Good morning. Thank you for coming to the session. We will go ahead and get started in the interest of starting in time and saving plenty of time for discussion as all of you in the room know that we really don't have definite answers in this area. I'll remind everyone to read the session through the mobile app and that the rights of this audio and video presentation are reserved. And please try to occupy as many seats as possible and move forward. How we have worked on this session is that we were each going to talk for 10 to 12 minutes and then save perhaps the last 15 minutes for discussion and audience participation. And I'll get started first. My name is Akram Khan. I am at Oregon Health and Science University. I do a lot of clinical trials and none of them are associated with what we are discussing today. Reminder again to rate the session in the app. So our main goal is to provide a guideline for the respiratory care of patients with neuromuscular disease and find the best possible evidence for you. And I'll point out that the evidence that we have in this area is not great and that's why perhaps as all of you as researchers go look at this question this would be an important area for us to consider some future clinical trials. The QR code refers you to the guideline that was published in CHEST earlier during the year and that we are discussing today. And basically it has seven main areas for recommendations. The ones in blue we'll be talking about today. I will talk about pulmonary function testing. Then Lisa is going to talk about non-invasive ventilation. Peter is going to talk about secretion and airway clearance. And David is going to discuss pediatric considerations. Lisa, I wasn't able to find a recent picture for you other than the sleeping beauty in the CHEST app. Yeah, I wanted to be sleeping beauty. Next time I'm going to get the, you know, the headdress and the whole thing, the tiara and the whole thing, absolutely. Excellent. All right, so this is how we'll proceed. And I'll keep my part very brief talking about the use and timing of pulmonary function testing. Start with a case that Lisa very kindly provided me. 68-year-old gentleman presents to your clinic with a new diagnosis of ALS. He has limb-onset disease, vesiculations, EMG shows some diffused denervations, and he has dyspnea now with mild activities. You're seeing him for the first time. And you have a choice for starting where you want to start. And we had considered all of these as where to start in our testing algorithm for patients. I'll give people some time to find the app and cast their votes. I think we have around about 30 people or so who voted. And that's what we ended up choosing also as our determination. And although none of those answers are wrong, we had to start somewhere. And we chose with starting with spirometry with maximum respiratory and maximum inspiratory and expiratory pressures. And these are the results for this particular patient. And you notice that FVC and FEV1 are markedly low. And even the FEV1-FVC ratio is slightly low, although the flow volume loop is not scooped like an obstructive airways disease. And the volume time curve is slightly reduced. And the other point of thing to note is that the bicarbonate level that we frequently used is raised and the MIP is low. So talking about the data behind pulmonary function testing. And I'm going to give you these three different disorders. And what you notice here is that all three of them, although they are neuromuscular disease related disorders, are markedly different. An ALS patient will typically present between 40 to 70 years of age with progressive neuromuscular weakness and fasciculations and swallowing issues. A Duchenne muscular dystrophy patient might present between one to six years of age with delayed ability to sit stand, while a limb girdle muscular dystrophy patient might present much later, like in their teenage years or in their 20s, with this progressive muscular weakness. So three very different disorders. And that was the problem that we faced when deciding how frequently to recommend pulmonary function testing. So this is baseline data on ALS. And what you notice here is that an average ALS patient will have a 2% decline in FVC on a monthly basis. And younger patients have slightly lower decline versus older patients. And this is the placebo group of two large studies. And what you notice here is that over a period of 68 weeks, there is this slow and steady decline. And the faster the rate of decline, the higher the mortality of this group. Looking at Duchenne muscular dystrophy, these are individuals who presented, on average, between 10 to 18 years of age. And their FEV1 was approximately 64% of predicted. And what you notice here is that they had an average of 8% decline a year. And a faster decline was associated with increased mortality. And limb girdle muscular dystrophies, an average person was presenting in this particular cohort. And all these three trials are in our references for the neuromuscular disease guideline, was presenting at an average of 30 years of age with an FEV1 of 30% and maximum inspiratory and expiratory pressure around about in the 30s. And what you also notice here is that a third of them were already on home mechanical ventilation that Lisa is going to discuss a little bit. And what you notice over a period of roughly six years is that you have a decline in FVC over time. And the reason I bring these three separate things together is that we could not really come to a consensus on how frequently we should do testing. So we came up with a good clinical practice statement because we could not tell you not to do pulmonary function testing. We don't have data on that. We recommended all four for you to consider depending upon your availability of your institution and try to do testing every six months. This was consensus based because the people who do ALS wanted us to do much more frequently and that, you know, and different disorders have a different rate of progression. So what we came up with the consensus was that you try to adjust testing based on the rate of progression of the individual neuromuscular disease. I'll skip the screening of respiratory failure and sleep related disorders and just point out that in the guideline, we have provided you with a very nice algorithm on how to proceed. Starting out with pulmonary function testing and then repeating testing, moving on to overnight oximetry, polysomnography, or non- and towards non-invasive ventilation as and when it is needed. I'm going to skip all of these slides and go back to my summary, which is that one, respiratory failure is common. It's probably one of the most common causes of death in these patients. Neuromuscular diseases are a heterogeneous group of disorders and we have to adjust testing based on the rate of progression of an individual patient using your local resources as a guide of what you are able to do. And you may also require to refer these patients to a specialist center where they, you know, like Lisa Center has a big intake of these patients where you can use them to be seen by a specialist and provide maybe better care. I'll go ahead and stop here and give the lectern to Lisa. Yeah, it is right in here. Can you guys turn the lights down just a wee bit? There's a lot of glare. Akram, first of all, before I start, I need to say that this was a project that took a lot to accomplish. It's going to have a fabulous impact, we hope, but what people don't realize is that getting this group to work together was like herding cats. And so you deserve a great amount of both praise and thanks. Okay, let me see if I can get this to work here. And Lindsey, too. Lindsey's not here, is she? No? Well, anyway, let's just say the college and the group for guidelines has done a great deal of benefit for us. So what was our goal in writing this document? So the first is that we wanted to reflect worldwide standards. There was a tremendous feeling within our group that the American standards were not keeping up with the Canadian standards or with any of the European standards. And so we wanted to make sure that what we wrote reflected something that we thought was more timeless. We wanted to do that because we wanted to influence U.S. regulators. That was a big goal. The next goal is that we knew families were going to read this, right? This is openly available on the CHEST website. You don't have to have an account for PubMed to get it. And we wanted families to understand that NIV was about therapy. It wasn't about symptoms. And that they should understand when they go to speak to their doctor, they should be asking about NIV. And we wanted to support both respiratory therapists and home care companies as they lobby for access to NIV in the home. So I wanted to bring out some of the very classic literature so that you can look at what our group worked with. And this is one of the most important. This study from 2006 was the first large randomized control trial done in patients with ALS, both bulbar and non-bulbar onset. And showed, importantly, that there was an 18-month survival benefit for those that were randomized to NIV versus those that weren't. So therefore, we had a strong recommendation, even though there was a low sense of certainty because there's so many diseases, right? So Akram just talked about this. And this is very much ALS-focused. But we found that whether it was our bulbar or our non-bulbar patients, we saw it. Now, clearly, the biggest benefit is here. I don't know if you can see this. There it is. The biggest benefit is here. And these are the limb-onset patients in terms of the mortality. But for those of you that work closely with neurologists like I do, and we look at the three currently available drugs for ALS, the greatest impact is three months. Three months. Nobody walks out without the Realiazole. And frequently, ALS is not being offered to our patients. We wanted to make a change. The next thing is that we wanted to look at the mechanisms. We felt that reduction in CO2 was one of the most important mechanisms behind which the use of NIV was a therapeutic intervention, not just a Band-Aid. Now, this is data actually from mice. And these are totally normal, healthy mice that live in Chicago at Yascha Schneider's lab in our division. And what Yascha does is he takes these mice, and they get the myocytes, and they either put them in a hypercapnic state or in a eucapnic state. And here, what you're just looking at is numbers of cells. And we see that the growth of the muscle is significantly inhibited. Why is it inhibited? Because the CO2 and the change in the environment changes the function of mitochondria. The muscles are weaker. They're lower in number. They have a great amount of inflammation. And the function of the mitochondria to help is greatly impaired. So we think of this mechanistically as an answer. The next thing that we look at was the initiation of NIV itself. And in our clinical recommendations, we say that the indication for NIV can vary depending on the disease, the age, and the rate of disease progression. And so we recommend looking at spirometry values, which you see here, as a way of deciding is it time? Now, notably here, you will see at the top that it says the fall in FVC, less than 80%, in association with symptoms, should be an important reason to start a BiPAP. Now, when this paper first came out, my good partner, John Coleman, called me. And he said, were you drinking that night? Listen, here's the reality. We cannot allow what Medicare says to dictate the care that we're giving. The rest of the world knows that, especially in the setting of ALS, less than 80 plus symptoms is important. Why is this important? Well, it's important because spirometry was evaluated and developed to treat obstructive lung disease, OSA, asthma, COPD, et cetera. What it's not looking at is the fact that frequently in neuromuscular disease, you've got one good blow in you. And then after that, you're totally fatigued. And you can't keep up anymore. And we don't want our patients to be punished because they got one good blow. This also is recognized within the on-map papers, which were headed by our fearless leader here, Dr. Gay. And the same recommendation is there. It saves a tremendous amount of money, allowing us to do early start of RADs or BiPAP machines without having to use a full mechanical ventilator. And this is the standard of care that's seen outside the US. The use of NIV and its initiation for patients with neuromuscular disease should focus on sleep disordered breathing. In other words, we know if we wait until you have daytime hypercapnia and daytime symptoms, we've waited too long. We have a strong reference in this paper that says, even though it's a conditional recommendation, that we should start early. And we should look at sleep. And we recommend that our partner within this series, the American Academy of Sleep Medicine, that we use their standards for evaluating hypoventilation in the lab. We also recommend, and I think that Dr. Zielinski is going to talk more about this, using the European standards for children. I'll let him get into that. This allows us to use most community-based pulmonologists because it's the standards from the AASM. And we want this to be available for our patients. Most sleep labs currently don't use a neuromuscular-specific pattern. And so we do encourage you to teach your techs and get that on the books. And it's helpful for insurance. The next is that we say, OK, when we are documenting the spirometry, these are the numbers we should look at. FEC, MIP, MEP, overnight oximetry, or polysomnography. But what's interesting is you don't need to have all of them. And because you don't need to have all of them, you only have to have one abnormal number. Especially in adults, Dr. Zielinski is going to tell you different in children, polysomnography is not 100% necessary. And for those of us who travel in a bigger circle than just the U.S., we know that polysomnography can be a problem. So I threw this slide in because I believe that this is a fundamental paper that helps us to best understand this. Nicole, are you here? Yeah, there's Nicole. So afterwards, when we have questions, we can grab her. This is Nicole's study that was published in 2014 that looked at this question of, should we bring people in for full nights either in the hospital or the sleep lab? Or should we be able to do what we call a pap nap, where we bring them in in the afternoon and we do about four hours of monitoring and we use that to let us get NIV started. And what we know is it saves lives. And here again, you see an extension of the difference between 278 days versus 580 days. It takes those medications the neurologists are using right now and shoots them out of the water. Why is it? It's access. We know that the access to full polysomnography for these patients is a big challenge because of the inavailability of the lab and the difficulty of the lab to care for disabled patients. We know that polysomnography probably does a better job for getting rid of dyssynchrony, better mask fits, increased comfort, teaching of the patients on how to use their equipment. But if you can't get it realistically, it's a problem. So in the realm of selfless promotion, and for those of us who are active in the neuromuscular network, I'd like to remind people that the Fromer lecture will be tomorrow at 7.15 featuring Dave Berlowitz who is part of the PAPNAP study that I just showed you. And Dave's going to talk a little bit, I believe, about this struggle between do we need a PAPNAP or a full study. So let's all be there at 7.15 tomorrow so we can hear what he has to say. The use of NIV for optimization. Our group is strong that individualization is a big factor. And we gave that a conditional but pretty good level of certainty that really individualizing therapy is important. I'm just going to throw this out here to say, look, we didn't have enough data on specific modes to tell you guys which mode to use in neuromuscular disease. But what we do know is that we need to pay attention to things like trigger sensitivity, cycling time, and the ability to have even breath-to-breath data like here where the use of TI-MIN extension makes a big difference. And to save time because this slide has been used several times today, I'm going to skip that slide and say the next thing that we talked about was the use of daytime support. We made a strong recommendation that patients with neuromuscular disease, if they have preserved bulbar function, should be recommended for mouthpiece ventilation during the daytime as an adjunct to their nocturnal mask use in order to reduce CO2, improve cough strength, improve speech, et cetera. And that condition is a conditional recommendation. And although the evidence is very low, we believe that it's a very strong therapy that should be used. And so this is a picture for those of you who haven't seen it before. You take your typical home mechanical ventilator and add a mouthpiece to it. And when you do that, you're going to see a couple of things. This is a nice paper, fundamental paper, from Michelle Toussaint showing that if we look at patients who are getting daytime use of SIP, whoops, go back, where am I going here? There it goes. If we look at nighttime, great, we can reduce Borg scores, their dyspnea is better, their cough is better, but it really gets worse throughout the day. And if we add to that the use of mouthpiece during the day, we can support dyspnea, we can support cough strength, and we can really help to improve CO2. For those of you who have never used mouthpiece, raise your hands. How many people have never heard of mouthpiece and are like, Wolf, what the hell are you talking about? I would say that that is the common thing that I hear. I would recommend that you pull this paper and take a look at what's going on in terms of the technical issues and what we have to do to set up mouthpiece ventilation in the community. So thank you, Akram. And who's next, David? Oh, Dr. Gay. So I'm going to turn Dr. Peter Gay up, who is very fundamental to getting this off the ground, and have him talk to you guys about airway clearance. Thanks, Lisa. It's always great to hear the U.S. world expert on neuromuscular disease here. Let's see, I've got to get out of Lisa here. Let's escape. Let's find me here. And there we go. So I'm Peter Gay. I'm from Mayo Clinic in Rochester, Minnesota. I actually came into this world as a gift from Phil Westbrook, who ran the AASM as the initial president. And he was leaving Minnesota to go to sunnier areas. And he had this bevy of 21 neuromuscular disease patients. And he just handed me this data and said, here, you figure this out. So that's how I got interested in neuromuscular disease. And I've been with it ever since 1991. I have no real conflicts. So I'm going to do a tiny bit of off-label use. So I hope I don't get shot for that. But I got a lot of bullet wounds. I don't care anymore. So I'm going to discuss the ACCP guidelines. And this is not to denigrate. It's at least five years since we got in that room and said we're going to do this. And you get 47 people who said, me, me, me. And then you end up with five people left at the end who have this mountain of data to kind of go through. So it was a struggle. And it's a credit to Akram. He just bulldogged this way that we are going to get this done. So quite a golf clap for Akram here. Then I want to talk about the practical application. I mean, OK, this is really cool. And who in this room actually looks at the evidence tables of these things? There may be one psychotic person in the corner there. But in any case, tell me what to do. And you look through these things. You say, nothing matters. Now, why did I get up in the morning to hear so many talks? I went to the critical care thing. Nothing matters. And if it did, they talked too fast. I didn't get it anyway. So I'll try to be simple and practical. What do I do when I come home after I've noticed guidelines for this? Thank god there are guidelines. And I don't know what they say. Well, here's an example of what's going on. This is a very famous ALS functional rating score. And for me in particular, you're looking at secretion clearance and things like that. Notice that the mainstay of all this just talks about salivation. And basically, do they drool? Well, do I need to salivate? Well, do I need a score to see if somebody's got a towel in their hand on my couch? And do you drool? Yeah. Can I help you with something like that? So all of these rating scales, to me, the answer is always sitting on your couch or lying in the bed. That's where you decide whether an intervention that you're going to give these poor souls are looking for a better quality of life. So you can put a 4. You can put a 5. But figure out whether if you go to the trouble of getting a device, and that's a big deal, is it going to make their life any better? And that, to me, is the only rating scale. And then how do you assess these people? Well, is it up here? You hear it pooling in the valley. You just want to reach in. You're just going to grab it out. And then is it down here? They just have so weak a cough that secretions either are turning to concrete or they just can't move them. So when you're thinking of oropharyngeal secretions, you're really talking about salaria. And when you're thinking it's just down here and I've got to shake and bake or do something to get it up, that's the laryngeal tracheal secretion clearance. So I separate that out in my mind as to what's going on because there are different toys that I can give them. All right. Let's talk about the PICO questions. And actually, I apologize for the PICOs because I noticed I took some of these when Akram's first drafts. And he likes to spell cough, C-U-F-F. So we'll give him a little levity there. But basically, for the PICO 9 questions that deal with salaria management, we said, should airway clearance techniques be used for patients with neuromuscular disease? Well, duh. But when should you use what? That's what you want to know. So for excessive salaria, what's the first thing? Anticholinergic agents. You dry them up with whatever way you can do that. But then you're going to get side effects. Males can't pee in the morning and it's T-Y-A-K-H-A-R. So somewhere between that is a balance. But the balance is right there. You can balance it with each patient. And the recommendation is to use simple oral medications there. So we suggested a trial of inexpensive stuff. Oral anticholinergics are really very cheap. And then you balance those risk and benefits there. And then if that doesn't work, the next area to go is recommended for botulinum toxin. But you've got to have somebody who knows how to do this. It's uncomfortable. It's expensive. Getting them to a place. You've got to move them to a locale where somebody can actually do this. But the nice thing about botulinum toxin, if you do it right, you can see, is it a benefit? And whether you're going to prolong this or not. And some patients are just absolutely in tears. This is finally some relief. But it's going to be temporary. And it helps you make some decisions, I think. So we recommended this if you're going to be more aggressive about it. But figure out the dosage. You really have to have somebody who knows what they're doing to embark upon this. Things are getting darker for you. You went on to the botulinum toxin. And you got some benefit, but it's temporary. And they're really struggling. And they really want this taken care of. I have one patient, actually a spinal muscular atrophy. And he told me, actually, this is the worst thing I do. I can't talk. I'm 24-7 dependent. But the salivation just drives me crazy. We went through all of this line, got him through botulinum toxin. This is OK, but just get rid of it. And now you're talking about radiation therapy. And again, through all of this evidence table that you look at, different rating scales, people combine things. It's very hard to get a handle on this. But it gives you an idea of what's out there. And I think the fact that it can be done. You read through these studies. People figured out how to put together a team to deliver this therapy. And then it meant something to the patient you were taking care of. But by the time you got to radiation therapy, here there's no turning back. Once you go ahead and do this, and it's a struggle sometimes to get some reimbursement. But in our institution, I think most of the others here, you come with a really sick ALS patient. They don't get that. They're like kids. I mean, they don't say no. So you could work at this and pretty much get the therapy that you want. So the recommendation here was that, yeah, there's a reasonable progression here. And if they really want to take care of this, radiation therapy is a reasonable thing. So now we talked about salivary. How do you think about this? So we talked about the anticholinergics. Amitriptyline is a pretty good dose. You give it to them at bedtime. Maybe they sleep a little bit better with the NIV that Lisa gave them. And ultimately, it is a very drying agent. It has a significant antihistaminic effect. Glycopyrrolate is probably what most of us use. But I'll tell you what we use, and this is kind of the off-label stuff. So if you have to escort me out now, this is what it's all about. We just use eye drops. They're cheap. You can drip the atropine eye drops right in the mouth, and bada boom, bada bing, it works. But now, any time you're getting to this salivary level, they need a suction device. And whether you find something that makes a hell of a lot of noise, and nobody can talk to them in the room, or you find something that's muffled. I have a patient who puts this in a box. He made a little box to quiet it down. But it is a tremendous benefit. It's a real crutch that these people with a lot of salivary really benefit from. So by the time you're using one of these things, you're thinking about getting a suction device. And then moving on from there to the Botox, either initial injection, just to say, how far should I go to really dry this up? And a good Botox injection will dry them up. But ultimately, the frequency, and they like it. So OK, I've had enough of this. Can you really just now get rid of it? Then they're going to probably go on to radiation therapy. But try the atropine eye drops. It's cheap, and it's easy to use. The actual airway clearance approach to these things, glossopharyngeal breathing, frog breathing, just really getting lung volume so you can expel a cough. What does a cough have? A cough has two aspects of it. It has a pull in to get some air, and it has a push out. And there, when they can't push out, you have a good assistance device. People using additional manual cough assisting is really the easiest, and it's not charged for. This is where you get into a little bit of trouble, that once you're getting onto the airway clearance devices, either the handheld cough assist for those still in a non-invasive situation, or when you're using high-frequency chest wall oscillation, there you're going to get some pushback from these companies. And there comes the spectacular vernacular that you learned to get devices delivered through your own local coverage determination. Make a friend. Pick up the phone. What do I have to write to get this from my patients? Well, you've got to say something about you tried. Tried something manual first. So put it in your note. It's the documentation in the physician's note. Remember, this is a high school clipboard mentality. All their job is to say, why would you say no to money coming into you? But that's their job. No. No. So you've got to be 10% smarter than the object you're dealing with. If you can predict what they're going to do, then you jump that hurdle, and you've got a device for your patients. I've never, some of you have done this. I don't know how to do it. I've never gotten two devices, either high-frequency or, this is for Medicare patients, that you can have one or the other. You can't have both. So that's what I run into. I'm treading a little bit into the next thing I want to get to is the tracheostomy, which really was blended into the PICO-8 question for the non-invasive ventilation. But those who really have unresolvable secretion problems, and you really have to get to the airway, tracheostomy is an option. I'll say, over the 30 years I've been doing this, the number of patients I've trached outpatient ambulatory status, I could count on my hand. That you don't trach a patient, you trach a family. And it often displaces a neuromuscular patient. So it's a deal breaker for a lot of these. The patients that I have done, the few that I'm talking about, usually have pure bulbar function and have pretty good limb function. They're ambulatory. They can stay at home. So if that can be managed in the home situation, it seems reasonable. But it's pretty rare that we'll go on to that situation. I think that's true for most adult populations. So again, for this, using the manual techniques, you just got to say you at least tried them. And some patients get some benefit from this, the high frequency percussive therapies that you can use, and then the trach for deep suctioning is kind of the line of therapy here. The hardest part of all of this is getting the equipment. Develop a relationship with your vendor, and then you can kind of walk through where you can get these devices. And walking through the high frequency chest wall oscillation and the cough assist is going to be the most challenging. In my experience, most of the older patients, the ALS patients, if you do give them a chest wall oscillator, they want it nice and slow, like a massage technique. It doesn't really do much of anything. If you really shake and bake them like you have to do it, it's uncomfortable. If you've ever worn that thing, it kind of hurts. If you do it effectively, it's a bzzz. And the cystics love it, but the older ALS patients don't. So you need a suction device for the breast stacking, and you need a bag. I want to say something about the cough assist therapy. Most people look at this machine, oh, I don't understand it. I need my respiratory therapist. And it's good to have a guy. I got a guy, Boynton. I say, set this patient up, bada boom, bada bing, it happens. But it's a simple thing. Minus 20, plus 20 kind of thing. Just get some number in your head that says start. You can do it. And it's easy enough, and the patients can use it for a relatively short period of time. And that pleasure of getting that junk out of there is immense for some of these patients. The chest wall oscillator, whether you use a full vest or a short vest, take them out on the freeway, and you're going to see people who don't want to drive the car right away, and you're going to see people who like it. I want to say something about the combined therapies. There was a warning about using these combined therapies in kids in a ventilator situation. But if you can have an excuse for one, and you can get all three, where you get a percussive, you can get a cough assist, and a nebulizer in this thing, there are products out there. And I won't name them by specifics right here. I'm just going to finish up with this, that fundamentally, as you get more complicated, obviously you get more cost, and you're going to need more help. And that's where, again, as Lisa's already said, we're just really not providing the services that we need in the home. There's no payment for a respiratory therapist that's provided in this system. Well, you've got all these guidelines to look at, and there's limited data, but you can figure it out. It provides a backdrop for you to develop a local program. And then you've got to figure out the reimbursement support, so that the choice of all these therapies, as you individualize them to your patients, you can obtain the equipment. And the best results for all of this are always answered in the couch sitting next to you, or in the bed that you cross them in the hospital. Thank you for your time, and we'll talk at this time. Thank you. Peter, I am going to put one shout out about Cough-Assist. I'm just going to put one quick shout out about Cough-Assist. As you guys may know, two weeks ago, Phillips put out a warning or whatever. They've stopped making the Cough-Assist, which may make it difficult in your area to obtain a device. So if people have questions specifically, you can come up and ask us afterwards. I will give people two warnings. One is that companies are still taking orders for a device they cannot provide. So when you put the order in, if they say yes, they better damn well be able to do it. Number two, the Byways, which is one of the popular alternatives in the US, is now at 30. I'm not exaggerating, 30 week wait time. So you've got to think strongly about that, and then there will be other times this week that we can talk about what your other options are. But sorry, Dave, I thought it was too important. No, perfect, thank you very much, Lisa. And thank you to this great group for inviting me to be part of this. So I'll be talking about the pediatric considerations from these guidelines. So I'm Dave Zielinski. I'm a pediatric gastroenterologist. I've got no disclosures, but I do want to also shout out to the other pediatric members of the panel, including Dr. Girish Sharma, who's here in the audience, and then Dr. Reshaman, who couldn't come to Hawaii. We're not really going to do a whole approach towards, well, we'll do the approach more towards monitoring, because I think the goal here is to point out what's different in kids than the adults, and how we have to interpret some of these recommendations a little bit differently for the children. And part of it has to do with the heterogeneity of the different neuromuscular diseases, the difference of the normative data across lifespans, and different standards that we have. So we're going to start with a 10-year-old, Duchenne muscular, muscular, Duchenne muscular dystrophy, sorry about that. Clearly, I changed my mind partway through. He's on deflazocort and remains ambulatory. No respiratory complications to date. He's on medications for ADHD since age six, and his BMI is 23 kilograms per meter squared, which is above the 95th percentile for age. So the question is, how should we monitor and follow this child? So let's go and see what the guidelines say. Well, as we've kind of learned already from Akram, is that for patients with neuromuscular disease, we should be doing pulmonary function tests. And that includes vital capacity, peak cough flow, and your muscle strength testing. And we should probably be doing about every six months. So does this work for kids as well? And I think Dr. Akram has already hinted at that, is that we have very different diseases, and the clinicians should adjust based on the progression of individual neuromuscular diseases. The other subtle thing to look between these two recommendations is the first one talks about at-risk of complications, whereas the second one talks about at-risk of respiratory failure. Now, it's really hard to define who's gonna be at risk of respiratory failure, but it kind of brings about who we should be looking at doing the PFTs much more frequently on. You know, one of the limitations of our guidelines that we've stated in there as well is that a lot of our literature comes from ALS. So these are our seven topic areas. And you'll see in some of these areas, 90 to 95% of all of our patients that we are using to make these recommendations are ALS patients. And I think there's a pediatric person in every one of these questions, but the reality is this is where the better literature was, and that's what was used to guide us. And as was already pointed out, ALS is a very rapid-moving neuromuscular disease compared to most others. So here is, you know, we're talking about the 2% a month rate of decline. So for patients starting their NIV, in the one year before that, they've probably dropped off by 30% on their lung function testing. So probably even every six months might not be long enough. In kids, however, we're talking about a whole lot of different diseases. Historically, spinal muscular atrophy was our kind of our ALS, but this guidelines are specific for ages six and up. We really want to focus on kids who could start doing pulmonary function tests. And now with all the disease modifying treatments, it's a very, very different disease as well. When we get to spinal muscular atrophy type two, most of the natural history studies suggest that we're dropping about 2% a year. So compared to ALS, which is 2% a month, some of our milder SMAs are 2% a year. So the same curves are decades instead of months on what we're looking at for the drops. Duchenne muscular dystrophy. I mean, you know, I think for you adult providers, I think you probably see a whole hodgepodge still, but most of us in pediatrics, almost all of our kids are on deflazocort or prednisone or whatever's available in your area. And it's a very different disease now too. The typical drop-off still typically happens when you lose ambulation, but it gets delayed even further and pushed down further. Our congenital muscular dystrophy, which I'll show in a second, is a whole variety of them. And I don't even know how to keep them all straight. Who do I expect to drop how quickly? Who do I expect to get how sick and try to remember that as well? And then finally, we have our myotonic dystrophies as well. So just as an example, within our congenital muscular dystrophies, there's a whole different groups of them. But even for example, if we look at our collagen six related myopathies, you can have Ulrich, which you're gonna expect ventilation the first or second decade of life, or you can go all the way down to Bethlehem, which won't be till the fifth decade of life or more. So really trying to remember, kind of having an idea of what your patient in front of you is expected is gonna help drive us to see how often we should be doing these monitoring or if we should be doing the monitoring at all. So I think it's very reasonable to do the regular PFTs as stated and adjust based on patients. So if we go back to our child here, he's at risk for complications. He's got DMD, and we certainly know he may be at risk as well for OSA. He's still ambulatory, so he's still probably before the more rapid drop off. So probably doing PFTs once a year during the ambulatory phase is reasonable. Then once they start becoming non-ambulatory, we'll probably start going twice a year. There's different disease specific guidelines and some of it is a little bit of kind of trying to gestalt what you think that should be going on there. The other part of things is how do we interpret PFTs? Well, this is our PFT criteria for NIV for our guidelines here. And what you'll notice is in a few cases, we're saying over the age of 12 only. And only one of them is actually have predicted. The other numbers are absolutes. And we know vital capacity increases with age. And that's why we tend to use percent predicted numbers with them. But we probably have the same with some of these other numbers. Not my prettiest slide, but on the left here, we've got, if you look at the peak cough flow, there's one study looking at normative data across the age range. And if we use the 270 cutoff here, below the age 10, that's within the normal limits. And it's not until you start getting past the age of 12 where it actually starts being well above the fifth percentile but even when we start using the age of 12, we have to consider, here you're about this close to the normal limit or you get to 18, you're much, much further up. So even there, there's still some limitations. The older you are, probably the better these numbers become. Likewise with SNPs and MIPS, they also increase with age whereas we kind of tend to use more static numbers for them both. So I think those are things that we have to just factor in when we start looking at these numbers and interpreting them. What age are they and how are they doing? So kind of, as we mentioned, we do the tests, do them on a regular basis, but we really have to really think about our ages and how we wanna interpret them and what we're gonna use those numbers for. So now we're gonna stick with the same child and he's 15. He does not have Duchenne muscular atrophy. He still has Duchenne muscular dystrophy. And he's still, now he's non-ambulatory, no respiratory complications to date, but he's complaining of daytime fatigue and he still has ADHD. His BMI has increased and his vital capacity has now dropped to 70%. So do we do a PSG or do we start on non-invasive ventilation? The recommendations we have, we have two. One is for symptomatic patients who have normal PFTs and normal overnight oximetries, we probably should consider PSG to look for symptoms. But in this case, his PFTs are not normal. They're at 70%. For patients with neuromuscular disease, we suggest the use of one of, it's already been mentioned, FEC, MIPS and MEPS. And those could be used to start on NIV without a PSG. But if you look a little bit more into the body and the remarks, there's a few other statements that we have thrown in here. Oh, maybe they come up after, sorry. So I think let's have a look at this here. So in this case, so he's, yes, he's getting his PFTs, he has fatigue, school performance issues, and he's met those criteria. So by and large, this would probably mean that he, based on our guidelines, meets the criteria for starting NIV. However, these are the other statements that we've kind of included. Clinical indication may vary based on patient's age and disease progression. PSG may be the preferred option for pediatric patients. And PSG is not necessary for adults to initiate NIV, and PFT criteria alone may be adequate. So between those, the suggestion is that for pediatrics, we really should be thinking about doing PSGs when we can and have the ability to. And I think there's several advantages to PFTs. Number one, you can actually diagnose and define your sleep disorder better. Is it predominantly obstructive or pseudo-obstructive, or have we already moved on to hypoventilation? We could potentially avoid unnecessary intervention. So we know DMDs, we still, most of them will start on non-invasive ventilation sometime in the adolescent period. Adolescence is tough, it's tough for everyone. It's even tougher when you've got chronic diseases, and it's certainly tougher when you have chronic diseases that may limit your ambulation and movement around. So some of the ways that some patients can kind of have their own independence is trying to avoid therapies, not do their therapies. And I think it certainly behooves us that if we have the time and resources, so let's make sure they actually need the treatment before we give it to them. And it's another way to help monitor progression. So here you can, in this case here, this is a patient with SMA2, but you can kind of see they have got their obstructions and desaturations, but they're also got paradoxing throughout most of their breathing as well. So you have other information that can be kind of provided when you get the PSGs. But you do need to factor in what your availability is. If you can't get them for a PSG for years, then maybe you should start them for the symptom control. Some patients just do not want to go to the lab, do not want to leave their home, and there's other things involved. So maybe those cases you can look at it as well. And other modalities such as oximetry and home TCO2 are emerging. Full disclosure, we use a lot of overnight oximetry where I am because we don't have a lot of access to PSG. We actually use it more as a screening or prioritization tool. And we use kind of other criteria than our guidelines, but that are kind of our own. But I think the PSG is still kind of the gold standard for looking at these here. So as Lisa mentioned, is that the panel recommended the ASM guidelines for hyperventilation in adults, but an ERS one for pediatrics. And the reason for that is if we look at the ASM criteria for hyperventilation, it's different between pediatrics and adults. So all the pediatrics people know this, but I'm not sure if all you adult sleep doctors know this. In adults, as you know, it's over 55 millimeters of mercury of TCO2 or end tidal CO2 for at least 10 minutes or a 10 millimeter rise in CO2 for at least 10 minutes. While in pediatrics, it's having a CO2 over 50 for over 25% of your sleep time. Now, there's a lot of data out there showing that different hyperventilation definitions lead to different incidences, but I do wanna point out one study here that looked at in DMD, if you use the ASM criteria compared to a DMD paper criteria that Lisa was part of, how does this impact on your incidence of sleep, hyperventilation or sleep disordered breathing? I'll point out the ASM criteria as we mentioned, whereas in the DMD criteria, they're using 50 for 2% instead of the 25% or a rise of 10 millimeters for at least 2% of sleep time. And lo and behold, it's what you can clearly see is while a third of patients had no sleep disordered breathing in this group, half met both criteria, an additional quarter met only the DMD criteria would not have met the ASM criteria for being abnormal initiating an IV. Looking closer where the differences come out is if you look at the pediatric definition of hyperventilation, only two patients met that versus if you look at the modified one of 2%, 24 made that. And this number is all so much closer to what we use in adults. So it really seems to correlate much, much better than adults. So when we were left, as part of this guideline, we did not do a literature search to define hyperventilation. So we couldn't kind of come up with our own criteria. We had to go and pick and choose from ones that were out there already. And trying to use the ASM one, we were very, very worried that for pediatrics we'd be under diagnosing hyperventilation significantly. So as such, we kind of came up with coming from another one from what was stated from the ERS where like the 50 millimeters for 2% of the sleep time and or SpO2 less than 90% for at least 2% of the recording time. And I will point out that these guidelines are endorsed by the American Academy of Sleep Medicine. So while it is not the ASM criteria, it is probably something that we in the pediatric lab should be looking at using specifically for our neuromuscular patients, as it is a much higher index of suspicion leading into this. So going back to our case, he had an abnormal PSG, no hyperventilation as would probably be expected in an adolescent still at this stage on the flaccid cord, and he was started on NIV. So overall, I'll try to point out some of the limitations and differences, but the guidelines really do work well, I think across the entire age span of starting at age six. You really do though need to factor in the patient and disease specific courses. It's not all just ALS and especially in pediatrics, kind of the specific criteria for PFT and PSG interpretations. And my initial version of this talk was much longer, but I took out the different things with NIV and airway clearance and the principles are mostly the same. Just keeping in mind sometimes for pediatrics, the minimum weights may not work on some of the BiPAP machines, especially for the smaller kids. So that's a factor of mask fitting can be a bit more of a factor. And some techniques and modalities may be more challenging in school aged kids. I mean, I know some people probably got advice with mouse feed ventilation in a seven, eight year olds. I tend to find that that does not work very well until they're much, much older. Likewise, glossopharyngeal frog breeding in a eight year old is probably not the best technique. I'm sure someone has learned it, but it's just not that it's not there. So some of the recommendations are probably more adult basis on the things that Peter Gay was talking about. But we just have to kind of factor in what can the child do and how we can move about for the next step. Okay, thank you very much. Thank you.

respiratory care

neuromuscular disease

monitoring guidelines

intervention guidelines

pulmonary function testing

non-invasive ventilation

pediatric considerations

individualizing therapy

limited evidence