now I think a more likely explanation that's emerging now is what we call the infectious theory. That is that early in life, that is within the first six weeks of birth, children are, for reasons we're not clear about yet, are being exposed to and getting infected by a variety of different viruses and that these viruses themselves are beginning to program the response towards a greater risk of developing asthma.
PORTER
Later in the programme we will be hearing more from Stephen Holgate on how this latest theory has opened an avenue of research that could lead to new treatments, and possibly even a cure.
But, first let's look at existing treatments.
My guest today is Clive Page, he's Professor of Pharmacology at King's College London.
Clive, what's actually happening in the lung of someone with asthma?
PAGE
Well what's happening in the lung when you have an asthma attack is that the muscle that surrounds the airway is actually closing down in response to stimuli in the environment, for example, if you breathe in cold air. And that happens because the wall of the airway becomes inflamed, a bit like a joint will become inflamed with arthritis, and that leads to the whole airway becoming twitchy. And really what we are trying to do I suppose in treating asthma is reduce that twitchiness, because it's the twitchiness that allows you to have the symptoms of wheezing and this breathlessness that so troubles patients.
PORTER
How do we confirm the diagnosis? Obviously we look for the classic story of cough and wheeze - at night, after exercise etc. - but do we have any tests that we can use that definitely confirm what's going on?
PAGE
Well there are a number of tests that are used to confirm the diagnosis of asthma. One of them, of course, is just if you take two puffs of a bronchidilator that opens up the airways, do you actually see improvement?
PORTER
Drugs like ventolin.
PAGE
Drugs like ventolin.
PORTER
To be fair in general practice that's a test we use a lot on trial by drug really.
PAGE
Yes. And I think the other test of course that is often done in hospital settings is to measure the twitchiness of the airway, which we can actually do by putting a - getting someone to inhale a substance that we know can contract the smooth muscle around the airway and we can determine that these people with asthma have more twitchy airways than the general population.
PORTER
And what about the peak flow test, which is something that a lot of people - that's where you blow in to see how much air we can blow out in a minute?
PAGE
There are also of course - there are tests for actually measuring lung function, you can get people to blow out through a tube and you can do more sophisticated things and put them into a box. And unfortunately, one of the problems we have in asthma is that people will often be prescribed their medicine to treat their symptoms without ever lung function being measured and this is a big issue because we wouldn't treat diabetes without measuring blood glucose, we wouldn't treat hypertension without measuring blood pressure. But we are unfortunately still - there are many, many people I'm sure out there at the moment being treated for their asthma who've probably never had their lung function measured.
PORTER
I want to come back to that a little bit later on. First of all, let's run through the various treatment options that we've got and what's used at what stage because asthma treatment these days is subject to some well established guidelines.
PAGE
Yes, the British Thoracic Society and other leading medical bodies around the world have pretty much come to a consensus about how asthma should be treated and the vast majority of asthma is actually mild and many times the asthma can be controlled just when you have the occasional symptom by taking a short acting blue inhaler, for example, ventolin.
PORTER
And that's working as a bronchidilator.
PAGE
That relaxes the muscle around the airway and it's a bronchidilator or what is called a reliever. But the reason of course you're having these symptoms is because you've got this grumbling inflammation in the airway wall and so what these guidelines are saying and increasingly the practitioners who are experienced in this area is that we should be introducing anti-inflammatory drugs much earlier in the disease.
PORTER
And that would be at step two. So what might - at what level would you think of going from just using the occasional blue puffer - the reliever - to an anti-inflammatory?
PAGE
For example, if you're using more than two to four puffs a day of a blue inhaler and that suddenly goes up and you start increasing the amount of that blue inhaler you need that is a sure sign that your asthma is getting worse and you should initiate one of these anti-inflammatory drugs, of which the best example we have are the inhaled corticosteroids, they're very, very effective.
PORTER
And they're dampening down infection which makes it less likely that the airways will constrict?
PAGE
Yes, they dampen down the inflammation of the airway wall and therefore the triggers that normally cause you to wheeze, for example, when you run out and are about in cold air, or as we heard from one of the patients at the beginning of the programme, when they exercise or go to work and run for a bus, that it dampens it down and it makes you less likely to have the symptom.
PORTER
And there are more steps in the programme, you can add drugs in as required, and we'll perhaps come back to some of those a little later. Thank you for the moment.
Well stepped care following the guidelines that Clive mentioned there helps optimise therapy, but a test that accurately measures how inflamed the lungs are, could provide a much better guide. That's the rationale behind a new type of desk top analyser, or breathalyser, that measures levels of nitric oxide - a marker for inflammation.
Dr Mike Thomas is a Asthma UK research fellow at the University of Aberdeen, and a GP in Gloucestershire. His surgery is only a few miles away from mine, so I popped along to try out his new machine.
THOMAS
Okay Mark, let's measure your exhaled nitric oxide. What I'd like you to do is just breathe steadily out into this mouthpiece. Very good. Excellent. Good. And so the machine's - the online reading's coming up now. And your exhaled nitrous oxide is 12 parts per billion, which is a normal reading. So what that tells us is that if you'd come to see me with respiratory symptoms and I'd have thought maybe you had asthma then that would make that diagnosis most unlikely. So I would then have to look for other explanations. If however it was high then to me that would confirm the fact that you must have asthma because an inflammatory process is going on in your lungs, which is almost certainly the cause of the symptoms.
PORTER
Traditionally sitting here in your GP's surgery, the way that you and I would have deduced that, would be symptoms from the patient and possibly using their peak flow - measuring how much air they can expel rapidly. Is nitrous oxide a better indicator of inflammation than those two parameters that we've used up until now?
THOMAS
The problem is that the symptoms by which we diagnose asthma are very non-specific - breathlessness, cough and wheeze - although they certainly are symptoms of asthma they can be produced by other diseases and other disease processes. For instance people with rhinitis - with nasal problems - can have cough; people with cardiac problems can have wheeze; people who breathe abnormally - who have hyperventilation or what we call functional breathing disorders - can also get symptoms that can be very like those of asthma.
PORTER
So the nitric oxide is, we think, a more accurate measure. Do we know if it's a more accurate measure yet?
THOMAS
We know that it's a very good measure of inflammation in the lungs, particularly a type of inflammation that we call eosinophilic inflammation, which is very characteristic of asthma. From my standpoint there are two things that this equipment may enable us to do. First of all, spot those patients who have inflamed lungs, in spite of having apparently few symptoms and so enable us to perhaps increase their treatment and so prevent asthma attacks. And the second thing that it may enable us to do is spot patients who actually haven't got inflamed lungs, so either they've got the wrong diagnosis or their treatment is excessive - they're taking more of the inhaled steroids than they need. So potentially this may enable us to lower the steroid dose that patients are taking in, that has both cost savings and it has benefits for the patients because we know that many patients do have real concerns about taking inhaled steroid drugs.
PORTER
Can young children use this device?
THOMAS
Technically the manoeuvre at the moment, that's required, is a slow steady inhalation into the machine and we found in our pilot work that children of six and upwards were able to do this quite satisfactorily. Unfortunately, below that age it's difficult to get the children to breathe out in the controlled manner that's needed. There are groups working in various places around the world that are trying to get round this problem by collecting exhaled air in bags and things like that but at the moment this is still kind of at a experimental level. Certainly the technology we have at the moment is usable from six and upwards.
PORTER
Mike Thomas talking to me in Gloucestershire.
You're listening to Case Notes, I'm Dr Mark Porter and I'm discussing asthma with my guest Professor Clive Page.
Clive, what about those children under six - you heard Mike there talking about the fact that he can't use this test, even if it proved to be a good test it's not going to be useful in children under six? You mentioned earlier that we treat asthma without an objective measure of how bad a person's asthma is, other than their symptoms in most cases. Parents - a lot of parents are concerned about the amount of drugs we give children, particularly the inhaled steroids, how safe are these drugs, does it matter if we're over treating?
PAGE
I think it is very clear that there is concern when you mention the word steroid to the point that in some areas of the world there's steroid phobia. And of course steroids can have unwanted side effects. But I think one of the big advances we've had in the asthma treatment over the last two decades is the gradual introduction of new inhaled steroids where they're very potent, very active at doing exactly what you want in the lung but have minimal effects in the rest of the body. Now of course if you take too much or we take them too frequently they can have adverse effects and they have to be used with caution. But I think most people in this field would rather that the patient got the steroid to reduce the inflammation than not.
PORTER
But if I put you on the spot slightly - if we look at the average child on a relatively low dose of beclometasone, one of the most common steroids we use, is that actually going to have any long term significant effect on their health?
PAGE
I think most of the studies that are out there, if you look at the growth of children, that if you're using the recommended dose for mild to moderate asthma of most of the common steroids that the evidence is that they're actually relatively safe over time. And the issue only comes when you have to use high doses or you get into more severe asthma where you're using much bigger doses of the steroid and then of course there is an issue if you have the steroid for too long of having adverse effects.
PORTER
As they say the steroids probably won't affect your child's growth but poorly controlled asthma almost certainly will.
Let's move on to self-help measures. What about things like smoking, pollution, avoiding allergens - do they help?
PAGE
There's a huge amount of discussion, as you know, in the media about pollution and various factors that may be causing asthma and triggering asthma and I think there's good evidence that certain types of air pollution will exacerbate asthma and you can see this from people going into hospital when there's certain levels of pollution in the air. And I think it's just common sense that avoiding pollutants like that, whether they be in the form of cigarette smoke or any kind of industrial smog is sensible. I think with allergen avoidance, if you know you're allergic to house dust mite or a particular....
PORTER
Common trigger.
PAGE
Common trigger - such as a pet or the hair from your horse, the best thing to do is avoid it because if you don't have the trigger your asthma's going to be obviously not as bad. And there are some very good studies in fact that have taken people with allergic asthma, allergic to house dust mite, moved them up into the high Alps, there are hospitals in Davos in Switzerland where ...
PORTER
They don't have house dust mites?
PAGE
Well they have - they have very clean air and there have been very well documented studies of taking patients out of European industrial cities and moving them up into altitude where their asthma improves over time. But it takes a long time to get that sort of reversal back. And I think one of the problems we have is that no one's ever been cured of asthma, you can lose your symptoms at different times of your life, maybe through puberty but we still don't have the ability at the moment to actually take someone and cure them.
PORTER
Well breathing exercises are another possible self-help approach and one that could have some basis in science. There is evidence that some people with asthma are prone to over breathe or hyperventilate. Something that might affect them in one of two ways.
First, the tendency to hyperventilate could be confused with real shortness of breath and get them reaching for an inhaler when they don't actually need one. And secondly, it can alter the concentration of gases in the lungs. The faster you breathe, the more waste carbon dioxide or CO2 you get rid off, and low CO2 levels encourage the airways to constrict, reducing air flow and worsening asthma. A vicious cycle all too familiar to Jill Horsefield.
HORSEFIELD
I woke up in the middle of the night, no pre-empting at all about having an attack coming, just very suddenly unable to breathe, getting very, very panicky. Despite the fact that I'm a nurse I was actually quite shocked at my reaction when I first had an attack because I was thinking about all the things that I would normally say to my patients like breathe slowly, try to calm down but actually it didn't work at all and I actually found myself getting quite frightened by it. I found myself starting to hyperventilate and that in itself just kind of increases the vicious cycle really - the more you try and calm down the worse it gets, and the worse it gets the more you start to hyperventilate and eventually you just find yourself locked in this awful spiral of not really being able to cope with it.
PORTER
Here at the University of Southampton, physiotherapist Ann Bruton is in the middle of a research project looking at breathing patterns in people with asthma - patterns that she monitors using a smart vest to measure changes in the shape of the chest wall as the volunteer breathes in and out. It wasn't long before she had me strapped in.
BRUTON
Right okay Mark we've got you into the shirt, we've put the sensors on and I'm now going to zip you up. So there you go.
PORTER
Right, so I'm wearing a tight Lycra type vest and it's full of different sorts of sensors and it's connected to a screen that I'm holding in my hand here. What does it tell you about my breathing?
BRUTON
It tells you various things. It can tell us how deep you're breathing, it can tell us how often you're breathing - so your rate of breathing. And what it's got in it round the top here you can feel there's a band at the top part of the chest and there's a band around the abdomen.
PORTER
Around my belly button and around my nipples, yeah.
BRUTON
Yeah, and both of those inside there's coiled wires, which as they pass a small electrical current through that, that creates an electromagnetic field and essentially that's telling you the movement within the ribcage and within the abdomen, so we know how deep people are breathing and whether they're breathing more with their abdomen or more with their ribcage.
PORTER
And why is that important - do people with asthma tend to breathe differently from normal people, in inverted commas?
BRUTON
We think they do. People who hyperventilate tend to have more frequent sigh breaths, so they have deeper breaths every now and then, more often than other people would do. People who present with abnormal symptoms, like maybe tingling in the fingers, lower carbon dioxide than normal people, people who breathe, as I say, faster and deeper than normal but it's not always obvious, there's what you'd call obvious hyperventilation, which is when someone's running for a bus or whatever, but there's also what's called hidden hyperventilation which maybe that they have this abnormal or dysfunctional breathing pattern. People with asthma may have lower carbon dioxide levels or they may be more sensitive to carbon dioxide and may be by retraining them you can either raise their CO2 or you can get them used to the higher CO2, whichever.
PORTER
The idea being that if you hyperventilate you tend to have a lower CO2 in your blood, so by teaching them to breathe properly that'll raise and that might help their asthma.
BRUTON
It's probably better if I take you and show you some patients and actually see it in action, so you can see how it works.
GIBSON
Hello I'm Denise Gibson, I'm consultant physiotherapist here at Southampton General Hospital and I'm just about to teach Darren some breathing exercises for his asthma. Okay? I'm just going to pop my hand on your tummy Darren, just want you to try and relax your shoulders if you can and to try and breathe in and out through your nose. Okay then I want you to try and focus your breathing where my hand is if you can. So when you breathe in try and just push down and out with your tummy into my hand. That's great, well done.
HORSEFIELD
The thing that I found really helpful was being taught to slow breathe and the physiotherapist on the research project taught me how to breathe deeply and slowly from my diaphragm and slow my breathing right down and I did find that after doing this I went away and practised and I did do what was suggested, instead of reaching for my inhaler if I felt I was getting a bit breathless or wheezy, then to do the breath holds and I did find that actually the wheeziness kind of subsided without having to use an inhaler.
GIBSON
That's great, well done. Now you're trying to get your breath rate right down to about between six and eight breaths per minute, so really trying to slow it down. Great, remember to breathe in and out through your nose if you can.
DARREN
Why is it important to breathe through your nose when you're doing these exercises?
GIBSON
Well it's much more natural for you to breathe in and out through your nose, it allows you to sort of have a much more of a relaxed breath. Try and keep your shoulders relaxed if you can.
BRUTON
Breathing through the nose is actually very important, particularly in things like asthma. It's one of those areas again where it's quite difficult to assess which way people will normally breathe because without sticking again mouthpieces or face masks or [indistinct word] in front of people ...
PORTER
Which make them think about it.
BRUTON
Which make them think about their breathing, it's hard to know what their normal route of breathing is. But there is some research suggesting that people with asthma tend to breathe with their mouths more often than people without asthma. And that again means that you haven't got the warming, the humidification that you normally would have through your nose. So again could exacerbate your asthma.
PORTER
Ann Bruton.
Clive, let's get back to treatments. There really have only been two advances in the last 20 or 30 years.
PAGE
Yes unfortunately this area we've tried very hard to find new medicines and we're essentially doing the same as we were in the - were treating in the 1960s - we're using brochidilators and inflammatory - anti-inflammatory steroids. We've just improved their safety profile. And I think this is a big challenge. And I think it reflects really what we heard from Professor Holgate earlier, that we had some very good ideas about what we thought caused asthma but we haven't yet translated them into medicines that can be used by people.
PORTER
So will the next decade be more fruitful than the last. Well Professor Stephen Holgate from Southampton thinks we may be on the cusp of a major breakthrough in asthma therapy.
HOLGATE
I think we were under the assumption for many years that asthma was an allergic disease and driven by exposure to allergens, like dust mites and cats and pollens and so on, that your listeners will be familiar with. I think now that whole view is changing.
PORTER
So have we exhausted that avenue do you think at the moment?
HOLGATE
Yeah I do. Undoubtedly allergens are important in stirring up asthma and contributing to its ongoing development but I don't think it's actually involved in the origins of asthma. I think probably we've gone too far down that route, we have to come back now and ask very serious questions about how asthma originates. And I think most of the research now is looking at the early life. There are also important areas of biomedical research now that are exposing environmental exposures that we haven't previously thought about. The indoor environment, for example, breathing in various chemical substances, may be more important than we previously appreciated.
PORTER
And this is things like your cleaning agents and fire retardants and sort of things - modern chemicals?
HOLGATE
Yeah modern chemicals that our bodies just aren't adapted to.
PORTER
In our hermetically sealed houses.
HOLGATE
In our hermetically sealed houses, quite correct. The second area, which is I think quite interesting, is that the increase in asthma seems to have its onset in childhood and whether the pregnant mother and what the mother's doing in programming the child in the uterus, in terms of what she eats, how she interacts with her environment, whether she smoked cigarettes for example, may be another important factor that's changed over the last three decades. So I think we need to take much higher ground here, we should be aiming to cure this disease and prevent it, not just be satisfied in suppressing it with steroids and bronchidilators.
PORTER
The only way I can see that we could cure things is looking at a vaccine, in inverted commas, what's happening in that area?
HOLGATE
Well I think there are several sides to the vaccine story. I think personally we should be moving away from thinking of asthma as a series of sort of interactions with allergens, more towards a disease where the human being has a lung that's susceptible to the environment more broadly. In other words what we're looking at here is a lung and airways that haven't got the resistance to defend themselves against a variety of different environmental factors. And by this I mean viruses, air pollutants, allergens - a variety of different substances. And that puts the responsibility of the disease firmly back into the lung again and not into the sort of allergy side of things and focuses our attention on the lining cells that are meant to protect us from the environment. For example, most of your asthmatic population will know that when they get a common cold it goes down into their chest and causes a problem and they have to do things about that. But the question is why should the common cold virus, which is quite innocuous to many of us, cause such a problem in asthma? The reason being, which we discovered and reported last year, is that the principle defence mechanism in the airways of patients with asthma against common cold viruses is highly defective and is missing the protein that actually neutralises these viruses. So maybe a therapeutic strategy would be to try and increase the ability of the epithelium to defend itself against viruses, like common cold viruses, like the influenza virus. In other words, to concentrate the research on trying to increase the human's resistance against its environment, rather than concentrating all the effort on trying to block individual pathways.
PORTER
But if we're looking for a cure, in inverted commas, then presumably we've got to find some way of permanently altering that lung's response, are we talking things like gene therapy?
HOLGATE
Well yes I mean because as we're moving more towards this area we recognise that these lining cells of the airways have what we call pattern recognition receptors. They're sometimes called toll receptors. And these are the receptors that sample the environment and program the subsequent behaviour of the immunological system and the lung to what's going to happen next. And it seems that this so called pattern recognition receptor area of what we call innate immunity is where a lot of the abnormality seems to be lying. And this is where the vaccines early in life might come. For example, if one understood that there were particular pattern recognition receptors that were not being activated properly because of our environment in the first six months of life, say, then we could actually design a vaccine, either by inhalation or as drops or as an injection if necessary, to actually stimulate those receptors and obviously try and produce the immune response that's necessary.
PORTER
Stephen Holgate talking to me earlier.
Clive whatever treatment we use, whether it's existing ones or some of these new exciting ones that Stephen was talking about there, they need to be taken properly and they need to get to where they're needed and that's one of the big problems with asthma isn't it.
PAGE
Yes, one of the biggest problems really is the fact that people if they're given a blue inhaler for their reliever or a brown inhaler for the steroid will always take the blue inhaler because it makes them feel better immediately, whereas what the doctor wants is you to take the brown one. And I think one of the big challenges is really how we improve compliance because a lot of these devices are quite difficult for both the young and the elderly, you need coordination properly and to deliver the drugs most effectively. And so there is I think too still a tendency for people to take their reliever rather than their brown ...
PORTER
For the rapid symptom relief but it does nothing about the underlying condition.
PAGE
Exactly and I think the analogy perhaps I can leave the listeners with is really this issue that if you have toothache today and you have pain that of course you're going to take aspirin to relieve your symptoms tonight until you can get to see a dentist but no one would take aspirin for toothache for the next fives years and yet there are still many asthmatics out there, that even if they're prescribed these medications, aren't necessarily taking the anti-inflammatory one.
PORTER
And your reliever or preventer isn't going to do any good if it's being squirted into your mouth.
PAGE
Absolutely, if you don't take it properly the drug gets in the wrong place and has no effect whatsoever.
PORTER
Professor Clive Page, thank you very much.
Just time to tell you about next week's programme which is all about hernias - a problem that affects one in four men and 1 in 25 women at some stage. I'll be leaving the studio to spend a day in the operating theatre to discover the best way to repair them.
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