Gerry Lee, MD: Hello everyone, and welcome to another episode of Allergy Talk, a roundup of the latest in the field of allergy and immunology from the American College of Allergy, asthma and Immunology. this episode, we'll be reviewing more, articles from Allergy Watch a bimonthly publication, which provides research summaries for the latest journals of allergy and immunology.

And you can earn CME Credit by just listening to this podcast or our new thing, a video podcast. To get CME credit, go to education.ac ai.org. And again, if you're listening to some audio, please visit our YouTube channel. youtube.com/at sign allergist. And of course, we also have the ACA AI Committee on Doc Matter, where we can continue the conversations about the articles review today.

Hello everyone. My name is Jerry Lee. I'm an allergist immunologist at Emory University, and I'm an assistant editor of Allergy Watch, and I'm here joined by the editor-in-chief of Allergy watch, Dr. Stan Feinman.

Stanley M. Fineman, MD: Hello again, and thanks for having me. for the next, one more month, I'm going to, I'm the editor in chief of Allergy Watch and I'm gonna be turning it over and we'll talk about that a little bit later to Dr. Josie. and, I'm also an adjunct faculty at Emery and I've been in allergy practice for over 45 years.

Gerry Lee, MD: And for the third chair, we're excited to be joined once again by Dr. Sham Joshi, an associate professor and section chief at Oregon Health and Science University and Associate Editor. Soon to be editor-in-chief of Algae. Watch Sham. Welcome back to Algae Talk.

Shayam Joshi, MD: Thank you so much for having me. I'm really excited to talk about some articles today.

Gerry Lee, MD: Okay, well, I could not think of a better way to kick off our inaugural video podcast by these three so interesting articles. Stan, we have to start with you. We're on this technology theme, so let's talk about ai. What do you got for us? I,

Stanley M. Fineman, MD: So this was a, fascinating article that was published in the Annals of Allergy, earlier this year, and it's entitled Can Chat, GPT Provide. Parent education for oral immunotherapy. and it's from, Canada, from Montreal. And what they did is they did, a questionnaire. They took 14 common questions and parents have regarding oral, immunotherapy.

This is food. Now food oral for food allergy. And they entered them into a chat, GPT specific version, and they then categorized the responses that the chat GPT made for either basic, advanced or medical. And then they had, allergy immunotherapy, healthcare practitioners, professionals from the North America, and even some from the United Kingdom.

We were reviewing their responses and they measured them basically on a 10 point Likert scale, and they checked for response readability for understandability, for reproducibility. And these were all, assessed using, something called a Flesh Reading Ease, scale, And also a Flesh King card, grade level score. and, these are basically tools that can, estimate at what grade level and how complex the answer is in terms of.

Trying to understand it. we all know that, we're all doing oral immunotherapy now for food allergy. we know parents have a lot of questions. we know everybody's busy and unable to spend the time that, we'd like a lot of times, to try to help the patient's answer questions. And of course, a lot of times parents are just going to Google and, chat GPD to ask them the questions to find out themselves.

So, This is a real. a real happening here. And I thought this was a fascinating attempt to try to, quantify, the responses And so what they did. Okay. Let me, talk about the results here. So basically the results, the 14 questions And the questions included things like, what is oral immunotherapy, how effective is immunotherapy?

how does it progress? can you do multi allergen immunotherapy? And then those were basic type que or those were basic questions. Then the advanced questions were, what happens if my child misses a dose of immunotherapy? Or, can we do multi allergen immunotherapy? Then medical questions were categorized as things like, will oral immunotherapy worsen my child's eczema or asthma, or can my child eat a normal diet?

During oral meth therapy, You know, Those are type, medical type, questions. So Those are the three categories that the, authors separated the questions into. And then they, ran it through their chat, GPT and had the, experts, read the, responses and evaluate on a Likert scale. what it was like, And the bottom line was that the basic advanced and medical were really within a similar mean ranking of a 8.6, 8.4 and 7.8.

So they're all pretty similar. The length of the responses varied between 450 words to 650 words, which is obviously a lot and. the bottom line, and I don't want to go through all the numbers here because too complex. It's, we're just, talking about this, but they, the, they ba basically had multiple comments suggesting that the chat GPT response was repetitive, was long-winded and had information overload So, It wasn't that it was that incorrect.

In fact, it was correct about 80% of the time, roughly, but it was just. Repetitive, long-winded and had information overload. They also checked the readability. we mentioned that a specific score, they felt that there was low readability scores because it corresponded with a very high grade level, the responses.

So the responses grade level were between. 13 to 17 years of education, which is pretty high when we consider, a lot of times when we write instructions for our patient's, we try to keep it on a, sixth grade level, which is like the normal newspaper. then the Understandability was another one I thought was interesting.

The understandability scores were between 73 and 84%. So, And then in terms of similarity, those were between 80 and 90%. So the bottom line was that the medical specific questions, including the ones including diet and adverse results, they received the lowest scores for chat, GPT. And, the other problem was the fact that it was not that readable.

It was too complicated so what the authors concluded was that there are significant barriers to implementing AI as a formal tool in medical education right now. And that chat, DPT may have some potential in the future as an assistant, to assist, patient education. But right now, it's not ready for prime time.

And the results, as I said, 80% of the healthcare participants recommended, that even though 80% recommended the use for patient education, it still has a long way to go. So, I, still think the human touch is important and, I think that's what we lose when we do too much with ai.

And I'd be interested in y'all's comments.

Gerry Lee, MD: I think my first comment is it, sounds like they talked to the physicians who knew what they were reviewing and not the patient's. Is that right? Stan?

Stanley M. Fineman, MD: That's correct. They did not talk to patient's. they only were talking with, physicians And so, well, I shouldn't say they, I don't know what, they said healthcare providers, allergy specialists. So I don't know exactly their education. That wasn't.

Gerry Lee, MD: get where this paper's coming from, but don't know. I, think I'd be interested what the patient's think, like when they get this information, maybe they like that or they have the opportunity to ask follow-up questions to clarify. I think the third issue is that, even this paper, I think it was using 3.5, chepe, 3.5 is so much different from the latest metal at time.

We're recording, we're in like. I think GPT five now. So I personally notice a large difference over time, and I would assume that most caregivers are just not gonna ask one question. They're gonna have a dialogue. So ultimately, Stan, I'm not saying that I don't appreciate the human touch either.

Absolutely asking someone immediately versus like, sending on my chart and getting a message back. I don't know. Patient's might prefer that. Sam, are people using AI in your clinic? What do you, what have you

Shayam Joshi, MD: Yeah, the, I think what makes this really challenging is OIT is done so differently at different clinics, at different hospital systems, And what the ChatGPT is learning from are, is what's available online. Right. So if, if certain clinics are publishing some stuff online or the very few papers that are not behind a paywall that are being accessed, Those are all what ChatGPT is learning off of.

And there's gonna be difficulty because all the protocols are slightly different. All the kind of, what are you gonna do if you miss a dose? What do you do if you have a reaction or slightly different, which I do think complicates how ChatGPT is synthesizing the information and, pushing it back out.

I'm wondering if. In the future, if we're able to retrain a specific AI model with a certain set of documents that are, let's say, most frequently asked questions or everything you can know about one OIT protocol, and you ask that system, that seems like a much more usable, method, whether the college does that or whoever to create a, packet of information that you can learn off of, that seems like a much more usable.

Tool for ai. cause right now I do think hard when you have so much alternate information out there that chat gpt is learning from.

Stanley M. Fineman, MD: Yeah, I think you're right about that. And, in fact, I look back, Jerry, this was the free accessible version from April, 2024. So wasn't that long ago, but uh,

Gerry Lee, MD: was a long time ago in AI terms.

Stanley M. Fineman, MD: Okay, well, I guess it was anyway, and I do agree with Sham. I think that, unless you're using some sort of a standard guideline or standard type of protocol, then that would be, uh, challenge.

Gerry Lee, MD: right, well we're definitely gonna hear more about this and a, again, I think I agree with everything we're saying. We just want our patient's to get accurate information that's evidence-based and aligns with the treatment plan. So. We continue the partnership between physicians and patient's, and I would love AI to help us with that and not make that more challenging.

Well, anyways, let's just go to the next article. And Sharon, we continue to try to educate, our, patient's as well as our colleagues about anaphylaxis. And it looks like there was this attempt to try to harmonize all these different guidelines. Tell us about it.

Shayam Joshi, MD: Yeah, I think This is a really important paper for everybody to be aware of. as stewards of patient's with anaphylaxis and understanding anaphylaxis. It is. Is our job to talk with other specialties, especially our er, urgent care, brethren that understanding really how to define anaphylaxis in a way that's easy for clinicians as well as patient's is key.

so this was, the title of the paper was Anaphylaxis Definition Overview and Clinical Support Tool, the 2024 Consensus Report. And so this was an international consensus guideline from about 46 members. International expert panels. These are from around the world, really, the experts in anaphylaxis. but what was unique about this was that they didn't just include experts.

They included 31 medical, stakeholder organizations, and probably most importantly, they included 15 patient advocacy organizations. Because when we're take putting this information out there, if patient's can't understand it, and it's not important to the patient's. It's, there's a lot of limitations around it. And so why they decided to do this was that the kind of classic or traditional way that we look at anaphylaxis was, first by the N-I-A-I-D, And the food allergy and asthma network definition.

This consensus definition came back, came out in 2006 and was great. It was very important for harmonizing how we think about anaphylaxis. How we use anaphylaxis in terms of research. but it had some holes in it. And so in 2020, the WAO, the World Allergy Organization, they created a updated criteria.

and they changed how we thought about it. It was always in three kind of categories of, unknown ingestion, likely ingestion and ingestion of a known allergen. What the WAO did was that they actually. Narrowed it down to just two criteria. So they had skin symptoms plus some other secondary organ system, or they had known or likely allergen exposure plus respiratory, see, cardiovascular, GI symptoms, but didn't really have to have the cutaneous manifestation.

While in theory that's great, but now we have two sets of anaphylaxis criteria. And that's a problem. so patient's are getting a little bit more confused. We're when you're looking at research papers. Now some are using the original ANI a ID definition, and some are using the WAO definition.

And so it's even making it harder for us to compare research studies now. So this group got together and they're like, all right, let's use both of these definitions. Let's include lay people in this definition. and let's define it. Let's create an overview. This is not meant to be a practice parameter, right?

We just had our joint task force practice parameters come out in anaphylaxis. This is not meant to replace that. This is more of a, Hey, let's create a clinical support tool that patient's can use, that allergists can use, that ER physicians can use, primary care, can use a consensus that everybody can look at and be like, okay, This is how we're gonna look at anaphylaxis.

This is gonna. Help support the patient the best way we can. and really just to promote ease in clinical practice. And so what they did, I think the most important part about this entire article is they created this figure, it's figure two in the actual paper. so if you're pulling it up at some point, but it breaks it down into.

What defines anaphylaxis. And so they still stuck with the three definition, approach. So if you have no known allergen exposure And then you have skin plus some secondary organ system, or if you had likely or known allergen exposure and you had two or more symptom involvement, that's what we generally use.

And most of the time when we're thinking about anaphylaxis, there's two system involvement. And then there's also a third option. If you had known allergen exposure. And isolated respiratory or isolated cardiovascular involvement. And I like this. I think This is the N-I-A-I-D consensus guidelines is how we've, most of us have kind of been trained and thought about anaphylaxis, and I like how they still stuck with this three tier approach.

I think it's a visually put in a way that's really nice for ER physicians in urgent care to really be able to look at it and implement it. But beyond just the definition, they also have a portion in this figure that shows what's the treatment. And I love how they just put epinephrine.

They didn't put diphenhydramine, they didn't put steroids. They just put epinephrine here. And so again, This is something we see all the time. I don't know how it is in, in, in Atlanta, but oftentimes my patient's, especially kids with food allergies, they end up in the emergency room. They end up getting antihistamines, systemic steroids, maybe albuterol.

They get watched for a few hours. Things progress. They eventually get epinephrine like an hour and a half after they're in the ER instead of. Recognizing it is anaphylaxis and treat them for anaphylaxis, treat them with epinephrine. And so they just have this kind of red box in here.

The treatment is epinephrine. Here's the dosing, for manual and autoinjector and how frequently you can give it. And then the last bottom part is just looking at the organ systems And what symptoms specifically, constitute skin manifestations or respiratory manifestations or cardiovascular manifestations. And so. As allergists. I think This is something that we are very well aware of, but I do think This is an I really important tool when we, that we can use for patient's, that we can use for our colleagues, especially PPAR, colleagues that are gonna be seeing anaphylaxis more often.

so that's really the, main purpose of this. I think it's just something allergists need to be aware of and need to see this figure a few times. Just So, it could be disseminated appropriately across the medical field.

Gerry Lee, MD: one thing I wanted to add, sham is that. They actually help clarify some of the infant symptoms as well. I, think sometimes that's underappreciated where if you go by strict guidelines, the subtle signs of, especially someone who's not a trained pediatrician or has never seen infant anaphylaxis before may miss.

So I think that was also. Very good that they put that front and center in each specific organ system. and again, for those who want to be familiar with that, I think in the show notes we'll link that article and, I think that graphical, abstract or figure is just freely available.

I.

Shayam Joshi, MD: Yeah, I guess we can call that out really quickly on the podcast in case you can't see it, but the infant symptoms that they call out here are modeling. they call about, call it repetitive lip licking as a mucocutaneous symptom. They call out a horse cry in the respiratory and persistent and unexplained tachycardia in the cardiovascular side.

So these are all things that infants may display that, again, won't be caught with urticaria or kind of what do we classically think of anaphylaxis. But they do call it out in bold as some of the symptoms. So good call out Jerry.

Stanley M. Fineman, MD: Yeah, I think it's great that they did this. I mean, we've had trouble for years, as you mentioned, so that we could try to compare studies And also use of epinephrine. I mean, I recall when we, we're still trying to, get people away from using Benadryl as a first-line drug.

And now, fortunately This is just clearly states. Use epi. We're gonna talk on the next podcast about, different ways that people treated anaphylaxis. and we'll talk about some of the fact that, and a lot of times, especially in emergency rooms, they're not always using epinephrine as a first-line. so we can talk about that a little bit more, but, clearly There are, evidence-based, guidelines that, we can hang our hat on.

So that's good. Thanks for bringing it up.

Gerry Lee, MD: Yeah, making it simple, easy to read, clear. I think it hits all the boxes. So again, definitely, share that and disseminate with your colleagues. We highly recommend it. okay, well, let me just wrap up this, uh. Inaugural video podcast with just a really interesting article that hit the press a few months ago.

This is a study that, is entitled Cytal Leukotriene Stimulate Gut Absorption of Food Allergens to Promote Anaphylaxis in Mice. So this was published in science in August, and again, This is relying on mouse models. To explore questions that we think about in the field of food allergy, and one is that some people, even with IgE to food react and some don't.

And why is that? And there's probably multiple reasons, but they actually have seen this in mouse models of food allergy as well. So there's different genetic backgrounds and mice that you can purchase and, study. But they all respond differently to traditional allergen models. And the one That is most resistant to this classical oral, food allergy model where you would give an adjuvant, in this case, cholera, toxin, and some sort of allergen, like peanut or egg is, a background called C 57 black.

so they could do the typical ejection anaphylax action models where you do an injection in the peritoneum, sensitize them, they make IgE, And then they would have a reaction if you injected them again. But if you give them the food, they don't undergo anaphylaxis as opposed to other backgrounds.

So, so these investigators kind of wanna understand this, like, how is this, what's the difference? And maybe does that give us insight on the variability? Allergen responses amongst food allergen individuals. So, they show their model again. They give multiple doses of peanut plus an adjuvant like chole toxin and, we'll have little blood pressure cuffs on mice or anything.

So they look at temperature drops. So anaphylax is, usually measured by a drop in temperature when it occurs in mice. And so they did show that the susceptible strains did develop. Anaphylaxis And then the C 57 black mouse, even though injection, it causes anaphylaxis, it's resistant to the oral reaction.

And so they did this for genetic screen to try to determine what genetically is different about that C 57 block. What is their responsible gene or group of genes or genetic region? And they were able to localize. Using this for genetic screen, a specific difference that explains a lot of this resistance to anaphylaxis.

If they take it orally and it was di peptidase one, so what the heck is di peptidase? One. Well, back, back, back, back, back. And we all know that we're either studying for a b, AI or we took a b ai and essentially you may remember. In the leukotriene pathway, we have the Al Leukotrienes, LTCD and E, And the conversion of LTD four to LTE four is catalyzed by di Peptidase, And so these mice seem to have increased D di peptidase one activity.

Therefore much lower levels of the earlier Cissin, leukotrienes, LTC and LTD. And interestingly, if you were able, if you actually gave LTD four to these resistant mice, they have similar oral anaphylaxis like their colleagues. And then what they did was very interesting is then they administered anti leukotriene therapy.

Now, Lucas unfortunately only blocks one of the receptors cys sustain leukotriene receptor one. That didn't seem to do much, But when you go upstream and block five lipo oxygenase with dilutant, and you take out all the cysto leukotrienes, they actually had an impairment in this oral anaphylaxis. Even in the susceptible mice.

And the mechanism of That is really this oral absorption that the, food allergen is not trans litigating through the gut to cause a reaction. Now obviously a. All this was boiled down into a medial article that says is Z Lutin the Next Treatment for food allergy, which is obviously the title of this podcast as well.

And, certainly again, we're not saying that mice are human, that, we give color toxin to sensitize people. That's not what we're doing here, but. Interestingly, that just talks about then is there a potential role of cissin leukotrienes in the intestinal permeability, and is that one of the co-factors responsible for these variable responses that we're seeing with food allergy?

as you can imagine, they want to test this hypothesis in humans. There are some description of maybe human clinical trials to see does giving z lutin. When you eat a food allergen, modify your allergic response. I think that that's one of the questions they wanna see if they can bring this, translational project to the bedside.

But again, I thought it was a very intriguing article. It makes us think about, all the different factors of why two food allergy patient's with IgE to food react differently. And I think I'm looking forward to what we learned from this.

Shayam Joshi, MD: I love the idea how they're, we're trying to repurpose medications that we've used before. Right? I still use, I have a pretty large A ERD population And we still use diluting, not infrequently 'cause it does help in that specific population. 'cause we know they have increases the leukotrienes as well.

And so, I think this will be a very interesting, Option, especially if it can give selective ability to, like if patient's are traveling they need some level of protection for a short period of time versus our current options do take some time to kind of build up and provide that protection.

If, This is an option that they can take starting a few days beforehand or whatnot that be able to have some level of protection, be a great option for a lot of our patient's.

Stanley M. Fineman, MD: I mean, I agree and I mean, I remember using the X lutin, especially in our, aspirin sensitive patient's. and, this could be a repurpose, the fact that somebody's thinking about the mechanism of, the whole, cascade of. OB mediators, and I guess this, I'm gonna make another plug for allergy watch because, This is in the journal science.

I mean, allergists don't routinely look at that. And so I think that the fact that we're bringing this forward, for the allergists to know And the allergy community, kudos to Allergy Watch for, uh, doing that. And Jerry, you were the editor who brought that up. so kudos to you and, thank you.

Gerry Lee, MD: Well, social media brought it to me, so that's. I bring it forward to y'all. So anyways, well, again, I appreciate you listening and potentially watching our first, video and audio podcast if you enjoy what you're listening to or watching. Please rate us on YouTube. Please rate us on your favorite podcast app and maybe you have thoughts.

Please give us your emails, your comments. What do you think about AI and allergy immunology? What do you think about the potential of Z lutin for food allergy or even the new anaphylaxis guidelines? That email to contact us is allergy Talk one word@acaai.org. And just remember we have all these other episodes available for you to get CME on.

The website is education.ac ai.org/allergy talk. And of course, the published issues of Allergy Watch are archived on college.ac ai.org. Slash publications slash allergy wash. Well, again, I'm excited. I enjoyed this very much and I hope to see you for the next one. Everyone have a wonderful day.

Stanley M. Fineman, MD: Bye.

Shayam Joshi, MD: Take care.

Gerry Lee, MD: The A-C-A-E-I is presenting this podcast for educational purposes only. It is not medical advice. Or intended to replace the judgment of a licensed physician. The college is not responsible for any claims related to the procedures, professionals, products, or methods discussed in the podcast, and it does not approve or endorse any products, professional services, or methods that might be referenced.