This Podcast Will Kill You - Ep 122 Asthma: A phlegmy episode

Episode Date: August 8, 2023

Most of us are familiar with asthma. Maybe you have the disease yourself or maybe a friend, family member, or coworker has it. Or maybe you’ve just watched a tv show or movie featuring a character with asthma. However you learned about this disease, you probably still have some lingering questions about it, like “how do inhalers work?”, “what are the different types of asthma?”, “where does the word asthma come from?”, “can other animals get asthma?”, and “can Erin and Erin tell me everything they possibly can about asthma?” The answer to that last question is a resounding yes, and the answers to the others you’ll find in today’s episode, where we take you through the complicated but somehow also straightforward biology of this disease, the long history of asthma peppered with firsthand accounts, and the promising research that may transform the way we live with this disease. See omnystudio.com/listener for privacy information.

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Listen to Dirty Rush on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Then she says, have you seen a photo of my son? And I'm like, who is this person? Welcome to the Boys and Girls podcast. Arranged Marriage is basically a reality show and you're auditioning for your soulmate. And who's judging? Only your entire family? I sacrificed myself to this ancient tradition, hoping to find a reality.

mind love the right way. And instead, I found chaos, comedy, and a lot of cringe. Listen to boys and girls on the Iheart radio app, Apple Podcasts, or wherever you get your podcast. Hi, my name is Lindsay, and I wasn't officially diagnosed with asthma until I was a teenager, but I do remember when I was a kid having exercise-induced asthma, but just not knowing how to describe it. My asthma was very well managed with just your standard preventative and albuteril until my early 30s. Something changed, not sure what it was. And then March of 2020, I had my first really bad exacerbation. Beforehand, it was just like I could maybe have one, maybe two exacerbations, if any, in a year. So I got an oral steroids in March of 2020, and it cleared up pretty fast. Usually

that's how it happens with asthma exacerbations. And, I finished the course of steroids, and then about a week later, I started having asthma symptoms again. And again, I had to go back to my doctor and get back on steroids. And this happened pretty much every six weeks. I would get on steroids and then finish my course of steroids, and then gradually the symptoms would return. And then with my first pulmonologist that I had, we were kind of in a struggle between testing my blood levels for the eosinifal levels that they thought would be the problem in excess of eosinophils kind of aggravating things. But unfortunately, I wasn't able to stay off of steroids for long enough for them to get an

accurate eosinophil count. So it was kind of this, let's get off of steroids, but then I would have an exacerbation. So that was frustrating. And that happened throughout the spring and summer of 2020. I'm a paramedic, so it was extremely difficult at work. Even when I wasn't having a full-blown exacerbation, I was having to wear masks and feeling very short of breath with my patients. And I got very tired of explaining that, no, I don't have COVID, my lungs are just trying to kill me. The exacerbations were intense. It would start off as shortness of breath. I would get very short of

breath for a few days, just with regular exertion. I would get winded climbing a fight of stairs. I would get winded getting dressed. And then eventually they would degrade until I was having to take albuterol treatments, regular albuterol treatments every two hours maybe. And then eventually we switched to duoneb. And even the duoneb was only effective for about four hours at a time. The worst by far was the sudden nocturnal dyspnea. I would be asleep and then I would find myself awake.

And then it would be like it would feel like a train would just hit me in the chest and I couldn't breathe and I would be scrambling to find my nebulizer and set that up before I passed out basically. I did have a little at-home pulse oxymeter. The lowest that I ever saw my pulse socks go was 74%. That was scary, especially because I'm a medical professional and I know what that means. And like my head was swimming and pounding and I'm just trying to work through that work of breathing to bring my oxygen levels up. I got into a pretty sticky situation. I had to a pretty sticky situation. I an asthma exacerbation that landed me in the ER in October of 2020. And in that ER setting, I actually found out that I was pregnant. That was pretty scary. Things got pretty complicated because the normal

course of action at this point would just be on a low daily dose of steroids until we could figure out what was going on and find a better treatment. However, the implications of taking long-term steroids while pregnant were not great. There was a lot of complications that could go along with that. Luckily, moving into the winter season, my asthma is pretty mild, so I was able to just kind of fuddle through, take very short bursts of steroids if I needed it. That got me pretty much through all the way to the spring right before I delivered, where I inadvertently had an anaphylactic reaction to something that I've never had an anaphylactic reaction to before. My palmologist at the time didn't say it was anaphylaxis, but anaphylactoid, an anaphyloid reaction, I guess. So I don't really

know what the difference is, but either way, it was very scary. So I ended up going on a short burst of stories after that. And then I delivered in June of 2021, a very healthy baby girl. And I had another exacerbation immediately after I delivered, which was rough. At this point, I was working with one palminologist who had mentioned biologics before, but was nervous about starting biologics to kind of change my immune system while we were in the middle of a pandemic. I suffered through about one more exacerbation with that palminologist, and then I decided to get a second opinion. So I switched palmologists, and I was immediately allergy tested and then started on the first biologic that they usually go to called DuPixen. DuPixen helped a bit. It's a monthly

injection. It's a monoclonal antibody. That helped manage some of my symptoms to the point where I was able to wean down from the prednisone, but not all the way. So in February of 2022, I started on a medicine called fesenra. And that was wonderful. That was an immediate difference. I was able to wean off all of my prednisone, just kind of stick to my regular albuterol and my preventatives. And it's been great. I've been able to get back to exercising. I don't feel like I'm suffocating, having to wear a mask at work anymore. So yeah, it's been definitely a journey. Now we are working on a kind of like a third biologic option because the Thesenra was supposed to be able to be weaned off of it, but I've not successfully been able to be weaned off of it. So we're going to try a new medication called Enkala, which is supposed to control sinus polyps as well. So we'll see how that goes.

And yeah, that's it. That's been my journey with asthma. Oh, my gosh. That sounds so scary. I just, oh, I know. Goodness. Thank you so much for sharing your story with us. I can't imagine reliving that is easy. Yeah, and just how, like, what a confusing time and how, like, difficult and, like, long this process can be sometimes. Yeah. Yeah. Oh, yeah. Thank you. Hi. I'm Erin. Welsh. And I'm Aaron Allman Updike. And this is, this podcast will kill you. And today we're talking about asthma. Yeah. I know we say this a lot, but big topic. Is asthma even like, I think it was near the

end of my research when I came across a phrase that was in some 2006 journal article in the Lancet that was like, has asthma as a term outlived its usefulness? Right. Like, is asthma even a thing? Right, is it? I guess we'll find out. We'll find out, I guess. Yeah, it is a very big topic. There's a lot of, it just feels very amorphous. So I'm curious to see how it all goes. I have a feeling at the end of this episode, it's going to still feel amorphous, but hopefully we can like put some boxes around it maybe. I don't know. Yeah, I think so. We'll try. Okay. But first things first. It's quarantini time. It is.

What are we drinking this week? Well, nothing other than the inhaler. It works well on paper. It does. Just go to our social media. You'll see it written. Uh-huh. Uh-huh.

You basically with the ale emphasized. It's the inhale. Wait, the inhaler. Ailer. That's, yeah, really rolls off the tongue. Does not translate well to audio. That's okay, though. That is okay.

What's in the inhaler, Aaron? It is based on a new drink, new to me, that my friend actually told me about called the Spaghetti. I don't know its provenance, but it is delicious. It's basically like a cheap logger, and you get a bottle, you drink a little bit down, and then you pour in some apparel and lemon juice. It's kind of like an apparel spritz, but with cheap beer. And I love it.

It sounds delicious and I can't wait to try one. And we will post the full recipe for this quarantini as well as the non-alcoholic placebo rita on our website, This Podcast Will Kill You.com, as well as on all of our social media channels. Our website is this podcast will kill you.com. Have you heard of it? Have you gone to there? We have so many things there. Check it out.

We've got merch. We've got a good reads list. We've got there's so much more. We've got music by Bloodmobile. We've got a Patreon. You know what? Just check it out. Check it out.

There's actually a really cute new merch. There's like a muscle tea. I'm wearing it right now. You are. You look great in it. Oh, thanks. Okay. Enough flathering.

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Just visit O'Keefscom. This Podcast and code this podcast at checkout. This season on Dear Chelsea with me, Chelsea Handler, we've got some incredible guests like Kumail Nanjiani. Let's start with your cat. How is she? She is not with us in. Okay, great, great way to start.

So this is a great beginning and hopefully you'll be able to, I don't know, maybe you will cry. Amanda Seifred. Life is so short. If you feel something like that, you have that fire in you for this experience. It's not for a guy. It's for the experience of being in love.

And, like, it's bigger than a guy. Elizabeth Olson. I love swimming naked so much. And I know you love taking pictures of yourself naked. I love to be naked. I just want to be in my brown underwear all the time. Ross Matthews. You know what kids always say to me?

Are you a boy or a girl? Oh, my God. That's so funny. I know. So I'm always like, hi. I try to butcher it up for kids, you know, so they're not confused. Yeah, but you're butching it up is basically like Doris Day. Right?

Right, no, I turn into be Arthur. Listen to these episodes of Dear Chelsea on the Iheart Radio app, Apple Podcasts, or wherever you get your podcasts. So there are various definitions of asthma that exist out there. They're all probably slightly different based on which society or expert panel or which set of guidelines you're looking at. But for this biology section, the way that I decided to structure it is just to jump into describing being what asthma looks like or feels like what the symptoms are, because that will inevitably lead us to the big question of this section. And that really is what on earth are these underlying causes or mechanisms of what we know of as asthma? Like what is going on in our bodies

if we are living with asthma? So let's get into it. I think that asthma is a common enough condition that probably everyone listening has heard of it and either has asthma or knows someone with asthma personally. So when we think of asthma, we probably have a picture in our mind of what we think of. We might think of someone who has these discrete episodes or asthma attacks, where they might have wheezing, right, this sound in their airways, like a squeaking sound when they exhale. They might be really short of breath feel like they just can't catch their breath. Maybe we think of someone who is coughing a lot and just kind of can't stop coughing during these episodes or complains of a feeling of tightness in their chest, like they just can't get enough air in because of the feeling of

this tightness. And we probably think of this person using an inhaler of some kind, like a puff and then being able to breathe a little bit easier. Maybe we we think of someone who has to use an inhaler before they can start soccer practice or run the mile in PE because otherwise they get short of breath? Or maybe we've actually seen or experienced a very severe exacerbation where someone can barely get any air in. They're wheezing so much that you can hear it across the room without a stethoscope and they have to go to the emergency room for systemic treatment with steroids and breathing treatments. And many of us might think of asthma as a childhood condition that people outgrow and then no longer need their inhalers once they're

adults. And those kind of are the symptoms of asthma. But as we'll see, not only is asthma not only a childhood condition, it's a chronic potentially lifelong condition or one that can arise for the first time in adulthood. But it's also a lot of different things. So while these episodes all might sound similar, there is a lot going on underneath the surface in every different person that has asthma. So is asthma as a term more like a collection of symptoms rather than any like one pathophysiological process? Pretty much. Yeah. Let's get into it, shall we? Yeah. Because we can talk about some of the pathophysiology, but as we'll see, yes, there's a lot of different sort of pathways that get you to that same endpoint where you have these episodes with wheezing,

shortness of breath, chest tightness, etc. Right? Mm-hmm. Okay. Yeah. So on a very basic level, asthma is a chronic inflammatory disorder that's affecting the airways, right, of our lungs. And it essentially results in these episodes in widespread and uneven constriction or

narrowing of the small and large airways of the lungs. And that results in obstruction of airflow. And that constriction, that obstruction, is usually reversible, either spontaneously, like with time or with medications, those inhalers that you see people using or that you've maybe use themselves. That is what causes the wheezing sound, right? Is this restriction, constriction of the airways and air trying to get out through a very small opening. It's also what causes the shortness of breath. You literally can't move air back and forth because of how small these airways are. But that's a pretty bare bones description.

We don't do bare bones. So let's drill down as deep as we can on this podcast into what's going on in asthma and in these asthma attacks or exacerbations. So like you alluded to, Aaron, asthma is not just. one thing. It's not one discrete pathophysiologic process that's underpinning these exacerbations or these episodes. And it's not just these episodes. All of the different pathophysiologic processes that I'll get into at least a little bit of detail of first start with an underlying chronic inflammatory state. So in all people with asthma, there's an increase in

inflammation of the airways even in the absence of an acute episode. So there's these chronic low-level inflammation that's happening all the time. And then there are these acute or discrete worseninges of that. That's what we call an asthma attack or an exacerbation. These attacks tend to happen with some kind of trigger, smoke, exercise, allergens like pollen or cat dander, very often a cold or a viral infection. But it could even be just cold air. Really, it's any number of things that cause a sudden increase in inflammation and immune system activation that then causes inflammatory cells and messengers and all this stuff being sent to the airways. That leads to both cells and debris in the area, which that alone can cause some

obstruction of the airways. But in people with asthma, what this does is it triggers a hyper reactivity of the smooth muscle cells that surround our airways, and it causes those airways to constrict. This, again, obstructs the airway. So it's these two things. Inflammation, which is both an underlying chronic inflammation and episodes of increased inflammation, and smooth muscle constriction, also called bronco constriction. And that together is what causes the shortness of breath, the wheeze, the chest tightness, all of these things that we associate with asthma exacerbations. Okay, I can wrap my head around like the hyper-reactivity part of this leading to super-inflammation. But where does the smooth muscle constriction come in? Like, why does that happen? Does that happen under other

circumstances, when is that, like, is it too much of a good thing kind of a deal? Yeah, it's a good question. So, yes, our airways have smooth muscles so that they can expand and contract as needed. Right. What happens in asthma is a hyperactive response. If you think of like when you get a tickle in your throat or you inhale your own saliva by accident and you cough, right? That, Cough response, part of what's happening in that is airways are constricting. Smooth muscle cells are being activated, right? That's a normal physiologic response. What's happening in asthma is a hyperreactivity to irritants or to triggers of some kind.

That's also happening unevenly across all of the different small and large airways in your lungs. So it's not like the whole lung. It's like patchy throughout the lungs. That's really interesting. And it's like a sustain. gained response to? Such a good question, Erin. So it's not like just all of the airways in the lungs constrict and stay constricted, but

it's, you can think of it as like this hyperactive response happening throughout the lungs, and that is also going to trigger more immune activity and inflammation, right? So it's like a, it's more like a cycle. Yeah, dominoes or cycles. Okay, so why certain areas? Like, is there any rhyme or reason to which areas are? constricted or have this hyper-reactivity or anything like that? Not that I know of.

Okay. Yeah. Yeah. It's just sort of, it's happening throughout the lungs. Yeah, yeah. Patchy. Debris. Like mucus?

Can be mucus, cells, all of the immune mediators that are coming to the quote-unquote rescue because of this trigger that we have to respond to, right? All the cells that are there. It's just all that stuff. And again, this is not happening in this. the same way in everyone, so it's not the same stuff in everyone. There are a lot of different types of asthma, and they're classified in different ways. So in a clinical setting, like your doctor's office or whatever, you might often hear asthma classified by its severity. Is it an

intermittent asthma that really happens pretty rarely under very certain circumstances? Or is it persistent? Is it kind of always there or happens really often but can be controlled with medications? Is it mild? Is it moderate or is it severe? But those different definitions change based on what society's guidelines you might be looking at. And by society, I mean, you know, like the asthma federation of this country or that country, not like our society. Yeah. High society, whatever. But on top of those type of clinical definitions, there's also a lot of other ways to classify asthma. There's allergic asthma, which often coincidental. sides with things like, you know, allergies, food allergies, environmental allergies, eczema, non-allergic asthma, so not associated with allergies or allergic responses. There's like cough predominant asthma.

There's eosinophilic asthma. There's exercise-induced asthma. There's late onset asthma. There's a lot. And these are sometimes called different phenotypes of asthma. For anyone who hasn't taken general bio in a while, a phenotype is like what you observe. It's a set of like observable characteristics. So these are other ways to classify asthma based on how it appears clinically, how you seem.

It's another system aside from just mild, moderate, severe, and these can kind of go together. But none of these ways of classifying get into the fact that within and across each of these classifications, there are in fact different underlying mechanisms of that asthma. These are sometimes called different asthma endotypes or different subsets of a disease that are actually based on distinct pathophysiological mechanisms. On that, I want to shout out a paper called Understanding the Immunology of Asthma, Pathophysiology Biomachers, and Treatments for Astmoctypes from 2020, because not only does that paper highlight a lot of the complexity of these different endotypes, and I am not going to get into a lot of that complexity. but it had this really great schematic diagram of some of the possible mechanisms that underlie the development of these different types of asthma, which you can all just call asthma, really, in a way that connects these seemingly disparate pathways that all happen to lead to the same

end result, right? And that end result is chronic underlying inflammation and airway hyper-reactivity, with certain triggers, aka asthma. It's so interesting because on the one hand, it seems like you can break down asthma into so many discrete types and in terms of phenotype, like you said, or the underlying mechanism or treatment or whatever. But at the same time, it's this big overarching thing. And at the same time, treatment, I assume, is highly individual where it's like based on this person. Like, you could have two people that have allergic asthma, but maybe their triggers are something different. And so then the management is different. Well, is it, Aaron? Because right now it isn't. And that is,

that is such a good point, right? That is why understanding these different underlying mechanisms matters. because if all the treatment is the same, then these underlying mechanisms are interesting, but don't necessarily matter. Right now, our treatment is based on symptoms, and symptoms are things that you can see and experience, right? So treatment is based on how often do you have exacerbations? Yes, maybe what are your triggers will determine when you might use a treatment, but at its core, the treatment guidelines are mostly the same for everyone based on the severity of your asthma, but not based on any of these underlying mechanisms. So two people with the same severity are going to end up falling on the same treatment algorithm,

even if they have totally different types of asthma, how it stands today. But it doesn't work the same way for everyone. And that's because the underlying mechanisms aren't necessarily the same. So in asthma, we have now learned that understanding these disparate mechanisms is actually really important because even though it ends with the same response, the ways and pathways in which you get there, if we can better target those, we can have individualized treatment. And then we can have better outcomes. Right now, we have that for pretty small subsets of populations just based on like what's available today.

Huh. So it's like it's within reach. It's like we know this now. Now let's turn to application. Right. Exactly. I think that's kind of where we are and where we're going. So that's like spoilers for later this episode.

So that is kind of the as much as we'll get into on the nitty gritty of like these different mechanisms of asthma and the types of asthma. If you want more real nitty-gritty, I will post plenty of papers for you. But the other big question is like, who gets asthma? Right. Right. Everyone. Right. Everyone.

What are these risk factors? Like, and I think a really interesting part of that question from a public health perspective is, is it inevitable that a person is going to develop asthma if they are a person who's going to develop asthma? or is this something potentially preventable? And I'm sure it will be no surprise to you, Erin, or to listeners, that we don't know the answers to that question. Asthma is a multifactorial disease. Since we know now just how variable it is, and we're only in the relatively early stages of really understanding all of that variability, we don't really know and can't pinpoint this person's going to develop asthma, this person's not.

If we change these things about the environment, we could prevent this asthma, but not this asthma. We don't know that. But we do know that there are both genetic and environmental factors that play into the development of asthma. There are a lot of different potential genes that could be involved, like a whole host of them. And there's some thought that there might also be epigenetic factors that are involved because there's evidence that asthma is more strongly maternally linked than paternally linked in terms of genetics. But overall, heritability is like between 35 and 80 percent, depending on which study you read. And in terms of environmental factors, there are so many. It's just like you could spend the rest of this episode listing them and not even.

get close. Exactly. And I know, Erin, that you're going to get into some of the fun hypotheses that have come out as to... Just a tiny little sprinkling. Yeah. That's good. That's good. That's all we need is a sprinkle of some of those. But some things that we know are real risk factors for asthma are things like tobacco smoke. Pollution, right? Air pollution is a huge factor in the development of asthma and also asthma exacerbation. So there's a lot of just overall environmental changes that can affect the development of asthma. And that's a large part of why we see, as we'll talk about in the current event section, such variation in asthma prevalence across the globe.

There are so many layers to every aspect of asthma. I know. And I have nowhere that I'm going with that, just saying that. But I do have a question. So you talked about how, for the most part, treatment and management is more or less very similar, if not the same for most people. What is that treatment? Oh, great question. I'll talk a little bit more about this in the current event section, but the basic, very basicness is inhalers of some kind.

Inhalers allow for medication to be delivered directly to the lungs. So that's where we want the effect of this medication to be. This is a disease that's really happening in the lungs. So by having an inhaled medication, you have pretty minimal systemic absorption, which is good. There's two different major types of inhalers. There's inhalers that mostly serve to bronchodilate, so they relax the smooth muscle of those airways and open them up, right? All of those rescue inhalers that people think of, those are usually really short-acting broncholidylate. violators. So they turn on quickly and turn off quickly to just open up your airways if you can't

breathe for a short time. Then there are longer acting versions of those that people might use as controller medications. And then there are inhaled steroids. Steroids, of course, are anti-inflammatory. So these are serving to reduce the overall inflammation and immune activation that's causing a lot of this underlying issue. more and more inhaled corticosteroids have become the mainstay of asthma management, even in mild asthma. It used to be probably overreliance on bronchidilators. And now more and more, it's inhaled steroids plus or minus these broncholidators. And I think that that makes sense when you go back to what we just talked about with the fact that this is an inflammatory disease.

There's underlying chronic inflammation even in people with mild or intermittent asthma. And so anything that's just acting to bronchodilate is like a bandaid. It's treating the symptoms, but it's not addressing that underlying immune dysfunction and inflammation. So the steroids are doing a better job of that. But as I said, especially as we understand more and more about these different types of asthma, there are already and will likely continue to be other probably systemic options like monoclonal antibodies and things like that that are directly targeting the dysfunctional immune cells involved. But we're not there quite yet.

I think it was in our lupus episode that we talked about how long-term use of steroids can be not so great sometimes. Is that different for inhaled steroids because it's so localized? Exactly. That's why it's so important that it's inhaled and not systemic because you have very minimal systemic absorption. It's really just like coding your airways and acting in those airways. Very different than like taking steroid pills. Yeah. Okay. That's interesting. Yeah. Although we know that asthma is not strictly a childhood disease or disease of childhood, it does happen in children and then go away. way, do we know anything about why that is? Good question. I don't have an answer to that question. It is possible that I just didn't read the right papers and that there is a very good answer to that

question that I didn't find. So if anyone has a better answer than what I'm about to say, please do let us know. But I suspect a lot of it just has to do with how much our immune systems are still under development when we're little. And our airways are also a lot of smaller. Okay. So anything that's causing obstruction or constriction, it's going to have a greater effect when you're smaller and your airways are small. And so a lot of kids have wheeze. And a lot of that wheeze may never truly be labeled as asthma, right? They might get wheezing with every viral infection but never like meet the definition of asthma by whoever's defining it in their region. and then they'll grow out of that because their airways are growing and their immune system is, you know, figuring itself out.

That's the best answer that I can give you. There might be a better one out there. Okay. Yeah. So I know that this next question, the answer is probably it depends on what country or what organization or whatever. But how is asthma diagnosed? Yeah. What happens? What are the diagnostic criteria? Excellent question. So in some places it's diagnosed. with what are called pulmonary function tests. So that means you actually have to like sit in this chamber and blow and this tube and they measure the flows and blah, blah, blah. And then on top of that, you have to give a bronchodilator and see if the values improve because that tells us that it's a reversible process. That really helps distinguish asthma from something like COPD or chronic obstructive

pulmonary disease. So that's more like adults are more likely to undergo that whole pulmonary function testing process. In kids, a lot of times they can't do those testing or that testing is really difficult and just not available where they live. So really it's based on those symptoms that I talked about way at the very beginning. These discrete episodes of shortness of breath and wheezing, which is something you're going to hear with a stethoscope.

And that happen in response to really any kind of trigger, doesn't matter what the trigger is, and that will get better with some of these medications in general. So I don't have in front of me like the very specific this number of episodes or of wheezing or anything like that, but that's the general rule. And you don't have to have those pulmonary function tests in order to make the diagnosis. Okay. I feel like I saved all my questions for the end somehow, but I do have another one. Okay. Give it to me. And that is. is the breakdown between mild, moderate, and severe? Like, what determines whether something is mild, moderate, or severe is that the frequency or intensity of exacerbations and question part two

is, are there certain types of asthma that are more likely to be severe or more likely to be mild or is it super individual? Excellent question. So again, I don't have the exact numbers in front of me in terms of mild, moderate, severe. I will point all listeners who want to know to and will link to the Global Initiative on Asthma or Gina Report, which is one of the main organizations that defines these. But it is based on how many exacerbations you have, whether you've needed to be hospitalized or had systemic steroids to treat an exacerbation versus if your exacerbations get better with just inhaled medications because sometimes they're so bad that you do need those systemic steroids to actually calm down that inflammation and actually treat that

exacerbation. So yeah, at its core, it's about how many exacerbations and how bad those exacerbations are. Okay. When we're talking about the different classification. To answer your question about are certain types of asthma more likely to be severe? Yes, potentially, especially adult onset asthma or late onset asthma, is maybe more likely to be severe than childhood asthma or asthma that's been there since forever. And I'm sure that there are other types that also are more likely to be severe than others. Then there are also some people with asthma that we maybe don't have a good classification for, but that is very severe that we really don't have great treatments for yet. And so I think that gets to why it's so important that we really

understand all of the different underlying mechanisms because there are people who have very difficult to control asthma with severe symptoms that we right now don't have great ways of treating. Okay. Yeah. So yeah, that's, unless you have more questions. That's the biology of asthma. There's so much to it. Yeah. And I probably didn't cover it all.

I mean, it's impossible to, though. Even if you did one type of asthma. Let's say like allergic or allergy associated asthma or whatever. How do you even begin? We'd be here all night, Erin. Yeah, we would. So on that note of being here all night. night, Erin. I'm guessing, I mean, have we had asthma since we've been humans? Where did the, again,

I don't even know how to ask where did this come from? Like what, what's up with this? How about that? That's a good way to put it. I don't know, but I'll do. We'll, we'll try to get into it as much as we can right after this break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for

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Kumail Nanjiani. Let's start with your cat. How is she? She is not with a thing. Great, great, great way to start. So this is a great beginning and hopefully you'll be able to, I don't know, maybe you will cry. Amanda Seifred. Life is so short. If you feel something like that, You have that fire in you for this experience. It's not for a guy. It's for the experience of being in love. And like, it's bigger than a guy. Elizabeth Olson.

I love swimming naked so much. And I know you love taking pictures of yourself naked. Yes. I love to be naked. I just want to be in my brown underwear all the time. Ross Matthews. You know what kids always say to me? Are you a boy or a girl?

Oh, my God. That's so funny. I know. So I'm always like, hi. I try to butcher it up for kids, you know, so they're not confused. Yeah, but you're butching it up is basically. An angry woman. It's like Doris Day.

Right? No, I turn into Be Arthur. Listen to these episodes of Dear Chelsea on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Hi, I'm Danielle Robe. Host of Bookmarked, the podcast by Reese's Book Club.

And this week on Bookmarked, we're basically hosting the Ultimate Girls' Night. Reese Witherspoon, Jennifer Garner, Judy Greer, Rita Wilson, and Gauri Rice, and author Laura Dave. These are the women behind season two of the Apple TV series

the last thing he told me. We're talking about turning a book into a hit show and what it really takes to bring a story to life. The most important metric for me is do I want to share this book with somebody?

That's what creates community and that's the main thesis of our book club and why we started it was just to connect people together. Listen to the bookmarked by Rees's Book Club podcast on the IHeartRadio app,

Apple Podcasts, or wherever you get your podcasts. The thing that surprised me most about the history of asthma isn't how far back and wide-ranging the descriptions go. So, Aaron, you asked, have we had this since we were humans? First of all, yes, it's an ancient disease that's been written about since ancient times, and we absolutely have had it for as long as we've been humans, which makes sense because other animal species can also have asthma, like catch-get asthma.

I really wanted to ask you that question, and I was afraid that it was a silly question. No, I definitely Googled it, and that's what Google tells me. Oh, my goodness. Poor kitty cats. I know, I know. How do you get an inhaler for a cat? You need a nebulizer. Sure.

I don't know how at-home management is for cats with asthma. Maybe we have a lot of people who are in the veterinary field that listen, so reach out. Yeah, let us know. Please. It's so sad. But I forget where I was even being. going with this, but... That we've had it since forever.

Oh, yeah, yeah, yeah. Another thing that did not surprise me, or it didn't surprise me the most, about asthma, the history of it, is that asthma has undergone many revisions since these earliest descriptions, right? Like, that's not that surprising. It started out as a disease of humors,

then of lungs, then of personality, then of allergy, then as inflammation, and many other forms along the way sort of crisscrossing each other and happening simultaneously and borrowing parts of each other. Makes sense. The thing that actually surprised me the most about the history of asthma was how prominent a role the personal experience of asthma played in the way that this disease was written about, the attention it got, and in my view, the greater sense of empathy that it invited.

And this is true for much of the history of this disease. really, or at least until we get to the early 20th century with the depersonalization of medicine, as per usual. Basically, this is my way of preparing you for the sizable number of sizable quotes that I've sprinkled in throughout the history section one first-hand account per century. Just kidding, that would be like a ridiculous amount. That would be a lot. But I honestly probably could have given how many there are, which I think is really

interesting and unusual. Yeah. Is it just that a lot of people had asthma? So, or why? Why is that? Yeah. I think it just comes down to how prevalent it was and how much it was a part of people's lives. Right. Because people were just like living with it on a day to day. It wasn't this thing that came one time and then killed you. Right. Like a lot of diseases we talk about is something that people lived with for their whole lives. Yeah. I think that the most similar one that we've covered on the podcast is gout. But the other thing, too, is that, like, we've covered a lot of chronic diseases, but it's also who is doing these medical writings. Who writes about it.

Who was able to be a physician, who was allowed to be a physician. Right. So, like, endometriosis, we could absolutely have had some. centuries worth of firsthand accounts, but we don't. Mm-hmm. Mm-hmm. This makes a lot of sense. Yeah.

Anyway, but I think in terms of asthma, what these historical firsthand accounts show is that while there have been enormous improvements made in terms of how it's treated or understood or even defined, some things haven't changed. I also think that they're a good reminder in this day and age with medicine being so depersonalized and reduced to statistics and charts and test results to not discount the value of personal stories because I think that it can be really important in, well, first of all, just like recognizing that patients are people, but also in how maybe this person wants to manage their asthma and the things that exacerbate asthma. Anyway, I should probably stop at this point, philosophizing

and, you know, talking about asthma and start talking about actually the history of asthma, beginning with the ancient stuff. Because the evolutionary history of asthma, like, it's impossible to... Yeah, absolutely. Yeah. Yeah. So it feels like it's been a little bit since I've gotten to say the word papy or talk about ancient Greece or China or India. So this is exciting.

The word asthma is actually from an ancient Greek word that first made an appearance in the Iliad from the 7th or 8th century BCE. In a scene describing the Trojan leader Hector, quote, lying on the plane while about him sat his comrades and he was gasping with painful breath, asthmati, distraught in mind and vomiting blood. in this context and for the few hundred years that followed, the word asthma was used in ancient Greece to describe labored or painful breathing or gasping, especially as induced by exertion. So you can find it a lot in descriptions of battle or death scenes in epic plays or poems. But by the time of Hippocrates around the 5th century BC or so, the word, asthma had shifted to have a more medical meaning, with a specific set of symptoms, causes, prognosis, treatments, et cetera, a chronic condition rather than just solely an acute attack.

Okay. And in this recognition, ancient Greek physicians were a bit behind the times. The Iber's papyrus from around 1550 BCE includes a description of what is likely asthma and treatments that ranged from your simple enema to the application of various animal dung mixed with herbs. Just spread that on your skin, I guess. On your skin? What? Sure. Asma was written about extensively in ancient China as well, with the earliest descriptions coming from around 1000 BCE, including a mention of the plant Mahwang, which was used to treat asthma. And in modern times, has been, been used to extract ephedrine, which has also been used to treat asthma. So that's kind of,

that's kind of cool. Yeah. The inhalation of stramonium from thorn apple or jimson weed was also used in modern times to treat asthma and was also mentioned in some ancient texts. But anyway, Aswell was widely written about across the ancient world, like in so many different historical texts. It's kind of incredible. And I think that just goes to show how prevalent it was and how much interest there was in finding ways to alleviate symptoms. And yeah, some of those treatments seemed a bit questionable. You know, you've got your bloodletting, your enemas, your plasters to ease the chest, your diuretics, your emetics, your emetics, exercise, massage, honeywater, mead, eating the liver of a fox after it's been. dried and pounded and sprinkled into a cupful of wine, or just eating the freshly roasted lungs

of that fox. Oh dear. You know, just your standard treatments. Standard. Standard. Pretty, pretty regular. Not to mention the dozens upon dozens of herbal remedies and plant extracts, which could be applied as tinctures, consumed in a cocktail, inhaled, so many ways to administer. Even though there's this huge variety in the types of treatments, like from roasted fox lungs to enumas, their purpose was largely the same thing, to restore balance in the body. At the time in ancient Greece, the humeral theory of disease predominated. And I know I've mentioned this in so many episodes, but in case this is someone's first time tuning in, first welcome, second, the humoral theory of disease was essentially this idea that there are four

bodily humors and an imbalance in one of those humors like too much or not enough is what led to disease. Treatment then was focused on restoring that balance. In the case of asthma, an excess of phlegm was to blame, specifically as the phlegm moved from the brain to the chest. I feel like excess of phlegm is a lot of diseases. Oh yeah. Mm-hmm. Mm-hmm. I mean, when you only have four, humor. Right. You could do the math on how many. Is it like four times, three times, two times one? I'm not sure how you do that math. That's my Aaron math. I don't know. I really like it. But for asthma, like why was there more phlegm? That's a reasonable question. It has a thousand different answers, right? Maybe it's because you lived in a dry climate or maybe it was a certain season or maybe you had a certain

personality that just led you to have more phlegm. Maybe you were a certain age. Really, it could be anything. And this flemy explanation for asthma hung around for about a thousand years in one shape or another and continued to influence how European physicians viewed the disease through the 1700s. But of course it wasn't just flamens. But of course it wasn't just flam. equals asthma, asthma was recognized to be incredibly varied in its presentation and severity, with most cases thought to be mild, but others recognized as severe and even life-threatening. And here we come to our first ancient firsthand account. So the ancient Roman philosopher Seneca had asthma, and he described his disease in around

the first century CE. Quote, its onslaught is a very brief duration. Like a squall, it is generally over within the hour. One could hardly, after all, expect anyone to keep on drawing his last breath for long, could one? I have suffered every kind of unpleasant or dangerous physical complaint, but none is worse than this. Not surprising, for anything else is just an illness, while this is gasping out your life breath. That is why doctors call it a, quote, rehearsal for death, since eventually the breath does what it has often been trying to do, end quote. Whoa. Right?

That sounds awful. I mean, yeah. Yeah. And that tracks. It tracks, right? Like, you could imagine someone describing that today. Yeah. I have seen that.

Yeah. Yeah. But yeah, I mean, yeah, first century C.E. I could probably spend the rest of the history section, actually, in the first century C.E. Not really, but like at least in ancient times, talking about how asthma was perceived and written about in the ancient and medieval world. But I should probably move on to when we started suspecting that it wasn't just about the phlegm coming from your brain. I only mentioned a few specific writings or scholars. But the ancient world gave us truly an abundance of descriptions of asthma in its varying forms, the range of symptoms, prognosis, patterns in development, treatments, even the first connection with hay fever by Al-Razi, medieval physician from Iran. But what I think stands out the most about asthma in the ancient world is how consistent these writings were across the globe.

it came down to balance at its core. Asthma was thought to be caused by an imbalance and treatment focused on restoring that balance largely through herbal remedies or lifestyle changes like diet, exercise, and reducing stress. But I feel like it's not often that we see such agreement across the ancient world. So I thought that was interesting.

So this idea about humoral balance in asthma persisted through much of the Renaissance, but it's also around this time that we start seeing people recognizing that that might not be all there is to it. One of these people, Juan Baptista Van Helmut, in the late 1500s, early 1600s, who had asthma,

rejected the Hippocratic idea that asthma was caused by phlegm descending from the brain to the lungs. He was like, no, it's definitely not a nervous condition from my brain. I can feel it, my lungs, specifically in the contraction of them. And in any case, if Hippocrates was right, then there would be better treatments by now. And Van Helmont would be proven right, and Hippocrates wrong, not too long after, with anatomical demonstrations showing that phlegm from the brain to

the lungs did not seem to be at the root of this disease. And I think it's pretty cool that Van Helmont used his personal experience to question the dogma of the time. But he wasn't right about everything. He believed that asthma could be sorted into types, one that affected women and one that affected everyone with guess where the women-only asthma came from? Oh dear. Quote, foul or stinking vapors ascending from the womb to block the pores in the lungs. I'm sorry. I just had to throw that in. It was too good to pass up. I, oh God. It's great. It's good stuff. Fowl or stinking vapors. Fowl or stinking vapors. By the end of the Renaissance, the concept of asthma had undergone a pretty big shift from this phlegmy nervous disease to one primarily of the lungs. And this would continue to be

refined as anatomical dissections increased in the 1700s and 1800s. But before I move on, let me hit you with another first-hand account. Let's do it. This one from physician Thomas Willis, as in the circle of Willis. Oh, wow. That's exciting. So this is from the 17th century. Quote, among the diseases whereby the region of the breast is want to be infested, if you regard their tyranny and cruelty, an asthma doth not deserve the last place. For there is scarce anything more sharp and terrible than the fits hereof. The organs of breathing and the precordia themselves, which are the foundation and pillars of life, are shaken by this disease, as by an earthquake. For breathing, whereby we chiefly live,

is very much hindered by the assault of this disease and is in danger or runs the risk of being quite taken away. Wow. Yeah. Okay. As we move into the 1700s and 1800s, physicians were making small adjustments to their understanding of the pathophysiology of asthma, to the borders around the definition of the disease, distinguishing it from things like bronchitis, recognizing the wide variety of symptoms and presentations, and leading many to wonder whether these all truly fit under one disease name. I guess we're still wondering that. But the thing is, kind of like in the way that you were talking about how our increased understanding of the different mechanisms that underlie different types of asthma hasn't yet translated into treatments. This similarly, like all of this information, all of this knowledge that we had gained by the 1800s about asthma, it didn't lead to any improvements in.

like any sort of relief for people who had asthma. Yeah. And if anything, quality of life was actually at risk of getting worse for people with asthma who lived in cities or worked in factories as the Industrial Revolution was underway. Mm-hmm. Which isn't to say that people didn't try to alleviate their symptoms. During this time, if you went to 10 different doctors, you could get handed 100 different prescriptions, all promising complete symptomatic relief.

none actually delivering on that promise, even if they appeared to do so because asthma is so idiosyncratic like you talked about. Yep. So it's not, I mean, it's really not that surprising. Like I think some of these doctors were probably just looking to make a quick buck. I'd be being like, oh, yes, this is how you do it or people who made patent medicines. But I think other people were like, maybe one time you prescribed like, oh, eat the liver of the snake. and then your asthma would go away and then maybe it did

randomly, just not associated with the liver of a snake or any reptile or animal, but just because it went away, but then you believed. But other people were certainly just peddling, not just non-helpful, but potentially harmful, quote-unquote,

cures, such as asthma-specific cigarettes that contained various compounds. Yeah. I know. It's enough to just make your cringe. So this is from an advertisement for Potter's asthma cure. Oh gosh. Quote, you know how exhausting asthma is. You know how prostrated you are by an attack. Year after year you have suffered in this way. The slightest thing brings on the dreaded paroxysms of coughing and the perpetual fear of an attack coming on makes life a misery. Not only,

is the attack painful and prostrating, but the loss of time during your absence from business is another serious item in the account. And that is why you would give anything for a remedy that would afford you prompt and certain relief and freedom from attacks. That is why you ought to know about Potter's asthma cure, because it gives relief, instant relief. Potter's asthma smoking mixture is purely herbal in its composition, and it may be smoked in a pipe either with or without ordinary tobacco. Oh, no. All that has to be done to prevent the paroxysm of asthma is to draw the smoke well into the lungs and bronchial passages, and relief will immediately be obtained. Oh, gosh. Oh, dear. I know. I know. People swore by these. Mixing them with their tobacco and their pipes. Uh-huh.

Okay, so like Potters was one of many. What were in these, right? They're like you could add tobacco or not ad tobacco. So I found a paper that actually did like a chemical analysis of what was in some of these asthma cigarettes. Okay. And they found in the brand that they looked at, which might have been potters, I'm not sure, leaves from detoura stramonium, aka Thorneapple, Jimsonweed, Devil's Trumpet, etc. You know, like toxic stuff. But this paper also found that these compounds may have had a slight broncholidator ability, but like certainly not enough to warrant. Probably it was like it made your lungs inflamed and worse and then it lessened it a bit. I don't know.

Erin, you remember our Belladonna episode. Oh, yeah. Okay. Way back when. So Jimson Weed is related to Belladonna. Right. And has the similar compounds in it, which include musculos, Antagonists, which in fact are bronchodilators.

So it probably did make people feel a little bit better. That's one of the types of medicines that we actually use today, although we tend to use beta agonists more than muscarinic medications for asthma. But yeah, so it probably did help, but also had a whole bunch of other things in it and are not specific to lungs and so would have systemic effects, etc. So not recommended to smoke gyps and weed or anything. Absolutely not. But I could understand why that would make people feel better.

Yeah. Well, and along the same lines, apparently things like opium, which were also prescribed, that could also have worked, you know, to help relieve some of the, as an antispasmodic is what this says. Yeah. And as like a pain reliever, but also it's going to decrease your respiratory rate. So that sounds like a bad combination. Yeah, it, I think, yeah, some of these came with their own suite of problems, right? Even if they did help a little bit.

Yeah. But what's the cost here? Right. They'll make you feel better. Yeah. But inhalation of things in general became super popular from carbolic acid to the aforementioned strimonium. Animas were a longstanding option, something called the milk diet. Mm.

Caffeine. nose cauterization, all kinds of things, none of which provided any long-term relief. The frustration people felt must have been huge, right? Here was this disease on which treatise after treatise had been written, which had been known about for thousands of years, for which hundreds of treatments had been tried out that affected so very many people and yet nothing. Like nothing. Yeah. The famous French novelist Marcel Proust wrote extensively about his asthma which dominated his life. Hmm.

Quote. And ever since that moment, up to today and until I don't know when in the future, I haven't stopped choking and having incessant attacks. And that is why, although you were in my thoughts practically all day long, I haven't written. I haven't had the courage to take up. my pen. Wow. Yeah. He spent a large portion of his life trying as best he could to avoid any environmental pollutants that seemed to trigger his asthma, even lining his bedroom walls with cork to prevent pollen and perfumes from coming in. Wow. Yeah. So at this point, I feel like I've been talking about the history of asthma for about, no, 25, 30 minutes or so. And we've covered about a couple

thousand years and in many ways I feel like we're kind of right at where we started. It's like, yeah, it's hard to breathe sometimes. Right. And the lungs are involved. And there's bronchon constriction or whatever. Like, yep. If you read, like I had in my early draft of notes two descriptions of asthma, one from the first century CE. So, So when like around the time of Seneca, when he wrote that. And another from the early 1800s. So like 1,700 years apart. And they are eerily similar.

Like they're, it's describing the same exact thing. And I don't know why that just strikes me so much because it seems like, okay, we got a pretty good handle on what this looks like. And yes, we made some improvements in terms of like our understanding that it's the long. and not the brain or your personality, although stereotypes persisted still persist to this day. You know, but treatment is limited. Yeah. That's putting it mildly, I think.

But yeah, in all this time, it just, maybe this is harsh of me, but there just doesn't seem to be very much progress made. But finally, now that we're in the late 1800s, fortunately, all that. is about to change. All right. Although slowly. Germ theory offered the idea that perhaps asthma was directly caused by a pathogen, like a pathogenic infection, but that didn't really amount to anything, even though throughout this people did recognize that some cases of asthma could result

from or be exacerbated by respiratory infection. But it was when autoimmunity and allergy began to be studied, especially at the cellular level, that a bit more of the puzzle was put together. Researchers had long recognized that asthma often co-occurred with conditions like hay fever and eczema, but how they were connected was still an open question. Then, in the early 1900s, concepts of anaphylaxis, allergy, and hypo and hypersensitivity were introduced, and physiologist Samuel Meltzer observed that asthma bore a strong resemblance to anaphylaxis. quote the theory is here offered that asthma is an anaphylactic phenomenon that is that

asthmatics are individuals who are sensitized to a specific substance and the attack of asthma sets in whenever they are intoxicated by that substance we know now that that's not the complete picture right of course we're you know still working on our our knowledge and asthma throughout the 20th century would undergo many paradigm shifts and how it was understood or in the different like models of asthma as a disease. But this was a big step forward in finally putting together like a cellular framework almost for what was going on. Like a mechanistic connection. Yeah, exactly. This new understanding of asthma didn't immediately translate into improvements in patient experience. Those would come about pretty shortly.

though, but almost immediately it did leave to improvements in managing the condition in the form of the first vacuum cleaner, which was invented and patented in 1908 by James Murray Spangler, a janitor from the U.S. who also happened to have asthma. What? Yeah. So he developed the vacuum to try to reduce his exposure to dust at work, which had long been thought to contribute to asthma irritations even before the link to allergy. was made.

Huh. Yeah. That's so cool. But the first treatment that showed real promise for asthma came in the form of allergy shots. By the early 1900s, many researchers had considered and discarded the idea that pollen or bacterial toxins directly caused asthma. But they started to wonder whether the same principles used in preventing infectious diseases could work on allergic disorders.

anti-serum didn't really seem to work, but what about vaccines? In 1911, researchers John Freeman and Leonard Noon at a London inoculation department published their findings from a study where they vaccinated volunteers who had hay fever with increasing doses of pollen. And their findings were amazing, so amazing that they encouraged researchers to try desensitization, as it's called, on acts. using various preparations like animal danders, dust, bacterial vaccines, etc. Desensitization grew to be extremely popular into and beyond World War II, and it seems to me like this gave hope to so many researchers. Greatly increasing interest in asthma and leading to the formation of groups like the Asma Research Council, which brought together clinicians, scientists, philanthropists, and

people who had asthma. The work of these organizations not only broke new ground in asthma research or improvements in treatment, but also in bringing that treatment and other resources to people with asthma. Then in the mid-20th century, the development of steroids for use in inhalers revolutionized long-term management for asthma. And epidemiological studies and new lung function or cellular test to assess asthma revealed patterns in who was most likely to develop the disease, the role of family history, which environmental triggers could cause the most problems, and so on. There was an incredible amount of progress made in like the first 50 years of the 20th century. It's amazing. And we have made more since then. But I do think that one key thing was left behind,

or at least that's the sense that I got in doing the research for this. And that's the personal experiences of people with asthma, which up until then had been a key feature in writings about the disease. Like even as medicine was becoming depersonalized in the late 19th century and it became more about the measurement and more about statistics, asthma was still viewed largely as a very individual disease. This person's asthma is exacerbated by this. This person developed it at this age. this person, their asthma is more severe. You know, it was incredibly varied. And I think that recognition in that variation was really important, even if it didn't translate

necessarily into treatment. I don't know. But I think that it's interesting because you can ask the question like, what is asthma for you? What is happening during your asthma attack? How did this treatment? provide relief. And you could answer those questions by saying how it actually felt for you.

Like what is, how does asthma change your day-to-day life? Does it? Does it not? What is happening during an exacerbation for you? What does that feel like? How does this treatment work compared to this treatment? Or you could answer all those questions by describing the cellular mechanisms, the pathophysiological response.

And that second way was becoming, had been, become much more the norm in the 20th century. And of course, asthma is not unique in this, but I do think that shift is really striking. And I think that's especially so because it was happening around the same time that cases seem to be on the rise. So it's hard to say how the prevalence of asthma changed over the course of history, considering that diagnostic criteria have been extensively revised. And statistics didn't really exist until fairly. recently, but it seems pretty clear that cases of this disease have increased throughout the 20th century. Is this increase real? It's the first question. I mean, it could be in part

inflated due to changes in how asthma is diagnosed and being able to reach more people to make more diagnoses, but that doesn't explain all of it. Like, there's a real increase. What's driving it then? Mm-hmm. Worsening air quality or increasing exposure to pollutants, possibly. Those had long been linked to asthma development or exacerbation. An increase in dust mites from more carpeting? Sure, that seems reasonable. Yeah.

More pollen from changing agricultural practices? Sure. Why not? Something else? Probably. The bottom line. is that many, many things are likely contributing to the rise in asthma cases. And also that the drivers are probably not the same across the entire globe.

As always, it's complicated. But there is one idea that people have gotten really excited about as an explanation for this rise. And that is the hygiene hypothesis. We couldn't not. We couldn't not. The hygiene hypothesis is this idea introduced in the 1970s and refined in the 1980s that says that by growing up in a more sanitized environment with less dust and dirt and dander and lower exposure to pathogens overall than in past millennia. This is also more specific to people living in industrialized countries, that our immune systems aren't getting the proper training that they used to. and end up being overactive or improperly sensitized.

This has been used to explain the apparent rise in allergic diseases and autoimmune disorders. The hygiene hypothesis isn't the first to claim that our modern lives may have come at the cost of increasing certain diseases. Since the 18th and 19th centuries, at least asthma has been thought of as a quote-unquote disease of civilization. Huh. In the late 1700s, physician Thomas Withers wrote about what he perceived as a rise in the prevalence of asthma. Quote, the greater irritability and weakness of the Constitution in these days may, in some measure, account for the greater frequency of the asthma, especially if we add the inventive genius and the rapid progress of mankind in all the various arts of modern luxury and refinement. So that's like the prequel hygiene hypothesis.

Yeah, it really is. His advice was essentially to toughen up or, quote, unquote, cast off the effeminacy of the present times, abandoned the destructive luxury of heat. I, I. Oh, my goodness. Yeah. And he wasn't the only one. A few decades later, physician Henry Hyde Salter, who also happened to have asthma, wrote that, quote, the rich might be really more liable to asthma. than the poor from a more irritable nervous organization engendered by the state of hyper-civilization

in which we live." Hyper-civilization. Yeah. Okay. Anyway, so the hygiene hypothesis, it's different. It's a bit more mechanistic. It's a bit based more in biology than just a general sense of feeling. But I do think that the parallels are kind of funny there.

The hygiene hypothesis is a really interesting and exciting. idea. But is there any evidence that asthma is caused by a lack of exposures to antigens in early childhood? It's hard to say. So I dug a little bit into the literature, mostly looking at refuse and like retrospective. Is the hygiene hypothesis still an appropriate, you know, model for asthma or whatever? And it's mixed, right? There are studies showing that kids who were exposed to farms or raised near farms had lower rates of asthma than those who were not, for example. But at the same time, rates of asthma are increasing in children who live in conditions of poverty in North American cities. Long-term exposure to things like cockroaches and dust mites is associated

with the development of asthma. So cleaner should be better, but it's also not better. Like maybe it depends on the specific antigen or the timing of exposure or all of that could change depending on season or geography or individual genetics, there is no consistency with the hygiene hypothesis. And there's a lot of contradictory evidence. Don't get me wrong. Like I think this is a really fascinating framework to think about early immune system development and how that sets our immune system on a certain course for the rest of our lives.

But at this point, it seems that the studies that investigate its role in asthma are not very consistent. Yeah. I think, too, there's also been maybe like a combining or a shifting of this idea of just allergen, exposure with also microbiome exposure, which kind of, yeah, I know. It was the whole thing was reminding me of like, I mean, and it is entangled with microbiome, but I was just like, these sound so cool conceptually, but we're not, like, maybe we just don't have the studies yet to show specifically enough.

Yeah. Which isn't to say that like, this. there aren't specific instances that could be, oh, if you had been exposed to a dog, you know, if you touched the dog when you were 15 days old or something. Yeah, instead of a cockroach. Like, how does it all fit together? I think we're a long way from knowing the answer to that. I think it's, I think how it fits together, though, is is what's the interesting part about it.

Because I think from the diversity of data that we have, it's very clearly not one thing. Right. Right. It's never going to be one exposure or lack of one exposure. And we don't understand necessarily what all of those exposures are, which I think is why it's so interesting. Like even with pets, it's like dogs, you know, reduce the risk of asthma more than cats. But like cockroaches increase it. And this and that. So it's, I mean, it's just it's. Yeah. There's a lot and it's interesting. But I agree. We don't have the data to say that this is true versus not true or anything. like that. This is not the answer. And I don't think that most of the people who study the hygiene hypothesis believe that it is the answer. I think that they're using it in the way that they should, which is like, hey, this is a really interesting framework. Yeah. To test. To test. To investigate. Exactly. Yeah. Yeah. That's the point of a hypothesis. It is. But yeah. I mean, I think, that it does hold a lot of promise and I think that's probably where at least one area of research

for asthma is probably pretty active. Speaking of which, Erin, where do we stand with asthma today? What's going on? I can't wait to tell you all about it right after this break. We'll start with some possibly quite depressing statistics. All right. One paper that that I read said, estimated that in the UK, a child is admitted to the hospital due to an asthma exacerbation every 20 minutes. What? That was my exact response and what I wrote,

what with three question marks. Oh my gosh. That is so frequent and so many, I was astounded. Worldwide, it's estimated by the Global Asthma Network. and other organizations, that at least 300 million people are living with asthma across the globe. And because asthma is a chronic disease, even if it does go away in adulthood, it's still a chronic disease for kids and for adults.

There are over 20 million disability-adjusted life years attributed to asthma. across all ages globally. So 21 million disability-adjusted life years every year globally. And it's ranked 34th among the leading causes of burden of disease. So that's huge. It's massive. And while asthma is a rare cause of death, thankfully, it is responsible for deaths every year.

The global burden of disease, collaboration estimates that in 2019, almost 500,000 people died from asthma. That's more than 1,000 people a day across the globe. Oh, my gosh. I know. It's way worse than I thought. And like you mentioned, incidents has been increasing globally, though there has been some evidence of potentially plateauing incidents in higher income countries, in some high-income countries.

And it likely is environmental factors that contribute to a lot of these discrepancies and prevalence as well as this increasing incidence and prevalence overall. But like we said, we really don't know what those factors are in detail. If we look at the U.S. specifically, about 25 million people in the U.S. are living with asthma. Over six million of those are kids. That's about 8% of the U.S. population, which is a lot of people. A lot of people. And a really important part of asthma in the U.S. specifically is that it disproportionately affects black kids especially, as well as those living below the federal poverty line in the U.S. So while asthma is a disease that can and does affect anyone, it has a disproportionate effect on vulnerable.

segments of populations, largely because of environmental exposures and systemic inequities that have existed throughout our country's history that have contributed to these disparities. So I think that's a really important part is that there's really no evidence that any of these disparities are genetic-based, they're environmental and structural. Right. The other aspect is that asthma is a chronic condition that's not always easy to manage and sometimes very expensive. And so there's also discrepancies in access to health care for diagnosis and in access to medications as well. Yeah. And I did want to say one thing, Aaron, because you talked a lot about this individualization and I know that I said that treatment is kind of the same. And that is

true in that we use like kind of a handful of medicines for asthma in general. But the individualization of each person's asthma treatment is still a thing. And it's actually called an asthma action plan. So access to someone who can help develop an asthma action plan is actually really, really important and is associated with much better outcomes, reduced exacerbations, reduced hospitalizations, et cetera. So that all contributes to these huge disparities that we see, especially in the U.S. Right. Across the globe as well. So obviously there's a lot of lot of work to be done when it comes to asthma, not only to better understand maybe the genetics that underpin it, the environmental risk factors, differentiating these different endotypes or

phenotypes or whatever, all of the different types of asthma, it wouldn't be surprising to me if this does end up leading to either splitting of this diagnosis or at least specifying these diagnoses, right, where you have really more specific definitions of asthma and therefore different and more individualized treatments beyond just how do you use your inhaler for your specific action plan. But along those lines and with regards to treatment and the future of treatment, I wanted to mention something. Shout out to my friend and colleague Kat who brought this article to my attention. That is really important part of how we decide on medications and we as like a whole medical community decides on

medications for chronic, often lifelong diseases. The recent guidelines that came out of Gina, the global initiative for asthma, these are kind of like big time global guidelines that a lot of different countries use. And these treatment guidelines very strongly endorsed using a combination of inhaled steroids, like I mentioned, and a short-acting bronchodilator. But they specifically endorse this combination of one type of bronchodilator and one type of inhaled corticosteroid, which happens to be found in combination in a drug called Symbicort in the U.S., which is made by a company called AstraZeneca, which happened to have $2.5 billion in sales of this drug in 2021.

And 12 of the 17 members of the GINA board have received payments from this company, AstraZeneca. That doesn't seem like it should be okay. Now, the GINA guidelines more strongly recommend this drug, this combination, than a couple of other guidelines that have less fewer board members that have received payments from AstraZeneca. But what I'm saying is not necessarily that people are being corrupted by these payments. The problem here is that if you look at a Cochrane review from 2021, four of the five studies that were included in this study, which in fact showed that using this combination of inhaled corticosteroids and a bronchodilator had better outcomes than using short-examined. contracting bronchidilators alone.

The data is pretty clear from these studies that that leads to better outcomes. But four of five studies that were included in this Cochrane review were funded by AstraZeneca. I mean... So it's not necessarily inherently bad that the pharmaceutical industry is financing these studies. These studies are important. they're integral to be able to develop better treatments and to know, is this treatment going to be better than what we have currently? The problem is not only these conflicts of interest in that these studies were funded by these companies, the guidelines are being written by people who are

getting money from these companies based on the studies that were funded by these companies. But it's also that we don't have any other studies of similar medications to actually compare to, right? There are a lot of other combinations of these two types of drugs that exist. But right now we only have data that says this particular one that we have studied because we paid for it, because we made it, is the best. So that's the one that we should use. You know, and also considering that it's a chronic use medication. Exactly. Exactly.

This is something people are going to be buying every month. for their whole childhood or their whole life. And again, I'm not saying that there's not data that this medication absolutely reduces exacerbations, reduces hospitalizations, improves outcomes. The problem is that when we only have data on this one specific combination from this one company, how do we then make a decision about how to treat not only everyone who doesn't have access to this one specific medication by this one specific company, but also, also how do we compare that and make sure that we're funding studies that are non-biased to compare that

to all of the other drugs that already exist. Right. Right. And I just wanted to mention that and bring that up because I think it's a really important part of chronic disease especially, right? Like you mentioned, Aaron. This is a disease that people are going to need potentially lifelong treatment for. And so it's especially important that.

the studies that are done are being done in as non-biased away as possible so that our data is as good as possible so that people can have the outcomes that we want without corruption, really. I mean, yeah, I think it's difficult because it's like they're, at every step of the way, there should be a focus or like a check point to be like, is there potentially bias introduced at this step versus this step or how could that bias be introduced? and how do we acknowledge it? Like not saying, you know, it's just like what you said,

these studies should be done. And they are important. And these drugs do work. Right. But I think finding a better way to disallow the monopolization, I guess. I don't know. I think what it comes down to is something we talk about a lot on this podcast. And that is the need for funding, for public health funding and for research funding that's

coming from places that are not trying to make a profit off of that research, right? Yeah. That's what it comes down to. And that's usually governmental funding. So. Which is extremely limited. Yeah. So that's our best.

Let's make a case yet again. Funding, funding, funding. Yep. But just, I think, an interesting part and an important part of how we conduct research, not just the research that needs to be done, but how it's, needs to be done going forward. And that is asthma. Was that fun?

It was something. Sources. I have a bunch, but I'm only going to shout out right now, a book that I read by Mark Jackson called Asma the Biography. Oh, love that. I mentioned already one of my favorite papers for deep, deep, nitty, eager-dy-dive on asthma pathophysiology, and that is the paper from 2020 by Gans and Gavri-Leva. I also have several other papers on the pathophysiology, and I will, of course, link to those

2022 Gina guidelines that I mentioned, as well as the AFP article that brought to attention the potential conflicts of interest in those guidelines. But we'll post all of our sources from this episode and all of our episodes. on our website. This Podcast Will Kill You.com under the episodes tab. A big thank you again to Lindsay for providing your first-hand account. We appreciate it so very much.

So much. Thank you to Bloodmobile for providing the music for this episode and all of our episodes. And thank you to Leanna Skulachi for our amazing audio mixing. We love it. Thank you to Exactly Right Network. And thank you to you, listeners.

this was a long one. Thanks for hanging in there with us, and we hope you learned something. Yeah, I hope so. And a special shout out, as always, to our patrons. Thank you so much. Your support means the world to us. It really does.

Thank you, thank you. Okay, well, until next time, wash your hands. You filthy animals. Welcome to Dirty Rush, the truth about sorority life. Good, the bad, and the sisterhood. With your host, me, Gia Judice, Daisy Kent, and Jennifer Fessler. The reality of Greek life has been a mystery

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Then she says, have you seen a photo of my son? And I'm like, who is this person? Welcome to the Boys and Girls podcast. Arranged Marriage is basically a reality show and you're auditioning for your soulmate. And who's judging? Only your entire family?

I sacrificed myself to this ancient tradition hoping to find love the right way. And instead, I found chaos, comedy and a lot of cringe. Listen to Boys and Girls on the IHeart Radio app, Apple Podcasts, or wherever you get your podcast. This season on Dear Chelsea with me, Chelsea Ham. We've got some incredible guests like Kumail Nanjiani. Let's start with your cat.

How is she? She is not with us. She. Great, great, great way to start. Maybe you will cry. Ross Matthews. You know what kids always say to me? Are you a boy or girl?

Oh my God. All the time. That's so funny. I know. So I try to butcher it up for kids so they're not confused. Yeah, but you're butching it up is basically like Doris Day. Right. No, I turn into Be Arthur.

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