Gerald Lee, MD, FAAAAI (Host): Hello everyone, 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 this episode, we'll be reviewing a few more articles from Allergy Watch, a bi-monthly publication that provides research summaries from the major journals of allergy and immunology.

And you can earn CME credit just by listening to this podcast.

For information about CME credit, head over to education.acaai.org/allergytalk and make sure you check out the ACAAI community on docmatter where we continue the discussion about the articles today. Well, hello everyone. My name is Gerry Lee. I'm an Associate Professor at Emory University and Assistant Editor of Allergy Watch, and today I'm joined by the editorial team at Allergy Watch. First the Editor in Chief, Dr. Stan Fineman.

Stanley M. Fineman, MD (Host): Hello again everybody, and it's great to be here. And, I'm also a adjunct faculty at Emory.

Gerald Lee, MD, FAAAAI (Host): And for the third chair, we have the Associate Editor of Allergy Watch, Dr. Shyam Joshi, an Associate Professor and Section Chief at Oregon Health and Science University. Welcome back to Allergy Talk.

Shyam Joshi, M.D.: Yeah. Thank you so much for having me again. Had a great time last time and look forward to our discussion today.

Gerald Lee, MD, FAAAAI (Host): Okay. We got a few more real interesting articles to review. Stan, we'll start with you. I think we all know how important allergy and immunology consultation is, but we actually continue to find data of the importance of our specialty. What have we found out, Stan?

Stanley M. Fineman, MD (Host): So this article is from the Journal of Pediatrics. It was published in February, 2025, and it's entitled The Association of Allergy Specialty Care and Asthma Outcomes for Medicaid Enrolled Children. And it's data collected by the Arkansas All Payers claims database to identify Medicaid enrolled children who had asthma who either saw an allergy specialist and they also had them matched with children who did not see an allergy specialist in 2018. And then they looked at their clinical outcomes regarding their asthma related adverse events such as emergency department visits or hospitalizations in 2019. So it's an interesting concept. What they're trying to do is to see if the intervention of seeing an allergy specialist made any difference in their asthma outcomes.

Now, one of the problems of this study, of course, is that they're using the payer's claims database. But one of the advantages is there was a large population, so the matched sample was 5,900 children, which is very large. And they were able to match the cohorts with a sampling that had similar asthma diagnoses, but did not see an allergy specialist in 2018, the year before their target year where they were looking at things. And this is a very carefully done study, I think, certainly big data. It's another advantage of big data. And the bottom line, was the fact that overall in an adjusted model, children who visited an allergy specialist had a 21% lower odds of asthma related adverse events compared to those children who did not see a specialist. Now, there were some other things that were interesting where they teased it out. They found that the children who were teenagers from 12 to 18 years of age, they were a little more likely to have inpatient hospitalizations compared to those that were younger and Black children, had an even, more challenging outcome.

They were more likely to be hospitalized and had ER visits, but when they saw an allergist, they also reduced their risk for having emergency visits or hospitalizations as well. Not quite down to the 21%, but still, you know, very significant and, there've been other studies that have looked at the care of patients by allergists for asthma and how it's reduced their morbidity.

And it's been reported over and over. But I think this is the first one that really looked at it with this big data numbers. And then some of the other studies that have been published previously also called it asthma specialist because it combined allergists and pulmonologists.

But this study particularly only focused on allergy specialists. They had very low pulmonology visits. It was only about 2.8%. So these were really asthma specialists. The other thing interesting about the asthma specialist is that there were higher rates of spirometry, 80% versus 18% who did not see an allergist, 6% had pheno measurements versus 1.2% who did not see an allergist and the use of controllers was double that for let's say first for leukotriene receptors was 4.1% versus 2.4. The use of inhaled steroids was 60% versus 40%, and the use of combined ICS LABAs was 12.9% versus 1.2%. So the patients who did not see allergist had way under utilization of the combo ICS LABAs. So there's some good reasons in terms of the prescription patterns and of course things that we know just inherently from seeing our patients. But, I think this is good data. I think it really supports the fact that what we're doing for patients is helpful and I'm glad it's in the Journal of Pediatrics and I hope that many primary care saw it so that we can see more consultations.

Gerald Lee, MD, FAAAAI (Host): I struggle with the question when a student or a resident comes up to me and say, so where should I refer my patient? Should I refer it to allergy or pulmonary? And you know, there's like this inherent conflict of interest, right? We want business. Right. And so I say that I'm very honest. I said, you know, all right, just let us recognize that you're asking me this question and you're asking an allergist.

So we clearly, we going to be very biased. But I think some of the aspects where subspecialty consultation makes us very unique amongst subspecialties is, number one, the unified airway hypothesis. I think in general we care about the entire airway. And so we are going to treat both their rhinosinusitis, and the asthma with intensity.

I think other subspecialties don't focus on as much. I think number two, exposure. I've worked with many pulmonary fellows who didn't even tell me what was in their home environment, and don't want to make a generalization, but I think, the attitude to just treat asthma as a disease with medicine, rather than the holistic approach where we think about exposure and doing testing to identify environmental control, I think is basically dogma in our specialty. Right. And then the flerma is desensitization, right? Where we do have the option if someone's on like eight drugs to treat respiratory allergy, to desensitize them and greatly decrease their medication load and, that is something unique that we offer. I think anytime a patient with allergic asthma is not aware that immunotherapy is even an option, is a shame. I'm not saying that all people should get desensitization, but I think people should know it exists.

It should be a choice for the care of your own child. So that's the pitch I give to students. I don't know if I'm being fair or not, but clearly if someone has interstitial lung disease or you know, bronchiectasis or something with complexity, I've definitely, I can't bronch patients. I'm going to definitely send them to pulmonary specialists, but for the unique disease of asthma, at least that's how I kind of see it.

I don't know Shyam, if you have any thoughts one way or the other.

Shyam Joshi, M.D.: No, I think that's spot on. We get students come and asking that exact question. Even residents are asking that exact question of where's the best place for this patient. And what we've done here in the Pacific Northwest is really trying to engage with the pediatricians early and often.

And so I think a huge asset to our field is allergists going to the community, going to local pediatric talks and conferences and being present. Just being there, being a sounding board for a lot of these pediatricians makes a big difference. Then they truly understand that just because it's the lungs doesn't have to go to pulmonary, it can absolutely go to allergy.

And the unique aspects, like you were saying, Gerry, about the immunotherapy and looking at the other environmental factors that are playing a role here. We do all that. We can do that and we can do some things that they can't do and they can do some things we can't do and we, are in a very collaborative relationship with pulmonary.

And if they do understand that and there's availability for pediatric allergists in the area, I think the referrals will significantly increase. And I think that's better for the patients. It's better for the population because we can take really good care of these patients. And just what Stan was saying, like there's data out there that we do a good job in this field.

Stanley M. Fineman, MD (Host): I think that that data needs to be presented and at least talked about when you go to these conferences. 20% lower odds ratio of adverse events is really major, I think. And, this study didn't even talk about allergy testing or immunotherapy, which is a whole nother tool as Gerry mentioned that we have that's been shown to really benefit patients with allergic triggered asthma, which most children have.

So, I'm glad that you're out there you know with the primary cares teaching them about what we do.

Shyam Joshi, M.D.: I would just say that that improvement that you're seeing just by seeing an allergist is almost the same as being put on a biologic, right? These, that is a huge, huge, huge benefit for just having that ability to talk to an allergist, let alone being on expensive medications, let alone being on medications for long periods of time, like just that conversation and being put on the appropriate therapies makes such a big difference.

Gerald Lee, MD, FAAAAI (Host): And on previous episodes of Allergy Talk, we have talked about the impact on exacerbations on future lung function. I think practitioners who've seen a lot of patients with asthma and at a point you sort of normalize the lifestyle of an asthma person of needing medical attention and the emergency department visits. I don't want to say anyone normalizes hospitalization, but it's sort of accepted as part of the disease and it is not, like we absolutely can achieve outcomes that normalize lung function. And yes, if a pediatrician has a checklist with a ton of stuff to get through, I mean choices are made about how to triage that precious visit time. And so therefore, subspecialty care, I think is available to make sure we are optimizing outcomes and asthma absolutely should be treated with the care that it needs because of the impacts on long-term lung health and so on. So I think for all the reasons, I'm so glad Stan you're highlighting this article and I agree we should absolutely be sending out this message.

All right, well, let's go to the next article. Dr. Joshi's got something also talking about how we should be achieving health equity when we assess them as a patients, because some of the tools that we're using may be misleading. So what have we learned?

Shyam Joshi, M.D.: This is a great article out of JAMA, Open Network and it was entitled Race Specific and Race Neutral Equations for Lung Function and Asthma Diagnosis in Black Children. And it was this multi-institutional study and thinking back about 2023 is when the American Thoracic Society came out and said, Hey, we've probably been doing this wrong for quite some time and using these race specific equations.

So when we're doing spirometry, we're thinking of gender, age, height, but also race and should we be thinking of race? And so over the past few decades, we've consistently seen this health disparity. Right. We've identified in pediatric asthma that Black children have higher prevalence of asthma. They have increased rates of asthma morbidity compared to white children. More exacerbations, more ER visits. And is not a simple answer, it's not a single thing that's causing this, but one thing that has been looked at, and that's what led to the ATS changing the recommendations is we're probably under diagnosing Black children because we're including their race in this equation.

And so instead of them being reported as having abnormal spirometry, we're saying, oh, they're actually normal because they're Black and they have a different equation than a equivalent white child. And so, The Global Lung Function Initiative, the GLI has been around for a while now and we've been using the GLI 2012 equation for quite a while.

And, we know that if we actually switch that to the more updated race neutral equation, which is the GLI 2022, that we're reclassifying a lot of people. We're reclassifying over 12.5 million Americans as either, oh, they do have lung impairment, or no, they actually don't have lung impairment. This is kids and adults. We're increasing classification for Black people from not having a lung impairment to having impairment by 141% by using a race neutral equation. And so this study specifically looked at three large cohorts and these are cohorts from back in the nineties to the 2010s.

And they have a lot of spirometry data for them. And so what they did was they took these cohorts, and the first one was the CAMP. It was the Childhood Asthma Management Program. We have the Cincinnati Childhood Allergy and Air Pollution Study, and the mechanisms of progression from atopic dermatitis to asthma.

There's about 1500 kids total, and they looked at their spirometry through the lens of using a race specific equation. So using race as part of the equation of determining is this normal or abnormal? Then they looked at them from a race neutral standpoint, so using the new equation, the GLI2022, and they said, what are the difference are we gonna see here? So outta the 1,533 kids in this three cohorts, about 20% of them were Black. They saw that using the race neutral equation, the FEV1 of these kiddos decreased by nearly 12 percentage points of predicted. 12. That is a huge, huge difference. 39% of the Black children changed from normal lung function, which they defined as greater than 90% predicted to abnormal.

So below 90% predicted. So they're saying 39% of these Black children who are in this study, who are high risk patients, whether they have asthma or are at high risk of having it, were probably incorrectly classified as having normal lung function. And so they may not have been treated appropriately.

They may not have been treated as aggressively, which obviously will lead to poorer outcomes. They also went further and looked at, okay, let's look at those kids that have asthma symptoms and what's the difference are we seeing here now? If they found that it labeled two and a half to four times more children that had asthma symptoms with having reduced lung function. So again, these kids that have symptoms and they come back with normal spirometry, clinicians are often like, oh, see how things go. But now that we, we could see that they probably actually have lung impairment, we're much more likely to step up therapy, much more likely to start therapy.

And so just being a little bit more aggressive in managing these kids upfront instead of this kind of wait and see approach because we thought their lung volume was not looking great. So I think this is really, hopefully more data, especially in the pediatric population. We have some similar data on the adult side, but really on the ped side to be like, we need to make this change and if your clinic hasn't made that change yet, really going forward and trying to make sure that we can make those race neutral changes so we can support this community better.

One major limitation to the study was that they didn't look at Asian populations, unfortunately. So it was really the Black population, the white population and, and how this change makes an effect, but we need more data on Asian children and what the effect will be for those kids specifically.

Gerry and Stan, have you guys changed from, uh, race specific to race neutral equation at your clinics?

Gerald Lee, MD, FAAAAI (Host): So I raised this issue when the ATS came out, two to three years ago, I believe. And interestingly, some of my group are like, well, why do we need to do that? And interestingly, a lot of the push came from respiratory therapists. Our respiratory therapists who are most up to date, definitely pushed our staff to meet the standard of care, and I have definitely seen what you've been talking about, Shaym. Like in my office, I have seen children, Black children who have like FBCs of like 110 or 115%. And so like their FEV1 is like higher too, right? But if you actually look at their ratio and you look at that delta, that FEV1 are 80% based on that reference equation we used, if you actually used like a white specific equation or race neutral equation, the FEV1 one drops before 80% very easily. But we're talking about ratios of like in the sixties, like high 60-70%. So in my mind, first of all, I think the FVC-FEV1 ratio is the most unbiased measure you can take at any patient, right?

 You're comparing two parameters specific to the patient, and that's not against a reference population. You're comparing to the own patient. You can't mess up that. If someone has significant obstruction, you're going to pick that up. Alright? I don't care what the percentage predicted is of the FEV1.

If someone has intrinsic obstruction on a ratio, we need to treat that patient. Our goal is to normalize lung function in these patients, like that is our goal. So I think that was a lesson I learned very early about how it's very misleading to use these absolute, oh, anything 80% or above is fine, right?

Not necessarily. We're using the wrong equations and I don't know. I, personally have switched a lot to the ratio because of that. That was the lesson I learned. Stan, I don't know your practice has been interpreting PFTs.

Stanley M. Fineman, MD (Host): No. I also, you know, recently has changed over to the, looking at the ratio, but I was going to ask Shyam about, I think it's a challenge for the community-based allergists to incorporate these new percentages, the corrected, percentages and obviously we all see why they need to be in your interpretation. But I'm not sure how easy it is for them to do that with their equipment.

Shyam Joshi, M.D.: Yeah, I think it's really just having a discussion with the manufacturer. A lot of the large manufacturers of spirometry, they are fully able to do this. And a easy way to do it without having to make major changes if it is kind of a financial barrier or the manufacturer's not actually able to do it for their specific equipment or not, or they don't exist anymore, is you could just actually put the kids that are Black as white.

And so that'll get closer to it. Unfortunately, the race neutral equation isn't the same as the white populations. What actually it did was it brought down the white numbers. It brought up the Black numbers, so it's actually somewhere in between where the previous Black children and white children equations were.

So it's not a perfect way to do it, but you can actually get pretty close to the race neutral by using white as the race instead of Black.

Stanley M. Fineman, MD (Host): Good suggestion. Thank you.

Gerald Lee, MD, FAAAAI (Host): This is so wonderful to remind ourselves that if we really believe in health equity and closing disparities, we should be treating patients the same, including applying the same test and interpretation. So I'm really glad that you are highlighting this article and, and again, I appreciate the tip for people who are still trying to update their software.

So we've got one more article and I always like to dig into the basic immunology stuff once in a while. Not that I understand it. There's probably going to be someone going to be listening to this podcast and someone is going to say Dr. Lee doesn't know what he's talking about with these immunology articles. But there's just this really interesting stuff coming out all the time and anything that hits Nature, I think is worth a read in our field.

So this, out of a talk I saw on Mast Cell Disease at one of the national meetings, and it comes out of Duke and it is titled, or article is Anaphylactic Degranulation by Mast Cells Require the Mobilization of Inflammasome Components. So, you know, the process of degranulation, we're pretty familiar with it, right?

We're taking this payload of histamine and other enzymes through the cytoskeleton and, having it attach through this near complex for release it across the cell membrane and interestingly, this article is finding an association between that degranulation mechanical process and the inflammasome.

And we kind of know the inflammasome is somewhat involved in mast cells. We know that certain inflammasome disorders, like as you know, some of the familial cold urtricarias where there's a gain of function in the inflammasome like cryopyran and you get hives. So I mean, we kind of knew that there was association.

But what this group did is they took knockout mice. And they did an anaphylaxis model on it. And if you knock out key components of the inflammasome, like NLRP3 or ASC, it actually attenuates anaphylaxis. So again, mice don't really have food allergy. They kind of don't have anaphylaxis as you know.

They, their temperature goes down when you induce anaphylaxis, and that's what they call it. But again, it attenuates that temperature drop when you do an anaphylaxis model. And when you look at some of the proteins associated with the outer surface of the granule, like CD63, as you know, is an activation marker.

They kind of co-localize with components of the inflammasome, and it's this sort of CD63 poly normalization, which we call the granulosome. I learn about stuff all the time. And so what you find is, is that there is this interaction through confocal microscopy and co-precipitation where inflammasome components and CD63 are actually co-localized and interact together in this granulosome complex.

And when you disrupt inflammasome components, it actually impairs the degranulation process of the mast cell. Now the other function of the inflammasome you may be aware of is that it activates a caspase. It's like an enzyme that takes the inactive form of interleukin1 beta and cleaves it to the active form.

And you know, we know that that's part of its process. That's why we treat gain of function inflammasome disorders with IL1 blockade. The interesting thing they found is that one of the enzymes in the granule kinase does the same thing outside of the cell. So they were able to show that pro IL1 beta actually is cleaved by kinase in the mast cell to go to the active form of IL1.

So it actually shows that the mast cell and its granule kinase is actually important for the innate immune system on the other way. And if you disrupt IL1 beta, if you disrupt the inflammasome, like an NLRP3 inhibitor, you actually attenuate this anaphylactic severity. So if you want to take this together.

When I saw this talk in the national meeting, the first thing I thought of was co-factors of anaphylaxis. We don't like to give allergy shots when someone is sick. We asked the question if someone had an event due to anaphylaxis, if they were sick at the time, and there was possibility, that because infection can activate the inflammasome; is it possible that it's actually augmenting degranulation, that the mechanism of infection as a cofactor for anaphylaxis is through augmenting or facilitating degranulation of the mast cell? I think it's very theoretical. It's very interesting, but there was someone like on the other row of the audience who asked the question, I was thinking, and I think the speaker was talking something about gut bacteria, but like, I looked at her, I'm like, I'm thinking exactly what you're thinking.

We're thinking like de de de, we're thinking the same thing. So just you always want to know why stuff happens, and this was just one explanation that sort of answers the why question. So that's why I thought it was worth bringing up, and I dunno, maybe in the future we'll have these treatments that address the inflammasome that can modify allergic disease.

That's obviously very theoretical, but again, it's just another target when we think about how we're going to help our patients with significant, uh, like food allergy or prone to anaphylaxis or so on.

Stanley M. Fineman, MD (Host): You know, Gerry, I'm really glad that you brought this up and I'm going to make a plug for Allergy Watch. This was in the journal Nature Immunology, and Shyam's article was in a JAMA type article, mine was a Journal of Pediatric. These are not journals that most allergists sort of review on a regular basis, but here you have three articles that are pretty germane to allergies.

So, uh, I just want to make another plug for Allergy Watch.

Gerald Lee, MD, FAAAAI (Host): I like to plug Allergy Watch too, because it forces me to read this stuff. I don't typically read this stuff, but then I want to contribute and so I appreciate the experience.

Shyam Joshi, M.D.: So, Gerry, I'm going to put you on the spot here. Are you able to fit in the other augmenting factors for anaphylaxis, let's say, like NSAIDs or exercise into the same mechanism that you're thinking of with the inflammasome?

Gerald Lee, MD, FAAAAI (Host): To my knowledge, I don't know the influence of sleep deprivation, NSAIDs, or hormones on the inflammasome. So I'll be honest with you, I dunno that. So if you know something, you can tell me.

Shyam Joshi, M.D.: Expect you to. I have no idea. No, I think, your theory I love it. We're always telling patients like, your immune system is just on, and so you have a higher chance of having a more severe reaction or significant reaction. But this is actually something concrete that we potentially look into more.

I agree it's far from prime time, but it's a really, really interesting theory.

Gerald Lee, MD, FAAAAI (Host): Yeah, I Just like learning. That's why I do medical education and do a fellowship. The fellows teach me stuff all the time, and again, Allergy Watch teaches me a lot too. So, segue, if you learned something and you really like what you're hearing, please rate us. If you listen to Apple Podcasts or Spotify, please give us a review.

And I also want to hear your thoughts. If you have the answer of Dr. Joshi's question or any feedback or suggestions, you just email us at allergytalk one word@acaai.org. And of course, we're all learning. We offer CME credit for you participating in this activity. Just go to our website, education.acaai.org/allergytalk.

And then of course we also have the archive issues for the other articles we have not reviewed today. And that's at college.acaai.org/publications/allergywatch. Well, that's what we have for today. We're going to review a few more articles on the next one, so we'll see you then. So enjoy the rest of your day.

Thanks y'all.

 The A-C-A-A-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, or products or methods discussed in the podcast, and it does not approve or endorse any products, professional services, or methods that might be referenced.