Sleep apnea is the most common sleep disorder in childhood and even mild OSA can affect neurocognitive function, so prompt and fitting care is essential. To help providers find the right method for individual patients, pediatric pulmonologist Gwynne Church, MD, describes recently developed and emerging treatments, providing data on efficacy and explaining key considerations, which range from palate shape to the specific needs of kids with trisomy 21. Learn when watchful waiting is an appropriate choice and hear about a drug combination under investigation.
All right. So I'm just gonna talk about new and you know, emerging treatments for sleep apnea and um uh how to have an individualized approach. Um First, just really briefly, just about sleep. Um I think we're learning more and more about how important sleep is to well being. Um it does have minor effects on our immune system, our mood, our neurocognitive functioning, our cardiovascular health and in adults associated with high blood pressure and stroke. Um and also our pulmonary health, especially asthma and just our general well-being. So I think as time goes on, we're realizing that sleep is probably as important as diet or exercise for a healthy life. Um So diving right into sleep apnea, which is the most common sleep disorder in childhood and just going over some definitions. So, mild obstructive sleep apnea is defined as an obstructive apnea, hypopnea index between one and 4.9 and at that level, even though it's mild, um you, you will see neurocognitive impairment in some people, especially with problems with attention and focus and also um memory and um which would be a little bit more common in adults than kids. Um but even at these mild levels, you can see a change. So if someone is symptomatic, like a patient with a DH D and they have mild OS A, we'd still try to treat it. Um, moderate OS A would be an H I between five and 9.9 and at that level, um, you're still gonna have, of course, your neurocognitive impairment, but now you'll also have signs of cardiac strain, um, including your blood pressure, not going down as low as it should when you're sleeping and having blood pressure at the upper limit of normal for age. So, not really hypertension, but the blood pressure is gonna be higher than it is for their peers. And so, um also markers of inflammation uh um that are associated with poor cardiovascular health and adulthood do become elevated in Children. So, so, you know, once you're getting to moderate severe Os A, you're probably impacting their future cardiovascular health and then severe, always say we define as an A H I greater than 10. So our main state therapies um are really still probably the most effective. Um I'm not gonna go over them today cause we're gonna talk about new treatments but just didn't breathe. So, um removing tonsils still like really is gonna be your primary, you know, treatment for almost all kids with sleep apnea because it really works. And um it, you know, basically cures about 80% of people. Um And it, it has it doesn't work as well if you have other problems like severe obesity, um, other heart and lung disease. Um, also treating the nose works really well, especially in the younger child, like younger than age seven, if they have allergic rhinitis or enlarged adenoids, decreasing that inflammation with a nasal steroid spray or mono Leucas is beneficial. CPAP. Um, works really well. I mean, there are some Children where they're just never going to acclimate. Um, or if they're young, it's, it's hard to commit to a lifetime of CPAP, but it does work quite well. And then weight loss, of course, in the obese patient, but it's, it's really kind of a, a really hard battle. So, um currently, if we're looking for an individualized approach for sleep apnea for a non surgical options, um, after the tonsils have been removed and you've mild to moderate sleep apnea, we're really looking at, well, do you have allergies? And if you do, should we think about a nasal spray or Mono Lucca if you don't have allergies, but you're symptomatic should we use CPAP? Um And then for the moderate to severe O they were really looking at CPAP. So our, our choices are somewhat limited in the traditional model. Um Today we'll talk about new and emerging treatments, um which are non-surgical, um except for the hypoglossal nerve stimulator. Um, but um there are multiple uh surgical options of the upper airway that we're not gonna talk about today. Um So these would be those non-surgical treatments. So the first is a watchful waiting. And um, this became an option after the chat trial, which is the first randomized controlled trial in pediatrics where they took a bunch of school age Children, um, over 400 they randomized to let's take your tonsils out for no treatment and followed up at seven months following and, you know, with a repeat sleep study and checking in on their attention scores. And this um study was in Children aged 5 to 9 years and the study found that the H I decreased in the treatment, but also the placebo group. And so it actually normalized in 80% of those who had their tonsils removed, but also in 50% who had no treatment whatsoever, which is kind of a surprise to everyone that 50% of people would get better on their own. There was no improvement in the treatment group in the attention or executive function, which was the primary outcome, which was also a surprise, but then it turned out that the um the attention score they were using was later found to be kind of flawed. So that was an issue with the study. Um It did find that there was in the treatment group, an improved quality of life, um and also improved parental scores for behavior, daytime sleepiness as well, more so for moderate than mild Os A. So there did seem to be some improvement from tonsillectomy. Um, although it wasn't in the primary outcome and there was more improvement in those who had moderate than those who had mild OS A. So the takeaway from the study could, people could take away different things. Um, but in general, um, a takeaway is with the tonsillectomy is beneficial in those patients with especially moderate Os A. But watchful waiting can be considered in patients with mild Os A. So, um I find the study to actually be helpful, um because especially if you have a child who, you know, the parents are concerned about snoring. And so you do a sleep study and it's mild but they never really had concerning symptoms. So they weren't tired, they didn't have attention issues, they're doing fine in school and you finally just have mild o say, then you're really not obligated to do anything and you can reassure families that there's 50% chance that they'll improve on their own and that you can monitor over time. Um Likewise, if someone has moderate Os A and they're symptomatic or mild Os A and they're symptomatic, this wouldn't change the recommendation for treatment um, in watchful waiting. Um, in younger Children aged 2 to 4 years, this, the study was done and basically has the same design and the same results as that for older Children. Um which was that the H I decreased in both the treatment and placebo groups more so in the treatment group though. And more so if you had moderate than mild OS A, a quality of life improved in both groups or in the treatment group. And in summary, watchful waiting can be considered in patients with mild Os A while tonsillectomy should be considered if you have more moderate OS A. So I think the study, these studies didn't really change that much of what we do, but it, it does give you a little wiggle room as a provider. If you have someone who's relatively asymptomatic to feel comfortable, reassuring that things, you know, have a good chance of getting better on their own for other treatments. Um We're gonna talk about orthodontic devices which would be a rapid maxillary expander and mandibular advancement devices. So, um chronic mouth breathing in early childhood disrupts the growth of the jaw such that it grows more in a back position and forward and it also changes um the palate to grow as a more high arched palate. So on the right picture is a high arched palate on the left would be more of a normal palate. So that chronic mouth breathing is kind of, you know, changing the face in such a way that as you get older, it, you will have more risk for sleep apnea. The problem with the high arch palate is it takes up the the base of the nose. So you've increased nasal resistance which contributes to snoring. Um And so if you treat nasal obstruction in early life um with like your mono leucas or nasal steroids or removing adenoids. Um For that chronic mouth breather, that child with recurrent ear infections and chronic congestion. If you can clear that up, you know, you may be helping to prevent problems down the line once the jaw or not the jaw, the palate is high arched. At that point, you can use a rapid maxillary expander to widen the palate and decrease nasal resistance. And it's a um orthodontic device that anchors to the back teeth of the upper jaw um and will widen the palate along the mid palates, suture before it fuses in Children aged 5 to 15 years, reducing the nasal resistance and not breathing. This is a meta analysis of using the rapid maxillary expander in pediatrics and um in general, um using it it on the right hand of the Scor plot shows how much it improves the A H I and in general, um if you pull it all, it improves it by about six points and it's really only been studied in mild to moderate Os A um which again would be somewhere between, you know, one and 10 for your A H I. So improving by six points is actually pretty meaningful difference. Our mandibular repositioning devices are really, you know, a mainstay of treatments in adults with OS A. Um they have many different kinds and they're very effective uh especially in more moderate Os A and um for adults who can't tolerate CPAP, this is, you know, really beneficial treatment. We're kind of starting to use this in Kis more recently and it's not on, you know, only for um nighttime use. It also is really considered as a functional appliance to stimulate growth of the jaw to a more forward position. So an orthodontist considers it really more for that patient with uh retro naia because the child's growing. So it's gonna affect how the job grows. So it's a little bit different. Um And this is a meta analysis of these devices used for pediatric isa. Um they use different devices and keep them in place for different amounts of time. So sometimes it's only for sleep and then also some of the studies they're using it for 24 hours. So there's some variability there. Um But um in general, um it does show an improvement of pool data would be by about four points. Um And so again, this has really been studied just in mild to moderate OS A but four points is a meaningful difference. Um The functional devices stimulate growth of the mandible into the more forward position. They work best if you start before age 13 and use it for at least six months, they're also more effective if you use it during the day and at night. Um there aren't that many studies in Children. Um But there are high dropout rates because the kids don't want to wear it during the day because it's not comfortable, there's excessive salivation, they don't want to wear it at school. Um There's also concern for long term effects of stress on the temperament, TT MJ. Um and possible orthodontic effects of really moving the jaw too much in a forward position, but it does appear to be effective in kids in with Os A who have that retro nathia. So if you have a patient who has that, um that is like the person who would be a good candidate. Um And then moving on to myofunctional therapy. So, myofunctional therapy um is been around for a long time for kids with speech and swallow issues and is more recently being adapted to kids with OS A and um it consists of a series of oral fringe exercises to improve lip seal, lip and tongue, tongue, the resting tongue position and nasal breathing and the exercises are performed um 2 to 3 times a day for 45 minutes a day, although there's a lot of variability there and what's prescribed. Um This patient in the picture is just doing, you know, typical type exercises where to improve her tongue tone. So she's protruding her tongue, curling her tongue, um touching it to the roof of her mouth and trying to lift it up towards her nose. Um But there are a lot of different exercises that are out there. Um These are more geared towards the tongue. They are also exercises that an ot will prescribe to, uh, foster more nasal breathing. And, um, and that analysis, um, of myofunctional therapy in kids with OS A indicates it is effective for mild to moderate OS A. There was a lot of heterogeneity in the studies in terms of what exercises they did and how long they did them and their outcome measures. And there was a high rate of dropout compliance with the exercises. Um, you know, wasn't great and uh parents were often not as involved as people wanted them to be. And uh, but it did appear to improve OS A on the order of 1 to 2 events per hour. So it's not a huge difference, but it's also not nothing. So if you have that symptomatic child with mild Os A, I have a DH D chronic mouth breather tonsils and adenoids removed already on allergy therapy. This gives you something else to kind offer which can have some help as well. Um It does help mouth breathing. Um But we do need more studies really to help us know who's, who's the right candidate for this and what, what um what treatments can we offer them if, especially if you're not an occupational therapist, what kind of advice can we give that we feel will be beneficial? Moving on to um heated high flow, uh so heated high flow, we're used to it in a hospital setting. Um But now it is available for home use and um it's that humidified oxygen, so it's more comfortable um with the warm humidification and you can have it at higher flows through a nasal cannula. And um with that higher flow, you do get some CPAP. It's not a lot of CPAP, it's usually just about four, maybe five centimeters of water. Um And this is an example of a, a study of a patient who had the high flow. So, here's a pretreat diagnostic study, a non rem and RM. And we can see the airflow is interrupted from, you know, obstructive apneas and there's some variable effort um in our uh chest and abdominal leads, which is something that we commonly see in Children and stage well, especially stage two and rem sleep. Um and then when they put them on high flow, the airflow improved and the apneas were gone and also it stabilized the breathing um similar to what you would see with CPAP. And so even though it's a small amount of pressure, it's, it's having it can have a pretty big effect and no one really knows exactly why that is. But the airflow um may stimulate the meccano receptors in the back of the throat to kind of stimulate breathing. And also you have an improved FRC, but we don't really know why exactly it works, but it does seem to be seem to help having said that there are limited studies. Um They're pretty small numbers, they usually like, you know, 8 to 10 patients. Um So we don't have a lot of information about it. But um and there are no comparison trials to other treatment modalities. But limited studies do suggest it's effective for patients who can't tolerate CPAP insurance reimbursement is a pretty big barrier um that I've encountered so far, I've definitely um wanted to prescribe it more than I've been able to. Um there are some treatment concerns, especially in the infants because there's no alarm um or um there's no integrated battery. So if it came unplugged from the wall, you might have the cannula blocking the nose, but no flow going through. Um And that would be more really in the case of prescribing it for, you know, chronic respiratory failure than CPAP. But um I'm still hopeful about this treatment. I, I've, I've seen it be pretty effective on some sleep studies and I've definitely had patients who do really well with it. Um It's really a matter of reimbursement. So we have these units in our sleep lab and I just keep plugging away at it cause I think it really works. Um So moving on to the hypoglossal nerve stimulator, um This is an implanted device that synchronizes the hypoglossal nerve um stimulation with inspiration to move the tongue into a more interior position. And so the surgeons um implant this device and there's a sensing lead in the intercostal space. So when you generate your negative pressure and taking a breath in. At the same time, it sends a signal to your hypoglossal nerve um stimulating not to move the tongue out of the way basically. And this has, you know, been around for a while now with adults and seems to work quite well. Um This is a picture of a patient um of the posterior pharynx and the soft flat palate pre and post um stimulating the hypoglossal nerve. And you can see it really does increase airway caliber quite a bit. The um this is the trial in adult patients that kind of got this kick started. Um and it was a child of 100 and 26 patients who served as their own controls and their median H I at one year uh decreased by 68% which is, you know, a huge improvement um similar to CPAP. And um they also had significant improvement in their oxygenation quality of life and upward sleepiness scores. And this is used in patients with moderate to severe OS A. So in adults with moderate to severe Os A on that analysis, the A I is reduced by at least 50% and overall less than 20 moving them into a more mild to moderate category. Um it's effective for at least five years on follow-up trials and the adherence is really good, especially compared to CPAC. It seems to be safe and well tolerated. Severe obesity is considered a risk factor for poor response. Uh, unfortunately people are continuing to have their obesity problem, get worse and worse. So the BMIs keep getting higher and higher. Um, and I think this is an area where we'll have to study, you know, in the past it was, oh, if your BM I is over 32 this isn't an option. I think they're gonna probably have to do some more studies to see if that's really the case or if we can get to a higher BM I to get it approved. So because of the severity and prevalence of trisomy tw of OS A and trisomy 21. And because they have a crowded hypotonic upper airway, um hypoglossal nerve stimulation has been studied in this population. So by mid childhood, there's a very high prevalence of Os A in kids with twice 21 up to 66 to 80%. And only a third of them will be cured by tonsillectomy, meaning their A H I is less than one. An important caveat here though is I always still consider tonsillectomy in uh patients which has to be 21 enlarged tonsils because um you know, over 50% of them will have a pretty significant improvement, they just don't have cure. Um But since the other treatments are, are challenging, it's still worth worth doing most of the time. Um CPAP therapy, you know, associated with poor adherence. Um I think that it can vary quite a bit. Um And what kind of support you have and um, and, and on patients as well. Um We tend to not even try CPAP if Children can't have anything on their face because of sensory issues or if they have self injurious behavior, um then it's just probably not gonna work, but in other situations, most of the time we can get it to work. Um So um the hypoglossal nerve stimulation, augments neuromuscular tone and reduces the anatomical obstruction of the tongue base. So it makes sense to, to try this for these patients and it was newly approved by the FDA in March of 2023. Um There's a large prospective trial of non obese adolescent patients which has to be 21 who could not tolerate CPAP. Um and they had severe A I in their inclusion criteria. They're excluded if their BM I was greater than 90 uh 5%. And um 65% were classified as responders, which is pretty good, defined as an improved H I by 50% or more the mean H I in this um study improved from 23 to 11. So moving from a pretty severe to more moderate to severe category at 12 months, 73% had their A H I less than 10, so no longer severe and 34% had their A H I less than five. So had moved from a severe to a mild category which is pretty impressive improvement. Their quality of life scores also significantly improved and they um the adherence was great. It was nine hours a night and safe and well tolerated. This is a, a meta analysis of, of using the stimulator in patients with Trisomy 21. Um on the top are prospective trials and then on the bottom of these case series. But um they all kind of improved the A H I uh between 10 and 20 points in general, um which is again a pretty, pretty huge improvement and their quality of life scores also improved. So, um at um, you know, we're, we're, we're starting to hopefully work towards using this for our patients that you see as of now that it's been approved, our ENTs are getting training on how to do the surgery and um we are looking, you know, we're, we're looking for patients who might be good candidates to get this started. I think it is definitely an exciting new treatment, especially for those kids who can't tolerate CPAP. One of the cha challenges is that, you know, it is there is an external lead. Um and that if you, if you have a child with self injurious or combative behavior, you can't use this device because they'll pull it out. So that's, that's the limit to it. So finally, we have um A OXY, which is the new medical treatment, sorry. Um Excuse me, it's currently being studied and it's not yet approved So, um, during sleep, our neurogenic activity and um cholinergic inhibition, both um contribute to increasing the upper airway time. And so, um, a oxy is, um, these medications both have that have that effect of increasing upper airway to and have been um studied in adults. Um, Adam um increases norepinephrine and is FDA approved for kids for A DH D OXY minin is an anticholinergic that is FDA approved for kids with an overactive bladder. And um together they do increase the upper airway muscle tone during sleep and have been studied in adults and shown to have about a 50% improvement in their A H I. And so this is undergoing study currently in pediatrics and this is a preliminary trial um where they include in patients with trom me 21 between ages 6 to 17, who couldn't tolerate CPAP and who didn't have large tonsils basically. And they had to have mild to moderate O SS A or moderate to severe OS A. Um they only um enrolled 12 patients. So it's a very small number in this preliminary trial of um really safety. Um and what they found was that um they did a high dose and a low dose um in these patients and then they started them off on one and crossed over to the other one. and they found that um with a higher dose, they are pretty high um incidence of fatigue and mood change. Um and amox Aine, um, has been associated with causing depression. So, just something to keep in mind, um, on the lower dose they did better. Um, but still, you know, 20% of patients with a mood change definitely catches your attention, um, with something you would need to talk about with the family. And certainly if they already had a history of that, it would make you a little wary. But, um, and then they evaluated the effect on the A H I and, um, at baseline, most of these patients, I guess the average A H I is about seven and then for the low and high dose treatment groups, um, it improved by a similar amount to about 3.5. So I had about a 50% improvement going from a moderate to mild category and it didn't really matter if they were low or high dose, which is. So, um, there, there were the fewer side effects in the low dose group. Um, they also found small improvements in quality of life and they weren't statistic statistically significant, but that may be related to the small sample size. I mean, so currently, um, the investigators are planning a six month study of 36 patients, um, which has to be 21 on a lower dose at OXY. And so we'll find out more. But, um, I think it could be a promising medication in the, you know, in a patient who has significant OS A T toy 21 but can't tolerate CPAP. So this is where we started. Um in terms of what we had to offer for residual sleep apnea after your tonsils are removed. Um And it was really treating your allergies or CPAP and now there's a few more options out there. So if you have a high arched palate, you can consider rapid maxillary expansion. If you have a reus retrusion bite or retro mandible, you can think about a mandibular repositioning device um for patients with um especially mouth breathing. Um You can think about mild functional therapy for those patients with moderate to severe os A. Um We're always gonna be thinking about CPAP. Um It's still gonna be our number one choice. But for those who are CPAP intolerant, we can think about high flow nasal cannula and for those with twice toy 21 about the hypoglossal nerve stimulation and I think eventually a oxy as well. And so that is it.