Episode 25: Is eczema inevitable for some kids? Breakthrough research suggests that testing and intervention for newborns could change the trajectory.

Research

Dec 8

Written By Global Parents for Eczema Research

Imagine if doctors could use a non-invasive test on newborns to predict their risk of developing eczema? Now it might be possible. What’s more, new research suggests there is something you can do for high risk babies. Join us as we learn about an innovative test for eczema and what you might do with this information. Our guest speakers are Dr. Anne-Sofie Halling who is completing a PhD on biomarkers of atopic dermatitis at Copenhagen University, Denmark; Prof. Alan Irvine a professor of dermatology at Trinity College, Dublin Ireland; and, Prof. Jonathan Hourihane a professor of pediatrics and child health at Royal College of Surgeons in Ireland. (If you like our podcast consider supporting it with a tax deductible donation.) Read the transcript.

[00:00:00] Lynita: Welcome to the podcast. my name is Lynita Howie. I am an eczema parent and manager of the podcast for Global Parents for Eczema Research. This episode is about research breakthroughs in 2022 for children with eczema.
We dig into two recent publications that we hope will one day pave the way for preventing eczema in our kids. The first interview is from Denmark and describes skin biomarkers that are linked to eczema in newborns. The innovation here is a non-invasive way. The test is performed.
In the second interview, we discuss a surprising finding out of Ireland that using emollients in the first weeks of life can decrease the chance of a baby developing eczema. It's surprising because the results are opposite to that found in other recent studies.
We discuss why these results are so different and what it means for babies of the future. And here is our host for today's podcast, founder of global parents for eczema research, Korey Capozza.
[00:01:00] Korey: Welcome to the podcast. I'm pleased to introduce our guest, Dr. Anne-Sofie Halling. She studies predictive biomarkers of childhood eczema at Bier Hospital in Copenhagen University in Denmark, and we're really pleased to have her today to discuss her latest research on using tape strips to detect biomarkers that can predict eczema. So, Dr. Halling, welcome to the show.
Anne-Sofie: Thank you very much,
Korey: We wanted to dig a little bit into your paper, which was presented at EADV Conference. Can you talk a little bit about how you did this study? It was, I believe, a cohort study in 450 babies in Denmark. Yes? You were able to look at both those that were born on time as well as those that were preterm, and then to look at their skin barrier as well as markers of the immune system, and try and figure out if any of those could predict whether or not the babies developed eczema during the first two years of life. Can you say more about the cohort and how you went about doing that?
[00:02:06] Anne-Sofie: Yes, of course. So, as you said, it is a birth cohort and we included 450 newborns, from Copenhagen in Denmark. So 150 children were born premature, and then 300 children were born at term.
And then we examined them when they were born within a few days, and then again when they were two months old. And all children were then followed until two years old, where we ask questions on whether they develop any signs of eczema and if they did, We had them in for one more visi .
So when we examine the children at birth and at two months of age, we applied these tape strips on the back of the hand. And when you take these tape strips off again, there is these dead skin cells on the tape. And these dead skin cells were analyzed for skin biomarkers that potentially could be associated with an increased risk of atopic dermatitis.
[00:03:13] Korey: Great. And the tape strip itself, which is kind of the innovation here, it's basically like putting a bandaid on the skin and taking it off, right? It's not painful but it tells you a lot.
[00:03:24] Anne-Sofie: Yeah, it's, not painful at all. I can tell. We, do it eight times just after each other, and it doesn't hurt at all on the children. I mean, they were newborns and they were two months old. We would never have done that if it was hurtful in any way.
So it's, really a non painless method, even though you just get these dead skin cells, they can tell us so much about the skin and also it appears that it can actually tell us who will develop eczema in the future.
[00:03:56] Korey: Yeah, it's a fantastic breakthrough. And so when you looked at these tape strips for different biomarkers or I guess indicators that might tell you if the baby would go on to develop eczema, what did you find?
[00:04:11] Anne-Sofie: Well, what we found was that children who had elevated levels of one of the immune biomarkers called TARC they have twice a risk of developing atopic dermatitis during the first two years of life.
[00:04:28] Korey: And just to explain a little bit so TARC, what is it? I mean, it's a indication that the immune system is active in some way, right? Isn't that what it's telling you? Overactive,
[00:04:42] Anne-Sofie: Exactly, yeah. It is what we call type two mediator, which means we have something called a type two inflammation in the skin, which we see is up regulated in children who have atopic dermatitis. So in these children where there are high levels of this, immune biomarker. There are an increased risk of developing atopic dermatitis.
We also found that beside the immune Biomarker TARC, two other immune biomarkers called IL eight and IL 18 also increased the risk of developing moderate to severe atopic dermatitis.
[00:05:25] Korey: So the IL eight and IL 18 um, maybe really useful for being able to screen those kids who are likely to have more severe eczema.
[00:05:35] Anne-Sofie: Yeah.
[00:05:35] Korey: Yeah, really helpful. I think we primarily serve children with moderate to severe eczema, so to be able to identify those is hugely beneficial.
Anne-Sofie: And then further in a sub group of 88 children, we also identified that lower levels of lipid biomarkers in these children, aged two months was associated with development of atopic dermatitis so, just to sum up, we found that by using these tape strips to measure both lipid and immune biomarkers, which is a very simple, a painless, and noninvasive method, we were actually able to identify the children at highest risk of developing atopic dermatitis.
Korey: So these markers are a way of telling if, the immune system is headed in a certain direction, basically.
[00:06:30] Anne-Sofie: Exactly, yeah.
[00:06:32] Korey: So what are the implications for parents? Is there anything that they can take from this research now?
[00:06:38] Anne-Sofie: Well, as we are the first to identify these predictive biomarkers of atopic dermatitis, there is of course need for further studies to confirm our results. And it is also possible that studies will be able to find even better predictive biomarkers of atopic dermatitis using, using the same method.
But in the future it will probably mean that by using this method to identify the children at high risk of developing atopic dermatitis, preventative therapies
could be used against these children only. Thereby decreasing the incidence of atopic dermatitis. So for parents who are concerned about atopic dermatitis, they would be able to find out if their child is at high risk of developing atopic dermatitis, and if preventive therapies can be initiated,
Korey: Fantastic. And does your group have any studies to look at that piece? Like how we can use this now to prevent
Anne-Sofie: Well, that's the next thing. It is, it's of course, important to address that. Currently there are no recognized preventive therapies against atopic dermatitis.
And in my group, we are currently not examining any preventive therapies, but a recently published clinical trial called AD Stop Trial. They found that OLS during the first two months of age was associated with a decreased prevalence of atopic dermatitis during the first year of life. So these data supports our findings that there probably is an open window during the first two months of life where identifying children at high risk of atopic dermatitis are possible, and where preventive therapies may also reduce the risk of atopic dermatitis.
Korey: Yes. And that's an excellent segue because actually our next guest is going to be talking exactly about that issue. Uh, Dr. Halling, thank you so much for joining us today and for the excellent research that you're doing.
[00:08:48] Anne-Sofie: Thank you for having me today.
Korey: And next we want to take up that topic of early intervention to prevent eczema. And I'm excited to have two guests on our show today.
Professor Alan Irvine, who is a professor of dermatology at Trinity college in Dublin, Ireland. He has a research interest in the genetics and disease mechanisms of eczema. And we also have Dr. Jonathan Hora, hun. He is a professor of pediatrics and child health at Royal college of surgeons in Ireland. And his research focuses on the link between skin barrier, dysfunction and allergic disorders. Thank you so much for coming to the podcast today
So we're really excited to talk a little bit about your paper, which came out last year. On using short term emollients to prevent atopic dermatitis or eczema in high risk infants it was called the stop a d trial and we wanted to first ask you why you did this study
[00:09:44] Jonathan: So with Alan We did a birth cohort study looking at the outcomes of allergic diseases. We were measuring their skin barrier function with the thing called trans epidermal water loss, which is where you measure the amount of water that comes out of a defined area. And we were looking at our data, once we completed the study, which had over 1200 children and we saw that there was an increase in trans epidermal water loss measured very soon after birth, before the children went home from hospital up to about eight weeks, and then it was stable after that. And we thought that might represent an early window where the changes were most dynamic. And, would a short term intervention have an effect that lasted to the time points where can be defined which are six months and 12 months.
[00:10:32] Jonathan: So babies were recruited after birth by us going to the bedside and mothers being asked to join the study and have had measurements of their trans epidermal, water loss and once they had those measurements done babies were randomized to being put onto an eight week program of a ceramide and node based, commercially available product and told to stop using it eight weeks later. Or going onto ordinary care, moms and dads could do as they wished with the skin. The nurses who were recruiting and randomizing were not communicating the randomized status of the babies to the medical doctor who was evaluating their skin.
[00:11:10] Korey: Did you give any guidance about how to apply it? Like with gloves or you know anything like that
[00:11:16] Jonathan: yeah, Great question. They had to walk their hands. They weren't to wear gloves and it was to be applied just as minimally as possible using the fingertip unit measurements that are used for steroid, We wanted them to use as little as would reasonably cover the skin, we were using really small amounts of moisturizer for a short period of time, and I think they may both be important factors in the success of the findings.
[00:11:41] Korey: Was it applied everywhere or just in certain areas?
[00:11:45] Jonathan: All over the body, including the faces.
[00:11:47] Korey: Okay. And then you compare this group of babies who are receiving this regular moisturizer therapy. Two babies who weren't and the babies in the other group were just doing their usual care. Can you talk about how you tracked what those other babies were doing,
[00:12:03] Jonathan: We we were we were asking questions each time how have you applied moisturisers. So the what's called the contamination rate is how many people in the control group did the active treatments that was very low.
[00:12:14] Alan: Yeah, I think that's important. The adherence rates they were very high through the treatment arm. And the use of emollients was really quite low in the control arm. So there was quite a good contrast in the skin experiences, if you like, of those babies.
[00:12:28] Korey: Yeah, good points. how large was the effect that you saw.
[00:12:32] Jonathan: A 50% reduction in the rate of at 12 months and a 37% reduction in the rate of at six months in the children who had treatment. And one of the powerful things about that is that's the short term intervention and the readout was months later. So it's kind of impressive.
Starting something so early in life reduced the condition by 50% when measured six months later and 12 months later. So that was kind of gratifying in a scientific way, but also impressive in a social way that wow, that effect, we didn't measure eczema at eight weeks, but you have to wait until the last baby went through the 12 month appointment to see these results.
[00:13:15] Alan: We saw an even bigger effect on the babies who had atopic dermatitis at six and 12 months, and those are the kids who we believe are more likely to convert into moderate to severe AD's and have additional comorbidities, which is just a fancy term for saying food allergies, rhinitis, asthma, that kids.
Moderate to severe AD kind of accumulate quite easily as they go through life. So we saw an even bigger effect size there. Just one other thing that was interesting, we did stratify the kids as to whether they had filaggrin mutations or did not. So we sequenced everyone's filaggrin gene, So So we were very certain about who had a mutation and who did not have a mutation, and we could see the value of the intervention was much greater in those who had filaggrin mutations. And they're also the highest risk kids. So it was another little bit of a reassurance that there was a bit of science in this.
[00:14:12] Korey: What's exciting about it too is it's getting us closer to being able to really identify those high risk kids and do something about it early in
life. Whereas before, we just weren't really able to stratify risk very well.
[00:14:25] Jonathan: We're coming to that with some secondary analysis, but we're trying to use trans epidermal water loss, and filaggrin status. So we're trying to build an early life model so that we could maybe do a few little tests in the first few weeks and then go, hey, you are actually in the high risk group, so we might have to do something about you.
But that stuff that's gonna evolve. So, I mean, it really is the golden fleece trying to find how to tell you in the first two weeks of life who, who will or won't have eczema. We're close with this, but, we're not close enough.
[00:14:55] Alan: That comes down to an area where you guys are experts really. The question is who is likely to do these? And it's probably parents like yourselves or your listeners who are gonna be most motivated because they're aware of the impact of having a child with moderate to severe AD on the child and the family and, you know, it's a long term burden.
[00:15:15] Jonathan: There's two parts to this if we could find out who's got high risk, but most children who get eczema are not high risk, they just get eczema, you know, their background may matter or not. So whether this is so simple that everybody should do it, is a discussion that's for us to have.
Korey: Yes. Is it really something that parents will be willing to do? I think that's a great question. It also sounds like we're not quite there yet with the science. And I wanted to ask you about the prior studies on this topic. Which i found quite the opposite to your finding so how do we make sense of that as parents and can you talk a little bit about what those large prior studies found on the use of moisturizer therapy early in life Life
[00:15:58] Alan: What what they find each of them that the use of emollients was no overall benefit atopic dermatitis. incidence at two years, there was also a trend towards sensitization for food allergy and a low level increase in the intervention arm in skin infections. So, that was obviously a negative and perhaps some early signals that they may even have caused some harm with infections and food allergies, although those were not statistically significant. There was a trend in that direction.
[00:16:31] Korey: And I think it was really surprising to everybody, the findings, because here we were all thinking that this was gonna be a really
promising way to prevent eczema. And then we saw sort of the opposite of what we were expecting in terms of benefit, but also some additional risks.
[00:16:46] Jonathan: We'll never know why they failed unless we dig down and go into each of those variables in a separately, adequately powered trial of each of them. I think they were a little bit over-complicated in the beauty of our study in comparison, which is it's simplicity.
[00:17:02] Alan: So compared to our trial, BEEP and PREVENTADALL they went in a little bit later with their intervention. They intervened for a lot longer for up to a year, and they intervened with petrolatum based and some mixtures of emollients, and PREVENTADALL also had a food introduction piece as well. And then the Cochran Review was built on those two trials
[00:17:24] Korey: Yeah, great summary. I mean there's so many variables there, right? Like you were just saying, like which emollient, for how long and which kids, how you apply the emollient. Like are you introducing peanut onto the skin inadvertently, you know, there's like so many things to consider, you really have to figure out all of those things to perhaps get it right.
[00:17:43] Jonathan: That's why the field is still wide open.
[00:17:46] Korey: Yeah, what was it about your approach that led to the benefit? Was it the the, window of this very early childhood period? Mm-hmm. you know, answering, perhaps those questions next seem important, but what are your thoughts on next steps from here.
[00:18:00] Alan: Yeah, all of that and is it generalizable can other groups benefit from it? Maybe people living in very urban centers, in areas where there's a lot of multiethnic families living. Would it work there too? So I think those are where we'd like to do our next studies really, but the other variables like timing and duration and emollients, the only way you can answer those is through larger well conducted clinical trials.
[00:18:25] Korey: Yep. Good points. Well, we're excited to see where this goes. And I think , this is one of the frustrating things about research for parents is, you know, I think this question is answered, and then it gets reopened again. But I think this is one to watch as we go into 2023 and subsequent years, and hopefully there'll be some additional research groups looking at this question now as well, since you've kind of reopened the chapter in some.
[00:18:49] Alan: I think just Korey's right, research can be frustrating, you know? And it's good to be careful and reflective just about things and replicate results. That's really what we want to do. And then you begin to get a much clear review. But I think it's exciting.
[00:19:02] Jonathan: Yeah. pleased to reopen the area, you know, because we, the one at risk that everyone's gonna move on, but we haven't closed the area.
[00:19:10] Korey: Fantastic. Well, thank you both for doing this research. There's not a lot of people looking at prevention of eczema and it's so important. Treatment is important too, but if we can get upstream of the condition and prevent these kids from suffering in the way that they do now, I think it's fantastic. So again, you know, thank you for the work that you're doing to benefit kids with eczema and also thanks for being on the podcast.
[00:19:31] Jonathan: Thank you for inviting us. It's a pleasure. Thank you. Pleasure