Speaker 1: Hi.
Speaker 2: My name is Lindsay and I wasn't officially diagnosed with
Speaker 2: asthma until I was a teenager. But I do remember
Speaker 2: when I was a kid having exercise induced asthma, but
Speaker 2: just not knowing how to describe it. My asthma was
Speaker 2: very well managed with just your standard preventative and albuterel
Speaker 2: until my early thirties. Something changed, not sure what it was,
Speaker 2: and then March of twenty twenty, I had my first
Speaker 2: really bad exacerbation. Beforehand, it was just like I could
Speaker 2: maybe have won maybe two exacerbations, if any, in a year.
Speaker 2: So I got an oral steroids in March of twenty
Speaker 2: twenty and I cleared up pretty fast usually that's how
Speaker 2: it happens with asthma exacerbations. And I finished the course
Speaker 2: of steroids, and then about a week later I started
Speaker 2: having asthma symptoms again, and again I had to go
Speaker 2: back to my doctor and get back on steroids.
Speaker 1: And this happened pretty much every six weeks.
Speaker 2: I would get on steroids and then finish my course
Speaker 2: of steroids, and then gradually the symptoms would return. And
Speaker 2: then with my first pominologists that I had, we were
Speaker 2: kind of in a struggle between testing my blood levels
Speaker 2: for the EOSINFL levels that they thought would be the problem,
Speaker 2: and excess of usnfl's kind of aggravating things. But unfortunately,
Speaker 2: I wasn't able to stay off of steroids for long
Speaker 2: enough for them to get an accurate USINFYL count. So
Speaker 2: it was kind of this, let's get off of steroids,
Speaker 2: but then I would have an exacerbation. So that was frustrating,
Speaker 2: and that happened throughout the spring and summer of twenty twenty.
Speaker 2: I'm a paramedic, so it was extremely difficult at work.
Speaker 2: Even when I wasn't having a full blown exacerbation, I
Speaker 2: was having to wear masks and feeling very short of
Speaker 2: breath with my patients, and I got very tired of
Speaker 2: explaining that no, I don't have COVID, my lungs are
Speaker 2: just trying to kill me.
Speaker 1: So the exacerbations.
Speaker 2: Were in tech. It would start off as shortness of breath.
Speaker 2: I would get very short of breath for a few
Speaker 2: days just with regular exertion. I would get winded climbing
Speaker 2: a fight of stairs, I would get winded getting dressed,
Speaker 2: and then eventually they would degrade until I was having
Speaker 2: to take albuter all treatments regular albauter of all treatments
Speaker 2: every two hours maybe, and then eventually we switched to
Speaker 2: DUOEB and even the duo EB was only effective for
Speaker 2: about four hours at a time. The worst, by far
Speaker 2: was the sudden nocturnal dismea. I would be asleep and
Speaker 2: then I would find myself awake, and then it would
Speaker 2: be like it would feel like a train would just
Speaker 2: hit me in the chest and I couldn't breathe, and
Speaker 2: I would be scrambling to find my nebulizer and set
Speaker 2: that up before I passed out. Basically, I did have
Speaker 2: a little at home pul sac siminar. The lowest that
Speaker 2: I ever saw my pulsacks go with seventy four percent.
Speaker 2: That was, Yeah, that was scary, especially because I'm a
Speaker 2: medical professional and I know what that means. And like
Speaker 2: my head was swimming and pounding and I'm just trying
Speaker 2: to work through that work of breathing to bring my
Speaker 2: action levels up. I got into a pretty sticky situation
Speaker 2: and as the exacerbation that landed me in the er
Speaker 2: in October of twenty twenty, and in that er setting,
Speaker 2: I actually found out that I was pregnant. That was
Speaker 2: pretty scary. Things got pretty complicated because the normal course
Speaker 2: of action at this point would just do be on
Speaker 2: a low daily dose of steroids until we could figure
Speaker 2: out what was going on and find a better treatment. However,
Speaker 2: the implications of taking long term steroids while pregnant were
Speaker 2: not great. There was a lot of complications that could
Speaker 2: go along with that. Luckily, moving into the winter season,
Speaker 2: my asthma is pretty mild, so I was able to
Speaker 2: just kind of fuddle through take very short bursts of
Speaker 2: steroids if I needed it, and that got me pretty
Speaker 2: much through all the way to the spring right before
Speaker 2: I delivered, where I inadvertently had an anaphylactic reaction to
Speaker 2: something that I've never had an anaphyalactic reaction to before.
Speaker 2: My palminologists at the time didn't say it was anaphylaxis,
Speaker 2: but anaphylactoid and anaphylactoid reaction, I guess, so I don't
Speaker 2: really know what the difference is, but either way, it
Speaker 2: was very scary. So I ended up going on a
Speaker 2: short burst of storids after that, and then I delivered
Speaker 2: in June of twenty twenty one, a very healthy baby girl,
Speaker 2: and I had another exacerbation immediately after I delivered, which
Speaker 2: was rough. At this point, I was working with one
Speaker 2: palminologist who had mentioned biologics before, but was nervous about
Speaker 2: starting biologics to kind of change my immune system while
Speaker 2: we were in the middle of a pandemic. I suffered
Speaker 2: through about one more exacerbation with that palminologist, and then
Speaker 2: I decided to get a second opinion. So I switched
Speaker 2: palminologists and I was immediately allergy tested and then started
Speaker 2: on the first biologic that they usually go to, called Dupixend.
Speaker 2: Dupixend helped a bit. It's a monthly injection. It's a
Speaker 2: monoclonal antibody that helped manage some of my symptoms to
Speaker 2: the point where I was able to wean down from
Speaker 2: the predna zone, but not all the way. So in
Speaker 2: February of twenty twenty two, I started on a medicine
Speaker 2: called Ficenra and that was wonderful.
Speaker 1: That was an immediate difference.
Speaker 2: I was able to wean off all of my predmo
Speaker 2: zone just kind of stick to my regular albuterol and
Speaker 2: my preventatives, and it's been great. I've been able to
Speaker 2: get back to exercising. I don't feel like I'm suffocating
Speaker 2: having to wear a mask at work anymore. So yeah,
Speaker 2: it's been definitely a journey. Now we are working on
Speaker 2: a kind of like a third biologic option because the
Speaker 2: fsenra was supposed to be able to be weaned off
Speaker 2: of it, but I've not successfully been able to be
Speaker 2: weaned off of it. So we're going to try a
Speaker 2: new medication called Nkala, which is supposed to control signus
Speaker 2: polyps as well, So we'll see how that goes.
Speaker 3: And yeah, that's it.
Speaker 1: That's been my journey with asthma.
Speaker 4: Oh my gosh, that sounds so scary.
Speaker 3: I just.
Speaker 5: I know, goodness, thank you so much for sharing your
Speaker 5: story with us. I can't and imagine reliving that is easy.
Speaker 4: Yeah, and just how like what a confusing time and
Speaker 4: how like difficult and like long this process can be sometimes. Yeah, yeah, yeah,
Speaker 4: thank you.
Speaker 1: Hi.
Speaker 3: I'm Aaron Welsh and I'm Aaron almant Updike.
Speaker 4: And this is this podcast will Kill You. And today
Speaker 4: we're talking about asthma. Yeah. I know we say this
Speaker 4: a lot, but big topic is asthma. Even like I
Speaker 4: think it was near the end of my research when
Speaker 4: I came across a phrase that was in some two
Speaker 4: thousand and six journal article in The Lancet that was like,
Speaker 4: has asthma as a term outlived its usefulness, right, like like,
Speaker 4: right is it? I guess we'll find out.
Speaker 5: We'll find out.
Speaker 3: I guess.
Speaker 5: Yeah.
Speaker 4: It is a very big topic. There's a lot of
Speaker 4: it just feels very amorphous. So I'm curious to see
Speaker 4: how it all goes.
Speaker 5: I have a feeling at the end of this episode
Speaker 5: it's going to still feel amorphous. But hopefully we can
Speaker 5: like put some boxes around it. Maybe I don't know. Yeah,
Speaker 5: I think so, we'll try.
Speaker 4: Okay, but first things first, it's quarantiney time. It is
Speaker 4: what are we drinking this week?
Speaker 5: Well, nothing other than the inhaler. It works well on paper,
Speaker 5: it does. Just go to our social media, you'll see
Speaker 5: it written.
Speaker 4: Uh huh uh huh you basically with the ale emphasize.
Speaker 5: It's the inhale Wait, the inn ale er that's yeah,
Speaker 5: really rolls off. The tongue.
Speaker 4: Does not translate well to audio. That's okay, though, that
Speaker 4: is okay.
Speaker 3: What's in the inhaler erin it is based.
Speaker 4: On a new drink new to me that my friend
Speaker 4: actually told me about, called the spaghette. I don't know
Speaker 4: it's provenance, but it is delicious. It's basically like a
Speaker 4: cheap logger and you get a bottle, you drink a
Speaker 4: little bit down, and then you pour in some apparol
Speaker 4: and lemon juice and it's kind of like an apparol sprits.
Speaker 5: But with cheap beer.
Speaker 4: And I love it.
Speaker 5: I it sounds delicious and I can't wait to try one.
Speaker 4: And we will post the full recipe for this quarantini
Speaker 4: as well as the non alcoholic polacy rita on our
Speaker 4: website This Podcast will Kill You dot Com, as well
Speaker 4: as on all of our social media channels.
Speaker 5: Our website is this Podcast will Kill You dot Com.
Speaker 5: Have you heard of it? Have you gone to there?
Speaker 5: We have so many things there. Check it out. We've
Speaker 5: got merch, we've got a good Reads list, We've got
Speaker 5: there's so much more. We've got music, pipeline mobile, we've
Speaker 5: got a Patreon.
Speaker 4: You know what.
Speaker 5: Just check it out.
Speaker 4: Check it out right. There's actually a really cute new merch.
Speaker 4: There's like a muscle tea.
Speaker 5: I'm wearing it right now.
Speaker 4: You are? You look great in it?
Speaker 5: Oh?
Speaker 4: Thanks? Okay, enough gathering. Should we get on to the
Speaker 4: actual content of this episode.
Speaker 5: We should let's all take a deep breath and a
Speaker 5: quick break, okay, and get into it. So there are
Speaker 5: various definitions of asthma that exist out there. They're all
Speaker 5: probably slightly different based on which society or expert panel
Speaker 5: or which set of guidelines you're looking at. But for
Speaker 5: this biology section, the way that I decided to structure
Speaker 5: it is just to jump into describing what asthma looks
Speaker 5: like or feels like, what the symptoms are, because that
Speaker 5: will inevitably lead us to the big question of this section,
Speaker 5: and that really is what on earth are these underlying
Speaker 5: causes or mechanisms of what we know of as asthma,
Speaker 5: like what is going on in our bodies if we
Speaker 5: are living with asthma? So let's get into it. I
Speaker 5: think that asthma is a common enough condition that probably
Speaker 5: everyone listening has heard of it and either has asthma
Speaker 5: or knows someone with asthma personally. So when we think
Speaker 5: of asthma, we probably have a picture in our mind
Speaker 5: of what we think of. We might think of someone
Speaker 5: who has these discrete episodes or asthma attacks where they
Speaker 5: might have wheezing. Right, this sound in their airways like
Speaker 5: a squeaking sound when they exhale. They might be really
Speaker 5: short of breath, feel like they just can't catch their breath.
Speaker 5: Maybe we think of someone who is coughing a lot
Speaker 5: and just kind of can't stop coughing during these episodes,
Speaker 5: or complains of a feeling of tightness in their chest,
Speaker 5: like they just can't get enough air in because of
Speaker 5: the feeling of this tightness, and we probably think of
Speaker 5: this person using an inhaler of some kind, like a puff,
Speaker 5: and then being able to breathe a little bit easier.
Speaker 5: Maybe we think of someone who has to use an
Speaker 5: inhaler before they can start soccer practice or run the
Speaker 5: mile in pe because otherwise they get short of breath.
Speaker 5: Or maybe we've actually seen or experienced a very severe
Speaker 5: exacerbation where someone can barely get any air in their
Speaker 5: wheezing so much that you can hear it across the
Speaker 5: room without a stethoscope, and they have to go to
Speaker 5: the emergency room for systemic treatment with steroids and breathing treatments.
Speaker 5: And many of us might think of asthma as a
Speaker 5: childhood condition that people outgrow and then no longer need
Speaker 5: their inhalers. Once they're adults, and those kind of are
Speaker 5: the symptoms of asthma. But as we'll see, not only
Speaker 5: is asthma not only a childhood condition. It's a chronic,
Speaker 5: potentially lifelong condition or one that can arise for the
Speaker 5: first time in adulthood. But it's also a lot of
Speaker 5: different things. So while these episodes all might sound similar,
Speaker 5: there is a lot going on underneath the surface in
Speaker 5: every different person that has asthma.
Speaker 4: So is asthma as a term more like a collection
Speaker 4: of symptoms rather than any like one path of physiological process.
Speaker 5: Pretty much, Yeah, let's get into it, shall we. Yeah,
Speaker 5: because we can talk about some of the path of physiology,
Speaker 5: but as we'll see, yes, there's a lot of different
Speaker 5: sort of pathways that get you to that same endpoint
Speaker 5: where you have have these episodes with wheezing, shortness of breath,
Speaker 5: chest tightness, et cetera. Right, m hmm okay, Yeah, So
Speaker 5: on a very basic level, asthma is a chronic inflammatory
Speaker 5: disorder that's affecting the airways right of our lungs, and
Speaker 5: it essentially results in these episodes in widespread and uneven
Speaker 5: constriction or narrowing of the small and large airways of
Speaker 5: the lungs, and that results in obstruction of airflow, and
Speaker 5: that constriction, that obstruction is usually reversible, either spontaneously like
Speaker 5: with time, or with medications. Those inhalers that you see
Speaker 5: people using or that you've maybe used themselves. That is
Speaker 5: what causes the wheezing sound, right, is this restriction, constriction
Speaker 5: of the airways and air trying to get out through
Speaker 5: a very small opening. It's also what causes the shortness
Speaker 5: of breath. You literally can't move air back and forth
Speaker 5: because of how small these airways are. But that's a
Speaker 5: pretty bare bones description. We don't do barebones. So let's
Speaker 5: drill down as deep as we can on this podcast
Speaker 5: into what's going on in asthma and in these asthma
Speaker 5: attacks or exacerbations. So, like you alluded to, aerin asthma
Speaker 5: is not just one thing. It's not one discrete pathophysiologic
Speaker 5: process that's underpinning these exacerbations or these episodes. And it's
Speaker 5: not just these episodes. All of the different pathophysiologic processes
Speaker 5: that I'll get into at least a little bit of
Speaker 5: detail of first start with an underlying chronic inflammatory state.
Speaker 5: So in all people with asthma, there's an increase in
Speaker 5: inflammation of the airways even in the absence of an
Speaker 5: acute episode. So there's this chronic, low level inflammation that's
Speaker 5: happening all the time, and then there are these acute
Speaker 5: or discrete worsenings of that. That's what we call an
Speaker 5: asthma attack or an exacerbation. These attacks tend to happen
Speaker 5: with some kind of trigger smoke, exercise, allergens like pollen
Speaker 5: or cat dander, very often a cold or a viral infection,
Speaker 5: but it could even be just cold air. Really, it's
Speaker 5: any number of things that cause a sudden increase in
Speaker 5: inflammation and immune system activation that then causes inflammatory cells
Speaker 5: and messengers and all this stuff being sent to the
Speaker 5: airways that leads to both cells and debris in the area,
Speaker 5: which that alone can cause some obstruction of the airways.
Speaker 5: But in people with asthma, what this does is it
Speaker 5: triggers a hyper reactivity of the smooth muscle cells that
Speaker 5: surround our airways, and it causes those airways to constrict.
Speaker 5: This again obstructs the airway. So it's these two things. Inflammation,
Speaker 5: which is both an underlying chronic inflammation and episodes of
Speaker 5: increased inflammation and smooth muscle constriction also called bronco constriction,
Speaker 5: and that together is what causes the shortness of breath,
Speaker 5: the wheeze, the chest tightness, all of these things that
Speaker 5: we associate with asthma exacerbations.
Speaker 4: Okay, I can wrap my head around, like the hyperreactivity
Speaker 4: part of this leading to super inflammation. But where does
Speaker 4: the smooth muscle constriction come in, Like why does that happen?
Speaker 4: Does that happen under other circumstances? When is that like
Speaker 4: is it too much of a good thing?
Speaker 5: Kind of a deal? Yeah, it's a good question. So, yes,
Speaker 5: our airways have smooth muscles so that they can expand
Speaker 5: and contry at as needed. What happens in asthma is
Speaker 5: a hyperactive response. If you think of like when you
Speaker 5: get a tickle in your throat, or you inhale your
Speaker 5: own saliva by accident and you cough, right, that cough response.
Speaker 5: Part of what's happening in that is airways are constricting,
Speaker 5: smooth muscle cells are being activated, right, that's a normal
Speaker 5: physiologic response. What's happening in asthma is a hyper reactivity
Speaker 5: to irritants or to triggers of some kind that's also
Speaker 5: happening unevenly across all of the different small and large
Speaker 5: airways in your lungs. So it's not like the whole
Speaker 5: lung it's like patchy throughout the lungs.
Speaker 4: That's really interesting, and it's like a sustained response to.
Speaker 5: Such a good question erin So it's not like just
Speaker 5: all of the airways and the lungs constrict and stay constricted.
Speaker 5: But you can think of it as like this hyperactive
Speaker 5: response happening throughout the lungs, and that is also going
Speaker 5: to trigger more immune activity and inflammation. Right, So it's
Speaker 5: like a it's more like a cycle, yeah, dominoes or cycles.
Speaker 4: Okay, so why certain areas, Like is there any rhyme
Speaker 4: or reason to which areas are constricted or have this
Speaker 4: hyperreactivity or anything like.
Speaker 5: That, not that I know of. Okay, Yeah, Yeah, it's
Speaker 5: just sort of it's happening throughout the lungs and it's
Speaker 5: patchy debris like mucus can be mucus cells, all of
Speaker 5: the immune mediators that are coming to the quote unquote
Speaker 5: rescue because of this trigger that we have to respond to, right,
Speaker 5: all the cells that are there, it's just all that stuff,
Speaker 5: And again this is not happening in the same way
Speaker 5: in everyone, so it's not the same stuff in everyone.
Speaker 5: There are a lot of different types of asthma and
Speaker 5: they're classified in different ways. So in a clinical setting
Speaker 5: like your doctor's office or whatever you might in here,
Speaker 5: asthma classified by its severity. Is it an intermittent asthma
Speaker 5: that really happens pretty rarely under very certain circumstances. Or
Speaker 5: is it persistent? Is it kind of always there or
Speaker 5: happens really often but can be controlled with medications. Is
Speaker 5: it mild? Is it moderate? Or is it severe? But
Speaker 5: those different definitions change based on what society's guidelines you
Speaker 5: might be looking at. And by society, I mean you know,
Speaker 5: like the Asthma Federation of this country or that country,
Speaker 5: not like urgiety, yeah, high society, whatever. But on top
Speaker 5: of those type of clinical definitions, there's also a lot
Speaker 5: of other ways to classify asthma. There's allergic asthma, which
Speaker 5: often coincides with things like you know, allergies, food allergies,
Speaker 5: environmental allergies, exzema. Non allergic asthma, so not associated with
Speaker 5: allergies or allergic responses. There's like cough predominant asthma. There's
Speaker 5: eosynophilic asthma. There's extra size induced asthma, there's late onset asthma.
Speaker 5: There's a lot. And these are sometimes called different phenotypes
Speaker 5: of asthma. For anyone who hasn't taken general bio in
Speaker 5: a while, a phenotype is like what you observe. It's
Speaker 5: a set of like observable characteristics. So these are other
Speaker 5: ways to classify asthma based on how it appears clinically,
Speaker 5: how you seem. It's another system aside from just mild, moderate, severe,
Speaker 5: and these can kind of go together. But none of
Speaker 5: these ways of classifying get into the fact that within
Speaker 5: and across each of these classifications there are in fact
Speaker 5: different underlying mechanisms of that asthma. These are sometimes called
Speaker 5: different asthma endotypes or different subsets of a disease that
Speaker 5: are actually based on distinct pathophysiological mechanisms. On that, I
Speaker 5: want to shout out a paper called Understanding the Immunology
Speaker 5: of Asthma Pathophysiology by and Treatments for Asthma Endotypes from
Speaker 5: twenty twenty, because not only does that paper highlight a
Speaker 5: lot of the complexity of these different endotypes, and I
Speaker 5: am not going to get into a lot of that complexity,
Speaker 5: but it had this really great schematic diagram of some
Speaker 5: of the possible mechanisms that underlie the development of these
Speaker 5: different types of asthma, which you can all just call asthma,
Speaker 5: really in a way that connects these seemingly disparate pathways
Speaker 5: that all happen to lead to the same end result, right,
Speaker 5: and that end result is chronic underlying inflammation and airway
Speaker 5: hyper reactivity with certain triggers aka asthma.
Speaker 4: It's so interesting because on the one hand, it seems
Speaker 4: like you can break down asthma into so many discrete
Speaker 4: types and in terms of phenotype like you said, or
Speaker 4: the underlier mechanism or treatment or whatever. But at the
Speaker 4: same time it's this big overarching thing. And at the
Speaker 4: same time, treatment i assume is highly individual, where it's
Speaker 4: like based on this person, Like you could have two
Speaker 4: people that have allergic asthma, but they're maybe their triggers
Speaker 4: are something different, and so then the management is different.
Speaker 5: Well is it, Aaron Guse Right now? It isn't. And
Speaker 5: that is such a good point, right, That is why
Speaker 5: understanding these different underlying mechanisms matters because if all the
Speaker 5: treatment is the same, then these underlying mechanisms are interesting
Speaker 5: but don't necessarily matter. Right now, our treatment is based
Speaker 5: on symptoms, and symptoms are things that you can see
Speaker 5: and experience, right so treatment is based on how often
Speaker 5: do you have exacerbations? Yes, maybe what are your triggers
Speaker 5: will determine when you might use a treatment. But at
Speaker 5: its core, the treatment guidelines are mostly the same for everyone,
Speaker 5: based on the severity of your asthma, but not based
Speaker 5: on any of these underlying mechanisms. So two people with
Speaker 5: the same severity are going to end up falling on
Speaker 5: the same treatment algorithm, even if they have totally different
Speaker 5: types of asthma. How it stands today, but it doesn't
Speaker 5: work the same way for everyone, and that's because the
Speaker 5: underlying mechanisms aren't necessarily the same. So in asthma we
Speaker 5: have now learned that understanding these disparate mechanisms is actually
Speaker 5: really important because even though it ends with the same response,
Speaker 5: the ways and pathways in which you get there, if
Speaker 5: we can better target those, we can have individualized treatment
Speaker 5: and then we can have better outcomes. Right now, we
Speaker 5: have that for pretty small subsets of populations just based
Speaker 5: on like what's available today.
Speaker 4: Huh, It's like it's within reach. It's like you know
Speaker 4: this now, now let's turn to application.
Speaker 5: Right exactly? I think I think that's kind of where
Speaker 5: we where we are and where we're going. So that's
Speaker 5: like spoilers for later this episode. So that is kind
Speaker 5: of the as much as we'll get into on the
Speaker 5: nitty gritty of like these different mechanisms of asthma and
Speaker 5: the types of asthma. If you want more real nitty gritty,
Speaker 5: I will post plenty of papers for you. But the
Speaker 5: other big question is like who gets asthma? Right? Right? Everyone?
Speaker 5: What right? And everyone? What are these risk factors like?
Speaker 5: And I think a really interesting part of that question
Speaker 5: from a public health perspective is is it inevitable that
Speaker 5: a person is going to develop asthma if they are
Speaker 5: a person who's going to develop as or is this
Speaker 5: something potentially preventable? And I'm sure it will be no
Speaker 5: surprise to you, AARIN or to listeners that we don't
Speaker 5: know the answer to that question. Asthma is a multi
Speaker 5: factorial disease, since we know now just how variable it
Speaker 5: is and we're only in the relatively early stages of
Speaker 5: really understanding all of that variability. We don't really know
Speaker 5: and can't pinpoint this person's going to develop asthma, this
Speaker 5: person's not. If we change these things about the environment,
Speaker 5: we could prevent this asthma, but not this asthma. We
Speaker 5: don't know that. But we do know that there are
Speaker 5: both genetic and environmental factors that play into the development
Speaker 5: of asthma. There are a lot of different potential genes
Speaker 5: that could be involved, like a whole host of them,
Speaker 5: and there's some thought that there might also be epigenetic
Speaker 5: factor that are involved, because there's evidence that asthma is
Speaker 5: more strongly maternally linked than paternally linked in terms of genetics,
Speaker 5: but overall heritability is like between thirty five and eighty
Speaker 5: percent depending on which study you read. And in terms
Speaker 5: of environmental factors, there are so many it's.
Speaker 4: Just like you could spend the rest of this episode
Speaker 4: listing them and not even get close exactly.
Speaker 5: And I know, Aaron, that you're going to get into
Speaker 5: some of the fun hypotheses that have come out.
Speaker 4: As to just just a tiny little sprinkling.
Speaker 5: Yeah, that's good, that's good. That's all we need is
Speaker 5: a sprinkle of some of those, but some things that
Speaker 5: we know are real risk factors for asthma are things
Speaker 5: like tobacco, smoke pollution right air pollution is a huge
Speaker 5: factor in the development of asthma and also asthma exacerbations.
Speaker 5: So there's a lot of just overall environmental changes that
Speaker 5: can affect the development of asthma. And that's the large
Speaker 5: part of why we see, as we'll talk about in
Speaker 5: the current event section, such variation in asthma prevalence across
Speaker 5: the globe.
Speaker 4: There are so many layers to every aspect of asthma.
Speaker 4: I know, and I have nowhere that I'm going with
Speaker 4: that just saying that, But I do have a question.
Speaker 4: So you talked about how for the most part, treatment
Speaker 4: and management is more or less very similar, if not
Speaker 4: the same, for most people. What is that treatment?
Speaker 5: Great question. I'll talk a little bit more about this
Speaker 5: in the current event section, but the basic, very basicness
Speaker 5: is inhalers of some kind. Inhalers allow for medication to
Speaker 5: be delivered directly to the lungs, so that's where we
Speaker 5: want the effect of this medication to be. This is
Speaker 5: a disease that's really happening in the lungs, so by
Speaker 5: having an inhaled medication, you have pretty minimal systemic absorption,
Speaker 5: which is good. There's two different major types of inhalers.
Speaker 5: There's inhalers that mostly serve to broncho dilate, so they
Speaker 5: relax the smooth muscle of those airways and open them
Speaker 5: up right. All of those rescue inhalers that people think of,
Speaker 5: those are usually really short acting broncho dilators, so they
Speaker 5: turn on quickly and turn off quickly to just open
Speaker 5: up your airways if you can't breathe for a short time.
Speaker 5: Then there are longer acting versions of those that people
Speaker 5: might use as controller medications. And then there are inhaled steroids. Steroids,
Speaker 5: of course are anti inflammatory, so these are serving to
Speaker 5: reduce the overall inflammation and immune activation that's causing a
Speaker 5: lot of this underlying issue. More and more inhaled corticosteroids
Speaker 5: have become the mainstay of asthma management. Even in mild asthma.
Speaker 5: Used to be a probably over reliance on bronchodilators, and
Speaker 5: now more and more it's inhaled steroids plus or minus
Speaker 5: these bronchodilators. And I think that that makes sense when
Speaker 5: you go back to what we just talked about with
Speaker 5: the fact that this is an inflammatory disease. There's underlying
Speaker 5: chronic inflammation even in people with mild or intermittent asthma,
Speaker 5: and so anything that's just acting to bronchodilate is like
Speaker 5: a band aid. It's treating the symptoms, but it's not
Speaker 5: addressing that underlying immune dysfunction and inflammation. So the steroids
Speaker 5: are doing a better job of that. But as I said,
Speaker 5: especially as we understand more and more about these different
Speaker 5: types of asthma, there are already and will likely continue
Speaker 5: to be other, probably systemic options like monoclonal antibodies and
Speaker 5: things like that, that are directly targeting the dysfunctional immune
Speaker 5: cells involved. But we're not there quite yet.
Speaker 4: I think it was in our lupus episode that we
Speaker 4: talked about how long term use of steroids can be
Speaker 4: not so great sometimes. Is that different for inhaled steroids
Speaker 4: because it's so localized exactly.
Speaker 5: That's why it's so important that it's inhaled and not systemic,
Speaker 5: because you have very minimal systemic absorption. It's really just
Speaker 5: like coding your airways and acting in those airways. Cool
Speaker 5: very different than like taking a steroid pills.
Speaker 4: Yeah, okay, that's interesting.
Speaker 5: Yeah.
Speaker 4: Although we know that asthma is not strictly a childhood
Speaker 4: disease or disease of childhood, it does happen in children
Speaker 4: and then go away. Do we know anything about why?
Speaker 5: That is good question. I don't have an answer to
Speaker 5: that question. It is possible that I just didn't read
Speaker 5: the right papers and that there is a very good
Speaker 5: answer to that question that I didn't find. So if
Speaker 5: anyone has a better answer than what I'm about to say,
Speaker 5: please do let us know. But I suspect a lot
Speaker 5: of it just has to do with how much our
Speaker 5: immune systems are still under development when we're little, and
Speaker 5: our airways are also a lot smaller. Okay, So anything
Speaker 5: that's causing obstruction or constriction, it's going to have a
Speaker 5: greater effect when you're smaller and your airways are small.
Speaker 5: And so a lot of kids have wheeze, and a
Speaker 5: lot of that wheeze may never truly be labeled as asthma. Right,
Speaker 5: they might get wheezing with every viral infection, but never
Speaker 5: like meet the definition of asthma by whoever's defining it
Speaker 5: in their region. And then they'll grow out of that
Speaker 5: because their airways are growing and their immune system is,
Speaker 5: you know, figuring itself out. That's the best answer that
Speaker 5: I can give you. There might be a better one
Speaker 5: out there.
Speaker 4: Okay, Yeah, so I know that this next question, the
Speaker 4: answer is probably it depends on what country or what
Speaker 4: organization or whatever. But how is asthma diagnosed? Yeah, what happens?
Speaker 4: What are the what are the diagnostic criteria?
Speaker 5: Excellent question. So in some places it's diagnosed with what
Speaker 5: are called pulmonary function tests, So that means you actually
Speaker 5: have to like sit in this chamber and blow and
Speaker 5: this tube and they measure the flows and blah blah blah,
Speaker 5: and then on top of that, you have to give
Speaker 5: a Bronco dilator and see if the values improve. Because
Speaker 5: that tells us that it's a reversible process that really
Speaker 5: helps distinguish asthma from something like COPD or chronic obstructive
Speaker 5: pulmonary disease. So that's more like adults are more likely
Speaker 5: to undergo that whole function pulmonary function testing process. In kids,
Speaker 5: a lot of times they can't do those testing or
Speaker 5: that testing is really difficult and just not available where
Speaker 5: they live. So really it's based on those symptoms that
Speaker 5: I talked about way at the very beginning, these episodes
Speaker 5: of shortness of breath and wheezing, which is something you're
Speaker 5: going to hear with a stethoscope, and that happen in
Speaker 5: response to really any kind of trigger, doesn't matter what
Speaker 5: the trigger is, and that will get better with some
Speaker 5: of these medications in general. So I don't have in
Speaker 5: front of me like the very specific this number of
Speaker 5: episodes or of wheezing or anything like that, but that's
Speaker 5: the general rule, and you don't have to have those
Speaker 5: pulmonary function tests in order to make the diagnosis.
Speaker 4: Okay, I feel like I saved all my questions for
Speaker 4: the end somehow. But I do have another.
Speaker 3: One, Okay, give it to me.
Speaker 4: And that is the breakdown between mild, moderate, and severe.
Speaker 4: Like what determines whether something is mild, moderate, or severe
Speaker 4: is that the frequency or intensity of exacerbations. And question
Speaker 4: part two is are there certain types of asthma that
Speaker 4: are more likely to be severe or more likely to
Speaker 4: be mild or is it super individual?
Speaker 5: Excellent question. So again I don't have the exact numbers
Speaker 5: in front of me in terms of mild, moderate, severe.
Speaker 5: I will point all listeners who want to know to
Speaker 5: and we'll link to the Global Initiative on Asthma or
Speaker 5: GENA report, which is one of the main organizations that
Speaker 5: defines these But it is based on how many exacerbations
Speaker 5: you have, whether you've needed to be hospitalized or had
Speaker 5: systemic steroids to treat an exacerbation, versus if your exacerbations
Speaker 5: get better with just inhaled medications, because sometimes they're so
Speaker 5: bad that you do need those systemic steroids to actually
Speaker 5: calm down that inflammation and actually treat that exacerbation. So yeah,
Speaker 5: at its core, it's about how many exacerbations and how
Speaker 5: bad those exacerbations are. Okay, when we're talking about the
Speaker 5: different classification to answer your question about our certain types
Speaker 5: of asthma more likely to be severe, Yes, potentially, especially
Speaker 5: adult onset asthma or late onset asthma is maybe more
Speaker 5: likely to be severe than childhood asthma or asthma that's
Speaker 5: been there since forever, and I'm sure that there are
Speaker 5: other types that also are more likely to be severe
Speaker 5: than others. Then there are also some people with asthma
Speaker 5: that we maybe don't have a good classification for, but
Speaker 5: that is very severe that we really don't have great
Speaker 5: treatments for yet. And so I think that gets to
Speaker 5: why it's so important that we really understand all of
Speaker 5: the different underlying mechanisms, because there are people who have
Speaker 5: very difficult to control asthma with severe symptoms that we
Speaker 5: right now don't have great ways of treating.
Speaker 3: Okay, yeah, so yeah, that's unless you have more question.
Speaker 5: That's the biology.
Speaker 3: Of asthma.
Speaker 4: There's so much to it.
Speaker 5: Yeah, and I probably didn't cover it all.
Speaker 4: I mean it's impossible too though, like it even if
Speaker 4: you did one type of asthma, let's say, like allergic
Speaker 4: or allergy associated asthma or whatever. Yeah, how did they
Speaker 4: even begin?
Speaker 5: We'd be we'd be here all night erin, Yeah, we would.
Speaker 5: So on that note of being here all night erin,
Speaker 5: I'm guessing, I mean, have we had asthma since we've
Speaker 5: been humans? Where did the again? I don't even know
Speaker 5: how to ask, where did this come from? Like? What's
Speaker 5: up with this? How about that?
Speaker 4: That's that's a good way to put it. I don't know,
Speaker 4: but I'll well, we'll try to get into it as
Speaker 4: much as we can. Right after this break. The thing
Speaker 4: that surprised me most about the history of asthma isn't
Speaker 4: how far back and wide ranging the descriptions go. So, Aaron,
Speaker 4: you asked, have we had this since we were humans?
Speaker 4: First of all, yes, it's an ancient disease that's been
Speaker 4: written about since ancient times, and we absolutely have had
Speaker 4: it for as long as we've been humans, which makes
Speaker 4: sense because other animal species can also have asthma. Like,
Speaker 4: my gosh, get asthma.
Speaker 5: I really wanted to ask you that question, and I
Speaker 5: was afraid that it was a.
Speaker 4: Silly question, and bil I definitely googled it, and that's
Speaker 4: what Google tells me.
Speaker 5: Oh my goodness, poor kitty cats. I know, I know,
Speaker 5: how do you get an inhaler for a cat? You
Speaker 5: need a nebulizer?
Speaker 4: Sure, I don't know how at home management is for
Speaker 4: cats with asthma. Maybe we have a lot of people
Speaker 4: who are in the veterinary field that listen.
Speaker 5: So yeah, please, it's so sad.
Speaker 4: But the I forget where I was even going with this,
Speaker 4: but that we've had it since forever. Oh yeah, yeah, yeah.
Speaker 4: Another thing that did not surprise me, or it didn't
Speaker 4: surprise me. The most about asthma, the history of it
Speaker 4: is that asthma has undergone many revisions since these earliest descriptions, right, Like,
Speaker 4: that's not that surprising. It started out as a disease
Speaker 4: of humors, then of lungs, then of personality, then of allergy,
Speaker 4: than as inflammation, and many other forms along the way,
Speaker 4: sort of crisscrossing each other and happening simultaneously and borrowing
Speaker 4: parts of each other.
Speaker 5: Makes sense.
Speaker 4: The thing that actually surprised me the most about the
Speaker 4: history of asthma was how prominent a role the personal
Speaker 4: experience of asthma played in the way that this disease
Speaker 4: was written about, the attention it got, and in my view,
Speaker 4: the greater sense of empathy that it invited. And this
Speaker 4: is true for much of the history of this disease really,
Speaker 4: or at least until we get to the early twentieth
Speaker 4: century with the depersonalization of medicine as per usual. Basically,
Speaker 4: this is my way of preparing you for the sizeable
Speaker 4: number of sizable quotes that I've sprinkled in throughout the
Speaker 4: history section one first hand account per century. Just kidding
Speaker 4: that would be like a ridiculous amount a lot, but
Speaker 4: I honestly probably could have given how many there are
Speaker 4: which I think is really interesting and unusual.
Speaker 5: Yeah, Is it just that a lot of people had
Speaker 5: so or why? Why is that?
Speaker 1: Yeah?
Speaker 4: I think it just comes down to how prevalent it
Speaker 4: was and how much it was a part of people's lives,
Speaker 4: right because.
Speaker 5: People were just like living with it on a day
Speaker 5: to day. It wasn't this thing that came one time
Speaker 5: and then killed you, right, Like a lot of diseases
Speaker 5: we talk about, it's something that people lived with for
Speaker 5: their whole lives.
Speaker 4: Yeah, I think that the most similar one that we've
Speaker 4: covered on the podcast is gout. But the other thing
Speaker 4: too is that, like we've covered a lot of chronic diseases,
Speaker 4: but it's also who is doing these medical writings, who
Speaker 4: writes about it and was able to be a physician,
Speaker 4: who was allowed to be a physician, Right, So, like endometriosis,
Speaker 4: we could absolutely have had centuries worth the first hand accounts,
Speaker 4: but we don't.
Speaker 3: M this makes a lot of sense, yeah anyway.
Speaker 4: But I think in terms of asthma, what these historical
Speaker 4: first hand accounts show is that while there have been
Speaker 4: enormous improvements made in terms of how it's treated or
Speaker 4: understood or even defined, some things haven't changed I also
Speaker 4: think that they're a good reminder in this day and age,
Speaker 4: with medicine being so depersonalized and reduced to statistics and
Speaker 4: charts and test results, to not discount the value of
Speaker 4: personal stories, because I think that it can be really
Speaker 4: important in well, first of all, just like recognizing that
Speaker 4: patients are people, but also in how maybe this person
Speaker 4: wants to manage their asthma and the things that exacerbate asthma. Anyway,
Speaker 4: I should probably stop at this point philosophizing and you know,
Speaker 4: talking about asthma and start talking about actually the history
Speaker 4: of asthma, beginning with the ancient stuff, because the evolutionary
Speaker 4: history of asma, like it's impossible.
Speaker 5: Yeah, absolutely, yeah. Yeah.
Speaker 4: So it feels like it's been a little bit since
Speaker 4: I've gotten to say the word papyri or talk about
Speaker 4: ancient Greece or China or India. So this is exciting.
Speaker 4: The word asthma is actually from an ancient Greek word
Speaker 4: that first made an appearance in the Iliad from the
Speaker 4: seventh or eighth century BCE, in a scene describing the
Speaker 4: Trojan leader Hector quote lying on the plane while about
Speaker 4: him sat his comrades and he was gasping with painful
Speaker 4: breath as Mahdi distraught in mind and vomiting blood. In
Speaker 4: this context and for the few hundred years that followed,
Speaker 4: the word asthma was used in Ancient Greece to describe
Speaker 4: labored or painful breathing or gasping, especially as induced by exertion,
Speaker 4: so you can find it a lot in descriptions of
Speaker 4: battle or death scenes in epic plays or poems. But
Speaker 4: by the time of Hippocrates around the fifth century BCE
Speaker 4: or so, the word asthma had shifted to have a
Speaker 4: more medical meaning, with a specific set of symptoms, causes, prognosis, treatments,
Speaker 4: et cetera, a chronic condition rather than just solely an
Speaker 4: acute attack, and in this recognition, ancient Greek physicians were
Speaker 4: a bit behind the times. The Ebers Papyrus from around
Speaker 4: fifteen fifty BCE includes a description of what is likely
Speaker 4: asthma and treatments that ranged from your simple enema to
Speaker 4: the application of various animal dung mixed with herbs. Just
Speaker 4: spread that on your skin your skin.
Speaker 5: What sure.
Speaker 4: Asthma was written about extensively in ancient China as well,
Speaker 4: with the earliest descriptions coming from around one thousand BCE,
Speaker 4: including a mention of the plant mahuang, which was used
Speaker 4: to treat asthma and in modern times has been used
Speaker 4: to extract ephedrin, which has also been used to treat asthma.
Speaker 4: So that's kind of that's kind of cool. Yeah, the
Speaker 4: inhalation of stramonium from thorn apple or gymsen weed was
Speaker 4: also used in modern times to treat asthma and was
Speaker 4: also mentioned in some ancient texts. But anyway, asma was
Speaker 4: widely written about across the ancient world, like in so
Speaker 4: many different historical texts. It's kind of incredible, and I
Speaker 4: think that just goes to show how prevalent it was
Speaker 4: and how much interest there was in finding ways to
Speaker 4: alleviate symptoms. And yeah, some of those treatments seemed a
Speaker 4: bit questionable. You know, you've got your blood letting, your enemas,
Speaker 4: your plasters to ease the chest, your diuretics, your emetic exercise, massage,
Speaker 4: honeywater mead, eating the liver of a fox after it's
Speaker 4: been dried and pounded and sprinkled into a cupful of wine,
Speaker 4: or just eating the freshly roasted lungs of that fox. Oh, dear,
Speaker 4: you know, just your standard treatments, standard standard, pretty pretty regular,
Speaker 4: not to mention the dozens upon dozens of herbal remedies
Speaker 4: and plant extracts which could be applied as tinctures, consumed
Speaker 4: in a cocktail, and hailed so many ways to administer.
Speaker 4: Even though there's this huge variety in the types of treatments,
Speaker 4: like from roasted fox lungs to enemas, their purpose was
Speaker 4: largely the same thing, to restore balance in the body.
Speaker 4: At the time. In ancient Greece, the humoral theory of
Speaker 4: disease predominated. And I know I've mentioned this in so
Speaker 4: many episodes, but in case this is someone's first time
Speaker 4: tuning in first, welcome second. The humoral theory of disease
Speaker 4: was a essentially this idea that there are four bodily humors,
Speaker 4: and an imbalance in one of those humors, like too
Speaker 4: much or not enough, is what led to disease. Treatment
Speaker 4: then was focused on restoring that balance. In the case
Speaker 4: of asthma, an excess of FLEM was to blame, specifically
Speaker 4: as the phlem moved from the brain to the chest.
Speaker 5: I feel like excess of FLEM is a lot of diseases, oh, yeah.
Speaker 4: I mean when you only have four humors.
Speaker 3: Right, you can do the math on Yeah, how many?
Speaker 4: Is it? Like? Four times, three times, two times one?
Speaker 4: I'm not sure how you do that. That's my air
Speaker 4: and math. I don't know.
Speaker 3: I really like it.
Speaker 4: But for asthma, like, why was there more flem? That's
Speaker 4: a reasonable question. It has a thousand different answers. Right,
Speaker 4: Maybe it's because you than a dry climate, or maybe
Speaker 4: it was a certain season, or maybe you had a
Speaker 4: certain personality that just led you to have more phlegm.
Speaker 4: Maybe you were a certain age. Really, it could be anything.
Speaker 4: And this flemy explanation for asthma hung around for about
Speaker 4: one thousand years in one shape or another, and continued
Speaker 4: to influence how European physicians viewed the disease through the
Speaker 4: seventeen hundreds. But of course it wasn't just phlem equals asthma.
Speaker 4: Asthma was recognized to be incredibly varied in its presentation
Speaker 4: and severity, with most cases thought to be mild, but
Speaker 4: others recognized as severe and even life threatening. And here
Speaker 4: we come to our first ancient first hand account. Ooh,
Speaker 4: so the ancient Roman philosopher Seneca had asthma and he
Speaker 4: described his disease in around the first century CE. Quote.
Speaker 4: It's onslaught is a very brief duration, like a squall.
Speaker 4: It is generally over within the hour. One could hardly,
Speaker 4: after all, expect anyone to keep on drawing his last
Speaker 4: breath for long could one. I have suffered every kind
Speaker 4: of unpleasant or dangerous physical complaint, but none is worse
Speaker 4: than this, not surprising, for anything else is just an illness,
Speaker 4: while this is gasping out your life breath. That is
Speaker 4: why doctors call it a quote rehearsal for death, since
Speaker 4: eventually the breath does what it has often been trying
Speaker 4: to do.
Speaker 5: End quote. WHOA right? That sounds awful?
Speaker 2: I mean.
Speaker 4: Yeah, yeah, and that tracks it tracks right like that?
Speaker 4: You could you could imagine someone describing that today.
Speaker 5: I have seen that, Yeah, yeah.
Speaker 4: But yeah, I mean yeah, first century CE. I could
Speaker 4: probably spend the rest of the history section actually in
Speaker 4: the first century CEE, not really, but like at least
Speaker 4: in ancient times, talking about how asthma was perceived and
Speaker 4: written about in the ancient and medieval world. But I
Speaker 4: should probably move on to when we started suspecting that
Speaker 4: it wasn't just about the phlegm coming from your brain.
Speaker 4: I only mentioned a few specific writings or scholars, but
Speaker 4: the ancient world gave us truly an abundance of descriptions
Speaker 4: of asthma in its varying forms, the range of symptoms,
Speaker 4: prognosis patterns, and development treatments, even the first connection with
Speaker 4: hay fever by al Razzi, medieval physician from Iran. But
Speaker 4: what I think stands out the most about asthma in
Speaker 4: the ancient world is how consistent these writings were across
Speaker 4: the globe. It came down to balance. At its core.
Speaker 4: Asthma was thought to be caused by an imbalance, and
Speaker 4: treatment focused on restoring that balance, largely through herbal remedies
Speaker 4: or lifestyle changes like diet, exercise, and reducing stress. But
Speaker 4: like I feel like it's not often that we see
Speaker 4: such agreement across right the ancient worlds. I thought that
Speaker 4: was interesting. So this idea about humoral balance in asthma
Speaker 4: persisted through much of the Renaissance. But it's also around
Speaker 4: this time that we start seeing people recognizing that that
Speaker 4: might not be all there is to it. One of
Speaker 4: these people, Juan Baptista van Helmont, in the late fifteen
Speaker 4: hundred's early sixteen hundreds who had asthma rejected the Hippocratic
Speaker 4: idea that asthma was caused by phlegm descending from the
Speaker 4: brain to the lungs. He was like, no, it's definitely
Speaker 4: not a nervous condition from my brain. I can feel
Speaker 4: it in my lungs, specifically in the contraction of them.
Speaker 4: And in any case, if Hippocrates was right, then there
Speaker 4: would be better treatments by now, and Van Helmont would
Speaker 4: be proven right and Hippocrates wrong not too long after
Speaker 4: with anatomical demonstrations showing that phlegm from the brain to
Speaker 4: the lungs did not seem to be at the root
Speaker 4: of this disease. And I think it's pretty cool that
Speaker 4: Van Helmont used his personal experience to question the dogma
Speaker 4: of the time. But he wasn't right about everything. He
Speaker 4: believed that asthma could be sorted into types, one that
Speaker 4: affected women and one that affected everyone with guess where
Speaker 4: the women only asthma came from, Oh, dear quote foul
Speaker 4: or stinking vapors ascending from the womb to block the
Speaker 4: pores and the lungs. I'm sorry, I just had to
Speaker 4: throw that in. It was too good to pass up.
Speaker 3: I Oh god, it's great.
Speaker 4: It's good stuff.
Speaker 5: Foul or stinking vapors, stinking vapors.
Speaker 4: By the end of the Renaissance, the concept of asthma
Speaker 4: had undergone a pretty big shift from this flemy nervous
Speaker 4: disease to one primarily of the lungs, and this would
Speaker 4: continue to be refined as anatomical dissections increased in the
Speaker 4: seventeen hundreds and eighteen hundreds. But before I move on,
Speaker 4: let me hit you with another first hand account, this
Speaker 4: one from physician Thomas Willis, as in the Circle of Willis.
Speaker 3: Oh wow, that's exciting.
Speaker 4: So this is from the seventeenth century quote among the
Speaker 4: diseases whereby the region of the breast is wont to
Speaker 4: be infested if you regard their tyranny and cruelty, And
Speaker 4: asthma doth not deserve the last place, For there is
Speaker 4: scarce anything more sharp and terrible than the fits here
Speaker 4: of the organs of breathing, and the precordia themselves, which
Speaker 4: are the foundation and pillars of life, are shaken by
Speaker 4: this disease as by an earthquake. For breathing, whereby we
Speaker 4: chiefly live, is very much hindered by the assault of
Speaker 4: this disease and is in danger or runs the risk
Speaker 4: of being quite taken away.
Speaker 5: Wow, yeah, Okay.
Speaker 4: As we move into the seventeen hundreds and eighteen hundreds,
Speaker 4: physicians were making small adjustments to their understanding of the
Speaker 4: path of physiology of asthma, to the borders around the
Speaker 4: definition of the disease, distinguishing it from things like bronchitis,
Speaker 4: recognizing the wide variety of symptoms and presentations, and leading
Speaker 4: many to wonder whether these all truly fit under one
Speaker 4: disease name, because we're still wondering that. But the thing
Speaker 4: is kind of like in the way that you were
Speaker 4: talking about how our increased understanding of the different mechanisms
Speaker 4: that underlie different types of asthma hasn't yet translated into treatments.
Speaker 4: This similarly, like all of this information, all of this
Speaker 4: knowledge that we had gained by the eighteen hundreds about asthma,
Speaker 4: it didn't lead to any improvements in any sort of
Speaker 4: relief for people who had asthma, and if anything, quality
Speaker 4: of life was actually at risk of getting worse for
Speaker 4: people with asthma who lived in cities or worked in factories.
Speaker 4: As the Industrial Revolution was underway, which isn't to say
Speaker 4: that people didn't try to alleviate their symptoms during this time.
Speaker 4: If you went to ten different doctors, you could get
Speaker 4: handed one hundred different prescriptions, all promising complete symptomatic relief,
Speaker 4: none actually delivering on that promise, even if they appeared
Speaker 4: to do so, because asthma is so idiosyncratic, like you
Speaker 4: talked about yep, so it's not I mean, it's really
Speaker 4: not that surprising. I think some of these doctors were
Speaker 4: probably just looking to make a quick buck, being like, oh, yes,
Speaker 4: this is how you do it, or people who made
Speaker 4: patent medicines. But I think other people were like maybe
Speaker 4: one time you prescribed like, oh, eat the liver of
Speaker 4: the snake, and then your asthma would go away, And
Speaker 4: then maybe it did randomly just not associated with the
Speaker 4: liver of a snake or any reptile or animal, but
Speaker 4: just because it went away, but then you believed. But
Speaker 4: other people were certainly just peddling not just non helpful,
Speaker 4: but potentially harmful quote unquote cures such as asthma specific
Speaker 4: cigarettes that contained various compounds. Yeah, I know, it's enough
Speaker 4: to just make your cringe. So this is from an
Speaker 4: advertisement for Potter's Asthma Cure. Oh gosh, quote, You know
Speaker 4: how exhausting asthma is. You know how prostrated you are
Speaker 4: by an attack? Year after year you have suffered in
Speaker 4: this way. The slightest thing brings on the dread paroxysms
Speaker 4: of coughing, and the perpetual fear of an attack coming
Speaker 4: on makes life a misery. Not only is the attack
Speaker 4: painful and prostrating, but the loss of time during your
Speaker 4: absence from business is another serious item in the account.
Speaker 4: And that is why you would give anything for a
Speaker 4: remedy that would afford you prompt and certain relief and
Speaker 4: freedom from attacks. That is why you ought to know
Speaker 4: about Potter's Asthma cure, because it gives relief, instant relief.
Speaker 4: Potter's Asthma smoking mixture is purely herbal in its composition,
Speaker 4: and it may be smoked in a pipe either with
Speaker 4: or without ordinary tobacco. Oh no, all that has to
Speaker 4: be done to prevent the paroxysm of asthma is to
Speaker 4: draw the smoke well into the lungs and bronchial passages,
Speaker 4: and relief will immediately be obtained.
Speaker 5: Oh gosh, Oh dear, I.
Speaker 4: Know, I know people swore by these.
Speaker 5: Mixing them with their tobacco and their pipes.
Speaker 4: So like Potters was one of many what we're in
Speaker 4: these right there, Like you could add tobacco or not
Speaker 4: add tobacco. So I found a paper that actually did
Speaker 4: like a chemical analysis of what was in some of
Speaker 4: these asthma cigarettes, okay, And they found in the brand
Speaker 4: that they looked at, which might have been Potters, I'm
Speaker 4: not sure, leaves from Detura stramonium aka thorn apple, gimson weed,
Speaker 4: Devil's trumpet, et cetera. You know, like toxic stuff. But
Speaker 4: this paper also found that these compounds may have had
Speaker 4: a slight broncho dilator ability, but like certainly not enough
Speaker 4: to warrant. Probably it was like it major lungs inflamed
Speaker 4: and worse, and then it lessened it a bit.
Speaker 5: I don't know, Aaron, you remember our Belladonna episode? Oh yeah, okay,
Speaker 5: way back when. So Jimson weed is related to belladonna, right,
Speaker 5: and has the similar compounds in it, which include muscarinic antagonists,
Speaker 5: which in fact are bronchodilators. So it probably did make
Speaker 5: people feel a little bit better. That's one of the
Speaker 5: types of medicines that we actually use today, although we
Speaker 5: tend to use beta agonists more than muscarinic medications for asthma.
Speaker 5: But yeah, so it probably did help, but also had
Speaker 5: a whole bunch of other things in it and are
Speaker 5: not specific to lungs and so would have systemic effects,
Speaker 5: et cetera. So not recommended to soak gimson weed or
Speaker 5: anything not. But I could understand why that would make
Speaker 5: people feel better.
Speaker 4: Yeah. Well, and along the same lines, apparently things like
Speaker 4: opium which were also prescribed, that could also have worked,
Speaker 4: you know, to help relieve some of the as an
Speaker 4: anti spasmotic is what this says.
Speaker 5: Yeah, and as like a pain reliever, but also it's
Speaker 5: going to decrease your respiratory rate. So that sounds like
Speaker 5: a bad combination.
Speaker 4: Yeah it I think. Yeah, some of these came with
Speaker 4: their own suite of problems, right, even if they did
Speaker 4: help a little bit. Yeah, but what's the cost here?
Speaker 3: Right?
Speaker 5: They'll make you feel better?
Speaker 4: Yeah, But inhalation of things in general became super popular,
Speaker 4: from carbolic acid to the aforementioned stramonium. Animas were a
Speaker 4: long standing option, something called the milk diet MMM. Caffeine
Speaker 4: nose cauterization, all kinds of things, none of which provided
Speaker 4: any long term relief. The frustration people felt must have
Speaker 4: been huge. Right here was this disease on which treatise
Speaker 4: after treatise had been written, which had been known about
Speaker 4: for thousands of years, for which hundreds of treatments had
Speaker 4: been tried out, that affected so very many people, and
Speaker 4: yet nothing like nothing.
Speaker 5: Yeah.
Speaker 4: The famous French novelist Marcel Proust wrote extensively about his asthma,
Speaker 4: which dominated his life. Quote and ever since that moment,
Speaker 4: up to today and until I don't know when in
Speaker 4: the future, I haven't stopped choking and having incessant attacks.
Speaker 4: And that is why, although you were in my thoughts
Speaker 4: practically all day long, I haven't written. I haven't had
Speaker 4: the courage to take up my pen.
Speaker 5: Wow. Yeah.
Speaker 4: He spent a large portion of his life trying as
Speaker 4: best he could to avoid any environmental pollutants that seemed
Speaker 4: to trigger his asthma, even lining his bedroom walls with
Speaker 4: cork to prevent pollen and perfumes from coming in.
Speaker 5: Wow.
Speaker 4: Yeah. So at this point I feel like I've been
Speaker 4: talking about the history of asthma for about twenty five
Speaker 4: thirty minutes or so, and we've covered about a couple
Speaker 4: thousand years, and in many ways, I feel like we're
Speaker 4: kind of right at where we started. It's like, yeah,
Speaker 4: it's hard to breathe sometimes, right, and the lungs are involved,
Speaker 4: and there's fronco constriction or whatever. Like yep, if you
Speaker 4: read like I had in my early draft of notes,
Speaker 4: two descriptions of asthma, one from the first century CE,
Speaker 4: so when like around the time of Seneca when he
Speaker 4: wrote that, and another from the early eighteen hundreds, so
Speaker 4: like seventeen hundred years apart, and they are eerily similar,
Speaker 4: like it's describing the same exact thing. And I don't
Speaker 4: know why that just strikes me so much, because it
Speaker 4: seems like, Okay, we got a pretty good handle on
Speaker 4: what this looks like. And yes, we made some improvements
Speaker 4: in terms of like our understanding that it's the lungs
Speaker 4: and not the brain or your personality, although stereotypes persisted
Speaker 4: still persist to this day, you know, but treatment is limited. Yeah,
Speaker 4: that's putting it mildly, I think, But yeah, in all
Speaker 4: this time, it just maybe this is harsher to me,
Speaker 4: but there just doesn't seem to be very much progress made.
Speaker 4: But finally, now that we're in the late eighteen hundreds,
Speaker 4: fortunately all that is about to change.
Speaker 5: Right although slowly.
Speaker 4: Germ theory offered the idea that perhaps asthma was directly
Speaker 4: caused by a pathogen, like a pathogenic infection, but that
Speaker 4: didn't really amount to anything. Even though throughout this people
Speaker 4: did recognize that some cases of asthma could result from
Speaker 4: or be exacerbated by respiratory infection. But it was when
Speaker 4: autoimmunity and allergy began to be studied, especially at the
Speaker 4: cellular level, that a bit more of the puzzle was
Speaker 4: put together. Researchers had long recognized that asthma often co
Speaker 4: occurred with conditions like hay fever and egzema, but how
Speaker 4: they were connected was still an open question. Then, in
Speaker 4: the early nineteen hundreds, concepts of anaphylaxis, allergy, and hypo
Speaker 4: and hypersensitivity were introduced, and physiologist Samuel Meltzer observed that
Speaker 4: asthma bore a strong resemblance to anaphylaxis. Quote the theory
Speaker 4: is here offered that asthma is an anaphylactic phenomenon. That is,
Speaker 4: that asthmatics are individuals who are sensitized to a specific substance,
Speaker 4: and the attack of asthma sets in whenever they are
Speaker 4: intoxicated by that substance. We know now that that's not
Speaker 4: the complete picture. Of course, We're still working on our knowledge,
Speaker 4: and asthma throughout the twentieth century would undergo many paradigm
Speaker 4: shifts and how it was understood or in the different
Speaker 4: like models of asthma as a disease. But this was
Speaker 4: a big step forward in finally putting together like a
Speaker 4: cellular framework almost for what was going.
Speaker 3: On, like a mechanistic connection.
Speaker 4: Yeah, exactly. This new understanding of asthma didn't immediately translate
Speaker 4: into improvements in patient experience. Those would come about pretty
Speaker 4: shortly though, but almost immediately. It did lead to improvements
Speaker 4: in managing the condition in the form of the first
Speaker 4: vacuum cleaner, which was invented and patented in nineteen oh
Speaker 4: eight by James Murray Spangler, a janitor from the US
Speaker 4: who also happened to have asthma. What Yeah, so he
Speaker 4: developed the vacuum to try to reduce his exposure to
Speaker 4: dust at work, which had long been thought to contribute
Speaker 4: to asthma irritations. Even before the link to allergy was made.
Speaker 3: Huh, Yeah, that's so cool.
Speaker 4: But the first treatment that showed real promise for asthma
Speaker 4: came in the form of allergy shots nineteen hundreds. Many
Speaker 4: researchers had considered and discarded the idea that pollen or
Speaker 4: bacterial toxins directly caused asthma, but they started to wonder
Speaker 4: whether the same principles used in preventing infectious diseases could
Speaker 4: work on allergic disorders. Anti serum didn't really seem to work,
Speaker 4: but what about vaccines. In nineteen eleven, researchers John Freeman
Speaker 4: and Leonard Noon at a London inoculation department published their
Speaker 4: findings from a study where they vaccinated volunteers who had
Speaker 4: hay fever with increasing doses of pollen, and their findings
Speaker 4: were amazing, So amazing that they encouraged researchers to try
Speaker 4: desensitization as it's called, on asthma, using various preparations like
Speaker 4: animal danders, dust, bacterial vaccines, et cetera. Desensitization grew to
Speaker 4: be extremely popular into and beyond World War Two. Oh
Speaker 4: and it seems to me like this gave hope to
Speaker 4: so many researchers, greatly increasing interest in asthma and leading
Speaker 4: to the formation of groups like the Asthma Research Council,
Speaker 4: which brought together clinicians, scientists, philanthropists, and people who had asthma.
Speaker 4: The work of these organizations not only broke new ground
Speaker 4: in asthma research or improvements in treatment, but also in
Speaker 4: bringing that treatment and other resources to people with asthma. Then,
Speaker 4: in the mid twentieth century, the development of steroids for
Speaker 4: use in Inhaler's revolutionized long term management for asthma, and
Speaker 4: epidemiological studies and new lung function or cellular tests to
Speaker 4: assess asthma revealed patterns in who was most likely to
Speaker 4: develop the disease, the role of family history, which environmental
Speaker 4: triggers could cause the most problems, and so on. There
Speaker 4: was an incredible amount of progress made in the first
Speaker 4: fifty years of the twentieth century. It's it's amazing, and
Speaker 4: we have made more since then. But I do think
Speaker 4: that one key thing was left behind, or at least
Speaker 4: that's the sense that I got in doing the research
Speaker 4: for this, and that's the personal experiences of people with asthma,
Speaker 4: which up until then had been a key feature in
Speaker 4: writings about the disease, like, even as medicine was becoming
Speaker 4: depersonalized in the late nineteenth century and it became more
Speaker 4: about the measurement and more about statistics, asthma was still
Speaker 4: viewed largely as a very individual disease. This person's asthma
Speaker 4: is exacerbated by this this person developed it at this age,
Speaker 4: this person had their asthma is more severe.
Speaker 5: You know, it was.
Speaker 4: Incredibly varied, and I think that recognition in that variation
Speaker 4: was really important, even if it didn't translate necessarily into treatment.
Speaker 4: I don't know, but I think that it's interesting because
Speaker 4: you can ask the question like what is asthma for you?
Speaker 4: What is happening during your asthma attack? How did this
Speaker 4: treatment provide relief? And you could answer those questions by
Speaker 4: saying how it actually felt for you, like how does
Speaker 4: asthma change your day to day life? Does it, does
Speaker 4: it not? What is happening during an exacerbation for you?
Speaker 4: What does that feel like? How does this treatment work
Speaker 4: compared to this treatment? Or you could answer all those
Speaker 4: questions by describing the cellular mechanisms, the path of physiological response,
Speaker 4: and that second way was becoming had become much more
Speaker 4: the norm in the twentieth century, and of course asthma
Speaker 4: is not unique in this, but I do think that
Speaker 4: shift is really striking, and I think that's especially so
Speaker 4: because it was happening around the same time that cases
Speaker 4: seem to be on the rise. So it's hard to
Speaker 4: say how the prevalence of asthma changed over the course
Speaker 4: of history, considering that diagnoster criteria have been extensively revised
Speaker 4: and statistics didn't really exist until fairly recently. But it
Speaker 4: seems pretty clear that cases of this disease have increased
Speaker 4: throughout the twentieth century. Is this increase real, It's a
Speaker 4: first question. I mean, it could be in part inflated
Speaker 4: due to changes in how asthma is diagnosed and being
Speaker 4: able to reach more people to make more diagnoses, But
Speaker 4: that doesn't explain all of it, Like there's a real increase.
Speaker 4: What's driving it then, worsening air quality or increasing exposure
Speaker 4: to pollutants possibly those had long been linked to asthma
Speaker 4: development or exacerbation. An increase in dust mites from more carpeting, Sure,
Speaker 4: that seems reasonable. Yeah, more pollen from changing agricultural practices, Sure,
Speaker 4: why not something else? Probably. The bottom line is that many,
Speaker 4: many things are likely contributing to the rise in asthma cases,
Speaker 4: and also that the drivers are probably not the same
Speaker 4: across the entire globe. As always, it's complicated, But there
Speaker 4: is one idea that people have gotten really excited about
Speaker 4: as an explanation for this rise, and that is a
Speaker 4: hygiene hypothesis.
Speaker 5: Couldn't we could not, We couldn't not.
Speaker 4: The hygiene hypothesis is this idea introduced in the nineteen
Speaker 4: seventies and refined in the nineteen eighties that says that
Speaker 4: by growing up in a more sanitized environment with less
Speaker 4: dust and dirt and dander and lower exposure to pathogens
Speaker 4: overall than in past millennia. This is also more specific
Speaker 4: to people living in industrialized countries, that our immune systems
Speaker 4: aren't getting the proper training that they used to and
Speaker 4: end up being overactive or improperly sensitized. This has been
Speaker 4: used to explain the apparent rise in allergic diseases and
Speaker 4: autoimmune disorders. The hygien hypothesis isn't the first to claim
Speaker 4: that our modern lives may have come at the cost
Speaker 4: of increasing certain diseases. Since the eighteenth and nineteenth centuries
Speaker 4: at least, asthma has been thought of as a quote
Speaker 4: unquote disease of civilization. In the late seventeen hundreds, physician
Speaker 4: Thomas Withers wrote about what he perceived as a rise
Speaker 4: in the prevalence of asthma. Quote. The greater irritability and
Speaker 4: weakness of the constitution in these days may in some
Speaker 4: measure account for the greater frequency of the asthma, especially
Speaker 4: if we add the inventive genius and the rapid progress
Speaker 4: of mankind in all the various arts of modern luxury
Speaker 4: and refinement. So that's like the prequel hygiene hypothesis.
Speaker 3: Yeah, it really is.
Speaker 4: His advice was essentially to toughen up or quote unquote
Speaker 4: cast off the effeminacy of the present times, abandoned the
Speaker 4: destructive luxury of heat.
Speaker 3: I I oh my goodness.
Speaker 4: Yeah. And he wasn't the only one. A few decades later,
Speaker 4: physician Henry Hyde Salter, who also happened to have asthma,
Speaker 4: wrote that quote the rich might be really more liable
Speaker 4: to asthma than the poor, from a more irritable, nervous
Speaker 4: organization engendered by the state of hyper civilization in which
Speaker 4: we live end quote hypercivilization. Yeah, okay, anyway, so the
Speaker 4: hygiene hypothesis, it's different. It's a bit more mechanistic, it's
Speaker 4: a bit based more in biology than just a general
Speaker 4: sense of feeling. But I do think that the parallels
Speaker 4: are kind of funny there. The hygiene hypocthesis is a
Speaker 4: really interesting and exciting idea. But is there any evidence
Speaker 4: that asthma is caused by a lack of exposures to
Speaker 4: antigens in early childhood. It's hard to say. So I
Speaker 4: dug a little bit into the literature, mostly looking at
Speaker 4: refuse and like retrospective is hygien hypothesis still an appropriate
Speaker 4: model for asthma or whatever? And it's mixed right. There
Speaker 4: are studies showing that kids who were exposed to farms
Speaker 4: or raised near farms had lower rates of asthma than
Speaker 4: those who were not, for example, But at the same time,
Speaker 4: rates of asthma are increasing in children who live in
Speaker 4: conditions of poverty in North American cities. Long term exposure
Speaker 4: to things like cockroaches and dust mites is associated with
Speaker 4: the development of asthma.
Speaker 5: So cleaner is.
Speaker 4: Should be better, but it's also not better, Like maybe
Speaker 4: it depends on the specific antigen or the timing of
Speaker 4: exposure or all of that could change depending on season,
Speaker 4: or geography or individual genetics. There is no consistency with
Speaker 4: the hygiene hypothesis, and there's a lot of contradictory evidence,
Speaker 4: don't get me wrong, Like, I think this is a
Speaker 4: really fascinating framework to think about early immune system development
Speaker 4: and how that sets our immune system on a certain
Speaker 4: course for the rest of our lives. But at this
Speaker 4: point it seems that the studies that investigate its role
Speaker 4: in asthma are not very consistent.
Speaker 5: Yeah, I think too. There's also been maybe like a
Speaker 5: combining or a shifting of this idea of just allergen
Speaker 5: exposure with also microbiome exposure, which kind of yeah, yeah,
Speaker 5: I know.
Speaker 4: Like the whole thing was reminding me of like I mean,
Speaker 4: and it is entangled with microbiome, but I was just
Speaker 4: absolutely these sound so cool conceptually, but right we're not, like,
Speaker 4: maybe we just don't have the studies yet to show
Speaker 4: specifically enough. Yeah, which isn't to say that like there
Speaker 4: aren't specific instances that could be Oh, if you had
Speaker 4: been exposed to a dog, you know, if you touched
Speaker 4: the dog out of a concrete fifteen days old or something, Yeah,
Speaker 4: instead of a cockroach. Like, how does it all fit together?
Speaker 4: I think we're a long way from I am knowing
Speaker 4: the answer to that.
Speaker 5: I think it's I think how it fits together though,
Speaker 5: is what's the interesting part about it, because I think
Speaker 5: from the diversity of data that we have, it's very
Speaker 5: clearly not one thing right. It's never going to be
Speaker 5: one exposure or lack of one exposure, and we don't
Speaker 5: understand necessarily what all of those exposures are, which I
Speaker 5: think is why it's so interesting. Like even with pets,
Speaker 5: it's like dogs, you know, reduce the risk of asthma
Speaker 5: more than cats, but like cockroaches increase it. And this
Speaker 5: in that sense, I mean, it's just it's, yeah, there's
Speaker 5: a lot and it's interesting. But I agree, we don't
Speaker 5: have the data to say that this is true versus
Speaker 5: not true or anything like that.
Speaker 4: This is not the answer. And I don't think that
Speaker 4: most of the people who study the hygien hypothesis believe
Speaker 4: that it is the answer. I think that they're using
Speaker 4: it in the way that they should, which is like, hey,
Speaker 4: this is a really interesting frameworkwork.
Speaker 5: Yeah, to test, to test, to investigate exactly, Yeah, Yeah,
Speaker 5: that's the point of a hypothesis.
Speaker 3: It is.
Speaker 4: But yeah, I mean I think that it does hold
Speaker 4: a lot of promise, and I think that's probably where
Speaker 4: at least one area of research for asthma is probably
Speaker 4: pretty active. Speaking of which, Karon, where do we stand
Speaker 4: with asthma today? What's going on?
Speaker 5: I can't wait to tell you all about it right
Speaker 5: after this break. We'll start with some possibly quite depressing statistics.
Speaker 5: All right, One paper that I read said estimated that
Speaker 5: in the UK, a child is admitted to the hospital
Speaker 5: due to an asthma exacerbation every twenty minutes. What that
Speaker 5: was my exact response and what I wrote? What with
Speaker 5: three question marks? Oh my gosh, so frequent and so many.
Speaker 5: I was astounded. Worldwide, it's estimated by the Global Asthma
Speaker 5: Network and other organizations that at least three hundred million
Speaker 5: people are living with asthma across the globe. And because
Speaker 5: asthma is a chronic disease, even if it does go
Speaker 5: away in adulthood, it's still a chronic disease for kids
Speaker 5: and for adults. There are over twenty million disability adjusted
Speaker 5: life years attributed to asthma across all ages. Globeobally, So
Speaker 5: twenty one million disability adjusted life years every year globally,
Speaker 5: and it's ranked thirty fourth among the leading causes of
Speaker 5: burden of disease. So that's huge. It's massive. And while
Speaker 5: asthma is a rare cause of death, thankfully, it is
Speaker 5: responsible for deaths every year. The Global Burden of Disease
Speaker 5: Collaboration estimates that in twenty nineteen, almost five hundred thousand
Speaker 5: people died from asthma. That's more than a thousand people
Speaker 5: a day across the globe. Oh my gosh, I know
Speaker 5: it's it's way worse than I thought. And like you mentioned,
Speaker 5: incidence has been increasing globally, though there has been some
Speaker 5: evidence of potentially plateauing incidents in higher income countries. In
Speaker 5: some high income countries, and it likely is environmental factors
Speaker 5: that contribute to a lot of these discrepancies in prevalence
Speaker 5: as well as this increasing incidence and prevalence overall, but
Speaker 5: like we said, we really don't know what those factors
Speaker 5: are in detail. If we look at the US specifically,
Speaker 5: about twenty five million people in the US are living
Speaker 5: with asthma. Over six million of those are kids. That's
Speaker 5: about eight percent of the US population, which is a
Speaker 5: lot of people, a lot of people. And a really
Speaker 5: important part of asthma in the US specifically is that
Speaker 5: it disproportionately affects black kids, especially as well as those
Speaker 5: living below the federal poverty line in the US. So,
Speaker 5: while asthma is a disease that can and does affect anyone,
Speaker 5: it has a disproportionate effect on vulnerable segments of populations,
Speaker 5: largely because of environmental exposures and systemic inequities that have
Speaker 5: existed throughout our country's history that have contributed to these disparities.
Speaker 5: So I think that's a really important part is that
Speaker 5: there's really no evidence that any of these disparities are
Speaker 5: genetic based their environmental and structural right. The other aspect
Speaker 5: is that asthma is a chronic condition that's not always
Speaker 5: easy to manage and sometimes very expensive, and so there's
Speaker 5: also discrepancies in access to healthcare for diagnosis and in
Speaker 5: access to medications as well. Yeah, and I did want
Speaker 5: to say one thing erin because you talked a lot
Speaker 5: about this individualization, and I know that I said that
Speaker 5: treatment is kind of the same, and that is true
Speaker 5: in that we use like kind of a handful of
Speaker 5: medicines for asthma in general, but the individualization of each
Speaker 5: person's asthma treatment is still a thing, and it's actually
Speaker 5: called an asthma action plan. So access to someone who
Speaker 5: can help develop an asthma action plan is actually really
Speaker 5: really important and is associated with much better outcomes, reduced exacerbations,
Speaker 5: reduced hospitalizations, et cetera. So that all contributes to these
Speaker 5: huge disparities that we see, especially in the US, right
Speaker 5: across the globe as well. So obviously there's a lot
Speaker 5: of work to be done when it comes to asthma,
Speaker 5: not only to better understand maybe the genetics that underpin it,
Speaker 5: the environmental risk factors differentiating these different endotypes or phenotypes
Speaker 5: or whatever, all of the different types of asthma. It
Speaker 5: wouldn't be surprising to me if this does end up
Speaker 5: leading to either splitting of this diagnosis or at least
Speaker 5: specifying these diagnoses right where you have really more specific
Speaker 5: definitions of asthma and therefore different and more in visualized
Speaker 5: treatments beyond just how do you use your inhaler for
Speaker 5: your specific action plan, but along those lines and with
Speaker 5: regards to treatment and the future of treatment, I wanted
Speaker 5: to mention something. Shout out to my friend and colleague
Speaker 5: Kat who brought this article to my attention. That is
Speaker 5: a really important part of how we decide on medications,
Speaker 5: and we, as like a whole medical community, decides on
Speaker 5: medications for chronic, often lifelong diseases. The recent guidelines that
Speaker 5: came out of GINA, the Global Initiative for Asthma, These
Speaker 5: are kind of like big time global guidelines that a
Speaker 5: lot of different countries use. And these treatment guidelines very
Speaker 5: strongly endorse using a combination of inhaled steroids like I
Speaker 5: mentioned and a short acting broncho dilator, but they specifically
Speaker 5: endorse this combination of one type of bronchodilator and one
Speaker 5: type of inhaled cortico steroid, which happens to be found
Speaker 5: in combination in a drug called Symbacourt in the US,
Speaker 5: which is made by a company called Astrosenica, which happened
Speaker 5: to have two point five billion dollars in sales of
Speaker 5: this drug in twenty twenty one, and twelve of the
Speaker 5: seventeen members of the GINA board have received payments from
Speaker 5: this company.
Speaker 4: Astrasenca not doesn't seem like it should be okay.
Speaker 5: Now, the GINA guidelines more strongly recommend this drug this
Speaker 5: combination than a couple of other guidelines that have less
Speaker 5: fewer board members that have received payments from Astrosenca. But
Speaker 5: what I'm saying is not necessarily that people are being
Speaker 5: corrupted by these payments. The problem here is that if
Speaker 5: you look at a Cochrane review from twenty twenty one,
Speaker 5: four of the five studies that were included in this study,
Speaker 5: which in fact showed that using this combination of inhaled
Speaker 5: corticosteroids and a bronchodilator had better outcomes than using short
Speaker 5: acting bronchodilators alone. The data is pretty clear from these
Speaker 5: studies that that leads to better outcomes. But four of
Speaker 5: five studies that were included in this Cochrane review were
Speaker 5: funded by AstraZeneca. I mean, so it's not necessarily inherently
Speaker 5: bad that the pharmaceutical industry is financing these studies. These
Speaker 5: studies are important. They're integral to be able to develop
Speaker 5: better treatments and to know is this treatment going to
Speaker 5: be better than what we have currently. The problem is
Speaker 5: not only these conflicts of interest, in that these studies
Speaker 5: were funded by these companies. The guidelines are being written
Speaker 5: by people who are getting money from these companies based
Speaker 5: on the studies that were funded by these companies. But
Speaker 5: it's also that we don't have any other studies of
Speaker 5: similar medications to actually compare to. Right there are a
Speaker 5: lot of other combinations of these two types of drugs
Speaker 5: that exist, but right now we only have data that
Speaker 5: says this particular one that we have studied, because we
Speaker 5: paid for it, because we made it is the best,
Speaker 5: So that's the one that we should.
Speaker 4: Use, you know, And also considering that it's a chronic
Speaker 4: use medication.
Speaker 5: Exactly exactly, this is something people are going to be
Speaker 5: buying every month, right for their whole childhood or their
Speaker 5: whole life. And again I'm not saying that there's not
Speaker 5: data that this medication absolutely reduces exacerbations, reduces hospitalizations, proves outcomes.
Speaker 5: The problem is that when we only have data on
Speaker 5: this one specific combination from this one company, how do
Speaker 5: we then make a decision about how to treat not
Speaker 5: only everyone who doesn't have access to this one specific
Speaker 5: medication by this one specific company, but also how do
Speaker 5: we compare that and make sure that we're funding studies
Speaker 5: that are non biased to compare that to all of
Speaker 5: the other drugs that already exist, right, right, And I
Speaker 5: just wanted to mention that and bring that up because
Speaker 5: I think it's a really important part of chronic disease,
Speaker 5: especially right, like you mentioned, Aaron, this is a disease
Speaker 5: that people are going to need potentially lifelong treatment for,
Speaker 5: and so it's especially important that the studies that are
Speaker 5: done are being done in an as non biased a
Speaker 5: way as possible so that our data is as good
Speaker 5: as possible so that people can have the outcomes that
Speaker 5: we want with out corruption.
Speaker 4: Really, I mean, yeah, I think it's I think it's
Speaker 4: difficult because it's like they're at every step of the way.
Speaker 4: There should be a focus or like a check point
Speaker 4: to be like, is there potentially bias introduced at this
Speaker 4: step versus this step? Or how could that bias be introduced?
Speaker 4: And how do we acknowledge it? Like not saying you know,
Speaker 4: it's just like what you said, These studies should be
Speaker 4: done and they are important, and these drugs do work, right,
Speaker 4: But I think finding a better way to disallow the monopolization,
Speaker 4: I guess I think what.
Speaker 5: It comes down to is something we talk about a
Speaker 5: lot on this podcast, and that is the need for funding,
Speaker 5: for public health funding and for research funding that's coming
Speaker 5: from places that are not trying to make a profit
Speaker 5: off of that research.
Speaker 1: Right.
Speaker 5: Yeah, that's what it comes down to, and that's usually
Speaker 5: governmental funding, so which is extremely limited.
Speaker 4: Yeah, so that's our best let's make a case yet
Speaker 4: again funding funding funding, yep.
Speaker 5: But just I think an interesting part and an important
Speaker 5: part of how we conduct research, not just the research
Speaker 5: that needs to be done, but how it needs to
Speaker 5: be done going forward, and that is asthma.
Speaker 4: Was that fun, it was something sources sources. I have
Speaker 4: a bunch, but I'm only going to shout out right
Speaker 4: now a book that I read by Mark Jackson called
Speaker 4: Asthma The Biography Oh Love.
Speaker 5: That I mentioned already one of my favorite papers for deep, deep,
Speaker 5: nitty gritty dive on asthma path of physiology, and that
Speaker 5: is the paper from twenty twenty by Ganz and gaffree Leva.
Speaker 5: I also have several other papers on the path of physiology,
Speaker 5: and I will of course link to those twenty twenty
Speaker 5: two GENA guidelines that I mentioned, as well as the
Speaker 5: AFP article that brought to attention the potential conflicts of
Speaker 5: interest in those guidelines. But we'll post all of our
Speaker 5: sources from this episode and all of our episodes on
Speaker 5: our website, This podcast will Kill You dot Com under
Speaker 5: the episodes tab A.
Speaker 4: Big thank you again to Lindsay for providing your first
Speaker 4: hand account. We appreciate it so very.
Speaker 5: Much, so much. Thank you to Bloodmobile for providing the
Speaker 5: music for this episode at.
Speaker 4: All of our episodes, and thank you to Leana Sculaci
Speaker 4: for our amazing audio mixing.
Speaker 5: We love it. Thank you to Exactly Right Network.
Speaker 4: And thank you to you listeners. This was a long one.
Speaker 4: Thanks for hanging in there with us and we hope
Speaker 4: you learned something.
Speaker 5: Yeah, I hope so. And a special shout out as
Speaker 5: always to our patrons. Thank you so much. Your support
Speaker 5: means the world to us.
Speaker 4: It really does. Thank you.
Speaker 5: Thank you.
Speaker 4: Okay, Well, until next time, wash your hands you feel
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