Dr Pamela Ewan, Addenbrookes Hospital
Chris - We’re talking allergy this week and food allergies, it turns out, are relatively common. Figures we’ve seen from the US suggested up to 8% of young children and perhaps 3 1/2 % of adults are affected by them. In many cases, it’s a bit more than a nuisance but that's about all, but for some people it can actually be a fatal problem. Pamela Ewan is with us from Addenbrookes Hospital where she’s trying to develop a way to help people who have peanut allergies. Hello, Pam. Thanks for coming on the program.
Pam - Hello.
Chris - First of all, for people who just have an allergy, what actually is allergy? What's going on chemically in their bodies?
Pam - Well in people with allergy, the problem is they've made an unwanted immune response so they make allergic antibody in which under normal circumstances, at least in our civilised environment, westernised environment, we don't need. So we first of all make this harmful antibody or unwanted antibody, and when you're then exposed to the protein to which this antibody is directed against, you get a reaction causing cells in the body to fire off, releasing a whole lot of chemicals which produce the symptoms.
Chris - What are the antibodies that do that and what are the chemicals that then unleash the unpleasant symptoms that we all associate with, having an allergic reaction?
Pam - Well, there's a whole range that can cause this. From things we breath in like pollens, or cat or dog allergens, dusts; to foods, to drugs, almost anything that is a protein can do this.
Chris - And what’s it binding onto? You said antibodies. What sort of antibodies and where are they?
Pam - These antibodies, these allergic antibodies are called IgE and they're fixed onto cells in the body called mast cells which are really surrounding every place in the body where you meet the outside world. So it’s the eye, the lining of the nose, the lining of the airways into the lung, the lining of the gut, and so on, but also in the skin. So, they're a sort of defence.
Chris - And when these IgE antibodies see the thing that they're reacting to, the thing you're allergic to, what do they then do?
Pam - They link up and cause activation pathways in the cells, allowing chemicals, particularly histamine, which are stored in these cells in little granules to be released and this whole thing can happen really quickly. So say, we were talking about cat allergy and you have cat IgE antibody within 30 seconds to a minute of inhaling the cat allergen, getting it up your nose, getting it in your eye. It binds with this antibody, fires off the cell and these mediators are released.
Chris - Now under normal circumstances they're there to protect us, presumably, these cells and they wouldn’t normally react to the things that people are reacting to when they have an allergy. They would be reacting to bad things to warn the body there is a bad thing coming and so, those mechanisms will be good under certain circumstances but they just go into overdrive in people with allergy.
Pam - In allergy, these antibodies are directed against common environmental allergens which you should normally tolerate, so that's the primary problem.
Chris - So why do people make them?
Pam - Well, we think it’s because the immune system becomes reprogrammed probably because you're not using this part of the immune system, because it’s mainly important to parasitic infections. So preventing you getting infections with various parasites, worms, and so on. If you don't use it for that, it seems in allergy, you switch and use this pathway against allergens or proteins that should be normally tolerated.
Chris - So why is it then that –I have a little bit of hayfever, I will get itchy eyes and a runny nose, but I certainly wouldn’t get anaphylaxis so I won't have to be resuscitated; but somebody who has, say a peanut allergy, I had somebody who lived in our house once and we had to be very careful with where she stored her food and where we kept our food because just a trace of peanut was enough to provoke this enormous and dramatic reaction in her that could be fatal.
Pam - Well it depends on where the allergen, the thing you're allergic to is getting to. So with pollen, with hayfever, you're breathing it in. It’s in the air, so a little bit of it gets up your nose, gets in your eyes, and there, it meets the allergic antibody and fires off the reaction. Most of it is probably filtered out in your nose, so very little gets into your lung. Within a few people, it could cause asthma if it has got down there. Peanut or foods get absorbed into the circulation quite quickly. So although you eat them, they rapidly get absorbed from your mouth and so, quite quickly, they're all over the body and that's why you get these bad reactions.
Chris - Do we know whether they really are becoming more common? It seems that everyone you meet these days, either knows someone or themselves have some kind of dramatic allergy like this. Is it just that awareness has gone up or are they much more common?
Pam - No. There’s a really well documented increase. There's a massive increase in the last 30 to 40 years and even bigger increases in certain allergies in the last 10 to 15, but there are quite good studies in similar populations comparing incidents of disease 30 or 40 years back and more recently, and there's a substantial rise. So most of it is real. There will be a bit of better recognition. There will be a bit of people thinking they're allergic when they're not, but there is a very big increase. So now, potentially about 1 in 3 of our population in the UK have an allergy.
Chris - Gosh! That's very high. Do you have any feeling for why that might be happening?
Pam - Well, this is complex but put simply, it’s thought to be due to modern westernised lifestyle. So it’s factors in our lifestyle, infection, or lack of infection may be an important component. There are probably lots of other things that we still haven’t dissected out but it could be a whole variety of things. We have very different diet. We have different exposure to chemicals. There could be lots of reasons.
Chris - I did read there was an association between being exposed to big doses of antibiotics under a certain threshold age and this may have an impact on the kind of microorganisms that flourish in the gut, and they in turn educate the immune system and this may distort the ability of the immune system to tell friend from foe for a while, and therefore encourage allergies to establish.
Pam - It could be that. A lot of these theories focus on lack of infection or antibiotics or other things in early childhood. What is also interesting though is that we’re seeing much older people who’ve been fine all their lives, at 16, 17-years-old becoming allergic. So you can't blame that on early programming.
Chris - And what are you doing to try and help the people who you've been dealing with, with these quite profound peanut allergies?
Pam - Well perhaps first of all, to say peanut allergy is a very severe allergy or potentially very severe. So of the food allergies, it’s the one that is most likely to cause either fatal or near fatal reaction, so it’s a big problem. So it’s a frightening diagnosis to have and it’s also quite hard to avoid peanuts even if you're intending to. They're hidden in things and so, it’s quite a difficult disease to manage. What we’ve done is we’ve tried to see if we could desensitise children with peanut allergy. In other words, switch off the allergy. Really, a cure we’re aiming at.
What we’ve done is we’ve taken children with proven peanut allergy. We test them at the beginning to establish exactly how much of the peanut is needed before they kick in with an allergic reaction. We then give them peanut by mouth. We use peanut flour. So that's obtained by crushing and defatting peanuts. So we give them peanut flour hidden in some other food, starting with really tiny doses, something like a 300th of a peanut, so way below of what we know is their threshold for reaction. And then we very slowly step up, increasing the doses. The way we do this is we have them up to the hospital once a fortnight, we give them a dose, they go home and take the same dose every day for 4th night. They come back, we step up a bit, two more weeks on the same dose, and so it goes on until we get up to 800 milligrams which is equivalent to about 5 whole peanuts. So by the end of this updosing regime, they're eating and tolerating 5 peanuts. Then they go on having 5 peanuts a day for ages and then we do another challenge test where we give them 12 peanuts and we do that at about 6 weeks after they've been on the maintenance dose. And then 30 weeks out, we try a really huge challenge where we give them 32 peanuts.
Chris - And just very briefly to finish us off Pam, not literally obviously, can you tell us, why is it then that they can have a whiff of peanut and it can be fatal or near fatal for them, but after this kind of therapy that you give to them, they are able to tolerate it? What is changing?
Pam - Well we’re looking at that as we go along and what we know so far is that their allergic antibody, this IgE to peanut has gone down. It hasn’t gone away but it’s gone down quite a bit and we know from other forms of desensitisation say, for pollen, the same thing happens and we’re also looking at other immunological mechanisms including these T-regulatory cells you were hearing about earlier in the program to see if we can show that the immune system is being reprogrammed from an immune response which is pro-allergy into one that is anti-allergy.
Chris - Terrific! Well it’s fantastic work. Thank you very much for coming in to the show. That's Pam Ewan. She is at Addenbrookes Hospital where she’s doing that work.