Best of: The future of allergies

0:00Hi everyone, it's your host Russ Altman from the Future of Everything. Spring is right around the corner and as the weather changes and things begin to bloom, that also means the onset of allergy season. Last fall, I sat down with Tina Sindher who shared that while allergies may be affecting more people worldwide, prevention is playing catch-up. If you're someone or know someone who lives with the scourge of environmental and food allergies, I'm one of them. I hope you'll tune in to this episode to hear some of Tina's strategies for better managing those conditions.

0:40So we're all aware of allergies. In general, they come in two types. There's allergies to food. That means you have to worry about exposures to peanuts or seafood or a variety of other things. It means when you go out to dinner or to lunch or to breakfast, you have to make sure that you're not being exposed to the wrong kinds of food. And then there's allergies to the environment. Pollen, hay fever, flowers, the forest. People can have very different relationships to both food and to their environment if every time they're exposed, they get itchy eyes, trouble breathing, rashes, eczema. So allergies are a big deal.

1:20And one of the parts of that big deal is that they're on the rise. It turns out that climate change, as we will learn, is affecting the rates of allergies. On the other hand, our ability to prevent, diagnose, and treat is also getting better. Tina Sinder is a professor of medicine, pediatrics, and allergy at Stanford University, and an expert especially on food allergies, but really all allergies. She's going to tell us that it's a problem, but we're starting to find good solutions. Tina, you're an expert on allergies. Why do allergies happen? And why do so many of us suffer from them? Oh my gosh, that is a great question.

2:00It is something we think about all the time. So when my emphasis is mostly on food allergies, so I'll come at it from that angle, but really that can be extrapolated to any type of allergy. So essentially what happens is that our immune system, when we get exposed to allergens for the first time, our antigen-presenting cells take up that antigen, or let's say peanut, and it breaks it up into little proteins and exposes our naive T cells to those proteins or epitopes. And in an environment where there's already a predisposition to allergy, we call this an atopic milieu or a Th2 skewed system, that exposure to the allergen causes our B cell antibodies to produce allergen specific IgE antibodies, which are bound on our mast cells and basophils.

3:02So the next time your body recognizes the protein, let's say the child is eating peanut for the first time or it's the third or fourth time, those allergen-specific IgE antibodies recognize the peanut and cause the mast cells and basophils to degranulate, which release the histamine, the leukotrienes, all the inflammatory cells that are associated with an allergic response. And that's what you end up seeing. Okay. So let me go back because you had a lot there, but one of the things you just said is you have that first exposure to the peanut and you said it depends a little bit about the environment.

3:41And when you say environment, do you mean the bigger environment that the individual is living in and their previous kind of life exposures? Or do you mean their internal biology environment and like how they're genetically made up? And which of those two or both are important factors? It is actually both. So that is in one of our studies, it's called the Sunbeam study where we are enrolling pregnant moms and then watching the growth of the child until three years of age, that is one of the things we're trying to understand. Is it just the immune environment inside? And when is that environment changing as well as the external environment?

4:23What is their diet like? Is there a pet in the home? What kind of medications or exposures have they had, what genetic factors are involved. We have testing for parents, both father and mother, to get a sense of what are their risk factors or genetic features that play a role in it. So it really is a combination of all of the above, which makes it such a complicated disease to study. Yes. But from what you just said, it sounds to me that one of the initial conclusions is that allergies can like kind of run in the family. It can be a genetic. And so if grandma and mom or dad, if they have allergies, it might not be a completely done deal, but it might increase the chances that you have an allergy.

5:11Is that correct? That's absolutely right. And the first degree relative that is allergic increases the risk of the child. For instance, when we're evaluating young children in our clinic to suss out, are they allergic? Are they not? What kind of intervention plans should we undertake? One of the first things we ask is, do you have an older, or we ask the parent, do they have another child who is also food allergic? Is the parent food allergic? Because all of those things kind of play into your decision plan for the individual in front of you. Yes. And when there is a genetic connection, do they tend to have the same allergies?

5:48So like I have suffered in the past, and I think I talked about it on this show, from a shrimp crab lobster allergy. Does it mean that my children or my siblings might have that same allergy or does it just raise the chances that they have some allergy of some kind? So it is the latter. It is that it raises their risk for having a form of allergy. And this, I know we say allergy for food allergy, but really it could be asthma, eczema, and food allergy, environmental allergies, as well as a condition we see a lot. It's eosinophilic esophagitis, where it's almost like eczema in your esophagus. So all of those fall into this allergic phenotype and having one or more of any of those conditions can increase your risk for food allergy.

6:39Great. And then the other thing I have to ask you about is there has been a theory, and I don't know if it's still the one that drives the field, that part of the problem was that we were keeping our children too clean, that we were worried about like, don't let them hug the cat, don't let them walk on the dirty floor, make sure they eat everything, including things that are not really food, but like sand and dirt. Is that still part of the equation? Yes, absolutely. As we learn more and we're learning about our environment, we're understanding that microbiome plays a huge role in effective functioning of our immune system.

7:20So as my mentor, Kari Nado, used to say, really food allergy or allergy prevention were the six Ds. So you got to focus on dry skin, diet, playing out in the dirt, having exposure to dogs or pets that kind of bring in allergies from the outside, vitamin D exposure, so being out in the sun, and then minimizing detergent use, which can also cause barrier dysfunction on your skin. Well, there will be our future of everything quiz will be, can you recall Tina's and Kari's six Ds? Now, I know that you've also written and thought about climate change, which is a little bit surprising, but does climate change actually factor into this equation?

8:07Yes. So actually, you know, we were talking about, before we started this recording, you were talking about your allergy to flowers and pollen allergy. And what we're finding is in this warming climate where the temperatures are rising and there's increased CO2, what we're seeing is that the pollen seasons are actually getting longer and longer. And with the high CO2 and the high temperature, the allergenicity of the pollen is stronger. So you're getting longer pollen seasons with stronger allergens that are impacting, you know, that are really causing much more severe symptoms and more individuals are impacted.

8:50I must say, climate change comes up all the time and it's rarely good news. And even for allergies, It's taking its toll. Thinking about the global and, you know, as climate change is a global phenomenon, are allergies a global phenomenon or do different cultures have different allergies or do you see the kind of same types of things across the board? Yes. You know, it really is a global phenomenon. We did, our team did a review a few years ago. We were trying to find data from really every continent. And we did find that across the globe, ER visits related to food allergic reactions or anaphylaxis were rising up.

9:33More and more individuals are being impacted. In Australia, where they've actually followed entire cohorts in categorizing food allergy, it has been rising despite some early intervention strategies. So it really is a global phenomenon. And in terms of what allergen we see, it really is much more area dependent for it. Generally, the same allergens pop up everywhere, meaning the peanuts, the tree nuts, shellfish, but kind of the distribution of each of the allergens. There is some variability. For instance, we see a lot of peanut and hazelnut, but in Italy, hazelnut is much more prevalent than peanut, even though both of them are high up there.

10:20And it really kind of ties into the processing of the foods, how the child is exposed, and how much of that allergen they have in their environment. So let me just ask about this. You mentioned these two allergies, the nut allergies and the seafood allergies. Do we have any idea what it is about those two types of food? I know that you can see allergies of anything across the board, but those ones just pop up so much. Do we understand what it is? You know, and even within those allergens, we see that some of the nuts are more potent, as in they trigger reactions. Yeah, I saw you had a paper on the difference between cashew and peanut.

11:03And I thought that was amazing. Like, wow, she's really splitting hairs here. But I guess it matters. It does matter. And, you know, this is anecdotal, but in our outpatient clinic and research clinic and in research, we are blinded. So we don't always know what they're getting. But if it's a severe reaction and they keep having symptoms, we're like, oh, I bet that was a cashew challenge. And then when we are in blind, more often than not, we are correct. And in our outpatient clinic where we do a lot of food challenges and oral immunotherapy, the second our team hears cashew, they are on higher alert than usual.

11:39Just because among the allergens, we do see some variation in how patients are reacting and at what dose they're reacting. That's just amazing. And I was so surprised to see the cashews come up because I hadn't been aware of a cashew allergy. Of course, I have been treated for allergies. And it was me and a bunch of little kids who had peanut allergies and a lot of fun stories there, which I won't go into. But basically, they were very impressed at how much I could breathe because, of course, I was three times their size, even though I'm not such a great breather. Compared to a seven-year-old, I have a good lung capacity.

12:18And so we were all getting very competitive about our ability to blow into the machine. I did want to ask about a thing that has just recently gotten on my radar. And I know that you're a food specialist, but I suspect that you're aware of this syndrome called beta-gal, which has started to pop up. And I have a relative, actually, who has it. And I know it's very debilitating. It manifests as, and this doesn't really capture the whole thing, but as basically like a meat allergy. And I'm wondering if you can just tell me about that and what is known. It seems to have just popped up recently, but maybe that's wrong.

12:53No, no, you are right. Alpha-gal syndrome. Alpha-gal, I'm sorry, not beta-gal. It's almost, it starts off, I will preface this with saying we don't see a lot of alpha-gal in our area. And being pediatrics focused, I haven't done a lot of work or research in that area. In fact, I don't even really test for it unless I have a really strong suspicion. But certain areas, and we have collaborators who are working on this in Arkansas, and where it's a tick-borne condition that you basically start, you get sensitized to this protein, and then it cross-reacts with different meats. And then when you eat the meat, and this can pop up out of the blue, similar to your shellfish allergy, where you are totally fine.

13:49And then all of a sudden you start having symptoms and you have anaphylaxis. It happens quickly. And it's just hard to diagnose because it can cross-react among different meats. And there are some studies going on right now that are led by the NIH. It's an area of special interest for the NIH where they are trying to further categorize this condition. It's hard to test for. It's just very unusual. And you're right. It is popping up more and more. Yeah. So the family member that I'm thinking of lives in Kansas and is 30-something, you know, a young mom. And all of a sudden, the anaphylaxis, and they kind of narrowed it down, that whatever, and an exquisite sensitivity.

14:37So we had a family gathering and she had to stay outside and she had to ask that none of the meat, even the smell of the meat on the barbecue, she said, could have triggered her symptoms. So it was very disabling and it's having a big effect. And we're going to obviously we're going to be talking about treatments because that's, you know, you're an allergist MD and your whole thing is to try to treat these folks. But I know that that's been a very big challenge for them. so so uh before we go to treatment i did want to ask about um multiple allergies um so um sometimes you have a single person like um my main problem was shrimp and seafood but other people have kind of across the board and i know you've written a lot about multi-food allergies um is this the same deal or do you think these people who suffer from this have special features that makes it kind of different from the people who have single allergies?

15:35Yes. You know that? So the majority of patients, maybe not majority, but a lot of the patients we are seeing in our research unit who are coming in for severe treatment or treatment of their severe allergies tend to be multi-allergic. In the literature, up to 45 % of food allergic individuals have multi-food allergies. One of the things we are trying to better understand, there's so much unknown about food allergy, is the phenotypic differences between those that are just monoallergic versus multi-food allergic. And at this time, we are not seeing obvious differences between these individuals.

16:19Also, we're trying to better understand children who outgrow their food allergies. What is different about them and their immune response versus the kids who don't outgrow their food allergies? So all of these are areas of better research. At this time, from the clinical perspective, when a patient's in front of you, the reason whether it's one food or multiple food comes into play is your shared decision-making on how best to treat it. Because if it's multiple foods, it might change your decision-making on how to treat it versus just a single food. This is The Future of Everything, and I'm Russ Altman.

16:55We'll have more with Tina Cinder next.

17:07Welcome back to The Future of Everything. I'm Russ Altman, and I'm speaking with Tina Cinder from Stanford University. In the last segment, we learned a lot about allergies, the rates are going up, the difference between food allergies and environmental allergies, and the different ways that we can start to understand how allergies form and what we can do to stop them. In this segment, we're going to specifically focus on prevention, diagnosis, and treatment, of course. There's some new drugs that are very exciting. I want to talk about prevention. I don't think about prevention of allergies because usually it's kind of a surprise and like the game's over.

17:43We already have it. But I know that you've been doing work on prevention, what could be the strategy for preventing allergies? Yes. So one of the ways that we are thinking that we can prevent food allergy is early introduction of food and a diversity of food introduction. And this all came about around 2015. So ahead of that time, the American Academy of Pediatrics would recommend that you delay introduction of allergenic food. So peanut, tree nuts, till beyond one year of age. In fact, fish and shellfish were at three years of age. So it really was pushing out the introduction. And then the LEAP trial was published out of UK, where they found that children who were sensitized to peanuts, so testing was positive, if they introduced peanut into their diet, they were less likely to develop peanut allergy down the line.

18:36And so there were two groups, ones who avoided peanut and ones who didn't. And the children who avoided peanut were five times more likely to develop peanut allergy later in life. So with that study and then subsequent other studies showing similar findings, the AAP reversed guidance in 2017 and started recommending early introduction of peanut. And now that has really been expanded across the globe. Different societies and academic committees have put out guidance on early introduction. There is still a lot of, I won't say controversy is the right word, but it's hard to get consensus of which allergens, how often, how early.

19:23So there are some continued discussions on the exact timing. So it's possible that some things might be best early, some things you might want to eat. And so people are trying to sort that all out. And there's a lot of different foods. So it's a lot of different decisions. A lot of times you give a baby a little bite and it's hard to keep it in their diet because they might develop taste for something else. So there is a lot of research ongoing in that front. And it really is a global effort trying to find the right balance. So that's one strategy. Another strategy is through the skin. So early, other studies have found that when you have dry skin or eczema at a very young age, so maybe from the time you're born, before two months of age, if you have moderate to severe eczema, you are at a much higher risk of developing food allergy.

20:15Oh, interesting. And so studies have shown that if you treat that eczema early, it may reduce your risk of food allergy. So one of our studies, it's called the SEAL trial. It's different than the Sunbeam trial. You have very beautifully named trials, I must say. We are enrolling babies less than two months of age who have dry skin and eczema. And one group is getting standard of care, no treatment. The other group is getting aggressive moisturization along with steroid treatment for their skin. and then we're following to see who develops food allergy and who doesn't to see if really aggressively treating the skin will lead to a lower incidence of food allergy.

21:03And the reason the two of these play a role is there's a hypothesis out there called the dual allergen exposure hypothesis. And essentially what folks are thinking is that you are getting sensitized when the allergen is entering and interacting with your immune system through the skin. And usually the skin provides a beautiful barrier, but in the setting of dry skin and eczema, that barrier doesn't work as well. So the allergens are entering, they're interacting with your immune system in an aberrant way, triggering that. You know, in the beginning, I talked about this allergic milieu and TH2 skewed immune system.

21:44So it's kind of driving that skewed immune system and causing you to develop the allergen-specific antibody. So the first time you eat peanut, you're already sensitized because you got it through the skin. Wow. That's exciting. That's exciting. And who would think that the skin of a two-month-old, which, of course, we always talk about a baby's bottom and a baby's skin, but they're not always perfectly intact. And that barrier is very important early on. That's right. Well, that leads us very naturally from prevention to diagnosis. Now, as I've intimated, I have suffered from allergies. And I think twice in my life, I've been laying belly down on a table where they gave me like 60 different pinpricks with had 60 different little samples.

22:33I know for one of them, 58 out of 60 were positive. but is that the state of the art or have we been able to get a little bit better at making these diagnoses? I am sad to say that we are still doing that method that's skin prick testing and essentially whatever we suspect you're allergic to we take that extract and we prick your skin essentially to get your mast cells activated so if you have allergen specific antibodies on those mast cells, they react and cause a wheel that looks like a mosquito bite. We have ways of measuring that specific antibodies through IgE testing, but both of these have a 50 % false positive rate.

23:16So they are not great diagnostic features. If they're negative, we feel confident. If they're positive without a clinical history, let's say it's a baby who's never eaten the foods before, we don't know how to interpret it. So the gold standard of treatment is actually food challenges, where we bring you into clinic and feed you the food you're allergic to, to see at what level you develop a reaction to. Wow. Yes. And that can be not fun, depending on how the reaction goes. And of course, I'm sure people come in very nervous because they've had bad experiences. So just to make sure I understand, when you are doing these pinpricks, this is literally ground up stuff.

24:05Like this is not high tech bioengineered molecules. This is, I took some peanuts, I mashed them up into be, you know, like a powder and maybe put them in some water or oil and that's what you're injecting. And it's, is there a standard? So there must be standards that somebody makes. We do use a step above that. We do use standardized product through a company where it follows strict guidance through the FDA. So we are getting very well characterized extracts. So we know exactly how much protein is in there. It is reconstituted in liquid formulation so that it is standardized across the board.

24:47But when folks bring it, folks come in with allergies to uncommon things that you don't have extracts to, what you describe is exactly what we do. We call it a fresh prick to prick testing and we have them bring in the food. We crush it up, add in some glycerin, and then we... I kind of love it. It's kind of like old-fashioned medicine, like what they did. But let me ask, you talk about the gold standard was an oral challenge. But some people have allergies like hay fever, like to pollens. You're not having them eat the... Is there a gold standard for them? Yeah. Because you can do the pinprick, but if you're not sure, what is the equivalent of having them swallow some?

25:29Or do you have them swallow pollen? No, no. So in research trials, we actually do something called a nasal allergen test. Oh my goodness. Where we insert small incremental doses of the allergen through the nose. It is not pleasant for anyone. In our clinical practice, we don't do that. We focus on symptoms. And then with the testing, it helps us guide how to prepare the immunotherapy regimen that we come up with. Great, great. And I didn't want to leave, of course, because there's been a revolution in treatment. So I want to give you some time to tell me and us about what are the frontiers of new treatments and what is kind of coming down the pike that you're excited about?

26:18Oh, yes. It actually has been a very exciting time when it comes to treatment of food allergies. So prior to 2020, the standard of care was avoidance. If you come into clinic, we diagnose you. We're like, OK, you have food allergy and just don't eat it. Good luck. here's some epi in case you have reaction but really we had no approved treatment option so the first medication that was approved is peanut oral immunotherapy where you take incremental doses of peanut and it desensitizes you so that over time if you come across a bite of a cookie you're not having severe anaphylaxis and ending up in the emergency room I think it's worth pausing here, this idea of desensitization.

27:04So they have a peanut allergy, but if you give them tiny amounts and then like increase it, you can maybe avoid these big reactions and get them to kind of tolerate the peanuts. It's kind of a kind of good news. Does it always work? And can you get that initial dose small enough so that it doesn't set off a big reaction? That is right. We start at a very low dose. So to put into perspective, let's say a one peanut is approximately 300 milligrams of protein. We start at three milligrams of protein. So 100. And in our outpatient clinic, if someone were to react at that dose, I just go down even lower.

27:43So you can titrate it to a lower dose where you don't induce severe reactions at that. Okay. I'm sorry. I interrupted, but that's the desensitization. I always tell families to think, I don't know if you're, um, if you watch the princess bride but it's the poison you know the poison in the cups where he's desensitized himself to the poison which is exactly how iocane powder so that's exactly oral immunotherapy so okay um and the downside is that you have to dose every day and if you stop dosing for a few weeks or a few months, you may go right back up to your prior sensitized state. And as children, I don't know if it's ever easy, but when they're little, parents can really be a part of this.

28:31But as they get older, preteens, teens, in college, it is very hard to accomplish. And then children and adults come across dosing fatigue when you're having to eat the same food every day. And we're just talking about peanut, but for the multi-allergic kids, that's so many foods that they're having to eat every day. So it's not easy. Kids have reactions, they can still have allergic reactions. So we have we need better ways. And that's where the next drug, which actually just got approved for food allergy in 2024, is omelizumab. And this That's a mouthful. That's a mouthful. An omelizumab is an IgE blocker.