Dr. Gerry Lee (Host): Hello and welcome to another episode of AllergyTalk, 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 more articles from AllergyWatch, a bi-monthly publication, which provides research summaries to college members from the major journals of Allergy and Immunology. And also to read archive issues of AllergyWatch, head over to college.acaai.org/publications/allergywatch. And finally, we do have an ACAAI community on the DocMatter app, where we can continue conversations about the articles we discussed today.

Well, again, my name is Gerry Lee. I'm an Associate Professor at Emory University. I'm an Assistant Editor of AllergyWatch. And today, once again, I'm joined by the Editor-in-Chief of AllergyWatch, Dr. Stan Fineman.

Dr. Stan Fineman: Hi, Gerry. And hello, everybody. It's good to be here. As Gerry said, I'm Editor-in-Chief of AllergyWatch. I'm also on the clinical faculty at Emory, and I'm the past president of the American College of Allergy, Asthma and Immunology.

Host: And for the third chair, we're excited to be joined by the Associate Editor for AllergyWatch, Dr. Shyam Joshi. Shyam, welcome back to AllergyTalk.

Dr. Shyam Joshi: Thank you so much for having me. I'm really excited to be here. I am an Associate Professor of Medicine at Oregon Health and Science University, and the Associate Editor of AllergyWatch. I look forward to our chat today.

Host: All right. Well, let's get into it. Stan, you selected an article giving some more information about what really happens when we do food challenges in clinical practice, because I know that's something that we know we want to do for our patients, but we have a concern about safety and anaphylaxis. What have we learned in this article?

Dr. Stan Fineman: So, this article, the first author, Dr. Mustafa, is up in Rochester, and he's done a lot of excellent work in food allergy and has been been active in the college as well. The title of the article is Outcomes of Oral Food Challenges in Real-World Setting with Predictors of Outcomes, and it was published in the annals, and it was just published this last year.

So, the interesting thing about food challenges, which I learned from this article, is that really 56% of the allergy fellows reported conducting less than 10 oral food challenges during their training. And in fact, a third are reporting not even conducting any food challenges at all. And when you think about oral food challenges, it's really the reference method for diagnosing food allergies. I think our training programs really need to beef up the experience for our fellows to make sure they can be able to do these oral challenges.

So, what they did up in Rochester, this is a single-- Well, not exactly a single-site because it's a single integrated health system organization, so it's really a sort of a single operation. This is their food challenges over a three-year period. They have three different offices. They're all under the same health system. And they did 1,132 oral food challenges. About half of them were to confirm or refute a food allergy diagnosis. A little more than a third were to test whether the food allergy had resolved, if the patient had grown out of it. And 182, a little more than 10%, were to see if the patient developed a tolerance to baked milk or egg. And then, there was another 10% or so that were because of family requests, the family wanted to know. The mean age was four years of age, 60% were male, which is very typical of what we see in our populations in children.

And interestingly, they had a specific protocol, which is standard, and they did it under a controlled situation. And the interesting thing, I think, is the fact that 76% of patients tolerated the food during the challenge. Only 21% experienced a reaction, and 3%, they refused to eat the food at all and they didn't complete the challenge, which is something we should really talk about, because we've seen that a number of times in practice.

The most common tolerated food was shellfish, and this was tolerated in 91% of the food challenges that they did for shellfish. So, of 35 of the 38 oral food challenges for shellfish, the patient passed and was able to eat it. The next lowest was for baked egg, 66% tolerated that; sesame, 68%; wheat and even peanut was 69%. The food allergy challenges were considered to be at high risk when they had larger skin tests, higher specific IgEs, and a stronger history of a reaction.

In those situations, the test was tolerated in about half the time. Of the patients who experienced the reaction, 30% did so after the first dose, which I think is a little unusual. We don't usually see it after the first dose, but we certainly can. Half the patients who experienced reactions were treated with antihistamines alone, and only a third needed epinephrine. And none of the patients required a third dose of epinephrine or additional treatment or going to the emergency room. So, as you said, Gerry, very safe procedure in terms of patient risk, as long as you do it properly and you monitor things.

The main characteristics of the patients who predicted tolerance were that they were older patients, they had smaller allergy skin tests, both flare and wheal, and they had lower specific IGEs, which that's kind of intuitive, I suppose, that you'd think those kind of patients would be more likely to tolerate it. Also, children who had a history of peanut allergy were less likely to tolerate the oral food challenges. They were the ones who seemed to have more trouble with it.

So, Dr. Hernandez-Trujillo, who's down in Miami, in her comments on this article felt that this article gives us very important information about these tests in a real-world setting, and I think that's why it's an important article, and I'd like to hear what you all think about it.

Host: You started talking the statistics of allergists performing food challenges. I don't want to disturb any of our audience, but the minimum requirement by the ACGME for a fellow to graduate a fellowship program procedure log-wise is five food challenges. And I think, you know, my boss, Dr. Vickery, has looked at that number, and it just blows his mind. I mean, as you know, it is now what I consider a cornerstone of our practice, food and drug challenges, and for five to be graduation. I mean, maybe obviously training can provide some sort of comfort level, but there's so much nuance to the procedure that, certainly, I think it is something that maybe lack of familiarity during training will lead to the reluctance to do it, but I think a lot of what the Rochester group has reported is sort of our experience.

When you talk about shellfish being so tolerated, I mean, I don't know how often you see cosensitization with dust mite and cockroach, but we see that all the time, and all these patients seem to tolerate. They have no clinical history. So, I think the quality of life increased by giving someone relief by something that, with a good history and cosensitization presence that could be potentially low risk, can provide a lot of benefit. Shyam, what do you think? What are you seeing up in Oregon about this?

Dr. Shyam Joshi: You're spot on. What I think we have to understand, though, too is you're going to have positive challenges. There are going to be times that patients are going to react. And I think if we're so reluctant on doing these challenges that you're getting nobody that's reacting, you're probably not challenging enough. And so, just getting comfortable with the fact that you are going to have a few positives, but the vast majority are going to be negative when you select your patient population well, it's so important for patients. And I truly believe it is a cornerstone of our practice now going forward as much as allergy shots or any of these other procedures that were taught so heavily in fellowship.

Dr. Stan Fineman: In full disclosure, the reference to those numbers was from a work group report from the Academy, work group on food allergy that was published in the JACI in Practice in 2020. So, that's data that's probably five years old. So, I would imagine, Gerry, that the requirements for fellows probably have been changed since then.

Host: Oh, no, the fellow requirement has not changed because I have to certify my fellows. But certainly, my hope is the numbers overall has improved over the years. But if you're asking me if we in Children's Healthcare of Atlanta get referrals for food challenges in the community that I think are low risk, I think we do get those referrals, and it may be infrastructure or familiarity or lack of comfort with children or infants. Whatever the barrier, I think there's a lot we can do to help community allergists or other practices take this on, just because we know the majority do great, and it just requires a little bit of experience and doing what's best for the patient, honestly.

Okay, let's go to the next article. I think this is a really interesting exploration about what we are learning about tryptase genetics and how it could reflect allergic disease. So, what do we know about tryptase genetics and food allergy?

Dr. Shyam Joshi: This was just a really well written article. It's from JACI and came out just a few months ago, and it's titled, Severe Food Allergy Reactions Are Associated With Alpha Tryptase. And it's out of the groups, the NIH and from Chicago, from Lurie Children's Hospital. And this was one that actually Gerry commented on, but I found so fascinating that I felt like I had to talk about it today.

A lot has been discussed with alpha tryptase and alpha tryptasemia over the past, let's say, five years. And I think we've learned a lot that there is something to this, but there's still a lot of unknowns. Really where we're at right now is, I don't know if you guys get this question, but almost every kid that comes in with food allergies, really one of the first questions that the parents ask is, "How severe is my kid's food allergy?" And I throw my hands up in the air and I'm like, "I don't know really. There's no real great way for me to tell you is this going to be severe or not. It's just really based off of what kind of reactions you've had in the past," which is not satisfying for a lot of parents, unfortunately. But we do know that there are some co-factors, right? Sleep deprivation, exercise, febrile illness, they do decrease the threshold dose and could increase the severity as well. But beyond that, there's very limited options. We know there's basophil activation testing, which has some promise, not really widely available, due to the limitations of the lab itself, but maybe something in the future.

But what we have learned about alpha tryptase, so when we think of a tryptase molecule, it's a heterotetramer, and there are alpha and beta subunits. Four of them compose a full tryptase, heterotetramer. And they can be alpha or beta. A normal kind of alpha tryptase coding number is usually zero, one or two, and then the rest are beta. So, somebody can have four beta, or they could have two beta, two alpha. And so, what has been looked at to date is really in the venom allergy space. And we have seen that in patients with increased number of alpha tryptase copies, especially those people with alpha tryptasemia, so they have three or four alpha tryptase copies, that those patients do have a higher risk of more severe reaction if they have a hymenoptera allergy or they have an underlying idiopathic anaphylaxis diagnosis.

And there's actually one really small study back from 2014 that's by Sahanar that was published in Allergy that showed a higher baseline tryptase level is associated with an increased risk of severe anaphylaxis in children with food allergies. Very small, hidden in there, but there is some suggestion here that tryptase level and the severity of food allergies could be related.

So, what this study tried to do is look at cohorts of patients, both from Lurie Children's as well as the NIH, and genotyped them all and looked at do the presence of alpha tryptase because, again, some patients don't have any alpha tryptase, and the number of alpha tryptase copies, does that correlate with the severity of reaction? So, they looked back at these couple of cohorts that have had food challenges, using the PRACTALL Oral Food Challenge Guidelines. So, it's really detailed because they're in previous studies. And they took 119 patients and they genotyped them all. And they, again, correlated severity of those reactions in the past to do they have alpha tryptase or not, and this is fascinating.

So, the presence of alpha tryptase, so this doesn't mean they have alpha tryptasemia, this just means that they have alpha tryptase compared to those patients that had only beta tryptase. So they had four beta tryptase as part of their heterotetramer, that those with an alpha tryptase had a much higher risk of severe reaction when they reacted at 65% versus those that had beta tryptase only, no alpha tryptase, only 17% of those patients ended up with severe anaphylaxis during their reaction, so 65% versus 17%. It's not perfect, but it does seem to suggest that just having alpha tryptase makes that difference. The big question is why, and we don't have a great answer there. There have been some mechanistic studies, again, in the venom population that suggests that having alpha tryptase, it interacts differently physiologically than beta tryptase does. And having more alpha copies would mean more of the tryptase has alpha tryptase in there. So, a lot to still be looked at and understood, but there does seem to suggest that the presence of alpha tryptase makes a difference.

In addition to that, they also showed that having more copies of alpha tryptase correlates with higher and more severe scores using the PRACTALL oral food challenge scoring system. And so, not only just having presence, but having more of them may put patients at higher risk for more severe reactions. So again, small study here. Not suggesting every kid with food allergies should have alpha tryptase evaluations right off the bat, but I do think that there is something here, and there needs to be further evaluation in a kind of prospective manner to really understand, Is this a biomarker we could potentially use to give some parents some comfort or to allow them to be a little bit more understanding that their kid's reaction may be more severe if they do get exposure. So, I thought it was really fascinating. I'd love to hear what your thoughts are, especially Gerry, who selected this paper in the first place.

Dr. Stan Fineman: I was going to ask you a question. Do you think that we should be getting just a plain serum tryptase on these kids when we diagnose them with a food allergy? We do that for venom now, so...

Dr. Shyam Joshi: Exactly. i don't think that's a bad idea. What this paper really showed, though, is it's not necessarily just having an elevated basal tryptase level is the issue, it may be more of, do you have alpha tryptase or not. So even in patients that had normal tryptase levels, if they had alpha tryptase at all, that's really what increased their risk. But yeah, you're right, there are other studies that have shown if somebody has a tryptase level of 15, they're probably going to have a more severe reaction to exposure to the food. It's just we don't have large studies, especially in the food allergy population for that situation.

Host: One argument for doing that tryptase screening is that HAT. Hereditary alpha tryptasemia is pretty prevalent, if you look at large studies. And so, again, we don't know how many copies of alpha tryptase is in that tryptase level. If it has predictive value about severity, we just had a discussion about can we quantify the risk of pursuing a food challenge other than the usual history and testing if genetics is going to let us get another piece of information when we're trying to do shared decision-making or counsel patients, I think it's useful. I think we all know what the issue is, insurers don't pay for the copy number. They pay out of pocket, I mean, as of this recording, which is early 2024. So, as of right now, you have to pay out of pocket for it, or get it funded somehow. But I think, yes, it's really made me think about what other pieces of data we're going to be using, especially when in the age of informatics, when we're really going to do risk assessments that are more precise, other than like, "I have a feeling," I feel it's very like gestalt and art of medicine, but that really doesn't fly now that we are in the age of big data.

Dr. Shyam Joshi: I completely agree. And for those of you who haven't tested for alpha tryptasemia in the past, again, at the time of this recording, it's $169 that patients do have to pay out of pocket, which is limiting for some patients, but I'm sure there are a good host of patients out there that would be interested in pursuing that if you give them the option.

Host: All right. Well, thanks for bringing that article up. I'm so excited to learn more about this in the future. So, let's wrap it up with one more. And when we talk about cost to patients and cost to society, there's no doubt that asthma is one of the biggest ones, right? Huge cause of significant morbidity, mortality, and healthcare utilization. And the populations that are most affected by epidemiologic studies, as you know, are those who live in disadvantaged urban neighborhoods. And of course, given our history of systemic racism, as you know, that Home Owner's Loan Corporation was less likely to give mortgages to certain ethnic groups, and that led them to be in disadvantaged neighborhoods, which over time, has the highest asthma morbidity that we know is environmental.

Anne Fitzpatrick at Emory has done some of the articles on this as have others, where you control for socioeconomic factors, you can equalize a lot of the exacerbation rates like ED visits or so on. So, this study came out of JAMA from Elizabeth Matsui. And you know, she's just a wonderful researcher studying the social economic effects in asthma, and I really love all of her work. And so, the title of this article is Association of Housing Mobility Program with Childhood Asthma Symptoms and exacerbations. And Shyam, you reviewed this article, so I was in awe of this article, so I had to bring this one up.

So, essentially, there is a program in inner city Baltimore. And it's called the Baltimore Regional Housing Partnership Mobility Program. And this came out of a lawsuit. It came out of the recognition that Baltimore's Family Public Housing violated the 1968 Fair Housing Act because of unequal treatment. And they are trying to compensate for those decisions by counseling for families, workshop, partnership with landlords, and assistance, particularly housing vouchers, where the cost of their rent utilities would be one-third of their household income. And a lot of these families that are targeted in this program lived in pretty disadvantaged areas. I mean, I think the definition is that at least 20% or 25% are at the poverty line. So, these patients not only are living in very challenging environments, but they also have the largest asthma morbidity, and so on.

So, what they did is that they were part of this housing program. And therefore, they decided to enroll these patients who had asthma who are part of this rehousing program into something called the Mobility Asthma Project. And so, they were able to find 123 children, 106 of those children moved. They had a baseline home visit, and then they did phone call check-ins or in-home visits every six months. And really, they only wanted to look at asthma-free days and exacerbations, but they also wanted to see when they were rehoused months later, was there a change in exposures or the stress that they're under or other potential confounders?

And eventually, at the end of the study, they had children, again, like I said, about 100 children, about 47% female, 97% black race, mean age of 8 years old. They had about 60% of them were allergic. They were living in high-poverty census tracts prior to the move. And after this move, they measured exacerbations and symptom days, there was a 54% reduction in asthma exacerbations, and there was a 59% greater odds they would have an asthma symptom-free day. And the interesting thing is it was not particularly associated with environmental allergen reduction. In fact, when they moved to the new places, dust mite exposure was increased in some of those areas. There was actually decreased environmental secondhand smoke exposure and cockroach, but it's interesting. It was not particularly allergen in itself. And one factor they did see that was significantly different is social measures like stress levels, the feeling of safety, social cohesion measures. And we can't measure what that means for a child, but we're thinking about stuff like being able to go outside and play because you feel safe about neighborhood crime or other influences.

And so, they did a very good comparison that I wanted to bring up, which is when you think about that reduction in exacerbation rates. They quoted that if you give someone a biologic, you start an asthma biologic on somebody, that's going to be a reduction of like 50%. If you start inhaled corticosteroids, that's going to be a reduction of exacerbations of 43%. This intervention reduced asthma exacerbations by 54%. And if we think about cost, cost to the system, well, you know, what's the estimated cost of biologic? Oh, it's in the neighborhood of $30,000 a year, something like that. And $30,000 a year can get you a pretty good apartment. I'm not saying it's like the best apartment. But I'm telling you, if you go all in, we're talking about an equal reduction in asthma exacerbations with similar costs, but benefits beyond asthma. You're talking about significant improvement in a child's quality of life. So, just that comparison is so interesting to me on how if we really want to move the needle on asthma, how do we best utilize our resources as a society to help our patients? And I think that this article just brings that to the fold and makes us really think carefully about how best to uplift patients. If we have scarcity of resources, how do we best utilize those resources to get to the root cause of what's affecting these children?

Dr. Shyam Joshi: Beautifully said, Gerry. I completely agree. And what I also found really interesting in this article is that we're just comparing asthma exacerbations and asthma indicators, but decreased stress, increased social cohesion, neighborhood safety, how does that affect other parts of people's quality of life? When we go beyond the asthma stuff, if we look at quality adjusted life years, the qualities, I'm sure that this would cause such an increase in quality of life within asthma and outside of asthma compared to a biologic, which may actually decrease quality of life outside of asthma, because you have to do the injections and all those kinds of things as well. So, I think we all know this probably makes a difference, but just the fact that they were able to put this into numbers is, I think, phenomenal, and really helpful to understand the magnitude of this issue.

Dr. Stan Fineman: Yeah, I agree. The evidence-based data that's collected with a study like this is very compelling. And as you all know, Dr. Cherie Zachary, the Vice President of the College now, gave a Bela Schick lecture in '22 meeting, all about the disparities of health, the racial disparities of health. And I think there's really a lot more underlying it that we really knew. So, studies like this that give us some evidence-based data really can help us learn how to deal with it and help improve all of our patients care.

Host: The college, as you've mentioned, has put a lot of outreach and informational guides, whether that was supporting the extreme skin of color, we have the mini series for the AllergyTalk Disparities Podcast, there's a whole bunch of mini series on atopic dermatitis and immunodeficiency and asthma, so please check that out.

I agree, I've seen the college promote this sort of work. They certainly support that. And again, when we do advocacy and when we think about how to advocate for patients, hopefully, we can keep this in mind and cite stuff like this to really have payers and communities and governments think about future investments.

Well, that's the last article. If you like what you heard, please give us rating on iTunes. And of course, we do want to hear from you. We have an email address, AllergyTalk, one word, at acaai.org. We do want your feedback, corrections, and suggestions. My name is Gerry Lee. Thank you so much for listening, and I hope you enjoy the rest of your day. Have a good one.

Disclaimer: The 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.

Today's speakers have the following disclosures. Drs. Lee and Fineman have nothing to disclose. Dr. Joshi has been an advisor for Genentech, Sanofi, Regeneron, Novartis, and Takeda, and a consultant in his executive role in Nectar Allergy.