Gerald B. Lee, MD (Host): Hello everybody, and welcome to another episode of Allergy Talk, a roundup of the latest in the field of allergy and immunology by the American College of Allergy, Asthma, and Immunology. For today's episode, we'll be reviewing articles from Allergy Watch a bimonthly publication, which provides research summaries to college members from the major journals in allergy and immunology.

And you can also earn CME Credit by listening to this podcast. For information about CME Credit, head over to education.acaai.org/allergytalk. And also make sure you check out the Doc Matter community where we can continue the discussion about these articles.

Well, hello again. My name is Gerry Lee. I'm an Associate Professor at Emory University and Assistant Editor of Allergy Watch. And today, once again, I'm joined by Editor-in-Chief of Allergy watch, Dr. Stan Fineman.

Stanley M. Fineman, MD, MBA (Host 2): Thanks, Gerry, and it's great to be here. I'm a past president of the college, and as Gerry said, Editor-in-Chief of Allergy Watch. I'm also an adjunct faculty at Emory.

Gerald B. Lee, MD (Host): And for the third chair, once again, we're joined by Dr. Sarah Spriet, a staff allergist immunologist at AT Augusta Military Medical Center and Associate Program Director for the AI Fellowship at Walter Reed, an Associate Professor of Pediatrics at Uniform Services University, and an Assistant Editor of Allergy Watch.

Sarah, welcome back to Allergy Talk.

Sarah Spriet, MD: Thanks for having me. Great to be here.

Gerald B. Lee, MD (Host): Okay. We have three more very interesting articles, and Sarah is going to start us off. Looks like we're going to have expanding more options for our allergic children. So tell us about it.

Sarah Spriet, MD: Here's hoping. If you're like me, you take care of a lot of kids with allergic rhinitis, and conjunctivitis. And so these authors in Europe, brought us a pivotal phase three trial entitled The SQ tree, Sublingual Immunotherapy Tablet is Effective and Well Tolerated in Children. And this was published in Allergy in September, 2024. And published by Gappa and Colleagues across multiple centers in Europe. So this phase three trial studied the safety and efficacy of a SLIT-tablet containing standardized BET. So a birch allergen in 12 SQ units. Over 950 children, ages five to 17 years with moderate to severe allergic rhinitis or allergic conjunctivitis were randomized one-to-one to treatment with daily SLIT-tablet or placebo for up to 52 weeks.

The primary endpoint was average total combined score, which is determined by their daily symptom score and their daily medication score. And that was recorded via electronic diaries during the study trial. These scores were recorded both during birch pollen season and the entire tree pollen season.

And the researchers analyzed the scores for the entire tree pollen season as a secondary endpoint. And so what they found was a significant reduction in the total combined score for the treatment group with 22% relative reduction compared to the placebo during birch pollen season, their primary endpoint.

They also found a 19% relative reduction in total combined scoring for the entire tree pollen season. The tablet was well tolerated with only mild local site reactions reported, and the safety profile was similar for those children with and without asthma. So the main takeaway from this was if this does become available to our patients here in the United States, it would certainly offer us a safe and convenient option for the young patients with allergic rhinitis or allergic conjunctivitis due to birch pollen, homologous groups of trees, and it would improve quality of life and potentially prevent disease progression. So very, very exciting and would be great to add to our armamentum for these pediatric allergic rhinoconjunctivitis patients if it becomes available.

Stanley M. Fineman, MD, MBA (Host 2): I, agree with you. I think it's a lot easier for children to take something sublingually, than it is to get a shot. There's a big pushback for the shots, obviously. But you said that this was a pivotal trial in Europe and it looked like the total symptoms score improvement was like a 29, 21.9%.

So would that, I'm not sure what the confidence interval was but would that, you think it would be approved by the FDA here for our kids in the United States?

Sarah Spriet, MD: That's a great question. Gerry, you have any insight on that?

Gerald B. Lee, MD (Host): Oh, goodness gracious. I'm not sure of the threshold. But, certainly there is a gap in this population, so I would imagine that information is going to be useful when they're going to seek FDA approval in the United States. I guess my question is, if I think back to my population, I don't see a lot of patients that are mono sensitized to birch.

So I guess I always struggle with that. I'm curious, how often have y'all given sublingual to poly sensitized patients, and what's been your experience? I can tell you that and, and this is biased, so I haven't tried, but the patients that who have been mono sensitized, for example, I remember someone who had, was on like five drugs during the summer, and she had, Timothy grass allergy. I put her on sublingual Timothy grass, she was off zero. Like she was on nothing. Like it was amazing. But I don't have very many patients like that. Most patients are off for like five or six pollens. So what you all been experience with poly synthesized patients? Have you tried it before?

Stanley M. Fineman, MD, MBA (Host 2): So I've used it off-label and that's the thing we have to qualify because, sublingual immunotherapy except for the tablets is really off-label, here in the United States. And I remember, a debate really in the college meeting a few years ago. And what came out of the debate was the fact that we were basically presenting some of the data that we developed for some of our sublingual patients that we're using poly sensitized, sublingual immunotherapy.

And the problem is there are other studies that show that it didn't work when it was, they were poly sensitized and there were multiple allergens in the sublingual solution. So the problem is there's really no good data. There's no good study like this, showing a very good positive effect on your total symptom scores, with multi sensitized sublingual, treatment.

So that I think is our problem. And I guess we're using it off label. And that's a challenge in and of itself too.

Sarah Spriet, MD: But I think if we can find the younger patient who it's only oak or birch, which granted, to your point, it's going to be case by case, right? It, which is typically my SLIT-tablet patients are the exception. They're not the majority that I take care of, but if we can prevent that progression to poly sensitization, and I actually find the five or 6-year-old who it's only oak and birch pollen allergy right now, that's probably the optimal patient to start this in based on, the reduction in symptom scores. But I also recognize that that's far and few in between patients that I'm going to find who are mono sensitized to that birch homologous, tree induced allergic rhinitis, conjunctivitis.

Gerald B. Lee, MD (Host): And maybe I'm being a little closed-minded or restrictive. So I mean, that's where the email's for. So anyone listening, if anyone has experience with something like grass pollen, when you have both tree and grass pollen allergy, and you want to tell me your experience. I'm just so curious.

 I think that certainly we are huge believers in desensitization. Like why not get to the root cause rather than just using medicine to control the symptoms. If we desensitize and try to get them off medicine. I mean, the patient wants that, we want that. It's just, I guess we have this idealism that we gotta hit everything by doing multi allergen, but if a single allergen immunotherapy gets them the majority of the way there, I don't want to withhold that or present it in a negative light. And so anyways, that's just my curiosity. I'm just, again, maybe overly skeptical, but I'm willing to learn, I'm willing to consider it for sure.

Especially if it's going to avoid a kid getting an injection.

Sarah Spriet, MD: I think it's shared decision making like so much of our practice, right? So I have started a few poly sensitized patients on the single SLIT-tablet to grass or to dust mite, but I certainly present the pros and the cons of that approach and come to that shared decision making with the patient.

Gerald B. Lee, MD (Host): Alright. Yeah, great point. Let's go to the next article. So, Stan, I get whiplash hearing about cat and dog and early and late and that sort of thing. So I don't think we'll ever have like the definitive study, but you have a very interesting article that adds to the conversation. So what did this study teach us?

Stanley M. Fineman, MD, MBA (Host 2): Okay, so this was a study that was published in our annals of Allergy in November of 2024. It was entitled Persistent Cat Ownership and Asthma in a Longitudinal Study in Puerto Rican Youth. And, it was basically, a study where they were trying to see the effect of having cat or dog exposure during their childhood, how it impacted their childhood asthma.

It was a prospective study. It was really done in two different prospective studies. One was the prospective study of Puerto Rican youth and asthma or called the Propa Study, which the participants were visited during their first visit between ages of six and 14, one was Progo and one was Propa. Anyway, the bottom line was, the second one was the epigenetic variation in childhood asthma, and that was, they looked at those kids in February of 14 through 17. The other one was in 2009 through 2010. So they were able to look at the children when they were younger and when they were older, just by a few years. So, the first one, the baseline visit ages were six to 14. The second visit the ages were nine to 20. And then they, through a questionnaire, they asked were they exposed to a cat or a dog during the whole time that they were either an infant, even in utero, and, did that impact the existence of their asthma? And interestingly, the children who had a cat, both, during the early life as well as when they were older in school, had a 68% odds lower, or lower odds of having asthma compared to children who never owned a cat at all and having a cat in one stage only was not associated with asthma and neither was dog ownership, which, I thought was a little bit surprising. So the only statistical association found between dog ownership in school aged children was having a positive IgE test to dog allergen. And so that's what they found there.

But, the bottom line was that this, statistically they, through their various analysis found that the 68% lower odds of having asthma in school age when the children were continually exposed to a cat, I thought was pretty unique. Now, when you look at some of the e study data, the electronic tables, and you look and see the amount of allergen in the sensitivity, the sensitivity to the dog was much higher, than in the cat. It was almost double. So the, specific IgE to, uh, dog was in the early life, 22% had it in one and 16% had it in the other. And for the cat was 11.8% in the early life, in school age, and only 6.4 who had never been exposed before at all. So, they were trying to use a statistical analysis to figure out whether this was significant and they were able to find the significance.

Now, does that mean I'm going to tell my patients to go get a cat? No, I'm not, because I don't think that's really a helpful thing.

Gerald B. Lee, MD (Host): Yeah.

Stanley M. Fineman, MD, MBA (Host 2): I'm even going to tell them to get a dog. Even though there've been other studies that showed that having a dog or having two dogs seemed to reduce the risk of asthma when you were a child.

So this is just another study trying to prove the hygiene hypothesis and anyway it's a little complicated when you look at the statistics, but I thought it was interesting. Because I'm a big fan of the hygiene hypothesis, and I always like to look at studies like that.

Sarah Spriet, MD: I'll just say that I appreciate that they controlled for some of the socioeconomic variables in this, including household income, even body habitus and unhealthy diet, which I think are important factors to control for when you're doing a multi-variable analysis. I would've liked for them to also maybe assess the dust mite sensitization in this group too. They collected dust samples to look for the pet allergen levels, but I think that would've been a useful factor to also include in their analysis.

Gerald B. Lee, MD (Host): Stan, did any of the patients have both or was these like exclusive sort of things or they didn't even get into that? I'm just curious.

Stanley M. Fineman, MD, MBA (Host 2): I don't think they got into it. They did separate like they found that statistical, at least for dog ownership when they were older and they also had a positive IgE, that seemed to have some benefit as well. But.

Gerald B. Lee, MD (Host): And it wasn't like the quantity, like they didn't say like how many of each animal and stuff like that too. Right? Because I've seen that too, like multiple pets and stuff like that. I guess they didn't do that either, right?

Stanley M. Fineman, MD, MBA (Host 2): No. You know, it's interesting. I didn't, notice that. I don't, remember seeing anything about the number of cats or the number of dogs in there. They did talk about the amount of can levels in the dog annal allergen levels in the homes and cat levels in the homes.

But they didn't look at dust mite, unfortunately, like, Sarah was suggesting. So there's some deficiencies in the study, but again, I'm just a fan of hygiene hypothesis studies and this is just another one.

Gerald B. Lee, MD (Host): Yeah, just taking a peek at this article. I can say that the numbers are on the small side. So for example, again the number of people who owned a cat early in life, who had asthma was like 11 versus nine, and for dog it was four. Yes. Early life. One, not in early life, and I'm not saying that that's going to move the needle, for both. It was like more, the numbers were more robust. But for cat ownership, the persistence was defined as both early life and school age, I believe. And I can see it was only 13 for asthmatics and 10 for non asthmatics. So I'm wondering, and again, I can't prove this, could this just be a function of just low N? Once you get like small numbers, these differences get magnified that kind of even out when you get big time N. I think we just were waiting for that study. We're waiting for a study that has. I mean, that's what going to seal the deal, like big time numbers, like thousands of people.

Which is going to be really hard to do. So yeah, I think the low numbers, I'm concerned about this study at least. But again, I think ultimately, no matter what I say, people are going to have their pets. So I think, if you ask me how many people have rehoused the animal based on what the allergy does, I would say very few.

Overall, like it's like you're like your own kid. It's like your own child. We're not like orphan your own kid, you know, that sort of thing. Okay. Alright, so that's a tangent. I apologize. Okay, so let's wrap it up. And I really enjoyed reading this report sponsored by FARE Food Allergy Research Education.

This was published in Journal of Pediatrics. The title of the article is Awareness and Application of United States Food Allergy Prevention Guidelines amongst Pediatricians and other Clinicians, which was the most interesting part of this. That's what I really liked about the study. The other clinicians, when they get to that in a second, so we are all aware that after the LEAP study, the National Institute of Allergy Infectious Disease had the peanut allergy prevention guidelines. We're aware of the three risk groups, no eczema, mild eczema or moderate to severe, and the timing of introduction, and you ask an allergist, we are all in, but guess what? We don't see these babies. We don't see these babies.

These babies are seeing generalists. They're not seeing specialists. I mean, they've referred to us. They'll still see them. So the frontline are generalists. And let me tell you, they're all over the place, right? We're a very small specialty, right? There's way more pediatricians and family physicians, and what this study particularly looks at, is advanced practice providers. They are talking about nurse practitioners and physician assistants, and so in addition to pediatricians, family medicines and APPs, they also included dermatologists, who also treat eczema and are clearly are going to be asked, is this a food allergy? I mean, they're going to be asked that question.

You know, they are, right. So the purpose of this study is asking are they aware of the guidelines? How often do they adhere to the guidance and the barriers? Because wouldn't you know it, it's not often implemented. So let's talk about this. So they were able to use a third party company to recruit 250 of each group pediatricians, family medicine, NPs, PAs, and dermatology, about 250 of each.

And they did an online survey, asking a couple things, right? And they had about an 8% response rate. So, first question, are you aware of the 27 peanut allergy prevention guidelines. Pediatricians 76%, dermatology, 58%, family medicine, 52% APPs, 45% less than half. And interestingly, when they're looking at the distribution, APPs were more likely to work in hospital, community clinic settings and had the highest level of rural representation. Right. So I think there's like an access issue too, where we want certain, specialties at the front lines here, where some people can't get access of specialty care. And so we rely on certain types of clinicians to provide medical advice.

So when they looked further into some of their implementation, they gave the three scenarios right out of the guideline. They presented a infant with no atopic dermatitis or food allergy. They presented a infant who had mild eczema or a third child with severe eczema or egg allergy, ie the high risk criteria according to the NIAD and interestingly, when you ask about peanut, would you recommend peanut introduction?

For the lowest risk group among dermatology, 41% would recommend peanut introduction, aPPs, 60%, family medicine 54%, lower than APPs, right? Pediatricians, 84%. I love it. I love it. I love it. I love it. All right. These are ones aware of the guidelines. I'm just choosing the ones aware of the guidelines, alright?

Let's go to the high risk group, right? So let's, we're talking about those who have severe atopic dermatitis or egg allergy. Would you recommend some sort of, intervention like referral to allergy, let's say referral to allergy; pediatricians 63% ,family medicine 51%, APPs 68%, dermatology 54%. So not bad. How many would say, we should do some sort of testing, right? So order peanut specific IG test. Among pediatricians it's 16%, and amongst family medicine it is 20%. So what are some of the other interesting things I've noticed is that overall there was some barriers named for the implementation, for the guidelines and the number one barrier amongst most clinicians was the lack of clinic time, except for APPs. Their number one concern, and this was named by 53% of APPs, was a parental concern of allergic reactions as the major barrier, other than lack of clinic time and parental concern, other common top cited barriers will be amongst dermatologists legal liability 28%. And then lack of interest by the parent, and I'm not sure if that's perceived interest or real interest. And then 37% of family medicines were concerned about allergic reactions.

So not the parent but the provider. So I mean, if I wanted to sort of sum up the article, there are certain groups that are at the front lines of seeing these babies who are either not aware of the guidelines or don't give guidance that are aligned with the guidelines. And there are certain barriers that we're going to need to overcome beyond awareness.

Not just knowing the guidelines, but actually implementing it. And that's really addressing some of these barriers. And then again, I don't have a magic wand, but I attempted to do a quality improvement project in the Atlanta metro area about, early introduction and reducing inappropriate food allergy testing.

And I heard similar themes, regarding this parental concern and clinic time. And so some of the things that I attempted to do was give handouts and information and it's actually pre-reading. So like they could read it ahead of time and then like ask about it in the visit so you don't have to do all the teaching.

But the concern about allergic reactions was a difficult barrier for me to address, and I think when out of my interviews, the number one reason why food allergy testing was done and introduction was delayed, was eczema. And I think the core knowledge gap amongst most generalists when I was talking to them is actually most generalists don't know why eczema happens.

And the interpretation of eczema as a manifestation of food allergy, like food allergy causing eczema is a very prevalent belief when I was talking to generalists. And I even met a graduating dermatology resident, I sat down with her and I asked her, could you tell me why eczema happens?

And I, think she's told me something about T 2 inflammation or something like that, which is, I'm not saying it was wrong, but like the core defect of a skin barrier dysfunction, I mean, did not even come up. So even amongst dermatologists, just the core explanation of explaining to the parents the intervention of eczema as a skin disease and not principally what you're eating right, it's more of like skin management is a significant knowledge gap, and we're going to really need to address that knowledge gap if we're going to move the needle because the scenario that these generalists are seeing, in my opinion, at least in my experience, is they're coming in and the parent is either worried, so they're worried about risk, so we have to do reassurance about the safety, but also misinterpreting things that they're seeing as food allergy and therefore has fear or uncertainty that we need someone confident to explain what is happening, ie it's not IG mediated. And then also, maybe this manifestation increases the urgency for introduction. Actually, the response to this of the presence of eczema is not removal. It's actually introduction to protect the child, which is sort of like a paradigm shift and a different approach where parents who request testing or come in with testing with eczema.

My response to that testing is, okay, well, your child at risk for developing food allergy this, we have to get into your kid. Like, I want to protect your child. They don't show me that test of like, we better take this out to just make your eczema worse. I'm like, we gotta fix the eczema, get the food into your kid.

So we fix the eczema and protect your child. So until we get there, we're going to see studies like this, and I think we need sort of national educational efforts to do this. Now, I did present the QI project that I did, and I, I have to say that it didn't work that great. I would say that I still do work on it.

We reduced the percentage of practices doing panel testing for eczema, but the number of tests kind of stayed the same because certain practices are heavy utilizers. So the next phase is to, buy them lunch and be a drug rep and talking about that. So I'm working on that right now. But anyways, sorry for the long-winded speech, but I just, just thought it was very interesting.

We have APPs, dermatologists, family medicine doctors who have lower awareness than pediatricians. We have to reach out to those groups and equip them to handle these conversations.

Sarah Spriet, MD: Totally agree. You are preaching to the choir. I think this study reaffirms what you're saying, Gerry, and what we're seeing in our practices. And my biggest concern is because of this knowledge gap, it's leading, as you said, to further delays in introduction to these high risk groups. So I don't think we're going to answer the challenge in this short discussion today, but I think studies like this are valuable in that they're validating our experience and really reinforcing the need for the process improvement, the quality improvement initiatives that you're speaking about.

Stanley M. Fineman, MD, MBA (Host 2): Yeah. I'm really glad to hear that you did that study as part of the college and, presented it there. It's very disconcerting to me to see how many advanced practitioners were involved in this study. There were double the number of any of the specialists or at least, or generalists, pediatricians, family practitioners or dermatologists.

But, and the fact that they had such a low understanding of the guidelines, you know, it really concerns me because obviously they're swayed by the public. The public wants to put some kind of, uh, a cause for their kids' eczema. And the cause that the general public thinks is that it's a food and we need to somehow or another figure out how to switch that paradigm.

Gerald B. Lee, MD (Host): So if y'all have an idea on the best way to deliver medical education, maybe you are a secret influencer or maybe just a master of persuasion or medical education. I would love to get your thoughts. Let's collaborate. You could email me directly at Emory, but also you could email the allergy talk email.

That's allergy talk@acaai.org. Of course if you have any feedback or corrections, further thoughts, I'd love to hear from you and remember, by just listening to this podcast, you can get CME credit. Just go to education.acaai.org/allergytalk, and you could also read archive issues on the same website. That's college.acaai.org/publication/allergywatch.

Well, I enjoyed the conversation. I learn every time I do this. Sarah, thank you, Stan, thank you. And y'all, thanks for listening. We'll catch you for the next one. Have a good one.

ACAAI 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, professionals, services, or methods that might be referenced.