Gerry Lee, MD (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 today's episode, we'll be reviewing more articles from Allergy Watch. It's a bi-monthly publication, which we provide research summaries to college members from the major journals of allergy and immunology.

And by listening to this podcast, you can earn a CME credit. For more information about that, head over to education.acaai.org/allergytalk. And we do have a Doc Matter community where we can continue discussion about these articles. So sign up for the app. Well, hello, everyone. My name is Gerry Lee.

I'm an associate professor at Emory University, an assistant editor of Allergy Watch. And today, once again, I'm joined by the Editor-in-Chief of Allergy Watch, Dr. Stan Fineman.

Stanley M. Fineman, MD, MBA: Hello and thanks for inviting me again. I'm a past president of the College of Allergy. I'm currently an adjunct faculty at Emory and look forward to our discussion.

Host: And for the third chair, once again, we're joined by Dr. Vivian Hernandez-Trujillo, the Division Director of Allergy Immunology at Nicholas Children's Hospital, and also an Assistant Editor of Allergy Watch. Viv, welcome back to Allergy Talk.

Vivian Hernandez-Trujillo, MD: Thank you so much, Gerry. It's very exciting to be back, and I'm looking forward to the discussion about these important articles.

Host: Okay, well, let's start with you, Viv. I know that we see tons of food allergy patients and it's very important for us to treat the whole patient and you're bringing an article that talks about a very important thing we should be thinking about. Let's talk about it.

Vivian Hernandez-Trujillo, MD: Great. So this article actually addresses mental health concerns of patients with food allergy. And I will say I'm a mom of two girls with anaphylaxis to peanut and tree nuts. So this is near and dear to my heart. And I think a lot of times I'm able to talk with parents about what it's like to be a parent.

And I also have my own food allergy. So this topic in particular is very near and dear to my heart. Dr. Sarah Spree actually reviewed it. And this article appeared in the World Allergy Organization Journal in March of 2024. So, the information here was from the FAIR patient registry, and really they were just looking to better understand the impact of food allergy on not only patients, but also caregivers.

And I think that's something that, especially those of us who are in pediatrics, we need to always remember that food allergy doesn't only affect the patient. It really does affect the whole family and in particular, the people who are responsible. So the caregivers. There were over 1600, almost 1700 US residents who reported at least one food allergy.

And this was actually a survey on mental health concerns. It's important to keep in mind that almost 80 percent were white, 61 percent were female and it was about half and half pediatric and adult patients. But as someone who, I'm very interested in healthcare disparities, obviously this particular group of patients was primarily white.

So, a total of 62 percent of the respondents did report mental health concerns, so more than half, and almost two thirds experienced concerns about living with food allergies, more than half of them. And especially after having had an allergic reaction, so that almost half of those.

Caregivers also reported being afraid to trust others with their child. That's something that I hear all the time. I'm sure you do, too. Like, they're scared to leave their child because something could happen, and more than half of those. And then fearing for their child's safety, again, over half of the respondents.

So these are important things that do affect your quality of life and certainly not only physical, but your mental health. In this particular group, patients who had experienced a greater number of reactions per year, those who had a single food allergy, those who were not admitted to the hospital or those who were either racial orethnic minorities did have a greater likelihood of experiencing mental health concerns.

 So, again, something for us as practicing allergists to just think about and consider. And then patients who had received a formal mental health diagnosis were less likely to report mental health concerns. So, so that also reminds us that if we're able to give support and help our patients find who they need to speak to, it may actually help addressing these concerns overall.

About a third of the patients reported that they would like to be screened. So again, this is something to keep in mind. We all, I think there was, there's really been a stigma about mental health, but I think that honestly, in the last four to five years, we've seen people are more open. We're openly talking about how mental health affects all of us, whether it was during the pandemic, and everybody was isolated, or if you're living with a chronic illness. This is an opportunity to further help our patients with food allergies and obviously the parents. So the reason that I thought it was important to talk about this in particular is just giving our patients and their caregivers adequate support is really going to help improve everything for them overall.

And I think as much as you know, we've had a lot of good studies and surveys. I think there's still more to this that really would benefit from us understanding. And obviously, and I talked a little bit about the disparities, but different groups, and they did find that, that some racial and ethnic minorities were more likely to have the mental health concerns.

So something to keep in mind, and hopefully we can help our patients with this.

Stanley M. Fineman, MD, MBA: You know, Viv, I really like this article because I found that a lot of times it's hard to talk to patients about suggesting that they get some mental health help. In other words, go see a psychologist or psychiatrist, somebody to really help them with dealing with these things.

But this study provides data that we can tell the patients that this is a fact, that these are patients who have the food allergy, just like your child, and this is the percentage, you know, half of them, had problems and a third of them wanted to get help that they're not alone, and I think it can, this can, this type of data can really help us reassure other patients.

Host: I love that you brought this article up for a couple reasons. Number one, this is a reminder that is our standard evaluation for the food allergy patient. Are we screening, right? Are we making sure that we know the high prevalence of the mental health burden on food allergy? Can we identify patients and address that part of the patient consistently in every patient? I think it's a good reminder for us. I kind of put that in my little ah we always have a little template in the EHR. I always put, make sure I asked a question because, there's definitely people who specialize in this. We're very lucky at Children's Hospital Atlanta to have a food allergy specific psychologist.

We do want people to have access. I think another thing that I wanted to bring up is when you presented this article, Viv, it reminded me of this report that came out. Oh gosh, it came out in JACI back in 2019. And what it was, it was stakeholders, like researchers and patients and caregivers about what are the research priorities the food allergy community should focus on and Brian Vickery, my boss presents this article often.

Why? Because when they talked about what were the focuses or research that the researchers felt was important and the patients felt was important. The biggest disparity was psychosocial issues; 2.3 percent researchers thought it was a priority, 10.5 percent of the patients felt psychosocial issues were important.

So that disparity shows that we are not in line with what's very important that our patients need and want us to help them with. So we can't say more about how we really need to go to our patients shoes and recognize what their needs are and how we need to step up and address them.

Vivian Hernandez-Trujillo, MD: I think one last thing to add, right, is, and I encounter this in the office a lot. We're now, thankfully, it's not all avoidance, avoidance, avoidance, right? There's a lot of different options, treatment options. However, you need to be in the right mental state for that. And the parents need to be in the right mental state because we can't offer oral immunotherapy to a child whose parents are so overly anxious and they jump at, right?

Like we all need. So it's another reason why we really do need to address it because in the long run, it's just going to help everybody.

Host: Okay. Well, again, we should be thinking about this continually in our patients. And there's another population that we see often and that's atopic dermatitis. So Stan, you and our article addressing that population.

Stanley M. Fineman, MD, MBA: Yeah, it's, they really do correlate. This was an article from the JAMA Dermatology, which again is not a journal on our radar screen, but I think however, hopefully after you hear the article, you'll see why Allergy Watch is really a helpful tool for all of us. It was published in April of this year, and it's entitled Stigmatization and Mental Health Impact of Chronic Pediatric disorders.

And what they did, they really were trying to answer the question about the impact of quality of life on patients who have skin disorders like atopic dermatitis in children and adolescents. And they were using validated tools to measure this stigma in children who have these chronic skin conditions.

The tools that they used were the PPS skin, that's the patient reported outcomes measurement instrumentation system of pediatric stigma a supplement for children with skin conditions and also a proxy that the caregivers could do. So each, there were dyads.

In other words, the child was one who answered the question and then the adult caregiver was the other. And there were 1,671 patient caregiver dyads in this study, and about 58 percent of the children were female, so more female, 56 percent were white majority. Their mean age was 13.7 years. Their diagnosis did include atopic dermatitis, but included other types of chronic skin conditions that you see in children, including acne, alopecia, and psoriasis. And more than half the children reported that their condition was highly visible at all times. And that's a very important factor, was the fact that if the children's, if the condition was visible, in other words, you couldn't cover it with clothing then they reported a higher stigmata. So three quarters, 73 percent of children reported the stigmata.

And for atopic dermatitis and ichthyosis, more than 10 percent of children reported very high stigmata at that point. Girls more than boys. And then the other thing, which was interesting was their caregivers, reported that bullying was associated when the child's stigmata skill was higher. In other words, the more stigma that the child felt because of their skin condition, the more likely they were going to get bullied.

At least the parent or the caregiver was going to notice that they were bullied. So there seems to be some kind of correlation between the severity of their skin condition, the itching and the discomfort, the ichthyosis they talked about, and the fact that you know, it negatively impacts the child, and the caregiver noticed that the child may be more likely to have bullying.

So, again, I think it's something that we just need to be aware of. I think they said 29.4 percent reported bullying, at least the parents were aware of that. And Shyam Joshi, who was the one who brought this article to our attention, in his comments, said that this was a unique cross sectional study showing that clinicians should be evaluating these additional metrics in children, especially girls, when their lesions, their skin lesions are visible and not covered by clothing and when the patient has more severe phenotype, like they're very itchy all the time. So it's kind of the same thing that Viv just talked about for food allergy, but it's in chronic skin conditions.

Vivian Hernandez-Trujillo, MD: Atopic derm, because in many patients, it's actually visible. One of the, one of the things I've learned with time is, especially with teenagers and especially teenage girls, Stan, I think that that is a good point, is asking, you know, if you're not using your emollients, why is that?

Because sometimes you may think, oh, well, they're itchy or whatever. No, I've had kids say to me, I don't want to look shiny. I don't want to, right? Because people will know something's wrong. And I think it's always important. I tell my fellows, ask why? If it's burning, we'll change the product. If it's because they look shiny, then we change the time that they're using it.

But there are different things. And if we don't know the reason for them not using it, we'll never be able to help them with that. But it all really does go back to what is the perception of other people? Because especially in teenage females, and I have three of them at home, that is very important. It impacts you, and it impacts your mental health and quality of life.

Host: Yeah, I mean, these pair of articles, again, is really sending home the message that this is something we really need to care about if we're going to support our patients who need us. I would say that one of my earliest experiences, straight out of fellowship, was a patient with severe eczema. He was a young school age boy, and he came to me for consultation. Withdrawn boy with a history bullying. I cleared up his skin. His skin looked great. He still had long term depression from years of just being asked, you know, are you burned? Like what's wrong with you? And like just these very hurtful questions and even when I cleared his skin, it still he still had a significant change in his personality from that mistreatment.

So, obviously we're going to protect our patients, but also support them, asking the questions, getting the help that they need and recognize that these patients, the chronic illness affects multiple organ systems, including mental health. I'll never forget that patient, but again, that's just sort of something that I'm really glad that we're talking about.

So I have one more, and I don't know if you're catching a theme here, I do like to go off the beaten path so I always have this feeling that if there is an article in our field published in Nature Science or Cell, it's probably worth reading. Again, sometimes a little over my head, but I just have a fascination with what's out there.

So the title of this article is Bronchoconstriction damages airway epithelia by crowding induced XL cell extrusion. Oh my goodness. Well, let's get into it. What am I talking about? All right. So bronchoconstriction, right? That's what asthma is, right? We get airways, with local tightening, and it's going to constrict airway. That's why we wheeze. Now what happens in the airway is interesting. So the airway naturally turns over, right? Just like your skin sloths off, your epithelia in the airway naturally sloths off. It's a process called extrusion. And what this paper decided to examine is like, when bronchoconstriction happens, what is happening to the process of the normal cell turnover excrusion, right?

And so they had this mouse model where they were able to do a, an allergic asthma model, but then take lung slices and then do like methacholine challenges on them to look at the airway. And there's like these, if you have a science subscription, the videos are super cool. Like I just think these videos are really neat.

All right, you got to be super nerdy obviously, but okay, so what they did was is that when they gave methylcholine to these asthmatic mice, like the epithelial wall is sloughing off. There's like increased cellular excrusion. Basically, the cell wall is being completely torn to pieces, right. It's pretty violent what's happening in the airway that's modeled in these mice.

And the degree of extrusion was correlated with the dose, and you know, you can give albuterol. And it doesn't reverse this process, right? You can relieve bronchoconstriction, but the damage to the airway that's done during constriction on these mice, it's happening. Like, there's literally, like, sloughing off of the airway when that constriction just pops off all your outer layer of epithelium.

So there's like airway injury with bronchoconstriction. Now, they know the pathophysiology of the normal turnover. It involves these channels called stretch activated channels, or SA channels, and also TRP channels. And the interesting thing is they know how to manipulate this pathway. You know, so gadolinium, gadolinium, interestingly, inhibits this pathway.

And so they treated these animals with gadolinium and did the methylcoline challenge again, and it improves the denuding and epithelial wall detachment they saw with bronchoconstriction, right? And interestingly, it also attenuated airway inflammation. So when you have this airway injury, you activate the innate immune system, and then you have inflammation induced by the mechanical injury to the airway.

And so when you give them the inhibitor, they actually have less airway inflammation after bronchoconstriction, as well as decreased mucus secretion, right? And so they're sort of proposing this model, they call it the mechanoinflammatory vicious cycle, where you get bronchospasm, you crowd out the epithelial cells and they get extruded and damaged and the wall gets denuded.

And because of that injury, the immune system activates and then you get inflammation. But then if inflammation is the precursor to bronchospasm, that's when we're getting to the vicious cycle of bronchoconstriction injury and further susceptibility to bronchoconstriction. It's quite interesting how we are tying those together.

And also, if we can interrupt this excrusion process, again, I'm not saying we give patients gadolinium, but if we find inhibitors that can stop this process and prevent the injury to the bronchial wall, potentially there's another therapeutic strategy to treat asthma during exacerbations. It's just, it's just like a unique thing.

Clearly, mice aren't humans. So, they have to look at this further, but I just thought it was a very interesting concept and we know that exacerbations can lead to loss of lung function. So maybe that ties into why exacerbations are so important with asthma, that exacerbations, as actually could be perpetuating inflammation by causing severe injury through this mechanical mechanism, essentially.

Stanley M. Fineman, MD, MBA: Gerry, I had a little confusion about how is albuterol related to the gadolinium because it seemed like the albuterol really didn't block this process per se, but the gadolinium does it act as an anti inflammatory or how do you think it's working there?

Host: Essentially, albuterol can attenuate bronchoconstriction, but it did not seem to have an effect on the cellular excrusion process, at least in a in vitro model, right, with lung slices. So again, it's hard to say. But yeah, I mean, as you know, albuterol doesn't completely attenuate bronchoconstriction in certain patients.

So again, if constriction is happening, this paper suggests that's hurting the airway. It's actually damaging the airway.

Vivian Hernandez-Trujillo, MD: Maybe there are some patients that are more susceptible to that, so you almost have to wonder, maybe that's why they're not responding, right, so interesting.

Host: Especially with all this crap in the airway now, now you have like denuded cells floating in your lumen. Right. Absolutely. So again, it's way early, but it's just another thing that we're learning about the pathophysiology of disease that we've taken for granted for decades. This field is just so interesting.

Stanley M. Fineman, MD, MBA: Let me make another plug for Allergy Watch because this is from the journal Science, and, Gerry, you may be the only person I know, allergist, who reads this on a regular basis, but, that's definitely not on my radar screen. It's not one that most clinicians would, but this is certainly a, an article that's germane to our clinical practice in the fact that we need to understand the mechanism. So I really appreciate your bringing this up.

Host: I just like learning. Allergy Watch for me is all about learning and just learning cool stuff.

Vivian Hernandez-Trujillo, MD: I'd also like to put in a plug for Allergy Watch. I think, we all say that we're so busy. But everybody can take 10 minutes, even if it's every other week, to pick up Allergy Watch and really have pearls and tips that are going to help us clinically. It's always relevant and I'm just so appreciative to be part of it because I truly feel that there's such value.

Host: Okay. We're plugging stuff. Y'all have probably a commute of between 10 and 20 minutes. Pop this on your podcast while you're driving. I just think that, there's just multiple ways to stay up to date. So I'm glad to be part of it. So if you liked the podcast, please rate us on Apple Podcasts.

It really helps us. We do want your feedback. If you have any corrections or suggestions for futures episode, the email is allergytalk@acaai.org. Don't forget about CME credit. The website is education.acaai.org/allergytalk. And then of course, on the same college website, you can get archive issues of Allergy Watch like we're talking about.

I always enjoy doing this. Viv, thank you so much for coming back. We'll see you on the next go around. And everyone have a wonderful day!

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