Journal Club | Asthma, Wheezing & Alpha-Gal: What the Evidence Says with Dr. Len Bacharier

How should emerging evidence change the way we approach common allergy and asthma concerns in pediatric practice?

In this episode of Cumberland Conversations Journal Club, we examine new research addressing three practical questions in pediatric allergy and respiratory care: whether children with mild asthma benefit from anti-inflammatory rescue therapy, whether antibiotics improve outcomes in young children with recurrent wheezing, and how clinicians should interpret testing for alpha-gal syndrome.

We begin with a discussion of emerging evidence supporting the use of an inhaled corticosteroid alongside a rapid-acting bronchodilator as rescue therapy for children with mild asthma. The conversation explores how this approach may reduce exacerbations and systemic steroid use while offering an alternative to traditional albuterol-only rescue treatment.

We then turn to antibiotic use in young children with recurrent wheezing, reviewing evidence that reducing detectable bacteria does not necessarily translate into improved respiratory symptoms. The discussion highlights the importance of connecting microbiologic findings with meaningful clinical outcomes when considering antibiotic treatment.

Finally, we explore alpha-gal syndrome, a tick-associated allergy characterized by delayed reactions to mammalian meat and other products containing alpha-gal. Particular attention is given to appropriate testing and diagnosis, including why a positive antibody result alone does not establish clinical disease and how testing without a compatible history can lead to unnecessary dietary restrictions.

Together, these studies highlight the importance of translating new evidence thoughtfully into practice—using clinical outcomes, patient history, and appropriate diagnostic interpretation to guide treatment decisions.

Articles discussed in this episode include: 

Azithromycin for Preschoolers with Wheezing in the Emergency Department

Alpha-gal Immunoglobulin E Seroprevalence Among Blood Donors — 10 States, 2024–2025

Budesonide–formoterol versus salbutamol as reliever
therapy in children with mild asthma (CARE): a 52-week,
open-label, multicentre, superiority, randomised controlled
trial

Transcript

SPEAKER_01 0:00

Hey there, welcome to Cumberland Conversations. This is the place where we talk about the issues that matter most to you, your patients, and your community. We're diving into real conversations with real people, sharing insights you can actually use. Let's get the conversation started. Hey, everybody, it's Rob Lillard, Medical Director of the Cumberland Pediatric Foundation, welcoming you back to another episode of Cumberland Conversations. And we're here again to do another Journal Club episode. And we're going to talk about some really great things today, mainly working with allergy, immunology, and asthma. We're going to talk about combined steroid and long-acting bronchodilator therapy in the routine care of mild asthma. We're going to talk about azithromycin in the use of wheezing children. And we're going to finish with a hot topic talking about alpha-gal allergy, which has been in the news a lot lately. So I'm excited to be joined today by Dr. Lynn Beccarier, who is Professor of Pediatrics in the Division of Allergy and Immunology at Vanderbilt. And thank you for joining me, Lynn. I appreciate it. Great to be here. But let's start with the care study. And this evaluation came out of New Zealand. And this was published in the Lancet uh in September of 2025. And I think you recommended this article, which was great. You just about overwhelmed me because when I got it, it was 120 pages. Uh, but a lot of that was appendices and uh other things. So we will get into the meat of this and try to summarize this the best we can. As I mentioned, this came out of New Zealand. Uh, this was a 52-week study where they follow children um and randomized them to basically either receive short-acting uh beta agonist. Um I'm gonna refer to as venelin because I get a when I talk about salbutamol, I get it confused with salmeterol. And so I think to avoid that, I'm gonna talk about venelin um to keep everybody straight who prescribes in America. Comparing that against the combination of butesinide and formaterol. And tell me a little bit about you look at that study, how it was set up, what you take from that.

SPEAKER_02 2:16

Sure. So this was a really important study because in adult medicine, this has now become the de facto standard for the management of mild disease. And it was done in an effort to see if you could improve asthma outcomes in children with mild asthma by instead of rescuing them with a bronchodilator alone. Anytime they were symptomatic, they would receive a bronchodilator combined with an inhaled corticosteroid and anti-inflammatory, an approach that's now referred to as air or anti-inflammatory reliever strategy. So this combination is very unique in that the bronchodilator for motorol is a long-acting bronchodilator. So, in unlike albuterol, which lasts four to six hours, this drug lasts nine to twelve, but they have identical onsets of action. So it is as effective an acute bronchodilator as is albuterol, which makes it amenable to its use as a rescue therapy and not just as a controller, how we've thought about it for more than a decade. So I think that's really important. It was an open label study. Um, so patients knew what they were getting, but it was indeed randomized.

SPEAKER_01 3:37

Yep. And so basically at the onset of symptoms, or we say they were to use this as a rescue inhaler.

SPEAKER_02 3:44

For any symptoms, however, they would have normally used their rescue inhaler, they would have either used albuterol or they would have used butestinite for motorol.

SPEAKER_01 3:57

Okay. And what they were able to show was when that was done, there was a 45% reduction in significant exacerbations. Um and there was a trend towards less severe exacerbations. I don't think it reached clinical significance, but it but it was but a significant enough trend to consider. Um so this has been, and we talked about this just a minute ago before we got started. This has been recommended, as you said, in adults and older adolescents, but it doesn't, hasn't really had the uptake that I think you would want or most of us would want. And I can understand that there's probably some concerns about adding the steroid or the long-acting bronchodilator, especially if people think about growth concerns in children. But actually, that was one of the things they looked at in this study and they saw no significant changes in growth. Um, is that correct? Correct. Yeah. Um so I mean it seems like uh well, let's let's talk about a couple things. Um they saw bigger effect in boys. Do you want to touch on the when they looked at the exhaled nitric oxide? Um, because I think some obviously I think they all had an elevated nitric oxide in the beginning, showing the inflammation. Um, but the uh effect I think was more noticeable in the older, in the adolescents. Is that correct? And so is that just because we think maybe it's more viral induced in younger children or as opposed to being more allergic older, or what did you make of that?

SPEAKER_02 5:27

I I think it's tough to make a full story out of their subgroup analyses. I think the higher level, the patients with higher levels of nitric oxide, those who had more type 2 airway inflammation at the start of the study, had an advantage if they used an anti-inflammatory reliever, and that makes an awful lot of sense. Um the age group I'm not overly concerned about. Both groups showed improvement. They were both in the direction of benefit of the combined therapy over albuterol alone. Um there was, as you mentioned, no meaningful growth effect. And I would suspect, this was only a one-year study, that fewer steroid-requiring exacerbations are of a great advantage to patients. So any therapy that we provide that allows children to have less exposure to systemic steroids pays them dividends over their lifetime. And that's really the key. It's preventing of those episodes. You know, this this is a therapy that is used for symptoms related to exercise. This is used when children need to pretreat. This is used when they visit grandma with a cat, and this is used in the setting of acute viral and nonviral triggered exacerbations. Those may differ by age group a bit, but I think across the board, what we've now seen is that use of a therapy that contains both an inhaled steroid and a rapid onset, long-acting bronchodilator reduces risk of exacerbations requiring oral steroids. And it does that safely, it does that effectively. And in that way, I think we need to as a we need to be moving our patients in that direction.

SPEAKER_01 7:24

Yeah. Well, and and like I said, it we've seen my experience as in primary care was that sometimes we really pushed the albuterol plus a separate steroid inhaler so far, um, but never really got the results we wanted. So it's it's really great to see that this is something that's showing indifference and something that we can do. Now, um, by the way, we just talked, they had a uh step up uh protocol as part of this too. So it started, and if they had an attack, then they um they used it as needed in the beginning, um, and then uh they stepped it up to twice a day with one puff of symbol cort, uh, and then twice a day if there was another severe attack after that.

SPEAKER_02 8:05

Um but it's important to point out that the children in the combined group needed less step up than the children in the albuterol alone group. So that's the whole point. Right.

SPEAKER_01 8:17

So we get a huge differentiation there. And so um one of the other barriers, if we talk about barriers to taking this study and instituting it, and we talked about this, we're using it off label. Symbicord is only approved uh for ages 12 and up. The dosing in this study was slightly different than than what we use here in the United States. But again, as as we were talking about, we use things off label all the time. Uh and uh as you mentioned, FlowVent at 110 is not approved for children, and yet it's been a part of kind of our step-up asthma theory for a long time. So um what is what is your message to to pediatricians or uh people that take care of children as far as those more difficult asthma patients, or no, not necessarily difficult, any asthma patient. How would you change at this point?

SPEAKER_02 9:03

Yeah, I think one point I don't think we've highlighted is that this was a trial done in children with mild asthma, children who did not need a daily controller. So these are children who would not have typically been recommended to use a daily controller. The only difference here is that they were given a combination inhaler for rescue as opposed to albuterol alone. As we get into children who need daily therapy, there's also advantages to this rescue strategy over albuterol alone. The FDA component to this is tricky, but not. Um, the FDA provides its recommendations and its approval for pharmaceutical manufacturers in terms of promotion. It does not say what physicians can or can't do with these therapies. These therapies are recommended as a first line in both the U.S. and international GENA guidelines. The groups that have evaluated the literature have made the conclusion that this is best care. And I think that is the recommendation to follow rather than the rather than the FDA label. The FDA label will not change because the companies that manufacture these products are not going to do the studies in the U.S. necessary to get that label change. That doesn't mean they don't work just the same. It's just a it's it's a regulatory issue more than a clinical issue. I think folks can feel very comfortable based on the strength of the literature, and that both national and international guidelines endorse and first line recommend these approaches should give comfort that you are providing the best of care when you treat children with anti-inflammatory rescue therapy.

unknown 10:58

Right.

SPEAKER_01 10:58

And to get back to your point, which is so important, a lot of the children were excluded from this study had they been on leucotriane and uh medicines or uh had corticosteroids within the last, I can't remember, a few months before the study, or maybe a year before the study. So this really focuses in on your everyday kind of occasional weezer uh who probably carries more of an inflammatory load than we kind of like to think about. Is that fair to say?

SPEAKER_02 11:24

It is. I think these are the children with mild disease where historically we've given them an albuterol inhaler. We say use it. They may or may not have had an asthma exacerbation in the past year, but we know they're at risk of having those. And by this simple change, this simple change that does not require daily therapy, that does not require ongoing therapy, it's just rescue. But it's better rescue, it's more effective rescue, and it prevents exacerbations in a substantially greater proportion of children than OPROLONED.

unknown 11:58

Yeah.

SPEAKER_01 11:58

Well, let's hope we can spread the gospel and and get that done. Of course, uh this was all done with um uh meter dose inhalers and spacers, and so just to say we should always be using spacers in these children as well. That's also the standard, correct? Yeah. Well, that's that's great. And so uh anything you want to add before we move on to our next paper?

SPEAKER_02 12:21

Yeah, I I just want to, you know, thank you for for bringing this um this concept out because I think this is really essential um that that our primary care colleagues really begin to think carefully about shifting our care to these patients who we have reflexively treated in what was for a long time, that's just the way we did it.

SPEAKER_03 12:48

Right.

SPEAKER_02 12:48

And it requires real effort to say, I'm gonna do it differently. Right.

SPEAKER_01 12:55

And and again, as we shift to a younger population, I think it's worth mentioning, and again, we discussed is um they're less likely to ask for their medications when they need it. They're gonna have to be directed by a parent. So as a parent, sometimes I think there's a slower response to symptoms that that an adolescent would probably self-treat much quicker.

SPEAKER_02 13:14

I think that's part of it. That may have explained in part the you know the trend toward an age difference. But I think as we retrain patients, we may get better at that. The other point here is we need to uh have an educational outreach to school nurses who may not be equally comfortable when we send in a non-albuterol medicine and say when the child needs pretreatment or acute relief, give them this instead of albuterol.

SPEAKER_01 13:45

And that's that's also going to take some time to sort of Is there an educational process going on currently in schools and there is.

SPEAKER_02 13:55

And um I'm very fortunate that I am currently president-elect of the American Academy of Allergy, asthma and immunology. Congratulations. And thank you. And as part of my efforts during that term, one of the initiatives that we're going to put forth is a broad approach to try to get this type of therapy into a sort of broader context and to help school nurses and other constituencies understand the importance of beginning to do things differently than we have for the last 30, 40 years. Right.

SPEAKER_01 14:34

Well, as someone who's practiced for 30 years, I think it's it is difficult when you're trying to turn something on its head that you that goes back as far as you remember. So exactly right. But uh, but this helps. And so thank you for talking about it and and bringing the paper to my attention. I think it's great. So uh, but let's let's move on, and we're gonna talk about another one that was in the news recently and and changes a lot of things. And um as a as kind of a historical reference for you, because I think you were involved in in looking at azithromycin uh when was that paper? 2015, I believe. Yeah. That you wrote 10 years ago. So what we're looking at is a paper that was published uh in the New England Journal of Medicine. Um, and this was in May of 2026, I believe. Uh yes. Okay. So azithromycin for preschoolers with wheezing in the emergency department. Now, this was a Picarne study, looked at 840 children, and the age range we're looking at here is the 18-month to 59-month, so basically the five-year-olds uh who had significant wheezing, moderate to acute wheezing. They used a uh a PRAM score, which I don't use routinely, but it basically defined the severity of the wheezing and then uh stratified them into a cohort uh based on um positive cultures. I guess they did cultures for a lot of the common uh pathogenic bacteria, H. flu, uh pneumococcus strep pneumonia, and uh Morxella cateralis. So they looked at those and then the intervention was to treat uh with 12 milligrams per kilogram once daily for five days of azithromycin versus a matched placebo. Um, so they actually matched the placebo to the same texture, taste, and all that sort of stuff to uh keep it all hidden. But it's uh uh it's interesting. They monitored these kids daily and they took us took a score, the asthma flare-up diary for young children, and they to my understanding, they scored it every day for five days. You could score anything from one to seven on that score, and then each day score was summed up and totaled uh and then analyzed. Um and the good news, I guess there's good news, the the antibiotic worked for eliminating the bacteria, right? Uh 58% clearance uh of the bacteria using the azithromycin versus 11% in the placebo group. So you would think that would be awesome, right? I mean, it should clear up everything right away. Uh unfortunately, this is a study that was stopped because of futility in the middle, because the difference in respiratory um distress or uh respiratory illness did not change a bit, right? Um so there was no differences in length of stay, hospital lengths of stay. These were all secondary outcomes they looked at, return visits and adverse events. So, you know, I remember being taught that of course this lethromycin has anti-inflammatory effects, antibacterial effects. And um, I think the paper that you wrote, which I didn't pull, but you can comment on obviously, uh, was a little bit different because you were looking at milder wheezer. I'll let you elaborate on that and tell me what you think of the paper.

SPEAKER_02 17:50

Yeah, thanks. So, you know, this study was based on a study we did about 10 years ago where we asked a fundamentally different question. We were interested in young preschool children who had recurrent wheeze. And using azothromycin as an anti-inflammatory andor antimicrobial, we asked if you gave it at the very first sign of a respiratory illness, before the low respiratory tract got involved, so signs of a runny nose, early signs of a cold, could you prevent progression to an episode that would have required systemic steroids for rescue? And we showed that that indeed did up, did work. It reduced the risk of prednisome by about a third.

unknown 18:36

Okay.

SPEAKER_02 18:37

So we were encouraged by that.

SPEAKER_01 18:40

And just to be clear, so these were children, you said recurrent wheeze, and they had a set number of episodes or hospitalizations or steroid.

SPEAKER_02 18:46

It was recurrent wheeze and um need for oral steroids previously. Um but this was done at home by the parents at the early signs of a respiratory tract illness.

unknown 18:56

Okay.

SPEAKER_02 18:57

Given the fact that uh a third of all preschool asthma wheezing encounters in the United States were associated with an antibiotic prescription, these investigators asked if you show up in an emergency department with a substantial episode where you're already wheezing and have moderate to severe severity, would that azithromycin hasten recovery from that episode? And the answer was a convincing no. Maybe it was timing, maybe giving it early has an effect, whereas giving it in the setting of acute um low respiratory tract involvement does not. Maybe there's just something different about giving it late. Whether it works as an antimicrobial or an anti-inflammatory, we still don't know. We've studied it in viral illnesses, we've shown anti-inflammatory effects that don't seem to have clinical correlates. We know that all the asthma guidelines discourage antibiotic use in the setting of asthma exacerbations despite its widespread use. And I think the takeaway here is that in this age group, if the children have enough disease to get you to acute care, the addition of azithromycin, on top of all the other things that were being done, bronchodilators, systemic steroids, did not make any meaningful impact. It killed germs. I mean, their colonization rates went way down, but there was no clinical correlate to it. And even in the children who had the nasopharyngeal bacteria, they didn't show a benefit either. So I think that's the risk. We always have concern about unnecessary antibiotic use, the concern for development of antimicrobial resistance. So I think this is one of those very important negative studies. And that's the reason it's in the New England Journal of Medicine, despite being stopped early for futility, because I think it's an encouragement that we have some things that work and some things that don't. And if you're reaching for a prescription of azothermycin in a s in this setting, you should think twice about it because there is not compelling evidence that the child will be better off for having added that to their regimen.

SPEAKER_01 21:30

Well, it's a good example of how science sometimes works at its best when studies don't go as planned, right? Because when when things don't work, we gain a lot from that too. So um so if we if we wrap this all in and we're looking at an audience that takes care of children, and I think that I think for a lot of us, or at least for me, I think azethromycin was something I can would consider in that situation where they're in my office and they're already sick and wheezing pretty heavily. So you're in the office, you're seeing lots of children in the Winter who have her wheezed before and they come in with cold, you hear a little wheezing again, but they're not sick. Um how do you bring that home? Would you lean on the side of being conservative, do you think?

SPEAKER_02 22:12

Or I mean, I would definitely try all bronchodilators. It helps more than you you think. Um, systemic steroids are iffy in this age group. Unless you are hospitalized or need emergency department care. The data for systemic steroids in outpatient episodes and preschool children is far from convincing. So I think it's frequent bronchodilators, it's conservative management, it's teaching families what symptom progression would look like and when to you know bring the child back for additional care. Um there are studies um using high-dose inhaled corticosteroids in this situation. That's another um strategy that that could be considered. Um I think I would do any and all of those before I would do azothromycin because I think that one in this setting, this this is this is as convincingly negative a study as you will ever read. There they dug deep, they dug wide, looking for somewhere where there was a signal. Yeah, none to be found. So I think I think this when they had adequate power, they had a DSMB that said you can enroll twice as many children, you're never gonna see a positive result. The trend is completely against it. And that's I think a really important lesson.

SPEAKER_01 23:47

I think that's one of the things they discussed in the potential weaknesses with stopping the study early, limited enrollment, but everything that they looked at statistically said it it's not gonna matter.

SPEAKER_02 23:56

Trevor Burrus Had they enrolled the remaining about 40 percent of children, there they would have had to have behaved so differently than the children they had already analyzed. I mean, it would have they they would have had to be completely the opposite. They would have had to not just have a response, but a remarkably positive response. And still they probably never could have hit statistical significance because this majority of patients already in the study had not a hint of uh of difference.

unknown 24:34

Yeah.

SPEAKER_01 24:35

All right, wonderful. We're to our ER folks and for our urgent care folks, pay attention to that study. Um, I think we always we're we're really, at least to the Vanderbilt system, we're trying to really pay attention to our stewardship with antibiotics, but this really brings it home that for the respiratory, we really don't need to be doing some of the things we're doing.

SPEAKER_02 24:52

Yeah, just one caveat though. These are children who did not undergo a thorough evaluation for concomitant suspicious pneumonia. This is wheezing alone. If you are convinced that there is a mnemonic process, ideally confirmed by chest radiograph and other features, then you would think differently. Right. That sort of asmonia phenotype. But in the straightforward efebrile, not happy, but not hospitalizable weezer, this this strategy does not add anything to the care other than cost, complexity, risk of side effects, and potentially the risk of antimicrobial resistance.

unknown 25:41

Right.

SPEAKER_01 25:43

All right. Wonderful. Great, great, great. All right, let's move on to the one that's really had a great headline in the news that we need to talk about, uh, and that is Alpha Gal. Um and maybe let's set the stage if you've got a minute to talk about what Alpha Gal is and how we've kind of evolved into this being more common, and then we'll talk about maybe the study a little bit. Sure.

SPEAKER_02 26:09

So Alpha Gal syndrome is now what's often referred to as red beet allergy. And it's a fascinating condition that is different than anything we had ever seen before. And it it's the result of a cross-reacting antigen, alpha-gal, alpha-1-3 alpha galactose, which is a component of mammalian meats. It is a carbohydrate, not a protein. And sensitivity to it is induced by the bite of the lone star tick. So people get bitten by the lone star tick. And a subset of them develop this IgE antibody against this carbohydrate. And then when they eat alpha gal-containing foods, red meats in particular, but sometimes there are some drugs that have this in them and some others, they develop delayed onset anaphylaxis. Normally anaphylaxis to foods occurs within, you know, five to sixty minutes. This takes four to six hours before its onset. And its onset can be profound, it can be GI, it can be um it can be respiratory, it can be the whole collection of anaphylactic symptoms. And these are patients who've reported tick bites. The more tick bites, the higher your chance. It's a very, very unique syndrome.

SPEAKER_01 27:48

Yeah. And I I thought it was fascinating because I started thinking about this, and you you think, well, alpha gal has been part of tick saliva forever. Um and you know, why is this suddenly coming to pass? It's an interesting story. I think it was found in 2009 as part of a study when they were doing a was it a monoclonal antibody that had a similar epitope to alpha gal. Cytoximab. Yeah.

SPEAKER_02 28:13

So there were these patients who, on first exposure to this monoclonal antibody, cytoximab, developed anaphylaxis. Yeah. And they studied what was unique about them, and allergists asked all these probing historical questions, and this concept of a tick bite kept coming up. So they fit said, well, what is it in these ticks saliva that is responsible for this? Now, is this truly a new problem? Or it has this been around for a while and we didn't know it. We've seen patients who we used to call idiopathic anaphylaxis.

SPEAKER_01 28:55

That's what I was thinking of, yeah.

SPEAKER_02 28:56

We we couldn't figure out what was causing their anaphylaxis. And the ones that are delayed onset, we didn't know it was anaphylaxis at all because we always say, well, come on, six hours, how is that possible? Um but now we are starting to understand this. And you know, by by way of uh a plug, we are now starting an NIH-funded study at Vanderbilt, centered at Vanderbilt, on further defining this condition where we're gonna do food challenges with an alpha gal deficient pork product. So there have been pigs that have been bred to not have alpha gal in them. And we're gonna use that as a comparator to standard conventional alpha gal containing. Figure out who really has allergy, what it looks like, identify biomarkers, identify other factors, because this paper brings out a really important point. And what this paper brings out is what they looked at is the seroprevalence of this alpha gal antibody in blood donors.

SPEAKER_03 29:57

Right.

SPEAKER_02 29:57

Okay, these are in people who showed up and said, I have alpha-gal syndrome. They said, I'm a good person. I want to donate blood.

SPEAKER_01 30:05

Right. And they they gave their consent, obviously, to keep the blood for future work, and they went back when they looked at the study. And we are we are kind of in the bullseye of this right in Tennessee. It's basically uh in the southeastern states, Tennessee, Kentucky, Missouri, Arkansas was sort of the hotbed, I think, uh, and with the highest incidence, which I believe was in the 30% range. So it's amazing, but and and I think also the older cohorts had a much higher um incidence of this as well. So something over time, rural areas, uh, I don't think it was significant maybe, but you saw a trend towards less urban areas, which makes sense. Um, that you would be more exposed to tick bites. I think it was interesting that North Carolina, the forestry and state park workers had a 60% incidence. But but the take-home message is just because you have IgE antibodies, which by the way is worth mentioning, we all have IgM and IgG antibodies from GI exposure, but through the tick bites, the IgG exposure does not correlate or the percentage of uh IgE uh presence doesn't correlate with the disease or the syndrome.

SPEAKER_02 31:15

Yeah, that's that's really the basis of the study we're doing. And the the point here is just because you have a positive test to Alpha Gal doesn't mean you have Alpha Gall syndrome. So there are patients who we say present in one of three phenotypes for Alpha Gaul. One is delayed onset anaphylaxis. They eat red meat, and four to six hours later, they have clear everything that looks like conventional anaphylaxis is just delayed. There's a group of patients who have chronic GI symptoms, irritable bowel type stuff, belly pain. Many of those folks get tested for alpha gal and they have a positive alpha gal test. Whether that collection of symptoms is in any way biologically related to that antibody is uncertain. And then there are patients who have chronic hives who also, you might imagine, have been tested for alpha gal and have positive tests. But again, we know now that in states where this um is common, 20 to 30 percent of people totally asymptomatic have this antibody. So the antibody does not define the disease. Just like in conventional food allergy, the antibody alone does not define food allergy. You need a clinical scenario that is also consistent. And I think that the point here is that if you think you have alpha gal because you have a positive test, you avoid red meat, which for some people is a huge concession.

SPEAKER_01 33:00

Especially in the south.

SPEAKER_02 33:01

In the south. So you're potentially unnecessarily avoiding something that isn't causing your problem. You don't know what is causing your problem because you thought it was the red meat. It's it leads to a lot of frustration, needs to, you know, real challenges, folks, you know, filler, you know, and then there's a long list of other food and other food products that have trivial amounts of alpha gal in them. So if you think you're allergic to it, then you start avoiding more than red meats. And then all of a sudden, you have a very complicated diet in front of you that may or may not be medically necessary.

SPEAKER_03 33:43

Yeah.

SPEAKER_02 33:44

And that's the whole point of the study we're doing is to try to really sort that out. The higher your alpha gal blood test, the more likely it is to be real.

SPEAKER_01 33:54

Okay, that makes sense.

SPEAKER_02 33:56

Okay. But if you're just at the lower limit of detection or a little bit above, you may not. The other thing we know is that the natural history is that a lot of people lose this allergy. So this antibody, unlike peanut allergy antibody, this antibody fades away. So people who are low might need to be retested over a series of years because this often seems to quote unquote go away. And that's really important, you know, unlike peanut allergy, which typically does not. So, you know, it's it's really important to understand the sort of natural course of this.

SPEAKER_01 34:36

Aaron Powell Do you think the break point of uh being a positive IgE for this would would change if you talk about that?

SPEAKER_02 34:44

Or we're gonna look at that in this study. Um, you know, all of the literature out there is based on case series and things like that. None of it's been done in a prospective controlled manner, where the confirmation of alpha gal allergy is made during food challenge where we feed you what we know you should react to, and we'll figure out if there's a if there's a better number other than positive.1 is almost certainly too sensitive. But I don't know if it's 0.3, I don't know if it's three, I don't know if it's 33. It's it's very hard. We'll we'll get a better sense. The higher, the more likely.

SPEAKER_01 35:22

But yeah, and I think the problem too is if you have a positive test or you've been flagged as a positive test, like you said, you start thinking about everything that you eat, and people say, well, alpha cows and dairy, you know, but so many people can be sensitive to dairy with GI effects. And so you know, it's hard to call that.

SPEAKER_02 35:38

And we see folks who can tolerate one red meat, but not the others. Yeah. So it's pretty variable. So, you know, that these things can take on lives of their own, and they can really make you a prisoner in your own body if you um if it isn't well worked out and well defined.

SPEAKER_01 35:58

Aaron Powell So are you saying 10 years from now we can walk into a restaurant and you have your gluten-free menu and you have your alpha gal-free menu?

SPEAKER_02 36:04

Is that it it's not impossible. I mean, there are we are using a uh pork product that comes from pigs that were bred specifically to be alpha gal deficient. They didn't do this because of alpha gal syndrome as we talk about it. So antibodies to alpha gal are important for acute organ rejection in transplantation. And these pigs were bred for their heart valves, for heart valve replacement surgery. Because if you take a standard pig heart valve and you put it in a patient with alpha gal, the valve falls apart. And that's not what you want after your heart valve replacement. And now there's a lot of research being done with these animals for xenotransplantation, because if you can get rid of alpha gal, maybe we can start using non-human organs in transplant because those that alpha gal in them makes them targets for ejection.

SPEAKER_01 37:09

Yeah. And it I it always fascinates me the overlap between blood types and certain diseases. And blood type B seems to be protective, but seems to be because there's a very similar epitope there as well.

SPEAKER_02 37:22

There's an alpha gal-like structure in Lewis antigen B. Um that and we know if you have an antigen, you usually don't become allergic to it. Um whereas the vast majority of blood donors are blood group zero blood group O. They don't have alpha gal, and therefore that's how this um study is informative. Okay.

SPEAKER_01 37:45

Well, I'm an A B, so I feel good about that.

SPEAKER_02 37:47

Well, yeah, it's a B, so I think you're go find I wouldn't go exploring for tick bikes.

SPEAKER_01 37:52

No, I'm not gonna do that.

SPEAKER_02 37:53

They have plenty, they have plenty of other horrors that they can bring.

SPEAKER_01 37:56

But the other interesting part of that, I think, is you the lone star tick uh has expanded in coverage across the states, and part of that may do to climate change and things like that. And that just is another reason why climate change affects medicine and epidemiology.

SPEAKER_02 38:11

It's yeah. The other thing is it's becoming increasingly clear that the lone star tick does not have the market cornered on this. There are other ticks that do this as well.

SPEAKER_01 38:20

But it's not in Maine with the black-legged tick, yeah.

SPEAKER_02 38:22

So so I mean, there's it it it was originally described with the lone star. It's clearly the the leader of the pack, but there's a lot of uh tick species that have alpha gal or alpha gal-like products that are capable of driving this disease just the same. I mean, they see it in Minnesota, they've they they see it in places where no lone star tick has ever gone. The other point that we we you know remind our fellows all the time is you got to take a travel history. You know, just because you live in Minnesota doesn't mean you don't go to the beach.

SPEAKER_01 38:57

Exactly. Or hike anywhere. So um so I think wrapping that all up, I think the key is it you you heard a lot in the media, people may want to be tested, but you really have to be thoughtful about testing. And and as I was taught a long time ago, know what you're gonna do with the test result before you order the test. And I think this paper helps us think through that, and you've helped us think through that. So I appreciate that. Any other final thoughts on any of the papers that we've reviewed today?

SPEAKER_02 39:24

Um, I I think we've seen a good display of what's new in the world of allergy. These are common problems. These are um patients who come to us with challenging concerns, and we need to be prepared with knowledge. Um, what we've seen today is that just because you have a positive test doesn't mean you have a disease. Um mothers, fathers of acutely sick children often find an antibiotic prescription to be reassuring, and it's harder to not write one than it is to write one. But at least in the setting we talked about today, we should hold strong that antibiotics don't help every situation, and we should be very thoughtful and judicious about it. Yet another reason to do so, and that asthma care in the coming decade is gonna look different than asthma care has looked in the last three or four decades, and that we have to embrace the fact that we are gonna be better at caring for these patients. It takes some reprogramming, it takes some rethought, but I think once we do it, we'll see fewer sick children.

SPEAKER_01 40:38

Yes. Well, speaking as an old dog, we can all learn new tricks. So I appreciate that input. So well, Dr. Pecari, thank you so much for your input today. And thank you for everyone out there who's been listening or watching. We appreciate you uh being a part of this uh podcast. And certainly if you have any questions about this episode, these articles, or you've got a paper that you really want us to focus on, reach out to us again. Our email is cpfnashville at gmail.com, cpfnashville at gmail.com. And uh we look forward to doing more of these and hopefully you get a lot out of them. So until next time, everybody, take care.

SPEAKER_00 41:16

Thank you for joining Cumberland Conversations. We're proud to support the people who care for Tennessee's children. Don't forget to subscribe so you never miss an episode and stay connected with CPF for more tools, trainings, and community essays. Until next time, take care.