0:00

My name is Caitlin.

0:01

I'm thirty two years old, and for

0:04

most of my life I hadn't experienced

0:06

severe allergies or allergic

0:08

reactions to anything, except for cats

0:11

sometimes. I went to school in Nebraska,

0:13

and after college I got a job in Denver

0:15

and moved. The first year living in Denver

0:18

was awesome. I got really into all

0:20

the outdoorsy things that Colorado has to offer,

0:22

like camping and hiking and skiing.

0:25

But about a year into my time in Denver,

0:27

in the spring of twenty seventeen, seasonal

0:30

allergies and hay fever hit me on like anything

0:32

I had ever experienced before. Every

0:34

day that spring, I remember, I would wake

0:36

up with a sore throat, hives, and

0:38

swollen eyes. My eyes would have

0:41

allergic conjunctivitis and chemosis,

0:44

which is when tiny bubbles form

0:46

on the surface of your eye from all the

0:48

allergens and pollen in the air. I had a

0:50

constant runny nose and couldn't breathe.

0:53

I had a lot of sinus infections. I

0:55

also couldn't hear very well because of all

0:57

of the post nasal drip that would happen and settle

0:59

in over I was beyond exhausted

1:01

all the time and unable to go outside

1:04

much at all. Every time I would leave my house,

1:06

I would get hot, painful hives on

1:08

any part of my skin that was exposed. I

1:10

remember taking cold showers all the

1:13

time to try to keep my hives from spreading

1:15

all over my body, and at the time I

1:17

was only using over the counter allergy

1:19

medications, which only helped a little bit. I

1:21

worked downtown in an office, and so riding

1:24

the train into the office, interacting with

1:26

coworkers and clients, and wearing business casual

1:28

clothing was incredibly uncomfortable

1:30

and embarrassing sometimes. And this

1:33

is all before COVID times, and I was

1:35

still really new at my job, so asking

1:37

to work from home was a challenge. I

1:39

was also really bummed because I couldn't eat a lot of fruits

1:41

that grew on trees where

1:43

you typically eat the skin, because the

1:46

pollen grows with the fruit instead of on

1:48

the hard outer layer. So fruits like

1:50

peaches and apples were off limits because

1:52

I would break out in hives on my neck and face

1:54

and sometimes experience breathing issues.

1:56

And sadly, Colorado is famous for their

1:59

palasaid peaches, and I could never have

2:01

them, even though it was my favorite fruit

2:03

growing up. Unfortunately, things got

2:05

exponentially worse the following fall

2:08

due to a mold issue in the rental house that

2:10

I was living in. I was exposed to penicillium

2:12

mold spores, which had a compounding

2:14

effect on my already maxed out immune system,

2:17

and I ended up developing severe

2:19

asthma. I was playing roller Derby at the time,

2:21

and I remember showing up to practices and scrimmages

2:24

feeling like I was breathing through a wet cloth

2:26

draped over my nose and mouth and felt

2:28

like I would pass out after one warm up lap.

2:30

I was devastated.

2:31

I didn't know what was wrong with me, and I was trying so hard

2:34

to get into the sport and develop a

2:36

community in my new place, but I was

2:38

not able to keep up at all. I ended up

2:40

taking a leave of absence to avoid further damage

2:42

and started seeking professional help. I

2:44

had skin testing done in January twenty

2:46

eighteen, and it was pretty awful.

2:49

Almost every single allergen that they had tested

2:51

me for came back with a flaming

2:54

positive. After this, I was introduced to

2:56

my allergist and met my immunotherapy

2:58

team. I got started with allergy shots by

3:00

doing a procedure called a rush treatment to

3:02

try to get my body as close to my

3:05

maintenance DOWS for allergy shots as soon

3:07

as possible. I was not able to finish

3:09

the entire rush treatment because my body

3:11

started to go into shock, which is actually

3:13

typical for the procedure. After that,

3:15

I began regular allergy shots every

3:18

three weeks for the next five years. I

3:20

was also put on a prescription strength antihistamine,

3:22

two, over the counter antihistamines two

3:25

Inhaler's, and an EpiPen in the event

3:27

I went into anaphylaxis. I was not allowed

3:29

to eat or touch anything that would cause any

3:31

sort of reaction, and I had to avoid being outside

3:34

on high pollen days. Springtime was always

3:36

the worst for me due to the presence of tree pollen,

3:38

and I would always see more intense reactions

3:40

during that time of year to my allergy shots.

3:43

Fortunately, I completed my immunotherapy

3:45

in July twenty twenty three and have been pretty good

3:47

ever since. I'm still on the prescription strength

3:50

antihistamine and one of the over the

3:52

counter antihistamines for any allergies

3:54

that might pop up, as well as both

3:56

Inhaler's for the now permanent asthma,

3:59

but overall things are pretty manageable for me.

4:01

I remember asking my allergist, why

4:03

now, why did allergies hit me now

4:05

and here and like this and never before

4:08

in my life? And she explained to me that I'd

4:10

probably experienced what they call a honeymoon

4:12

period when I first moved to Colorado. My

4:14

body is non reactive to the new allergens

4:16

because it had never seen them before, but almost

4:18

always a second time around or the following

4:20

season that your body encounters the allergen,

4:23

it overreacts and produces an excessive

4:25

histamine response. This whole experience

4:27

has been a very long and painful journey, and it took

4:29

a huge toll on my mental health at the time.

4:32

I'm not entirely sure how long I'll be without

4:34

allergic reactions, hopefully forever, but

4:36

I still get hives from time to time. Everyone's

4:39

body reacts differently, and sometimes you become

4:41

allergic to new things that you weren't before. Every

4:43

reaction I do have now is manageable.

4:46

My asthma is still very much there, but I've learned

4:48

to live with it, and I'm also really excited to

4:50

report that I can have feaches and apples again.

4:52

My life has been completely changed because

4:55

of this experience. I'm so fortunate

4:57

to have the support that I do, and I cannot think

4:59

my Meta Coole team and my family and my

5:01

friends enough for taking such good

5:03

care of me Throughout those five years. I've learned

5:06

so much about something I never even thought twice

5:08

about for two thirds of my life that ended

5:10

up having a major life altering impact

5:12

on me. The human body is so intensely

5:14

weird in particular sometimes, but I'm

5:17

so grateful that I was able to get through this experience

5:19

and to be where I am now, even with the lasting

5:21

effects it has left me with.

6:09

Ooh, that gosh

6:11

sounds truly miserable. Yeah,

6:14

truly miserable.

6:15

Oh my goodness.

6:16

I always think like, oh, yeah, I have seasonal

6:18

allergies. Sometimes I barely

6:21

do. Yeah, I have the hint of.

6:23

A seasonal allergy. And to deal with we have

6:25

seasonal allergies, the I

6:31

know, and to deal with it just like, oh my

6:33

goodness.

6:34

Yeah, all yeah, And when it's

6:36

everywhere, it is ever escapable, you

6:38

cannot ever escape it.

6:40

Yeah yeah, you just breathe it in.

6:43

That's brutal. But I'm glad that you're finding

6:45

some more relief. Now, thank

6:47

you so much, Kaylin for sharing your story

6:50

with us.

6:50

Thank you.

6:53

Hi.

6:54

I'm Aaron Welsh and I'm Aaron Allman

6:56

Updyke.

6:57

And this is this podcast will Kill You.

6:59

And today we're talking about allergies today

7:02

and next week today or next week?

7:04

You know, what do we get ourselves

7:06

into here?

7:07

Eron the same thing that we always

7:09

do aeron, which is a very very

7:12

large topic. Yeah,

7:14

yeah, here's the deal, everyone

7:16

listening. Here's what it's going to go like. This

7:19

week we are going to talk about

7:22

allergies. I'm going to call it capital

7:24

A allergies. That is all of them,

7:26

food allergies, seasonal allergies,

7:28

all of the allergies. What does that mean? What is

7:31

an allergy? Even we'll talk about it, and

7:33

we'll talk about how we figured

7:35

out what our allergies, why do we have

7:37

them, those kinds of things. Next

7:40

week we'll focus on what do you do

7:43

if you have allergies? And how

7:45

did we figure that out? How do we treat

7:47

them? And what are some of the options.

7:49

In that respect.

7:51

That's the way that we're trying to split it up.

7:52

We'll see how it goes, I think it will go great.

7:54

Aaron.

7:55

You have nothing to be worried about.

7:56

You.

7:56

You always do an amazing job.

7:59

I'm so she gets nervous

8:01

every time.

8:02

She's so nervous all the time, and I'm like, you're

8:05

you do a great job.

8:06

As soon as we start, thank you. As

8:08

soon as we start to record the biology section, my stomach

8:10

every time goes like you. So,

8:13

it's already there, but

8:16

I'm looking forward to it.

8:19

I think they're going to be a great couple of episodes.

8:21

There's a lot of stuff that we're getting

8:23

to explore from sort of this big picture perspective

8:25

on the energies that we haven't

8:28

really although we have covered allergies

8:30

or allergy related conditions

8:32

like asthma in the past. I think this

8:34

is a fun opportunity for us to kind

8:36

of go, Okay, let's take a step back. What are

8:38

the patterns that we see. How does this work

8:41

across the board?

8:42

Right?

8:43

Really big picture here? Yeah, so yeah,

8:45

yeah, but before we can start on

8:47

that, it's quarantin

8:49

any time.

8:50

It is, Aaron, what are we drinking

8:53

this week?

8:54

We're drinking the allergy shot.

8:56

Yeah, pretty straightforward, pretty straightforward.

9:00

But we won't talk.

9:01

About allergy shots other than this today.

9:03

We'll talk about them next week.

9:05

It's true.

9:06

What's in the allergy shot erin?

9:07

You know, it's just a little tropical

9:11

delight. You know, it's got some it's got

9:13

some rum in it. It's got some tropical

9:16

fruit juices like some pineapple, some

9:19

orange. It's

9:21

it's delicious and it's a

9:23

small contained thing,

9:25

so you know, it's great. We'll post

9:28

the full recipe for the allergy

9:30

shot quarantine and the non alcoholic

9:32

placey Berita on our website. This podcast

9:34

will Kill You dot Com, as well as on all

9:36

of our social media channels, which if you're

9:38

not following us on social media, you really

9:40

should be, because you know there's some pretty

9:42

good content if we do say so ourselves,

9:45

and.

9:45

We do we do every time. If

9:49

you haven't checked out our website yet, check

9:51

that out. It's phenomenal. This podcast

9:53

will kill You dot Com. We have sources

9:56

from all of our episodes. We have transcripts

9:58

from all of our episodes. We have a link to our

10:01

bookshop dot org affiliate account and our Goodreads

10:03

list. We have links to Bloodmobile, who does our music.

10:05

We have so much merch we

10:08

have more things.

10:11

We have two things. The website

10:13

is a great magical place. Check it out,

10:15

new.

10:16

Pictures, new pictures, promo codes,

10:19

this podcast okay dot com check it out.

10:22

And then one last thing before we get started

10:24

with the actual content of the episode, and that

10:26

is to please rate, review, and subscribe.

10:29

It really does help us out and we appreciate everyone

10:31

who has ever left a review or subscribed

10:34

or rated. You know.

10:35

Yeah, Also tell your friends

10:38

maybe they're not listening yet, and then you would have

10:40

something else.

10:41

To talk about, like

10:44

allergies.

10:45

Like allergies, speaking of things to

10:47

talk about.

10:49

Should we get started, let's.

10:51

Right after this break. This

11:07

is either going to be very

11:09

shocking to people listening or

11:12

entirely unsurprising, probably for longtime

11:14

listeners. But it's actually

11:17

a little hard to put a very strict

11:19

definition on the word allergy.

11:22

Aaron, there is a paper that I

11:24

found that was the evolution of the

11:27

term allergy. I think I read

11:29

that paper over time.

11:30

Yeah, I think I read that paper. I tried

11:32

not to read history and evolution papers, but

11:34

I think I did read that one. But

11:37

we will do it because in part because

11:39

we have to, because we're doing an episode on allergies, so

11:41

we have to tell you what we're talking about. But

11:43

I think that by the end of this and next

11:45

episode, everyone will appreciate that, like the

11:48

deeper you get into the weeds,

11:50

the more messy this idea

11:53

of allergy really becomes. But

11:55

we'll try and keep it a little less

11:57

messy and just cover the general

12:00

basics. So the American

12:02

Academy of Allergy, Asthma and Immunology,

12:05

and the UK's National Health Service and most

12:07

other major medical and public

12:09

health organizations agree on the basics

12:11

of what an allergy is. An

12:14

allergy is an abnormal,

12:17

over the top immune response

12:20

to substances that typically

12:22

do not and really kind

12:25

of should not cause any

12:27

substantial immune response. Aaron, you'r smiling,

12:29

which I know means that

12:32

this should not maybe doesn't apply, but that's

12:35

the way that I think about it.

12:36

There's some discussion, we'll get there.

12:38

I can't wait. But

12:41

so these substances, the stuff that our

12:43

immune system is recognizing and

12:45

reacting to in this over the top way.

12:48

These things are called allergens, and

12:50

we've talked a lot on this podcast about

12:53

the idea of antigens. Antigens

12:56

are just the stuffs that

12:58

our immune system sees and recognizes

13:00

and then responds to allergens

13:04

are just antigens. They really

13:06

are just antigens. The only differences

13:08

and the reason that they classify them differently

13:11

is that they are stuff. And first

13:13

of all, they're usually almost always proteins,

13:16

except as we talked about in Alpha gal

13:19

when they're not. But they are almost

13:21

always some type of protein. And

13:23

for most people these things

13:26

that we call allergens, our immune

13:28

system sees them but usually

13:30

goes ah, forget about it, like just

13:33

ignore that one. But in people

13:35

with allergies, these specific

13:38

kinds of antigens that we call allergens

13:41

trigger a severe hypersensitive

13:43

response. So let's talk about

13:46

how that ends up happening.

13:48

Okay, real quick, So all allergens

13:51

are antigens, but not all antigens are

13:53

allergens exactly.

13:54

It's like all squares are rectangles, but not all

13:56

rectangles are squares. Got it, So

13:59

let's see how that ends up happening.

14:02

We went over the basics

14:04

of this actually very recently in our alphagal

14:06

episode, but we're going to go over it again

14:09

because the basics of this are applicable

14:12

to essentially all types

14:14

of allergies with an asterisk,

14:16

because there are a lot of things that people might call

14:19

allergies that don't fit this mold.

14:21

But when we're talking about allergies for

14:23

this episode, this is the type of

14:25

process that we're going to be talking about. Is the pathway

14:27

I'm about to explain, and here it goes. The

14:30

pathway starts with an exposure, and

14:33

then there's a process called sensitization

14:36

which is making these specific

14:38

type of antibodies called IgE

14:40

antibodies, and we'll get there. Then

14:43

there's re exposure, and

14:46

then there's an allergic response. So

14:48

we can go into detail on each of those parts.

14:51

First, of course, we have

14:54

to be exposed to analergen

14:57

and we can be exposed to analergen

14:59

in so many different ways. It

15:01

can be in the air so we can breathe it

15:03

in, and they often call those arrow

15:06

allergens because if

15:08

we don't have confusing terminology

15:10

for every single thing, then what are we even doing in medicine.

15:14

Or it can be in our food. We

15:16

can scratch these allergens into our

15:18

skin, a tick could split them into us,

15:20

as we recently learned, we could rub

15:22

them into our eyes any way that they get

15:25

in. Eventually, these allergens make

15:27

it into our bloodstream. And as soon

15:29

as they make it into our bloodstream, our

15:31

immune system is all over it. So

15:34

let's say, as an example, it's

15:36

cat dander. There's a specific protein

15:38

called feld one or fell

15:40

d one that's in cat skin, saliva,

15:43

and urine, and that's the thing that's the allergen

15:45

in cat dander. So once cat

15:47

dander makes it into our bloodstream, a

15:49

whole bunch of cells like our macrophasias,

15:52

our dendritic cells, blah blah blah, all these immune

15:54

cells they find this stuff,

15:56

all of these allergens and antigens and the

15:58

cat dander protein, and they bring

16:01

it to our T cells. And

16:03

our T cells are the ones I

16:05

Aaron went back to my Vaccines episode

16:07

notes to be

16:10

like, how did I explain this once upon a

16:12

time? Our T cells

16:14

are the ones who are The way

16:16

that I think about it is they're kind of responsible,

16:19

and this is an oversimplification for

16:22

either doing something or

16:25

like not doing much of anything.

16:27

They're going to be the ones who like open

16:29

a door or don't open a door to

16:32

make the rest of our immune system react

16:35

or not react.

16:36

They're like the major part of the decision

16:38

tree exact. Is there going to be a cascade

16:40

of events after this, or do we shut it down

16:42

right now?

16:43

Exactly exactly. And

16:45

it turns out that we have a lot of different

16:48

kinds of T cells in our bodies,

16:51

and depending on what they're reacting

16:53

to what they find, they

16:56

can open one of many doors

16:58

in our immune system, and which door

17:00

they open fundamentally changes

17:03

all of the downstream immune response

17:06

that we see. So when T cells

17:08

open, say door number one, they're

17:11

going to release a whole bunch of cytokines,

17:13

right, these inflammatory things

17:16

that will help our immune system to

17:18

let's say, find bacteria or viruses

17:21

and target them and eliminate them.

17:24

If T cells instead open

17:26

a different door, call it door number two,

17:29

then they release different cytokines,

17:32

different inflammatory stuff, and

17:34

then they're maybe going to look for worms

17:37

or parasites or something like that.

17:40

Now, of course, in reality, our immune system

17:43

is doing all of these things and opening all the doors

17:45

at the same time, and there's more than just two. But

17:48

it turns out that what happens in the process

17:50

of allergic sensitization,

17:53

this is our second step in the pathway,

17:56

is that the proportion of doors that

17:58

our T cells are opening is skewed,

18:01

and it's skewed towards door number two.

18:04

So it just so happens that when our T cells

18:07

decide when they see an allergen, to

18:09

open a whole bunch of doors number

18:11

two, it ends up telling

18:13

our B cells, which are the ones that make

18:15

antibodies, to produce a

18:18

specific kind of antibody, and that

18:20

is IgE, And

18:23

that's the sensitization step of

18:25

an allergy formation. And

18:27

we talked about these IgE antibodies in

18:30

our alphagal episode, But

18:32

antibodies in general are like flags

18:34

that our immune system uses to recognize

18:37

and respond to harmful stuff more

18:39

quickly. We have to see

18:41

a pathogen or an antigen or

18:44

an allergen make an antibody,

18:46

and then the next time we see it is when that

18:48

antibody does its job. And

18:50

we talked about this particular IgE antibody

18:53

that it's different from the ones we think

18:56

of that we use for something

18:58

like vaccine responses because

19:01

they're bound to cells like our mass cells

19:03

and our base of fills. So

19:06

sensitization, we're making these weird,

19:09

kind of weird IgE antibodies.

19:12

Once we've been sensitized, then

19:15

we have to see that allergen

19:18

again. We have to be re exposed

19:21

to that same allergen. So you

19:24

made IgE against cat dander, and

19:27

then you go back to your friend's house

19:29

who has a cat. And because

19:31

this IgE is all over

19:33

our mass cells, it's going to find

19:36

and bind to that cat dander protein,

19:39

and that binding of

19:41

the mass cells to the

19:43

allergen triggers a reaction

19:46

that causes those mass cells to burst

19:49

open and spew forth

19:51

a whole bunch of highly reactive

19:54

inflammatory stuff. It's

19:56

things like histamine, leukotrienes,

19:58

a bunch of things called inter luken's, all

20:01

of this stuff that tells

20:03

our immune system something really serious

20:05

and horrible is happening and everyone

20:08

needs to get on board. It activates

20:10

our immune system in a really extreme

20:12

way. And it can do this on

20:14

both these short time scales like immediately,

20:17

these immediate responses, but

20:19

then it also triggers these longer term

20:22

like delayed responses, as

20:24

well as the rest of those inflammatory

20:27

stuffs are floating around our body.

20:30

That's the actual allergic reaction.

20:33

Okay, okay,

20:38

question, what's your question?

20:40

So IgE is involved

20:43

in this allergic pathway and

20:45

also parasites, But you know,

20:48

you'll get there. We'll get there. Yeah, But

20:50

there are so many different types of antibodies.

20:53

So is IgE generally associated

20:55

with this speedy, almost

20:57

immediate response and

21:00

the other antibodies

21:03

like, why what

21:05

do they do? Not to turn

21:07

listen to an immunology episode, but what

21:09

do they do?

21:10

Yeah? So all antibodies are serving

21:12

as ways to quickly identify

21:15

and respond to very specific

21:17

antigens. Right, So each

21:20

different antibody we have like bajillions

21:22

of antibodies in our body, all

21:24

of them are responding to one specific

21:27

protein or one specific carbohydrate

21:29

or whatever. It is, one specific thing. But

21:33

things like IgG antibodies the way

21:35

that I think of them, and immunologists might tell

21:37

me this is not a great way to

21:39

conceptualize it, but the way that I think of them is they're

21:41

more like a flag. So

21:44

they attach on they find like a bacteria

21:47

or something, and they attach themselves to it,

21:49

and then our other immune cells as they're

21:51

floating around, they see that flag,

21:53

that IgG flag before they see the

21:55

bacteria, and they're like, oh, hey, guys, that's

21:57

an antibody flag, so we should find that thing,

22:00

right, and then they can go and find all the bacteria

22:03

that have all these flags on them. The

22:05

difference with IgE is

22:08

that it's not just a flag. It's

22:10

attached. It's not free floating. It sometimes

22:12

can be, but it's not free floating in

22:14

our bloodstream. It's attached to these cells.

22:17

And something about the process of when

22:20

that antibody that's attached to a cell

22:23

attaches to its antigen

22:25

that we call allergens. In the case of allergies,

22:28

it triggers this response in the

22:30

mass cell itself that

22:32

causes an explosion of

22:35

the inflammatory stuff that's

22:37

inside of that mass cell. And

22:39

we don't see that with other types of antibodies

22:42

because they're not bound to cells. So

22:45

it's like a longer process, even

22:47

though it's all much quicker than like making

22:49

the antibodies the first time that you're ever

22:51

exposed to something.

22:52

And compared to IgE, is

22:55

the response to other types of antibodies

22:58

generally speaking, more directed,

23:01

more precise, or

23:03

is it also the systemic sort of

23:05

like just again

23:07

scorched earth? I think is the phrase

23:09

that I used in Alpha gal.

23:12

Yeah, that's a really it's a really good question.

23:14

I think it's

23:16

tough because the antibody response

23:19

itself, even in the case of IgE,

23:22

it is very highly specific, right,

23:24

like your IgE is only attaching

23:26

to cat dander protein. Yeah,

23:29

but yes, because you have this then

23:31

immediate release of all these general

23:34

inflammatory stuff, you see

23:37

a quicker onset of a more widespread

23:39

reaction than you would

23:41

potentially with other antibodies

23:45

because you just don't have that. It doesn't mean

23:47

that you don't have like a widespread

23:49

immune response in other scenarios,

23:51

because we definitely can. That's how you could end up with like

23:54

sepsis from a bacterial infection and blah

23:56

blah blah. But yeah,

23:58

that's it is not that

24:00

same antibodies kind

24:03

of causing the problem here, I

24:05

guess is the way that you can think of it, right,

24:07

Right, it's just bizarre,

24:09

it is. It's a really weird and interesting especially

24:12

like I know you're going to talk erin about the kind of evolution

24:14

of this, and like it is really really

24:16

interesting and weird to think about why

24:19

we evolved this type of response.

24:22

It's really interesting.

24:25

Especially when it seems like it can come at

24:27

a great cost. It can

24:29

when it kind of runs away. So what

24:31

right, there's such a huge range

24:34

of allergic responses, right, it

24:36

can just be like it she knows, it

24:38

can be coughing, it can be whatever,

24:41

Like, yeah, what determines

24:43

whether the response to an allergen is

24:46

mild versus extreme all

24:48

the way to anaphylaxis.

24:49

So let's talk about what the different responses can

24:51

be, because we are talking really generally

24:54

about this big picture allergic response

24:57

and the symptoms that you're going to get will

25:00

in large part depend on the

25:02

type of allergen that you're exposed to and

25:04

how you are exposed. So

25:07

if it's a cat dander protein,

25:09

for example, or even like a ragweed

25:11

pollen or a dust mite or cockroach

25:14

leg fuzz or whatever, then

25:16

you are being exposed to these arrow allergens,

25:19

right, so you are breathing them in

25:21

for the most part. So then where

25:23

you're going to get this inflammation

25:26

from this immune activation might

25:29

largely be in say your nose, So

25:31

you might have an itchy nose, you might have sneezing,

25:34

you might get a runny nose. Maybe your

25:36

eyes will start to itch or water because

25:38

the cat dander is getting into your mucous

25:40

membranes in your eyes and triggering inflammation

25:43

in your eyes. If,

25:45

on the other hand, we're not talking about an arrow allergen,

25:47

maybe we're talking about something like a peanut

25:50

protein or a soybean protein, or

25:52

a wheat protein, you're eating that, So

25:54

then you're being exposed through your gut

25:56

mucus membranes or maybe through your

25:58

mouth because they're there's a whole thing called

26:01

oral allergy syndrome where you have this

26:03

type of itching, watering,

26:06

numbness, tingling just in your mouth, but

26:09

if it makes it down into your guts

26:11

before you're having allergy

26:14

response, then maybe

26:16

you're having nausea, you're having vomiting.

26:19

So it depends in part in the way

26:21

that you're exposed. Is it through your

26:23

respiratory system, is it through your gi tract?

26:26

Is it limited to one mucous membrane

26:28

like your mouth or your eyes. But

26:30

then there's more than that, right because while

26:32

this is in some ways a localized

26:35

exposure, unless it's through your skin,

26:38

then it is still a

26:40

systemic response. So

26:43

in any of these cases, in any

26:45

way that you're exposed through your skin, through

26:47

your eyes, through your guts, you can also

26:49

see skin manifestations, and

26:52

most classically in allergies will see

26:54

these as like wheels or hives.

26:57

And hives are those red raised,

27:00

usually irregular shaped, kind of puffy

27:03

splotches, and you can

27:05

see those sometimes where you're exposed

27:08

like if you are eating

27:10

something that you're allergic to, you might start with

27:12

hives around the face or the mouth, but

27:15

very often and very quickly, they can become

27:17

generalized. It might start

27:19

with say, puffiness around a beasting,

27:22

but then spread to be hives across your

27:24

whole body. And those kind

27:26

of skin reactions can happen from any allergies.

27:29

They can happen from cat dander allergies

27:31

and from peanut allergies. And

27:33

then you mentioned already aaron. The most severe

27:35

thing that can happen with an allergic reaction

27:38

is anaphylaxis. And just

27:40

like the idea of allergies, the definition

27:42

of anaphylaxis, it's not one

27:45

perfect universal definition, but

27:48

mostly we think of anaphylaxis as

27:50

when in the case of allergies

27:52

at least, because you can get anaphylaxis without

27:54

allergies. But it's when

27:56

an allergic response is affecting

27:59

multiple systems and

28:02

becomes very extreme. So

28:04

it's when these mast cells and

28:06

our baso fills are sending out

28:08

so much inflammatory material

28:11

that our whole body's immune system starts

28:13

to react. What this causes

28:16

is massive vasodilation,

28:18

so your blood vessels are getting really wide,

28:21

and that makes sense because these

28:24

immune markers are telling your

28:26

body, hey, there's something big going on.

28:28

Send us all your blood, Send all

28:30

of the white blood cells, send all of the blood to

28:32

us. So vasodilation sends

28:35

all of your blood different places. But

28:37

that also causes swelling in

28:40

part because when our vessels expand,

28:42

they get more leaky, so fluid is

28:44

going to leak out. And if you get

28:46

that swelling in a place like your throat

28:49

or your mouth or your lungs, it can

28:51

make it really difficult to breathe. That's

28:53

why anaphylaxis, when

28:55

it causes that throat constriction, is a

28:57

severe, life threatening emergency.

29:00

It can also be life threatening because

29:02

when our blood vessels expand, that

29:05

causes a drop in blood pressure because

29:07

your blood vessels are now wide open, and

29:09

because of physics, when you have a pipe

29:11

that's wider, the pressure inside it is going

29:13

to be lower, and that again

29:16

is a life threatening emergency if your blood pressure

29:18

drops really quickly. So

29:20

that is like the ways that allergies

29:22

can manifest right, And it's such

29:25

a huge range and so many

29:27

different ways that you can be exposed, which can

29:29

cause like any in all of

29:31

these But why

29:37

I have so many questions because

29:41

first, why do some

29:43

allergens trigger, say,

29:46

anaphylaxis more commonly

29:48

than other allergens? Yeah?

29:50

What are those bees?

29:52

I mean utter is the most classic,

29:55

right, and a lot of times it is

29:57

the food allergies that like

29:59

tree nuts, peanuts, things like that, that are

30:02

even more likely. But people

30:04

can absolutely beastings or another one. Venoms

30:06

in general really commonly cause

30:08

anaphylaxis. It doesn't mean that you

30:10

can't have an anaphylactic reaction to something

30:13

like cat dander. There are absolutely people who

30:15

have severe reactions to something like cat

30:17

dander. But I

30:19

don't know. I do not know the answer

30:22

to that question. And that was something that I

30:24

have so many papers, and

30:27

none of them really even tried

30:29

to answer that question. What is it

30:31

about particular allergens

30:34

that are more likely to cause a

30:36

severe reaction versus a less severe reaction?

30:38

I don't know, right, But then it also

30:40

is individual differences. That's

30:43

like the genetic component of allergies.

30:45

Right.

30:45

So that's the other big question, right, It's why

30:48

some allergens and why some

30:50

people? Why do some people develop

30:52

allergies and other people don't?

30:55

And we still don't know, but we have a lot more

30:58

information at least about that part of

31:00

the question. All

31:17

allergies are really both

31:20

environmental and genetic diseases,

31:23

so you have to have a certain genetic

31:25

susceptibility in order

31:28

to develop allergies to begin with. But

31:31

that doesn't mean there's a single gene or

31:33

a couple of genes, or even like a

31:35

few genes. There's like bajillions.

31:38

That's an exaggeration, but

31:41

there's a really wide range of genes that

31:43

are associated with an increased risk of allergies,

31:46

and for the most part, we don't

31:48

know what they are or how

31:50

they work, Like why do these genes

31:52

that we might see in association with allergies

31:55

do they cause allergies? Or why is there

31:57

that association.

31:58

Right and allergies? Or

32:01

is it the degree of your reaction

32:03

or is it which allergies or

32:06

is it yeah, yeah.

32:08

And in all of the literature, a thing

32:10

that I want to get into, even though I already regret

32:13

it, is that one of the biggest

32:15

known risk factors for allergies

32:18

is this idea of something called a topy.

32:21

I had such a hard time wrapping my head around

32:23

this.

32:23

I know and you and we can't not

32:26

talk about it. So I'm going to try

32:28

so a topic diseases, this

32:30

idea of an atopic disease. It

32:33

includes asthma, egzema

32:35

or atopic dermatitis, and

32:38

allergies, which includes all of

32:40

our allergies, so food allergies, allergic

32:42

rhinitis or like hay fever, those seasonal

32:44

allergies, all of that, and

32:47

the word a topy or

32:49

atopic, it's like, it's

32:52

not specific. It doesn't like that

32:54

word in and of itself anymore

32:56

doesn't really mean much, and some people

32:58

mean it to mean this type of IgE

33:01

response, but it's not that

33:03

simple. But the point of

33:05

it is is that these big four

33:08

diseases, and there might be a couple

33:10

others that probably are under this umbrella,

33:12

but like eggzema, asthma, allergic

33:14

rhinitis, and food allergy, if you think of these

33:16

big ones, there

33:19

is something about them that links

33:21

them all together. And we think

33:23

that part of it might be an underlying

33:26

genetic susceptibility that

33:28

makes someone more susceptible to all

33:31

of these at once. But

33:34

really, in a lot of the literature it's

33:36

described as this a topic march.

33:39

You probably saw that in papers, and

33:41

that's because when we see these

33:45

four diseases develop through life.

33:47

There's often a progression from

33:49

one to the next to the next, and

33:53

there's a lot of different theories as to why

33:55

that is and what is this relationship

33:57

between these four big diseases.

34:00

So I'm going to go over what like the thoughts

34:02

are about what the relationship is

34:04

here. So one suggestion

34:07

is that it's allergens that cause all

34:09

of this, and it starts by allergens

34:11

causing atopic dermatitis

34:14

or exema, which is usually the first thing

34:16

that we see, like even in tiny babies who

34:18

don't have asthma and they don't have

34:21

any food allergies yet or anything,

34:23

they have exema first thing. And

34:26

so one hypothesis is that

34:28

you start by getting exposed and

34:30

sensitized to certain allergens

34:33

and first develop atopic dermatitis

34:35

or exzema, and then down the line,

34:38

because you have been exposed and

34:40

sensitized, you then might develop asthma

34:42

or other allergies as a result of this

34:45

allergen exposure. That's one hypothesis.

34:48

Another one that people seem

34:50

to really really like is

34:52

that exema is the

34:54

start of this. An exema

34:58

causes breakdown in the skin barrier,

35:01

and this breakdown allows

35:03

for allergen exposure through

35:06

the skin and

35:08

that and I like

35:11

this too, in part because of we've already talked

35:13

about on our Alpha gal episode, the idea

35:16

that when you are exposed to something

35:18

in an abnormal way i e.

35:20

Through breaks in your skin, that

35:23

that exposure is

35:25

what predisposes you to this abnormal

35:28

immune response i e. The development

35:30

of allergies. So

35:32

that's one hypothesis. And then

35:34

there's a third hypothesis, which is that

35:37

there's not necessarily a causal relationship

35:39

between exema and allergies

35:41

and asthma, but rather there's an

35:44

underlying genetic or immunologic

35:47

pathway that kind of pins

35:49

them all together, and EXAMA just happens to be

35:51

the first one that we see. Right, none

35:54

of these three hypotheses

35:56

are mutually exclusive, and

35:59

none of them like fully explain

36:01

the story, right, because there are plenty of people

36:04

with egzma who don't have any other allergies, plenty

36:06

of people with allergies who never had egzma. Asthma

36:09

oof really doesn't fit well into

36:11

this story, even though there are really

36:13

strong relationships between allergic rhinitis

36:16

and allergic asthma.

36:17

It's really interesting and I kind

36:20

of like the idea of just

36:22

the threshold being lowered

36:24

for that pathway to be exaccuated

36:26

where it's right, oh, you

36:28

know on once it's down, once you travel

36:30

down that road once, it's so easy to go back

36:33

down that road over and over.

36:34

Again, exactly exactly. And

36:36

these are not the only hypotheses. There's a lot

36:39

of other ideas as to like what ends

36:41

up causing or what are the risks

36:44

that are contributing to the

36:46

development of allergies. A

36:48

lot of it might be like environmental

36:50

exposures starting as early as

36:53

in utero, causing things

36:55

like DNA methylation or these like

36:57

epigenetic changes that change

37:00

our susceptibility to asthma, allergies,

37:03

et cetera. Then

37:05

we also can think of the

37:07

microbiomes, how

37:10

does that affect our risk of

37:12

allergies asthma et cetera. We

37:15

don't know, right, but we know

37:17

that all of these things and I know erin you're going to talk

37:19

more about this, I swear I'm almost done.

37:23

We know that all of these things contribute.

37:26

We just don't understand how,

37:29

which means that we don't yet know how do we prevent

37:32

all of this? And that is like next episode

37:34

we'll talk a lot more about that idea, because that's

37:36

like where a lot of the future research is going.

37:39

And there may not be I

37:42

think, one unifying cause

37:45

right, like, because one

37:47

of the questions that I had when when reading

37:49

about these allergies and just like in

37:51

general life, is some people

37:54

develop allergies at a very young age

37:56

and those allergies stay with them for the rest

37:58

of their lives. People develop

38:00

allergies at a very young age and then

38:03

over time they no longer have

38:05

those allergies.

38:06

And that's most true for food allergies.

38:09

Yes, So it's also really interesting to think

38:11

about, like when are you more likely to develop

38:13

what type of allergy? Because food

38:15

allergies you're more likely to start

38:18

developing when you're younger. Allergic

38:20

rhinitis usually not till you're older.

38:24

But then yeah, some people can develop

38:26

food allergies later in life. I

38:28

have several friends who developed

38:31

food allergies in their thirties.

38:33

Yeah, and like what

38:35

yah, Well, and food allergies

38:38

also, I think gets so much more confusing because

38:41

there's also a lot of other food

38:43

intolerances or sensitivities that

38:46

some people might classify as allergies

38:49

and other people would not classify as

38:51

allergies. So a really good

38:53

example of this is something called f PIES,

38:56

which stands for food protein induced

38:58

enterocolitis syndrome. And

39:01

this is on a lot of like allergy

39:03

websites, classified as an allergy,

39:06

but it is not an IgE mediated

39:08

response. But it causes

39:10

severe like vomiting diarrhea sometimes

39:13

bloody diarrhea in babies that

39:15

are exposed to certain foods, and most

39:17

kids outgrow this, and then in adults

39:19

there's a lot of different ways that you could become

39:22

intolerant of different foods, some

39:25

of which might be igmediated and

39:27

some of which are definitely not IgE mediated.

39:30

And so that's where

39:32

what I said, Like, the deeper you get into the weeds,

39:34

like what's an allergy? What's not an allergy,

39:37

it can get confusing. So,

39:40

yeah, allergies are very interesting.

39:42

Erin tell me, Yeah,

39:47

why can I ask you?

39:48

Why you can ask? Okay,

39:51

let's see if I can answer right after this break.

40:19

Allergies are so ubiquitous these days

40:22

that we don't often stop to

40:24

think about just how weird

40:27

they are. Like, here's this extreme

40:29

thing our body does in reaction to a

40:32

seemingly innocuous substance like

40:34

pollen, like a peanut and that

40:36

reaction can at times kill

40:38

us. Yep, it's not the peanut or

40:40

the shrimp itself doing the harm. It's

40:43

how our body responds that inflicts

40:45

the damage friendly fire, whether

40:47

it's seasonal allergies to ragweed, environmental

40:50

allergies like to cat dander, food

40:53

allergies like to tree nuts, or some other

40:55

type of allergy. We all know someone

40:57

who has allergies or we have them

40:59

ourselves, and we wished we didn't,

41:01

at least speaking for myself, at

41:04

the least, allergies are annoying,

41:06

disruptive, and at the extreme they

41:09

can be deadly. Why

41:11

do our bodies react in this way?

41:14

What have almonds ever done to us?

41:16

And on

41:18

top of that, has it always been

41:20

like this? In this first episode

41:23

of this two parter on allergies, I want

41:25

to explore those questions, the significance

41:28

of allergies in an evolutionary context,

41:30

and a little bit of how our knowledge of allergy

41:33

has changed over time. Ultimately,

41:36

I want to try to get at whether allergies

41:38

are increasing infrequency and

41:40

why that might be sort of unifying

41:43

all of this, and then next week

41:45

I'll pick it back up at how we devised

41:47

ways to deal with the self attack

41:49

using medications, allergy shots, the EpiPen,

41:52

and so on. Almost universally,

41:55

allergy or an allergic response

41:57

is described as an overreaction, an

42:00

exaggerated response to an innocuous

42:02

environmental trigger like pollen, like

42:05

dustmites, like peanuts. Since

42:07

scientists first characterized allergies

42:09

in the late eighteen hundreds early nineteen

42:11

hundreds, they referred to the phenomenon

42:14

as an idiosyncrasy, a biological

42:16

contradiction where our bodies harm

42:19

us in an attempt to protect us.

42:22

But more recently some researchers have

42:24

called into question two assumptions

42:26

that underlie this premise of allergy.

42:29

Number one, that this reaction is

42:32

always an overreaction, and

42:34

number two, that the substances

42:37

triggering an allergic response are

42:39

truly innocuous.

42:41

Oh, I can't tell you how

42:43

excited I am about this. I read I'm

42:45

a full disclosure. I read one

42:48

paper that talked about some of

42:50

the evolutionary hypothesis of the

42:52

worms and things that I was like, this is

42:54

my favorite thing I have ever. Yeah,

42:57

because you're right, like, that is the that

42:59

is an underlie I said it at the very top, this is how

43:01

we define an allergy. And those

43:03

assumptions no one that I have read

43:05

or spoken with has ever questioned,

43:08

and I love questioning it.

43:11

It's important, right, Like, yeah, maybe

43:14

it is an overreaction, and it is in some

43:16

certain situations, like definitely an

43:18

overreaction, as in, it is out

43:21

of proportion to the threat that whatever that

43:23

thing causes. Right, but maybe

43:25

not all of the time.

43:27

Right, right, There is a there

43:29

has to be a reason that that response

43:32

exists, exactly, So

43:34

just calling it a straight overreaction makes our immune

43:36

system seem dumb.

43:39

Right, a little overprotective, like

43:41

stop helicopter. Yeah,

43:45

allergies are incredibly widespread,

43:48

and they have grown in prevalence over the past

43:50

century. More on that later. They're

43:52

so widespread that it's difficult to just

43:54

discard them as a quirk

43:57

of the immune system, as our immune system being

43:59

dumb, as just an overreaction with

44:01

no benefit to that overreaction.

44:05

As we all know, an extreme allergic

44:07

reaction can be deadly. And

44:09

while maybe that reaction is just

44:12

a peculiar aspect of our immune

44:14

system, might it also be that there's

44:16

a very good reason that we still

44:18

possess it. And importantly,

44:21

are those two scenarios mutually

44:23

exclusive? Or is it both

44:25

a quirk and an advantage.

44:28

Since the early days of allergy research in

44:30

the first decades of the twentieth century,

44:32

allergies were labeled a modern disease,

44:35

a quote unquote pathology of progress,

44:38

the natural consequence of us living

44:40

what was perceived to be increasingly

44:43

unnatural lives, sedentary lifestyles,

44:46

spending large amounts of time indoors,

44:48

the growth of cities, consuming processed

44:51

foods, using chemicals in the

44:53

home and the environment, and so on. Allergies

44:56

are not the only disease said to result from

44:58

industrialization and develop If

45:00

you remember back to our gout episode, that

45:02

was another one. Yeah,

45:05

And in the case of allergies, there might

45:08

be something to it. So Aarin

45:10

you talked about how when someone is exposed

45:12

to an allergen like a DustMite, their body

45:14

begins producing IgE antibodies,

45:17

which is part of what triggers this rapid cascade

45:19

of symptoms. As it turns

45:22

out, our body ramps up production of

45:24

IgE in response to another

45:26

external threat helminth parasites,

45:30

so dust, MTE, hookworm very

45:32

similar initial responses. One

45:35

major difference, though, is in

45:37

the long term in people

45:39

who are chronically infected with helminth

45:41

parasites that IgE production

45:44

eventually scales down and the entire

45:46

inflammatory response is suppressed

45:49

in part by the parasite itself,

45:51

which allows these parasites to kind

45:53

of fly under the radar. That

45:56

suppression doesn't happen in an

45:58

allergic response. Instead,

46:00

it can just ramp up and up and up

46:02

until anaphylaxis. And

46:04

so, when researchers described IgE

46:07

antibodies in nineteen sixty seven

46:09

and began linking them to different

46:12

exposures to things like allergies

46:14

like parasites, a hypothesis

46:17

emerged that we have this exaggerated

46:19

allergic response and increasing

46:22

rates of allergies in regions

46:24

where parasitic infections are low

46:27

because those parasites are not

46:29

suppressing the immune system. So fewer

46:31

parasites, more allergies, and

46:35

more parasites, fewer allergies. Essentially,

46:38

the hypothesis goes improved sanitation

46:40

and treatments for parasites reduced

46:43

exposure to those parasites, which

46:45

makes our board immune system go

46:47

into overdrive overreacting

46:50

to any stimulus, aka

46:52

the hygiene hypothesis or the old

46:55

friends hypothesis. Now,

46:58

this might be part of what's going

47:00

on, because some studies show that

47:02

regions with higher rates of chronic parasite

47:05

infestation tend to have

47:07

lower rates of allergy,

47:09

and in experiments using mice, those

47:12

chronically infected with helmets

47:14

are protected from developing allergies.

47:18

Pretty compelling evidence. Also,

47:20

some of the genes associated with asthma

47:23

are also associated with increasing

47:25

susceptibility to some parasite

47:27

infections, so these genes might make you

47:29

both more likely to develop asthma and

47:32

more susceptible to parasite infections.

47:35

The hygiene hypothesis does have

47:37

some compelling support when it comes to allergies

47:40

or allergy like diseases, but

47:43

in recent decades some researchers

47:45

are starting to question whether it's

47:47

the only thing going on. If

47:50

you look at the vast array of substances

47:52

that trigger an IgE response, only

47:55

a tiny portion of them are helmets.

47:58

The rest are various nuts,

48:01

animal products, venoms, chemicals,

48:04

so very many different

48:06

things that we encounter regularly

48:09

that are not helmints, that are not parasites.

48:11

Not just worms.

48:13

Yeah, if the IgE response

48:15

evolved in response to helminth

48:18

infections alone, why

48:20

can it be so deadly? Wouldn't

48:22

that have been selected against at some point

48:25

and it's hundreds of millions years

48:27

old evolutionary history, because the IgE

48:29

response is very old, not

48:33

if the benefits outweigh the costs,

48:35

not if there's a reason to maintain it. As

48:38

to what that reason could be. How

48:41

do toxins sound?

48:43

Love toxins?

48:44

There?

48:44

And you know that?

48:45

I know you do? I know you love? You love a toxicologist.

48:48

You love toxins?

48:49

I do.

48:51

In nineteen ninety one, Marjorie Profit

48:54

introduced the toxin hypothesis

48:56

of allergy, and this hypothesis

48:58

suggests that the IG mediated

49:01

allergic response evolved

49:03

to protect us from immediate danger

49:05

posed by toxins. So

49:08

a strong IgE allergic response

49:10

like you described AARON is usually very

49:13

rapid onset, generally speaking within

49:15

seconds or minutes of exposure, and

49:18

it's often accompanied by things like a

49:20

sudden drop in blood pressure, vomiting,

49:23

tearing, diarrhea, coughing,

49:26

all things that would help to expel

49:28

a toxic substance or blow

49:31

it down from reaching vital organs.

49:33

Oh that is such an

49:35

interesting Oh

49:37

how did I never think about that?

49:39

I how did? Like it's

49:42

amazing, It's just like, oh

49:45

yeah, this.

49:46

Is sort of like in your eye. Your body's

49:48

like get it out. Of your eyes, watering

49:50

the heck out of it.

49:51

Right, and allergies do the same things.

49:53

Yeah.

49:54

Oh, I

49:57

hope there's support for this hypothesis because

49:59

I like it.

50:02

It's fascinating. Yeah, And

50:04

you know I was asking in the biology section.

50:06

Okay, Well, the IgE response versus

50:08

other types of antibody responses and

50:11

the allergic response, This IgE

50:13

mediated response is very different

50:16

than that caused by exposure

50:18

to a pathogen like a virus or bacterium,

50:21

and this allergic response wouldn't

50:24

really be effective against those

50:26

infections, which our immune system

50:28

deals with by killing rather than expelling,

50:31

which is what it does to allergens and

50:33

multicellular parasites. Huh

50:36

uh huh. Profit suggests

50:38

that some of the allergens that we think

50:41

of as innocuous, like pollens

50:43

like hay dust or shellfish, may

50:46

not be as harmless as they seem. Pollens

50:49

contain phenolic acids or alkaloids,

50:52

both of which can cause organ or

50:54

nerve damage. Hay Dust can

50:56

be contaminated by pathogenic fungal spores,

50:59

and shellfish can have toxins from algae

51:01

or plankton.

51:03

Fung i. Think fungi are are are

51:06

not well respected in

51:08

this regard in their they

51:11

trigger a similar especially some like asprogillis

51:13

and things like that that commonly can infect like

51:16

grains and blah blah blah. Yeah, sorry,

51:18

but I love this. I'm really excited.

51:21

Yeah. No, And there's also a lot of like I am

51:24

not getting into asthma here because we did

51:26

an asthma right episode, and so

51:28

there's there's a that's a whole separate literature

51:31

in many ways, but there are links between.

51:33

Like a lot of these papers that talk about the evolution of

51:35

allergies also group asthma

51:39

into that, which is entirely reasonable.

51:41

Like we talked about a topic

51:43

disease.

51:44

And there have

51:46

been a lot of links with asthma

51:48

and fungus as well a fungal

51:50

exposure. So yeah, super

51:53

interesting. But

51:56

being able to rapidly recognize

51:58

and deal with these toxic threat that's like

52:01

these alkaloids, like these toxins

52:03

from algae that could be vital

52:05

to our survival both from

52:07

an immunological standpoint as

52:10

well as just us experiencing

52:12

that deeply allergic response and

52:14

wanting to avoid exposure in the future.

52:17

Are allergies a signal to us?

52:20

Do they teach us which plants or foods

52:22

to stay away from.

52:23

Arin I

52:27

I can't tell you how much I love this idea

52:30

because you know what it feels like to me. It

52:32

feels like the difference between like what

52:35

is a weed and what is a desirable plant?

52:37

Mm hmm, like our allergies

52:40

responses to things that they shouldn't be, or

52:42

actually are they responding

52:44

to something that we should be because we shouldn't

52:47

be having so much grap like you

52:49

know.

52:49

What I mean?

52:49

I just yeah, oh.

52:52

I wow, this is mind

52:55

blowing to me.

52:56

I think if me too, because I

52:58

had never really considered I always was just like innocuous

53:01

substance overreaction.

53:02

Yeah are cases.

53:05

Yeah, but peanuts can

53:07

be contaminated with funk a lot.

53:09

Ants, and they also might

53:11

be like these different foods or

53:14

these different allergens might be

53:17

the compound structure itself could

53:19

be similar to similar to something else,

53:21

something that is much more toxic.

53:22

Right what you're saying too?

53:24

Yeah, yeah, it's an interesting

53:27

idea. We love it. But is their

53:29

support for there? I hope so yes

53:32

there is, And is it like the

53:34

most compelling support in the world. I don't

53:36

know. There are my studies, lab

53:38

studies, et cetera. But still but still

53:40

still so. There are a couple studies from

53:42

twenty thirteen that found that mice

53:45

that had previously been exposed to venom.

53:48

One study used a beasting and the

53:50

other used snake venom. The

53:52

mice that had been previously exposed

53:54

were more likely to survive a

53:56

big second dose of venom that should

53:59

have been fatal compared to those

54:01

who did not receive that initial dose,

54:04

suggesting that that big IgE

54:06

response in the second exposure might

54:09

be helpful rather than detrimental. And

54:12

of course this doesn't explain why a beasting in

54:14

humans can lead to a fatal anaphylaxis

54:17

response, because clearly that is very

54:19

helpful. Some

54:22

researchers suggest it's too much of a good

54:24

thing, kind of like sickle cellnemia and

54:26

malaria. Right, having one copy of

54:28

the gene protects you from malaria, but two copies

54:30

leads to disease. While

54:33

most experimental studies looking

54:35

at this toxin hypothesis have focused

54:38

on things like beastings, other epidemiological

54:40

studies have taken a broader view of toxins

54:43

and how they can harm us, such as

54:45

cancer. There's no clear pattern

54:47

when it comes to allergies in cancer, but

54:50

some studies have shown that higher

54:52

rates of allergies is linked to

54:54

lower rates of cancer. But

54:57

I would imagine that that depends on the type

54:59

of cancer and the other lifestyle

55:01

and genetic factors.

55:03

Right, And is it environmental?

55:05

No, that's interesting and weird because there's so much environmental

55:09

cancer exposure blah blah blah.

55:11

And then environmental allergy. Oh,

55:13

that's so weird and interesting.

55:14

Yeah, isn't it interesting? And

55:17

so while the hygiene hypothesis or

55:19

the old friends hypothesis and

55:21

the toxin hypothesis of allergy

55:24

can help to fill in some of the gaps

55:26

as to the why of allergies,

55:29

the complete picture is not yet clear. Yeah,

55:32

how can we take what we know about

55:34

helmets and allergies and apply it

55:36

to treatment? Right? Can we

55:38

make an allergen tree of life to predict

55:41

the groups of antigens that people are likely

55:43

to be sensitive to? Does it have to do with

55:45

evolutionary distance? The farther away

55:48

something is on that evolutionary tree

55:50

of life? Does that mean that we're more likely to

55:52

initiate an immune response to it? The

55:56

future of allergy research is exciting,

55:59

and to understand where we go from here,

56:02

we also have to take a look at where we've

56:04

come from. Yeah, are allergies

56:07

changing and if so, what

56:09

is driving that change.

56:12

Today allergies are one of the most common diseases

56:14

across the world, affecting ten to

56:16

thirty percent of the global population

56:19

and up to fifty percent of people in some regions.

56:22

For years, that number has been

56:24

on the rise, which is why you'll hear

56:26

people refer to this as an allergy epidemic,

56:29

sometimes broken down into two waves,

56:32

the first being respiratory allergies like

56:34

hay fever and the second being food allergies.

56:38

Of course, allergies themselves are not a new

56:40

phenomenon. IgE antibodies evolved

56:42

around three hundred million years ago, allowing

56:45

for this allergic response, and

56:48

we have evidence of allergies from ancient

56:50

times, descriptions of fatal beastings

56:53

what could be allergic rhinitis, and

56:55

of course asthma. But

56:57

the heyday of allergy awareness

56:59

pun intended, really only

57:02

began in the eighteen hundreds,

57:04

with the first description of hay fever

57:06

in eighteen nineteen by John Bostock

57:09

and the first case series published in eighteen

57:11

seventy three by Charles Blackley.

57:14

These observations didn't seem to

57:16

be a case of cool. There's finally

57:18

a name associated with this condition that we've noticed

57:20

for a long time, but a recognition

57:23

of a truly emerging phenomenon.

57:26

Huh.

57:27

Like one summer day in eighteen

57:29

seventy five, your nose starts running

57:32

and your eyes start itching, and you're sneezing

57:34

all over the place, and you find all of

57:36

your friends and family are similarly affected,

57:39

and you're just complaining about it. You form groups

57:41

to talk about it. But just a few

57:43

years ago, no doctor had ever

57:45

heard of such a thing. The sudden

57:47

increase in hay fever in Europe

57:49

and North America around the late eighteen hundreds

57:52

resulted from changes in agricultural

57:55

practices, changing

57:58

which crops were planning, planting

58:02

more pollinaceous. If

58:04

that's a word, it's not. I don't think my

58:06

word document is telling me there's a red underline.

58:08

It's angry, but it's the only thing

58:10

I could think of. Pollinaceous grass

58:12

varieties to feed the growing cattle herds,

58:15

and an increase in farmed land

58:17

in the US, leading to higher ragweed

58:20

growth. This marks

58:22

the beginning of the first wave of the

58:24

allergy epidemic.

58:25

Ladies, it's eighteen hundreds. Okay,

58:28

yeah, that's way further back. I mean it feels

58:30

like I should have expected, but like I

58:32

don't know.

58:33

And it's hard because like people generally

58:35

associate asthma with the first

58:37

wave, and that's like nineteen sixties is really

58:40

when those cases started to super

58:42

ramp up. But if we're talking

58:44

about allergic rhinitis, it really is like

58:46

eighteen eighties roughly.

58:48

Interesting.

58:49

There had been in decades previous descriptions

58:52

here and there, but not like

58:55

sudden recognition of this, whoa everyone

58:58

is experiencing?

59:00

Interesting.

59:01

Yeah. In nineteen

59:03

o six, Clemens von Pirquet coined

59:05

the term allergy to describe the hypersensitivity

59:08

reaction in serum sickness. So

59:11

when someone was given anti serum, let's say,

59:13

for like diphtheria, to treat

59:15

their diptheria infection. But they had extracted

59:17

that anti serum from an animal like a horse.

59:20

Yeah, they had, Yeah, caused the infection,

59:22

got the antibodies all that. Then you

59:24

inject an episode. Interesting,

59:28

we should but yeah, then

59:30

people got real sick from

59:32

them. And by that

59:34

time, so around the early nineteen hundreds,

59:36

other work had shown how anaphylaxis

59:38

can happen, how animals

59:41

negatively react to the introduction

59:43

of a foreign substance, and the

59:45

concept of an allergic response mediated

59:48

by your immune system began to gain

59:50

traction because up to this time,

59:52

germ theory had a pretty tight hold

59:55

on many explanations of disease, and

59:57

so the recognition that it was actually our immune

1:00:00

systems causing these allergic

1:00:02

responses, like the call is coming from

1:00:04

inside the house, took a bit of time

1:00:06

to gain traction. Von Pirquet

1:00:09

combined a bunch of observations from

1:00:11

hyposensitivity, hypersensitivity,

1:00:14

food allergy, hay fever, beasting reactions,

1:00:16

serum sickness, and so on to

1:00:18

create this organized concept

1:00:20

of allergy as it relates to immunity,

1:00:23

and it created momentum for more research

1:00:26

in the area, even if it was initially papooed

1:00:28

by like a lot of his peers.

1:00:30

Classic Classic.

1:00:32

The first decades of the nineteenth century saw

1:00:34

the formation of allergy research groups

1:00:37

and clinics across the globe, and

1:00:39

as far back as nineteen thirty six, the

1:00:41

phrase, quote unquote, the allergy epidemic

1:00:44

was used. Wow, right,

1:00:48

much earlier than I thought.

1:00:49

Yeah.

1:00:50

In nineteen forty six, ragweed

1:00:52

hay fever was such a huge problem

1:00:54

in New York City. That City Council started

1:00:57

a ragweed elimination campaign.

1:01:01

The tides were changing and fast.

1:01:04

Asthma, which prior to nineteen

1:01:06

sixty had been considered a rare disease,

1:01:08

shot up in incidents, doubling in Swedish

1:01:11

Army recruits from nineteen seventy one to nineteen

1:01:13

eighty one huge rise, as

1:01:15

did hospital admissions for the condition,

1:01:18

which increased tenfold between

1:01:20

nineteen sixty five and nineteen eighty In

1:01:23

Australia, the UK, New Zealand,

1:01:25

Canada, and the US tend

1:01:27

for afterasthma. In

1:01:29

the nineteen seventies, after the discovery

1:01:31

of IgE, researchers observed

1:01:34

a sharp increase in allergen

1:01:36

specific IgE antibodies against

1:01:38

environmental allergens, growing

1:01:41

to over fifty percent of the population in

1:01:43

some regions like I mentioned, and

1:01:45

the second wave of the allergy epidemic.

1:01:47

Food borne allergies began much more

1:01:49

recently. Around nineteen ninety is

1:01:51

most most papers I read, and that's

1:01:54

the same time that asthma case is actually

1:01:56

plateaued. One large

1:01:58

study found that between nineteen ninety seven

1:02:00

and two thousand and eight, allergies

1:02:02

to peanuts and tree nuts tripled,

1:02:06

tripled, huge. Yeah.

1:02:09

Reports from Australia indicate a tenfold

1:02:11

increase in referrals to food allergy

1:02:13

specialists and a five fold increase

1:02:15

in hospital admissions for food related

1:02:18

anaphylaxis. This

1:02:20

is not just a matter of doing a better job

1:02:23

of recognizing these allergies, No.

1:02:26

Especially not with food allergies because the reaction

1:02:28

is usually so severe.

1:02:30

Exactly. Yeah, what is

1:02:32

driving this explosive rise?

1:02:35

Yeah, that is the billion dollar

1:02:37

question. We don't fully

1:02:39

know, of course, here

1:02:42

is what we do know. We know

1:02:44

that while this is a global rise,

1:02:46

the highest increases are seen in

1:02:49

more industrialized countries. For

1:02:51

instance, following the reunification

1:02:54

of East and West Germany in nineteen eighty

1:02:56

nine, prevalence of allergy shot

1:02:59

up in East Germany, where it have been

1:03:01

much lower in previous decades.

1:03:02

I think that's one of the most interesting examples

1:03:04

because it's so like discrete and like

1:03:07

the regions are so close

1:03:09

to each other, so it's like not like

1:03:11

what is it because it's not just like

1:03:13

natural environment exposure clearly like.

1:03:15

Weather, right, pollen

1:03:19

is not does not respect the Berlin exactly

1:03:22

yeah. Yeah,

1:03:25

And on average, allergies

1:03:28

are twenty times more common

1:03:31

in affluent quote unquote westernized

1:03:33

countries compared to those with lower incomes.

1:03:36

And we know that this rise is not limited to

1:03:38

allergies or asthma, but it

1:03:41

also is seen in other autoimmune

1:03:44

or immune mediated diseases. We

1:03:47

know that these diseases are not rising

1:03:49

all at the same time, or in the same place

1:03:52

or at the same pace, which

1:03:54

could suggest different mechanisms behind

1:03:57

the rise in each of them. And

1:03:59

this has been you to challenge the old

1:04:01

friends or the hygiene hypothesis, since

1:04:03

countries that saw the biggest rise in allergies

1:04:05

only did so beginning really

1:04:07

in the nineteen sixties, which was around

1:04:09

forty years after major sanitation

1:04:12

changes would have reduced waterborne

1:04:14

pathogens and anti helmath

1:04:16

campaigns had reduced parasite burden

1:04:19

to almost nothing. So

1:04:21

what could be going on? Most

1:04:24

of the predominant ideas fall under

1:04:26

the hygiene hypothesis or the

1:04:28

old friends hypothesis or the biodiversity

1:04:31

hypothesis, which are kind of like more recent

1:04:33

offshoots, and both of these suggest

1:04:35

that our allergies are a result of

1:04:37

us not being exposed to as many

1:04:40

or as diverse microbes and parasites

1:04:42

that we used to throughout our evolutionary

1:04:44

history. Why

1:04:46

that would lead to more allergies depends

1:04:49

on who you ask. Maybe

1:04:51

it's that with decreasing family size,

1:04:54

kids are not coming into contact with as

1:04:56

many germs at a young age, although

1:04:59

some childhood pathogens like RSV

1:05:01

are positively associated with developing

1:05:03

allergies. So it's like the

1:05:06

right germs, right, right, Which germs

1:05:08

that's the Yeah, Yeah, it's

1:05:12

layers, compilators.

1:05:14

It's almost like our immune system is complicated.

1:05:16

I don't know what.

1:05:20

Maybe it's that our use of antibiotics

1:05:22

at an early age disrupts our gut

1:05:24

microbiome and primes us to develop

1:05:27

allergies. Maybe it's that we

1:05:29

spend more time inside and sedentary

1:05:31

early childhood. Exposure to pets or

1:05:33

farm animals seems to reduce the risk

1:05:36

of allergies, and exercise

1:05:38

reduces allergic inflammation. I

1:05:41

found a study looking at babies born during

1:05:43

COVID lockdown in twenty twenty, and this

1:05:45

study found higher rates of allergies

1:05:47

in that cohort. So it's

1:05:50

like, again, the limited exposure to the outside

1:05:52

world. Maybe it's

1:05:54

the chemicals and our soaps, food packaging,

1:05:57

microplastics, pollution, ozone, cigarette

1:05:59

smoke, that disrupts our protective

1:06:02

epithelial barriers and

1:06:04

sends our immune systems into overdrive.

1:06:08

If you think about it, the allergic

1:06:10

response is kind of like a

1:06:12

hail marry last resort option

1:06:15

to protect us from toxins. After

1:06:17

our skin or skin microbiota,

1:06:20

after our guts or gut microbiota,

1:06:22

our lungs and lung microbiota,

1:06:24

lets it get through, right like, there are so many other

1:06:27

layers of protection, and

1:06:29

then maybe it's that once it makes

1:06:31

it past all those layers, then

1:06:33

we have this last ditch effort

1:06:35

to protect us from whatever

1:06:37

perceived tosin there is. And

1:06:40

if those layers are continually broken down

1:06:42

by some of the things that

1:06:44

we encounter in our everyday lives,

1:06:46

like processed foods, you know, all

1:06:49

of these different things that all combine

1:06:51

together to increase

1:06:53

permeability of those barriers, does that

1:06:55

then lead to increase allergy?

1:06:57

And I think that's one of the things that makes the

1:06:59

there's a there's a lot of research being

1:07:01

done on like is exzema and

1:07:03

the breakdown of your skin barrier that happens

1:07:05

with egzema. Does it also result in this abnormal

1:07:08

presentation of these toxins

1:07:12

or of these allergens right where it's like, typically

1:07:14

you shouldn't be able to be exposed to, say,

1:07:16

cat dander through your skin because your skin

1:07:19

should be able to keep cat dander out. But if

1:07:21

it gets in that way, does that predispose you to

1:07:23

And cat dander might be a crappy example, I don't know,

1:07:25

but like, if you get peanut on

1:07:27

your skin, peanut protein shouldn't be able

1:07:29

to make it through your skin. If

1:07:31

it does, does that trigger your immune

1:07:33

response to think that it is something that is pathogenic?

1:07:36

So that's one of those kind of ideas.

1:07:40

Right, Yeah, novel exposure

1:07:42

roots exactly these things because

1:07:45

of a decreased barrier in permeability.

1:07:47

Which is why I think, like the AlphaGo story is

1:07:49

so interesting in that, like

1:07:52

because it applies so much to that. So yeah,

1:07:55

I don't know, Yeah, it's interesting.

1:07:57

Aaron.

1:08:00

Uh, we don't

1:08:02

have a single simple answer for

1:08:04

why tree nut allergies suddenly exploded

1:08:06

in the past few decades, although I do think

1:08:09

that part of it is, at least from my reading,

1:08:11

our response to them initially how

1:08:14

it was like, don't expose anymore.

1:08:16

If there's the slightest bit of reaction, then

1:08:18

it sort of Yeah.

1:08:19

I am really curious.

1:08:21

This is jumping so far ahead. I'm sorry, but I'm

1:08:24

so curious to see

1:08:26

what is going to happen in the next decade.

1:08:28

Like with like, because it was our generation

1:08:31

that has really high rates of things

1:08:33

like peanut and tree nut and all these food

1:08:35

allergies. And it was our

1:08:38

generation that very much was told by

1:08:40

physicians, do not expose your children

1:08:43

because we don't want them to develop allergies. And it turns

1:08:45

out, against spoilers, that that was exactly

1:08:47

the wrong advice. And now we know that because

1:08:50

of these phenomenal studies, and so early

1:08:52

introduction is now the recommendation. So

1:08:54

what are rates going to be like in kids

1:08:57

in five ten years. I'm super curious

1:08:59

about all this, like how the epidemiology

1:09:01

is going Is it going to change, I don't know, is it.

1:09:03

To help you? And

1:09:06

you know, like we probably won't

1:09:09

ever have one simple, unifying

1:09:11

answer to this. I agree,

1:09:14

and I will say also, like the hygiene hypothesis

1:09:16

or the old friends hypothesis, or the

1:09:19

toxin hypothesis or the epithelial

1:09:21

barrier hypothesis, these things aren't

1:09:23

attempting to explain away all cases

1:09:26

of allergies or autoimmune diseases

1:09:28

with one bottom line. Instead,

1:09:31

what they're doing is highlighting patterns of

1:09:33

allergy, pointing out where we can look

1:09:35

next. If it is certain detergent compounds

1:09:37

causing a rise in asthma because of increased

1:09:40

skin permeability, why

1:09:43

and how. If it is a disrupted

1:09:46

microbiome, what about it makes it disrupted?

1:09:48

And how can we restore balance. If

1:09:51

it is epigenetic effects, what are

1:09:53

those prenatal exposures that increase

1:09:56

someone's chance of developing allergies?

1:09:59

While the comp tx nature of allergies makes

1:10:01

all of this seem so overwhelming,

1:10:04

the truth is that people are doing incredible

1:10:07

research to answer these questions, to get

1:10:09

at the underlying triggers of different

1:10:11

allergies, and it really seems

1:10:13

like we're slowly going to be able

1:10:16

to put the puzzle pieces together, at

1:10:18

least for some pictures right,

1:10:20

for some bits of the allergy, and

1:10:23

come up with better ways to understand,

1:10:25

prevent and treat allergies. I

1:10:27

love it so now, Aaron, I'll

1:10:30

turn it over to you to tell us where

1:10:32

we are with allergies around the world today.

1:10:35

I'll give it my best shot right after this.

1:11:02

So you told us already, Aarin, that all

1:11:04

of these allergic disorders, from

1:11:07

hay fever, from seasonal allergies,

1:11:09

from food allergies. They're

1:11:11

all on the rise, that is certainly

1:11:14

true, and they have been for a while

1:11:16

longer than I realized, apparently. When

1:11:18

it comes to I'll break this down into

1:11:20

like the allergic rhinitis, which is

1:11:22

more you think of as the hay fever, the seasonal

1:11:24

allergies, it's the runny nose and the blah

1:11:26

blah blah running eyes. And I don't

1:11:29

say blah blah blah to discount it because

1:11:31

it has pretty significant effects on people's

1:11:33

lives, as we'll see. But

1:11:35

a paper from the Lancet from twenty eleven,

1:11:38

which is old now, estimated

1:11:40

that four hundred million people worldwide

1:11:43

are affected by allergic rhinitis,

1:11:46

and this number is likely higher

1:11:48

today as this, like all allergies,

1:11:51

has continued to increase. But

1:11:54

this varies a lot across

1:11:57

the globe. And while most

1:12:00

of allergic rhinitis develop

1:12:02

in like child or teen years, sometimes

1:12:05

they don't. There's plenty of adults who don't

1:12:07

develop seasonal or

1:12:10

environmental allergies until

1:12:13

much later in life. But

1:12:15

overall, in some areas of the globe,

1:12:17

prevalence is as high as like seventeen

1:12:20

to twenty percent. Those seem to be the highest

1:12:22

percentage numbers that I saw

1:12:25

and across the board, even though in

1:12:27

the International Study of Asthma and

1:12:29

Allergies in Childhood, which is also

1:12:32

now old because the Phase three

1:12:34

study finished in like the early two thousands,

1:12:37

but in this study, the rates of

1:12:39

allergic rhinitis were actually

1:12:41

greatest in Latin America

1:12:43

and African countries. But

1:12:46

even there the prevalence was higher

1:12:48

in urban areas compared to rural areas,

1:12:51

and that pattern is true pretty much across

1:12:53

the globe. Allergic

1:12:55

rhinitis also has pretty significant

1:12:58

burdens on our healthcare system. In

1:13:00

the nineties, way back in the nineties,

1:13:03

it was estimated to cost one point

1:13:05

nine billion US dollars every

1:13:07

year, and that increased

1:13:10

to three point four billion in

1:13:12

the early two thousands. And

1:13:14

that's not even counting indirect costs,

1:13:16

of which there are enormous indirect

1:13:18

costs, things like miss school, missed work.

1:13:21

Allergic rhinitis especially can result

1:13:23

in things like poor sleep or sleep apnea.

1:13:26

It can contribute which can then lead to

1:13:28

fatigue, memory problems, mood changes.

1:13:30

It can make school harder for kids,

1:13:32

like, it is not a minor like

1:13:34

we might think of it as, oh, it's just

1:13:37

a runny nose. It is not just a running

1:13:40

nose. Right, Food

1:13:42

allergies we have much credier

1:13:44

data for.

1:13:46

Which is interesting to me for

1:13:48

some reason. I don't know why.

1:13:50

Yeah, I think I think it's we have credit or like

1:13:52

global data.

1:13:53

Okay, but no doubt.

1:13:55

Food allergies are absolutely on the rise.

1:13:57

In some countries, as much as ten percent

1:14:00

of children have at least one

1:14:02

food allergy. And food

1:14:05

allergies are especially interesting

1:14:07

because for some foods,

1:14:11

up to like seventy or eighty percent of

1:14:13

kids will outgrow their food allergy,

1:14:15

and those foods tend to be things like egg and

1:14:18

milk, but things like peanuts

1:14:20

and tree nuts tends to

1:14:22

be much less likely that kids will outgrow

1:14:25

it. Usually it's twenty percent or less

1:14:27

of kids with a peanut or tree nut allergy

1:14:29

will outgrow them. Then

1:14:31

there's other food allergies like shellfish

1:14:34

and fish, which not only

1:14:36

do we have less data for the

1:14:38

idea that early introduction can

1:14:40

prevent sensitization for

1:14:43

things like fish and shellfish, but

1:14:45

it's also more likely that people don't develop

1:14:48

those allergies until adulthood.

1:14:50

Why why, Oh

1:14:53

you know, I have a quick question. Actually, yeah,

1:14:56

dose and relationship

1:14:58

to response one. You

1:15:00

know, one peanut, how much peanut or

1:15:03

almondors shellfish, shrimp

1:15:05

tail?

1:15:06

You know. So yeah, maybe it's worth talking a little bit

1:15:08

in more detail about this. So the study that showed

1:15:11

that early exposure can

1:15:13

reduce the risk of peanut allergy, the

1:15:15

big one was called Leap Learning

1:15:17

Early about Peanut Allergy, and then there was another one

1:15:19

I think called EAT and I

1:15:21

forget what that acronym stands for. But these

1:15:24

were like really landmark studies that showed

1:15:26

that early exposure and early exposure

1:15:28

meant like four months of life, but

1:15:31

definitely earlier than eleven months

1:15:33

of life. So before a baby turns one year

1:15:35

old, you start with exposure

1:15:38

to peanuts, and

1:15:40

you have to have persistent exposure.

1:15:43

So it's not like give them peanuts one time

1:15:45

and then you're good. These studies

1:15:48

were consistent exposure, like two

1:15:50

to three times a week every week for the

1:15:52

first five years of life. Okay, wow,

1:15:54

but in those kids and in these studies,

1:15:56

they took kids who were high risk,

1:15:59

kids who either had severe eggzema

1:16:03

or had a known allergy to

1:16:05

egg or In some of

1:16:07

the studies it was kids who had a family history

1:16:09

of peanut allergy, so

1:16:11

these were high risk kids because we know that there's

1:16:13

genetics in these associations. So

1:16:16

in those kids, the reduction

1:16:19

in risk of peanut allergy was like

1:16:21

seventy to eighty percent. It

1:16:24

was massive, massive

1:16:26

reduction in risk, and

1:16:28

so across the board. Now the recommendation

1:16:30

is early exposure, but it has

1:16:32

to be that consistent exposure, so it's not like

1:16:36

necessarily a one time dose, like give

1:16:38

this much peanut. It's really like start

1:16:41

small, but continued

1:16:43

exposure, so like a little peanut on the

1:16:45

finger when they're a tiny baby, continuing

1:16:47

that until they're like eating peanut butter and

1:16:49

their oatmeal like a couple times a week when

1:16:52

they're kids, and that significantly decreases

1:16:55

the risk. And so that data has

1:16:57

now been extrapolated to a lot of the

1:16:59

foods that the earlier exposure

1:17:01

to all of the main allergenic foods,

1:17:04

and in the US, those foods are

1:17:06

wheat, soy, tree

1:17:09

nuts, peanuts, milk,

1:17:12

egg, oh, crap,

1:17:14

I should have written all of these town fish,

1:17:18

shellfish, and now sesame. That's

1:17:20

the early net. The newest edition.

1:17:24

So early and consistent exposure to

1:17:26

all of those is what's now recommended

1:17:29

to try and prevent food allergies.

1:17:31

And we don't know what happens when someone just develops

1:17:34

an allergy, a food allergy at the age of thirty

1:17:37

five?

1:17:37

No, is it all alpha calerin? I don't know.

1:17:41

It all comes down to alpha cal.

1:17:43

Is it the ticks?

1:17:45

No?

1:17:45

Yeah, I don't know. Is it a

1:17:47

threshold thing like we kind of talked about,

1:17:49

Is it that maybe they had some level

1:17:51

of it? Here's the other thing, arin, Oh my gosh,

1:17:55

there is a proportion of the population who

1:17:58

if you test them, they develop

1:18:00

these IgE antibodies, aka, they

1:18:02

are sensitized to

1:18:05

various things, be they aero allergens

1:18:07

like cat dander. Cat dander is a good example

1:18:09

because if you test kids who live

1:18:11

in homes with cats, a higher

1:18:14

percentage of them will have a degree

1:18:16

of sensitization at a certain

1:18:18

age, but a lower percentage

1:18:20

of them will be allergic, will have

1:18:22

that allergic response to kings.

1:18:25

And so yeah, so like what is

1:18:27

it about sensitization versus then

1:18:30

who of those kids who are sensitized actually

1:18:33

then will have allergies.

1:18:35

We don't exactly know, so is there is

1:18:37

that what it is for adults who develop say a shellfish

1:18:39

allergy later in life, that maybe they were a

1:18:42

little bit sensitized, but it wasn't until

1:18:44

that built up enough in their system that

1:18:46

they had an allergic response.

1:18:48

I don't know, okay, but

1:18:50

the quantity of exposure,

1:18:52

or the amount of allergen that they're exposed

1:18:54

to, can lead to really different responses

1:18:57

than some people. Where some people are like even the

1:18:59

most minute amount can lead to

1:19:01

these horrible reactions, whereas

1:19:03

other people can have there's a threshold where

1:19:05

that causes Yes, I guess, okay, one hundred

1:19:08

percent.

1:19:08

Yes, that is absolutely true, and we don't

1:19:10

understand why. Okay,

1:19:14

ah, so yeah, that's

1:19:16

like what we know of. When it comes

1:19:18

to the most severe outcomes, that is anaphylaxis.

1:19:21

We again don't really have great data here because

1:19:24

most of the data that we have is on

1:19:26

hospital admissions for anaphylaxis,

1:19:30

and not all people

1:19:32

with anaphylaxis have to actually be admitted to

1:19:34

the hospital. And also it's not always

1:19:37

allergies that cause anaphylaxis. But

1:19:39

at least in some of the papers that I found,

1:19:41

it's estimated that about zero point three percent

1:19:44

of the population of Europe will experience

1:19:46

anaphylaxis at some point in their lives.

1:19:49

Wow, okay, yeah, higher than I expected.

1:19:52

And the data across the board is

1:19:54

that especially in most high income

1:19:56

countries, which is where we have data, incidents

1:19:59

of anaphylaxis is increasing,

1:20:02

which makes sense because

1:20:04

allergies across the board are increasing.

1:20:07

Anaphylaxis, especially due to food

1:20:10

born triggers, is increasing. Anaphylaxis

1:20:13

due to alpha gu specifically is

1:20:16

increasing big time. But

1:20:19

mortality does not seem

1:20:21

to be increasing, except

1:20:24

in Australia, which some of the data has

1:20:26

had increases in mortality associate with

1:20:28

anaphlexis.

1:20:30

So does that mean that we have developed

1:20:32

better tools or is that a tune in for next week to

1:20:34

find it?

1:20:35

That's a tune in for next week to find out how

1:20:37

do we treat it? That was my segue erin you

1:20:41

guessed it?

1:20:43

I love it.

1:20:45

So yeah, that's allergies for

1:20:47

now, but I can't wait for

1:20:49

next week to hear about how we figured

1:20:51

out how to treat these things, and then we'll talk

1:20:54

about how we treat them and

1:20:56

what our thoughts are about preventing them in

1:20:58

more detail next week.

1:21:01

But until then, if you would

1:21:03

like to learn more about things

1:21:05

like the how allergies

1:21:08

work, the IgE mediated response, the

1:21:10

evolution of allergies, the rise

1:21:12

and allergies. We've got sources.

1:21:14

For you, so many.

1:21:16

I have so many, and I highlighted

1:21:18

too right here just because

1:21:22

to list them all out would take another ten minutes.

1:21:24

So there's one by Dasher

1:21:26

and Fernandez from twenty nineteen titled

1:21:29

Allergy in an Evolutionary Framework

1:21:31

that's all about the evolution of allergies. And then

1:21:34

by Actus from twenty twenty one, does

1:21:36

the epithelial barrier hypothesis explain

1:21:39

the increase in allergy, autoimmunity,

1:21:41

and other chronic conditions?

1:21:43

Fascinating stuff for

1:21:46

the biology of allergies. Boy, do

1:21:49

I have plenty of rabbit holes that you can go down,

1:21:52

But I'm going to shout out like four or five

1:21:54

main papers that are really high

1:21:56

level overviews. One is from

1:21:58

the New England Journal of Medicae in from two thousand and one,

1:22:01

so it's old but still good, and that is

1:22:03

just called Allergy and Allergic Diseases.

1:22:05

There was one on titled food Allergy

1:22:08

from Nature Reviews Disease Primers

1:22:10

from twenty eighteen, and another one titled

1:22:13

food allergy from the Lancet two thousand and two,

1:22:15

and then two on allergic rhinitis, one

1:22:18

titled Allergic Rhinitis from the Lancet

1:22:20

twenty eleven and one titled

1:22:22

Allergic Rhinitis Definition, Epidemiology,

1:22:25

path of Physiology, Detection and Diagnosis

1:22:27

from the Journal of Allergy and Clinical Imminology

1:22:29

from two thousand and one. There's so many There's so many

1:22:32

more. We're not going to read them all, but you can find them on

1:22:34

our website, This Podcast will Kill You dot com under

1:22:36

the episodes tab for this episode and

1:22:38

everyone we've ever done, they're

1:22:41

all there.

1:22:43

Thank you again, Caitlin so much

1:22:45

for sharing your story with us and really

1:22:48

helping to illustrate that allergy

1:22:51

to environmental allergens

1:22:53

is not just a running nose.

1:22:55

No, it means so much more.

1:22:58

Thank you so much for being willing

1:23:00

to take the time and to share your story

1:23:02

with us and all the listeners. We really appreciate

1:23:04

it.

1:23:05

Thank you to Bloodmobile for providing the music

1:23:07

for this episode and all of our episodes.

1:23:10

Thank you to Leona Scuilatchi

1:23:12

and Tom Bryvocal for the audio mixing.

1:23:14

Thank you to everyone at Exactly Right.

1:23:17

And thank you to you listeners. We hope you

1:23:19

enjoyed this episode and that you're stoked for next

1:23:21

week to learn even more about allergies.

1:23:24

Yeah.

1:23:24

Why do EpiPens work the way they do?

1:23:26

I can't wait to find out.

1:23:28

Yeah, me too, got

1:23:30

some reading to do. Thank you also to

1:23:32

our wonderful, generous, amazing

1:23:34

patrons, We really truly appreciate

1:23:37

your support so much. Thank you, Thank

1:23:39

you well. Until

1:23:41

next time, wash your hands.

1:23:43

You feel the animals

1:24:05

U