Welcome back to My Weird Prompts. I am Corn, and I am sitting here in our living room in Jerusalem with my brother, the man who probably knows more about the internal workings of the human lung than most respiratory therapists I have met. We are looking out over the Judean hills today, and the air is surprisingly clear, but inside our apartment, things have been a bit more... biological.
That is a very specific compliment, Corn. Herman Poppleberry at your service. And yes, my obsession with physiology is once again relevant because our housemate Daniel has been on quite a journey lately. As many of you know from his previous prompts, he has been dealing with some pretty intense mold issues in the house, which has flared up his asthma. It has turned our hallway into a hazmat zone and Daniel into a temporary amateur immunologist.
It is interesting how a personal crisis turns into a scientific inquiry. Daniel sent us this prompt because he realized he did not actually know the technical classification of his own condition. He always assumed asthma was an autoimmune disease because, well, it looks like one. The immune system gets aggressive, there is massive inflammation, and the body seems to be attacking itself. But then he found out it is technically classified as an allergic or atopic condition. He asked us: Why is asthma not classified as an autoimmune disease, and what is the difference between it and other conditions where the immune system becomes dysfunctional?
It is a brilliant question because the line between allergy and autoimmunity can feel very thin when you are the one struggling to breathe. We are on episode four hundred seventy-two now, and we have touched on respiratory health before, specifically in episode three hundred forty-two where we talked about the physics of breathing, and episode three hundred forty-three about modern management. But we never really tore into the taxonomy of why asthma sits in the allergy bucket rather than the autoimmune bucket. It is a distinction that matters for everything from how we treat it to how we think about the future of human health.
Right, and I think for a lot of people, those terms feel interchangeable. They both mean the immune system is being a jerk, right? But in medicine and immunology, those labels represent two very different fundamental errors in the body's programming. So, Herman, let us start with the basics. If I have lupus or multiple sclerosis, my immune system is attacking my own tissues. Why is asthma different?
It comes down to the target. In an autoimmune disease, the immune system has a failure of self-tolerance. It looks at a protein that is a natural, healthy part of your own body, like the myelin sheath in your brain or the collagen in your joints, and it says, this is an invader. It is a civil war. The body is the target. The immune system is essentially trying to delete a part of you that is supposed to be there.
Okay, so autoimmunity is an internal identity crisis. What is the allergic response in asthma then?
Asthma, specifically atopic asthma, is a hypersensitivity. The immune system is not attacking the body itself. It is overreacting to something external that is objectively harmless. Pollen, dust mites, or in Daniel's recent case, mold spores. These things are not part of you, and they are not actually dangerous like a virus or bacteria would be. But the immune system treats them like a five-alarm fire. It is not a civil war; it is more like a homeowner who sees a ladybug and decides the only solution is to burn the whole house down to get rid of it. The house gets damaged, yes, but the house was never the enemy.
That is a vivid image. So, the inflammation in asthma is a side effect of the body trying to fight off an external ghost, whereas in an autoimmune disease, the inflammation is the result of a direct strike on your own cells. But biologically, how does the body tell the difference? What are the actual soldiers doing differently in these two scenarios?
This is where we get into the deep immunology. In the world of white blood cells, we have these things called T-helper cells. Think of them as the generals of the immune system. In most autoimmune diseases, like multiple sclerosis or rheumatoid arthritis, the generals are mostly what we call T-H-one or T-H-seventeen cells. They are specialized in fighting internal threats and bacteria. But in asthma and allergies, the generals are T-H-two cells. These are the specialists for external parasites.
So the type of soldier determines the type of war. And in asthma, the star of the show is an antibody called Immunoglobulin E, or I-G-E, right?
Precisely. This is a crucial distinction. Autoimmune diseases often involve I-G-G or I-G-M antibodies that target your own tissues. But I-G-E is the antibody that evolved to fight off parasites like helminths and worms. Since most of us in modern, sanitized environments do not have giant worms living in our gut, the I-G-E system is basically bored. It starts looking for things to do, and it decides that a grain of ragweed pollen or a mold spore looks suspiciously like a parasite.
So, when Daniel breathes in those mold spores, his I-G-E antibodies latch onto them and then signal these things called mast cells to explode with chemicals like histamine and leukotrienes. That is the riot you were talking about.
Exactly. And those chemicals cause the smooth muscles around the airways to tighten up, which we call bronchoconstriction, and they cause the lining of the lungs to swell and produce thick mucus. That is the asthma attack. It is an allergic cascade. It is messy, it is loud, and it causes collateral damage, but the immune system is not trying to eat the lung cells. It is trying to build a wall of mucus and muscle to keep the mold out. In contrast, in Type One Diabetes, the immune system is like a precision assassin. It goes into the pancreas and systematically kills the insulin-producing cells. There is no wall-building; there is just destruction.
I can see why the confusion exists, though. If you look at the lungs of someone with chronic, severe asthma, there is permanent structural change. We call it airway remodeling. The tissue gets thicker, scarred, and less flexible. If you just looked at the damage, you might think, wow, this looks like an organ under a sustained autoimmune attack.
You are hitting on a really sophisticated point, Corn. And this brings us to a theory that has been gaining a lot of ground recently, especially as we move into twenty twenty-six. It is called the Epithelial Barrier Hypothesis. It was popularized by researchers like Cezmi Akdis, and it actually bridges the gap between allergy and autoimmunity.
The Epithelial Barrier Hypothesis? That sounds like something you would find in a civil engineering textbook. What does it mean for Daniel's lungs?
Think of your epithelium as the skin of your internal organs. It is the barrier that separates your body from the outside world. It is in your skin, your gut, and your lungs. The hypothesis suggests that modern life is literally poking holes in these barriers. We are talking about laundry detergents, dishwashing liquids, microplastics, and air pollution. These chemicals break down the tight junctions between your cells.
So the wall is leaky. And if the wall is leaky, things get in that should not be there.
Exactly. When the barrier in the lungs is damaged, allergens like mold spores can penetrate deeper into the tissue than they ever should. This triggers that T-H-two allergic response we talked about. But here is the kicker: that same leakiness in the gut or the skin can allow bacteria to translocate into the blood, which can trigger a systemic autoimmune response. So, while asthma is not autoimmune, it might share the same root cause as autoimmunity: a broken fence.
That is fascinating. It means that Daniel's asthma and someone else's lupus might both be symptoms of the same modern environmental problem. We have introduced over three hundred fifty thousand new chemical molecules into our environment since the nineteen sixties, and our barriers just were not built for this.
That is the consensus. And it explains why we are seeing such a massive rise in these conditions. As of twenty twenty-five, it was estimated that over four hundred thirty-four million people worldwide are living with asthma. That is a staggering number. It is one of the most common non-communicable diseases on the planet.
It feels like we are talking about a spectrum of dysfunction. On one end, you have the perfectly calibrated immune system. In the middle, you have the allergic system that is over-sensitive to the outside world. And on the far end, you have the autoimmune system that has completely lost the ability to distinguish friend from foe. But why are some people protected? Daniel mentioned that he sees the incidence going up, but some communities seem almost immune to this trend.
This brings us to the Old Friends Hypothesis, which is the more modern, sophisticated version of what people used to call the Hygiene Hypothesis. The classic example is the study of Amish and Hutterite communities in the United States.
I remember this. They have very similar genetic backgrounds, right? Both are traditional farming communities.
Yes, they are genetically almost identical. But their farming styles are different. The Hutterites use modern, industrialized farm machinery. Their children are relatively isolated from the animals. But the Amish live on single-family dairy farms. Their barns are right next to their houses, and their children are in and out of those barns from the time they can crawl.
And the asthma rates were completely different.
Night and day. In the study, almost none of the Amish children had asthma, while about twenty percent of the Hutterite children did. When researchers looked at the dust in Amish homes, it was packed with microbial products called endotoxins. That dust was actually educating the Amish children's immune systems. It was teaching their innate immune cells how to stay calm and not overreact to every little thing. Their immune systems had plenty of old friends to play with, so they did not get bored and start attacking pollen or mold.
So, while Daniel is cleaning the mold out of his house, he might actually be wishing he had grown up in an Amish barn. It is a bit of a paradox. We need to be clean to avoid infections, but being too clean makes us allergic.
It is the ultimate modern trade-off. And the reason this classification matters is not just for the sake of medical trivia. It dictates how we treat it. If asthma were truly autoimmune, we would be using much more aggressive systemic immunosuppressants, the kind of heavy-duty drugs used for organ transplant rejection or severe rheumatoid arthritis. But because it is an allergic, inflammatory condition, we can often manage it with localized treatments.
Like the inhaled corticosteroids Daniel uses. Those are designed to just quiet down the local immune response in the lungs without shutting down the whole system. But what about the people for whom inhalers do not work? We have talked about biologics before.
We are in a golden age of biologics right now. We have drugs like Omalizumab, which targets I-G-E directly. But just recently, in late twenty twenty-five, the F-D-A approved a new biologic called Exdensur. It is an I-L-five antagonist, but it is the first one cleared for twice-yearly dosing. Imagine that—instead of a daily inhaler, you get two shots a year that specifically shut down the eosinophilic inflammation in your lungs.
Two shots a year? That would be a game-changer for Daniel. But you mentioned eosinophilic asthma. That goes back to what you said earlier about there being different types of asthma, right?
Exactly. This is the future of diagnostics. We are moving away from the broad label of asthma and toward what we call endotypes. About ten to thirty percent of adults have non-allergic or intrinsic asthma. Their triggers are not pollen or mold; it might be stress, cold air, or even just a state of chronic, hyper-responsive inflammation. In the future, A-I will look at thousands of biomarkers to tell you exactly which pathway is broken in your specific body.
It is all about the granularity of the data. I think for Daniel, and for anyone listening who has been frustrated by a diagnosis that feels vague, understanding these mechanisms is the first step toward better management. You are not just a person with bad lungs; you are a person with a specific immune system that has a specific set of misunderstandings about the world.
And those misunderstandings can be managed. One thing I want to mention before we move on to takeaways is the role of stress. Since the immune system and the nervous system are so tightly linked, stress can actually make the allergic response worse. It lowers the threshold for those mast cells to explode. It is a biological feedback loop.
So when Daniel is stressed about the mold, the stress itself is making him more reactive to the mold. It is a fake war that creates a real physical toll. He is exhausted, he is burning resources, and he is not getting anywhere.
Precisely. It is like a car with the engine revving at seven thousand R-P-M while it is in neutral. You are wearing out the parts, but you are not moving. The goal of modern treatment is to put the car back into a lower gear. Whether that is through biologics, environmental control, or even experimental things like hookworm therapy.
Wait, we have to talk about the hookworms. You mentioned that earlier. People are actually doing this?
It is a real area of study! The idea is that if you give the I-G-E antibodies an actual parasite to fight, like the hookworm Necator americanus, they stop bothering your lungs. Clinical trials have shown that a small, controlled infection can actually dampen allergic inflammation. It is like giving a bored dog a chew toy so it stops eating your sofa. We are not quite at the point where you can pick up a pack of hookworms at the pharmacy, but it shows how much we are learning about the balance of the immune system.
That is the most Herman Poppleberry thing I have heard all week. But it underscores the point. Asthma is a misdirected defense mechanism against the outside world, not a self-destructive attack from within.
Right. Now, let us address the part of Daniel's question about other dysfunctional immune states. He mentioned lupus and M-S. We should also think about things like Celiac disease. Is that an allergy or an autoimmune disease? Because that one always confuses people. You eat gluten, which is an external protein, but then your body attacks your own intestinal lining.
Celiac is a hybrid, right?
Exactly. It is triggered by an external substance, gluten, so it feels like an allergy. But the actual damage is done by the immune system attacking the tissue of the small intestine. It is classified as an autoimmune disorder because the end result is the destruction of self. Asthma is different because, while it causes swelling and mucus, the immune system is not trying to eat the lung cells. It is just trying to create a barrier against the pollen.
So, if you removed all the gluten from the world, Celiac would essentially disappear. If you removed all the pollen and mold, asthma would essentially disappear. But if you removed all external triggers for Lupus, the disease would still be there because the trigger is inside. It is part of the code.
Spot on. That is the fundamental divide. And for Daniel, this is actually good news. It means that as he cleans up the mold in the house and uses his maintenance inhalers to keep the inflammation down, his lungs can actually stay quite healthy. He is not in a state of inevitable self-destruction. He is just in a state of being very, very picky about his air quality.
Alright, let us break this down into some concrete takeaways for Daniel and everyone else. Because we have covered a lot of ground here from hookworms to the Judean hills.
First takeaway: Asthma is an allergic or atopic condition because it is a hypersensitivity to non-self substances. It is an overreaction to the world, not an attack on the self. This is why it is not classified as autoimmune, even though the inflammation looks similar. It involves T-H-two cells and I-G-E antibodies, which are the parasite-fighting specialists.
Second: The classification matters for treatment. Allergic conditions are managed by avoiding triggers and using localized anti-inflammatories or biologics that target specific allergic pathways. Autoimmune diseases require broader, more systemic immune modulation because the target is everywhere.
Third: The rise in these conditions is likely linked to our modern, ultra-clean environments and the breakdown of our epithelial barriers. Our immune systems are bored and twitchy, and our internal fences are leaky. Getting outside, being exposed to a variety of natural environments, and avoiding harsh detergents can all part of a long-term strategy for immune health.
And fourth: Classification is evolving. What we call asthma today is a broad umbrella. As we get better at looking at specific biomarkers and using A-I, we will be able to tailor treatments to the specific type of immune dysfunction each person has. We are moving toward precision medicine where we know exactly which riot we are trying to stop.
I think that is a solid summary. It is really about changing the perspective from my body is broken to my body is trying too hard to protect me from things that do not matter.
I like that. It is a more compassionate way to look at your own health. Daniel, I hope that clears up the confusion. You are not undergoing a civil war; you just have an over-eager security guard in your lungs who needs to be told that mold is not a lethal invader. Though, to be fair to the security guard, mold in the house is actually something you want to get rid of. The guard just does not need to choke you in the process.
I will bring the high-quality respirators for the cleaning project.
Good call. Well, this has been an enlightening deep dive. If you are listening and you found this helpful, or if you have your own weird prompts about how the human body works, we would love to hear from you. You can find us at myweirdprompts.com. There is a contact form there, and you can also find our full archive of over four hundred seventy episodes.
And hey, if you have been listening for a while and you enjoy these deep dives, please take a second to leave us a review on your podcast app or on Spotify. It genuinely helps other curious people find the show. We are trying to build a community of people who like to ask the why behind the what.
Absolutely. It makes a huge difference for us. Thanks for joining us for another episode of My Weird Prompts. I am Corn.
And I am Herman Poppleberry.
We will catch you next time.
Stay curious, and breathe easy.
That was a bit cheesy, Herman.
I have been waiting the whole episode to say it.
I know you have. Alright, let us go find those respirators.
On it. See you everyone.
Bye.
One more thing, Corn. Did you know that the word asthma comes from the Greek word for panting?
I did not, but I am entirely unsurprised that you did.
It is all about the etymology.
Of course it is. Let us go.
Going!
