Speaker 1: My name is Caitlin.
Speaker 2: I'm thirty two years old, and for most of my
Speaker 2: life I hadn't experienced severe allergies or allergic reactions to anything,
Speaker 2: except for cats sometimes. I went to school in Nebraska,
Speaker 2: and after college I got a job in Denver and moved.
Speaker 2: The first year living in Denver was awesome. I got
Speaker 2: really into all the outdoorsy things that Colorado has to offer,
Speaker 2: like camping and hiking and skiing. But about a year
Speaker 2: into my time in Denver, in the spring of twenty seventeen,
Speaker 2: seasonal allergies and hay fever hit me on like anything
Speaker 2: I had ever experienced before. Every day that spring, I remember,
Speaker 2: I would wake up with a sore throat, hives, and
Speaker 2: swollen eyes. My eyes would have allergic conjunctivitis and chemosis,
Speaker 2: which is when tiny bubbles form on the surface of
Speaker 2: your eye from all the allergens and pollen in the air.
Speaker 2: I had a constant runny nose and couldn't breathe. I
Speaker 2: had a lot of sinus infections. I also couldn't hear
Speaker 2: very well because of all of the post nasal drip
Speaker 2: that would happen and settle in over I was beyond
Speaker 2: exhausted all the time and unable to go outside much
Speaker 2: at all. Every time I would leave my house, I
Speaker 2: would get hot, painful hives on any part of my
Speaker 2: skin that was exposed. I remember taking cold showers all
Speaker 2: the time to try to keep my hives from spreading
Speaker 2: all over my body, and at the time I was
Speaker 2: only using over the counter allergy medications, which only helped
Speaker 2: a little bit. I worked downtown in an office, and
Speaker 2: so riding the train into the office, interacting with coworkers
Speaker 2: and clients, and wearing business casual clothing was incredibly uncomfortable
Speaker 2: and embarrassing sometimes. And this is all before COVID times,
Speaker 2: and I was still really new at my job, so
Speaker 2: asking to work from home was a challenge. I was
Speaker 2: also really bummed because I couldn't eat a lot of
Speaker 2: fruits that grew on trees where you typically eat the skin,
Speaker 2: because the pollen grows with the fruit instead of on
Speaker 2: the hard outer layer. So fruits like peaches and apples
Speaker 2: were off limits because I would break out in hives
Speaker 2: on my neck and face and sometimes experience breathing issues.
Speaker 2: And sadly, Colorado is famous for their palasaid peaches, and
Speaker 2: I could never have them, even though it was my
Speaker 2: favorite fruit growing up. Unfortunately, things got exponentially worse the
Speaker 2: following fall due to a mold issue in the rental
Speaker 2: house that I was living in. I was exposed to
Speaker 2: penicillium mold spores, which had a compounding effect on my
Speaker 2: already maxed out immune system, and I ended up developing
Speaker 2: severe asthma. I was playing roller Derby at the time,
Speaker 2: and I remember showing up to practices and scrimmages feeling
Speaker 2: like I was breathing through a wet cloth draped over
Speaker 2: my nose and mouth and felt like I would pass
Speaker 2: out after one warm up lap.
Speaker 3: I was devastated.
Speaker 2: I didn't know what was wrong with me, and I
Speaker 2: was trying so hard to get into the sport and
Speaker 2: develop a community in my new place, but I was
Speaker 2: not able to keep up at all. I ended up
Speaker 2: taking a leave of absence to avoid further damage and
Speaker 2: started seeking professional help. I had skin testing done in
Speaker 2: January twenty eighteen, and it was pretty awful. Almost every
Speaker 2: single allergen that they had tested me for came back
Speaker 2: with a flaming positive. After this, I was introduced to
Speaker 2: my allergist and met my immunotherapy team. I got started
Speaker 2: with allergy shots by doing a procedure called a rush
Speaker 2: treatment to try to get my body as close to
Speaker 2: my maintenance DOWS for allergy shots as soon as possible.
Speaker 2: I was not able to finish the entire rush treatment
Speaker 2: because my body started to go into shock, which is
Speaker 2: actually typical for the procedure. After that, I began regular
Speaker 2: allergy shots every three weeks for the next five years.
Speaker 2: I was also put on a prescription strength antihistamine, two,
Speaker 2: over the counter antihistamines two Inhaler's, and an EpiPen in
Speaker 2: the event I went into anaphylaxis. I was not allowed
Speaker 2: to eat or touch anything that would cause any sort
Speaker 2: of reaction, and I had to avoid being outside on
Speaker 2: high pollen days. Springtime was always the worst for me
Speaker 2: due to the presence of tree pollen, and I would
Speaker 2: always see more intense reactions during that time of year
Speaker 2: to my allergy shots. Fortunately, I completed my immunotherapy in
Speaker 2: July twenty twenty three and have been pretty good ever since.
Speaker 2: I'm still on the prescription strength antihistamine and one of
Speaker 2: the over the counter antihistamines for any allergies that might
Speaker 2: pop up, as well as both Inhaler's for the now
Speaker 2: permanent asthma, but overall things are pretty manageable for me.
Speaker 2: I remember asking my allergist, why now, why did allergies
Speaker 2: hit me now and here and like this and never
Speaker 2: before in my life? And she explained to me that
Speaker 2: I'd probably experienced what they call a honeymoon period when
Speaker 2: I first moved to Colorado. My body is non reactive
Speaker 2: to the new allergens because it had never seen them before,
Speaker 2: but almost always a second time around or the following
Speaker 2: season that your body encounters the allergen, it overreacts and
Speaker 2: produces an excessive histamine response. This whole experience has been
Speaker 2: a very long and painful journey, and it took a
Speaker 2: huge toll on my mental health at the time. I'm
Speaker 2: not entirely sure how long I'll be without allergic reactions,
Speaker 2: hopefully forever, but I still get hives from time to time.
Speaker 2: Everyone's body reacts differently, and sometimes you become allergic to
Speaker 2: new things that you weren't before. Every reaction I do
Speaker 2: have now is manageable. My asthma is still very much there,
Speaker 2: but I've learned to live with it, and I'm also
Speaker 2: really excited to report that I can have feaches and
Speaker 2: apples again. My life has been completely changed because of
Speaker 2: this experience. I'm so fortunate to have the support that
Speaker 2: I do, and I cannot think my Meta Coole team
Speaker 2: and my family and my friends enough for taking such
Speaker 2: good care of me Throughout those five years. I've learned
Speaker 2: so much about something I never even thought twice about
Speaker 2: for two thirds of my life that ended up having
Speaker 2: a major life altering impact on me. The human body
Speaker 2: is so intensely weird in particular sometimes, but I'm so
Speaker 2: grateful that I was able to get through this experience
Speaker 2: and to be where I am now, even with the
Speaker 2: lasting effects it has left me with.
Speaker 3: Ooh, that gosh sounds truly miserable. Yeah, truly miserable.
Speaker 1: Oh my goodness.
Speaker 3: I always think like, oh, yeah, I have seasonal allergies.
Speaker 3: Sometimes I barely do. Yeah, I have the hint of.
Speaker 4: A seasonal allergy. And to deal with we have seasonal allergies,
Speaker 4: the I know, and to deal with it just like,
Speaker 4: oh my goodness.
Speaker 3: Yeah, all yeah, And when it's everywhere, it is ever escapable,
Speaker 3: you cannot ever escape it.
Speaker 1: Yeah yeah, you just breathe it in.
Speaker 3: That's brutal. But I'm glad that you're finding some more relief. Now,
Speaker 3: thank you so much, Kaylin for sharing your story with us.
Speaker 1: Thank you.
Speaker 3: Hi.
Speaker 1: I'm Aaron Welsh and I'm Aaron Allman Updyke.
Speaker 3: And this is this podcast will Kill You.
Speaker 1: And today we're talking about allergies today and next week
Speaker 1: today or next week?
Speaker 3: You know, what do we get ourselves into here?
Speaker 1: Eron the same thing that we always do aeron, which
Speaker 1: is a very very large topic. Yeah, yeah, here's the deal,
Speaker 1: everyone listening. Here's what it's going to go like. This
Speaker 1: week we are going to talk about allergies. I'm going
Speaker 1: to call it capital A allergies. That is all of them,
Speaker 1: food allergies, seasonal allergies, all of the allergies. What does
Speaker 1: that mean? What is an allergy? Even we'll talk about it,
Speaker 1: and we'll talk about how we figured out what our allergies,
Speaker 1: why do we have them, those kinds of things. Next
Speaker 1: week we'll focus on what do you do if you
Speaker 1: have allergies? And how did we figure that out? How
Speaker 1: do we treat them? And what are some of the options.
Speaker 3: In that respect.
Speaker 1: That's the way that we're trying to split it up.
Speaker 3: We'll see how it goes, I think it will go great.
Speaker 2: Aaron.
Speaker 3: You have nothing to be worried about.
Speaker 1: You.
Speaker 3: You always do an amazing job.
Speaker 1: I'm so she gets nervous every time.
Speaker 3: She's so nervous all the time, and I'm like, you're
Speaker 3: you do a great job.
Speaker 1: As soon as we start, thank you. As soon as
Speaker 1: we start to record the biology section, my stomach every
Speaker 1: time goes like you. So, it's already there, but I'm
Speaker 1: looking forward to it.
Speaker 3: I think they're going to be a great couple of episodes.
Speaker 3: There's a lot of stuff that we're getting to explore
Speaker 3: from sort of this big picture perspective on the energies
Speaker 3: that we haven't really although we have covered allergies or
Speaker 3: allergy related conditions like asthma in the past. I think
Speaker 3: this is a fun opportunity for us to kind of go, Okay,
Speaker 3: let's take a step back. What are the patterns that
Speaker 3: we see. How does this work across the board?
Speaker 2: Right?
Speaker 1: Really big picture here? Yeah, so yeah, yeah, but before
Speaker 1: we can start on that, it's quarantin any time.
Speaker 3: It is, Aaron, what are we drinking this week?
Speaker 1: We're drinking the allergy shot. Yeah, pretty straightforward, pretty straightforward.
Speaker 3: But we won't talk.
Speaker 1: About allergy shots other than this today. We'll talk about
Speaker 1: them next week.
Speaker 3: It's true.
Speaker 1: What's in the allergy shot erin?
Speaker 3: You know, it's just a little tropical delight. You know,
Speaker 3: it's got some it's got some rum in it. It's
Speaker 3: got some tropical fruit juices like some pineapple, some orange.
Speaker 3: It's it's delicious and it's a small contained thing, so
Speaker 3: you know, it's great. We'll post the full recipe for
Speaker 3: the allergy shot quarantine and the non alcoholic placey Berita
Speaker 3: on our website. This podcast will Kill You dot Com,
Speaker 3: as well as on all of our social media channels,
Speaker 3: which if you're not following us on social media, you
Speaker 3: really should be, because you know there's some pretty good
Speaker 3: content if we do say so ourselves, and.
Speaker 1: We do we do every time. If you haven't checked
Speaker 1: out our website yet, check that out. It's phenomenal. This
Speaker 1: podcast will kill You dot Com. We have sources from
Speaker 1: all of our episodes. We have transcripts from all of
Speaker 1: our episodes. We have a link to our bookshop dot
Speaker 1: org affiliate account and our Goodreads list. We have links
Speaker 1: to Bloodmobile, who does our music. We have so much
Speaker 1: merch we have more things.
Speaker 3: We have two things. The website is a great magical place.
Speaker 3: Check it out, new.
Speaker 1: Pictures, new pictures, promo codes, this podcast okay dot com
Speaker 1: check it out.
Speaker 3: And then one last thing before we get started with
Speaker 3: the actual content of the episode, and that is to
Speaker 3: please rate, review, and subscribe. It really does help us
Speaker 3: out and we appreciate everyone who has ever left a
Speaker 3: review or subscribed or rated. You know.
Speaker 1: Yeah, Also tell your friends maybe they're not listening yet,
Speaker 1: and then you would have something else.
Speaker 3: To talk about, like allergies.
Speaker 1: Like allergies, speaking of things to talk about.
Speaker 3: Should we get started, let's.
Speaker 1: Right after this break. This is either going to be
Speaker 1: very shocking to people listening or entirely unsurprising, probably for
Speaker 1: longtime listeners. But it's actually a little hard to put
Speaker 1: a very strict definition on the word allergy.
Speaker 3: Aaron, there is a paper that I found that was
Speaker 3: the evolution of the term allergy. I think I read
Speaker 3: that paper over time.
Speaker 1: Yeah, I think I read that paper. I tried not
Speaker 1: to read history and evolution papers, but I think I
Speaker 1: did read that one. But we will do it because
Speaker 1: in part because we have to, because we're doing an
Speaker 1: episode on allergies, so we have to tell you what
Speaker 1: we're talking about. But I think that by the end
Speaker 1: of this and next episode, everyone will appreciate that, like
Speaker 1: the deeper you get into the weeds, the more messy
Speaker 1: this idea of allergy really becomes. But we'll try and
Speaker 1: keep it a little less messy and just cover the
Speaker 1: general basics. So the American Academy of Allergy, Asthma and Immunology,
Speaker 1: and the UK's National Health Service and most other major
Speaker 1: medical and public health organizations agree on the basics of
Speaker 1: what an allergy is. An allergy is an abnormal, over
Speaker 1: the top immune response to substances that typically do not
Speaker 1: and really kind of should not cause any substantial immune response. Aaron,
Speaker 1: you'r smiling, which I know means that this should not
Speaker 1: maybe doesn't apply, but that's the way that I think
Speaker 1: about it.
Speaker 3: There's some discussion, we'll get there.
Speaker 1: I can't wait. But so these substances, the stuff that
Speaker 1: our immune system is recognizing and reacting to in this
Speaker 1: over the top way. These things are called allergens, and
Speaker 1: we've talked a lot on this podcast about the idea
Speaker 1: of antigens. Antigens are just the stuffs that our immune
Speaker 1: system sees and recognizes and then responds to allergens are
Speaker 1: just antigens. They really are just antigens. The only differences
Speaker 1: and the reason that they classify them differently is that
Speaker 1: they are stuff. And first of all, they're usually almost
Speaker 1: always proteins, except as we talked about in Alpha gal
Speaker 1: when they're not. But they are almost always some type
Speaker 1: of protein. And for most people these things that we
Speaker 1: call allergens, our immune system sees them but usually goes ah,
Speaker 1: forget about it, like just ignore that one. But in
Speaker 1: people with allergies, these specific kinds of antigens that we
Speaker 1: call allergens trigger a severe hypersensitive response. So let's talk
Speaker 1: about how that ends up happening.
Speaker 3: Okay, real quick, So all allergens are antigens, but not
Speaker 3: all antigens are allergens exactly.
Speaker 1: It's like all squares are rectangles, but not all rectangles
Speaker 1: are squares. Got it, So let's see how that ends
Speaker 1: up happening. We went over the basics of this actually
Speaker 1: very recently in our alphagal episode, but we're going to
Speaker 1: go over it again because the basics of this are
Speaker 1: applicable to essentially all types of allergies with an asterisk,
Speaker 1: because there are a lot of things that people might
Speaker 1: call allergies that don't fit this mold. But when we're
Speaker 1: talking about allergies for this episode, this is the type
Speaker 1: of process that we're going to be talking about. Is
Speaker 1: the pathway I'm about to explain, and here it goes.
Speaker 1: The pathway starts with an exposure, and then there's a
Speaker 1: process called sensitization which is making these specific type of
Speaker 1: antibodies called IgE antibodies, and we'll get there. Then there's
Speaker 1: re exposure, and then there's an allergic response. So we
Speaker 1: can go into detail on each of those parts. First,
Speaker 1: of course, we have to be exposed to analergen and
Speaker 1: we can be exposed to analergen in so many different ways.
Speaker 1: It can be in the air so we can breathe
Speaker 1: it in, and they often call those arrow allergens because
Speaker 1: if we don't have confusing terminology for every single thing,
Speaker 1: then what are we even doing in medicine. Or it
Speaker 1: can be in our food. We can scratch these allergens
Speaker 1: into our skin, a tick could split them into us,
Speaker 1: as we recently learned, we could rub them into our
Speaker 1: eyes any way that they get in. Eventually, these allergens
Speaker 1: make it into our bloodstream. And as soon as they
Speaker 1: make it into our bloodstream, our immune system is all
Speaker 1: over it. So let's say, as an example, it's cat dander.
Speaker 1: There's a specific protein called feld one or fell d
Speaker 1: one that's in cat skin, saliva, and urine, and that's
Speaker 1: the thing that's the allergen in cat dander. So once
Speaker 1: cat dander makes it into our bloodstream, a whole bunch
Speaker 1: of cells like our macrophasias, our dendritic cells, blah blah blah,
Speaker 1: all these immune cells they find this stuff, all of
Speaker 1: these allergens and antigens and the cat dander protein, and
Speaker 1: they bring it to our T cells. And our T
Speaker 1: cells are the ones I Aaron went back to my
Speaker 1: Vaccines episode notes to be like, how did I explain
Speaker 1: this once upon a time? Our T cells are the
Speaker 1: ones who are The way that I think about it
Speaker 1: is they're kind of responsible, and this is an oversimplification
Speaker 1: for either doing something or like not doing much of anything.
Speaker 1: They're going to be the ones who like open a
Speaker 1: door or don't open a door to make the rest
Speaker 1: of our immune system react or not react.
Speaker 3: They're like the major part of the decision tree exact.
Speaker 3: Is there going to be a cascade of events after this,
Speaker 3: or do we shut it down right now?
Speaker 1: Exactly exactly. And it turns out that we have a
Speaker 1: lot of different kinds of T cells in our bodies,
Speaker 1: and depending on what they're reacting to what they find,
Speaker 1: they can open one of many doors in our immune system,
Speaker 1: and which door they open fundamentally changes all of the
Speaker 1: downstream immune response that we see. So when T cells open,
Speaker 1: say door number one, they're going to release a whole
Speaker 1: bunch of cytokines, right, these inflammatory things that will help
Speaker 1: our immune system to let's say, find bacteria or viruses
Speaker 1: and target them and eliminate them. If T cells instead
Speaker 1: open a different door, call it door number two, then
Speaker 1: they release different cytokines, different inflammatory stuff, and then they're
Speaker 1: maybe going to look for worms or parasites or something
Speaker 1: like that. Now, of course, in reality, our immune system
Speaker 1: is doing all of these things and opening all the
Speaker 1: doors at the same time, and there's more than just two.
Speaker 1: But it turns out that what happens in the process
Speaker 1: of allergic sensitization, this is our second step in the pathway,
Speaker 1: is that the proportion of doors that our T cells
Speaker 1: are opening is skewed, and it's skewed towards door number two.
Speaker 1: So it just so happens that when our T cells
Speaker 1: decide when they see an allergen, to open a whole
Speaker 1: bunch of doors number two, it ends up telling our
Speaker 1: B cells, which are the ones that make antibodies, to
Speaker 1: produce a specific kind of antibody, and that is IgE,
Speaker 1: And that's the sensitization step of an allergy formation. And
Speaker 1: we talked about these IgE antibodies in our alphagal episode,
Speaker 1: But antibodies in general are like flags that our immune
Speaker 1: system uses to recognize and respond to harmful stuff more quickly.
Speaker 1: We have to see a pathogen or an antigen or
Speaker 1: an allergen make an antibody, and then the next time
Speaker 1: we see it is when that antibody does its job.
Speaker 1: And we talked about this particular IgE antibody that it's
Speaker 1: different from the ones we think of that we use
Speaker 1: for something like vaccine responses because they're bound to cells
Speaker 1: like our mass cells and our base of fills. So sensitization,
Speaker 1: we're making these weird, kind of weird IgE antibodies. Once
Speaker 1: we've been sensitized, then we have to see that allergen again.
Speaker 1: We have to be re exposed to that same allergen.
Speaker 1: So you made IgE against cat dander, and then you
Speaker 1: go back to your friend's house who has a cat.
Speaker 1: And because this IgE is all over our mass cells,
Speaker 1: it's going to find and bind to that cat dander protein,
Speaker 1: and that binding of the mass cells to the allergen
Speaker 1: triggers a reaction that causes those mass cells to burst
Speaker 1: open and spew forth a whole bunch of highly reactive
Speaker 1: inflammatory stuff. It's things like histamine, leukotrienes, a bunch of
Speaker 1: things called inter luken's, all of this stuff that tells
Speaker 1: our immune system something really serious and horrible is happening
Speaker 1: and everyone needs to get on board. It activates our
Speaker 1: immune system in a really extreme way. And it can
Speaker 1: do this on both these short time scales like immediately,
Speaker 1: these immediate responses, but then it also triggers these longer
Speaker 1: term like delayed responses, as well as the rest of
Speaker 1: those inflammatory stuffs are floating around our body. That's the
Speaker 1: actual allergic reaction.
Speaker 3: Okay, okay, question, what's your question? So IgE is involved
Speaker 3: in this allergic pathway and also parasites, But you know,
Speaker 3: you'll get there. We'll get there. Yeah, But there are
Speaker 3: so many different types of antibodies. So is IgE generally
Speaker 3: associated with this speedy, almost immediate response and the other
Speaker 3: antibodies like, why what do they do? Not to turn
Speaker 3: listen to an immunology episode, but what do they do?
Speaker 1: Yeah? So all antibodies are serving as ways to quickly
Speaker 1: identify and respond to very specific antigens. Right, So each
Speaker 1: different antibody we have like bajillions of antibodies in our body,
Speaker 1: all of them are responding to one specific protein or
Speaker 1: one specific carbohydrate or whatever. It is, one specific thing.
Speaker 1: But things like IgG antibodies the way that I think
Speaker 1: of them, and immunologists might tell me this is not
Speaker 1: a great way to conceptualize it, but the way that
Speaker 1: I think of them is they're more like a flag.
Speaker 1: So they attach on they find like a bacteria or something,
Speaker 1: and they attach themselves to it, and then our other
Speaker 1: immune cells as they're floating around, they see that flag,
Speaker 1: that IgG flag before they see the bacteria, and they're like, oh, hey, guys,
Speaker 1: that's an antibody flag, so we should find that thing, right,
Speaker 1: and then they can go and find all the bacteria
Speaker 1: that have all these flags on them. The difference with
Speaker 1: IgE is that it's not just a flag. It's attached.
Speaker 1: It's not free floating. It sometimes can be, but it's
Speaker 1: not free floating in our bloodstream. It's attached to these cells.
Speaker 1: And something about the process of when that antibody that's
Speaker 1: attached to a cell attaches to its antigen that we
Speaker 1: call allergens. In the case of allergies, it triggers this
Speaker 1: response in the mass cell itself that causes an explosion
Speaker 1: of the inflammatory stuff that's inside of that mass cell.
Speaker 1: And we don't see that with other types of antibodies
Speaker 1: because they're not bound to cells. So it's like a
Speaker 1: longer process, even though it's all much quicker than like
Speaker 1: making the antibodies the first time that you're ever exposed
Speaker 1: to something.
Speaker 3: And compared to IgE, is the response to other types
Speaker 3: of antibodies generally speaking, more directed, more precise, or is
Speaker 3: it also the systemic sort of like just again scorched earth?
Speaker 3: I think is the phrase that I used in Alpha gal.
Speaker 1: Yeah, that's a really it's a really good question. I
Speaker 1: think it's tough because the antibody response itself, even in
Speaker 1: the case of IgE, it is very highly specific, right,
Speaker 1: like your IgE is only attaching to cat dander protein. Yeah,
Speaker 1: but yes, because you have this then immediate release of
Speaker 1: all these general inflammatory stuff, you see a quicker onset
Speaker 1: of a more widespread reaction than you would potentially with
Speaker 1: other antibodies because you just don't have that. It doesn't
Speaker 1: mean that you don't have like a widespread immune response
Speaker 1: in other scenarios, because we definitely can. That's how you
Speaker 1: could end up with like sepsis from a bacterial infection
Speaker 1: and blah blah blah. But yeah, that's it is not
Speaker 1: that same antibodies kind of causing the problem here, I
Speaker 1: guess is the way that you can think of it, right, Right,
Speaker 1: it's just bizarre, it is. It's a really weird and
Speaker 1: interesting especially like I know you're going to talk erin
Speaker 1: about the kind of evolution of this, and like it
Speaker 1: is really really interesting and weird to think about why
Speaker 1: we evolved this type of response. It's really interesting.
Speaker 3: Especially when it seems like it can come at a
Speaker 3: great cost. It can when it kind of runs away.
Speaker 3: So what right, there's such a huge range of allergic responses, right,
Speaker 3: it can just be like it she knows, it can
Speaker 3: be coughing, it can be whatever, Like, yeah, what determines
Speaker 3: whether the response to an allergen is mild versus extreme
Speaker 3: all the way to anaphylaxis.
Speaker 1: So let's talk about what the different responses can be,
Speaker 1: because we are talking really generally about this big picture
Speaker 1: allergic response and the symptoms that you're going to get
Speaker 1: will in large part depend on the type of allergen
Speaker 1: that you're exposed to and how you are exposed. So
Speaker 1: if it's a cat dander protein, for example, or even
Speaker 1: like a ragweed pollen or a dust mite or cockroach
Speaker 1: leg fuzz or whatever, then you are being exposed to
Speaker 1: these arrow allergens, right, so you are breathing them in
Speaker 1: for the most part. So then where you're going to
Speaker 1: get this inflammation from this immune activation might largely be
Speaker 1: in say your nose, So you might have an itchy nose,
Speaker 1: you might have sneezing, you might get a runny nose.
Speaker 1: Maybe your eyes will start to itch or water because
Speaker 1: the cat dander is getting into your mucous membranes in
Speaker 1: your eyes and triggering inflammation in your eyes. If, on
Speaker 1: the other hand, we're not talking about an arrow allergen,
Speaker 1: maybe we're talking about something like a peanut protein or
Speaker 1: a soybean protein, or a wheat protein, you're eating that,
Speaker 1: So then you're being exposed through your gut mucus membranes
Speaker 1: or maybe through your mouth because they're there's a whole
Speaker 1: thing called oral allergy syndrome where you have this type
Speaker 1: of itching, watering, numbness, tingling just in your mouth, but
Speaker 1: if it makes it down into your guts before you're
Speaker 1: having allergy response, then maybe you're having nausea, you're having vomiting.
Speaker 1: So it depends in part in the way that you're exposed.
Speaker 1: Is it through your respiratory system, is it through your
Speaker 1: gi tract? Is it limited to one mucous membrane like
Speaker 1: your mouth or your eyes. But then there's more than that,
Speaker 1: right because while this is in some ways a localized exposure,
Speaker 1: unless it's through your skin, then it is still a
Speaker 1: systemic response. So in any of these cases, in any
Speaker 1: way that you're exposed through your skin, through your eyes,
Speaker 1: through your guts, you can also see skin manifestations, and
Speaker 1: most classically in allergies will see these as like wheels
Speaker 1: or hives. And hives are those red raised, usually irregular shaped,
Speaker 1: kind of puffy splotches, and you can see those sometimes
Speaker 1: where you're exposed like if you are eating something that
Speaker 1: you're allergic to, you might start with hives around the
Speaker 1: face or the mouth, but very often and very quickly,
Speaker 1: they can become generalized. It might start with say, puffiness
Speaker 1: around a beasting, but then spread to be hives across
Speaker 1: your whole body. And those kind of skin reactions can
Speaker 1: happen from any allergies. They can happen from cat dander
Speaker 1: allergies and from peanut allergies. And then you mentioned already aaron.
Speaker 1: The most severe thing that can happen with an allergic
Speaker 1: reaction is anaphylaxis. And just like the idea of allergies,
Speaker 1: the definition of anaphylaxis, it's not one perfect universal definition,
Speaker 1: but mostly we think of anaphylaxis as when in the
Speaker 1: case of allergies at least, because you can get anaphylaxis
Speaker 1: without allergies. But it's when an allergic response is affecting
Speaker 1: multiple systems and becomes very extreme. So it's when these
Speaker 1: mast cells and our baso fills are sending out so
Speaker 1: much inflammatory material that our whole body's immune system starts
Speaker 1: to react. What this causes is massive vasodilation, so your
Speaker 1: blood vessels are getting really wide, and that makes sense
Speaker 1: because these immune markers are telling your body, hey, there's
Speaker 1: something big going on. Send us all your blood, Send
Speaker 1: all of the white blood cells, send all of the
Speaker 1: blood to us. So vasodilation sends all of your blood
Speaker 1: different places. But that also causes swelling in part because
Speaker 1: when our vessels expand, they get more leaky, so fluid
Speaker 1: is going to leak out. And if you get that
Speaker 1: swelling in a place like your throat or your mouth
Speaker 1: or your lungs, it can make it really difficult to breathe.
Speaker 1: That's why anaphylaxis, when it causes that throat constriction, is
Speaker 1: a severe, life threatening emergency. It can also be life
Speaker 1: threatening because when our blood vessels expand, that causes a
Speaker 1: drop in blood pressure because your blood vessels are now
Speaker 1: wide open, and because of physics, when you have a
Speaker 1: pipe that's wider, the pressure inside it is going to
Speaker 1: be lower, and that again is a life threatening emergency
Speaker 1: if your blood pressure drops really quickly. So that is
Speaker 1: like the ways that allergies can manifest right, And it's
Speaker 1: such a huge range and so many different ways that
Speaker 1: you can be exposed, which can cause like any in
Speaker 1: all of these But why I have so many questions
Speaker 1: because first, why do some allergens trigger, say, anaphylaxis more
Speaker 1: commonly than other allergens? Yeah?
Speaker 3: What are those bees?
Speaker 1: I mean utter is the most classic, right, and a
Speaker 1: lot of times it is the food allergies that like
Speaker 1: tree nuts, peanuts, things like that, that are even more likely.
Speaker 1: But people can absolutely beastings or another one. Venoms in
Speaker 1: general really commonly cause anaphylaxis. It doesn't mean that you
Speaker 1: can't have an anaphylactic reaction to something like cat dander.
Speaker 1: There are absolutely people who have severe reactions to something
Speaker 1: like cat dander. But I don't know. I do not
Speaker 1: know the answer to that question. And that was something
Speaker 1: that I have so many papers, and none of them
Speaker 1: really even tried to answer that question. What is it
Speaker 1: about particular allergens that are more likely to cause a
Speaker 1: severe reaction versus a less severe reaction?
Speaker 3: I don't know, right, But then it also is individual differences.
Speaker 3: That's like the genetic component of allergies.
Speaker 2: Right.
Speaker 1: So that's the other big question, right, It's why some
Speaker 1: allergens and why some people? Why do some people develop
Speaker 1: allergies and other people don't? And we still don't know,
Speaker 1: but we have a lot more information at least about
Speaker 1: that part of the question. All allergies are really both
Speaker 1: environmental and genetic diseases, so you have to have a
Speaker 1: certain genetic susceptibility in order to develop allergies to begin with.
Speaker 1: But that doesn't mean there's a single gene or a
Speaker 1: couple of genes, or even like a few genes. There's
Speaker 1: like bajillions. That's an exaggeration, but there's a really wide
Speaker 1: range of genes that are associated with an increased risk
Speaker 1: of allergies, and for the most part, we don't know
Speaker 1: what they are or how they work, Like why do
Speaker 1: these genes that we might see in association with allergies
Speaker 1: do they cause allergies? Or why is there that association.
Speaker 3: Right and allergies? Or is it the degree of your
Speaker 3: reaction or is it which allergies or is it yeah, yeah.
Speaker 1: And in all of the literature, a thing that I
Speaker 1: want to get into, even though I already regret it,
Speaker 1: is that one of the biggest known risk factors for
Speaker 1: allergies is this idea of something called a topy.
Speaker 3: I had such a hard time wrapping my head around this.
Speaker 1: I know and you and we can't not talk about it.
Speaker 1: So I'm going to try so a topic diseases, this
Speaker 1: idea of an atopic disease. It includes asthma, egzema or
Speaker 1: atopic dermatitis, and allergies, which includes all of our allergies,
Speaker 1: so food allergies, allergic rhinitis or like hay fever, those
Speaker 1: seasonal allergies, all of that, and the word a topy
Speaker 1: or atopic, it's like, it's not specific. It doesn't like
Speaker 1: that word in and of itself anymore doesn't really mean much,
Speaker 1: and some people mean it to mean this type of
Speaker 1: IgE response, but it's not that simple. But the point
Speaker 1: of it is is that these big four diseases, and
Speaker 1: there might be a couple others that probably are under
Speaker 1: this umbrella, but like eggzema, asthma, allergic rhinitis, and food allergy,
Speaker 1: if you think of these big ones, there is something
Speaker 1: about them that links them all together. And we think
Speaker 1: that part of it might be an underlying genetic susceptibility
Speaker 1: that makes someone more susceptible to all of these at once.
Speaker 1: But really, in a lot of the literature it's described
Speaker 1: as this a topic march. You probably saw that in papers,
Speaker 1: and that's because when we see these four diseases develop
Speaker 1: through life. There's often a progression from one to the
Speaker 1: next to the next, and there's a lot of different
Speaker 1: theories as to why that is and what is this
Speaker 1: relationship between these four big diseases. So I'm going to
Speaker 1: go over what like the thoughts are about what the
Speaker 1: relationship is here. So one suggestion is that it's allergens
Speaker 1: that cause all of this, and it starts by allergens
Speaker 1: causing atopic dermatitis or exema, which is usually the first
Speaker 1: thing that we see, like even in tiny babies who
Speaker 1: don't have asthma and they don't have any food allergies
Speaker 1: yet or anything, they have exema first thing. And so
Speaker 1: one hypothesis is that you start by getting exposed and
Speaker 1: sensitized to certain allergens and first develop atopic dermatitis or exzema,
Speaker 1: and then down the line, because you have been exposed
Speaker 1: and sensitized, you then might develop asthma or other allergies
Speaker 1: as a result of this allergen exposure. That's one hypothesis.
Speaker 1: Another one that people seem to really really like is
Speaker 1: that exema is the start of this. An exema causes
Speaker 1: breakdown in the skin barrier, and this breakdown allows for
Speaker 1: allergen exposure through the skin and that and I like
Speaker 1: this too, in part because of we've already talked about
Speaker 1: on our Alpha gal episode, the idea that when you
Speaker 1: are exposed to something in an abnormal way i e.
Speaker 1: Through breaks in your skin, that that exposure is what
Speaker 1: predisposes you to this abnormal immune response i e. The
Speaker 1: development of allergies. So that's one hypothesis. And then there's
Speaker 1: a third hypothesis, which is that there's not necessarily a
Speaker 1: causal relationship between exema and allergies and asthma, but rather
Speaker 1: there's an underlying genetic or immunologic pathway that kind of
Speaker 1: pins them all together, and EXAMA just happens to be
Speaker 1: the first one that we see. Right, none of these
Speaker 1: three hypotheses are mutually exclusive, and none of them like
Speaker 1: fully explain the story, right, because there are plenty of
Speaker 1: people with egzma who don't have any other allergies, plenty
Speaker 1: of people with allergies who never had egzma. Asthma oof
Speaker 1: really doesn't fit well into this story, even though there
Speaker 1: are really strong relationships between allergic rhinitis and allergic asthma.
Speaker 3: It's really interesting and I kind of like the idea
Speaker 3: of just the threshold being lowered for that pathway to
Speaker 3: be exaccuated where it's right, oh, you know on once
Speaker 3: it's down, once you travel down that road once, it's
Speaker 3: so easy to go back down that road over and over.
Speaker 1: Again, exactly exactly. And these are not the only hypotheses.
Speaker 1: There's a lot of other ideas as to like what
Speaker 1: ends up causing or what are the risks that are
Speaker 1: contributing to the development of allergies. A lot of it
Speaker 1: might be like environmental exposures starting as early as in utero,
Speaker 1: causing things like DNA methylation or these like epigenetic changes
Speaker 1: that change our susceptibility to asthma, allergies, et cetera. Then
Speaker 1: we also can think of the microbiomes, how does that
Speaker 1: affect our risk of allergies asthma et cetera. We don't know, right,
Speaker 1: but we know that all of these things and I
Speaker 1: know erin you're going to talk more about this, I
Speaker 1: swear I'm almost done. We know that all of these
Speaker 1: things contribute. We just don't understand how, which means that
Speaker 1: we don't yet know how do we prevent all of this?
Speaker 1: And that is like next episode we'll talk a lot
Speaker 1: more about that idea, because that's like where a lot
Speaker 1: of the future research is going.
Speaker 3: And there may not be I think, one unifying cause right, like,
Speaker 3: because one of the questions that I had when when
Speaker 3: reading about these allergies and just like in general life,
Speaker 3: is some people develop allergies at a very young age
Speaker 3: and those allergies stay with them for the rest of
Speaker 3: their lives. People develop allergies at a very young age
Speaker 3: and then over time they no longer have those allergies.
Speaker 1: And that's most true for food allergies. Yes, So it's
Speaker 1: also really interesting to think about, like when are you
Speaker 1: more likely to develop what type of allergy? Because food
Speaker 1: allergies you're more likely to start developing when you're younger.
Speaker 1: Allergic rhinitis usually not till you're older.
Speaker 3: But then yeah, some people can develop food allergies later
Speaker 3: in life. I have several friends who developed food allergies
Speaker 3: in their thirties.
Speaker 1: Yeah, and like what yah, Well, and food allergies also,
Speaker 1: I think gets so much more confusing because there's also
Speaker 1: a lot of other food intolerances or sensitivities that some
Speaker 1: people might classify as allergies and other people would not
Speaker 1: classify as allergies. So a really good example of this
Speaker 1: is something called f PIES, which stands for food protein
Speaker 1: induced enterocolitis syndrome. And this is on a lot of
Speaker 1: like allergy websites, classified as an allergy, but it is
Speaker 1: not an IgE mediated response. But it causes severe like
Speaker 1: vomiting diarrhea sometimes bloody diarrhea in babies that are exposed
Speaker 1: to certain foods, and most kids outgrow this, and then
Speaker 1: in adults there's a lot of different ways that you
Speaker 1: could become intolerant of different foods, some of which might
Speaker 1: be igmediated and some of which are definitely not IgE mediated.
Speaker 1: And so that's where what I said, Like, the deeper
Speaker 1: you get into the weeds, like what's an allergy? What's
Speaker 1: not an allergy, it can get confusing. So, yeah, allergies
Speaker 1: are very interesting. Erin tell me, Yeah, why can I
Speaker 1: ask you?
Speaker 3: Why you can ask? Okay, let's see if I can
Speaker 3: answer right after this break. Allergies are so ubiquitous these
Speaker 3: days that we don't often stop to think about just
Speaker 3: how weird they are. Like, here's this extreme thing our
Speaker 3: body does in reaction to a seemingly innocuous substance like pollen,
Speaker 3: like a peanut and that reaction can at times kill us. Yep,
Speaker 3: it's not the peanut or the shrimp itself doing the harm.
Speaker 3: It's how our body responds that inflicts the damage friendly fire,
Speaker 3: whether it's seasonal allergies to ragweed, environmental allergies like to
Speaker 3: cat dander, food allergies like to tree nuts, or some
Speaker 3: other type of allergy. We all know someone who has
Speaker 3: allergies or we have them ourselves, and we wished we didn't,
Speaker 3: at least speaking for myself, at the least, allergies are annoying, disruptive,
Speaker 3: and at the extreme they can be deadly. Why do
Speaker 3: our bodies react in this way? What have almonds ever
Speaker 3: done to us? And on top of that, has it
Speaker 3: always been like this? In this first episode of this
Speaker 3: two parter on allergies, I want to explore those questions,
Speaker 3: the significance of allergies in an evolutionary context, and a
Speaker 3: little bit of how our knowledge of allergy has changed
Speaker 3: over time. Ultimately, I want to try to get at
Speaker 3: whether allergies are increasing infrequency and why that might be
Speaker 3: sort of unifying all of this, and then next week
Speaker 3: I'll pick it back up at how we devised ways
Speaker 3: to deal with the self attack using medications, allergy shots,
Speaker 3: the EpiPen, and so on. Almost universally, allergy or an
Speaker 3: allergic response is described as an overreaction, an exaggerated response
Speaker 3: to an innocuous environmental trigger like pollen, like dustmites, like peanuts.
Speaker 3: Since scientists first characterized allergies in the late eighteen hundreds
Speaker 3: early nineteen hundreds, they referred to the phenomenon as an idiosyncrasy,
Speaker 3: a biological contradiction where our bodies harm us in an
Speaker 3: attempt to protect us. But more recently some researchers have
Speaker 3: called into question two assumptions that underlie this premise of allergy.
Speaker 3: Number one, that this reaction is always an overreaction, and
Speaker 3: number two, that the substances triggering an allergic response are
Speaker 3: truly innocuous.
Speaker 1: Oh, I can't tell you how excited I am about this.
Speaker 1: I read I'm a full disclosure. I read one paper
Speaker 1: that talked about some of the evolutionary hypothesis of the
Speaker 1: worms and things that I was like, this is my
Speaker 1: favorite thing I have ever. Yeah, because you're right, like,
Speaker 1: that is the that is an underlie I said it
Speaker 1: at the very top, this is how we define an allergy.
Speaker 1: And those assumptions no one that I have read or
Speaker 1: spoken with has ever questioned, and I love questioning it.
Speaker 3: It's important, right, Like, yeah, maybe it is an overreaction,
Speaker 3: and it is in some certain situations, like definitely an overreaction,
Speaker 3: as in, it is out of proportion to the threat
Speaker 3: that whatever that thing causes. Right, but maybe not all
Speaker 3: of the time.
Speaker 1: Right, right, There is a there has to be a
Speaker 1: reason that that response exists, exactly, So just calling it
Speaker 1: a straight overreaction makes our immune system seem dumb.
Speaker 3: Right, a little overprotective, like stop helicopter. Yeah, allergies are
Speaker 3: incredibly widespread, and they have grown in prevalence over the
Speaker 3: past century. More on that later. They're so widespread that
Speaker 3: it's difficult to just discard them as a quirk of
Speaker 3: the immune system, as our immune system being dumb, as
Speaker 3: just an overreaction with no benefit to that overreaction. As
Speaker 3: we all know, an extreme allergic reaction can be deadly.
Speaker 3: And while maybe that reaction is just a peculiar aspect
Speaker 3: of our immune system, might it also be that there's
Speaker 3: a very good reason that we still possess it. And importantly,
Speaker 3: are those two scenarios mutually exclusive? Or is it both
Speaker 3: a quirk and an advantage. Since the early days of
Speaker 3: allergy research in the first decades of the twentieth century,
Speaker 3: allergies were labeled a modern disease, a quote unquote pathology
Speaker 3: of progress, the natural consequence of us living what was
Speaker 3: perceived to be increasingly unnatural lives, sedentary lifestyles, spending large
Speaker 3: amounts of time indoors, the growth of cities, consuming processed foods,
Speaker 3: using chemicals in the home and the environment, and so on.
Speaker 3: Allergies are not the only disease said to result from
Speaker 3: industrialization and develop If you remember back to our gout episode,
Speaker 3: that was another one. Yeah, And in the case of allergies,
Speaker 3: there might be something to it. So Aarin you talked
Speaker 3: about how when someone is exposed to an allergen like
Speaker 3: a DustMite, their body begins producing IgE antibodies, which is
Speaker 3: part of what triggers this rapid cascade of symptoms. As
Speaker 3: it turns out, our body ramps up production of IgE
Speaker 3: in response to another external threat helminth parasites, so dust, MTE,
Speaker 3: hookworm very similar initial responses. One major difference, though, is
Speaker 3: in the long term in people who are chronically infected
Speaker 3: with helminth parasites that IgE production eventually scales down and
Speaker 3: the entire inflammatory response is suppressed in part by the
Speaker 3: parasite itself, which allows these parasites to kind of fly
Speaker 3: under the radar. That suppression doesn't happen in an allergic response. Instead,
Speaker 3: it can just ramp up and up and up until anaphylaxis.
Speaker 3: And so, when researchers described IgE antibodies in nineteen sixty
Speaker 3: seven and began linking them to different exposures to things
Speaker 3: like allergies like parasites, a hypothesis emerged that we have
Speaker 3: this exaggerated allergic response and increasing rates of allergies in
Speaker 3: regions where parasitic infections are low because those parasites are
Speaker 3: not suppressing the immune system. So fewer parasites, more allergies,
Speaker 3: and more parasites, fewer allergies. Essentially, the hypothesis goes improved
Speaker 3: sanitation and treatments for parasites reduced exposure to those parasites,
Speaker 3: which makes our board immune system go into overdrive overreacting
Speaker 3: to any stimulus, aka the hygiene hypothesis or the old
Speaker 3: friends hypothesis. Now, this might be part of what's going on,
Speaker 3: because some studies show that regions with higher rates of
Speaker 3: chronic parasite infestation tend to have lower rates of allergy,
Speaker 3: and in experiments using mice, those chronically infected with helmets
Speaker 3: are protected from developing allergies. Pretty compelling evidence. Also, some
Speaker 3: of the genes associated with asthma are also associated with
Speaker 3: increasing susceptibility to some parasite infections, so these genes might
Speaker 3: make you both more likely to develop asthma and more
Speaker 3: susceptible to parasite infections. The hygiene hypothesis does have some
Speaker 3: compelling support when it comes to allergies or allergy like diseases,
Speaker 3: but in recent decades some researchers are starting to question
Speaker 3: whether it's the only thing going on. If you look
Speaker 3: at the vast array of substances that trigger an IgE response,
Speaker 3: only a tiny portion of them are helmets. The rest
Speaker 3: are various nuts, animal products, venoms, chemicals, so very many
Speaker 3: different things that we encounter regularly that are not helmints,
Speaker 3: that are not parasites.
Speaker 1: Not just worms.
Speaker 3: Yeah, if the IgE response evolved in response to helminth
Speaker 3: infections alone, why can it be so deadly? Wouldn't that
Speaker 3: have been selected against at some point and it's hundreds
Speaker 3: of millions years old evolutionary history, because the IgE response
Speaker 3: is very old, not if the benefits outweigh the costs,
Speaker 3: not if there's a reason to maintain it. As to
Speaker 3: what that reason could be. How do toxins sound?
Speaker 1: Love toxins?
Speaker 3: There?
Speaker 1: And you know that?
Speaker 3: I know you do? I know you love? You love
Speaker 3: a toxicologist. You love toxins?
Speaker 2: I do.
Speaker 3: In nineteen ninety one, Marjorie Profit introduced the toxin hypothesis
Speaker 3: of allergy, and this hypothesis suggests that the IG mediated
Speaker 3: allergic response evolved to protect us from immediate danger posed
Speaker 3: by toxins. So a strong IgE allergic response like you
Speaker 3: described AARON is usually very rapid onset, generally speaking within
Speaker 3: seconds or minutes of exposure, and it's often accompanied by
Speaker 3: things like a sudden drop in blood pressure, vomiting, tearing, diarrhea, coughing,
Speaker 3: all things that would help to expel a toxic substance
Speaker 3: or blow it down from reaching vital organs.
Speaker 1: Oh that is such an interesting Oh how did I
Speaker 1: never think about that?
Speaker 3: I how did? Like it's amazing, It's just like, oh yeah, this.
Speaker 1: Is sort of like in your eye. Your body's like
Speaker 1: get it out. Of your eyes, watering the heck out
Speaker 1: of it.
Speaker 3: Right, and allergies do the same things.
Speaker 2: Yeah.
Speaker 1: Oh, I hope there's support for this hypothesis because I
Speaker 1: like it.
Speaker 3: It's fascinating. Yeah, And you know I was asking in
Speaker 3: the biology section. Okay, Well, the IgE response versus other
Speaker 3: types of antibody responses and the allergic response, This IgE
Speaker 3: mediated response is very different than that caused by exposure
Speaker 3: to a pathogen like a virus or bacterium, and this
Speaker 3: allergic response wouldn't really be effective against those infections, which
Speaker 3: our immune system deals with by killing rather than expelling,
Speaker 3: which is what it does to allergens and multicellular parasites.
Speaker 3: Huh uh huh. Profit suggests that some of the allergens
Speaker 3: that we think of as innocuous, like pollens like hay
Speaker 3: dust or shellfish, may not be as harmless as they seem.
Speaker 3: Pollens contain phenolic acids or alkaloids, both of which can
Speaker 3: cause organ or nerve damage. Hay Dust can be contaminated
Speaker 3: by pathogenic fungal spores, and shellfish can have toxins from
Speaker 3: algae or plankton.
Speaker 1: Fung i. Think fungi are are are not well respected
Speaker 1: in this regard in their they trigger a similar especially
Speaker 1: some like asprogillis and things like that that commonly can
Speaker 1: infect like grains and blah blah blah. Yeah, sorry, but
Speaker 1: I love this. I'm really excited.
Speaker 3: Yeah. No, And there's also a lot of like I
Speaker 3: am not getting into asthma here because we did an
Speaker 3: asthma right episode, and so there's there's a that's a
Speaker 3: whole separate literature in many ways, but there are links between.
Speaker 3: Like a lot of these papers that talk about the
Speaker 3: evolution of allergies also group asthma into that, which is
Speaker 3: entirely reasonable.
Speaker 1: Like we talked about a topic disease.
Speaker 3: And there have been a lot of links with asthma
Speaker 3: and fungus as well a fungal exposure. So yeah, super interesting.
Speaker 3: But being able to rapidly recognize and deal with these
Speaker 3: toxic threat that's like these alkaloids, like these toxins from
Speaker 3: algae that could be vital to our survival both from
Speaker 3: an immunological standpoint as well as just us experiencing that
Speaker 3: deeply allergic response and wanting to avoid exposure in the future.
Speaker 3: Are allergies a signal to us? Do they teach us
Speaker 3: which plants or foods to stay away from.
Speaker 1: Arin I I can't tell you how much I love
Speaker 1: this idea because you know what it feels like to me.
Speaker 1: It feels like the difference between like what is a
Speaker 1: weed and what is a desirable plant? Mm hmm, like
Speaker 1: our allergies responses to things that they shouldn't be, or
Speaker 1: actually are they responding to something that we should be
Speaker 1: because we shouldn't be having so much grap like you know.
Speaker 2: What I mean?
Speaker 3: I just yeah, oh.
Speaker 1: I wow, this is mind blowing to me.
Speaker 3: I think if me too, because I had never really
Speaker 3: considered I always was just like innocuous substance overreaction.
Speaker 1: Yeah are cases. Yeah, but peanuts can be contaminated with
Speaker 1: funk a lot.
Speaker 3: Ants, and they also might be like these different foods
Speaker 3: or these different allergens might be the compound structure itself
Speaker 3: could be similar to similar to something else, something that
Speaker 3: is much more toxic.
Speaker 1: Right what you're saying too?
Speaker 3: Yeah, yeah, it's an interesting idea. We love it. But
Speaker 3: is their support for there? I hope so yes there is,
Speaker 3: And is it like the most compelling support in the world.
Speaker 3: I don't know. There are my studies, lab studies, et cetera.
Speaker 3: But still but still still so. There are a couple
Speaker 3: studies from twenty thirteen that found that mice that had
Speaker 3: previously been exposed to venom. One study used a beasting
Speaker 3: and the other used snake venom. The mice that had
Speaker 3: been previously exposed were more likely to survive a big
Speaker 3: second dose of venom that should have been fatal compared
Speaker 3: to those who did not receive that initial dose, suggesting
Speaker 3: that that big IgE response in the second exposure might
Speaker 3: be helpful rather than detrimental. And of course this doesn't
Speaker 3: explain why a beasting in humans can lead to a
Speaker 3: fatal anaphylaxis response, because clearly that is very helpful. Some
Speaker 3: researchers suggest it's too much of a good thing, kind
Speaker 3: of like sickle cellnemia and malaria. Right, having one copy
Speaker 3: of the gene protects you from malaria, but two copies
Speaker 3: leads to disease. While most experimental studies looking at this
Speaker 3: toxin hypothesis have focused on things like beastings, other epidemiological
Speaker 3: studies have taken a broader view of toxins and how
Speaker 3: they can harm us, such as cancer. There's no clear
Speaker 3: pattern when it comes to allergies in cancer, but some
Speaker 3: studies have shown that higher rates of allergies is linked
Speaker 3: to lower rates of cancer. But I would imagine that
Speaker 3: that depends on the type of cancer and the other
Speaker 3: lifestyle and genetic factors.
Speaker 1: Right, And is it environmental? No, that's interesting and weird
Speaker 1: because there's so much environmental cancer exposure blah blah blah.
Speaker 1: And then environmental allergy. Oh, that's so weird and interesting.
Speaker 3: Yeah, isn't it interesting? And so while the hygiene hypothesis
Speaker 3: or the old friends hypothesis and the toxin hypothesis of
Speaker 3: allergy can help to fill in some of the gaps
Speaker 3: as to the why of allergies, the complete picture is
Speaker 3: not yet clear. Yeah, how can we take what we
Speaker 3: know about helmets and allergies and apply it to treatment? Right?
Speaker 3: Can we make an allergen tree of life to predict
Speaker 3: the groups of antigens that people are likely to be
Speaker 3: sensitive to? Does it have to do with evolutionary distance?
Speaker 3: The farther away something is on that evolutionary tree of life?
Speaker 3: Does that mean that we're more likely to initiate an
Speaker 3: immune response to it? The future of allergy research is exciting,
Speaker 3: and to understand where we go from here, we also
Speaker 3: have to take a look at where we've come from. Yeah,
Speaker 3: are allergies changing and if so, what is driving that change.
Speaker 3: Today allergies are one of the most common diseases across
Speaker 3: the world, affecting ten to thirty percent of the global
Speaker 3: population and up to fifty percent of people in some regions.
Speaker 3: For years, that number has been on the rise, which
Speaker 3: is why you'll hear people refer to this as an
Speaker 3: allergy epidemic, sometimes broken down into two waves, the first
Speaker 3: being respiratory allergies like hay fever and the second being
Speaker 3: food allergies. Of course, allergies themselves are not a new phenomenon.
Speaker 3: IgE antibodies evolved around three hundred million years ago, allowing
Speaker 3: for this allergic response, and we have evidence of allergies
Speaker 3: from ancient times, descriptions of fatal beastings what could be
Speaker 3: allergic rhinitis, and of course asthma. But the heyday of
Speaker 3: allergy awareness pun intended, really only began in the eighteen hundreds,
Speaker 3: with the first description of hay fever in eighteen nineteen
Speaker 3: by John Bostock and the first case series published in
Speaker 3: eighteen seventy three by Charles Blackley. These observations didn't seem
Speaker 3: to be a case of cool. There's finally a name
Speaker 3: associated with this condition that we've noticed for a long time,
Speaker 3: but a recognition of a truly emerging phenomenon.
Speaker 1: Huh.
Speaker 3: Like one summer day in eighteen seventy five, your nose
Speaker 3: starts running and your eyes start itching, and you're sneezing
Speaker 3: all over the place, and you find all of your
Speaker 3: friends and family are similarly affected, and you're just complaining
Speaker 3: about it. You form groups to talk about it. But
Speaker 3: just a few years ago, no doctor had ever heard
Speaker 3: of such a thing. The sudden increase in hay fever
Speaker 3: in Europe and North America around the late eighteen hundreds
Speaker 3: resulted from changes in agricultural practices, changing which crops were planning,
Speaker 3: planting more pollinaceous. If that's a word, it's not. I
Speaker 3: don't think my word document is telling me there's a
Speaker 3: red underline. It's angry, but it's the only thing I
Speaker 3: could think of. Pollinaceous grass varieties to feed the growing
Speaker 3: cattle herds, and an increase in farmed land in the US,
Speaker 3: leading to higher ragweed growth. This marks the beginning of
Speaker 3: the first wave of the allergy epidemic.
Speaker 1: Ladies, it's eighteen hundreds. Okay, yeah, that's way further back.
Speaker 1: I mean it feels like I should have expected, but
Speaker 1: like I don't know.
Speaker 3: And it's hard because like people generally associate asthma with
Speaker 3: the first wave, and that's like nineteen sixties is really
Speaker 3: when those cases started to super ramp up. But if
Speaker 3: we're talking about allergic rhinitis, it really is like eighteen
Speaker 3: eighties roughly.
Speaker 1: Interesting.
Speaker 3: There had been in decades previous descriptions here and there,
Speaker 3: but not like sudden recognition of this, whoa everyone is experiencing?
Speaker 1: Interesting.
Speaker 3: Yeah. In nineteen o six, Clemens von Pirquet coined the
Speaker 3: term allergy to describe the hypersensitivity reaction in serum sickness.
Speaker 3: So when someone was given anti serum, let's say, for
Speaker 3: like diphtheria, to treat their diptheria infection. But they had
Speaker 3: extracted that anti serum from an animal like a horse. Yeah,
Speaker 3: they had, Yeah, caused the infection, got the antibodies all that.
Speaker 3: Then you inject an episode. Interesting, we should but yeah,
Speaker 3: then people got real sick from them. And by that time,
Speaker 3: so around the early nineteen hundreds, other work had shown
Speaker 3: how anaphylaxis can happen, how animals negatively react to the
Speaker 3: introduction of a foreign substance, and the concept of an
Speaker 3: allergic response mediated by your immune system began to gain
Speaker 3: traction because up to this time, germ theory had a
Speaker 3: pretty tight hold on many explanations of disease, and so
Speaker 3: the recognition that it was actually our immune systems causing
Speaker 3: these allergic responses, like the call is coming from inside
Speaker 3: the house, took a bit of time to gain traction.
Speaker 3: Von Pirquet combined a bunch of observations from hyposensitivity, hypersensitivity,
Speaker 3: food allergy, hay fever, beasting reactions, serum sickness, and so
Speaker 3: on to create this organized concept of allergy as it
Speaker 3: relates to immunity, and it created momentum for more research
Speaker 3: in the area, even if it was initially papooed by
Speaker 3: like a lot of his peers.
Speaker 1: Classic Classic.
Speaker 3: The first decades of the nineteenth century saw the formation
Speaker 3: of allergy research groups and clinics across the globe, and
Speaker 3: as far back as nineteen thirty six, the phrase, quote unquote,
Speaker 3: the allergy epidemic was used. Wow, right, much earlier than
Speaker 3: I thought.
Speaker 1: Yeah.
Speaker 3: In nineteen forty six, ragweed hay fever was such a
Speaker 3: huge problem in New York City. That City Council started
Speaker 3: a ragweed elimination campaign. The tides were changing and fast. Asthma,
Speaker 3: which prior to nineteen sixty had been considered a rare disease,
Speaker 3: shot up in incidents, doubling in Swedish Army recruits from
Speaker 3: nineteen seventy one to nineteen eighty one huge rise, as
Speaker 3: did hospital admissions for the condition, which increased tenfold between
Speaker 3: nineteen sixty five and nineteen eighty In Australia, the UK,
Speaker 3: New Zealand, Canada, and the US tend for afterasthma. In
Speaker 3: the nineteen seventies, after the discovery of IgE, researchers observed
Speaker 3: a sharp increase in allergen specific IgE antibodies against environmental allergens,
Speaker 3: growing to over fifty percent of the population in some
Speaker 3: regions like I mentioned, and the second wave of the
Speaker 3: allergy epidemic. Food borne allergies began much more recently. Around
Speaker 3: nineteen ninety is most most papers I read, and that's
Speaker 3: the same time that asthma case is actually plateaued. One
Speaker 3: large study found that between nineteen ninety seven and two
Speaker 3: thousand and eight, allergies to peanuts and tree nuts tripled, tripled, huge. Yeah.
Speaker 3: Reports from Australia indicate a tenfold increase in referrals to
Speaker 3: food allergy specialists and a five fold increase in hospital
Speaker 3: admissions for food related anaphylaxis. This is not just a
Speaker 3: matter of doing a better job of recognizing these allergies, No.
Speaker 1: Especially not with food allergies because the reaction is usually
Speaker 1: so severe.
Speaker 3: Exactly. Yeah, what is driving this explosive rise? Yeah, that
Speaker 3: is the billion dollar question. We don't fully know, of course,
Speaker 3: here is what we do know. We know that while
Speaker 3: this is a global rise, the highest increases are seen
Speaker 3: in more industrialized countries. For instance, following the reunification of
Speaker 3: East and West Germany in nineteen eighty nine, prevalence of
Speaker 3: allergy shot up in East Germany, where it have been
Speaker 3: much lower in previous decades.
Speaker 1: I think that's one of the most interesting examples because
Speaker 1: it's so like discrete and like the regions are so
Speaker 1: close to each other, so it's like not like what
Speaker 1: is it because it's not just like natural environment exposure
Speaker 1: clearly like.
Speaker 3: Weather, right, pollen is not does not respect the Berlin
Speaker 3: exactly yeah. Yeah, And on average, allergies are twenty times
Speaker 3: more common in affluent quote unquote westernized countries compared to
Speaker 3: those with lower incomes. And we know that this rise
Speaker 3: is not limited to allergies or asthma, but it also
Speaker 3: is seen in other autoimmune or immune mediated diseases. We
Speaker 3: know that these diseases are not rising all at the
Speaker 3: same time, or in the same place or at the
Speaker 3: same pace, which could suggest different mechanisms behind the rise
Speaker 3: in each of them. And this has been you to
Speaker 3: challenge the old friends or the hygiene hypothesis, since countries
Speaker 3: that saw the biggest rise in allergies only did so
Speaker 3: beginning really in the nineteen sixties, which was around forty
Speaker 3: years after major sanitation changes would have reduced waterborne pathogens
Speaker 3: and anti helmath campaigns had reduced parasite burden to almost nothing.
Speaker 3: So what could be going on? Most of the predominant
Speaker 3: ideas fall under the hygiene hypothesis or the old friends
Speaker 3: hypothesis or the biodiversity hypothesis, which are kind of like
Speaker 3: more recent offshoots, and both of these suggest that our
Speaker 3: allergies are a result of us not being exposed to
Speaker 3: as many or as diverse microbes and parasites that we
Speaker 3: used to throughout our evolutionary history. Why that would lead
Speaker 3: to more allergies depends on who you ask. Maybe it's
Speaker 3: that with decreasing family size, kids are not coming into
Speaker 3: contact with as many germs at a young age, although
Speaker 3: some childhood pathogens like RSV are positively associated with developing allergies.
Speaker 3: So it's like the right germs, right, right, Which germs
Speaker 3: that's the Yeah, Yeah, it's layers, compilators.
Speaker 1: It's almost like our immune system is complicated. I don't
Speaker 1: know what.
Speaker 3: Maybe it's that our use of antibiotics at an early
Speaker 3: age disrupts our gut microbiome and primes us to develop allergies.
Speaker 3: Maybe it's that we spend more time inside and sedentary
Speaker 3: early childhood. Exposure to pets or farm animals seems to
Speaker 3: reduce the risk of allergies, and exercise reduces allergic inflammation.
Speaker 3: I found a study looking at babies born during COVID
Speaker 3: lockdown in twenty twenty, and this study found higher rates
Speaker 3: of allergies in that cohort. So it's like, again, the
Speaker 3: limited exposure to the outside world. Maybe it's the chemicals
Speaker 3: and our soaps, food packaging, microplastics, pollution, ozone, cigarette smoke,
Speaker 3: that disrupts our protective epithelial barriers and sends our immune
Speaker 3: systems into overdrive. If you think about it, the allergic
Speaker 3: response is kind of like a hail marry last resort
Speaker 3: option to protect us from toxins. After our skin or
Speaker 3: skin microbiota, after our guts or gut microbiota, our lungs
Speaker 3: and lung microbiota, lets it get through, right like, there
Speaker 3: are so many other layers of protection, and then maybe
Speaker 3: it's that once it makes it past all those layers,
Speaker 3: then we have this last ditch effort to protect us
Speaker 3: from whatever perceived tosin there is. And if those layers
Speaker 3: are continually broken down by some of the things that
Speaker 3: we encounter in our everyday lives, like processed foods, you know,
Speaker 3: all of these different things that all combine together to
Speaker 3: increase permeability of those barriers, does that then lead to
Speaker 3: increase allergy?
Speaker 1: And I think that's one of the things that makes
Speaker 1: the there's a there's a lot of research being done
Speaker 1: on like is exzema and the breakdown of your skin
Speaker 1: barrier that happens with egzema. Does it also result in
Speaker 1: this abnormal presentation of these toxins or of these allergens
Speaker 1: right where it's like, typically you shouldn't be able to
Speaker 1: be exposed to, say, cat dander through your skin because
Speaker 1: your skin should be able to keep cat dander out.
Speaker 1: But if it gets in that way, does that predispose
Speaker 1: you to And cat dander might be a crappy example,
Speaker 1: I don't know, but like, if you get peanut on
Speaker 1: your skin, peanut protein shouldn't be able to make it
Speaker 1: through your skin. If it does, does that trigger your
Speaker 1: immune response to think that it is something that is pathogenic?
Speaker 1: So that's one of those kind of ideas.
Speaker 3: Right, Yeah, novel exposure roots exactly these things because of
Speaker 3: a decreased barrier in permeability.
Speaker 1: Which is why I think, like the AlphaGo story is
Speaker 1: so interesting in that, like because it applies so much
Speaker 1: to that. So yeah, I don't know, Yeah, it's interesting.
Speaker 2: Aaron.
Speaker 3: Uh, we don't have a single simple answer for why
Speaker 3: tree nut allergies suddenly exploded in the past few decades,
Speaker 3: although I do think that part of it is, at
Speaker 3: least from my reading, our response to them initially how
Speaker 3: it was like, don't expose anymore. If there's the slightest
Speaker 3: bit of reaction, then it sort of Yeah.
Speaker 1: I am really curious. This is jumping so far ahead.
Speaker 1: I'm sorry, but I'm so curious to see what is
Speaker 1: going to happen in the next decade. Like with like,
Speaker 1: because it was our generation that has really high rates
Speaker 1: of things like peanut and tree nut and all these
Speaker 1: food allergies. And it was our generation that very much
Speaker 1: was told by physicians, do not expose your children because
Speaker 1: we don't want them to develop allergies. And it turns out,
Speaker 1: against spoilers, that that was exactly the wrong advice. And
Speaker 1: now we know that because of these phenomenal studies, and
Speaker 1: so early introduction is now the recommendation. So what are
Speaker 1: rates going to be like in kids in five ten years.
Speaker 1: I'm super curious about all this, like how the epidemiology
Speaker 1: is going Is it going to change, I don't know,
Speaker 1: is it.
Speaker 3: To help you? And you know, like we probably won't
Speaker 3: ever have one simple, unifying answer to this. I agree,
Speaker 3: and I will say also, like the hygiene hypothesis or
Speaker 3: the old friends hypothesis, or the toxin hypothesis or the
Speaker 3: epithelial barrier hypothesis, these things aren't attempting to explain away
Speaker 3: all cases of allergies or autoimmune diseases with one bottom line. Instead,
Speaker 3: what they're doing is highlighting patterns of allergy, pointing out
Speaker 3: where we can look next. If it is certain detergent
Speaker 3: compounds causing a rise in asthma because of increased skin permeability,
Speaker 3: why and how. If it is a disrupted microbiome, what
Speaker 3: about it makes it disrupted? And how can we restore balance.
Speaker 3: If it is epigenetic effects, what are those prenatal exposures
Speaker 3: that increase someone's chance of developing allergies? While the comp
Speaker 3: tx nature of allergies makes all of this seem so overwhelming,
Speaker 3: the truth is that people are doing incredible research to
Speaker 3: answer these questions, to get at the underlying triggers of
Speaker 3: different allergies, and it really seems like we're slowly going
Speaker 3: to be able to put the puzzle pieces together, at
Speaker 3: least for some pictures right, for some bits of the allergy,
Speaker 3: and come up with better ways to understand, prevent and
Speaker 3: treat allergies. I love it so now, Aaron, I'll turn
Speaker 3: it over to you to tell us where we are
Speaker 3: with allergies around the world today.
Speaker 1: I'll give it my best shot right after this. So
Speaker 1: you told us already, Aarin, that all of these allergic disorders,
Speaker 1: from hay fever, from seasonal allergies, from food allergies. They're
Speaker 1: all on the rise, that is certainly true, and they
Speaker 1: have been for a while longer than I realized, apparently.
Speaker 1: When it comes to I'll break this down into like
Speaker 1: the allergic rhinitis, which is more you think of as
Speaker 1: the hay fever, the seasonal allergies, it's the runny nose
Speaker 1: and the blah blah blah running eyes. And I don't
Speaker 1: say blah blah blah to discount it because it has
Speaker 1: pretty significant effects on people's lives, as we'll see. But
Speaker 1: a paper from the Lancet from twenty eleven, which is
Speaker 1: old now, estimated that four hundred million people worldwide are
Speaker 1: affected by allergic rhinitis, and this number is likely higher
Speaker 1: today as this, like all allergies, has continued to increase.
Speaker 1: But this varies a lot across the globe. And while
Speaker 1: most of allergic rhinitis develop in like child or teen years,
Speaker 1: sometimes they don't. There's plenty of adults who don't develop
Speaker 1: seasonal or environmental allergies until much later in life. But overall,
Speaker 1: in some areas of the globe, prevalence is as high
Speaker 1: as like seventeen to twenty percent. Those seem to be
Speaker 1: the highest percentage numbers that I saw and across the board,
Speaker 1: even though in the International Study of Asthma and Allergies
Speaker 1: in Childhood, which is also now old because the Phase
Speaker 1: three study finished in like the early two thousands, but
Speaker 1: in this study, the rates of allergic rhinitis were actually
Speaker 1: greatest in Latin America and African countries. But even there
Speaker 1: the prevalence was higher in urban areas compared to rural areas,
Speaker 1: and that pattern is true pretty much across the globe.
Speaker 1: Allergic rhinitis also has pretty significant burdens on our healthcare system.
Speaker 1: In the nineties, way back in the nineties, it was
Speaker 1: estimated to cost one point nine billion US dollars every year,
Speaker 1: and that increased to three point four billion in the
Speaker 1: early two thousands. And that's not even counting indirect costs,
Speaker 1: of which there are enormous indirect costs, things like miss school,
Speaker 1: missed work. Allergic rhinitis especially can result in things like
Speaker 1: poor sleep or sleep apnea. It can contribute which can
Speaker 1: then lead to fatigue, memory problems, mood changes. It can
Speaker 1: make school harder for kids, like, it is not a
Speaker 1: minor like we might think of it as, oh, it's
Speaker 1: just a runny nose. It is not just a running nose. Right,
Speaker 1: Food allergies we have much credier data for.
Speaker 3: Which is interesting to me for some reason. I don't
Speaker 3: know why.
Speaker 1: Yeah, I think I think it's we have credit or
Speaker 1: like global data.
Speaker 3: Okay, but no doubt.
Speaker 1: Food allergies are absolutely on the rise. In some countries,
Speaker 1: as much as ten percent of children have at least
Speaker 1: one food allergy. And food allergies are especially interesting because
Speaker 1: for some foods, up to like seventy or eighty percent
Speaker 1: of kids will outgrow their food allergy, and those foods
Speaker 1: tend to be things like egg and milk, but things
Speaker 1: like peanuts and tree nuts tends to be much less
Speaker 1: likely that kids will outgrow it. Usually it's twenty percent
Speaker 1: or less of kids with a peanut or tree nut
Speaker 1: allergy will outgrow them. Then there's other food allergies like
Speaker 1: shellfish and fish, which not only do we have less
Speaker 1: data for the idea that early introduction can prevent sensitization
Speaker 1: for things like fish and shellfish, but it's also more
Speaker 1: likely that people don't develop those allergies until adulthood.
Speaker 3: Why why, Oh you know, I have a quick question. Actually, yeah,
Speaker 3: dose and relationship to response one. You know, one peanut,
Speaker 3: how much peanut or almondors shellfish, shrimp tail?
Speaker 1: You know. So yeah, maybe it's worth talking a little
Speaker 1: bit in more detail about this. So the study that
Speaker 1: showed that early exposure can reduce the risk of peanut allergy,
Speaker 1: the big one was called Leap Learning Early about Peanut Allergy,
Speaker 1: and then there was another one I think called EAT
Speaker 1: and I forget what that acronym stands for. But these
Speaker 1: were like really landmark studies that showed that early exposure
Speaker 1: and early exposure meant like four months of life, but
Speaker 1: definitely earlier than eleven months of life. So before a
Speaker 1: baby turns one year old, you start with exposure to peanuts,
Speaker 1: and you have to have persistent exposure. So it's not
Speaker 1: like give them peanuts one time and then you're good.
Speaker 1: These studies were consistent exposure, like two to three times
Speaker 1: a week every week for the first five years of life. Okay, wow,
Speaker 1: but in those kids and in these studies, they took
Speaker 1: kids who were high risk, kids who either had severe
Speaker 1: eggzema or had a known allergy to egg or In
Speaker 1: some of the studies it was kids who had a
Speaker 1: family history of peanut allergy, so these were high risk
Speaker 1: kids because we know that there's genetics in these associations.
Speaker 1: So in those kids, the reduction in risk of peanut
Speaker 1: allergy was like seventy to eighty percent. It was massive,
Speaker 1: massive reduction in risk, and so across the board. Now
Speaker 1: the recommendation is early exposure, but it has to be
Speaker 1: that consistent exposure, so it's not like necessarily a one
Speaker 1: time dose, like give this much peanut. It's really like
Speaker 1: start small, but continued exposure, so like a little peanut
Speaker 1: on the finger when they're a tiny baby, continuing that
Speaker 1: until they're like eating peanut butter and their oatmeal like
Speaker 1: a couple times a week when they're kids, and that
Speaker 1: significantly decreases the risk. And so that data has now
Speaker 1: been extrapolated to a lot of the foods that the
Speaker 1: earlier exposure to all of the main allergenic foods, and
Speaker 1: in the US, those foods are wheat, soy, tree nuts, peanuts, milk, egg, oh, crap,
Speaker 1: I should have written all of these town fish, shellfish,
Speaker 1: and now sesame. That's the early net. The newest edition.
Speaker 1: So early and consistent exposure to all of those is
Speaker 1: what's now recommended to try and prevent food allergies.
Speaker 3: And we don't know what happens when someone just develops
Speaker 3: an allergy, a food allergy at the age of thirty five?
Speaker 1: No, is it all alpha calerin? I don't know.
Speaker 3: It all comes down to alpha cal.
Speaker 1: Is it the ticks?
Speaker 3: No?
Speaker 1: Yeah, I don't know. Is it a threshold thing like
Speaker 1: we kind of talked about, Is it that maybe they
Speaker 1: had some level of it? Here's the other thing, arin,
Speaker 1: Oh my gosh, there is a proportion of the population
Speaker 1: who if you test them, they develop these IgE antibodies, aka,
Speaker 1: they are sensitized to various things, be they aero allergens
Speaker 1: like cat dander. Cat dander is a good example because
Speaker 1: if you test kids who live in homes with cats,
Speaker 1: a higher percentage of them will have a degree of
Speaker 1: sensitization at a certain age, but a lower percentage of
Speaker 1: them will be allergic, will have that allergic response to kings.
Speaker 1: And so yeah, so like what is it about sensitization
Speaker 1: versus then who of those kids who are sensitized actually
Speaker 1: then will have allergies. We don't exactly know, so is
Speaker 1: there is that what it is for adults who develop
Speaker 1: say a shellfish allergy later in life, that maybe they
Speaker 1: were a little bit sensitized, but it wasn't until that
Speaker 1: built up enough in their system that they had an
Speaker 1: allergic response.
Speaker 3: I don't know, okay, but the quantity of exposure, or
Speaker 3: the amount of allergen that they're exposed to, can lead
Speaker 3: to really different responses than some people. Where some people
Speaker 3: are like even the most minute amount can lead to
Speaker 3: these horrible reactions, whereas other people can have there's a
Speaker 3: threshold where that causes Yes, I guess, okay, one hundred percent.
Speaker 1: Yes, that is absolutely true, and we don't understand why. Okay, ah,
Speaker 1: so yeah, that's like what we know of. When it
Speaker 1: comes to the most severe outcomes, that is anaphylaxis. We
Speaker 1: again don't really have great data here because most of
Speaker 1: the data that we have is on hospital admissions for anaphylaxis,
Speaker 1: and not all people with anaphylaxis have to actually be
Speaker 1: admitted to the hospital. And also it's not always allergies
Speaker 1: that cause anaphylaxis. But at least in some of the
Speaker 1: papers that I found, it's estimated that about zero point
Speaker 1: three percent of the population of Europe will experience anaphylaxis
Speaker 1: at some point in their lives. Wow, okay, yeah, higher
Speaker 1: than I expected. And the data across the board is
Speaker 1: that especially in most high income countries, which is where
Speaker 1: we have data, incidents of anaphylaxis is increasing, which makes
Speaker 1: sense because allergies across the board are increasing. Anaphylaxis, especially
Speaker 1: due to food born triggers, is increasing. Anaphylaxis due to
Speaker 1: alpha gu specifically is increasing big time. But mortality does
Speaker 1: not seem to be increasing, except in Australia, which some
Speaker 1: of the data has had increases in mortality associate with anaphlexis.
Speaker 3: So does that mean that we have developed better tools
Speaker 3: or is that a tune in for next week to
Speaker 3: find it?
Speaker 1: That's a tune in for next week to find out
Speaker 1: how do we treat it? That was my segue erin
Speaker 1: you guessed it?
Speaker 3: I love it.
Speaker 1: So yeah, that's allergies for now, but I can't wait
Speaker 1: for next week to hear about how we figured out
Speaker 1: how to treat these things, and then we'll talk about
Speaker 1: how we treat them and what our thoughts are about
Speaker 1: preventing them in more detail next week.
Speaker 3: But until then, if you would like to learn more
Speaker 3: about things like the how allergies work, the IgE mediated response,
Speaker 3: the evolution of allergies, the rise and allergies. We've got sources.
Speaker 1: For you, so many.
Speaker 3: I have so many, and I highlighted too right here
Speaker 3: just because to list them all out would take another
Speaker 3: ten minutes. So there's one by Dasher and Fernandez from
Speaker 3: twenty nineteen titled Allergy in an Evolutionary Framework that's all
Speaker 3: about the evolution of allergies. And then by Actus from
Speaker 3: twenty twenty one, does the epithelial barrier hypothesis explain the
Speaker 3: increase in allergy, autoimmunity, and other chronic conditions?
Speaker 1: Fascinating stuff for the biology of allergies. Boy, do I
Speaker 1: have plenty of rabbit holes that you can go down,
Speaker 1: But I'm going to shout out like four or five
Speaker 1: main papers that are really high level overviews. One is
Speaker 1: from the New England Journal of Medicae in from two
Speaker 1: thousand and one, so it's old but still good, and
Speaker 1: that is just called Allergy and Allergic Diseases. There was
Speaker 1: one on titled food Allergy from Nature Reviews Disease Primers
Speaker 1: from twenty eighteen, and another one titled food allergy from
Speaker 1: the Lancet two thousand and two, and then two on
Speaker 1: allergic rhinitis, one titled Allergic Rhinitis from the Lancet twenty
Speaker 1: eleven and one titled Allergic Rhinitis Definition, Epidemiology, path of Physiology,
Speaker 1: Detection and Diagnosis from the Journal of Allergy and Clinical
Speaker 1: Imminology from two thousand and one. There's so many There's
Speaker 1: so many more. We're not going to read them all,
Speaker 1: but you can find them on our website, This Podcast
Speaker 1: will Kill You dot com under the episodes tab for
Speaker 1: this episode and everyone we've ever done, they're all there.
Speaker 3: Thank you again, Caitlin so much for sharing your story
Speaker 3: with us and really helping to illustrate that allergy to
Speaker 3: environmental allergens is not just a running nose.
Speaker 1: No, it means so much more. Thank you so much
Speaker 1: for being willing to take the time and to share
Speaker 1: your story with us and all the listeners. We really
Speaker 1: appreciate it.
Speaker 3: Thank you to Bloodmobile for providing the music for this
Speaker 3: episode and all of our episodes.
Speaker 1: Thank you to Leona Scuilatchi and Tom Bryvocal for the
Speaker 1: audio mixing.
Speaker 3: Thank you to everyone at Exactly Right.
Speaker 1: And thank you to you listeners. We hope you enjoyed
Speaker 1: this episode and that you're stoked for next week to
Speaker 1: learn even more about allergies. Yeah.
Speaker 3: Why do EpiPens work the way they do?
Speaker 1: I can't wait to find out.
Speaker 3: Yeah, me too, got some reading to do. Thank you
Speaker 3: also to our wonderful, generous, amazing patrons, We really truly
Speaker 3: appreciate your support so much. Thank you, Thank you well.
Speaker 3: Until next time, wash your hands.
Speaker 1: You feel the animals
Speaker 2: U