Ep 122 Asthma: A phlegmy episode

really bad exacerbation. Beforehand, it was just like I could maybe have won maybe two exacerbations, if any, in a year. So I got an oral steroids in March of twenty twenty and I 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.

but then I would have an exacerbation. So that was frustrating, and that happened throughout the spring and summer of twenty twenty. 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.

was the sudden nocturnal dismea. 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 pul sac siminar. The lowest that I ever saw my pulsacks go with seventy four percent. That was, Yeah, 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 action levels up. I got into a pretty sticky situation and as the exacerbation that landed me in the er in October of twenty twenty, 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 do 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, and 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 anaphyalactic reaction to before.

My palminologists at the time didn't say it was anaphylaxis, but anaphylactoid and anaphylactoid 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 storids after that, and then I delivered in June of twenty twenty one, 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 palminologists and I was immediately allergy tested and then started on the first biologic that they usually go to, called Dupixend.

Dupixend 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 predna zone, but not all the way. So in February of twenty twenty two, I started on a medicine called Ficenra and that was wonderful.

weaned off of it. So we're going to try a new medication called Nkala, which is supposed to control signus polyps as well, So we'll see how that goes.

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 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 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 their 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.

chest tightness, et cetera. Right, m 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 used 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 barebones. 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, aerin 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 this chronic, low level inflammation that's happening all the time, and then there are these acute or discrete worsenings 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.

physiologic response. What's happening in asthma is a hyper reactivity 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.

they're classified in different ways. So in a clinical setting like your doctor's office or whatever you might in here, 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 urgiety, 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 coincides with things like you know, allergies, food allergies, environmental allergies, exzema. Non allergic asthma, so not associated with

allergies or allergic responses. There's like cough predominant asthma. There's eosynophilic asthma. There's extra size 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 by and Treatments for Asthma Endotypes from twenty twenty, 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.

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 they're maybe their triggers are something different, and so then the management is different.

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.

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 as or is this something potentially preventable? And I'm sure it will be no surprise to you, AARIN or to listeners that we don't know the answer to that question. Asthma is a multi factorial 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 factor 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 thirty five and eighty percent depending on which study you read. And in terms of environmental factors, there are so many it's.

can affect the development of asthma. And that's the 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's inhalers that mostly serve to broncho dilate, 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 broncho dilators, 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. Used to be a probably over reliance on bronchodilators, and now more and more it's inhaled steroids plus or minus

these bronchodilators. 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 band aid. 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.

our airways are also a lot 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.

pulmonary disease. So that's more like adults are more likely to undergo that whole function 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 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.

I will point all listeners who want to know to and we'll link to the Global Initiative on Asthma or GENA 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 our 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.

sense because other animal species can also have asthma. Like, my gosh, get asthma.

that's not that surprising. It started out as a disease of humors, then of lungs, then of personality, then of allergy, than as inflammation, and many other forms along the way, sort of crisscrossing each other and happening simultaneously and borrowing parts of each other.

century with the depersonalization of medicine as per usual. Basically, this is my way of preparing you for the sizeable 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 a lot, but I honestly probably could have given how many there are which I think is really interesting and unusual.

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 asma, like it's impossible.

breath as Mahdi 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 fifth century BCE 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, and in this recognition, ancient Greek physicians were

a bit behind the times. The Ebers Papyrus from around fifteen fifty 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 your skin.

also mentioned in some ancient texts. But anyway, asma 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 blood letting, your enemas, your plasters to ease the chest, your diuretics, your emetic 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, and hailed so many ways to administer.

Even though there's this huge variety in the types of treatments, like from roasted fox lungs to enemas, their purpose was largely the same thing, to restore balance in the body. At the time. In ancient Greece, the humoral 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 a 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 FLEM was to blame, specifically as the phlem moved from the brain to the chest.

And this flemy explanation for asthma hung around for about one thousand years in one shape or another, and continued to influence how European physicians viewed the disease through the seventeen hundreds. But of course it wasn't just phlem 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 first hand account. Ooh, so the ancient Roman philosopher Seneca had asthma and he described his disease in around the first century CE. Quote. It's 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.

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, and development treatments, even the first connection with hay fever by al Razzi, 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 like I feel like it's not often that we see such agreement across right the ancient worlds. 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 Helmont, in the late fifteen hundred's early sixteen hundreds 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 in 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 and the lungs. I'm sorry, I just had to throw that in. It was too good to pass up.

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.

disease name, because 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 eighteen hundreds about asthma, it didn't lead to any improvements in any sort of relief for people who had asthma, 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, which isn't to say that people didn't try to alleviate their symptoms during this time.

If you went to ten different doctors, you could get handed one hundred 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. I think some of these doctors were probably just looking to make a quick buck, 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 dread 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.

Devil's trumpet, et cetera. You know, like toxic stuff. But this paper also found that these compounds may have had a slight broncho dilator ability, but like certainly not enough to warrant. Probably it was like it major lungs inflamed and worse, and then it lessened it a bit.

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, et cetera. So not recommended to soak gimson weed or anything not. But I could understand why that would make people feel better.

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.

and there's fronco 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 when like around the time of Seneca when he wrote that, and another from the early eighteen hundreds, so like seventeen hundred years apart, and they are eerily similar, like 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 lungs 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 harsher to me, but there just doesn't seem to be very much progress made.

But finally, now that we're in the late eighteen hundreds, fortunately all that is about to change.

put together. Researchers had long recognized that asthma often co occurred with conditions like hay fever and egzema, but how they were connected was still an open question. Then, in the early nineteen hundreds, 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. Of course, We're still working on our knowledge, and asthma throughout the twentieth 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.

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.

but what about vaccines. In nineteen eleven, 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 asthma, using various preparations like animal danders, dust, bacterial vaccines, et cetera. Desensitization grew to

be extremely popular into and beyond World War Two. Oh 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 Asthma 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 twentieth century, the development of steroids for use in Inhaler's revolutionized long term management for asthma, and epidemiological studies and new lung function or cellular tests 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 the first fifty years of the twentieth century. It's 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 nineteenth 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 had their asthma is more severe.

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 path of physiological response, and that second way was becoming had become much more the norm in the twentieth 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 diagnoster 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 twentieth century. Is this increase real, It's a

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, 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 a hygiene hypothesis.

end up being overactive or improperly sensitized. This has been used to explain the apparent rise in allergic diseases and autoimmune disorders. The hygien hypothesis isn't the first to claim that our modern lives may have come at the cost of increasing certain diseases. Since the eighteenth and nineteenth centuries at least, asthma has been thought of as a quote unquote disease of civilization. In the late seventeen hundreds, 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.

sense of feeling. But I do think that the parallels are kind of funny there. The hygiene hypocthesis 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 hygien hypothesis still an appropriate

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.

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.

instead of a cockroach. Like, how does it all fit together? I think we're a long way from I am knowing the answer to that.

more than cats, but like cockroaches increase it. And this in that sense, 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.

I was astounded. Worldwide, it's estimated by the Global Asthma Network and other organizations that at least three hundred 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 twenty million disability adjusted

life years attributed to asthma across all ages. Globeobally, So twenty one million disability adjusted life years every year globally, and it's ranked thirty fourth 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 twenty nineteen, almost five hundred thousand

people died from asthma. That's more than a thousand people a day across the globe. Oh my gosh, I know it's it's way worse than I thought. And like you mentioned, incidence 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 in 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 US specifically, about twenty five million people in the US are living

with asthma. Over six million of those are kids. That's about eight percent of the US population, which is a lot of people, a lot of people. And a really important part of asthma in the US specifically is that it disproportionately affects black kids, especially as well as those

living below the federal poverty line in the US. 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 their 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 healthcare for diagnosis and in

access to medications as well. Yeah, and I did want to say one thing erin 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 US, right

across the globe as well. So obviously there's a 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 in visualized 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 a 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 endorse using a combination of inhaled steroids like I mentioned and a short acting broncho dilator, but they specifically endorse this combination of one type of bronchodilator and one type of inhaled cortico steroid, which happens to be found in combination in a drug called Symbacourt in the US, which is made by a company called Astrosenica, which happened to have two point five billion dollars in sales of

this drug in twenty twenty one, and twelve of the seventeen members of the GINA board have received payments from this company.

corrupted by these payments. The problem here is that if you look at a Cochrane review from twenty twenty one, 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 acting bronchodilators 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.

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 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 an as non biased a way as possible so that our data is as good as possible so that people can have the outcomes that we want with out corruption.

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 think what.

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 dot Com under the episodes tab A.