Ep 162 Allergies Part 2: Shots, pills, & pens

Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:00):
My name is Samantha.

Speaker 2 (00:01):
I am forty two, and I've never really paid much
attention to allergies. I am allergic to mosquitoes, but my
allergy has lessened in severity as I've gotten older, and
I really don't even take many precautions anymore.

Speaker 1 (00:15):
And I have an acquired allergy to penicillin that I've
had since I was a child.

Speaker 2 (00:20):
I moved to Florida five years ago and had my
first interaction with a fire ant. I was leaving work
and one fell down my shirt and stung my chest.
It hurt and was itchy, but I didn't give it
a second thought, and it really was just a funny
story to tell my coworkers. I don't even think I
had a welt to the next day. About two months ago,

(00:42):
I was mowing my lawn in flip flops, and I
know you're not supposed to do that, but it is
Florida and it's August, and I really don't like wearing
shoes and socks. I felt something itchy on my foot.
It didn't hurt, and when I looked down, I only
saw grass. So I brushed my foot off and just
went about my business that evening. The top of my
foot started to turn red and swell.

Speaker 1 (01:05):
It was itchy.

Speaker 2 (01:07):
It just looked like maybe a bug bite or I'd
brushed up against some plant that I shouldn't have. The
next day, though, I had two little white pustules form
and the red area had doubled in size.

Speaker 1 (01:18):
I still wasn't really worried.

Speaker 2 (01:20):
But by the afternoon my foot was much more swollen
and still very itchy, and several more white pustules had formed.
I went to a clinic and they gave me a
ten day round of antibiotics and told me to go
to the er if it got worse. By the time
I got home that evening, part of my foot had
kind of a yellowish tint, and I wasn't sure if

(01:43):
that was from the bite or whatever I had interacted with,
or because I had been driving, or because I had
been standing that day, so I just went back to
the er to be sure.

Speaker 1 (01:54):
There they said it looked like ampstings.

Speaker 2 (01:57):
And a few days later I was out mowing my
lawn again, yes still in flip flops.

Speaker 1 (02:02):
I had not yet learned my lesson.

Speaker 2 (02:04):
And I mowed over a fire ant hill that was
hidden in the grass, and then I stepped on it.
I immediately felt pain and itchy. When I looked down,
my foot was covered with hundreds of ants all over
my left.

Speaker 1 (02:19):
Foot and ankle.

Speaker 2 (02:20):
They were on my right foot, they were all over
my mower. When I went to brush them off, they
got on my hands and stung my hands. I was
able to get them off I moved away. The pain
subsided really quickly, but I was definitely feeling the itch.
After I regained my composure, I realized I was fine.
I finished mowing and we'd whacked my fence line. When

(02:43):
I went inside, I put ice on my feet and
sat down for a few minutes. By now, it had
been about twenty minutes since I had stepped on the
ant hell, and I noticed that I was itching on
my braw and my waistline. But I figured, you know,
I just saw a whole bunch of insects, and people
get itchy after they see insect So I went to
take a cold bath, and when I got undressed, I

(03:05):
saw red patches all over my skin, chest, trunk, down
my arms, down my legs, front and back, and I
was like, oh, a rash. Because I've never had hives
that I remember, so I didn't realize right.

Speaker 1 (03:18):
Away that's what that was.

Speaker 2 (03:20):
I was in the bath for about fifteen minutes when
I started coughing and having difficulty taking deep.

Speaker 1 (03:25):
Breaths, and I said, this is not normal. I need
to go to the AR.

Speaker 2 (03:30):
So I drove back into town and it's about a
thirty minute drive to get to the EAR from my house.
And they took me back pretty quickly into a consult
room and I was chatting with the nurse while they
were starting IV. I was in good spirits and everything,
and then all of a sudden, my visions started to
get blurry. I texted my friend, I need you er
on forty third and after that, I don't remember much,

(03:54):
but here's what I do remember. I said, several times,
my vision is blurry. I'm going to be sick. I
need a bag. I'm going to throw up. The nurse said,
several times, take a deep breath and try to stay calm.
I told her that my hearing was fuzzy. It sounded
like I was underwater. I said, please help, I'm going
to be sick. And I remember an oxygen canula going

(04:15):
on my nose. I remember the nurses trying to wheel
me out in the chair. That I was in but
hitting a door or a wall several times. They were
having difficulty maneuvering in the chair. My body convulsed. I
don't know what that looked like, but it felt terrifying.
I heard someone say something about fifty somethings of benaderyl.

(04:37):
I felt a sharp jab in my arm, followed by pain,
and after a while I.

Speaker 1 (04:43):
Was able to open my eyes.

Speaker 2 (04:45):
I saw my friend had arrived, and I said to
no one in particular, well that was fun, and no
one laughed, so I realized it was maybe more serious.
A doctor came in and explained that my blood pressure
had dropped to eighty six over fifty four, my heart
rate had dropped forty seven, and I had had a

(05:06):
false positive to something, so they had to do a
ct with contrast. After a couple hours, they discharged me
with prednizone, doxycyclin, femididine, and epinephrine pens. Obviously, I don't
go walking through my yard barefoot or on flip flops,
and I carry my EpiPens in a cute little fanny pack.
It kind of stinks, but dying is worse. That's my

(05:27):
allergy story.

Speaker 1 (05:28):
Thanks.

Speaker 3 (05:30):
My parents found out that I was allergic to peanuts
when I was eighteen months old. After rubbing bits of
a peanut butter and jelly sandwich all over myself, as
babies do, I broke out in hives and was rushed
to the hospital where my allergy was confirmed. From that
day forward, I was taught to have the utmost caution
around peanuts, and I did. I've been lucky enough to

(05:54):
only really go into anaphylactic shock twice because it's been
so rare for me. I never truly knew what all
the warning signs could be for an episode, only that
if I got hives, I had a very short amount
of time to use my EpiPen and get immediately to
a hospital. And while that advice was helpful for my
first run in with anaphol axis, it unfortunately wasn't enough

(06:18):
for my second. In February twenty twenty three, I was
visiting friends in San Francisco and we went out as
a group for dinner for dim sum. I made sure
to ask the wait staff about peanuts and inform them
of my allergy while ordering, as I always do when
dining out. After my friends and I confirmed in both
English and Mandarin that all of the food we ordered

(06:40):
was safe, we dug in. As soon as the meal ended,
I felt a bit flushed. I went to the bathroom
and I couldn't see any hives or swelling, so I
attributed the flesh to digestion and a bit of anxiety
and carried on. About ten into the walk back to

(07:01):
our airbnb, I started to feel a little winded, and
five minutes after that I started to feel faint. I
figured that I must be having an asthma attack. Since
I couldn't really explain this constellation of symptoms otherwise, I
pulled one of my friends aside and asked her if
we could sit together at the nearest bus station while

(07:21):
I called an uber back to the airbnb, since I
didn't think I could make the last ten minutes of
the walk. As soon as we sat down, I started
to throw up and I was unable to stop.

Speaker 1 (07:34):
At this point, I still didn't.

Speaker 3 (07:36):
Know what my body was reacting to, and I was
starting to dip in and out of consciousness. The friend
I'd pulled aside and a kind business owner from the
corner store called nine one one when I was no
longer verbally responsive, and it was only then that we
learned from the nine one one operator that I was
in the middle of an anaphylactic episode. I had an

(07:57):
EpiPen on me, but before the operator could finished telling
my friend how to use it, an ambulance arrived and
gave me a double dose of epinephrine, saving my life.
While we will never know with one hundred percent certainty
whether my reaction was due to cross contamination or peanut
butter mixed into a sauce and forgotten, what we do

(08:18):
know is that I took every step possible to avoid
exposure to peanuts, and for whatever reason, it wasn't quite
enough this time. I am incredibly lucky and grateful for
my friend and that business owner, as by the time
I'd realized something was seriously wrong, I'd lost the motor
skills to do anything about it. Since then, I've told

(08:40):
as many people as I can about the different presentations
of anaphylaxis with the hopes of saving another person's life.
After twenty eight years of caution, I still almost died
of anaphylaxis. So I would urge anyone else with a
fatal allergy to please stay aware of the different presentations

(09:00):
of anaphylaxis, and I would urge everyone else to learn
how to use an EpiPen just in case.

Speaker 1 (09:52):
Oh just terrifying.

Speaker 4 (09:56):
Like so, there's so many different ways that allergies terrify me.
And these are both just incredible stories and I'm so
glad that you're both Okay.

Speaker 1 (10:08):
Yeah, yeah, thank you so much for sharing those stories
with us and with our listeners. We really appreciate it.

Speaker 4 (10:15):
And wow, yeah, thank you.

Speaker 1 (10:19):
Hi.

Speaker 4 (10:19):
I'm Aaron Welsh and I'm Erin Alman Updyke.

Speaker 1 (10:22):
And this is this podcast will Kill You.

Speaker 4 (10:25):
We're bringing you a part two of our Allergies episode
we Are.

Speaker 1 (10:29):
I am really excited for this. I gotta say, like, yeah,
anyistamines and other allergy treatments I feel like have become
so much a part of our daily lives or our
medicine cabin.

Speaker 4 (10:40):
Our medicine cabinets one hundred percent.

Speaker 1 (10:42):
But how do they work? And also, Erin the first
time I heard of allergy shots, my mind was first
like do those work? How does that actually work?

Speaker 4 (10:54):
I this is not accurate, but I feel like I'm
really curious about the history of allergy shots because they
feel a little bit like homeopathy even though they're not,
Like they're not but it's a little bit like that, right,
It's like give the smallest little dose and then yes, so.

Speaker 1 (11:12):
It's yeah, treating like with like I mean, it actually
does have its roots in homeopathy, which I'm not going
to talk about, but that is kind of the way
that it all started, was like, oh, if a lot
hurts you, then a little bit, maybe you'll get used
to it.

Speaker 4 (11:25):
Right, Yeah, but it actually works in this case, actually works.

Speaker 3 (11:29):
I know.

Speaker 4 (11:29):
Yeah, So we will talk about how it works and
where it came from and all the things for all
the treatments, well most of them at least for allergies. Today,
that's what we're focusing on is how last week, if
you haven't listened by the way to last week's episode,
it's all about what are allergies? What are they even?
How do they work? Where did they come from? Evolutionarily?

(11:52):
Why are we stuck with these things? Yeah, it's a
great episode. Check it out. But this week we're talking
about what do we do at them? Once you have them?

Speaker 1 (12:01):
What do we do about them? But before we get
into all of that, we've got some very important business
to get into. We do.

Speaker 4 (12:08):
It's quarantine. Ay time, Aaron, what.

Speaker 1 (12:11):
Are we drinking again? This week.

Speaker 4 (12:12):
Well, of course we're drinking the allergy shots this week
especially yep, it is.

Speaker 1 (12:19):
It's a shot, right, Like, what else could we have done?

Speaker 4 (12:22):
We could have called it oral immunotherapy. Just kidding. It
is not, but that's that's what you call it when
you give some an oral allergy shot.

Speaker 1 (12:31):
Good blood, Aaron, that's a great one.

Speaker 4 (12:35):
I thank you.

Speaker 1 (12:37):
In the allergy shot is it's a pretty simple concoction
of rum, orange juice, pineapple juice, and Quantroe dill ish.

Speaker 4 (12:46):
Check it out. The recipe's already posted on our social
media channels, so if you're not following us there, you
definitely should be. Also, did you know we're on TikTok?

Speaker 1 (12:55):
We are?

Speaker 4 (12:55):
We are? We have videos there.

Speaker 1 (12:57):
On our website Podcast will Kill You dot com, you
can find so many varied things, right. You can find
the notes for each and every one of our episodes,
which has the sources. In case you wanted to read more,
you can find links to our bookshop dot or affiliate account,
our Goodreads list, music by Bloodmobile, links to our Patreon,

(13:19):
links to merch links to savings. In case you're like, oh,
I heard a discount code for this podcast? What was
that product? What was that code? Check out our website
This podcast will kill You dot com. You can find
all sorts of things. Transcripts. Did I mention that transcripts?

Speaker 4 (13:34):
Find them? We've got them. Well, then with that, should
we get started?

Speaker 1 (13:42):
I think we should. Let's take a quick break and begin.

Speaker 4 (14:07):
It feels like we need to start this section off
with the briefest of reviews of how an allergy works,
you know, just to be thorough. So we're gonna basically
do my whole episode from last week in like one paragraph.
You ready for this, I'm ready. In allergies, you get
exposed to an allergen, which is almost always some type

(14:29):
of protein. It gets into your bloodstream, your immune system
decides to do a wacky thing and start making these
IgE antibodies in a process known as sensitization. And then
the next time that you're re exposed to that allergen,
these IgE antibodies, which happen to be bound to these

(14:50):
cells called mass cells and besa fylls, they bind to
the allergen, causing those cells to burst open and spew
forth all of the inflammatory junk, and our immune system
goes hogwild. So in mild cases of allergies. This might
lead to inflammation just near the site of exposure, like itchy, runny,

(15:11):
watery nose and sneezing when you breathe in cat dander,
itchy eyes when you get dust mite gunk into your eyes,
or upset stomach and vomiting if you eat a tree nut.
And in the worst case scenarios, this inflammation triggers an
extensive immune response that affects the whole body and can
cause anaphylaxis, where we see swelling in the mouth and

(15:32):
throat and lungs that leads to airway constriction and difficulty breathing.
We see dilation of our blood vessels leading to blood
pressure drops, which is sudden and dangerous, and this is
an emergency, life threatening scenario. Was that a good summary
of allergies in seconds?

Speaker 1 (15:51):
Yeah, it made me want to ask more questions that
I was like erin, this is not about allergies. That
was last week. You had your opportunity for the medications part, right.

Speaker 4 (16:03):
So that's the question we're trying to get to today
is what the heck do we do about these? How
do we treat them? It's probably logical to most people
that the treatment is going to vary in part depending
on the type of allergy and the severity across the board.
The first answer that most people will get on how

(16:25):
do I deal with my allergies is oh, avoid allergens,
and A that's not always possible, and B sometimes there's
not really that much data that it's helpful, like in
the cases of things like dust mites, Like you can
do all these things, and there's not necessarily that much
data that it helps your allergies that much because they're
ubiquitoused there every right, right, So once this allergic response

(16:47):
kicks off and starts to run away like a boulder
down a hill, what do we do about it? There
are three main categories of treatment options that will talk
in detail about, and then there are some others, and
then at the end of this episode we'll talk about
the really exciting, more novel treatments. But the three main

(17:08):
treatments that we'll focus on today are anahistamines, allergy shots,
and EpiPens. That's a brand name, so I should say
epinephrine autoinjectable devices.

Speaker 1 (17:19):
Can we say EpiPen because it's such a mouse.

Speaker 4 (17:22):
You can say not sponsored EpiPen. Okay. We'll also give
honorable mention to steroids, and I'll talk about them a
little bit as well.

Speaker 1 (17:32):
Honorable honorable mention steroids, one of the most important classes
of drugs, just gets an honorable mention for allergies.

Speaker 4 (17:41):
I know, I know, well, you know you gotta make
choices here, erin, it's a podcast.

Speaker 1 (17:46):
It's true, It's true.

Speaker 4 (17:48):
Okay, So anna histamines, let us start there, shall we?
Anna histamines are things like diphen hydromene. That's your benadryl. Again,
I'm gonna say a lot of brand names this episode,
which is not typical for us, but that way people
know what we're actually talking about. Also things like hydroxyzine.
So these are the types of anahistamines that people might
think of that they're like, oh my god. If I

(18:09):
take that, I am knocked out. They make you super sleepy.
And then you have all these other anahistamines, things like setyrazine,
xertech fexophenidine. I think that one's alegra loraatidine. Pretty sure
that's Clarton. I could have gotten those mixed up. Who
cares all of these types of medications. They're called anahistamines
because they block histamine, simple as that. So histamine is

(18:37):
one of the many, many compounds that our mast cells
are spewing out when they burst open and release inflammatory
juices in response to an allergen. So that is why
we can use anahistamines in cases of allergic responses, because
you have a ton of histamine floating around and it

(19:00):
is very involved in the symptoms that we see. Histamine
does literally so much in our body erin it is
involved in regulating our gastric secretions in our guts. Histamine
is involved in the regulation of our sleep wake cycle.
You might only think of melatonin. It's way more complicated

(19:20):
than that. Histaminees involved.

Speaker 1 (19:22):
Well, I guess that makes sense considering that some of
these knock you out right.

Speaker 4 (19:26):
Huh yeah, I'll talk about why only some of them.
But in the case of allergies, histamine is involved in
things like vasodilation, so it helps to cause vasodilation of
our blood vessels. It also is involved in the smooth
muscle constriction that we see like bronchospasm that we see

(19:46):
in asthma, but also in the cases of anaphylaxis and allergies,
it causes increased vascular permeability, so that leakiness of our
blood vessels which again in the context of an immune response,
is forcing all of your blood and all of the
immune reactants in your blood to the area for help. Right,

(20:07):
that's the idea. It also is a big part of
the itchiness that we feel, and so anahistamines are really
useful in reducing the itchiness from allergies and other things
that cause itch when it's a histamine related itch. Don't
ask me how and why can.

Speaker 1 (20:24):
I was gonna ask again. I was like, I just
asked this a few episodes ago. Why do we itch?

Speaker 3 (20:29):
Why?

Speaker 1 (20:29):
Why do we?

Speaker 4 (20:30):
Yeah, I don't have an answer. But histamines in the
case of allergies, and so specifically the ana histamines that
we use for allergies, they tend to there's a bunch
of different receptors for histamine and they're numbered like one
through four. So the anahistamines that we use for allergies

(20:50):
block a receptor that histamine binds too, specifically the H
one receptor. So what happens then is that we're still
really leasing histamine. There's still plenty of histamine floating around
when you're having an allergic reaction if you take it
in a histamine, but it just can't do its job
because that receptor is blocked by the medication. And so

(21:12):
this is also like an even wider class of medications
because since there are multiple types of histamine receptors, something
that you might take for like acid reflux might be
something like pepsid or fomodidine. That's an H two blocker,
so it blocks different receptors of histamine. But sometimes if
someone is having really severe allergies, they might need multiple

(21:35):
types of histamine blockers, so they might be on a
whole camaraderie. Is that a good word. I don't know
a whole bunch.

Speaker 1 (21:43):
Of these medication, Okay, could I ask a question about it? Sure?
Histamine receptors, So there are multiple histamine receptors that do
different things. So that like if your body's like, hey,
we need a histamine response because of this allergy or
because of this thing, then come join this receptor, right,

(22:04):
That's exactly how it codes, right.

Speaker 4 (22:06):
Yea pot.

Speaker 1 (22:08):
But the histamine molecule itself is always the same, but
it's the anahistamines that are different to match those different
receptors exactly.

Speaker 4 (22:16):
So histamine think of it as one one histamine, and
this histamine binds to different receptors usually in different parts
of our body. So like we have different receptors in
our guts than we do in our brain, than we
do in our blood vessels, And so the medicine that
you take is going to block more or less specifically
these different types of receptors. But like I said, there

(22:38):
are different versions of these, right, So the things like
benadryll or hydroxyzine, these are called first generation anahistamines, and
these there's a few downsides to these compared to the
newer ones that we use, like zertex and the aligres,
et cetera. First is that they don't last as long,
so you have to take them more frequently throughout the

(22:59):
day because they're like therapeutic effect is only a few
hours as opposed to like twelve or twenty four hours.
But they also are able to cross the blood brain barrier,
which is why benadrills and things make people so drowsy,
because histamine is important in your brain. Histamine crosses the
blood brain barrier, but the medication can also do that

(23:22):
and then block those receptors and then cause sleepiness in
your brain. They also tend to be a little bit
less specific. So you said, like Okay, these different medications
are blocking different receptors, yes, but some of them are
better at that than others, and so some of these
older antihistamines block a wider range of not just histamine receptors,

(23:46):
but other things as well, which is why they tend
to have more side effects across the board and interact
with other medications. The newer anahistamines that we use for allergies,
which are called second generation anta histamines zertex alecres not sponsored.
These don't cross the blood brain barrier, and so they
have less sedating side effects. They're more specific for those

(24:08):
H one receptors, and they tend to last longer, so
you can take them maybe once or twice a day.

Speaker 1 (24:15):
Okay, how do you know which ones to take?

Speaker 4 (24:20):
Oh? I don't know if I want to answer that question.
I have answers to that question, but it feels like
a doctor question.

Speaker 1 (24:26):
This is not an advice podcast.

Speaker 4 (24:28):
This is not I have a lot of like those
caveats in this episode. In particular, we are not your doctors.
This is not medical advice, but it really will depend.
All of these anahistamines can be used to treat a
lot of the symptoms of allergic reactions. Right, they're not
treating the allergy at all, They're just treating the symptoms

(24:49):
by blocking histamine from having an effect. But so no
matter what the type of manifestation, be it allergic rhinitis, hives,
food allergy where you're not having a phylaxis, of course,
itching all of these symptoms that histamine is involved in,
in the whole suite of allergic reactions that we talked

(25:10):
about last week, they can help be mediated by anahistamines.
Which one you choose will depend on what your allergies
are and which one you respond better to, because some
people respond better to some than others. What's really interesting is,
especially when it comes to things like benadryl, some people
have like paradoxical effects where it makes them really agitated,

(25:31):
especially kids, which is why it's usually not recommended to
give kids those because they can either be way too
sedating or make them super hype or which is not fun.
But all of these can potentially have a role, and
sometimes people will respond really well to one for a
long time and then it will just like stop working

(25:51):
and then they have to switch to another one. Why why,
we don't really know.

Speaker 1 (25:56):
Okay, but you can get used to a certain antihistamine.

Speaker 4 (26:00):
Absolutely, yeah. And is it just because all of your
receptors are so saturated that then your body is like, well,
I'm just not gonna like I'm gonna upregulate my receptors
or what is it? We don't really know, but for
some reason, at some point, that particular type of anahistamine
for some people might not work as well. And if
they switch to another one, which all of these are

(26:20):
just different shapes of molecules binding to the same receptor,
then it usually will work for them. But across the board,
anahistamines are rarely the only thing that he's used to
treat allergies. So let's keep going, shall we. Yeah, Steroids,
honorable mention, have a role to play in the treatment

(26:41):
of allergies, allergic rhinitis especially so like nasal and eye
and like your face, symptoms from allergies really benefit from
specifically nasal sprays that have glucocorticoids. And the reason is
because steroids, kids are general anti inflammatories. They are blocking

(27:04):
not just histamine, they're blocking your whole inflammatory response. So
they're incredibly effective at calming down the inflammation in this
tiny area that is your nasal passages, and they tend
to be very safe and well tolerated because even though
steroids might sound scary, in the case of nasal sprays,

(27:25):
they're not super well absorbed systemically, so they're really locally
treating this inflammation. So they are really awesome and like
generally recommended as first line treatment for things like allergic rhinitis.
Not all nasal sprays are steroid nasal sprays, okay, And
so I think it can be really easy to get
confused between all the different types. And there are some

(27:49):
nasal sprays that you can really only use for like
a day or two at a time before you start
having pretty severe side effects from the nasal spray.

Speaker 1 (27:57):
Wow, Like what would those side effects be and why?

Speaker 4 (28:01):
It's because they're not steroids, so they're working in a
way to just like constrict your blood vessels. It's for
when you have like really bad like sinus infection or
something and you just need to dry up your sinuses.
They'll do that, but then they can cause like rebound
worsening of symptoms and blah blah blah. So those are
not what I'm talking about the types of medicine. I'm

(28:21):
talking about are things like flow, Nase and nase achord.
Those are the brand names in the US, but they're
things like fluticozone and mometazone. Those are the steroids that
are in it. There are also in a histamine nasal
sprays that people can use, which again are going to
do the same thing as your oral anahistamines, except locally

(28:42):
just in your nose. Same thing with eye drops. There
are anahistamine eye drops. Those tend to be less effective
than steroid nasal sprays because they're more specific. They're only
targeting the histamine rather than a more generalized inflammatory response.
The way that steroid nasal sprays are doesn't mean there's
no downside to steroid nasal sprays. The biggest side effect

(29:03):
tends to be that it can increase the risk of
nose bleeds for some people. Okay, and they usually take
some time to work, so they're not like automatic. It
takes several days for that steroid to build up in
your nasal passages to actually then reduce that inflammation.

Speaker 1 (29:17):
Got it.

Speaker 4 (29:18):
We use steroids also topically for things like egzema or
other allergic dermatitis type reactions, So topical ointments and creams
that contain steroids are phenomenal. But in terms of oral medications,
like we were talking about the scorched earth philosophy, Yeah, raw,
that's steroids, like right, they're just wiping out your entire

(29:39):
immune response indiscriminate exactly. So in cases of severe allergies
or a severe allergic reaction, then yes, there might be
like a short course of steroids, but they're really not
a great option for long term treatment for oral steroids.
Another honorable mention I will say it so that no
one gets mad that I didn't is a medicine called

(30:01):
Monte lucast singular is the brand name. Okay, it's controversial
enough that I'm not going to go into it, but
it's used mostly for asthma plus allergic rhinitis. So when
you have both of those things together, this, unlike anahistamines,
blocks another inflammatory bazouge called leukotrienes.

Speaker 1 (30:23):
But isn't that you find it in the index of
a medical text book, right.

Speaker 4 (30:29):
Yeah, it's one of the other things that your mass
cells spit out in the case of allergies, is a leucotriene,
and so this medication blocks some of those, but it
has a potential for more severe side effects, and we're
learning more about the neuropsychiatric potential side effects of this medication,
and so it is used, but not as commonly and

(30:53):
in very more specific indications compared to these other medicines
we're talking about today, okay, which include for the allergy shots. Yeah,
so how does an allergy shot work? Allergy shots are
something that we use really for again a wide range,
but an as far as all allergies go, a narrow subset.

(31:15):
And yet it is a wide range of different allergies,
mostly inhaled allergens, things like danders mites, cockroaches, pollens, also beastings,
fire ants, and other venoms. And this process most often
is done subcutaneously, so it's called subcutaneous immunotherapy SCI. And

(31:40):
essentially what happens is the person has to go usually weekly,
sometimes even more frequently like a couple times a week
to start, and an allergist will inject teeny tiny amounts
of the thing that they're allergic to underneath their skin.

Speaker 1 (31:57):
It's just like iocane powder in The Princess Bride. But
it works.

Speaker 4 (32:02):
I don't I have watched that movie, but I don't remember.

Speaker 1 (32:05):
Can he's building up a tolerance to iyakane powder.

Speaker 4 (32:08):
Oh okay, now I do remember.

Speaker 1 (32:10):
Yeah, so he doesn't die and he puts it in
both of the drinks.

Speaker 4 (32:15):
Yeah yeaheah, I do remember that now, thank you. It's
just like that, Aaron. That's how allergy shots it is,
literally what that is. So you start out weekly or
multiple times a week, and then you slowly are building
up the amount of allergen that this person's being exposed to,
and over time you space it out to less frequently
every couple of weeks, every month, every few months, and

(32:38):
this goes on for usually a couple of years, at
least many many months, and then eventually you can stop
doing the shots altogether and people don't have allergies or
have significantly less of a response to allergens.

Speaker 1 (33:11):
Aaron, Why does that continuous exposure result in decrease sensitivity
rather than increase sensitivity.

Speaker 4 (33:20):
It's a really good question. I think if we fully
understood why this works, then we'd have a lot better
treatment for all of our other allergies. And we don't.
But what we do know what is happening. So what
is happening is that this very minute, really really really
small amount but frequent and repeated exposure. What it does

(33:42):
is it kind of retrains our immune system and it
induces a level of tolerance. So the way that I
think of it is this repeated exposure over time trains
our immune system to be like, hey, listen, remember in
last week's episode, we talked about door number one and
door number two and how allergies they're opening too much

(34:04):
of door number two. So what this process is doing
is telling our immune system listen, like, we've opened up
enough of door number two. Like we've done it. It's overplayed.
Chill out with that over response. And then what our
immune system does is it starts to shift to the
production of IgA and IgG antibodies and away from the

(34:27):
production of IgE antibodies.

Speaker 1 (34:30):
And what do IgA and IgG do.

Speaker 4 (34:32):
Well, they don't trigger this mass cell type response, right.
It means that our bodies can still see and flag
these allergens because we have these other antibodies to them,
but we're never going to trigger that severe immune response
unless you have IgG antibodies. And so we are shifting
production to where we can be like, yes, immune system

(34:54):
recognize this, you can remember this allergen, but you don't
need to freak out about it.

Speaker 1 (35:00):
Okay.

Speaker 4 (35:01):
Unsurprisingly, this can also backfire and can induce anaphylaxis because
you are literally exposing somebody on purpose to something that
their body has already been trained to identify and attack.
So it's like Owen Grady is training velociraptors. That's like
the process of have you seen Jurassic Worlds?

Speaker 3 (35:22):
No?

Speaker 1 (35:23):
I just I stopped at Jurassic Park three.

Speaker 4 (35:26):
Okay, well everyone else is going to know what I'm
talking about. Imagine someone trying to train a velociraptor, right, Like,
it might work because they're very smart, right, and so
they might learn, okay, don't attack this thing. But you
also could get your arm bit off. And that is
why allergy shots are always done in a very highly
regulated and monitored setting under direction of an allergist. And

(35:48):
it's not something that people do like at home.

Speaker 1 (35:50):
Right, and you have to wait in the office and
make sure that's a certain amount of time. Yeah.

Speaker 4 (35:55):
Now, there also are newer options to do this with
having to poke somebody, and this process is called sublingual.
Usually it's called sublingual immunotherapy, and that's when you are
exposed to the allergen under your tongue and so it
absorbs into your mucous membranes of your mouth rather than
under your skin. It's approved for some allergens, a smaller

(36:16):
subset of allergens than subcutaneous immunotherapy. And again we don't
know exactly why, but is it because like absorption isn't
as good whatever it is, We don't have as good
of protocols for all the allergens for sublingual immunotherapy, but
it is possible for some. So especially for kids, that's
a great option because getting shots is scary.

Speaker 1 (36:36):
But you can't get shots for food allergies.

Speaker 4 (36:39):
Oh aarin or can you white? Oh? Everything that I
just talked about. It's for the types of allergies that
mostly are like allergic rhinitis or rhinoconjunctivitis or venoms toxins.
It's not for food allergies. And it's not for lack
of trying. There have been so many studies where people

(37:00):
have tried to use subcutaneous immunotherapy or sublingual immunotherapy for
food allergies. They haven't panned out, mostly because especially with
subcutaneous people were just having really severe reactions. So like
the reactions were more severe and then more dangerous and
so nothing ever got approved. Asterisk because we'll talk more

(37:22):
at the end of this episode about some newer therapies
that are similar to this for food allergies.

Speaker 1 (37:30):
Teaser. Wow.

Speaker 4 (37:31):
I know, But until very very recently, like this year,
really the only real advice for people with food allergies
was avoid it, avoid it, avoid it, avoid it along
with an EpiPen, which brings us to our third and
final medication that we use to treat.

Speaker 1 (37:49):
Allergies, epinephrine autoinjector. There you go.

Speaker 4 (37:56):
I am really interested to hear the history of this.

Speaker 1 (37:59):
It's a good one.

Speaker 4 (37:59):
But what I'm going to talk about is like, what
the heck is in an EpiPen or an epinephrin autoinjector. Well,
it's epinephrine. That's easy, yep epinephrin. The other name for
it that people might have heard of is adrenaline, and
so epinephrin or adrenaline, it's literally the same thing, two
different names.

Speaker 1 (38:17):
Why it's bizarre. I mean, it's like a little bit
in the history, but mostly it was just like someone
liked this and someone liked that.

Speaker 4 (38:23):
That's what I figured. Two different people came up with that. Again, Yeah,
we picked one This is a hormone that we make
in our bodies. And this hormone is our like fighter
flight hormone. It's our fight or flight response hormone. So
epiephyrine is the thing that makes your heart pound when
you get anxious. It's the thing that makes you feel

(38:44):
jittery when you're feeling jittery when you're anxious, or when
you're nervous, or when you're super excited. Epinephrin acts on
these receptors in our body across our entire body, called
alpha receptors, and these receptors are present on our blood
vessels and they so to constrict our blood vessels. Anaphylaxis,
like we talked about last week, dilates our blood vessels,

(39:07):
so when we give this drug, we constrict them boom logic.
But epinephrin does even more than that. It also works
on these receptors called beta receptors, and we have a
lot of these on our heart. And when epinephrin binds
to these receptors on our heart, it makes our heart
beat faster, and it makes our heart beat harder, so

(39:30):
it's pumping blood through these more narrowed vessels. It also
through these beta receptors in our lungs, relaxes the muscles
in our airways to reverse that broncho constriction or bronchospasm
that we see. So that is why epinephrine is the medicine.

(39:51):
It is the medicine to treat anaphylaxis. Like, point blank period,
this is what you use. Okay, I kind of have
a silly there's no such thing.

Speaker 1 (40:01):
Okay. Well, so let's say that you know that you
are really really allergic to beastings and you see a bee.
Presumably does that mean that you're adrenaline would shoot up?
Would that make you less likely to have an anaphylactic reaction?

Speaker 4 (40:17):
Aaron, that's not a silly question. That is such a
fun question.

Speaker 1 (40:21):
Or like a snake bite. You see a snake and
you're like, ah, and then it bites you, and you're
freaked out that the snake bit you, and then your
body is like anaphyl access time, and then your body's
also like but we just saw a snake.

Speaker 4 (40:30):
So Aaron, this is such a fun question in the
context of the history, and like the toxin hypothesis from
last week. Yeah, I have no idea.

Speaker 1 (40:41):
I have no idea either.

Speaker 4 (40:46):
I have absolutely no idea. I like, I don't even
know how you would study that, Like if someone is
anxious before they Yeah, I have no idea how you
would study that because we can't even do like placebo
controlled trials on epinephrine because it would be unethical.

Speaker 1 (41:03):
And how durable is an adrenaline spike, right versus the anaphylaxis, etcetera?

Speaker 4 (41:13):
Right? And is it just that in anaphylaxis do you
just not have enough endogenous adrenaline? Are you just not
making enough epinephrin? And that is why, right, Because here's
the other thing, and this is where epiephrin gets a
little bit weird. These beta receptors they also do vasodilation,
which is what is happening in anaphylaxis. So if you

(41:37):
give someone some epiephrin but not enough, like a lower
dose of it, then those effects can override and be
stronger than the vaso constriction effects on the alpha receptors.
And so the dose is actually really important in epinephrine.

Speaker 1 (41:53):
Okay, So each EpiPen contains a dose specific to the
person that it is prescribed for.

Speaker 4 (41:58):
Absolutely not aaron be personalized medicine, and we don't have that. Wait,
so an epinephrin autoinjector EpiPen. I will throw out other
trade names and a penn emorad fast jecked that's what
one is called in German. Love that these devices are
fixed dose injectors in the US, they're mostly in two doses.

(42:23):
For kids they're point one five milligrams and for adults
they're point three milligrams. That's it. Those are the two
dose options, and you get prescribed them based on weight.
So babies and small kids are going to get the
small dose. Everyone else is going to get the big dose,
which means some people might be overdosed, some people might
be underdosed. But across the board, I know your face

(42:45):
is like, that sounds horrible. Why yeah, But it's also
like across the board, even though there are potential side effects,
how long ago side effects last are usually not that long.
And so these are the doses that are considered across
the board safe. And so you give the dose that
is closest to that person's weight based on their weight.

Speaker 1 (43:05):
Why would we not have a finer system for doing this?

Speaker 4 (43:09):
Oh my gosh, Arin, that is a question for pharmaceutical
companies and who's making the most money off of.

Speaker 1 (43:13):
This, and there's already price gouging going on, like yeah,
with EpiPens or epinephrin autoinjectors. Excuse me, I don't know
which companies are doing the price gouging, but does happen?

Speaker 4 (43:27):
I don't have an answer to that. But these doses
work for most people. When I say like underdose or overdose,
it's not a large segment of the population. It's more
likely that somebody might be underdosed, but at least you're
still buying time.

Speaker 1 (43:41):
Okay.

Speaker 4 (43:41):
It's also the case that many people, regardless of whether
it was the perfect like weight based dose or not,
might need more than one because this epiphyrin doesn't last
for very long. The effects are very rapid onset but transient,
and so a lot of times they will help, but
then that's not enough going to need multiple doses. People

(44:01):
might even need an infusion of epinephrin running over a
really long time period, like multiple hours, before their body
is really out of the woods.

Speaker 1 (44:10):
Wow. Yeah.

Speaker 4 (44:11):
So in general, one of the benefits of these autoinjectors
is that they are standardized across the board, so no
matter what pen you can find, if someone needs one,
you can use it right it's the same dose for everyone,
so it's easy in that way. They're also designed to
deliver the epinephrin directly into the muscle, and we usually

(44:31):
use the thigh muscle because it's a nice, juicy, beefy
muscle that has a ton of really good blood vessels
and really good blood supply, which means that the epinephrin
gets delivered in a really predictable way to the blood
as opposed to intravenous, which you can have much higher
side effects. Plus then you have to find somebody's vein,

(44:53):
which in an emergency isn't easy to do, and subcutaneous administration,
so just putting it into the se skin or like
just under the skin rather than into the muscle. What
happens is that you have so much local vasoconstriction from
the medicine that you don't have as much penetration quickly
into the bloodstream, so it doesn't work quite as well.

(45:15):
Still better than nothing.

Speaker 1 (45:16):
And seconds matter, like, yeah, seconds absolutely matter. Yeah.

Speaker 4 (45:20):
These pens also are designed to work through clothing, so
they can be delivered incredibly rapidly. You don't have to
worry about like exposing someone's thigh. You just can get
the medicine.

Speaker 1 (45:29):
In how do you know when to use one?

Speaker 4 (45:33):
That is a really good question, Aaron, and that is
it is not something I can fully answer. But and
there have also been studies and there's a paper that
I'll link to in our sources about like pros and
cons of at what point in an allergic response, like
do you wait for things to get more severe or
do you not? And the thing is that even when

(45:56):
there are cases where yeah, maybe you could have weighted,
the side effects of epinephrine generally are less severe than
the risks of waiting. So usually across the board, the
recommendation is if you have a known like especially if
you've ever had anaphylaxis before, or if you have had

(46:16):
severe enough reactions where maybe it's not anaphylaxis, but you're
really at high risk of anaphylaxis, then the recommendation is
once you see signs of a systemic response and not
just like oh, just one hive or something like that,
then you give it, because the risks of waiting often
outweigh the risks of the medication itself.

Speaker 1 (46:39):
Okay, but again it's.

Speaker 4 (46:40):
Gonna be I'm not your doctor, so this is not
medical advice. Also not medical advice. I feel very strongly
that everybody should learn how to use one of these pens,
even if you don't have allergies, because allergies are so common.
So there's lots of great YouTube videos out there. Most
of them are really similar, even though all the pens
look different. Some look like a box, some look like

(47:01):
a pen. Never ever, ever, ever put your finger over
the top anyone. You hold it like it's a I
don't know, a turkey leg, not.

Speaker 1 (47:14):
Like a I honestly, I can't think of anything else
that's perfect, thank you. Why you hold a turkey leg.
You're not going to hold it with like You're not
going to hold it like end over the top of
the time, and.

Speaker 4 (47:25):
Over the top. You can you can die that way anyways.
And we'll talk more about other newer options for epinephrine administration,
because also injecting your like shoving a needle into your
leg or your child's leg, that's traumatic. Yea, So there
are some really awesome newer options. But one of the

(47:47):
biggest issues you mentioned cost Aaron. These pens can be
incredibly expensive. I went on good RX and I looked
them up, and the cheapest one I could find in
the US is one hundred and forty dollars for two pens.
If you don't have insurance or if your insurance doesn't cover,
that's not cheap.

Speaker 1 (48:03):
No, it's not cheap.

Speaker 4 (48:04):
But an even bigger problem in terms of access is that,
according to the World Allergy Organization of a survey of
all of its member states, this type of epinephrine autoinjector
is only available in sixty percent of the countries that
they surveyed sixty percent.

Speaker 1 (48:20):
And then I would still imagine, like you know, we
talked about, oh do you wait? Do you not wait?
How do you know when to? And I wonder for
how many people. Cost is a factor in them one.

Speaker 4 (48:30):
Hundred percent because then if you use it, and they
also degrade within twelve to eighteen months, so they have
to be replaced, so you need a new one. Even
if you don't use it, you have to carry it
with you all of the time because you have no
idea when you might be exposed to something that could
give you an anaphylactic reaction. I mean, it's it is.

(48:51):
They are life saving medication and it is incredible and
we need better options and more affordable options. So we'll
talk about that a little later. But Aaron, first, tell
me how did we come up with all of these
different medications?

Speaker 1 (49:06):
Yeah, there's a lot of story to cover, so let's
take a break and then I'll get started. If you

(49:48):
look in my bathroom cabinet, you will find, among a
million other things like cough drops and ibuprofen, about ten
different types of anahistamine medications.

Speaker 4 (49:58):
Wow, that's a lot.

Speaker 1 (49:59):
It's a lot. Yeah, drowsy, non drowsy, generic name brand
in a cold medicine combo. Ten is I don't really
think it's an exaggeration. Maybe it's more like eight, but
it's it's honestly, there's a lot. I'm ready for when
someone visits during ragweed season and asks if we have
any cleraton or walletin which is what we actually have?
Which is the question?

Speaker 3 (50:21):
Brand?

Speaker 1 (50:22):
No, it's Walgreens, Okay. I don't know if we would
go through a Costco size thing of Clareton Costco Allertech.

Speaker 4 (50:29):
Have gone through many many a bottle of Children's Alertech.

Speaker 1 (50:35):
My husband gets allergy shots every Saturday. I think he's
actually down to every other Saturday because they seem to
be helping. Yep. And while I don't personally own an EpiPen.
I probably should, just in case I have family and
friends who do. Considering the extremely high prevalence of allergies
around the globe, it's not all that surprising that medicine

(50:55):
has put together a stocked and diverse toolkit for dealing
with this condition. But it is pretty amazing even considering
the limitations of these treatments, because even though allergies were
only described and linked to an exposure roughly one hundred
and fifty years ago, even though we don't have a
full grasp on why we develop allergies in the first

(51:17):
place and how to prevent them entirely, we do have
effective treatments and plenty more promising ones on the horizon.
So what I want to do today is talk about
the big three, as we've already discussed, to pay them
homage right in order of their development. So we'll start
with allergy immunotherapy aka allergy shots I know are theomulars

(51:40):
I know, and histamines and epinephrine auto injectors aka your EpiPens. Okay,
and let me just acknowledge that these treatments are not perfect, right,
They don't work for everyone, they aren't the only ones
out there, and there is certainly room for improvement, because
allergy remains a debilitating condition for many people, even with
these treatments available, or even with the threat of allergies

(52:04):
out there. Right. But in most respects allergy treatment is
a huge medical success story, and it's one that I'm
excited to tell in three chapters, Chapter one, Thank You Vaccines.
In last week's episode, I mentioned that English physician John
Bostock was the first to describe allergy in eighteen nineteen

(52:27):
hay fever, and that it was Charles Blackley in eighteen
seventy who first linked hay fever to a specific exposure,
in this case, grass pollen. Blackley's evidence was pretty compelling.
He stuck grass pollen up his nose out of season
to show that it still caused symptoms. He correlated pollen
counts with prevalence and severity of hay fever symptoms, and

(52:50):
his conclusions were simultaneously corroborated by a physician in the
US who was inhaling ragweed to induce his symptoms. Wow,
sounds really pleasant, right, It's hardcore, like for you, very hardcore.

Speaker 4 (53:04):
Would not subject myself to that. Sorry.

Speaker 1 (53:08):
Despite this, many scientists still doubted that grass pollen could
cause such a response, and that it must be some
undescribed microbe or good old hysteria. Fortunately, others were convinced
enough to take matters into their own hands, like William Dunbar, who,
as a hay fever sufferer himself, was personally invested in

(53:28):
understanding what caused his seasonal symptoms. So Dunbar confirmed Blackley's
findings by injecting undiluted grass pollen extract into himself and
his colleague, who also had hay fever. It's just like
a shot of undiluted, straight up grasp polowing.

Speaker 4 (53:48):
He was miserable.

Speaker 1 (53:49):
Yeah, yeah, both both he and his colleague had awful
systemic reactions like I can't imagine. And instead of that
experience persuading them from pursuing this area of study, they
were like, more, we must keep doing this.

Speaker 4 (54:07):
Oh my god.

Speaker 1 (54:09):
And granted they didn't inject themselves with like full on
pollen again. Instead, they took the diphtheria antitoxin approach, and
they tried to produce pollen anti serum by injecting horses
with grass pollen.

Speaker 4 (54:22):
Huh.

Speaker 1 (54:23):
They then turned the serum into powder which could be
applied to the eyes and nose prophylactically during hay fever season.

Speaker 4 (54:30):
Did it work?

Speaker 1 (54:32):
Results were mixed, okay, some people got worse. They developed
a sensitivity to the horse serum itself, something that had
been known to happen with other serum antitoxins. Dunbar didn't
give up hope, though, and he took one of these
patients who had developed this sensitivity and started them on
a pallen exposure journey. Over many weeks, he injected teeny

(54:54):
tiny amounts of grass pollen extract alternating with horse serum,
trying to get them dec sensitized to both, and at
the end of fifteen increasing dosages, the patient had become
much more tolerant of pollen. During that first hay fever season,
they reported much more mild symptoms compared to previous years.

Speaker 4 (55:13):
Wow.

Speaker 1 (55:15):
Dunbar published his results in nineteen oh three. Nineteen oh
three wow right, and he wasn't even necessarily the first
to try out this concept. A few other small reports
came out in a five or so years before, but
it was Dunbar's paper that would catch the eye of
one young researcher, Leonard Noon. Noon was on board with

(55:37):
hay fever being caused by grass pollen, specifically quote, a
soluble toxin found in the pollen of grasses. It is
also undoubted that hay fever patients sometimes become cured of
their idiosyncrasy. The most reasonable explanation of this phenomenon would
seem to be that the cured patients have had the
good fortune to develop an active immunity against the toxin

(56:00):
to the action of which they have been liable for
so long end quote.

Speaker 4 (56:04):
I love this, Aaron, and so.

Speaker 1 (56:08):
Using this logic, Noon rounded up some human volunteers and
tested their sensitivity to pollen by dropping a little bit
of pollen extract into their eye. Sounds horrible. And also
I just wanted to note that the pollen had been
collected by his sister, which I just love, Like, I
love that detail so much.

Speaker 4 (56:29):
He's like, hess, go out, no, no, no, in this grat,
just this subcrat. Okay that collected at all? Just like,
just bring it back to me. It's cool. He is
a glass tube, is fine.

Speaker 1 (56:38):
Yeah. And then in the winter and spring, outside of
hay fever season, he proceeded to administer very precise doses
of this pollen extract to his two groups. Those with
and those without hay fever, and he increased the concentration
of these doses slowly over the weeks. He experimented with

(57:00):
different intervals between injections and found that longer intervals could
actually make the patient become resensitized, and shorter intervals seemed
to meaningfully reduce symptoms. Unfortunately, Nune was not able to
see his experiment to the full conclusion, nor would he
live to see his landmark research honored in the decades

(57:23):
to come as the first allergen immunotherapy trial. None had tuberculosis,
and over the course of the study he grew sicker
and sicker, and he eventually had to turn his work
over to his friend John Freeman to finish carrying out.
Nune published what would be his last paper, Prophylactic Inoculation

(57:44):
against hay Fever, in nineteen eleven, and he died two
years later at the age of thirty five. Ah, that's tuberculosis,
Yeah it is. Freeman continued this work for the next
few years and showed that using this immunotherapy approach, in
thirty per of participants, hay fever was effectively cured.

Speaker 4 (58:04):
Wow.

Speaker 1 (58:05):
In thirty five percent, symptoms were greatly improved in twenty
four percent slightly improved, and only twelve percent had no
improvements whatsoever. Wow, it's pretty impressive. Yeah, noon, and Freeman's
work was truly foundational for the field of immunotherapy. Not
only did it demonstrate that long term improvement was possible

(58:26):
for at least one type of allergy, it also provided
a roadmap for healthcare practitioners to try this out on
their patients, and for researchers to tweak the protocol, testing
it out with other allergens, developing a combo shot, improving
safety standardization, and so on. And I'm not going to
go into those later improvements. Instead, I wanted to focus

(58:47):
on these early years because I want us to consider
the timing. The time from description, identification of cause, and
effective treatment happened lightning fast for hay fever in science years.
But if we placed it in the context of what
else was happening in the science world at the time,

(59:07):
it's clear to see why, or at least partially why. Vaccines.
Although the smallpox vaccine had been around since the late
eighteen hundreds, no other vaccines were developed until the end
of the nineteenth century. Around the eighteen seventies, and eighteen eighties,
which is right when Blackley's work on hay fever came out,

(59:28):
and with the growing number of vaccine success stories and
the development of anti tooxin, everyone with a remote interest
in microbiology or immunology began trying their hand at developing
a vaccine and using the germ theory framework to describe
what happens with an allergen exposure. Along with the concepts
of immunity, immunization, susceptibility, toxin, antiitoxin, and so on, it

(59:53):
seemed entirely reasonable that if vaccines worked for pathogens introduced
a little bit to prevent someone from getting sick in
the future, then maybe that could work for allergens. Voila
allergy shots. Yeah, so in a sense, we have vaccines
to think.

Speaker 4 (01:00:10):
That is so interesting, Arin, I really love that.

Speaker 1 (01:00:14):
I just can't believe how old it is, Like it
makes sense, but it's also like I just can't believe it.
It's also just like.

Speaker 4 (01:00:23):
So so so interesting immunologically that it works and that
it works the way that it does, and like it
just it makes me have so many more questions about
our immune response and like tolerance versus resistance, you know
what I mean?

Speaker 1 (01:00:39):
Oh, tolerance versus resistance is such a fascinating question.

Speaker 4 (01:00:42):
It really is, and it's like, oh.

Speaker 1 (01:00:45):
Yeah, yeah, And it doesn't work like vaccines in a
way either, right, like vaccines sensitize you to see exactly.

Speaker 4 (01:00:52):
It is like the opposite of vaccines. Yeah, but also
the same as vaccines, right, because it is it is
shifting your immune RESCE response to be an IgG response,
which is what we see with vaccines. But they a
didn't know that, of course, and B like it is
because you already had an abnormal Well is it abnormal?

(01:01:12):
We don't know, but you had this IgE response and
you're having to shift it. So it is it is
tolerance rather than this like prime rebility to resist in
the future. What I know, it is so weird.

Speaker 1 (01:01:27):
It's weird, and I love it.

Speaker 4 (01:01:29):
I love it. I love it.

Speaker 1 (01:01:31):
Are you ready for our next chapter? I really am
okay chapter two? Thank you. Pharmacology. Just as allergy shots
were a product of their time and the excitement surrounding vaccines,
any histamines came out of an era that saw the
birth of modern pharmacology. By the mid to late eighteen hundreds,

(01:01:53):
the fields of chemistry and biochemistry had made huge technological
advancements that allowed scientists to isolate and refine more and
more compounds, especially those from living organisms. The goal of
this work was basically to understand how stuff works, link
a compound to its function. Then if a certain compound

(01:02:14):
did something interesting or helpful, like quinine treating malaria, you
could take steps to either isolate larger quantities of it
from natural sources or try your hand at producing it Artificially,
it sounds like a straightforward process, but in reality this
type of work often led researchers down unexpected roads, which

(01:02:35):
is exactly what happened for Henry Dale and George Barker.

Speaker 4 (01:02:39):
Okay.

Speaker 1 (01:02:40):
Dale and Barker were working at Sir Henry Welcome's research
lab in England of Welcome Collection Welcome Library. When they
turned their sites to ergit. Welcome became interested in the
commercial potential of ergot as a medication to speed up
labor during childbirth and reduce postpartum bleeding, both of which
ergot had been shown to do. But no one really understood.

Speaker 4 (01:03:02):
How I love this. We talked about er way.

Speaker 1 (01:03:06):
Back in a dancing plague. Dancing plague, that's right, we
should do just an ergic episode, really Okay.

Speaker 4 (01:03:16):
I mean we say, like we could make anything into
an episode, so like, I don't know.

Speaker 1 (01:03:20):
I mean, this could have been three additional episodes. Let's like,
let's be real. But ergo on its own is not
something you really want to mess with, and so the
key was to find the compound that had these desired effects,
isolate it, and then turn it into a medication with
fewer side effects than straight up ergo. So Dale, Barger

(01:03:43):
and another researcher, laid Law, began this process of isolating
various compounds from ergo and then injecting them into various animals.
One compound in particular caught their eye. Beta. I'm gonna
try to say this Beta Emma dazzle eel, folamine, or
as we know it, histamine. Okay, so glad I don't

(01:04:04):
have to say that again. It was brutal. Histamine had
been isolated previously, but Dale and laid Law were the
first to look into what it actually did, and what
they found was pretty compelling. It caused all the things
you talked about aaron phasodilation, the contraction of smooth muscles

(01:04:24):
in the airways, in the uterus, in the intestines. It
increased heart rate and stimulated contraction. Overall, injection with histamine
induced a response in animals that looked a whole lot
like anaphylactic shock, which they pointed out at the very
end of their nineteen ten paper as a possible avenue
for future research.

Speaker 4 (01:04:45):
Wow. Nineteen ten, nineteen ten.

Speaker 1 (01:04:49):
I know anaphylaxis, by the way, had only been described
eight years prior in nineteen oh two, which is pretty
early by Rochet and Portier. Dale and Laidlaw's paper went
a long way towards linking histamine and allergy slash anaphylaxis,
but the connection wasn't quite complete. This compound from ergo

(01:05:10):
can cause this reaction, but does it have biological significance?

Speaker 3 (01:05:14):
Like?

Speaker 1 (01:05:14):
Is this something that animals regularly encounter? The answer to
that would arrive in nineteen twenty seven, when Charles Best
of insulin fame. He was one of the people who yep,
he isolated histamine from liver and lungs, showing that this
compound is produced regularly in animal tissue and that it

(01:05:35):
plays a strong role in allergy and anaphylaxis.

Speaker 4 (01:05:39):
This is so fun, Eric, I can't tell you how
much I love learning this stuff that I've never learned
about like where we got anahistamines from.

Speaker 1 (01:05:47):
I know, I just also I love I think it's
so fascinating to read about that period of science where
it was just sort of like throwing a dart and
being like cool, let's check out this compound. Yeah, and
it does this thing. Let's look at this microbe. It's
just everything. Yeah. Yeah, open questions so many. Once this

(01:06:09):
link was made between animals produce histamine on the rag
and it seems to be linked to allergy and anaphylaxis
in some way, then the logic followed that if you
could find a way to block the action of histamine,
you could reduce those unpleasant and deadly effects that it caused.
But how do you do that? Yeah, you look for

(01:06:30):
compounds that bind to histamine receptors, blocking histamine from binding.

Speaker 4 (01:06:35):
I mean, straightforward when you say it like.

Speaker 1 (01:06:37):
That, straightforward, right, easy enough? I mean, but in a way,
it was only ten years after Best isolated histamine from
animal tissues that the first antihistamines emerged. So it was
nineteen thirty seven is when Daniel Beauvet, who identified the
first antihistamine and then was later awarded a Nobel Prize

(01:06:58):
for his efforts. Nineteen thirty seven is one that happened.

Speaker 4 (01:07:01):
Wow.

Speaker 1 (01:07:01):
And they were on the market by the mid nineteen forties.

Speaker 4 (01:07:05):
Wow, I know that's so much earlier. Same today, I
think of the nineteen fifties, it's like medicines didn't exist,
which I know I had antibiotics.

Speaker 1 (01:07:20):
Yeah that's true. But yeah, that first antihistamy I feel
like Benaedrux was nineteen forty six something like that. Wow.

Speaker 4 (01:07:29):
Yeah, that is so cool.

Speaker 1 (01:07:31):
And again, these are the first generation, right. I could
tell a whole separate story about the research that followed
from this first generation of antaistamines. You know, how we
discovered the second generation histamines, all the different receptors, the
recognition that they could help with things like motion sickness,
the discovery that some antihistamines could have potentially harmful cardiac

(01:07:52):
side effects, the identification of their sedative effect. I mean,
there's a lot more to the history of antihistamines. I
would read that book erin Well, I'll have to save
that story for another day because we've still got the
last of the big three allergy treatments to get into,
and that is the epinephrine autoinjector SLASH the EpiPen, love

(01:08:16):
it chapter three, Thank you Sheldon, Sheldon Sheldon. The EpiPen
is one of the most powerful medical devices you hope
you never have to use. It has saved countless lives
from anaphylaxis since its initial introduction, and millions of people

(01:08:36):
around the world rely on EpiPens to save their lives
from severe allergic reactions. We owe the existence of this
amazing device to two separate but equally crucial developments in medicine,
the discovery of adrenaline slash epinephrine and the invention of
the autoinjector. Let's begin with adrenaline again, placing ourselves in

(01:09:00):
the late eighteen hundreds, when, alongside the fields of vaccinology
and pharmacology, the study of hormones was also kicking off.
Two researchers, George Oliver and Ea Shaeffer, ground up a
bunch of adrenal glands from various animals, swirled them up
with some alcohol and glycerine, and injected it into dogs

(01:09:20):
just to see what would happen.

Speaker 4 (01:09:24):
Oh my goodness.

Speaker 1 (01:09:25):
Okay, yeah, not great. This idea didn't come out of
thin air, though several other researchers had attempted something similar,
but no one had thoroughly characterized a typical response. Usually
it was just death, yeah, because it was like not
very purified, right, hormone.

Speaker 4 (01:09:44):
Extra, lots of ways that that could kill a dog.

Speaker 1 (01:09:47):
Just yeah, yeah, yeah absolutely. Oliver and Schaeffer were the
first to actually say, Okay, this is what happens. They
noted that the dogs receiving the adrenal gland extract had
elevated heart rate, vasodilation, increased blood pressure, and reduced respiratory rate.
It's kind of a messy suite of symptoms. Yes, it's

(01:10:07):
not messy.

Speaker 4 (01:10:08):
Adrenal glands are messy.

Speaker 1 (01:10:10):
Yeah, there's a lot of stuff going on there.

Speaker 4 (01:10:12):
They make a lot more than just adrenaline.

Speaker 1 (01:10:15):
Yeah, inducing this type of response, they recognized could come
in handy, But first you needed to find out exactly
what was triggering this response or the different parts of
this response. Several researchers set to isolating the responsible compound,
and in nineteen oh one, Jokichi Takamine would ultimately claim

(01:10:36):
the title calling the substance adrenaline, which Park Davison Company,
later owned by Pfizer, patented in nineteen oh three. What
I don't know that, yeah, yeah.

Speaker 4 (01:10:48):
So that's why we call it up enprind because.

Speaker 1 (01:10:50):
A trade name. Yeah. Once people were able to synthetically
produce adrenaline in nineteen oh six, it quickly became one
of the most studied hormones over the first few decades
of the twentieth century, as researchers sought to identify possible
therapeutic targets among those asthma and hay fever. Since at

(01:11:12):
least eighteen fifty nine, physicians had observed that quote asthma
is immediately cured in situations of either sudden alarm or
violent fleeting excitements.

Speaker 4 (01:11:23):
When you're activating the sympathetic nervous system eric.

Speaker 1 (01:11:26):
Uh huh, And so researchers figured, look, here's this thing,
adrenaline that causes the same sensations as sudden alarm or
violent fleeting excitements. Maybe we injected into people with asthma
and hay fever and just see what happens. And in
the first few years of the nineteen hundreds, that's exactly
what Solomon solis Cohen, Jesse Bulowa, and David Kaplan did,

(01:11:49):
finding that both oral and injected doses of adrenaline relieved
symptoms of both conditions, but a major question remained, well,
I mean several major quests remained, like what is adrenaline
doing at a cellular level? But for the purposes of
this history, the main unanswered question was what is the
best way to get adrenaline into someone? As a treatment

(01:12:13):
for hay fever and asthma. You really had to get
adrenaline into someone as fast as possible to be effective,
which meant injection, specifically intramuscular injection, over oral tablet or
other kinds of injections. But how many people are lucky
enough to have a syringe and vial of adrenaline on
hand during an attack? And even if you are like

(01:12:35):
drawing up the liquid into the needle while your throat
is constricting not an ideal delivery system, especially when, as
we talked about, every second counts. By the nineteen thirties,
researchers had developed nebulizers, which helped to solve the problem
for people with asthma, but getting adrenaline into someone going

(01:12:56):
into anaphylaxis was still a huge challenge. Fortunately, a solution
was on the horizon, but it wasn't initially created with
adrenaline in mind. During the Cold War, a big fear
was that troops would encounter nerve gas which acted rapidly
to incapacitat or kill like nerve gas would be within seconds, right,

(01:13:19):
and so the military was understandably very motivated to find
a way to deliver an antidote as quickly as possible.

Speaker 4 (01:13:27):
Oh my gosh, Aaron.

Speaker 1 (01:13:29):
I know. Sheldon Kaplan an engineer working at Survival Technology Incorporated.
What a name for?

Speaker 3 (01:13:37):
What a name?

Speaker 1 (01:13:38):
Right?

Speaker 4 (01:13:38):
Survival Technology? Does it still exist?

Speaker 1 (01:13:44):
But Sheldon had just the thing. One of his projects
at the company was redesigning the astropen, which was an
autoinjector that had limited usefulness since it used stainless steel
to hold the medication rather than glass, which was thought
to be too fragile. And I think, I think that
this was developed with astronauts in mind. But again, you

(01:14:04):
could only do certain medications because some medications when they
come into contact with stainless steel, not a good thing.

Speaker 3 (01:14:10):
Interact.

Speaker 1 (01:14:11):
Yeah, okay, But this problem didn't stop Sheldon. He rebuilt
the pen entirely using glass and developing a system to
carefully calibrate the dose. Sheldon's new pen was called the
combo pen, and this is what the military used to
deliver antidotes to nerve gas.

Speaker 4 (01:14:31):
Wow.

Speaker 1 (01:14:32):
But Sheldon saw the great potential that this pen had
outside of the military for the general population. He reworked
it to contain adrenaline epinephrine, and the world's first epinephrine autoinjector,
developed in nineteen seventy six, was officially approved by the
FDA to treat anaphylaxis in nineteen eighty seven.

Speaker 4 (01:14:55):
Wow.

Speaker 1 (01:14:56):
I know he had the vision right. He saw this
and was like, there's so much more that we can
do with this. Wow. Yeah. The EpiPen would go on
to become a household name and make pharmaceutical companies billions
of dollars, thanks especially to price gouging. Yet again, but

(01:15:16):
Sheldon Caplin never received any money for his invention, even
though his name is on the patent. And I bet
that most people have never heard of this incredible inventor
whose work and brilliance has saved untold lives. Oh wow,
So let's give it up to Sheldon.

Speaker 4 (01:15:32):
Kaplay gave it up for Sheldon, Oh my goodness.

Speaker 1 (01:15:36):
And there have been so many interesting developments and like
you talked about different delivery systems like a box versus
n you know, and there have been studies looking at well,
if you conceal the needle, it makes people more likely
to use it because it's less scary.

Speaker 4 (01:15:49):
Also, I am sure, and like I don't know enough
about the history of development of other medications, but like
we use similar types of delivery systems for so many medications. Now,
It's not just epinephrine, right, yeah, even all of the
ozempics of the world. The tide is the non brand name, right,
Like all of these kinds of medications, insulin pens, like

(01:16:11):
all of these things that have the ability to deliver
a fixed dose amount in a way where you in
a lot of cases have very minimal contact with the needle.
Part of It's wow, that is so interesting, Arin.

Speaker 1 (01:16:25):
Yeah, so all from cold war nerve Gas, the genius
of Sheldon Kaplan. I love it.

Speaker 4 (01:16:32):
How fun Aaron?

Speaker 1 (01:16:34):
Yeah.

Speaker 4 (01:16:34):
Also nineteen eighty seven. I don't know if that feels
earlier late. I don't know, but I love to know
that date.

Speaker 1 (01:16:40):
Yeah, I don't know how I feel about it. I'll
search my soul.

Speaker 4 (01:16:44):
Yeah, same.

Speaker 1 (01:16:44):
Yeah. Well, well, Aarin, that was a quick tour through
the histories of some allergy treatments, and I know that
we've got a lot of interesting potential on the horizon.
And so I'm going to turn it over to you
to let us know where we might be going allergy
treatments today.

Speaker 4 (01:17:02):
I'll do that right after this break. So we talked already, Aaron,

(01:17:41):
because you asked, like, well, allergy shots, food allergies, what's up? Okay, Well,
let me tell you there is a very new and
by very new, I mean it was approved in the
US in twenty twenty, oral immunotherapy OI as opposed to

(01:18:02):
scit or slit for subcutaneous or sublingual. This is oral
in your mouth imminotherapy for peanut allergy. It exists arin Yes, nice.
Peanut allergy affects in the US one point two percent
of the entire population and two and a half percent
of kids. And peanut allergy specifically is associated with like

(01:18:26):
a disproportionate amount of anaphylaxis cases that end up in
the emergency room. So that is why peanut allergy has
been the one that people have been studying to try
and come up with treatment for. So this new treatment
that exists, I didn't even write down the brand name
because I didn't and now I forget. But it's a
powder and it's made from peanuts, like it's just made

(01:18:47):
from peanut protein erin, but it's used as oral immunotherapy
in a very similar type of desensitization therapy. And the
difference between this and just feeding a kid peanuts to
try and desensitize them are a few things. One, it's
been very well studied to be safe and well tolerated. Two,

(01:19:08):
it is made to have a very specific and predictable
level of allergen exposure, right. That is why it is
approved and safer than just trying to eat peanuts to
desensitize yourself. And the therapy regimen itself seems pretty complex.
It is multiple exposures per day. It is daily exposure.

(01:19:32):
It's not like subcutaneous immunotherapy where you just go like
weekly exposures or something like that. And so it often
starts in an allergist office or in your physician's office
with these monitored, very well controlled exposures, and then has
to continue at home where you're doing this every single day,
often multiple times a day. And then every time that
you increase the dose, which happens slowly over weeks to months,

(01:19:57):
every time you increase that dose, you've got to go
back to your allergis off to do that safely under
guidance to make sure that you don't have an anaphylactic reaction.
But it exists, Aaron.

Speaker 1 (01:20:07):
And Okay, So what is the success rate for this
great question?

Speaker 4 (01:20:12):
Not perfect? I don't have an exact number. The biggest
downside with this and another medicine that we'll talk about
in a minute, is that it doesn't seem to produce
as long lasting effects as allergy shots do. Okay, but
it does have significantly increased tolerance for peanuts. Does it

(01:20:36):
mean that somebody is going to no longer have a
peanut allergy? No? Does it mean that they're going to
be able to accidentally have peanuts or to have a
little bit of peanuts in something they didn't know had
peanuts without having a severe reaction or dying. Yes, And
that is.

Speaker 1 (01:20:50):
Huge, right, And I imagine that it probably helps to
then reduce a little bit of the anxiety and fear
of a peanuts exposure.

Speaker 4 (01:21:01):
Exactly, aerin exactly, And along those same lines, there's another
new medication that is really exciting and mere months ago
February twenty twenty four was approved in the US for
treatment of food allergy more broadly not es peanuts. And
this is called oma lizumab. This is a monoclonal antibody.

(01:21:23):
Anytime you see a medication like on TV that ends
in mab, mab is monoclonal animal antibody.

Speaker 1 (01:21:29):
Wow, I just made that connection.

Speaker 4 (01:21:33):
So this is a medication that targets, wait for it,
IgE antibodies. So we are using an antibody, an IgG
antibody to find and target IgE annabodies in our body.

(01:21:54):
What I know.

Speaker 1 (01:21:57):
That's wild.

Speaker 4 (01:21:58):
It's it's incredible, Aaron, It's so interesting.

Speaker 1 (01:22:01):
I love it.

Speaker 4 (01:22:02):
And it's so like the way that you do this
is very similar to allergy shots in that people had
to be getting shots multiple times. You don't do like
a small dose and build up kind of a thing,
but you have to have multiple doses over a pretty
long time period. Most the study that I read that
was the phase three trial of this drug before it
got approved was like sixteen to twenty weeks, and then

(01:22:26):
they were even checking like if we went for longer,
would it have a better effect, et cetera. And what's
incredible is that this showed in this trial where they
took people who had at least two food allergies, so
peanut allergy plus at least one other, and the ones
that they ended up studying were egg, milk, cashew, wheat, hazelnut, walnut.

(01:22:48):
That's just what happened people who happened to be in
the trial. Sixty seven percent of people with multiple food allergies,
including peanut, were able to tolerate by the end of
the study at least one thousand milligrams of peanut protein,
which is equivalent to four peanuts four peanuts. So that also,

(01:23:09):
I think gives you a sense of just how little
peanut it takes for many people with peanut allergy to
have severe reaction, because in order to be included in
the trial, they would have reacted to less than one
hundred milligrams of peanut protein.

Speaker 1 (01:23:25):
That's wow, right, Yeah, So.

Speaker 4 (01:23:27):
By the end of the study, sixty seven percent of
people were able to tolerate at least four peanuts worth
of peanut protein. Forty four percent of participants tolerated up
to twenty five peanuts by the end of this trial.

Speaker 1 (01:23:42):
That's awesome, it's incredible.

Speaker 4 (01:23:44):
And they saw similar results for cashew, egg milk, wheat,
hazel nut. Some of these were statistically significant, some of
them weren't. But here's the other thing I want to say.
I feel like in a recent episode, we talked about
the difference between like, is it significant clinically, is it
significant statistically? Yeah, so sixty seven percent. Depending on who

(01:24:04):
you are, that might sound like a lot like Okay,
there's like a almost seventy percent chance that if I
have food allergies, if I can get access to this medication,
I might not be as allergic as I am now.
But that means there's also like a thirty three percent
chance that I wouldn't write. But if you break down
that thirty three percent, there was like a portion of

(01:24:25):
those people who did respond to the medication, as in
before they maybe would respond to like one milligram or
like a couple of milligrams of peanut protein, and by
the end they didn't react until they hit maybe three
hundred milligrams of peanut protein. So it wasn't statistically significant
for the purposes of the study. But that might be

(01:24:48):
the difference between I take one bite of a cookie
and I realize I'm starting to have a mild reaction
and I can stop, versus I take one bite of
a cookie and all of a sudden I'm going into anaphylaxis,
so clinically that is still significant. There was about fourteen
percent of people in the study who were true failures,
as in they did not sorry, they weren't failures, but

(01:25:11):
they did not have any improvement in their response to this.

Speaker 1 (01:25:15):
Medication, which is interesting in and of itself, like why, yes,
why are some people Why does the treatment work for
some people but not others exactly?

Speaker 4 (01:25:24):
And so we don't know the answer to that because
it does not work for everyone, but it works for
a pretty good proportion of people. So this was just
approved and again, like you mentioned Aarin, the potential that
this has to improve the lives of people even though
it does not mean that they're not having an allergy
at all. And we still don't know because this is

(01:25:45):
so new and these trials weren't that long. How long
is this tolerance going to last? We don't know. Are
you going to have to get this medication again? If so,
is it going to work as well? There's still a
lot of unanswered questions, but this medication has been shown
to be safe and to be effective in increasing tolerance
to so many of these food allergens, including these multiple

(01:26:07):
food allergens, and that has just such a huge potential
for impact on not only alleviating anaphal access saving lives,
but also on reducing that anxiety. And that's something that's
not like, maybe we didn't even emphasize it quite enough
in last week's episode, just how severe that amount of

(01:26:29):
stress can be to never know when you are going
to be exposed and how severe your reaction might be.
Who's going to believe you at a restaurant and who's
not right?

Speaker 1 (01:26:40):
The fact that there are people who are like I
don't believe in allergies. I mean, it's like not surprising
given just the current state of everything in the world.

Speaker 4 (01:26:48):
But what I know, I know it's not just food
allergies too. Like we talked a little bit last episode
about allergic rhinitis, how it can contribute to things like
difficulties in schools, anxieties. All these allergies have been shown
to have significant effects on people and their families, especially
for families with kids with food and other allergies. It

(01:27:09):
can lead to social isolation. Like it's a These are
big deals, and so the fact that we have treatments
that can help to alleviate that is major and There's
one more that I want to throw out there, and
that is nasal epinephrine. Ah nice, even newer erin This
medication was just approved in August of twenty twenty four

(01:27:31):
by the FDA.

Speaker 1 (01:27:32):
Awesome.

Speaker 4 (01:27:34):
This is a no needle way to get epinephrine straight
into your bloodstream in the case of an anaphylactic reaction.
And I found it I'm good RX for only one
hundred ninety nine dollars, which is pretty surprising considering it's
not generic. Because it was just approved. This is a
really exciting, like really really exciting medication. And I'm sure
there's a really interesting history of this because I will

(01:27:54):
link to a really cool paper that went into like
what it took to be able to develop this because
we needed not only the type of nasal sprayer that
could spray out a fixed dose of a medication, so
that technology had to develop. We also then had to
develop a medication that could help other medicines be more
well absorbed by your nasal mucosa so that we could

(01:28:16):
more reliably get Remember I said, how like if it's
absorbed into your skin, it's not gonna work as well
as in your muscle. So we had to have another
medicine to help it get into your bloodstream, and so
we have that now, and so nasal sprays for so
many medications, I think they're gonna just take off. And
so this is one where now there is a nasal version,

(01:28:38):
which means that it's going to be easier for people
to use no needles, easier to give your kid because
you don't have to poke them, which means kid might
be less afraid of it. Like, there's just so many
incredible things that are now possible because there's a nasal
spray version of an EpiPen. It's called nefi. But all
of these are new treatment options. What we still don't
have is prevention aside from what we talked about in

(01:29:01):
last week's episode, the leap trial and the eat trial,
which I looked at back upstands for inquiring about tolerance.
And these are big deals because we know that early
exposure repeated exposure can reduce the risk of food allergies,
especially peanuts, but for other types of allergies, we still

(01:29:22):
just don't know. There's a lot of work being done.
Does treating ezema early in life help to prevent allergies?
Studies are so far pretty inconclusive, but there's a lot
of people doing so much incredible research trying to understand
what are those immunologic triggers and what can we do
to try and prevent these allergies from starting in the

(01:29:43):
first place, at the same time that we're trying to
develop better treatments for people who already are living with allergies.
It's an exciting time in the world of allergy research.

Speaker 1 (01:29:53):
It really is. It seems like there is going to
just be more and more incredible developments and we're going
to look back at this time and go, oh, wow,
we didn't have like we have so much right now. Yeah,
but we're going to have so much more in the future,
I know, to bring people home. It's very exciting relief.

Speaker 4 (01:30:10):
If you want to know more, to learn so that
you can be one of those future researchers. Oh my gosh,
thank you. Well directly to some sources.

Speaker 1 (01:30:20):
Oh wow, I have so many for this, I don't
even know where to begin, So I'll just shout out
a few in particular and list the rest on the website.
I'm going to shout out that one by Noon and
Cantab from nineteen eleven called prophylactic inoculation against hay fever.
For the antihistamine and histamine section, I'll shout out of
paper by Ostrom from twenty fourteen called the History and

(01:30:43):
Progression of Treatments for Allergic Rhinitis, and then for the
epinephrine autoinjector. How about a paper by Arthur from twenty
fifteen titled epinephrin A Short History.

Speaker 4 (01:30:53):
I have also a number of papers. A couple that
I really liked that were more broad overviews was a
paper from two thousand and eight from Nature Reviews Immunology
called Treatment Strategies for Allergy and Asthma, and then an
update from twenty twenty three, also from Nature Reviews Immunology
called Allergy and Immunotherapy Past, Present, in Future. But I
have a whole bunch more specifics on anahistamines, more specifics

(01:31:16):
on food, allergy treatment, and epinephrine. You can find the
list of the sources from this episode and all of
our episodes on our website this podcast wikill you dot
Com under the episodes tab.

Speaker 1 (01:31:26):
Thank you again so much to the providers of our
first hand accounts and for being willing to relive those
experiences through sharing your story.

Speaker 4 (01:31:36):
Yeah, thank you so much, we really appreciate it.

Speaker 1 (01:31:39):
Thank you to Bloodmobile for providing the music for this
episode and all of our episodes.

Speaker 4 (01:31:44):
Thank you to Tom Briifogel and Leona Scolacchi for the
audio mixing.

Speaker 1 (01:31:47):
Thank you to everyone exactly right, and.

Speaker 4 (01:31:50):
Thank you to you listeners. We hope that you enjoyed
this two parter and that you learned a little bit
or a lot of bit about allergies and how they
work and why we treat them.

Speaker 1 (01:31:58):
I've certainly learned all the lot of it me too.
And a special thank you, of course, to our lovely
generous patrons. We appreciate the support that you give us
so so very much.

Speaker 4 (01:32:11):
We do, we do well.

Speaker 1 (01:32:12):
Until next time, wash your hands

Speaker 4 (01:32:14):
You feel the animals

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Erin Welsh

Erin Allmann Updyke

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