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CHEST 2023 On Demand Pass
Canadian Thoracic Society (CTS) 2023: Honorary Lec ...
Canadian Thoracic Society (CTS) 2023: Honorary Lecture: Helping Kids Live Their Best Lives Using Respiratory Technology
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My name is Chris Hergott. I'm an Inventional Respirologist at the University of Calgary. It's my pleasure to welcome everyone to the Canadian Thoracic Society's Honorary Lecture, delivered as part of the CTS Annual Scientific Program at CHEST. I'm very pleased to announce and introduce Dr. Sherry Katz as this year's recipient of the CTS Honorary Lecture Award. This award honours an individual, Dr. Katz, for their major contributions to the advancement of research, education and clinical excellence in the field of Canadian respiratory medicine. Dr. Katz is the Division Head of Pediatric Respirology at the Children's Hospital of Eastern Ontario and a Senior Scientist at the CHEO Research Institute. She's a full Professor of Medicine at the University of Ottawa and holds a cross-appointment at the School of Epidemiology and Public Health. She's here to talk today about helping kids live their best lives using respiratory technology. So please give me a warm welcome for Dr. Katz. Thank you so much for the kind introduction. I am very touched and very honoured to be here amongst friends and colleagues and many mentors of mine as well. So the title of the talk is Helping Kids Live Their Best Lives Using Respiratory Technology. I will be the first one to admit I am not a techie, but I believe in simple interventions and using technology when possible to help kids improve their quality of life. I need to tell you I have a few disclosures. I'll grant funding from a variety of organisations posted here. And now we can jump into our lesson objectives. So the first is to examine diagnostic tools and clinical predictors of sleep-disordered breathing in children. The second, to assess outcomes of non-invasive ventilation in children. And the third, to examine the role of lung volume recruitment therapy for children with neuromuscular disease. And really my research, although it feels sometimes quite scattered, has been informed by clinical practice and the challenges that have been encountered when we try to take care of patients and families. When it comes to the diagnosis of sleep-disordered breathing, we're going to talk about clinical predictors, diagnostic tools, and considerations in high-risk populations. We'll look at outcomes of sleep-disordered breathing in children, an attempt to avoid surgical complications after adenoton selectomy, whether NIV or non-invasive ventilation treatment actually improves outcomes, and the factors that affect adherence, which of course is the biggest barrier to successful positive airway pressure therapy. We're also going to discuss airway clearance with lung volume recruitment with the goal of slowing lung function decline in children with neuromuscular disease and improving cough efficacy. So here's our first challenge, predicting sleep-disordered breathing. And we'll start with a clinical vignette, which really was the driver to start looking at some of these questions related to this topic. A five-year-old boy came to my office with attentional problems, snoring at night, and symptoms present for two years. The parent is incredibly frustrated because they've been waiting for over a year for a sleep study to evaluate possible sleep apnea. Sound familiar? So the research foci that really came out of this were looking at the importance of early diagnosis of sleep-disordered breathing in children, evaluating the scope of resources available in Canada for diagnosis, and to be honest, I don't think it's so different elsewhere in the world, and trying to identify which kids actually have obstructive sleep apnea, the most common form of sleep-disordered breathing. We've looked at high-risk groups with neuromuscular disease, obesity, and Down syndrome, but also focused on the general population who can't access testing easily. So first, a bit of background. Obstructive sleep apnea affects 1 to 4% of the general population of children, more common in children with underlying medical conditions such as neuromuscular disease, obesity, and genetic syndromes like Down syndrome. The most common contributors to pathophysiology include adenotonsillar hypertrophy, particularly in young children, obesity, and some contribution from neuromotor tone. It's certainly true that not all children who have large tonsils and adenoids will have obstructive sleep apnea, nor that all kids with obesity will have it, but there's some other constellation of factors that contribute. Obstructive sleep apnea is often quantified on a sleep study. Unlike in adults, an obstructive apnea hypopnea index over 1 event per hour is associated with morbidity. 1 to 5 events per hour is considered mild sleep-disordered breathing, 5 to 10 moderate, and more than 10 severe, just to orient you. While treatment with adenotonsillectomy and positive airway pressure can be quite effective, there are long delays in diagnosis, and as a result, there's a lot of morbidity, which we'll dive into a bit more now. The most common is neurocognitive morbidity. We know that sleep apnea affects learning, memory, language skills, school performance, executive function, and behavior, all pivotal at a time when children are learning and growing and attending school. The mechanism for this is repetitive episodes of desaturation, sleep fragmentation, and decreased cerebrovascular perfusion. We know that treatment with adenotonsillectomy can improve cognition and behavior, but important to note, it's less effective the older the kids are. Cardiovascular morbidity, something very well known to adult physicians, starts in children. There's autonomic dysfunction associated with sleep-disordered breathing that results in systemic and pulmonary hypertension, endothelial dysfunction, metabolic syndrome, and systemic inflammation. The mechanisms here are the constant arousals from sleep that activate the sympathetic nervous system, releasing catecholamines and raising heart rate and blood pressure. Respiratory acidosis and intermittent hypoxemia results in oxidative stress, inflammation, and endothelial damage. And finally, there's increased left ventricular wall tension and myocardial oxygen consumption that happens with high negative intrathoracic pressures that are generated during obstructive events. Quality of life is also impaired. Children with obstructive sleep apnea have reduced quality of life similar in magnitude to that of children who have juvenile rheumatoid arthritis or cancer. The parents report financial burden, missing work and school, because sleep apnea is associated with an increased risk of needing health services and healthcare visits. There are also moderate associations of obstructive sleep apnea with depression. So none of it's good. And the burden lasts and is significant. Severe obstructive sleep apnea in children is associated with at least a two-fold hazard ratio for all-cause mortality in adulthood. There's a two-fold increase in risk of cardiovascular events, a risk of incident and recurrent stroke, and nocturnal hypoxemia increases risk for major cardiovascular events. We know that pap therapy can actually decrease this risk in a dose-dependent fashion. But again, we have a window of opportunity in children to reverse this. Morbidity does become irreversible over time and affects health throughout the lifespan, but if you can catch it early, you can turn this around. So then comes our second challenge. How do you diagnose obstructive sleep apnea or sleep-disordered breathing in children? Well, the gold standard is a polysomnogram. But as I'll show you, the availability of this test is really quite limited. Polygraphy or home sleep studies may underestimate the severity because they don't measure arousals or carbon dioxide. They're not fully validated in children, although there's increasing data and increased usage of this testing modality because there simply isn't another option. It has been indicated and can be used for diagnosis of moderate to severe obstructive sleep apnea in instances where polysomnography is not available. Oximetry is a simpler test. It can be done at home, often through a home care company. The challenge in many Canadian centres is that there's a cost associated with it. If there isn't a program set up at your particular institution, as is the case with ours, that the cost is then passed on to the families, and it costs $50 to $150, Canadian, to get an oximetry done. There are metrics from the oximetry that can be relatively useful in identifying sleep-disordered breathing, but as you can see here, they're not perfect. And the two that I'll mention are the oxygen desaturation index, an index of the number of dips in oxygen saturation of 3% or more, which has a sensitivity of 83% and specificity of 75%, and the McGill oximetry score, which has a sensitivity of 58-ish percent and specificity of 90%. That one counts the number of clusters and the depth of desaturations. Pediatric sleep questionnaire, unfortunately, does not have great sensitivity or specificity for diagnosis of obstructive sleep apnea in children, and history and physical exam on which we judge most of our diagnoses is really not that helpful in this case. So here's our problem. This work was done back in 2014. I will tell you that we've just repeated a similar survey. The results aren't published yet, but the magnitude of the problem has only grown. So in Canada in 2014, there was capacity across the country to do just over 9,000 polysomnograms per year. If you take a conservative estimate of the number of children affected by obstructive sleep apnea, remember I told you 1 to 4% in the general population, you would expect that 69,000 children are affected by sleep-disordered breathing. Now we know we can't pick out the kids who have sleep-disordered breathing, but even if we only tested those kids who actually had it, there are 7.5 times more children with sleep-disordered breathing than our capacity to do polysomnograms per year. So we have a problem. We have a real shortage of pediatric sleep studies. And the problem is more challenging in populations that are deemed high-risk. So in children with Down syndrome who have a much higher prevalence and incidence of sleep-disordered breathing, their symptoms don't reliably predict sleep-disordered breathing, much like the general population. What we found in a meta-analysis is that children with OSA in this population are often older. And in a longitudinal study, we found that the sleep-disordered breathing, even if you identified it early, would persist or recur in three-quarters of the children. And it was not predicted by age, by how bad their sleep-disordered breathing was, by how obese they were. So it was really challenging to know. The reason I highlight this is that in the American Academy of Pediatrics guidelines for surveillance for children with Down syndrome, it's recommended that they have a sleep study by the age of four years. There's really nothing magical about the four-year point in time. And as you can see here, these are the trajectories of the children that were in our study. Their incidence of sleep-disordered breathing occurred later in many cases. The type of sleep-disordered breathing changed, and they just went on to continue to have it. So the lack of ability to predict sleep apnea and a high recurrence rate highlights the need for proactive and longitudinal screening. So this high-risk population doesn't just need one sleep study. They need many, and many over time. This is probably one of my favorite studies. It wasn't huge, but it was the one I started when I was a fellow. We took a group of asymptomatic children in the neuromuscular clinic who all had a variety of progressive diseases. And our intent was to try to screen them for sleep-disordered breathing, particularly nocturnal hypoventilation, and then to use our clinical predictors, including pulmonary function tests, to see if we could identify a threshold that would be associated with sleep-disordered breathing. What we found instead, 15% of them, these are asymptomatic individuals with neuromuscular disease, 15% of them had clinically significant nocturnal hypoventilation. So we can't tell who has it. And while there have been many other studies in addition to ours that have tried to identify pulmonary function thresholds for when these kids get into trouble, we're not so great at it. So here's another population, super high-risk, with really no clear metric for identifying when they're getting into trouble, but another group with progressive disease that also probably needs longitudinal and regular screening. We also looked in obesity and found that while there's a 2-to-1 male predominance in adolescents, consistent with what happens in adults, and that the males with OSA who also had obesity were more likely to snore and gasp, they also had an increased waist-to-height ratio, so where they deposited adiposity made a difference, but it was hard to predict their sleep-disordered breathing as well. So this let us just try and find a new biomarker. And this little tape measure here I think would make my grandfather, who is a tailor, very proud. In adults, it's known that neck circumference or neck size is a predictor of obstructive sleep apnea. In kids, this is a more difficult question to answer. Why? Because how do you know what's a normal neck size in a child? They're growing and they're changing. What's normal for a 2-year-old boy is not going to be the same as for a 14-year-old girl. So our first task was to try to determine what is a normal neck size for children, and we were lucky to partner with the Canadian Health Measures Survey, which is a government-run national survey that was collecting information on anthropometrics and demographics across Canada. And with this, we were able to screen children between the ages of 2 and 18, and we were able to create these growth curves of what is a normal neck circumference. Our next hypothesis was that those who had a neck circumference above the 95th percentile for sex and age would have a higher risk of obstructive sleep apnea, which is in fact what we found, but this was particularly true in boys who were over 12. And what was interesting is that it was a better predictor than their BMI. So it's not just whether they're obese, but whether they carry their weight in their neck and centrally that also contributes to sleep apnea. Not a surprise likely to those in the audience who treat adults because that's been known, but in kids this hadn't been shown before. The challenge is when you have a group of children with obesity, most of them have a neck circumference above the 95th percentile. So then your discriminatory ability becomes a lot less. And so we turned to neck-to-waist ratio to try to predict obstructive sleep apnea better in children who were overweight and obese. And this actually performed relatively well with an area under the curve of 0.74 unless your BMI was over the 99th percentile and then we didn't have as much discriminatory ability. This was from a cohort study that Indra Narang and I were part of through the Canadian Sleep and Circadian Rhythm Network. We had a group of 74 children with obesity with a median age of 14 1⁄2 years, about half of which were male, all of whom were obese, and 40% of them had moderate to severe OSA. In this study, we looked at their anthropometrics and found that each 0.1 increase in a neck-to-height ratio was associated with a 57% increase in their obstructive apnea hypopnea index. We were also able to identify neck-to-height ratio thresholds for girls and boys that would help to identify who was likely to have OSA. But this wasn't perfect, so we strived for better. So we looked at video clips next, and this is the work that's ongoing with Rafiqa Ersi, who's in the audience. This study was looking at whether a parent-recorded video clip on a smartphone, in other words, the picture worth 1,000 words, was better at detecting obstructive sleep apnea and could be used for screening. And we started doing this really based in part on pilot work that came out of Australia. This pilot study was published last year in 43 children, and they developed a scoring system for the video clips to help identify children who had obstructive sleep apnea. The scoring system is out of eight and based on the presence of inspiratory noises, obstructive events, evidence of increased work of breathing, the presence of mouth breathing, and neck hyperextension. If you had a Monash score greater than three or equal to three, then you could identify children who had obstructive sleep apnea with a sensitivity of 100% but a specificity of 36%. This translates to a positive predictive value of 53% or a negative predictive value of 100%, so a useful screening tool. We then tried to figure out if we were good at doing this video scoring thing. So we took 38 children who had been referred to our center for polysomnography for evaluation of suspected obstructive sleep apnea. We had two raters, and we looked at the weighted Kappa score for inter-rater agreement. They were scored based on the Monash score, which was dichotomized to three or more or below three, the score severity, the overall clinical impression of whether we thought a child had sleep apnea or not, and whether we thought it was mild, moderate, or severe. And you can see that the rating scores have really a high inter-rater agreement. Now, our next step is to try to compare this video clip and see how good it is compared to a gold standard test. And while we have several studies ongoing in different populations looking at the comparison of the video clips to polysomnography, we started this work, unfortunately, during the COVID pandemic. So this is work that Rafiqa presented yesterday, but our pilot in 50 children so far between the ages of 3 to 18 years found a sensitivity of 75% and specificity of 85% of the video clips for the presence of obstructive sleep apnea based on polygraphy with an obstructive apnea-hypopnea index of at least 1.5 events per hour. We also compared it to other screening tools for moderate to severe OSA. And as you can see here, it performed better. Sorry, there. Better than the Pediatric Sleep Questionnaire. Not quite as well as the oximetry, but as I've told you, the oximetry is challenging to get. So if you're looking for an easy test that may be more broadly applicable, this may be something that's worth pursuing. We certainly think it is. We'll have, hopefully, more to present in the years to come. So let's turn our attention to the second challenge. That one is treatment of sleep-disordered breathing. If you can identify it, I've told you there's a window of opportunity in which you can make a difference in reverse morbidity and complications. But does the treatment work? So here's the clinical problem. Parents have a 7-year-old girl with moderate obstructive sleep apnea, adenotonsillar hypertrophy, and obesity. The parents are afraid of surgical complications, but really don't think their child's going to tolerate positive airway pressure therapy, and they're trying to decide on the best way to proceed with treatment. So here, the research foci are looking at outcomes of sleep-disordered breathing treatment, avoiding surgical complications after adenotonsillectomy, looking at whether non-invasive ventilation or positive airway pressure treatment improves outcomes, and looking at predictors of PAP adherence. So we know that adenotonsillectomy in young children is curative in most kids. The complications are typically dehydration, bleeding, and airway edema or obstruction that can result in apnea. We tend to use non-invasive ventilation when the adenotonsillectomy is either contraindicated or unsuccessful. It might be more strongly considered in the presence of obesity, and certainly in the presence of neuromuscular disease, and if there's central sleep apnea or hypoventilation. But as in all patients and all treatments, adherence is a challenge. So our first task was to look at predictors of postoperative complications in a cohort of children who were undergoing adenotonsillectomy for sleep disordered breathing. We looked at their perioperative respiratory adverse events, which we defined as needing oxygen, airway support, and ventilation. Not surprisingly, we found that they had an increased risk of such events if they had underlying cardiac comorbidities or airway anomalies, or if they were very young. What did surprise us is that while the oximetry metric of the McGill oximetry score in younger age predicted the presence of PRAEs, the apnea-hypopnea index and the other polysomnogram metrics really didn't. And Lena's sitting in the audience there. This was a lot of her work during her residency and fellowship. Next we tried to see if there were other factors that we could identify that contributed to postoperative risk of events. Same cohort of children. This time we were looking at the median postoperative morphine dose that they received. And over time, different types of opioids had been used, so we standardized them by converting them all to morphine dose equivalents. The median dose was .17, which is considered a moderate dose of opioid that most children received. 66 children, or 17.5% of them, had one of these adverse events. And the morphine equivalent dose was a strong predictor, not surprisingly, of the adverse events. What was interesting, though, is that together, a higher preoperative AHI, apnea-hypopnea index, and higher morphine equivalent dose were both independent contributors, but combined, they really increased the risk of postoperative adverse events. I mention this because it's often a challenge to determine which kids need to be watched in hospital after one of these events. Some kids come in, get de-surgery, and go home. The kids that are at higher risk of having one of these adverse events are really ones that you need to pay attention to and monitor more closely postoperatively. Next we'll look at non-invasive ventilation. This lovely graph is from Maria Castro's work, looking at non-invasive ventilation use. And the reason I put it up here is that if you look at the number of children who are receiving non-invasive ventilation, it looks a little bit like a tsunami. And the number of children who are requiring non-invasive ventilatory support is increasing dramatically over time. This is from work done in Alberta, but there are similar graphs that you would see in children that were done from work in Toronto by Rishma and others around the world. But again, hard to know who's going to be adherent to therapy. We've done a few studies, some qualitative ones, some systematic reviews and meta-analyses to try and figure out who really needs the most support and who's most likely to struggle with adherence. In a retrospective cohort of 104 children, we found that those who were older, those who had milder sleep-disordered breathing and less disrupted sleep, were less likely to adhere to PAP therapy. A systematic review and meta-analysis found that the highest rates of PAP adherence were in females of a younger age who were Caucasian, who had higher maternal education, greater baseline AHI, and the presence of developmental delay. Finally, in a qualitative study of children with neuromuscular disease, we found that the dimension that most affected adherence was whether the youth felt well or unwell. In other words, if somebody feels better with the therapy and is supported at home to do this, they're more likely to be successful with treatment. We looked at this as well in children with obesity. So this was a prospective study that you'll hear me reference a few times. That one found that those with lower nocturnal oxygen saturation ADER were more likely to adhere to PAP therapy. This study was a cohort of youth between the ages of 8 to 16 years of age with obesity who were newly diagnosed and about to start on PAP therapy for moderate severe sleep disordered breathing. We followed them for a year. There were 24 children in this cohort with a median of 14 years of age. Excuse me. What we found interesting with this one was that their baseline CONERS, which is a measure of inattention and hyperactivity, and their child behaviour checklist, which is a measure of their behaviours, were abnormal. And they were abnormal in the whole cohort. Not super surprising. But the kids who went on to be non-adherent to PAP over the subsequent year had significantly more elevated baseline reported CONERS. In other words, if they were inattentive and hyperactive, they were going to struggle more. The difference in the CONERS scores was still present a year later for inattention, but not hyperactivity. And while behaviour improved for everybody over the year, the biggest takeaway was that this baseline characteristic was the one that was going to identify the kids that were going to be in trouble over that year. Here's a study looking at neuromuscular disease. Not a surprise that this is successful therapy. We know that non-invasive ventilation can improve survival, quality of life in individuals with neuromuscular disease. But we were surprised a bit by the magnitude of change. So again, a small study conducted when I was a fellow. 15 children with neuromuscular disease who had started on nocturnal non-invasive ventilation and had at least a year of follow-up. And the children served as their own controls. These were all individuals with progressive disease, so you would expect that they would have more hospital admissions in the subsequent year. Instead, what we found was that they had 85% fewer days in hospital, 68% fewer days in the intensive care after initiation of non-invasive ventilation. And not surprisingly, their sleep study parameters improved. OK, more about kids with obesity. So again, the same prospective cohort of kids 8 to 16 years, newly diagnosed with moderate to severe sleep disordered breathing, prescribed pap therapy, and followed for a year. The main reason for doing this study, and really our primary outcome, was to look at metabolic parameters over time. What we were a bit shocked at was how much disease was present at baseline. So 40% of the cohort had an abnormal HOMA-IR, which is a measure of insulin sensitivity. 44% of them were already hypertensive. 70% of them had lost their nocturnal blood pressure dip, which is a precursor to the development of hypertension. And 64% had an elevated CRP. So inflammation. Their total PEDS quality of life score was impaired in 70% by parent report and 62% by self-report. This is lower than studies of quality of life in children with obesity alone or of children who have OSA alone. So if you have both conditions, your quality of life is even more impaired. And the degree of quality of life impairment was comparable to that of children with cancer or juvenile rheumatoid arthritis. So, we thought we could make things better for them by treating them with pap therapy for a year. Now, we didn't show any statistically significant changes in their metabolic parameters of their blood pressure, and there weren't differences by whether or not they were adherent. What we did show was clinically relevant improvements in their insulin resistance parameters and their systolic blood pressure load, both of which are predictors of future cardiovascular disease. Who's to say if we had studied them for two years or three years and they were actually adherent if we would have made more of a difference? Or if the change that we've made, even though it seems small, may actually be preventing a great decline that would have otherwise been seen. The parents reported significant improvements in total and social functioning scales, regardless of adherence. The kids didn't notice any difference. Okay, our last challenge for today. This one's looking at airway clearance in neuromuscular disease. Clinical scenario here is a 14-year-old boy with Duchenne muscular dystrophy who's receiving nocturnal non-invasive ventilation, who is declining lung function, and parents describe a rattling in his chest all the time. So, the goal here is to look at the efficacy of lung volume recruitment in slowing lung function, maintaining chest wall distensibility, and enhancing cough efficacy. We know that respiratory complications in children with neuromuscular disease are primarily due to the inability to cough effectively and clear the airway of secretions, as well as restriction of the lung and chest wall expansion that result in a loss of lung function and ultimate hypoventilation. The lung volume recruitment is a means of stacking breaths, one on top of another, to expand the lungs and the chest wall, which aids in the clearance of secretions by enhancing cough peak flow. It maintains chest wall distensibility, much like putting any other joint or muscle through a range of motion exercise, and we think that it slows decline in lung function. Now, no matter where in the world you are, there are clinical care recommendations that recommend the use of lung volume recruitment and airway clearance techniques, but we really don't know the optimal timing of initiation or how much or how often you need to do this. A recent systematic review showed that there was no randomized control trial or long-term data on the use of LVR, and there are a few retrospective studies that I'll draw your attention to. This was work that I did under the mentorship of Doug McKim, looking at individuals with pretty advanced neuromuscular disease. These are young men with Duchenne muscular dystrophy with a baseline FEC of 22% predicted, and what we did was track their lung function trajectories in the two years before and after lung volume recruitment exercises twice daily were reduced. Here's the slope of the decline before and after. There was an 89% reduction in forced vital capacity percent predicted decline, so it looks like the stuff works. We also looked at other measures. The MICVC difference, the maximal insufflation capacity, is the most air that you can get into your lungs after a lung volume recruitment maneuver compared to your vital capacity, which is spontaneous, and what we found is that MICVC difference, so that ability to distend the chest wall and fill the lungs with air is maintained even as you're losing forced vital capacity and your MIPS and MEPS, measures of respiratory muscle strength, are decreasing, and lastly, with an assisted maneuver, a cough peak flow in a clinically effective range can be maintained for up to eight years after initiation of twice-daily lung volume recruitment. So this really prompted us to embark on a huge project. I'm looking around the audience and recognizing many people who have contributed in great ways to this, so thank you all. This was about a decade of work from everybody to try and do the steadfast study, which we called Stacking Exercises, Attenuate Decline in Forced Vital Capacity in Sick Time. The question that we posed was will adding twice-daily lung volume recruitment to the standard treatment received by children with Duchenne muscular dystrophy reduce the decline in forced vital capacity percent predicted by at least 30% over two years? It was ambitious. It was a multi-center, single-blind, parallel randomized control trial of conventional treatment versus conventional treatment plus LVR twice a day. There were nine tertiary care Canadian pediatric hospitals involved. The intervention itself, as you can see here, was an AmbuBag with a one-way valve in it, and this has a mask interface, but it could also have been a mouthpiece interface, and the idea was that this would be used twice daily. We had a data logger in line so that we could measure usage and monitor adherence, and the kids were followed for six months for up to 24 months. We recruited children between the ages of six to 16 years of age. We wanted them able to do pulmonary function tests, and we needed to have two years of follow-up before they transitioned to adult care. They all had Duchenne muscular dystrophy. We included those with a forced vital capacity of at least 30% predicted and excluded those who had more severe restrictive respiratory impairment because we weren't sure they would be able to reliably perform pulmonary function tests, and to be honest, most of them were already using some form of airway clearance at that point as well. They had to have a caregiver willing to provide the therapy, fluency in English and French, and they were excluded if they were already using some form of regular airway clearance, not just during exacerbations, which we allowed during the study, but regularly using it, if they had a susceptibility to pneumothorax, if they had a tracheostomy in situ, if they were unable to do the lung volume recruitment maneuver or the pulmonary function test, or if they were enrolled in other intervention studies. This actually proved to be quite a challenge because there were a number of drug studies that launched right at the same time as ours, so it was harder to recruit than we anticipated. So the baseline characteristics I'd like to draw your attention to, because the population that we ended up recruiting were actually reasonably well at the time of the start of the study. So there were 70 children, randomized to the two groups, with a median age of 11 and a half years. Their baseline median FEC percent predicted was in the normal range, 85%. About a third of them were wheelchair-assisted, a few of them had scoliosis, very few of them were receiving non-invasive ventilation, and the overwhelming majority were receiving glucocorticoids, which isn't a surprise. Now I'd love to stand up here and tell you that we really showed this great difference and that lung volume recruitment was fabulous, but that was not what happened. So while there was a small treatment benefit, the adjusted mean difference in force vital capacity between the two groups at two years was 1.9% predicted in the direction treatment benefit, and unfortunately this didn't achieve statistical significance. We also didn't see it when we looked at the per protocol analysis, or in the time to decline, 10% in pulmonary function. And what you see here is that the LVR group is in pink, and the control group, rather, is in blue. But those lines overlap, or curves do. So our conclusion from this was that no difference in decline and force vital capacity percent predicted was seen, with the use of twice daily lung volume recruitment for boys with Duchenne muscular dystrophy and relatively normal lung function. So we learned that the burden of associating, of making kids do this treatment, which takes 15 minutes twice a day, is probably not worth it for those who have normal lung function. Now please don't walk out of this talk thinking that I don't think lung volume recruitment works. It does. We just haven't figured out exactly when the right time to introduce it is, and when it's going to be most beneficial, and how. Remember the first graphs I showed you of the individuals with much more advanced disease who had a really big improvement in their rate of decline of lung function with the treatment. So where do we go next? What we need are better diagnostic tools for obstructive sleep apnea in children that don't rely on polysomnography, that we can't access, or at least help us identify which kids most need it. Hoping the video clips are gonna be the answer to some of that. We need real world data on outcomes of non-invasive ventilation and lung volume recruitment in neuromuscular disease. I hope we'll achieve that through international registry data. I don't think another randomized control trial is gonna work because it's now standard of care to receive lung volume recruitment or airway clearance on a regular basis. But hopefully we can answer those questions. And the last thing that I've embarked on which I have not discussed today with many of the people in the room as well is prediction of respiratory outcomes in extremely preterm born infants using MRI technology. Now I didn't get here alone. Certainly couldn't have done it without lots of friends and support and colleagues. But I have learned many lessons along the way. It is nice to play nicely in the sandbox and it does help to make friends and surround yourself with like-minded individuals who help and are interested in the same things. You're only as good as your team. You need a strong group of individuals who are engaged and interested in the same things. Mentorship is super important and I'm looking out and seeing a few people who've performed that role very well for me over the years. It's important to be curious and be brave and keep the end goal in mind. In reality, all of these projects, although they seem scattered in many different directions, were really born out of the desire to make things better for patients and to figure out how to improve care. And lastly, you need a high frustration tolerance in research. So that cartoon is worth reading for anyone embarking on a research career. Lastly, I'll leave with words of gratitude. Gratitude to the participating children and families, to all of you in the audience who have collaborated in all the research, my clinical colleagues who support me and allow me the time to do the research endeavors that I try to embark on, the mentors who paved the way for me and taught me, and my family who are always my support, and the people who give me money to do the work. And with that, I'll end and I'm happy to answer questions. Thank you. Thank you, Dr. Katz. Great talk. Important work. Open for questions. Anyone have any questions for Dr. Katz? What? And we've got a second one in the wings, so we're good. In the wings there, we're good, we're good. So I'm not a pediatrician, but I'll ask. I was curious about the FVC and having the normal FVC. So two things, two questions. One, do you think the rate of loss of FVC would be something to sort of look at and sort of maybe that's the target population to go after for the recruitment maneuvers? And then two, just piggybacking off of Brian Ross' talk, before about wearable technologies in this group and looking at some of the sympathetic markers at night that might be helpful to sort of screen. Just your thoughts on those two. Thank you, great questions. So the rate of decline of lung function and FVC percent predictive was actually the primary outcome for the study. That was what we were trying to look at. We also looked at the time to get a drop of 10%. Unfortunately, we didn't show differences in those. I think it's hard because the rate of decline fortunately is much slower in individuals who are earlier on in their disease process. And with the advent of glucocorticoid therapy for everyone which helps to maintain lung function until much longer. So I think if we'd been able to recruit individuals with more advanced disease and perhaps older individuals, we would have seen a very different outcome is my hunch. And the second part of your question with regards to wearable technology, I think it's coming. I think there's a lot of work being done. It's probably the way of the future for most individuals, but we're not there yet. Thank you. Sari, congratulations for your award, well-deserved. I want to be like you when I grow up. But because I'm not there yet, here's my question for you. In the era of disease modifying therapies for neuromuscular patients, a few that are lining up for DMD, what are the outcomes we can look at? Because it's possible that that FVC change becomes not significant anymore. You're absolutely right. I don't know what the outcome is. I think we have challenges, right? Because we'll have younger children who can't do pulmonary function tests at all where we need to look at outcomes and see if they're improving. And the respiratory outcomes are hugely important. They may be swallowing function. It may be their sleep parameters and their gas exchange during sleep. I don't think we know. We need research in that area for sure. And FVC hopefully will be well-preserved into adulthood and won't be the metric that we need to look at anymore. Thanks. Hi. Thank you very much for a great talk. Thank you. Maybe a question kind of marrying your research interests a little bit. When I think about the DMD population, they're all on corticosteroids, which we know affects hunger drive and the distribution of adipose tissue and things like that. Is there any work right now looking at the impact of whether it's BMI or neck circumference or those kinds of things on outcomes such as obstructive sleep apnea or nocturnal hypoventilation in this population? And do we need nutritionists or dieticians rather in our multidisciplinary DMD clinics? Great question. Definitely need the dieticians and the nutritionists. I think there is evidence emerging that obstructive sleep apnea is becoming more common in this population with greater adiposity. I don't know that anyone's looked at neck circumference, but you're right. It would certainly be interesting to look at. Great presentation, Dr. Katz. I'm struck by the profound lack of polysomnography available to a large population that needs it. Yeah. And your work with video clips. And I'm wondering if any sort of machine learning algorithms could be applied to standardized views of video clips in order to get a little bit more granular and predictive in trying to figure out who has obstructive sleep apnea. Thank you. I think that is a fantastic idea. Once we get through the pilot work, that is exactly where we want to go with it. It is time consuming to watch those videos. Even though they're only two or three minutes long, it adds up over time. And if it could be automated, it would be fantastic as a screening tool. So yes, my hope is that's where we'll go. Hey, Sherry. That was a great talk. So I'm a pediatrician, as you know. And I guess what I struggle with comparing our population to your population is glucocorticoid therapy, right? That's not something that's very ubiquitous in the U.S.? Yeah. And so, just to be provocative, do you think pulmonary function is not the right outcome? I mean, is it not the right appropriate measure? As you know, now even the DMV guidelines for hypoventilation criteria is much more sensitive, I would say, for identifying hypoventilation. In pediatrics, should we be looking at other measures? I mean, I know in the adult world, we're using like RISB and these types of outcomes during sleep. Yep. But I'm just wondering what your thoughts are for vital capacity. I think you're right. It's not a particularly sensitive metric. I think we saw that in our study. But it didn't detect differences. I don't think we've hit on the right one yet. But I agree that we need to look much more broadly. Maybe it's cough peak flow. We didn't see a difference in that either, to be honest. But I think that's probably a more sensitive measure, tough to do and hard to norm in kids. And yes, we need to be looking differently at this question from a variety of lenses, looking at sleep, looking at daytime respiratory function. And yes, we need better metrics, for sure. Excellent. Appreciate the questions. Any other questions? So, hi everyone. Thanks for allowing me to be here. I'm actually not Canadian. You don't have to be Canadian to be here. Everyone is welcome. Just so you know, pass that around. Thank you for coming. So one of the things that you said that I sort of struggle with is that this can't be done because there's such gross adaptation of the technology. Where would you find someone that doesn't use it? Come on down south. Where there is exactly one clinic in the United States that uses lung volume recruitment and it's mine. Yeah. But that's soon gonna stop, right? Because Philips has announced they're no longer gonna make Kaphasists. I think that's gonna change the lay of the land. I also agree with you tremendously that the deflays a court introduction to say nothing of ASO drugs and Exxon skippers and all the rest of it means that I think we're gonna start seeing this in adults more than seeing it in our pediatric population. So how do we take your lessons and sort of get the attention of the adult providers and the clinics outside of Canada? We take key thought and opinion leaders like yourself, Lisa, to spread the word. But I think, so I think there's room for looking at this in a few different ways. I think there are registries in the US that exist that have data looking at trajectories of lung function that can be compared to Canadian national data. I know David Bernkrant and others are quite interested in that question. So we started to try to tackle it that way. We compare individual trajectories and I'm looking at Nicole and David who we've been trying to get something going looking there. So I think we will be able to get the data in different ways. As far as exciting others to jump on the bandwagon, I think it's hard in the absence of data. And I think we need that first to convince people. Certainly this RCT is not the thing that's gonna convince people that they need to do twice daily lung volume recruitment. But I also think that it would be very hard to replicate and too long, it would take too long. So I think the landscape is changing. I think you're right. We think the trajectory for individuals with Duchenne muscular dystrophy is gonna look very different. But if we don't keep them healthy from a respiratory perspective until they get to those treatments, then we've done them a disservice. And spreading the word is probably the best way. Thank you, Sherry. I love your talk. I am also gonna be controversial because I'm really interested in the fact that you mentioned this is standard of care. If we look at the data, your RCT early in disease would suggest that it doesn't have an effect on our physiological measures. And as you know, we now have an RCT in adults that shows exactly the same thing albeit over a much shorter duration. So coming back to this question around being standard of care, my first question is, is it standard of care in a cough augmentation sense or is it standard of care in a respiratory range of movement exercise sense? Because I wonder whether or not there's something in being a bit more delineating exactly how we're using this technique and what for, particularly in the context of the MIE shortage. Is there something in there that we need to approach the use of this technique in a bit more of a sophisticated manner? I think definitely yes. What that metric is, I'm not sure. I don't know if it's in my CVC difference, if it's cough peak flow, if it's something else. I think part of the challenge is that change is small over time. Even though these are progressive diseases, they don't deteriorate quickly in the same way that somebody with ALS would deteriorate and lose lung function. It's harder to measure and show a difference. So no matter what the metric is, we may need to study this over years, which is why I think that looking at the registry data that already exists is probably gonna help us answer that question better. You know, this is a real fabulous talk. Thank you so much. So thoughtfully put together. A lot of work went into this. And Lisa, everybody loves you. You're a universal citizen. You're a citizen of the world. But if you were to come down south past Lisa and come to us in Cincinnati, yes, we are another place that does lung volume recruitment. The one thing that we found when, you know, some years ago, we did the study with Hank at CHOP where we looked at hyperinflations and the ability to preserve vital capacity in congenital muscular dystrophy. The reason we picked that is because it's much more consistently progressive and very aggressively so a restriction. And what we found was it was a small subset because CMD is rare. You can preserve vital capacity or even maybe up it a little bit compared to the control that actually happened to be a little better performing. The benefit is only measurable as long as they continue to do it. So there's a paper from the 70s. Sinha was the last name where he had six patients and used lung volume recruitment strategies to preserve function and actually measured respiratory compliance for every of those six patients every 30 minutes after doing hyperinflations and showed that the benefit was preserved up to two and a half hours and they didn't do further testing past the hyperinflation. So it does have an effect on the respiratory compliance. I think what people confuse this is with will my lung function get better and that's a separate issue and is a function of respiratory muscle strength which is not what we are addressing over here. The challenge that we found also was that people who are willing to do it tell us can you tell me how to do this and I'll be done with it once in the day and I don't have time for two times. When you look at the Duchenne trajectories of decline I wonder because you had a small subset whether your patients were at different stages of readiness to decline versus active decline because that mean age of 11 is like right at that drop off which we saw in our population when we published this with Brigitte is for steroid treated patients is 12 to 18 is their most rapid stage of decline. So if you hit somebody at 13 or 14 you might see a difference but someone at 11 may not show a difference that will obviate the significance of your global data. So I wonder if segregating that between later patient populations might actually give you better signaling. I think you're 100% right. That was I think the biggest downfall of the study is that everybody was at that early stage and not at that steep part of the slope and we did try to look at it. The numbers are so small and there were so few individuals who were in that more advanced stage that we weren't able to examine it but I completely agree that you're right and the answer is somewhere in the middle between our population and the individuals I showed you in that retrospective study who had very advanced disease where you can really make a big difference. And then I just wanted to throw out something else in terms of the problem with spirometry. You know spirometry is not the best test in the world and so what we have started to do especially because we wanted to address a lot of the issues that Haman was just talking about is to say that we have other outcome measures and the two biggest are swallow function and for those of you who may work with Stuart Cleary, I don't know if anybody does in the room, his data with ALS shows that the use of lung volume recruitment improves swallow in ALS patients significantly. So we time it toward like before you start your meal and then we have reduction in aspiration and improvement in eating satisfaction. Things that weren't looked at at all and then the other is voice quality. You know can you be used, okay let's face it this is what these boys worry about. How good am I at talking on the phone with my girlfriend and how much can I use voice production to help use my internet interfaces. So I think maybe it just may be looking at sort of those different outcomes to see a difference. I'm gonna throw out one other thing because you mentioned David Bernkrant. So the other thing with Dave was looking at the genetic phenotypes and to say look especially in Becker's we know that boys at 21 sort of declare themselves. I'm either gonna have rapid production and get to that point where I flow down or I'm gonna be pretty stable. And so I think the other thing that needs to be done as we replicate this is to get the genes and look at the genes. Yeah, you're quite right. Excellent, great discussion. Thank you for all those questions. I'm gonna invite Dr. Mohit Botani, our president of the Canadian Thoracic Society to come up and say a few words and present our award to Dr. Katz. Thanks Chris. All right, so first of all thank you for everyone joining us today. It is my distinct pleasure to award Sherry the CTS Honorary Lecture. And just in having listened to your talk and seeing the faces and the influences that have been on your career and what you're doing to other people, you embody everything that this award stands for. You are an excellent clinician, clearly a fantastic researcher who's on the cutting edge of the science due to the controversies that we've just had discussions about. So you know you're creating a ruffle when you're creating these types of questions. And just the humility of how you conduct yourself in terms of your work and the people and the respect that you have from the community, it is what this award is all about. And you're one of the most deserving candidates I think I've ever encountered for this. And so congratulations to you on this and thank you for presenting. Thank you.
Video Summary
Dr. Sherry Katz, an expert in pediatric respirology, was awarded the Canadian Thoracic Society's Honorary Lecture Award for her significant contributions to the field of Canadian respiratory medicine. In her lecture, Dr. Katz discussed her research on using respiratory technology to help improve the lives of children with respiratory conditions. She focused on three main topics: predicting sleep-disordered breathing in children, the outcomes of non-invasive ventilation in children, and the use of lung volume recruitment therapy in children with neuromuscular disease. Dr. Katz highlighted the challenges in diagnosing sleep-disordered breathing in children, including limited availability of sleep studies and the need for more accurate diagnostic tools. She also discussed the importance of early diagnosis and treatment of sleep apnea in children, as it can lead to significant health issues and reduced quality of life. In addition, Dr. Katz presented her research on the use of non-invasive ventilation and lung volume recruitment therapy to improve outcomes in children with respiratory conditions. She emphasized the need for further research in these areas to better understand the effects of these interventions and to identify predictors of treatment adherence. Overall, Dr. Katz's lecture highlighted the importance of using respiratory technology and interventions to improve the health and quality of life for children with respiratory conditions.
Meta Tag
Category
Respiratory Care
Session ID
2165
Speaker
Christopher Hergott
Speaker
Sherri Katz
Track
Pediatrics
Keywords
Dr. Sherry Katz
pediatric respirology
Canadian Thoracic Society
Honorary Lecture Award
respiratory medicine
sleep-disordered breathing
non-invasive ventilation
lung volume recruitment therapy
neuromuscular disease
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