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

like camping and hiking and skiing. But about a year into my time in Denver, in the spring of twenty seventeen, seasonal allergies and hay fever hit me on like anything I had ever experienced before. Every day that spring, I remember, I would wake up with a sore throat, hives, and swollen eyes. My eyes would have allergic conjunctivitis and chemosis, which is when tiny bubbles form on the surface of your eye from all the allergens and pollen in the air.

I had a constant runny nose and couldn't breathe. I had a lot of sinus infections. I also couldn't hear very well because of all of the post nasal drip that would happen and settle in over I was beyond exhausted all the time and unable to go outside much at all. Every time I would leave my house, I would get hot, painful hives on any part of my

skin that was exposed. I remember taking cold showers all the time to try to keep my hives from spreading all over my body, and at the time I was only using over the counter allergy medications, which only helped a little bit. I worked downtown in an office, and so riding the train into the office, interacting with coworkers and clients, and wearing business casual clothing was incredibly uncomfortable

and embarrassing sometimes. And this is all before COVID times, and I was still really new at my job, so asking to work from home was a challenge. I was also really bummed because I couldn't eat a lot of fruits that grew on trees where you typically eat the skin, because the pollen grows with the fruit instead of on the hard outer layer. So fruits like peaches and apples were off limits because I would break out in hives on my neck and face and sometimes experience breathing issues.

And sadly, Colorado is famous for their palasaid peaches, and I could never have them, even though it was my favorite fruit growing up. Unfortunately, things got exponentially worse the following fall due to a mold issue in the rental house that I was living in. I was exposed to penicillium mold spores, which had a compounding effect on my already maxed out immune system, and I ended up developing

severe asthma. I was playing roller Derby at the time, and I remember showing up to practices and scrimmages feeling like I was breathing through a wet cloth draped over my nose and mouth and felt like I would pass out after one warm up lap.

my allergist and met my immunotherapy team. I got started with allergy shots by doing a procedure called a rush treatment to try to get my body as close to my maintenance DOWS for allergy shots as soon as possible. I was not able to finish the entire rush treatment because my body started to go into shock, which is actually typical for the procedure. After that, I began regular allergy shots every three weeks for the next five years.

I was also put on a prescription strength antihistamine, two, over the counter antihistamines two Inhaler's, and an EpiPen in the event I went into anaphylaxis. I was not allowed to eat or touch anything that would cause any sort of reaction, and I had to avoid being outside on high pollen days. Springtime was always the worst for me due to the presence of tree pollen, and I would always see more intense reactions during that time of year

to my allergy shots. Fortunately, I completed my immunotherapy in July twenty twenty three and have been pretty good ever since. I'm still on the prescription strength antihistamine and one of the over the counter antihistamines for any allergies that might pop up, as well as both Inhaler's for the now permanent asthma, but overall things are pretty manageable for me. I remember asking my allergist, why now, why did allergies hit me now and here and like this and never

before in my life? And she explained to me that I'd probably experienced what they call a honeymoon period when I first moved to Colorado. My body is non reactive to the new allergens because it had never seen them before, but almost always a second time around or the following season that your body encounters the allergen, it overreacts and produces an excessive histamine response. This whole experience has been a very long and painful journey, and it took a

huge toll on my mental health at the time. I'm not entirely sure how long I'll be without allergic reactions, hopefully forever, but I still get hives from time to time. Everyone's body reacts differently, and sometimes you become allergic to new things that you weren't before. Every reaction I do have now is manageable. My asthma is still very much there, but I've learned to live with it, and I'm also really excited to report that I can have feaches and

apples again. My life has been completely changed because of this experience. I'm so fortunate to have the support that I do, and I cannot think my Meta Coole team and my family and my friends enough for taking such good care of me Throughout those five years. I've learned so much about something I never even thought twice about for two thirds of my life that ended up having

a major life altering impact on me. The human body is so intensely weird in particular sometimes, but I'm so grateful that I was able to get through this experience and to be where I am now, even with the lasting effects it has left me with.

why do we have them, those kinds of things. Next week we'll focus on what do you do if you have allergies? And how did we figure that out? How do we treat them? And what are some of the options.

on our website. This podcast will Kill You dot Com, as well as on all of our social media channels, which if you're not following us on social media, you really should be, because you know there's some pretty good content if we do say so ourselves, and.

this idea of allergy really becomes. But we'll try and keep it a little less messy and just cover the general basics. So the American Academy of Allergy, Asthma and Immunology, and the UK's National Health Service and most other major medical and public health organizations agree on the basics of what an allergy is. An allergy is an abnormal, over the top immune response to substances that typically do not

and really kind of should not cause any substantial immune response. Aaron, you'r smiling, which I know means that this should not maybe doesn't apply, but that's the way that I think about it.

they are stuff. And first of all, they're usually almost always proteins, except as we talked about in Alpha gal when they're not. But they are almost always some type of protein. And for most people these things that we call allergens, our immune system sees them but usually goes ah, forget about it, like just ignore that one. But in people with allergies, these specific kinds of antigens that we

call allergens trigger a severe hypersensitive response. So let's talk about how that ends up happening.

call allergies that don't fit this mold. But when we're talking about allergies for this episode, this is the type of process that we're going to be talking about. Is the pathway I'm about to explain, and here it goes. The pathway starts with an exposure, and then there's a process called sensitization which is making these specific type of antibodies called IgE antibodies, and we'll get there. Then there's re exposure, and then there's an allergic response. So we

can go into detail on each of those parts. First, of course, we have to be exposed to analergen and we can be exposed to analergen in so many different ways. It can be in the air so we can breathe it in, and they often call those arrow allergens because if we don't have confusing terminology for every single thing, then what are we even doing in medicine. Or it

can be in our food. We can scratch these allergens into our skin, a tick could split them into us, as we recently learned, we could rub them into our eyes any way that they get in. Eventually, these allergens make it into our bloodstream. And as soon as they make it into our bloodstream, our immune system is all over it. So let's say, as an example, it's cat dander. There's a specific protein called feld one or fell d one that's in cat skin, saliva, and urine, and that's

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

this once upon a time? Our T cells are the ones who are The way that I think about it is they're kind of responsible, and this is an oversimplification for either doing something or like not doing much of anything. They're going to be the ones who like open a door or don't open a door to make the rest of our immune system react or not react.

downstream immune response that we see. So when T cells open, say door number one, they're going to release a whole bunch of cytokines, right, these inflammatory things that will help our immune system to let's say, find bacteria or viruses and target them and eliminate them. If T cells instead open a different door, call it door number two, then they release different cytokines, different inflammatory stuff, and then they're maybe going to look for worms or parasites or something

like that. Now, of course, in reality, our immune system is doing all of these things and opening all the doors at the same time, and there's more than just two. But it turns out that what happens in the process of allergic sensitization, this is our second step in the pathway, is that the proportion of doors that our T cells are opening is skewed, and it's skewed towards door number two.

So it just so happens that when our T cells decide when they see an allergen, to open a whole bunch of doors number two, it ends up telling our B cells, which are the ones that make antibodies, to produce a specific kind of antibody, and that is IgE, And that's the sensitization step of an allergy formation. And we talked about these IgE antibodies in our alphagal episode, But antibodies in general are like flags that our immune system uses to recognize and respond to harmful stuff more quickly.

We have to see a pathogen or an antigen or an allergen make an antibody, and then the next time we see it is when that antibody does its job. And we talked about this particular IgE antibody that it's different from the ones we think of that we use for something like vaccine responses because they're bound to cells like our mass cells and our base of fills. So sensitization,

we're making these weird, kind of weird IgE antibodies. Once we've been sensitized, then we have to see that allergen again. We have to be re exposed to that same allergen. So you made IgE against cat dander, and then you go back to your friend's house who has a cat.

And because this IgE is all over our mass cells, it's going to find and bind to that cat dander protein, and that binding of the mass cells to the allergen triggers a reaction that causes those mass cells to burst open and spew forth a whole bunch of highly reactive inflammatory stuff. It's things like histamine, leukotrienes, a bunch of things called inter luken's, all of this stuff that tells our immune system something really serious and horrible is happening

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

But things like IgG antibodies the way that I think of them, and immunologists might tell me this is not a great way to conceptualize it, but the way that I think of them is they're more like a flag.

So they attach on they find like a bacteria or something, and they attach themselves to it, and then our other immune cells as they're floating around, they see that flag, that IgG flag before they see the bacteria, and they're like, oh, hey, guys, that's an antibody flag, so we should find that thing, right, and then they can go and find all the bacteria that have all these flags on them. The difference with IgE is that it's not just a flag. It's attached.

It's not free floating. It sometimes can be, but it's not free floating in our bloodstream. It's attached to these cells. And something about the process of when that antibody that's attached to a cell attaches to its antigen that we call allergens. In the case of allergies, it triggers this response in the mass cell itself that causes an explosion of the inflammatory stuff that's inside of that mass cell. And we don't see that with other types of antibodies

because they're not bound to cells. So it's like a longer process, even though it's all much quicker than like making the antibodies the first time that you're ever exposed to something.

other antibodies because you just don't have that. It doesn't mean that you don't have like a widespread immune response in other scenarios, because we definitely can. That's how you could end up with like sepsis from a bacterial infection and blah blah blah. But yeah, that's it is not that same antibodies kind of causing the problem here, I guess is the way that you can think of it, right, Right,

it's just bizarre, it is. It's a really weird and interesting especially like I know you're going to talk erin about the kind of evolution of this, and like it is really really interesting and weird to think about why we evolved this type of response. It's really interesting.

for the most part. So then where you're going to get this inflammation from this immune activation might largely be in say your nose, So you might have an itchy nose, you might have sneezing, you might get a runny nose. Maybe your eyes will start to itch or water because the cat dander is getting into your mucous membranes in

your eyes and triggering inflammation in your eyes. If, on the other hand, we're not talking about an arrow allergen, maybe we're talking about something like a peanut protein or a soybean protein, or a wheat protein, you're eating that, So then you're being exposed through your gut mucus membranes or maybe through your mouth because they're there's a whole thing called oral allergy syndrome where you have this type of itching, watering, numbness, tingling just in your mouth, but

if it makes it down into your guts before you're having allergy response, then maybe you're having nausea, you're having vomiting. So it depends in part in the way that you're exposed. Is it through your respiratory system, is it through your gi tract? Is it limited to one mucous membrane like your mouth or your eyes. But then there's more than that, right because while this is in some ways a localized exposure, unless it's through your skin, then it is still a

systemic response. So in any of these cases, in any way that you're exposed through your skin, through your eyes, through your guts, you can also see skin manifestations, and most classically in allergies will see these as like wheels

or hives. And hives are those red raised, usually irregular shaped, kind of puffy splotches, and you can see those sometimes where you're exposed like if you are eating something that you're allergic to, you might start with hives around the face or the mouth, but very often and very quickly, they can become generalized. It might start with say, puffiness around a beasting, but then spread to be hives across your whole body. And those kind of skin reactions can

happen from any allergies. They can happen from cat dander allergies and from peanut allergies. And then you mentioned already aaron. The most severe thing that can happen with an allergic reaction is anaphylaxis. And just like the idea of allergies, the definition of anaphylaxis, it's not one perfect universal definition, but mostly we think of anaphylaxis as when in the case of allergies at least, because you can get anaphylaxis

without allergies. But it's when an allergic response is affecting multiple systems and becomes very extreme. So it's when these mast cells and our baso fills are sending out so much inflammatory material that our whole body's immune system starts to react. What this causes is massive vasodilation, so your blood vessels are getting really wide, and that makes sense because these immune markers are telling your body, hey, there's

something big going on. Send us all your blood, Send all of the white blood cells, send all of the blood to us. So vasodilation sends all of your blood different places. But that also causes swelling in part because when our vessels expand, they get more leaky, so fluid is going to leak out. And if you get that swelling in a place like your throat or your mouth or your lungs, it can make it really difficult to breathe. That's why anaphylaxis, when it causes that throat constriction, is

a severe, life threatening emergency. It can also be life threatening because when our blood vessels expand, that causes a drop in blood pressure because your blood vessels are now wide open, and because of physics, when you have a pipe that's wider, the pressure inside it is going to be lower, and that again is a life threatening emergency

if your blood pressure drops really quickly. So that is like the ways that allergies can manifest right, And it's such a huge range and so many different ways that you can be exposed, which can cause like any in all of these But why I have so many questions because first, why do some allergens trigger, say, anaphylaxis more commonly than other allergens? Yeah?

know the answer to that question. And that was something that I have so many papers, and none of them really even tried to answer that question. What is it about particular allergens that are more likely to cause a severe reaction versus a less severe reaction?

couple of genes, or even like a few genes. There's like bajillions. That's an exaggeration, but there's a really wide range of genes that are associated with an increased risk of allergies, and for the most part, we don't know what they are or how they work, Like why do these genes that we might see in association with allergies do they cause allergies? Or why is there that association.

IgE response, but it's not that simple. But the point of it is is that these big four diseases, and there might be a couple others that probably are under this umbrella, but like eggzema, asthma, allergic rhinitis, and food allergy, if you think of these big ones, there is something about them that links them all together. And we think that part of it might be an underlying genetic susceptibility that makes someone more susceptible to all of these at once.

But really, in a lot of the literature it's described as this a topic march. You probably saw that in papers, and that's because when we see these four diseases develop through life. There's often a progression from one to the next to the next, and there's a lot of different theories as to why that is and what is this relationship between these four big diseases. So I'm going to go over what like the thoughts are about what the

relationship is here. So one suggestion is that it's allergens that cause all of this, and it starts by allergens causing atopic dermatitis or exema, which is usually the first thing that we see, like even in tiny babies who don't have asthma and they don't have any food allergies

yet or anything, they have exema first thing. And so one hypothesis is that you start by getting exposed and sensitized to certain allergens and first develop atopic dermatitis or exzema, and then down the line, because you have been exposed and sensitized, you then might develop asthma or other allergies as a result of this allergen exposure. That's one hypothesis. Another one that people seem to really really like is

that exema is the start of this. An exema causes breakdown in the skin barrier, and this breakdown allows for allergen exposure through the skin and that and I like this too, in part because of we've already talked about on our Alpha gal episode, the idea that when you are exposed to something in an abnormal way i e. Through breaks in your skin, that that exposure is what predisposes you to this abnormal immune response i e. The

development of allergies. So that's one hypothesis. And then there's a third hypothesis, which is that there's not necessarily a causal relationship between exema and allergies and asthma, but rather there's an underlying genetic or immunologic pathway that kind of pins them all together, and EXAMA just happens to be

the first one that we see. Right, none of these three hypotheses are mutually exclusive, and none of them like fully explain the story, right, because there are plenty of people with egzma who don't have any other allergies, plenty of people with allergies who never had egzma. Asthma oof really doesn't fit well into this story, even though there are really strong relationships between allergic rhinitis and allergic asthma.

affect our risk of allergies asthma et cetera. We don't know, right, but we know that all of these things and I know erin you're going to talk more about this, I swear I'm almost done. We know that all of these things contribute. We just don't understand how, which means that we don't yet know how do we prevent all of this? And that is like next episode we'll talk a lot more about that idea, because that's like where a lot of the future research is going.

not an IgE mediated response. But it causes severe like vomiting diarrhea sometimes bloody diarrhea in babies that are exposed to certain foods, and most kids outgrow this, and then in adults there's a lot of different ways that you could become intolerant of different foods, some of which might be igmediated and some of which are definitely not IgE mediated. And so that's where what I said, Like, the deeper you get into the weeds, like what's an allergy? What's

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

It's how our body responds that inflicts the damage friendly fire, whether it's seasonal allergies to ragweed, environmental allergies like to cat dander, food allergies like to tree nuts, or some other type of allergy. We all know someone who has allergies or we have them ourselves, and we wished we didn't, at least speaking for myself, at the least, allergies are annoying, disruptive, and at the extreme they can be deadly. Why do our bodies react in this way? What have almonds ever

done to us? And on top of that, has it always been like this? In this first episode of this two parter on allergies, I want to explore those questions, the significance of allergies in an evolutionary context, and a little bit of how our knowledge of allergy has changed

over time. Ultimately, I want to try to get at whether allergies are increasing infrequency and why that might be sort of unifying all of this, and then next week I'll pick it back up at how we devised ways to deal with the self attack using medications, allergy shots, the EpiPen, and so on. Almost universally, allergy or an allergic response is described as an overreaction, an exaggerated response to an innocuous environmental trigger like pollen, like dustmites, like peanuts.

Since scientists first characterized allergies in the late eighteen hundreds early nineteen hundreds, they referred to the phenomenon as an idiosyncrasy, a biological contradiction where our bodies harm us in an attempt to protect us. But more recently some researchers have called into question two assumptions that underlie this premise of allergy. Number one, that this reaction is always an overreaction, and number two, that the substances triggering an allergic response are truly innocuous.

And while maybe that reaction is just a peculiar aspect of our immune system, might it also be that there's a very good reason that we still possess it. And importantly, are those two scenarios mutually exclusive? Or is it both

a quirk and an advantage. Since the early days of allergy research in the first decades of the twentieth century, allergies were labeled a modern disease, a quote unquote pathology of progress, the natural consequence of us living what was perceived to be increasingly unnatural lives, sedentary lifestyles, spending large amounts of time indoors, the growth of cities, consuming processed foods, using chemicals in the home and the environment, and so on.

Allergies are not the only disease said to result from industrialization and develop If you remember back to our gout episode, that was another one. Yeah, And in the case of allergies, there might be something to it. So Aarin you talked about how when someone is exposed to an allergen like a DustMite, their body begins producing IgE antibodies, which is

part of what triggers this rapid cascade of symptoms. As it turns out, our body ramps up production of IgE in response to another external threat helminth parasites, so dust, MTE,

hookworm very similar initial responses. One major difference, though, is in the long term in people who are chronically infected with helminth parasites that IgE production eventually scales down and the entire inflammatory response is suppressed in part by the parasite itself, which allows these parasites to kind of fly under the radar. That suppression doesn't happen in an allergic response. Instead, it can just ramp up and up and up until anaphylaxis.

And so, when researchers described IgE antibodies in nineteen sixty seven and began linking them to different exposures to things like allergies like parasites, a hypothesis emerged that we have this exaggerated allergic response and increasing rates of allergies in regions where parasitic infections are low because those parasites are not suppressing the immune system. So fewer parasites, more allergies,

and more parasites, fewer allergies. Essentially, the hypothesis goes improved sanitation and treatments for parasites reduced exposure to those parasites, which makes our board immune system go into overdrive overreacting to any stimulus, aka the hygiene hypothesis or the old

friends hypothesis. Now, this might be part of what's going on, because some studies show that regions with higher rates of chronic parasite infestation tend to have lower rates of allergy, and in experiments using mice, those chronically infected with helmets

are protected from developing allergies. Pretty compelling evidence. Also, some of the genes associated with asthma are also associated with increasing susceptibility to some parasite infections, so these genes might make you both more likely to develop asthma and more susceptible to parasite infections. The hygiene hypothesis does have some compelling support when it comes to allergies or allergy like diseases, but in recent decades some researchers are starting to question

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

by toxins. So a strong IgE allergic response like you described AARON is usually very rapid onset, generally speaking within seconds or minutes of exposure, and it's often accompanied by things like a sudden drop in blood pressure, vomiting, tearing, diarrhea, coughing, all things that would help to expel a toxic substance or blow it down from reaching vital organs.

Huh uh huh. Profit suggests that some of the allergens that we think of as innocuous, like pollens like hay dust or shellfish, may not be as harmless as they seem. Pollens contain phenolic acids or alkaloids, both of which can cause organ or nerve damage. Hay Dust can be contaminated by pathogenic fungal spores, and shellfish can have toxins from algae or plankton.

Are allergies a signal to us? Do they teach us which plants or foods to stay away from.

and the other used snake venom. The mice that had been previously exposed were more likely to survive a big second dose of venom that should have been fatal compared to those who did not receive that initial dose, suggesting that that big IgE response in the second exposure might be helpful rather than detrimental. And of course this doesn't explain why a beasting in humans can lead to a

fatal anaphylaxis response, because clearly that is very helpful. Some researchers suggest it's too much of a good thing, kind of like sickle cellnemia and malaria. Right, having one copy of the gene protects you from malaria, but two copies leads to disease. While most experimental studies looking at this toxin hypothesis have focused on things like beastings, other epidemiological studies have taken a broader view of toxins and how

they can harm us, such as cancer. There's no clear pattern when it comes to allergies in cancer, but some studies have shown that higher rates of allergies is linked to lower rates of cancer. But I would imagine that that depends on the type of cancer and the other lifestyle and genetic factors.

The farther away something is on that evolutionary tree of life? Does that mean that we're more likely to initiate an immune response to it? The future of allergy research is exciting, and to understand where we go from here, we also have to take a look at where we've come from. Yeah, are allergies changing and if so, what is driving that change.

Today allergies are one of the most common diseases across the world, affecting ten to thirty percent of the global population and up to fifty percent of people in some regions. For years, that number has been on the rise, which is why you'll hear people refer to this as an allergy epidemic, sometimes broken down into two waves, the first being respiratory allergies like hay fever and the second being food allergies. Of course, allergies themselves are not a new phenomenon.

IgE antibodies evolved around three hundred million years ago, allowing for this allergic response, and we have evidence of allergies from ancient times, descriptions of fatal beastings what could be allergic rhinitis, and of course asthma. But the heyday of allergy awareness pun intended, really only began in the eighteen hundreds, with the first description of hay fever in eighteen nineteen by John Bostock and the first case series published in

eighteen seventy three by Charles Blackley. These observations didn't seem to be a case of cool. There's finally a name associated with this condition that we've noticed for a long time, but a recognition of a truly emerging phenomenon.

of such a thing. The sudden increase in hay fever in Europe and North America around the late eighteen hundreds resulted from changes in agricultural practices, changing which crops were planning, planting more pollinaceous. If that's a word, it's not. I don't think my word document is telling me there's a red underline. It's angry, but it's the only thing I could think of. Pollinaceous grass varieties to feed the growing cattle herds, and an increase in farmed land in the US,

leading to higher ragweed growth. This marks the beginning of the first wave of the allergy epidemic.

then people got real sick from them. And by that time, so around the early nineteen hundreds, other work had shown how anaphylaxis can happen, how animals negatively react to the introduction of a foreign substance, and the concept of an allergic response mediated by your immune system began to gain traction because up to this time, germ theory had a pretty tight hold on many explanations of disease, and so the recognition that it was actually our immune systems causing

these allergic responses, like the call is coming from inside the house, took a bit of time to gain traction. Von Pirquet combined a bunch of observations from hyposensitivity, hypersensitivity, food allergy, hay fever, beasting reactions, serum sickness, and so on to create this organized concept of allergy as it relates to immunity, and it created momentum for more research in the area, even if it was initially papooed by like a lot of his peers.

a ragweed elimination campaign. The tides were changing and fast. Asthma, which prior to nineteen sixty had been considered a rare disease, shot up in incidents, doubling in Swedish Army recruits from nineteen seventy one to nineteen eighty one huge rise, as did hospital admissions for the condition, which increased tenfold between nineteen sixty five and nineteen eighty In Australia, the UK,

New Zealand, Canada, and the US tend for afterasthma. In the nineteen seventies, after the discovery of IgE, researchers observed a sharp increase in allergen specific IgE antibodies against environmental allergens, growing to over fifty percent of the population in some regions like I mentioned, and the second wave of the allergy epidemic. Food borne allergies began much more recently. Around nineteen ninety is most most papers I read, and that's

the same time that asthma case is actually plateaued. One large study found that between nineteen ninety seven and two thousand and eight, allergies to peanuts and tree nuts tripled, tripled, huge. Yeah. Reports from Australia indicate a tenfold increase in referrals to food allergy specialists and a five fold increase in hospital admissions for food related anaphylaxis. This is not just a matter of doing a better job of recognizing these allergies, No.

is seen in other autoimmune or immune mediated diseases. We know that these diseases are not rising all at the same time, or in the same place or at the same pace, which could suggest different mechanisms behind the rise

in each of them. And this has been you to challenge the old friends or the hygiene hypothesis, since countries that saw the biggest rise in allergies only did so beginning really in the nineteen sixties, which was around forty years after major sanitation changes would have reduced waterborne pathogens and anti helmath campaigns had reduced parasite burden to almost nothing.

So what could be going on? Most of the predominant ideas fall under the hygiene hypothesis or the old friends hypothesis or the biodiversity hypothesis, which are kind of like more recent offshoots, and both of these suggest that our allergies are a result of us not being exposed to as many or as diverse microbes and parasites that we used to throughout our evolutionary history. Why that would lead

to more allergies depends on who you ask. Maybe it's that with decreasing family size, kids are not coming into contact with as many germs at a young age, although some childhood pathogens like RSV are positively associated with developing allergies. So it's like the right germs, right, right, Which germs that's the Yeah, Yeah, it's layers, compilators.

limited exposure to the outside world. Maybe it's the chemicals and our soaps, food packaging, microplastics, pollution, ozone, cigarette smoke, that disrupts our protective epithelial barriers and sends our immune systems into overdrive. If you think about it, the allergic response is kind of like a hail marry last resort

option to protect us from toxins. After our skin or skin microbiota, after our guts or gut microbiota, our lungs and lung microbiota, lets it get through, right like, there are so many other layers of protection, and then maybe it's that once it makes it past all those layers, then we have this last ditch effort to protect us

from whatever perceived tosin there is. And if those layers are continually broken down by some of the things that we encounter in our everyday lives, like processed foods, you know, all of these different things that all combine together to increase permeability of those barriers, does that then lead to increase allergy?

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

against spoilers, that that was exactly the wrong advice. And now we know that because of these phenomenal studies, and so early introduction is now the recommendation. So what are rates going to be like in kids in five ten years. I'm super curious about all this, like how the epidemiology is going Is it going to change, I don't know, is it.

where we can look next. If it is certain detergent compounds causing a rise in asthma because of increased skin permeability, why and how. If it is a disrupted microbiome, what about it makes it disrupted? And how can we restore balance. If it is epigenetic effects, what are those prenatal exposures

that increase someone's chance of developing allergies? While the comp tx nature of allergies makes all of this seem so overwhelming, the truth is that people are doing incredible research to answer these questions, to get at the underlying triggers of different allergies, and it really seems like we're slowly going to be able to put the puzzle pieces together, at least for some pictures right, for some bits of the allergy, and come up with better ways to understand, prevent and

treat allergies. I love it so now, Aaron, I'll turn it over to you to tell us where we are with allergies around the world today.

and the blah blah blah running eyes. And I don't say blah blah blah to discount it because it has pretty significant effects on people's lives, as we'll see. But a paper from the Lancet from twenty eleven, which is old now, estimated that four hundred million people worldwide are affected by allergic rhinitis, and this number is likely higher today as this, like all allergies, has continued to increase.

But this varies a lot across the globe. And while most of allergic rhinitis develop in like child or teen years, sometimes they don't. There's plenty of adults who don't develop seasonal or environmental allergies until much later in life. But overall, in some areas of the globe, prevalence is as high

as like seventeen to twenty percent. Those seem to be the highest percentage numbers that I saw and across the board, even though in the International Study of Asthma and Allergies in Childhood, which is also now old because the Phase three study finished in like the early two thousands, but in this study, the rates of allergic rhinitis were actually

greatest in Latin America and African countries. But even there the prevalence was higher in urban areas compared to rural areas, and that pattern is true pretty much across the globe. Allergic rhinitis also has pretty significant burdens on our healthcare system. In the nineties, way back in the nineties, it was estimated to cost one point nine billion US dollars every year, and that increased to three point four billion in the

early two thousands. And that's not even counting indirect costs, of which there are enormous indirect costs, things like miss school, missed work. Allergic rhinitis especially can result in things like poor sleep or sleep apnea. It can contribute which can then lead to fatigue, memory problems, mood changes. It can make school harder for kids, like, it is not a minor like we might think of it as, oh, it's

just a runny nose. It is not just a running nose. Right, Food allergies we have much credier data for.

allergy will outgrow them. Then there's other food allergies like shellfish and fish, which not only do we have less data for the idea that early introduction can prevent sensitization for things like fish and shellfish, but it's also more likely that people don't develop those allergies until adulthood.

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

a week every week for the first five years of life. Okay, wow, but in those kids and in these studies, they took kids who were high risk, kids who either had severe eggzema or had a known allergy to egg or In some of the studies it was kids who had a family history of peanut allergy, so these were high risk kids because we know that there's genetics in these associations. So in those kids, the reduction in risk of peanut allergy was like seventy to eighty percent. It was massive,

massive reduction in risk, and so across the board. Now the recommendation is early exposure, but it has to be that consistent exposure, so it's not like necessarily a one time dose, like give this much peanut. It's really like start small, but continued exposure, so like a little peanut on the finger when they're a tiny baby, continuing that until they're like eating peanut butter and their oatmeal like a couple times a week when they're kids, and that

significantly decreases the risk. And so that data has now been extrapolated to a lot of the foods that the earlier exposure to all of the main allergenic foods, and in the US, those foods are wheat, soy, tree nuts, peanuts, milk, egg, oh, crap, I should have written all of these town fish, shellfish, and now sesame. That's the early net. The newest edition. So early and consistent exposure to all of those is what's now recommended to try and prevent food allergies.

like cat dander. Cat dander is a good example because if you test kids who live in homes with cats, a higher percentage of them will have a degree of sensitization at a certain age, but a lower percentage of them will be allergic, will have that allergic response to kings. And so yeah, so like what is it about sensitization versus then who of those kids who are sensitized actually

then will have allergies. We don't exactly know, so is there is that what it is for adults who develop say a shellfish allergy later in life, that maybe they were a little bit sensitized, but it wasn't until that built up enough in their system that they had an allergic response.

that cause anaphylaxis. But at least in some of the papers that I found, it's estimated that about zero point three percent of the population of Europe will experience anaphylaxis at some point in their lives. Wow, okay, yeah, higher than I expected. And the data across the board is that especially in most high income countries, which is where we have data, incidents of anaphylaxis is increasing, which makes sense because allergies across the board are increasing. Anaphylaxis, especially

due to food born triggers, is increasing. Anaphylaxis due to alpha gu specifically is increasing big time. But mortality does not seem to be increasing, except in Australia, which some of the data has had increases in mortality associate with anaphlexis.

that is just called Allergy and Allergic Diseases. There was one on titled food Allergy from Nature Reviews Disease Primers from twenty eighteen, and another one titled food allergy from the Lancet two thousand and two, and then two on allergic rhinitis, one titled Allergic Rhinitis from the Lancet twenty eleven and one titled Allergic Rhinitis Definition, Epidemiology, path of Physiology, Detection and Diagnosis from the Journal of Allergy and Clinical

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