Ep 161 Allergies Part 1: Pollens, nuts, & bugs

Sometimes it seems like the world is out to get us: bees in our garden, pollen in the air, nuts in our brownies, any number of other things that could trigger an allergic reaction ranging from itchy eyes and a runny nose all the way to anaphylaxis. Why must our bodies react in such over-the-top ways to these seemingly innocuous substances? In the first episode of our two-parter on allergies, we explore that very question. From the biological basis of an allergic reaction to the potential evolutionary significance of allergies, from the history of their discovery to the global status of allergies today, we cover it all. Tune in today!

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Episode Transcript

Speaker 1 (00:00):
My name is Caitlin.

Speaker 2 (00:01):
I'm thirty two years old, and for most of my
life I hadn't experienced severe allergies or allergic reactions to anything,
except for cats sometimes. I went to school in Nebraska,
and after college I got a job in Denver and moved.
The first year living in Denver was awesome. I got
really into all the outdoorsy things that Colorado has to offer,

(00:22):
like camping and hiking and skiing. But about a year
into my time in Denver, in the spring of twenty seventeen,
seasonal allergies and hay fever hit me on like anything
I had ever experienced before. Every day that spring, I remember,
I would wake up with a sore throat, hives, and
swollen eyes. My eyes would have allergic conjunctivitis and chemosis,

(00:44):
which is when tiny bubbles form on the surface of
your eye from all the allergens and pollen in the air.
I had a constant runny nose and couldn't breathe. I
had a lot of sinus infections. I also couldn't hear
very well because of all of the post nasal drip
that would happen and settle in over I was beyond
exhausted all the time and unable to go outside much

(01:04):
at all. Every time I would leave my house, I
would get hot, painful hives on any part of my
skin that was exposed. I remember taking cold showers all
the time to try to keep my hives from spreading
all over my body, and at the time I was
only using over the counter allergy medications, which only helped
a little bit. I worked downtown in an office, and
so riding the train into the office, interacting with coworkers

(01:26):
and clients, and wearing business casual clothing was incredibly uncomfortable
and embarrassing sometimes. And this is all before COVID times,
and I was still really new at my job, so
asking to work from home was a challenge. I was
also really bummed because I couldn't eat a lot of
fruits that grew on trees where you typically eat the skin,
because the pollen grows with the fruit instead of on

(01:48):
the hard outer layer. So fruits like peaches and apples
were off limits because I would break out in hives
on my neck and face and sometimes experience breathing issues.
And sadly, Colorado is famous for their palasaid peaches, and
I could never have them, even though it was my
favorite fruit growing up. Unfortunately, things got exponentially worse the
following fall due to a mold issue in the rental

(02:10):
house that I was living in. I was exposed to
penicillium mold spores, which had a compounding effect on my
already maxed out immune system, and I ended up developing
severe asthma. I was playing roller Derby at the time,
and I remember showing up to practices and scrimmages feeling
like I was breathing through a wet cloth draped over
my nose and mouth and felt like I would pass
out after one warm up lap.

Speaker 3 (02:30):
I was devastated.

Speaker 2 (02:31):
I didn't know what was wrong with me, and I
was trying so hard to get into the sport and
develop a community in my new place, but I was
not able to keep up at all. I ended up
taking a leave of absence to avoid further damage and
started seeking professional help. I had skin testing done in
January twenty eighteen, and it was pretty awful. Almost every
single allergen that they had tested me for came back

(02:53):
with a flaming positive. After this, I was introduced to
my allergist and met my immunotherapy team. I got started
with allergy shots by doing a procedure called a rush
treatment to try to get my body as close to
my maintenance DOWS for allergy shots as soon as possible.
I was not able to finish the entire rush treatment
because my body started to go into shock, which is

(03:13):
actually typical for the procedure. After that, I began regular
allergy shots every three weeks for the next five years.
I was also put on a prescription strength antihistamine, two,
over the counter antihistamines two Inhaler's, and an EpiPen in
the event I went into anaphylaxis. I was not allowed
to eat or touch anything that would cause any sort
of reaction, and I had to avoid being outside on

(03:34):
high pollen days. Springtime was always the worst for me
due to the presence of tree pollen, and I would
always see more intense reactions during that time of year
to my allergy shots. Fortunately, I completed my immunotherapy in
July twenty twenty three and have been pretty good ever since.
I'm still on the prescription strength antihistamine and one of
the over the counter antihistamines for any allergies that might

(03:54):
pop up, as well as both Inhaler's for the now
permanent asthma, but overall things are pretty manageable for me.
I remember asking my allergist, why now, why did allergies
hit me now and here and like this and never
before in my life? And she explained to me that
I'd probably experienced what they call a honeymoon period when
I first moved to Colorado. My body is non reactive

(04:15):
to the new allergens because it had never seen them before,
but almost always a second time around or the following
season that your body encounters the allergen, it overreacts and
produces an excessive histamine response. This whole experience has been
a very long and painful journey, and it took a
huge toll on my mental health at the time. I'm
not entirely sure how long I'll be without allergic reactions,
hopefully forever, but I still get hives from time to time.

(04:38):
Everyone's body reacts differently, and sometimes you become allergic to
new things that you weren't before. Every reaction I do
have now is manageable. My asthma is still very much there,
but I've learned to live with it, and I'm also
really excited to report that I can have feaches and
apples again. My life has been completely changed because of
this experience. I'm so fortunate to have the support that
I do, and I cannot think my Meta Coole team

(05:00):
and my family and my friends enough for taking such
good care of me Throughout those five years. I've learned
so much about something I never even thought twice about
for two thirds of my life that ended up having
a major life altering impact on me. The human body
is so intensely weird in particular sometimes, but I'm so
grateful that I was able to get through this experience
and to be where I am now, even with the

(05:21):
lasting effects it has left me with.

Speaker 3 (06:09):
Ooh, that gosh sounds truly miserable. Yeah, truly miserable.

Speaker 1 (06:15):
Oh my goodness.

Speaker 3 (06:16):
I always think like, oh, yeah, I have seasonal allergies.
Sometimes I barely do. Yeah, I have the hint of.

Speaker 4 (06:23):
A seasonal allergy. And to deal with we have seasonal allergies,
the I know, and to deal with it just like,
oh my goodness.

Speaker 3 (06:34):
Yeah, all yeah, And when it's everywhere, it is ever escapable,
you cannot ever escape it.

Speaker 1 (06:40):
Yeah yeah, you just breathe it in.

Speaker 3 (06:43):
That's brutal. But I'm glad that you're finding some more relief. Now,
thank you so much, Kaylin for sharing your story with us.

Speaker 1 (06:50):
Thank you.

Speaker 3 (06:53):
Hi.

Speaker 1 (06:54):
I'm Aaron Welsh and I'm Aaron Allman Updyke.

Speaker 3 (06:57):
And this is this podcast will Kill You.

Speaker 1 (06:59):
And today we're talking about allergies today and next week
today or next week?

Speaker 3 (07:04):
You know, what do we get ourselves into here?

Speaker 1 (07:07):
Eron the same thing that we always do aeron, which
is a very very large topic. Yeah, yeah, here's the deal,
everyone listening. Here's what it's going to go like. This
week we are going to talk about allergies. I'm going
to call it capital A allergies. That is all of them,
food allergies, seasonal allergies, all of the allergies. What does

(07:30):
that mean? What is an allergy? Even we'll talk about it,
and we'll talk about how we figured out what our allergies,
why do we have them, those kinds of things. Next
week we'll focus on what do you do if you
have allergies? And how did we figure that out? How
do we treat them? And what are some of the options.

Speaker 3 (07:49):
In that respect.

Speaker 1 (07:51):
That's the way that we're trying to split it up.

Speaker 3 (07:52):
We'll see how it goes, I think it will go great.

Speaker 2 (07:54):
Aaron.

Speaker 3 (07:55):
You have nothing to be worried about.

Speaker 1 (07:56):
You.

Speaker 3 (07:56):
You always do an amazing job.

Speaker 1 (07:59):
I'm so she gets nervous every time.

Speaker 3 (08:02):
She's so nervous all the time, and I'm like, you're
you do a great job.

Speaker 1 (08:06):
As soon as we start, thank you. As soon as
we start to record the biology section, my stomach every
time goes like you. So, it's already there, but I'm
looking forward to it.

Speaker 3 (08:19):
I think they're going to be a great couple of episodes.
There's a lot of stuff that we're getting to explore
from sort of this big picture perspective on the energies
that we haven't really although we have covered allergies or
allergy related conditions like asthma in the past. I think
this is a fun opportunity for us to kind of go, Okay,
let's take a step back. What are the patterns that

(08:39):
we see. How does this work across the board?

Speaker 2 (08:42):
Right?

Speaker 1 (08:43):
Really big picture here? Yeah, so yeah, yeah, but before
we can start on that, it's quarantin any time.

Speaker 3 (08:50):
It is, Aaron, what are we drinking this week?

Speaker 1 (08:54):
We're drinking the allergy shot. Yeah, pretty straightforward, pretty straightforward.

Speaker 3 (09:00):
But we won't talk.

Speaker 1 (09:01):
About allergy shots other than this today. We'll talk about
them next week.

Speaker 3 (09:05):
It's true.

Speaker 1 (09:06):
What's in the allergy shot erin?

Speaker 3 (09:07):
You know, it's just a little tropical delight. You know,
it's got some it's got some rum in it. It's
got some tropical fruit juices like some pineapple, some orange.
It's it's delicious and it's a small contained thing, so
you know, it's great. We'll post the full recipe for

(09:29):
the allergy shot quarantine and the non alcoholic placey Berita
on our website. This podcast will Kill You dot Com,
as well as on all of our social media channels,
which if you're not following us on social media, you
really should be, because you know there's some pretty good
content if we do say so ourselves, and.

Speaker 1 (09:45):
We do we do every time. If you haven't checked
out our website yet, check that out. It's phenomenal. This
podcast will kill You dot Com. We have sources from
all of our episodes. We have transcripts from all of
our episodes. We have a link to our bookshop dot
org affiliate account and our Goodreads list. We have links
to Bloodmobile, who does our music. We have so much

(10:06):
merch we have more things.

Speaker 3 (10:11):
We have two things. The website is a great magical place.
Check it out, new.

Speaker 1 (10:16):
Pictures, new pictures, promo codes, this podcast okay dot com
check it out.

Speaker 3 (10:22):
And then one last thing before we get started with
the actual content of the episode, and that is to
please rate, review, and subscribe. It really does help us
out and we appreciate everyone who has ever left a
review or subscribed or rated. You know.

Speaker 1 (10:35):
Yeah, Also tell your friends maybe they're not listening yet,
and then you would have something else.

Speaker 3 (10:41):
To talk about, like allergies.

Speaker 1 (10:45):
Like allergies, speaking of things to talk about.

Speaker 3 (10:49):
Should we get started, let's.

Speaker 1 (10:51):
Right after this break. This is either going to be
very shocking to people listening or entirely unsurprising, probably for

(11:14):
longtime listeners. But it's actually a little hard to put
a very strict definition on the word allergy.

Speaker 3 (11:22):
Aaron, there is a paper that I found that was
the evolution of the term allergy. I think I read
that paper over time.

Speaker 1 (11:30):
Yeah, I think I read that paper. I tried not
to read history and evolution papers, but I think I
did read that one. But we will do it because
in part because we have to, because we're doing an
episode on allergies, so we have to tell you what
we're talking about. But I think that by the end
of this and next episode, everyone will appreciate that, like
the deeper you get into the weeds, the more messy

(11:52):
this idea of allergy really becomes. But we'll try and
keep it a little less messy and just cover the
general basics. So the American Academy of Allergy, Asthma and Immunology,
and the UK's National Health Service and most other major
medical and public health organizations agree on the basics of
what an allergy is. An allergy is an abnormal, over

(12:17):
the top immune response to substances that typically do not
and really kind of should not cause any substantial immune response. Aaron,
you'r smiling, which I know means that this should not
maybe doesn't apply, but that's the way that I think
about it.

Speaker 3 (12:36):
There's some discussion, we'll get there.

Speaker 1 (12:38):
I can't wait. But so these substances, the stuff that
our immune system is recognizing and reacting to in this
over the top way. These things are called allergens, and
we've talked a lot on this podcast about the idea
of antigens. Antigens are just the stuffs that our immune

(12:59):
system sees and recognizes and then responds to allergens are
just antigens. They really are just antigens. The only differences
and the reason that they classify them differently is that
they are stuff. And first of all, they're usually almost
always proteins, except as we talked about in Alpha gal

(13:19):
when they're not. But they are almost always some type
of protein. And for most people these things that we
call allergens, our immune system sees them but usually goes ah,
forget about it, like just ignore that one. But in
people with allergies, these specific kinds of antigens that we

(13:39):
call allergens trigger a severe hypersensitive response. So let's talk
about how that ends up happening.

Speaker 3 (13:48):
Okay, real quick, So all allergens are antigens, but not
all antigens are allergens exactly.

Speaker 1 (13:54):
It's like all squares are rectangles, but not all rectangles
are squares. Got it, So let's see how that ends
up happening. We went over the basics of this actually
very recently in our alphagal episode, but we're going to
go over it again because the basics of this are
applicable to essentially all types of allergies with an asterisk,

(14:16):
because there are a lot of things that people might
call allergies that don't fit this mold. But when we're
talking about allergies for this episode, this is the type
of process that we're going to be talking about. Is
the pathway I'm about to explain, and here it goes.
The pathway starts with an exposure, and then there's a
process called sensitization which is making these specific type of

(14:38):
antibodies called IgE antibodies, and we'll get there. Then there's
re exposure, and then there's an allergic response. So we
can go into detail on each of those parts. First,
of course, we have to be exposed to analergen and
we can be exposed to analergen in so many different ways.

(15:01):
It can be in the air so we can breathe
it in, and they often call those arrow allergens because
if we don't have confusing terminology for every single thing,
then what are we even doing in medicine. Or it
can be in our food. We can scratch these allergens
into our skin, a tick could split them into us,
as we recently learned, we could rub them into our

(15:23):
eyes any way that they get in. Eventually, these allergens
make it into our bloodstream. And as soon as they
make it into our bloodstream, our immune system is all
over it. So let's say, as an example, it's cat dander.
There's a specific protein called feld one or fell d
one that's in cat skin, saliva, and urine, and that's

(15:43):
the thing that's the allergen in cat dander. So once
cat dander makes it into our bloodstream, a whole bunch
of cells like our macrophasias, our dendritic cells, blah blah blah,
all these immune cells they find this stuff, all of
these allergens and antigens and the cat dander protein, and
they bring it to our T cells. And our T
cells are the ones I Aaron went back to my

(16:06):
Vaccines episode notes to be like, how did I explain
this once upon a time? Our T cells are the
ones who are The way that I think about it
is they're kind of responsible, and this is an oversimplification
for either doing something or like not doing much of anything.

(16:27):
They're going to be the ones who like open a
door or don't open a door to make the rest
of our immune system react or not react.

Speaker 3 (16:36):
They're like the major part of the decision tree exact.
Is there going to be a cascade of events after this,
or do we shut it down right now?

Speaker 1 (16:43):
Exactly exactly. And it turns out that we have a
lot of different kinds of T cells in our bodies,
and depending on what they're reacting to what they find,
they can open one of many doors in our immune system,
and which door they open fundamentally changes all of the

(17:04):
downstream immune response that we see. So when T cells open,
say door number one, they're going to release a whole
bunch of cytokines, right, these inflammatory things that will help
our immune system to let's say, find bacteria or viruses
and target them and eliminate them. If T cells instead

(17:26):
open a different door, call it door number two, then
they release different cytokines, different inflammatory stuff, and then they're
maybe going to look for worms or parasites or something
like that. Now, of course, in reality, our immune system
is doing all of these things and opening all the
doors at the same time, and there's more than just two.

(17:47):
But it turns out that what happens in the process
of allergic sensitization, this is our second step in the pathway,
is that the proportion of doors that our T cells
are opening is skewed, and it's skewed towards door number two.
So it just so happens that when our T cells
decide when they see an allergen, to open a whole

(18:10):
bunch of doors number two, it ends up telling our
B cells, which are the ones that make antibodies, to
produce a specific kind of antibody, and that is IgE,
And that's the sensitization step of an allergy formation. And
we talked about these IgE antibodies in our alphagal episode,

(18:32):
But antibodies in general are like flags that our immune
system uses to recognize and respond to harmful stuff more quickly.
We have to see a pathogen or an antigen or
an allergen make an antibody, and then the next time
we see it is when that antibody does its job.
And we talked about this particular IgE antibody that it's

(18:54):
different from the ones we think of that we use
for something like vaccine responses because they're bound to cells
like our mass cells and our base of fills. So sensitization,
we're making these weird, kind of weird IgE antibodies. Once
we've been sensitized, then we have to see that allergen again.

(19:19):
We have to be re exposed to that same allergen.
So you made IgE against cat dander, and then you
go back to your friend's house who has a cat.
And because this IgE is all over our mass cells,
it's going to find and bind to that cat dander protein,
and that binding of the mass cells to the allergen

(19:44):
triggers a reaction that causes those mass cells to burst
open and spew forth a whole bunch of highly reactive
inflammatory stuff. It's things like histamine, leukotrienes, a bunch of
things called inter luken's, all of this stuff that tells
our immune system something really serious and horrible is happening

(20:07):
and everyone needs to get on board. It activates our
immune system in a really extreme way. And it can
do this on both these short time scales like immediately,
these immediate responses, but then it also triggers these longer
term like delayed responses, as well as the rest of
those inflammatory stuffs are floating around our body. That's the

(20:30):
actual allergic reaction.

Speaker 3 (20:33):
Okay, okay, question, what's your question? So IgE is involved
in this allergic pathway and also parasites, But you know,
you'll get there. We'll get there. Yeah, But there are
so many different types of antibodies. So is IgE generally

(20:54):
associated with this speedy, almost immediate response and the other
antibodies like, why what do they do? Not to turn
listen to an immunology episode, but what do they do?

Speaker 1 (21:10):
Yeah? So all antibodies are serving as ways to quickly
identify and respond to very specific antigens. Right, So each
different antibody we have like bajillions of antibodies in our body,
all of them are responding to one specific protein or
one specific carbohydrate or whatever. It is, one specific thing.

(21:32):
But things like IgG antibodies the way that I think
of them, and immunologists might tell me this is not
a great way to conceptualize it, but the way that
I think of them is they're more like a flag.
So they attach on they find like a bacteria or something,
and they attach themselves to it, and then our other
immune cells as they're floating around, they see that flag,

(21:53):
that IgG flag before they see the bacteria, and they're like, oh, hey, guys,
that's an antibody flag, so we should find that thing, right,
and then they can go and find all the bacteria
that have all these flags on them. The difference with
IgE is that it's not just a flag. It's attached.
It's not free floating. It sometimes can be, but it's
not free floating in our bloodstream. It's attached to these cells.

(22:17):
And something about the process of when that antibody that's
attached to a cell attaches to its antigen that we
call allergens. In the case of allergies, it triggers this
response in the mass cell itself that causes an explosion
of the inflammatory stuff that's inside of that mass cell.

(22:39):
And we don't see that with other types of antibodies
because they're not bound to cells. So it's like a
longer process, even though it's all much quicker than like
making the antibodies the first time that you're ever exposed
to something.

Speaker 3 (22:52):
And compared to IgE, is the response to other types
of antibodies generally speaking, more directed, more precise, or is
it also the systemic sort of like just again scorched earth?
I think is the phrase that I used in Alpha gal.

Speaker 1 (23:12):
Yeah, that's a really it's a really good question. I
think it's tough because the antibody response itself, even in
the case of IgE, it is very highly specific, right,
like your IgE is only attaching to cat dander protein. Yeah,
but yes, because you have this then immediate release of

(23:33):
all these general inflammatory stuff, you see a quicker onset
of a more widespread reaction than you would potentially with
other antibodies because you just don't have that. It doesn't
mean that you don't have like a widespread immune response
in other scenarios, because we definitely can. That's how you

(23:53):
could end up with like sepsis from a bacterial infection
and blah blah blah. But yeah, that's it is not
that same antibodies kind of causing the problem here, I
guess is the way that you can think of it, right, Right,
it's just bizarre, it is. It's a really weird and
interesting especially like I know you're going to talk erin

(24:13):
about the kind of evolution of this, and like it
is really really interesting and weird to think about why
we evolved this type of response. It's really interesting.

Speaker 3 (24:25):
Especially when it seems like it can come at a
great cost. It can when it kind of runs away.
So what right, there's such a huge range of allergic responses, right,
it can just be like it she knows, it can
be coughing, it can be whatever, Like, yeah, what determines
whether the response to an allergen is mild versus extreme

(24:48):
all the way to anaphylaxis.

Speaker 1 (24:49):
So let's talk about what the different responses can be,
because we are talking really generally about this big picture
allergic response and the symptoms that you're going to get
will in large part depend on the type of allergen
that you're exposed to and how you are exposed. So
if it's a cat dander protein, for example, or even

(25:11):
like a ragweed pollen or a dust mite or cockroach
leg fuzz or whatever, then you are being exposed to
these arrow allergens, right, so you are breathing them in
for the most part. So then where you're going to
get this inflammation from this immune activation might largely be
in say your nose, So you might have an itchy nose,

(25:33):
you might have sneezing, you might get a runny nose.
Maybe your eyes will start to itch or water because
the cat dander is getting into your mucous membranes in
your eyes and triggering inflammation in your eyes. If, on
the other hand, we're not talking about an arrow allergen,
maybe we're talking about something like a peanut protein or
a soybean protein, or a wheat protein, you're eating that,

(25:54):
So then you're being exposed through your gut mucus membranes
or maybe through your mouth because they're there's a whole
thing called oral allergy syndrome where you have this type
of itching, watering, numbness, tingling just in your mouth, but
if it makes it down into your guts before you're
having allergy response, then maybe you're having nausea, you're having vomiting.

(26:19):
So it depends in part in the way that you're exposed.
Is it through your respiratory system, is it through your
gi tract? Is it limited to one mucous membrane like
your mouth or your eyes. But then there's more than that,
right because while this is in some ways a localized exposure,
unless it's through your skin, then it is still a

(26:40):
systemic response. So in any of these cases, in any
way that you're exposed through your skin, through your eyes,
through your guts, you can also see skin manifestations, and
most classically in allergies will see these as like wheels
or hives. And hives are those red raised, usually irregular shaped,

(27:02):
kind of puffy splotches, and you can see those sometimes
where you're exposed like if you are eating something that
you're allergic to, you might start with hives around the
face or the mouth, but very often and very quickly,
they can become generalized. It might start with say, puffiness
around a beasting, but then spread to be hives across

(27:24):
your whole body. And those kind of skin reactions can
happen from any allergies. They can happen from cat dander
allergies and from peanut allergies. And then you mentioned already aaron.
The most severe thing that can happen with an allergic
reaction is anaphylaxis. And just like the idea of allergies,
the definition of anaphylaxis, it's not one perfect universal definition,

(27:47):
but mostly we think of anaphylaxis as when in the
case of allergies at least, because you can get anaphylaxis
without allergies. But it's when an allergic response is affecting
multiple systems and becomes very extreme. So it's when these
mast cells and our baso fills are sending out so

(28:09):
much inflammatory material that our whole body's immune system starts
to react. What this causes is massive vasodilation, so your
blood vessels are getting really wide, and that makes sense
because these immune markers are telling your body, hey, there's
something big going on. Send us all your blood, Send

(28:30):
all of the white blood cells, send all of the
blood to us. So vasodilation sends all of your blood
different places. But that also causes swelling in part because
when our vessels expand, they get more leaky, so fluid
is going to leak out. And if you get that
swelling in a place like your throat or your mouth
or your lungs, it can make it really difficult to breathe.

(28:53):
That's why anaphylaxis, when it causes that throat constriction, is
a severe, life threatening emergency. It can also be life
threatening because when our blood vessels expand, that causes a
drop in blood pressure because your blood vessels are now
wide open, and because of physics, when you have a
pipe that's wider, the pressure inside it is going to

(29:14):
be lower, and that again is a life threatening emergency
if your blood pressure drops really quickly. So that is
like the ways that allergies can manifest right, And it's
such a huge range and so many different ways that
you can be exposed, which can cause like any in
all of these But why I have so many questions

(29:40):
because first, why do some allergens trigger, say, anaphylaxis more
commonly than other allergens? Yeah?

Speaker 3 (29:50):
What are those bees?

Speaker 1 (29:52):
I mean utter is the most classic, right, and a
lot of times it is the food allergies that like
tree nuts, peanuts, things like that, that are even more likely.
But people can absolutely beastings or another one. Venoms in
general really commonly cause anaphylaxis. It doesn't mean that you
can't have an anaphylactic reaction to something like cat dander.

(30:13):
There are absolutely people who have severe reactions to something
like cat dander. But I don't know. I do not
know the answer to that question. And that was something
that I have so many papers, and none of them
really even tried to answer that question. What is it
about particular allergens that are more likely to cause a

(30:36):
severe reaction versus a less severe reaction?

Speaker 3 (30:38):
I don't know, right, But then it also is individual differences.
That's like the genetic component of allergies.

Speaker 2 (30:45):
Right.

Speaker 1 (30:45):
So that's the other big question, right, It's why some
allergens and why some people? Why do some people develop
allergies and other people don't? And we still don't know,
but we have a lot more information at least about
that part of the question. All allergies are really both

(31:20):
environmental and genetic diseases, so you have to have a
certain genetic susceptibility in order to develop allergies to begin with.
But that doesn't mean there's a single gene or a
couple of genes, or even like a few genes. There's
like bajillions. That's an exaggeration, but there's a really wide

(31:42):
range of genes that are associated with an increased risk
of allergies, and for the most part, we don't know
what they are or how they work, Like why do
these genes that we might see in association with allergies
do they cause allergies? Or why is there that association.

Speaker 3 (31:58):
Right and allergies? Or is it the degree of your
reaction or is it which allergies or is it yeah, yeah.

Speaker 1 (32:08):
And in all of the literature, a thing that I
want to get into, even though I already regret it,
is that one of the biggest known risk factors for
allergies is this idea of something called a topy.

Speaker 3 (32:21):
I had such a hard time wrapping my head around this.

Speaker 1 (32:23):
I know and you and we can't not talk about it.
So I'm going to try so a topic diseases, this
idea of an atopic disease. It includes asthma, egzema or
atopic dermatitis, and allergies, which includes all of our allergies,
so food allergies, allergic rhinitis or like hay fever, those

(32:44):
seasonal allergies, all of that, and the word a topy
or atopic, it's like, it's not specific. It doesn't like
that word in and of itself anymore doesn't really mean much,
and some people mean it to mean this type of
IgE response, but it's not that simple. But the point

(33:05):
of it is is that these big four diseases, and
there might be a couple others that probably are under
this umbrella, but like eggzema, asthma, allergic rhinitis, and food allergy,
if you think of these big ones, there is something
about them that links them all together. And we think
that part of it might be an underlying genetic susceptibility

(33:28):
that makes someone more susceptible to all of these at once.
But really, in a lot of the literature it's described
as this a topic march. You probably saw that in papers,
and that's because when we see these four diseases develop
through life. There's often a progression from one to the

(33:50):
next to the next, and there's a lot of different
theories as to why that is and what is this
relationship between these four big diseases. So I'm going to
go over what like the thoughts are about what the
relationship is here. So one suggestion is that it's allergens
that cause all of this, and it starts by allergens

(34:11):
causing atopic dermatitis or exema, which is usually the first
thing that we see, like even in tiny babies who
don't have asthma and they don't have any food allergies
yet or anything, they have exema first thing. And so
one hypothesis is that you start by getting exposed and
sensitized to certain allergens and first develop atopic dermatitis or exzema,

(34:36):
and then down the line, because you have been exposed
and sensitized, you then might develop asthma or other allergies
as a result of this allergen exposure. That's one hypothesis.
Another one that people seem to really really like is
that exema is the start of this. An exema causes

(34:58):
breakdown in the skin barrier, and this breakdown allows for
allergen exposure through the skin and that and I like
this too, in part because of we've already talked about
on our Alpha gal episode, the idea that when you
are exposed to something in an abnormal way i e.

(35:20):
Through breaks in your skin, that that exposure is what
predisposes you to this abnormal immune response i e. The
development of allergies. So that's one hypothesis. And then there's
a third hypothesis, which is that there's not necessarily a
causal relationship between exema and allergies and asthma, but rather

(35:43):
there's an underlying genetic or immunologic pathway that kind of
pins them all together, and EXAMA just happens to be
the first one that we see. Right, none of these
three hypotheses are mutually exclusive, and none of them like
fully explain the story, right, because there are plenty of

(36:03):
people with egzma who don't have any other allergies, plenty
of people with allergies who never had egzma. Asthma oof
really doesn't fit well into this story, even though there
are really strong relationships between allergic rhinitis and allergic asthma.

Speaker 3 (36:17):
It's really interesting and I kind of like the idea
of just the threshold being lowered for that pathway to
be exaccuated where it's right, oh, you know on once
it's down, once you travel down that road once, it's
so easy to go back down that road over and over.

Speaker 1 (36:34):
Again, exactly exactly. And these are not the only hypotheses.
There's a lot of other ideas as to like what
ends up causing or what are the risks that are
contributing to the development of allergies. A lot of it
might be like environmental exposures starting as early as in utero,

(36:54):
causing things like DNA methylation or these like epigenetic changes
that change our susceptibility to asthma, allergies, et cetera. Then
we also can think of the microbiomes, how does that
affect our risk of allergies asthma et cetera. We don't know, right,

(37:16):
but we know that all of these things and I
know erin you're going to talk more about this, I
swear I'm almost done. We know that all of these
things contribute. We just don't understand how, which means that
we don't yet know how do we prevent all of this?
And that is like next episode we'll talk a lot
more about that idea, because that's like where a lot

(37:37):
of the future research is going.

Speaker 3 (37:39):
And there may not be I think, one unifying cause right, like,
because one of the questions that I had when when
reading about these allergies and just like in general life,
is some people develop allergies at a very young age
and those allergies stay with them for the rest of
their lives. People develop allergies at a very young age

(38:02):
and then over time they no longer have those allergies.

Speaker 1 (38:06):
And that's most true for food allergies. Yes, So it's
also really interesting to think about, like when are you
more likely to develop what type of allergy? Because food
allergies you're more likely to start developing when you're younger.
Allergic rhinitis usually not till you're older.

Speaker 3 (38:24):
But then yeah, some people can develop food allergies later
in life. I have several friends who developed food allergies
in their thirties.

Speaker 1 (38:33):
Yeah, and like what yah, Well, and food allergies also,
I think gets so much more confusing because there's also
a lot of other food intolerances or sensitivities that some
people might classify as allergies and other people would not
classify as allergies. So a really good example of this

(38:54):
is something called f PIES, which stands for food protein
induced enterocolitis syndrome. And this is on a lot of
like allergy websites, classified as an allergy, but it is
not an IgE mediated response. But it causes severe like
vomiting diarrhea sometimes bloody diarrhea in babies that are exposed

(39:15):
to certain foods, and most kids outgrow this, and then
in adults there's a lot of different ways that you
could become intolerant of different foods, some of which might
be igmediated and some of which are definitely not IgE mediated.
And so that's where what I said, Like, the deeper
you get into the weeds, like what's an allergy? What's

(39:36):
not an allergy, it can get confusing. So, yeah, allergies
are very interesting. Erin tell me, Yeah, why can I
ask you?

Speaker 3 (39:48):
Why you can ask? Okay, let's see if I can
answer right after this break. Allergies are so ubiquitous these

(40:21):
days that we don't often stop to think about just
how weird they are. Like, here's this extreme thing our
body does in reaction to a seemingly innocuous substance like pollen,
like a peanut and that reaction can at times kill us. Yep,
it's not the peanut or the shrimp itself doing the harm.

(40:43):
It's how our body responds that inflicts the damage friendly fire,
whether it's seasonal allergies to ragweed, environmental allergies like to
cat dander, food allergies like to tree nuts, or some
other type of allergy. We all know someone who has
allergies or we have them ourselves, and we wished we didn't,
at least speaking for myself, at the least, allergies are annoying, disruptive,

(41:07):
and at the extreme they can be deadly. Why do
our bodies react in this way? What have almonds ever
done to us? And on top of that, has it
always been like this? In this first episode of this
two parter on allergies, I want to explore those questions,
the significance of allergies in an evolutionary context, and a

(41:31):
little bit of how our knowledge of allergy has changed
over time. Ultimately, I want to try to get at
whether allergies are increasing infrequency and why that might be
sort of unifying all of this, and then next week
I'll pick it back up at how we devised ways
to deal with the self attack using medications, allergy shots,

(41:51):
the EpiPen, and so on. Almost universally, allergy or an
allergic response is described as an overreaction, an exaggerated response
to an innocuous environmental trigger like pollen, like dustmites, like peanuts.
Since scientists first characterized allergies in the late eighteen hundreds
early nineteen hundreds, they referred to the phenomenon as an idiosyncrasy,

(42:15):
a biological contradiction where our bodies harm us in an
attempt to protect us. But more recently some researchers have
called into question two assumptions that underlie this premise of allergy.
Number one, that this reaction is always an overreaction, and
number two, that the substances triggering an allergic response are

(42:39):
truly innocuous.

Speaker 1 (42:41):
Oh, I can't tell you how excited I am about this.
I read I'm a full disclosure. I read one paper
that talked about some of the evolutionary hypothesis of the
worms and things that I was like, this is my
favorite thing I have ever. Yeah, because you're right, like,
that is the that is an underlie I said it
at the very top, this is how we define an allergy.

(43:02):
And those assumptions no one that I have read or
spoken with has ever questioned, and I love questioning it.

Speaker 3 (43:11):
It's important, right, Like, yeah, maybe it is an overreaction,
and it is in some certain situations, like definitely an overreaction,
as in, it is out of proportion to the threat
that whatever that thing causes. Right, but maybe not all
of the time.

Speaker 1 (43:27):
Right, right, There is a there has to be a
reason that that response exists, exactly, So just calling it
a straight overreaction makes our immune system seem dumb.

Speaker 3 (43:39):
Right, a little overprotective, like stop helicopter. Yeah, allergies are
incredibly widespread, and they have grown in prevalence over the
past century. More on that later. They're so widespread that
it's difficult to just discard them as a quirk of
the immune system, as our immune system being dumb, as

(44:00):
just an overreaction with no benefit to that overreaction. As
we all know, an extreme allergic reaction can be deadly.
And while maybe that reaction is just a peculiar aspect
of our immune system, might it also be that there's
a very good reason that we still possess it. And importantly,

(44:21):
are those two scenarios mutually exclusive? Or is it both
a quirk and an advantage. Since the early days of
allergy research in the first decades of the twentieth century,
allergies were labeled a modern disease, a quote unquote pathology
of progress, the natural consequence of us living what was
perceived to be increasingly unnatural lives, sedentary lifestyles, spending large

(44:47):
amounts of time indoors, the growth of cities, consuming processed foods,
using chemicals in the home and the environment, and so on.
Allergies are not the only disease said to result from
industrialization and develop If you remember back to our gout episode,
that was another one. Yeah, And in the case of allergies,

(45:07):
there might be something to it. So Aarin you talked
about how when someone is exposed to an allergen like
a DustMite, their body begins producing IgE antibodies, which is
part of what triggers this rapid cascade of symptoms. As
it turns out, our body ramps up production of IgE
in response to another external threat helminth parasites, so dust, MTE,

(45:31):
hookworm very similar initial responses. One major difference, though, is
in the long term in people who are chronically infected
with helminth parasites that IgE production eventually scales down and
the entire inflammatory response is suppressed in part by the
parasite itself, which allows these parasites to kind of fly

(45:54):
under the radar. That suppression doesn't happen in an allergic response. Instead,
it can just ramp up and up and up until anaphylaxis.
And so, when researchers described IgE antibodies in nineteen sixty
seven and began linking them to different exposures to things
like allergies like parasites, a hypothesis emerged that we have

(46:18):
this exaggerated allergic response and increasing rates of allergies in
regions where parasitic infections are low because those parasites are
not suppressing the immune system. So fewer parasites, more allergies,
and more parasites, fewer allergies. Essentially, the hypothesis goes improved

(46:39):
sanitation and treatments for parasites reduced exposure to those parasites,
which makes our board immune system go into overdrive overreacting
to any stimulus, aka the hygiene hypothesis or the old
friends hypothesis. Now, this might be part of what's going on,

(47:01):
because some studies show that regions with higher rates of
chronic parasite infestation tend to have lower rates of allergy,
and in experiments using mice, those chronically infected with helmets
are protected from developing allergies. Pretty compelling evidence. Also, some
of the genes associated with asthma are also associated with

(47:24):
increasing susceptibility to some parasite infections, so these genes might
make you both more likely to develop asthma and more
susceptible to parasite infections. The hygiene hypothesis does have some
compelling support when it comes to allergies or allergy like diseases,
but in recent decades some researchers are starting to question

(47:47):
whether it's the only thing going on. If you look
at the vast array of substances that trigger an IgE response,
only a tiny portion of them are helmets. The rest
are various nuts, animal products, venoms, chemicals, so very many
different things that we encounter regularly that are not helmints,

(48:10):
that are not parasites.

Speaker 1 (48:11):
Not just worms.

Speaker 3 (48:13):
Yeah, if the IgE response evolved in response to helminth
infections alone, why can it be so deadly? Wouldn't that
have been selected against at some point and it's hundreds
of millions years old evolutionary history, because the IgE response
is very old, not if the benefits outweigh the costs,

(48:35):
not if there's a reason to maintain it. As to
what that reason could be. How do toxins sound?

Speaker 1 (48:43):
Love toxins?

Speaker 3 (48:44):
There?

Speaker 1 (48:44):
And you know that?

Speaker 3 (48:45):
I know you do? I know you love? You love
a toxicologist. You love toxins?

Speaker 2 (48:49):
I do.

Speaker 3 (48:51):
In nineteen ninety one, Marjorie Profit introduced the toxin hypothesis
of allergy, and this hypothesis suggests that the IG mediated
allergic response evolved to protect us from immediate danger posed
by toxins. So a strong IgE allergic response like you
described AARON is usually very rapid onset, generally speaking within

(49:15):
seconds or minutes of exposure, and it's often accompanied by
things like a sudden drop in blood pressure, vomiting, tearing, diarrhea, coughing,
all things that would help to expel a toxic substance
or blow it down from reaching vital organs.

Speaker 1 (49:33):
Oh that is such an interesting Oh how did I
never think about that?

Speaker 3 (49:39):
I how did? Like it's amazing, It's just like, oh yeah, this.

Speaker 1 (49:46):
Is sort of like in your eye. Your body's like
get it out. Of your eyes, watering the heck out
of it.

Speaker 3 (49:51):
Right, and allergies do the same things.

Speaker 2 (49:53):
Yeah.

Speaker 1 (49:54):
Oh, I hope there's support for this hypothesis because I
like it.

Speaker 3 (50:02):
It's fascinating. Yeah, And you know I was asking in
the biology section. Okay, Well, the IgE response versus other
types of antibody responses and the allergic response, This IgE
mediated response is very different than that caused by exposure
to a pathogen like a virus or bacterium, and this

(50:22):
allergic response wouldn't really be effective against those infections, which
our immune system deals with by killing rather than expelling,
which is what it does to allergens and multicellular parasites.
Huh uh huh. Profit suggests that some of the allergens
that we think of as innocuous, like pollens like hay

(50:44):
dust or shellfish, may not be as harmless as they seem.
Pollens contain phenolic acids or alkaloids, both of which can
cause organ or nerve damage. Hay Dust can be contaminated
by pathogenic fungal spores, and shellfish can have toxins from
algae or plankton.

Speaker 1 (51:03):
Fung i. Think fungi are are are not well respected
in this regard in their they trigger a similar especially
some like asprogillis and things like that that commonly can
infect like grains and blah blah blah. Yeah, sorry, but
I love this. I'm really excited.

Speaker 3 (51:21):
Yeah. No, And there's also a lot of like I
am not getting into asthma here because we did an
asthma right episode, and so there's there's a that's a
whole separate literature in many ways, but there are links between.
Like a lot of these papers that talk about the
evolution of allergies also group asthma into that, which is
entirely reasonable.

Speaker 1 (51:41):
Like we talked about a topic disease.

Speaker 3 (51:44):
And there have been a lot of links with asthma
and fungus as well a fungal exposure. So yeah, super interesting.
But being able to rapidly recognize and deal with these
toxic threat that's like these alkaloids, like these toxins from
algae that could be vital to our survival both from

(52:07):
an immunological standpoint as well as just us experiencing that
deeply allergic response and wanting to avoid exposure in the future.
Are allergies a signal to us? Do they teach us
which plants or foods to stay away from.

Speaker 1 (52:23):
Arin I I can't tell you how much I love
this idea because you know what it feels like to me.
It feels like the difference between like what is a
weed and what is a desirable plant? Mm hmm, like
our allergies responses to things that they shouldn't be, or
actually are they responding to something that we should be

(52:46):
because we shouldn't be having so much grap like you know.

Speaker 2 (52:49):
What I mean?

Speaker 3 (52:49):
I just yeah, oh.

Speaker 1 (52:52):
I wow, this is mind blowing to me.

Speaker 3 (52:56):
I think if me too, because I had never really
considered I always was just like innocuous substance overreaction.

Speaker 1 (53:02):
Yeah are cases. Yeah, but peanuts can be contaminated with
funk a lot.

Speaker 3 (53:09):
Ants, and they also might be like these different foods
or these different allergens might be the compound structure itself
could be similar to similar to something else, something that
is much more toxic.

Speaker 1 (53:22):
Right what you're saying too?

Speaker 3 (53:24):
Yeah, yeah, it's an interesting idea. We love it. But
is their support for there? I hope so yes there is,
And is it like the most compelling support in the world.
I don't know. There are my studies, lab studies, et cetera.
But still but still still so. There are a couple
studies from twenty thirteen that found that mice that had

(53:45):
previously been exposed to venom. One study used a beasting
and the other used snake venom. The mice that had
been previously exposed were more likely to survive a big
second dose of venom that should have been fatal compared
to those who did not receive that initial dose, suggesting
that that big IgE response in the second exposure might

(54:09):
be helpful rather than detrimental. And of course this doesn't
explain why a beasting in humans can lead to a
fatal anaphylaxis response, because clearly that is very helpful. Some
researchers suggest it's too much of a good thing, kind
of like sickle cellnemia and malaria. Right, having one copy
of the gene protects you from malaria, but two copies

(54:30):
leads to disease. While most experimental studies looking at this
toxin hypothesis have focused on things like beastings, other epidemiological
studies have taken a broader view of toxins and how
they can harm us, such as cancer. There's no clear
pattern when it comes to allergies in cancer, but some
studies have shown that higher rates of allergies is linked

(54:54):
to lower rates of cancer. But I would imagine that
that depends on the type of cancer and the other
lifestyle and genetic factors.

Speaker 1 (55:03):
Right, And is it environmental? No, that's interesting and weird
because there's so much environmental cancer exposure blah blah blah.
And then environmental allergy. Oh, that's so weird and interesting.

Speaker 3 (55:14):
Yeah, isn't it interesting? And so while the hygiene hypothesis
or the old friends hypothesis and the toxin hypothesis of
allergy can help to fill in some of the gaps
as to the why of allergies, the complete picture is
not yet clear. Yeah, how can we take what we
know about helmets and allergies and apply it to treatment? Right?

(55:38):
Can we make an allergen tree of life to predict
the groups of antigens that people are likely to be
sensitive to? Does it have to do with evolutionary distance?
The farther away something is on that evolutionary tree of life?
Does that mean that we're more likely to initiate an
immune response to it? The future of allergy research is exciting,

(55:59):
and to understand where we go from here, we also
have to take a look at where we've come from. Yeah,
are allergies changing and if so, what is driving that change.
Today allergies are one of the most common diseases across
the world, affecting ten to thirty percent of the global
population and up to fifty percent of people in some regions.

(56:22):
For years, that number has been on the rise, which
is why you'll hear people refer to this as an
allergy epidemic, sometimes broken down into two waves, the first
being respiratory allergies like hay fever and the second being
food allergies. Of course, allergies themselves are not a new phenomenon.
IgE antibodies evolved around three hundred million years ago, allowing

(56:45):
for this allergic response, and we have evidence of allergies
from ancient times, descriptions of fatal beastings what could be
allergic rhinitis, and of course asthma. But the heyday of
allergy awareness pun intended, really only began in the eighteen hundreds,
with the first description of hay fever in eighteen nineteen

(57:07):
by John Bostock and the first case series published in
eighteen seventy three by Charles Blackley. These observations didn't seem
to be a case of cool. There's finally a name
associated with this condition that we've noticed for a long time,
but a recognition of a truly emerging phenomenon.

Speaker 1 (57:26):
Huh.

Speaker 3 (57:27):
Like one summer day in eighteen seventy five, your nose
starts running and your eyes start itching, and you're sneezing
all over the place, and you find all of your
friends and family are similarly affected, and you're just complaining
about it. You form groups to talk about it. But
just a few years ago, no doctor had ever heard
of such a thing. The sudden increase in hay fever

(57:49):
in Europe and North America around the late eighteen hundreds
resulted from changes in agricultural practices, changing which crops were planning,
planting more pollinaceous. If that's a word, it's not. I
don't think my word document is telling me there's a
red underline. It's angry, but it's the only thing I

(58:10):
could think of. Pollinaceous grass varieties to feed the growing
cattle herds, and an increase in farmed land in the US,
leading to higher ragweed growth. This marks the beginning of
the first wave of the allergy epidemic.

Speaker 1 (58:25):
Ladies, it's eighteen hundreds. Okay, yeah, that's way further back.
I mean it feels like I should have expected, but
like I don't know.

Speaker 3 (58:33):
And it's hard because like people generally associate asthma with
the first wave, and that's like nineteen sixties is really
when those cases started to super ramp up. But if
we're talking about allergic rhinitis, it really is like eighteen
eighties roughly.

Speaker 1 (58:48):
Interesting.

Speaker 3 (58:49):
There had been in decades previous descriptions here and there,
but not like sudden recognition of this, whoa everyone is experiencing?

Speaker 1 (59:00):
Interesting.

Speaker 3 (59:01):
Yeah. In nineteen o six, Clemens von Pirquet coined the
term allergy to describe the hypersensitivity reaction in serum sickness.
So when someone was given anti serum, let's say, for
like diphtheria, to treat their diptheria infection. But they had
extracted that anti serum from an animal like a horse. Yeah,
they had, Yeah, caused the infection, got the antibodies all that.

(59:24):
Then you inject an episode. Interesting, we should but yeah,
then people got real sick from them. And by that time,
so around the early nineteen hundreds, other work had shown
how anaphylaxis can happen, how animals negatively react to the
introduction of a foreign substance, and the concept of an

(59:46):
allergic response mediated by your immune system began to gain
traction because up to this time, germ theory had a
pretty tight hold on many explanations of disease, and so
the recognition that it was actually our immune systems causing
these allergic responses, like the call is coming from inside
the house, took a bit of time to gain traction.

(01:00:08):
Von Pirquet combined a bunch of observations from hyposensitivity, hypersensitivity,
food allergy, hay fever, beasting reactions, serum sickness, and so
on to create this organized concept of allergy as it
relates to immunity, and it created momentum for more research
in the area, even if it was initially papooed by

(01:00:29):
like a lot of his peers.

Speaker 1 (01:00:30):
Classic Classic.

Speaker 3 (01:00:32):
The first decades of the nineteenth century saw the formation
of allergy research groups and clinics across the globe, and
as far back as nineteen thirty six, the phrase, quote unquote,
the allergy epidemic was used. Wow, right, much earlier than
I thought.

Speaker 1 (01:00:49):
Yeah.

Speaker 3 (01:00:50):
In nineteen forty six, ragweed hay fever was such a
huge problem in New York City. That City Council started
a ragweed elimination campaign. The tides were changing and fast. Asthma,
which prior to nineteen sixty had been considered a rare disease,
shot up in incidents, doubling in Swedish Army recruits from

(01:01:12):
nineteen seventy one to nineteen eighty one huge rise, as
did hospital admissions for the condition, which increased tenfold between
nineteen sixty five and nineteen eighty In Australia, the UK,
New Zealand, Canada, and the US tend for afterasthma. In
the nineteen seventies, after the discovery of IgE, researchers observed

(01:01:34):
a sharp increase in allergen specific IgE antibodies against environmental allergens,
growing to over fifty percent of the population in some
regions like I mentioned, and the second wave of the
allergy epidemic. Food borne allergies began much more recently. Around
nineteen ninety is most most papers I read, and that's
the same time that asthma case is actually plateaued. One

(01:01:58):
large study found that between nineteen ninety seven and two
thousand and eight, allergies to peanuts and tree nuts tripled, tripled, huge. Yeah.
Reports from Australia indicate a tenfold increase in referrals to
food allergy specialists and a five fold increase in hospital
admissions for food related anaphylaxis. This is not just a

(01:02:21):
matter of doing a better job of recognizing these allergies, No.

Speaker 1 (01:02:26):
Especially not with food allergies because the reaction is usually
so severe.

Speaker 3 (01:02:30):
Exactly. Yeah, what is driving this explosive rise? Yeah, that
is the billion dollar question. We don't fully know, of course,
here is what we do know. We know that while
this is a global rise, the highest increases are seen
in more industrialized countries. For instance, following the reunification of

(01:02:54):
East and West Germany in nineteen eighty nine, prevalence of
allergy shot up in East Germany, where it have been
much lower in previous decades.

Speaker 1 (01:03:02):
I think that's one of the most interesting examples because
it's so like discrete and like the regions are so
close to each other, so it's like not like what
is it because it's not just like natural environment exposure
clearly like.

Speaker 3 (01:03:15):
Weather, right, pollen is not does not respect the Berlin
exactly yeah. Yeah, And on average, allergies are twenty times
more common in affluent quote unquote westernized countries compared to
those with lower incomes. And we know that this rise

(01:03:38):
is not limited to allergies or asthma, but it also
is seen in other autoimmune or immune mediated diseases. We
know that these diseases are not rising all at the
same time, or in the same place or at the
same pace, which could suggest different mechanisms behind the rise
in each of them. And this has been you to

(01:04:00):
challenge the old friends or the hygiene hypothesis, since countries
that saw the biggest rise in allergies only did so
beginning really in the nineteen sixties, which was around forty
years after major sanitation changes would have reduced waterborne pathogens
and anti helmath campaigns had reduced parasite burden to almost nothing.

(01:04:21):
So what could be going on? Most of the predominant
ideas fall under the hygiene hypothesis or the old friends
hypothesis or the biodiversity hypothesis, which are kind of like
more recent offshoots, and both of these suggest that our
allergies are a result of us not being exposed to
as many or as diverse microbes and parasites that we

(01:04:43):
used to throughout our evolutionary history. Why that would lead
to more allergies depends on who you ask. Maybe it's
that with decreasing family size, kids are not coming into
contact with as many germs at a young age, although
some childhood pathogens like RSV are positively associated with developing allergies.

(01:05:04):
So it's like the right germs, right, right, Which germs
that's the Yeah, Yeah, it's layers, compilators.

Speaker 1 (01:05:14):
It's almost like our immune system is complicated. I don't
know what.

Speaker 3 (01:05:20):
Maybe it's that our use of antibiotics at an early
age disrupts our gut microbiome and primes us to develop allergies.
Maybe it's that we spend more time inside and sedentary
early childhood. Exposure to pets or farm animals seems to
reduce the risk of allergies, and exercise reduces allergic inflammation.

(01:05:40):
I found a study looking at babies born during COVID
lockdown in twenty twenty, and this study found higher rates
of allergies in that cohort. So it's like, again, the
limited exposure to the outside world. Maybe it's the chemicals
and our soaps, food packaging, microplastics, pollution, ozone, cigarette smoke,
that disrupts our protective epithelial barriers and sends our immune

(01:06:05):
systems into overdrive. If you think about it, the allergic
response is kind of like a hail marry last resort
option to protect us from toxins. After our skin or
skin microbiota, after our guts or gut microbiota, our lungs
and lung microbiota, lets it get through, right like, there

(01:06:26):
are so many other layers of protection, and then maybe
it's that once it makes it past all those layers,
then we have this last ditch effort to protect us
from whatever perceived tosin there is. And if those layers
are continually broken down by some of the things that
we encounter in our everyday lives, like processed foods, you know,

(01:06:48):
all of these different things that all combine together to
increase permeability of those barriers, does that then lead to
increase allergy?

Speaker 1 (01:06:57):
And I think that's one of the things that makes
the there's a there's a lot of research being done
on like is exzema and the breakdown of your skin
barrier that happens with egzema. Does it also result in
this abnormal presentation of these toxins or of these allergens
right where it's like, typically you shouldn't be able to
be exposed to, say, cat dander through your skin because

(01:07:18):
your skin should be able to keep cat dander out.
But if it gets in that way, does that predispose
you to And cat dander might be a crappy example,
I don't know, but like, if you get peanut on
your skin, peanut protein shouldn't be able to make it
through your skin. If it does, does that trigger your
immune response to think that it is something that is pathogenic?
So that's one of those kind of ideas.

Speaker 3 (01:07:40):
Right, Yeah, novel exposure roots exactly these things because of
a decreased barrier in permeability.

Speaker 1 (01:07:47):
Which is why I think, like the AlphaGo story is
so interesting in that, like because it applies so much
to that. So yeah, I don't know, Yeah, it's interesting.

Speaker 2 (01:07:57):
Aaron.

Speaker 3 (01:08:00):
Uh, we don't have a single simple answer for why
tree nut allergies suddenly exploded in the past few decades,
although I do think that part of it is, at
least from my reading, our response to them initially how
it was like, don't expose anymore. If there's the slightest
bit of reaction, then it sort of Yeah.

Speaker 1 (01:08:19):
I am really curious. This is jumping so far ahead.
I'm sorry, but I'm so curious to see what is
going to happen in the next decade. Like with like,
because it was our generation that has really high rates
of things like peanut and tree nut and all these
food allergies. And it was our generation that very much

(01:08:39):
was told by physicians, do not expose your children because
we don't want them to develop allergies. And it turns out,
against spoilers, that that was exactly the wrong advice. And
now we know that because of these phenomenal studies, and
so early introduction is now the recommendation. So what are
rates going to be like in kids in five ten years.
I'm super curious about all this, like how the epidemiology

(01:09:01):
is going Is it going to change, I don't know,
is it.

Speaker 3 (01:09:03):
To help you? And you know, like we probably won't
ever have one simple, unifying answer to this. I agree,
and I will say also, like the hygiene hypothesis or
the old friends hypothesis, or the toxin hypothesis or the
epithelial barrier hypothesis, these things aren't attempting to explain away

(01:09:25):
all cases of allergies or autoimmune diseases with one bottom line. Instead,
what they're doing is highlighting patterns of allergy, pointing out
where we can look next. If it is certain detergent
compounds causing a rise in asthma because of increased skin permeability,
why and how. If it is a disrupted microbiome, what

(01:09:47):
about it makes it disrupted? And how can we restore balance.
If it is epigenetic effects, what are those prenatal exposures
that increase someone's chance of developing allergies? While the comp
tx nature of allergies makes all of this seem so overwhelming,
the truth is that people are doing incredible research to

(01:10:07):
answer these questions, to get at the underlying triggers of
different allergies, and it really seems like we're slowly going
to be able to put the puzzle pieces together, at
least for some pictures right, for some bits of the allergy,
and come up with better ways to understand, prevent and
treat allergies. I love it so now, Aaron, I'll turn

(01:10:30):
it over to you to tell us where we are
with allergies around the world today.

Speaker 1 (01:10:35):
I'll give it my best shot right after this. So

(01:11:02):
you told us already, Aarin, that all of these allergic disorders,
from hay fever, from seasonal allergies, from food allergies. They're
all on the rise, that is certainly true, and they
have been for a while longer than I realized, apparently.
When it comes to I'll break this down into like
the allergic rhinitis, which is more you think of as

(01:11:23):
the hay fever, the seasonal allergies, it's the runny nose
and the blah blah blah running eyes. And I don't
say blah blah blah to discount it because it has
pretty significant effects on people's lives, as we'll see. But
a paper from the Lancet from twenty eleven, which is
old now, estimated that four hundred million people worldwide are

(01:11:44):
affected by allergic rhinitis, and this number is likely higher
today as this, like all allergies, has continued to increase.
But this varies a lot across the globe. And while
most of allergic rhinitis develop in like child or teen years,

(01:12:05):
sometimes they don't. There's plenty of adults who don't develop
seasonal or environmental allergies until much later in life. But overall,
in some areas of the globe, prevalence is as high
as like seventeen to twenty percent. Those seem to be
the highest percentage numbers that I saw and across the board,

(01:12:26):
even though in the International Study of Asthma and Allergies
in Childhood, which is also now old because the Phase
three study finished in like the early two thousands, but
in this study, the rates of allergic rhinitis were actually
greatest in Latin America and African countries. But even there

(01:12:47):
the prevalence was higher in urban areas compared to rural areas,
and that pattern is true pretty much across the globe.
Allergic rhinitis also has pretty significant burdens on our healthcare system.
In the nineties, way back in the nineties, it was
estimated to cost one point nine billion US dollars every year,

(01:13:08):
and that increased to three point four billion in the
early two thousands. And that's not even counting indirect costs,
of which there are enormous indirect costs, things like miss school,
missed work. Allergic rhinitis especially can result in things like
poor sleep or sleep apnea. It can contribute which can
then lead to fatigue, memory problems, mood changes. It can

(01:13:31):
make school harder for kids, like, it is not a
minor like we might think of it as, oh, it's
just a runny nose. It is not just a running nose. Right,
Food allergies we have much credier data for.

Speaker 3 (01:13:46):
Which is interesting to me for some reason. I don't
know why.

Speaker 1 (01:13:50):
Yeah, I think I think it's we have credit or
like global data.

Speaker 3 (01:13:53):
Okay, but no doubt.

Speaker 1 (01:13:55):
Food allergies are absolutely on the rise. In some countries,
as much as ten percent of children have at least
one food allergy. And food allergies are especially interesting because
for some foods, up to like seventy or eighty percent
of kids will outgrow their food allergy, and those foods

(01:14:16):
tend to be things like egg and milk, but things
like peanuts and tree nuts tends to be much less
likely that kids will outgrow it. Usually it's twenty percent
or less of kids with a peanut or tree nut
allergy will outgrow them. Then there's other food allergies like
shellfish and fish, which not only do we have less

(01:14:37):
data for the idea that early introduction can prevent sensitization
for things like fish and shellfish, but it's also more
likely that people don't develop those allergies until adulthood.

Speaker 3 (01:14:50):
Why why, Oh you know, I have a quick question. Actually, yeah,
dose and relationship to response one. You know, one peanut,
how much peanut or almondors shellfish, shrimp tail?

Speaker 1 (01:15:06):
You know. So yeah, maybe it's worth talking a little
bit in more detail about this. So the study that
showed that early exposure can reduce the risk of peanut allergy,
the big one was called Leap Learning Early about Peanut Allergy,
and then there was another one I think called EAT
and I forget what that acronym stands for. But these
were like really landmark studies that showed that early exposure

(01:15:28):
and early exposure meant like four months of life, but
definitely earlier than eleven months of life. So before a
baby turns one year old, you start with exposure to peanuts,
and you have to have persistent exposure. So it's not
like give them peanuts one time and then you're good.
These studies were consistent exposure, like two to three times

(01:15:50):
a week every week for the first five years of life. Okay, wow,
but in those kids and in these studies, they took
kids who were high risk, kids who either had severe
eggzema or had a known allergy to egg or In
some of the studies it was kids who had a
family history of peanut allergy, so these were high risk

(01:16:12):
kids because we know that there's genetics in these associations.
So in those kids, the reduction in risk of peanut
allergy was like seventy to eighty percent. It was massive,
massive reduction in risk, and so across the board. Now
the recommendation is early exposure, but it has to be

(01:16:33):
that consistent exposure, so it's not like necessarily a one
time dose, like give this much peanut. It's really like
start small, but continued exposure, so like a little peanut
on the finger when they're a tiny baby, continuing that
until they're like eating peanut butter and their oatmeal like
a couple times a week when they're kids, and that

(01:16:53):
significantly decreases the risk. And so that data has now
been extrapolated to a lot of the foods that the
earlier exposure to all of the main allergenic foods, and
in the US, those foods are wheat, soy, tree nuts, peanuts, milk, egg, oh, crap,

(01:17:14):
I should have written all of these town fish, shellfish,
and now sesame. That's the early net. The newest edition.
So early and consistent exposure to all of those is
what's now recommended to try and prevent food allergies.

Speaker 3 (01:17:31):
And we don't know what happens when someone just develops
an allergy, a food allergy at the age of thirty five?

Speaker 1 (01:17:37):
No, is it all alpha calerin? I don't know.

Speaker 3 (01:17:41):
It all comes down to alpha cal.

Speaker 1 (01:17:43):
Is it the ticks?

Speaker 3 (01:17:45):
No?

Speaker 1 (01:17:45):
Yeah, I don't know. Is it a threshold thing like
we kind of talked about, Is it that maybe they
had some level of it? Here's the other thing, arin,
Oh my gosh, there is a proportion of the population
who if you test them, they develop these IgE antibodies, aka,
they are sensitized to various things, be they aero allergens

(01:18:07):
like cat dander. Cat dander is a good example because
if you test kids who live in homes with cats,
a higher percentage of them will have a degree of
sensitization at a certain age, but a lower percentage of
them will be allergic, will have that allergic response to kings.
And so yeah, so like what is it about sensitization

(01:18:29):
versus then who of those kids who are sensitized actually
then will have allergies. We don't exactly know, so is
there is that what it is for adults who develop
say a shellfish allergy later in life, that maybe they
were a little bit sensitized, but it wasn't until that
built up enough in their system that they had an
allergic response.

Speaker 3 (01:18:48):
I don't know, okay, but the quantity of exposure, or
the amount of allergen that they're exposed to, can lead
to really different responses than some people. Where some people
are like even the most minute amount can lead to
these horrible reactions, whereas other people can have there's a
threshold where that causes Yes, I guess, okay, one hundred percent.

Speaker 1 (01:19:08):
Yes, that is absolutely true, and we don't understand why. Okay, ah,
so yeah, that's like what we know of. When it
comes to the most severe outcomes, that is anaphylaxis. We
again don't really have great data here because most of
the data that we have is on hospital admissions for anaphylaxis,

(01:19:30):
and not all people with anaphylaxis have to actually be
admitted to the hospital. And also it's not always allergies
that cause anaphylaxis. But at least in some of the
papers that I found, it's estimated that about zero point
three percent of the population of Europe will experience anaphylaxis
at some point in their lives. Wow, okay, yeah, higher

(01:19:51):
than I expected. And the data across the board is
that especially in most high income countries, which is where
we have data, incidents of anaphylaxis is increasing, which makes
sense because allergies across the board are increasing. Anaphylaxis, especially
due to food born triggers, is increasing. Anaphylaxis due to

(01:20:14):
alpha gu specifically is increasing big time. But mortality does
not seem to be increasing, except in Australia, which some
of the data has had increases in mortality associate with anaphlexis.

Speaker 3 (01:20:30):
So does that mean that we have developed better tools
or is that a tune in for next week to
find it?

Speaker 1 (01:20:35):
That's a tune in for next week to find out
how do we treat it? That was my segue erin
you guessed it?

Speaker 3 (01:20:43):
I love it.

Speaker 1 (01:20:45):
So yeah, that's allergies for now, but I can't wait
for next week to hear about how we figured out
how to treat these things, and then we'll talk about
how we treat them and what our thoughts are about
preventing them in more detail next week.

Speaker 3 (01:21:01):
But until then, if you would like to learn more
about things like the how allergies work, the IgE mediated response,
the evolution of allergies, the rise and allergies. We've got sources.

Speaker 1 (01:21:14):
For you, so many.

Speaker 3 (01:21:16):
I have so many, and I highlighted too right here
just because to list them all out would take another
ten minutes. So there's one by Dasher and Fernandez from
twenty nineteen titled Allergy in an Evolutionary Framework that's all
about the evolution of allergies. And then by Actus from
twenty twenty one, does the epithelial barrier hypothesis explain the

(01:21:39):
increase in allergy, autoimmunity, and other chronic conditions?

Speaker 1 (01:21:43):
Fascinating stuff for the biology of allergies. Boy, do I
have plenty of rabbit holes that you can go down,
But I'm going to shout out like four or five
main papers that are really high level overviews. One is
from the New England Journal of Medicae in from two
thousand and one, so it's old but still good, and
that is just called Allergy and Allergic Diseases. There was

(01:22:06):
one on titled food Allergy from Nature Reviews Disease Primers
from twenty eighteen, and another one titled food allergy from
the Lancet two thousand and two, and then two on
allergic rhinitis, one titled Allergic Rhinitis from the Lancet twenty
eleven and one titled Allergic Rhinitis Definition, Epidemiology, path of Physiology,
Detection and Diagnosis from the Journal of Allergy and Clinical

(01:22:29):
Imminology from two thousand and one. There's so many There's
so many more. We're not going to read them all,
but you can find them on our website, This Podcast
will Kill You dot com under the episodes tab for
this episode and everyone we've ever done, they're all there.

Speaker 3 (01:22:43):
Thank you again, Caitlin so much for sharing your story
with us and really helping to illustrate that allergy to
environmental allergens is not just a running nose.

Speaker 1 (01:22:55):
No, it means so much more. Thank you so much
for being willing to take the time and to share
your story with us and all the listeners. We really
appreciate it.

Speaker 3 (01:23:05):
Thank you to Bloodmobile for providing the music for this
episode and all of our episodes.

Speaker 1 (01:23:10):
Thank you to Leona Scuilatchi and Tom Bryvocal for the
audio mixing.

Speaker 3 (01:23:14):
Thank you to everyone at Exactly Right.

Speaker 1 (01:23:17):
And thank you to you listeners. We hope you enjoyed
this episode and that you're stoked for next week to
learn even more about allergies. Yeah.

Speaker 3 (01:23:24):
Why do EpiPens work the way they do?

Speaker 1 (01:23:26):
I can't wait to find out.

Speaker 3 (01:23:28):
Yeah, me too, got some reading to do. Thank you
also to our wonderful, generous, amazing patrons, We really truly
appreciate your support so much. Thank you, Thank you well.
Until next time, wash your hands.

Speaker 1 (01:23:43):
You feel the animals

Speaker 2 (01:24:05):
U