This week, we’re taking a closer look at allergies. What causes them, and what makes them so hard to cure? Along the way we find out what it's like to live with severe allergy, why the body has evolved such a self-destructive system in the first place, whether, as some claim, caesarian delivery is linked to allergy risk, and how scientists are working on ways to blind the immune system to the things we react to to prevent allergy symptoms in future...
In this episode
00:39 - Living with allergies
Living with allergies
Stephen Whitehead & Sarah Pandolfino, Allergy UK
As we head towards warmer weather here in the northern hemisphere, the air is filling up with pollen, causing hay fever havoc for many. But there are some for whom the allergy problem is year long. According to some sources, more than 1 in 3 people in the UK suffer from some form of allergy, and 10% of the health service drug budget is put towards allergy medication. And for some, it's an everyday struggle...
Will - Allergies can affect any one of us. In fact, some estimates put the number of people worldwide with an allergy as high as one in three. And for most people that suffer from an allergy, it's a case of taking an antihistamine and moving on. But for some, their allergy dictates and restricts parts of their lives. And I've been hearing from some of these people.
Sarah - I'm Sarah, I'm Max's mum. This time last year he had multiple, multiple allergies, like so many. But now we are only down to two. So at the moment we avoid peanuts and we avoid lentils. But this time last year we had milk, egg, sesame, chickpeas, peas, fish. There was a whole lot of things we avoided.
Stephen - Name is Stephen. I'm 46 years old and the allergy I have is that I have an autoimmune disorder or autoimmune disease that manifests itself primarily in atopic dermatitis, but it's also affecting me with hair loss in the form of alopecia universalis. I've sort of suffered with hay fever throughout my life also with eczema as well.
Will - Allergies can be caused or made worse by a wide variety of things. From pollen, to bee stings, to penicillin. And for certain people it's a great many of these things.
Stephen - I certainly suffer with certain foods. I suffer with periods of stress or when I've not had a lot of sleep, I suffer with temperature increases. It suffers as well when I exercise. So there's a lot of things for me really. But I do believe that food triggers it as well, certainly. Because I know that there's certain foods that I eat that I consider no-no's. Unfortunately, they're nice foods and I do treat myself to them now and again, but knowing that they're going to bite me.
Will - So how, then, can these people hope to manage or mitigate their exposure to allergens?
Sarah - Because I was still breastfeeding him, I had to give up everything that he was allergic to, which made my diet very restricted. And his diet was really restricted as well. Once we realised that he was allergic to many other things. It was hard because then everything we gave him for the first time, you were kind of on edge all the time.
Stephen - I certainly watch what I eat. I try and avoid foods that do trigger my allergic reaction. So I have to be really careful about if I'm going to be having any of these things. Weddings and parties and things seem to really affect me. So I have to be quite controlled at those events. I've had to stop going to the gym because I was suffering with the excessive sweat in the air conditioned environment. I'm uncomfortable traveling on airplanes. I have to be very careful going to foreign countries with the climate and the foods that they offer. So there's a lot of changes that I've had to make because of my allergies.
Will - It's also important to note that allergies do not just take a physical toll on people, but also a mental one.
Stephen - Yeah, it's had a negative effect on my mental health for sure. Obviously the alopecia is very, very visual. So when I lost my hair, I essentially just became a bit of a recluse for a couple of years. It was probably fortunate that this happened during lockdown in that, you know, people were not seeing as many people as they normally would. So it enabled me to hide away a little bit. So yeah, that did affect me really sort of quite seriously to the point where I went to see my doctor about how it was affecting me and how I was suffering psychologically.
Sarah - It's not just a case of, 'okay, well we'll just avoid that then.' Places like soft play for children, they really freak me out because you look around and you don't know what snacks parents have brought for their kids and you know, then they're running around the soft play or my child is also touching that. And again, I don't know how much of a peanut, for example, would cause an allergic reaction. So I feel like I'm constantly on edge and looking around for food really. At two and three years old, he puts everything in his mouth. So I'm constantly hovering over him in a park because I don't know what he's picking up. And I think the impact on myself was greater than anybody else. I'm quite a tense individual anyway. So I kind of really took my responsibility with that quite seriously. And it was really difficult and it still is quite difficult now to go to places like soft play.
Will - And for these extreme sufferers, what do they think of the public's perception of allergies and the way that they manifest?
Sarah - The industry I suppose that causes me the most anxiety is the food and restaurant and that kind of area. You know, eating out is really kind of anxiety provoking because you don't know how well the person who's taken your order understands what you've said. And if they've taken this seriousness of what you've said and taken that message to the kitchen. And so then the kitchen can be careful. And I would really like to see the food and drink sector move into a more inclusive headspace, if you like.
Stephen - I think people are becoming more aware, but I do think that there's still a mindset with a lot of people who just think eczema is just a bit of a rash. They don't understand the seriousness of it and how deeply and cruelly it can affect people's lives. To the point that some people get depressed with it. It can affect relationships, it can break relationships, it can make people not want to go out in public. It can make people not want to work. It can affect people with not wanting to do physical activities. It can affect people with, you know, struggling to form new relationships and feeling confident enough to go out there if they're single and try and meet someone new. So yeah, I think that people don't realise all those effects, that if you are a sufferer, you're fully aware of them and you know, they can have a very detrimental effect on your life.
06:46 - How does an allergic reaction happen?
How does an allergic reaction happen?
Sheena Cruickshank, University of Manchester
The effects that allergies can have on people can be life changing - but what exactly happens inside the body during an allergic reaction, and how has our understanding of allergies changed in the last few years? The University of Manchester's immunologist Sheena Cruickshank...
Sheena - What's happening is that you've already been sensitised to that allergen and you've made a particular type of antibody called IgE, immunoglobulin E. And that's stuck to these special white blood cells that are found in loads of our barrier sites like our skin, our lungs, or our gut. Depending on where those are, is where you're going to get the symptoms. Now, when the IgE sticks to it means your mast cells are armed, they're ready to go. And when you meet the allergen, that basically causes your mast cell to spew out its contents and it's like it's full of little weapons, these little packages of little chemical weapons, and they're what causes your symptoms. So one of the chemicals it makes is called histamine. And of course that's why we take antihistamines and it causes things like you to make mucus for you to sort of contract your muscles. So it's hard to breathe, for example, you to start getting these itchy eyes. It's all those sorts of symptoms and it's those naughty mast cells.
Chris - It seems strange that the body should do something so destructive in this way. Why do we have cells capable of unleashing this kind of maelstrom in our tissues at all? What's their intended role and why do they do this?
Sheena - Well, if you look back in history, particularly perhaps not always relevant to how we live now in a lot of countries, we have an ability to distinguish between lots and lots of different infections. And the arm of the immune response that is particularly associated with allergy, is the type that's really good at dealing with big parasitic worms and any kind of pathogen that sits outside our cells, what we call an extracellular pathogen. And worms were incredibly common all throughout the world, and they still are in many parts of the world. And in fact, you know, we've done research, in Quarry Bank Mill, which is just outside Manchester, and we found that that mill workers there clearly had evidence of worms back in the 18th century.
Chris - So these mast cells, which are in these, you mentioned them as barrier sites where our insides meet the outside world. Those are places where, historically, parasites like worms would've tried to get into us. And so these cells were a line of defense.
Sheena - Absolutely. They're there to be rapid defenders, but they also have a role in other types of infection. It's really important that we have cells that can act really, really quickly if we meet any kind of threat. And mast cells are brilliant at that.
Chris - Why does it go wrong and they become pro allergy then?
Sheena - Ah, that's the 10 billion question. We don't fully know the answer to that, but part of it is all in our genes. So some people are genetically more likely to develop an allergy, and we can see that when we look at family studies where we see, for example, if your parents have an allergy, you are more likely to develop an allergy as if you're a child of that parent and so on. And some of those genes that are associated with being more susceptible to allergy, they will affect the way that we respond. So they'll affect the way that we recognise an allergen, they'll affect the way that we then react to it. So often it's sort of centered around things around the response to IgE and how it sticks to cells or the response and barriers that would normally stop things getting in. But basically it's an immune response gone wrong. The other thing is that our world is changing and the things around us are changing. So climate change is changing how long and how intense the pollen seasons are. That has a real impact on us. And we know, and we and others have shown, that pollution has a really big impact and it can make the severity of your symptoms much, much worse. And also it means you have longer symptoms as well. So there's all sorts of factors that are coming into play.
Chris - I must admit to being surprised when I first read that, that people who live in cities, particularly ones with high traffic and therefore high pollution burden, often have worse allergy problems than people who live in the countryside.
Sheena - Absolutely. And we don't fully understand the reason for that. There's a lot of different hypotheses as to why that happens. But one idea is the way that our immune system gets trained and whether we have a really kind of nice diverse surroundings and microbes and different things that are in the air, our environmental microbiome, as well as the food that we, and the way that we develop our internal microbiome. So those microbes that live inside us and on us and around us seem to be really important in how our immune system develops. And it's been shown, for example, that babies who get a lot of antibiotics when they're very, very young and their immune system is developing, that changes the microbiome and that's been correlated then with them being more likely to develop an allergy. So there's something around that kind of relationship with the environment and our food and all sorts of things that is quite important.
Chris - This gets dubbed the hygiene hypothesis as well, doesn't it? The claim that our lives are so sterile in the modern era because of various cleansing agents that allegedly remove 99.9% of microbes and so on, that this leaves the immune system almost twiddling its thumbs. So it skews the way it develops and matures down a path that leads to allergy more often.
Sheena - I think that was the original idea. And this was coined by David Strachan, back in I think the eighties. And he noticed this observation that smaller family groups and people who lived in the city were more likely to develop an allergy, and he thought it was because they were getting less exposure to germs around them. But this idea of thinking about the types of infections that we get, for example, whether or not we get worm infections or the type of microbes that live inside us and on us has sort of overtaken that original idea. So now we think of the old friend's hypothesis and the idea that it's just that all that environment that's shaping the development of our immune system rather than how sterile we have been
Chris - When we try to manage allergy people usually reach for a box of antihistamines. How does that actually work and does it really work? Is there a better strategy?
Sheena - Well, there's lots of different strategies that you can use, but I think for most of us, antihistamines are very accessible and that's one of the main chemicals that those mast cells release, and it's one of the main effectors that cause the symptoms of allergy. So by blocking the action of the histamine, you should be able to block the system, the kind of the impacts that it's having. But you have to take those things regularly. You can't just take them and then leave it for a few days. It does sort of build up. But then there's other ideas about, well, could we just try and dampen down the inflammation? And that's things like taking steroids and inhalers. They're about dampening down more, sort of more generally that inflammatory response and relieving the symptoms and the effects that those chemicals are having. Or you know, there are more preventative treatments that are being investigated as well.
Chris - I had hay fever when I was little. I got enormous benefit through being desensitised, a sequence of injections that apparently made my body a lot more tolerant of the things that I was originally allergic to. Is there any merit in that?
Sheena - Yes, there is. There's been some fantastic studies, particularly in food allergies and I think it's, what's really happening is it's about redirecting the immune system so that you do not make IgE anymore. That you're either making a different type of antibody which won't stick to mast cells, or you're making a regulatory response and that stops you getting inflammation.
15:50 - Is birth by caesarean linked to allergy risk?
Is birth by caesarean linked to allergy risk?
Rachel Peters, MCRI
Allergies can appear at any time in our lives including in old age, but that doesn’t mean their foundations aren’t laid early on. And some studies have pointed a finger at caesarian birth as a risk factor for food allergies. But is it? Rachel Peters works for the MCRI, which is a medical research institute based in Melbourne in Australia.
Rachel - There's been a rise in food allergies over the last two to three decades and it's prompted researchers to look at, well, what other things have been going on in the environment around the same time that allergies have been rising? And one of the things that has changed is how babies have been born. So we've seen a rise in the number of babies born by caesarean over the last 30 years. And this occurred at around the same time that food allergies were on the rise as well. So it did seem that there was possibly a link. So we explored this question in the health nurse study and we found that around one third of babies are born by caesarean in Melbourne, Australia. And food allergy occurred in around 10% of infants who were born by caesarean.
Will - Is that higher than other methods of delivery?
Rachel - It's actually quite similar. So in the babies who were born by a vaginal birth, 11% had a food allergy.
Will - So that's seemingly going against the grain of previous studies that said there was a link between C-section and having food allergies.
Rachel - I have to admit we were a bit surprised by the findings. You know, there are some studies out there showing that caesareans may increase the risk and a lot of this previous research used sort of poor proxies for food allergy, not gold standard outcomes that we've used in our study.
Will - So when people looked at rising food allergies and correlated it with the rising number of C-sections, what do you think might have led them to this conclusion?
Rachel - The hypothesis that could explain the link between how babies are born and developing an allergy is called the microbial exposure hypothesis. And this suggests that a lack of exposure to a variety of microbes and infections in early life can influence the developing immune system and predispose it to an allergic phenotype. So there are millions of microbes and bacteria in our body, and this is called the microbiome. And the microbiome plays a really important role in how the immune system develops. Now, babies get their first microbiome from their mothers during birth, and if a baby is born by a caesarean rather than a vaginal delivery, then they have less exposure to their mother's microbiome. So previous research has shown that babies who are born by a caesarean have a different microbial composition compared to babies who are born by a vaginal delivery. And then there's other research which shows that children who have a food allergy have a different microbial composition in their gut compared to children who don't have a food allergy. So as well as the temporal association that we'd seen between an increase in babies being born by caesarean and rising food allergies, there is also a plausible link that how a baby is born could affect their risk of an allergy.
Will - If your study showed that c-sections do not increase the amount of food allergies, what might be responsible for the rising numbers instead then?
Rachel - I guess there are a number of factors that contribute to why children develop food allergies, and we can't pinpoint it on just one thing. We've seen that babies who grow up around pet dogs or have older siblings and are therefore going to be exposed to more germs and microbes from the environment, have a lower risk of having allergies. There's some evidence that vitamin D plays a role, but one of the biggest things we know is that the timing that babies are introduced to allergenic foods in the infant's diet can actually help to prevent food allergies. So this has sort of been one of the biggest findings in the last 10 years in the field of food allergy. And research has found that babies who are introduced to allergenic foods such as peanut and egg in the first year of life can actually help prevent them from developing food allergies.
Will - So exposing children to potentially allergy causing foods at an early stage might benefit them?
Rachel - This is a strategy with the strongest evidence to date. So in Australia, we recommend that babies should be introduced to allergenic foods such as peanut and egg in the first year of life. And once you've introduced that food in the diet, it's important to keep giving your infants that food. We also looked at the difference between an elective and an emergency caesarean because we initially thought when we first did this study that perhaps we didn't find an association because we combined all types of caesareans, but they could actually confer a different level of risk. So in an emergency caesarean, labour has often already started and the baby has an opportunity to be exposed to the mother's microbiome. But in an elective caesarean, often labour hasn't begun and these are sort of considered to be more sterile and that the babies then aren't exposed to the mother's birth canal. So when we analyse this data, reassuringly, we actually found that still there was no difference in risk of babies developing allergies, depending on whether it was an emergency or an elective caesarean, or whether the cesarean occurred with or without the initiation of labour.
21:01 - Better ways to manage allergy in future
Better ways to manage allergy in future
Clare Bryant, University of Cambridge
If allergies are so widespread and costly for medical services, what is being done to treat them? The University of Cambridge’s Clare Bryant...
Clare - Anybody who suffers from hay fever will of course be familiar with taking an antihistamine. So what that is is that's a drug that prevents the effect of an inflammatory mediator called histamine. So histamines are released from mast cells, which get activated by antibodies against the allergen in the body. And the histamine then produces itchy patches in your skin, produces a runny nose, produces red eyes, those kinds of things. So if you take an antihistamine, then that actually prevents those symptoms from occurring. And they're reasonably effective if you catch your allergic response fairly early. You can also take treatments such as inhaled nasal corticosteroids. They also help dampen down the immune reaction. They're a bit more preventative. And then all the way now through to something called allergen therapy, which is also known as immunotherapy. So when they know what the response is, you can give people, over a period of time, a low dose of allergy over a period of several weeks, and there seems to be a kind of immune tolerance that can come from this. When it works, it's really amazing and it's really good because that person eventually becomes tolerised or just not sensitive anymore to the allergen and the allergy symptoms go away. But obviously it's very directed against one particular protein trigger, one particular allergen trigger. And it doesn't work for everyone for reasons that we don't really understand. It's also very time consuming. And so as a consequence, immunotherapy as it's called is useful, but it's unfortunately not proven to be the great panacea that we all hoped it would be.
Will - And now that brings us to your line of research. We are hoping to hide the allergen from the body altogether.
Clare - We found, sort of a bit by mistake really, several years ago that the cat allergy protein was actually detected by a receptor in the body, so that's a protein that's on the cell membrane of immune cells, called toll-like receptor 4. This protein could actually detect the cat allergy protein and this then was contributing to part of the way in which an immune response against an allergy was generated. And it transpired the same protein could also detect house dust mite proteins and proteins from pollens. And this triggered us to actually go and look for drugs that could inhibit toll-like receptor 4. So the rationale being that if you took a drug that blocked toll-like receptor 4, it would then stop the allergy and being detected by the body, which would stop the aberrant immune response, the allergic to communal response from occurring.
Will - You're almost hiding the response from the body, is that what you're saying?
Clare - Yeah, you're hiding the allergen from the body. So it becomes useful as a preventative therapy. So imagine you're going into a house where somebody, your friends, got pet cats and you were allergic to them. You could take a dose of TLR4 antagonist, and when you went into the house because your receptors were blocked, your body wouldn't see the allergen protein from the cat and you wouldn't get an allergen response occurring. Because this receptor was common to many allergy proteins, then you go, okay, well this actually could be quite useful as a prevention. When you're going into an environment where, you know, the allergens are going to be.
Will - And if you were to put your super optimist hat on as a final thought, do you think we'll ever get to the stage where allergies might be removed from the human body altogether?
Clare - I hope so. Yes. We need to understand much more about the biology and I think things are now emerging that we're really starting to understand the biology much, much better, particularly with the genetic studies and the patient biobanks and all those kinds of things. As the genomic era pans out, I think we will stand a good chance of trying to understand some of the common triggers, which will then allow us to design a much more rational therapeutic strategy against allergies and potentially vaccines, which may be a bit more pan specific because often people who have one allergy have an allergy against many different allergen proteins. So that's kind of the great hope moving forward.
Will - So everyone who has horrible hay fever right now, there is a shred of hope.
Clare - There is a shred of hope. Yes, horrible hay fever, horrible allergies to pets. Our preventative therapy will hopefully help that if we're successful. In the long term, hopefully by understanding the biology of how allergies occur, there are potential to develop new therapies. But in the meantime, I'm afraid we just have to grin and bear it.