All right, everybody. I think it's time to start. Thank you so much for coming. My name is Sumit Bhargava. I'm a pediatric pharmacy and sleep medicine doctor currently at Stanford. I am co-chairing this session with Dr. Shahid Shaikh, who is my colleague and the chair of this section. He is going to actually get us going first by talking about updates in cystic fibrosis. We just have one request that we are trying to increase the pediatric presence here at ACCP. Not always easy. So if you can kindly rate the section in the app, feel free to rate it any way you like, but do rate it because then it shows that people actually came and did something. So thank you very much. And here is Dr. Shaikh, who is professor of pediatrics at Nationwide Children's Hospital and the Ohio State University, who has been a colleague and a mentor for many years to many of us. He is here to talk about updates in cystic fibrosis. Dr. Shaikh. Thank you, Sumit, and thank you, everyone. I think the topic for me today is that updates in cystic fibrosis. So I have no financial relationships to disclose, no copyright infringement is intended. If I've taken slides from any papers, it is just for the information sharing. The topic is to review the updates in CF care in the last one year. If you look at the PubMed, there are about 2,500 articles on CF alone in the last one year, but of them, about 1,600 are reviews and about 1,000 of them are about in pediatrics. And most of them are related to CFTR modulator therapies. So I don't think we have enough time to go over all of them, so we'll just try to focus it on a few topics, such as newer CFTR modulators, new indications or approvals for these therapies, impact of CFTRs on inflammatory markers, and impact on chest and sinus disease, just to cover the most important things right now. There are two FDA approvals in the last one year. One was in April 2023, which was approval of TREC-AFTA for children two to five years old, with at least one copy of Delta F508. With this approval, about 2,200 children will be eligible for TREC-AFTA. Among them, about 900 will be receiving CFTR therapy for the first time. Another approval was in May 2023, FDA also approved Kalydeco for infants as young as one month old. So as we stand now, the Kalydeco is approved for kids above one month of age, or Combi is approved for kids above two years of age, Simdeco is approved for kids above six years of age, and TREC-AFTA is approved for kids above two years of age. Let's briefly look at some of the studies in last year. This was on the role of ETI in two to five year olds, which showed that the therapy is safe and well tolerated. And in about 75 patients, this therapy did show improvement in CFTR function, which was noted by the improvement in decreased sweat chloride, and improvement in lung functions reported by the Lung Clearance Index. And it was also associated with stable BMI, a low rate of pulmonary exacerbations, and a trend toward improved pancreatic function over the six months study period. Another study, which was with Moorland Group, which is the role of ETI in six to 11 year olds. It was a randomized double-blinded placebo-controlled trial. Patients either received ETI or placebo for a six-month period. There was about 60 patients in each group, and the children who received ETI had a mean decrease in Lung Clearance Index of about 2.3 units compared to only 0.02 units in patients who received placebo. Similarly, sweat chloride difference between the group was about 50, and the person predicted FEV1 difference between the group was 11%, clearly showing that compared to placebo, ETI had a better clinical role. Now let's briefly look at inflammation. There are a couple of studies came last year. First one is Zhang's study, which looked at the macrophage function in the patients who received ETI. In this study, the samples were obtained at baseline, and then every three months for one year period in 56 subjects with CF, and the results were compared to the non-CF controls. Peripheral blood monocyte-driven macrophages were isolated, and functional assays were performed. They were able to note that in macrophages, there was increased CFTR expression function and localization to the plasma membrane. There was improvement in phagocytosis, intracellular killing of the CF pathogens, but there was no significant change in the cytokine profiles. At the same time, there was clinical improvement, both noted as improvement in FEV1 and BMI. Thus, ETI showed improvement in macrophage functions. Another study came from our group. In this study also, clinical data was obtained at initiation and every three months for the total of one year. Blood was analyzed at baseline and six months for cytokine and immune cell populations and compared to the non-CF controls. We had 48 patients, and with the mean age of 28, a significant increase in percent predicted FEV1 and BMI was noted, but at the same time, compared, the healthy controls had significantly lower levels of neutrophils, interleukin 6, 8, IL-17A, and increased level of IL-13. After six months of ETI therapy, there were significant decreases in all the cytokines and almost normalization of the peripheral blood immune cell populations, clearly showing that ETI do have an impact on inflammation. Now, let's quickly look at its impact on the lungs. There was one study by Gusho and her colleagues. In this study also, clinical data was obtained at initiation, and every three months for one year, the chest CTs were done at the initiation at one year on ETI therapy and were compared and was independently analyzed by two pulmonologists. Study sample was 67, mean age was 30. There was significant improvement in percent predicted FEV1 and BMI, just like all the other studies we have noted. There was also a significant reduction in the positive sputum or throat cultures of pseudomonas and MRSA, and none of the subjects with CF showed any deterioration on the chest CT throughout the study, showing clinical improvement. Now, if you look at the parameters which was noted, there was about 80% of the patient have decrease in bronchial wall thickening, and about 75% there was a significant decrease in mucous plugging. But there was no significant change in bronchiectasis, only 10, around 85% showed no change. So which clearly suggests that the more permanent changes like bronchiectasis may not be reversed by the ETI or the modulator therapies, but the early changes in chest CTs like mucous plugging and bronchial wall thickening does have a potential of decreasing, thus earlier start of the modulator therapy will be even more helpful. These are the few CT scans in the patients with mucous plugging and bronchial wall thickening before and after one year of therapy, and you can see the difference. Another study on lung disease was by Beck. They look at the changes on the lung CT after one year therapy with the ETI. Their total cohort was 12 patients, and the Brody 2 scoring was used. They showed significant improvement in the mucous plugging and peribronchial thickening, and they also showed improvement in paranasal sinus disease in some of these patients. Now let's quickly look at the chronic rhinosinusitis, and this is the study by Brody in which they had 43 subjects. They were treated with ETI and 20 CF controls who were not treated with ETIs, and they assessed their sinonasal symptoms retrospectively and in the interventional group at about 9, mean of 9 months on therapy, and they noted significant improvement in SNR2 scores, mean decreasing from 32 to 15 points in those who were treated compared to the controls, thus suggesting that the CFTR modulator therapy have significant positive impact on rhinosinus symptoms. Another study from our group, this was a prospective longitudinal cohort study, sinus CTs were obtained at initiation and at one year of ETI therapy and compared by the pulmonologist, ENT surgeons, and neuroradiologists. They were 64 participants, mean age 18. There was two scoring systems used to analyze by the standard non-manic sinus CT scoring system, mean decreased from 5.8 to 3.3, which was very significant. Similarly, our own CF-specific scoring system showed a significant decrease from mean 3.8 to 2.2, and there was also an improvement in FEV1 and BMI in this group. One interesting thing to note is that even though there were significant improvements, no matter which scoring system was used, the patients still have a sinus disease on follow-up CT scans, so it was not completely resolved, though improved. These are the few CT scans of the sinuses before and after one year of therapy, and you can see the difference in pre and post, side by side. When we compare the two scoring systems, as you can see, with Lund-Mäkki, the average total scores significantly improved, whereas in our scoring system, the average score also improved and the average total opacification score dropped by more than 50%, showing a significant improvement. And thank you for your time, and please don't forget to evaluate our session. Thank you. I think you have to go and give another talk. Yes. I will do so. All right. Good luck with the talk. So it's my pleasure to introduce our next speaker, that is going to be Dr. Swaroop Pinto, who is going to do our year-end review for sickle cell disease. So Dr. Pinto is currently at the Children's Hospital in Akron, Ohio, where she is a pediatric coronary and sleep medicine doctor with an interest in home sleep apnea testing in children. This review, however, is on sickle cell disease. So Dr. Pinto, let me just bring up your slides. Thank you. And when I was asked to do this topic, it was kind of interesting, because I was wondering what happened in this year in sickle cell disease. And honestly speaking, there was a little bit, but a lot of stuff that I'll be talking about happened, in fact, in two years prior to this, to 2023. I am the medical director at the Mahoning Sleep Valley Lab, and I also do pulmonary and sleep medicine. The objectives of my talk are basically to review the recent advances in the cardiopulmonary morbidity in the advances in diagnostic forms with regards to cardiopulmonary morbidity in patients with sickle cell disease, children and adults. I'm also going to review the recent advances in the therapies in decreasing morbidity of sickle cell disease and cure of the disease, and specific more about the hemopoietic stem cell transplantation and gene therapy, which is kind of the talk in the sickle cell disease world. Just as an overview of the guidelines that we have used over the last decade that have helped us modify our therapeutic management in these patients. And as you can see, there are very few guidelines out there. We have a couple of guidelines in 2014 from ATS, a couple of guidelines in 2015 along with the American Heart Association with regards to pediatric pulmonary hypertension, and nothing from 2015 to now. From 2022, the ERS came up with guidelines with diagnosis and treatment of pulmonary hypertension, but not in specific to sickle cell disease. In 2019, the American Society of Hematology came up with the guidelines, and these were kind of the latest guidelines out there. And this is just a summary of the cardiopulmonary part of the guidelines. And one of the most important things that stands out is that we have a conditional recommendation against routine screening of echocardiograms in asymptomatic children and adults compared to the 2014 guidelines that kind of was in favor of doing routine echograms kind of for risk strategization for therapeutic management. The other recommendations go in line with our previous guidelines of NHLBI in 2014 and the AHA guidelines in 2015. The need for right heart catheterization stays the same, and there's been no change with regards to that. With regards to pulmonary function test, again, they strongly recommend no routine screening for asymptomatic individuals. However, they have given us a wide range of symptoms that you can do screening in children and adults, and that kind of includes every small symptom that we see in our current pediatric practice, including wheezing, recurrent acute chest syndrome, any sort of pulmonary embolism, or our abnormal six-minute walk test. Polysomnogram guidelines, and I think, again, it goes no routine PSGs for individuals unless they're symptomatic. So what I take from these guidelines is that none of the asymptomatic individuals get any form of screening tests unless they have symptoms, but the symptoms are such a wide range that you have space to maneuver in getting these tests for your patients. So polysomnogram, again, they have anybody with snoring, anybody with unexplained hypoxemia, pulmonary hypertension, or any sort of recurrent acute chest syndrome and prayer prisms. I kind of put this slide because it kind of gives us an idea of what has happened in the sickle cell disease world and the various milestones that we have crossed from 1910 to today, almost to 2020. And as you can see from the initial description of a sickle cell disease case, we have come a long way from disease-modifying drugs to gene therapy and hemopoietic stem cell transplantation. The interesting thing with this chart is from 2010 to 2020, there's been a tremendous increase in trials, and probably because of increased awareness and also with increased funding from the NIH. Those of you who do sickle cell disease will agree with me that how there is very limited funding out there to do this research. And that has increased from 2010 to 2020, especially with regards to your hemopoietic stem cell transplantation and disease-modifying therapies. This is just like a summary of the disease-modifying therapies. The two big developments that we have seen in sickle cell is in 2019, which was FDA-approved, and two of them are monoclonal antibody to P. selectin, which helps in decreasing the vasoclusive crisis, and also the voxelotor, which increases oxygen affinity and inhibits polymerization, thereby decreasing adhesion and morbidity associated with that. With regards to complement inhibitors, there is no FDA-approved drug as of now, but there's a lot of research going out there with regards to that. The biggest thing with all the recommendations is the talk about allogenic hemopoietic stem cell transplantation, and the American Society of Hematology came up with specific guidelines to help us offer this therapy to a certain group of patients, and that was published in 2021, and this is the latest guidelines out there. With these guidelines, they specify that this is the standard curative option for patients with sickle cell disease with more than 90% cure rate. However, only less than 20% of patients have the availability of HLA-matched donors. For those who do not, they recommend using match-related donor transplant, cod blood transplant, and haploidentical familial donor transplant. The recommendation are basically eight recommendations, and the first three are who is eligible for a hemopoietic stem cell transplantation, and those include any form of neurological injury like stroke, frequent brain crisis, and acute chest syndromes that do not respond to the standard of care. The rest of the guidelines from four to eight are basically with regards to the hemopoietic stem cell transplantation on what kind of donor to use and what is the conditioning regimens used, including irradiation and chemotherapy. They do recommend hemopoietic stem cell transplantation in younger individuals compared to older because there's better outcomes in younger subjects. They also recommend kind of low-criteria recommendation for HLA-identical sibling cod blood instead of bone marrow. The reason these guidelines are not strong is because there are no randomized clinical trials comparing hemopoietic stem cell to any standard of care, and therefore, all these guidelines are supported by very low certainty. The complications that were derived from these, that were published in these guidelines include death, graft-versus-host disease, graft failure, infection, as with regards to any transplantation, infertility, and malignancy. As of now, the risk for malignancy is low with regards to hemopoietic stem cell transplantation. This data was obtained from by using various registries of transplantation and with blood and marrow, which involves more than 300 institutes that take part in these registries. This is from those registries, and it basically shows that all your complications are lesser in individuals less than 716 compared to individuals above 16. Cod blood transplant, there is limited data out there. One publication that was in 2017, and basically that shows that there are better outcomes and less rejection rates. Even a study done in pediatrics showed better outcomes. With regards to haploidentical familial, this also has shown to have better outcomes, especially when you use T-cell depletion, T-cell repletion, and high-dose post-transplant cyclophosphamide. Coming to gene therapy, a little background just to kind of understand the whole concept of gene therapy. Gene therapy first started in 2010 in sickle cell disease, and over time has really grown to an extent we are almost near to it being FDA approved. The gene therapy, the whole concept lies behind the beta globulin gene that is on chromosome 11. The locus is on chromosome 11, and the LCR, that is the single locus control region, that determines the expression of the various genes involving that genes like HPE, G2, G1, and your hemoglobin D, not hemoglobin D, sorry, HPD gene. Sickle cell occurs when there is a homozygous mutation in the HBB gene. The gene therapy is basically into two groups, gene addition and gene editing. And the advantage of gene therapy over the allergenic hemopoietic stem cell transplantation is there's decreased graft-versus-host disease and graft rejection, and there's rapid immune reconstitution, and also decreased risk of infection. The gene addition, which is also called as anti-sickling gene therapy, was first reported by using the lentiglobulin BB305, which is nothing but a lentiviral vector. As of now, it's just the same thing is being used in anti-sickling gene therapy. There are two papers that came out in 2022 that basically describe the biological and clinical efficacy of using lentiglobulin in sickle cell disease, including pediatric patients. This data is from one of those papers, the first one. And this basically shows that the hemoglobin levels increased tremendously over the six to 36 months, including the vaso-occlusive events also decreased. This is a pictorial description of the gene addition and gene editing. With the gene editing, you basically disrupt the HBB gene by using the HDR and various promoters. These are all the trials that have been done in gene editing. And as you can see, they're all in phase 1 and phase 2, and only a couple of them are in phase 3. And most of them use the BCLA11A gene. The complications and disadvantages is loss of certain genes, which all leads to genotoxicity. And there's a lot of research going out there how to prevent that. This is basically a summary slide. If you can take one thing from this talk, it's this slide, which basically summarizes all the various disease-modifying drugs, the HLA-matched transplant, and the various new drugs that are in research at this point. And you can see only the first five are in standard of care, and everything else is in research phase. So to conclude, I just want to reiterate that over the last 50 years, we have done a lot in understanding the pathobiology and pathophysiology of sickle cell disease. However, the cure is near, but still a long way to go. We are hopeful that over the next several years, the therapeutic landscape for sickle cell disease is going to change, especially with regards to the recent advancements in genetics and genomics. And this is all because of increased awareness, which we thrive for, and also the ability of funding from NIH. These are my references. And thank you. And don't forget to validate this session, please. Thank you so much, Dr. Pinto, for that great talk. So it's my pleasure to introduce our next speaker. That is Dr. Brooke Gustafson. She is an assistant professor of pediatrics at Ohio State University and Nationwide Children's Hospital. Her primary interest is in asthma, of course, and also in the chronic management of treatment children. Today, she is going to be giving us an update on pediatric asthma. Dr. Gustafson. Thank you so much for the introduction and for the opportunity to speak with you guys this morning. As he said, I'm going to be kind of going over updates that we have in the management of our patients who have asthma. And I have nothing to disclose for this talk this morning. So here you can see our lesson objectives and things we'll hopefully go over in this talk. There's been several updates to previous guidelines related to pediatric asthma management that have come about in the past few years, really relating to all severities of disease. And so we'll talk about those this morning. And then we'll also discuss some of the evidence and recommendations that we have in the subset of our pediatric patients who have more moderate to severe persistent asthma, reviewing the biologic therapies that are available for treatment there. So first we'll start with updates from the National Asthma and Education Prevention Program's Expert Panel 4, or EPR4, Working Group Guidelines. And these were published back in 2020. However, this is the first update that we've had from this group since 2007. And as you can imagine, since then there's been a considerable amount of progress in both diagnosis and then management and treatment of these patients. And so these focus guidelines really have recommendations across kind of multiple domains of asthma care, but three of them are specific to pharmacologic strategies that do apply to our pediatric patients. And so those include the use of intermittent inhaled corticosteroids with an as-needed short-acting beta agonist or SABA, include the use of single maintenance and reliever therapy or SMART. And then also includes some recommendations on adding on long-acting muscarinic antagonists or LAMA in terms of therapy for patients who are 12 years and older. And so we'll talk about each of these in a little bit more detail, starting first with the use of intermittent inhaled corticosteroids. So for children who are zero to four years of age who have intermittent asthma, the recommendations now are that you can start a short course of daily inhaled corticosteroid at the start of viral infection in this age group. This is specific to children who have had more than three lifetime episodes of wheezing or two episodes within the past year, but who are asymptomatic in between those episodes. This same approach is now also recommended in children who are 12 years of age and older who have mild persistent asthma. And while we know that daily inhaled corticosteroid with an as-needed SABA has really been the kind of long-stay maintenance therapy in this age group, we do know that adherence to daily therapy has historically been poor. There's some studies that say, you know, under 50% of patients are actually adhering to those daily maintenance regimens. And so using an as-needed concomitant ICS with a short-acting beta agonist at that first sign of asthma symptoms has been found to decrease severity of asthma exacerbations and has also been shown to be a cost-effective option as well. There's a nice meta-analysis by Kaiser and Associates that was published recently that really reviews a lot of the data going into what happens if we do start a medium or high-dose inhaled corticosteroid at the first sign of illness in these patients. And they found that doing so can reduce symptom duration and severity, can reduce the days of SABA use, reduce the frequency of oral steroid need, and reduce healthcare utilization as well. So next up we will talk about the recommendations for single maintenance and reliever therapy or SMART. And this uses treatment with an inhaled corticosteroid and a specific long-acting beta agonist or LABA, famotarol. And this is used for both daily therapy as well as rescue therapy. And famotarol is the selected LABA because it has a relatively rapid onset of action and can be used more than twice a day. This is now strongly recommended as the preferred therapy for children older than 4 years of age who are either not well-controlled on a daily low-dose or medium-dose inhaled corticosteroid or who are starting therapy. And we know that in patients who are 12 years and older with persistent asthma, there's been lots of studies that show using this combined therapy approach can be more effective in preventing exacerbations than using an inhaled corticosteroid alone. And then lastly, in terms of the EPR-4 updates from 2020, there's some brief recommendations regarding the use of add-on long-acting muscarinic antagonist or LAMA therapy. And we know that this can be effective in the management of uncontrolled persistent asthma in the specific subset of patients who are 12 years of age and older. In those who are not controlled on an ICS LABA, which again is going to be the preferred regimen in these patients, adding a LAMA is now conditionally recommended because it does offer a small potential benefit in these patients. And so they call that the triple therapy approach is something that we should be considering. Next up, we'll briefly review the global initiative for asthma or GINA guidelines. These unlike the EPR-4, these are updated annually. So we do have some updates in the last year related to asthma management. They now have similar recommendations regarding the use of SMART in patients who are six years of age and older. And you'll see in their recommendations now they recommend using this technique as the preferred controller and reliever in steps three to four of treatment, which you can see here. So again, preferred controller and reliever as you move more towards steps three and four of management is going to be to use the SMART technique with ICS famotarol and use this as a reliever as well, which you can see at the bottom. And then in children who are 12 years of age and older, so moving more towards our adolescent population, GINA now has recommendations to use this low-dose ICS with famotarol combination as not only the preferred controller but also the reliever regardless of asthma severity in all of these patients, which you can see here. So this kind of goes against what we've done for a long time with asthma management where we're now removing that short-acting beta agonist as a reliever entirely. And the preferred approach should be to use an anti-inflammatory reliever, which again is going to be that low-dose ICS combined with famotarol as a reliever in all steps of management in this specific age group. And there's lots of rationale that goes into these updates, which you can see here. Compared with using an as-needed SABA alone, using as-needed ICS famotarol has been shown to reduce the risk of severe exacerbations by 60 or to 64% depending on the study that you look at as compared with using that as-needed short-acting beta agonist. And then the risk of exacerbations was similar or lower for those using ICS famotarol as needed versus just using that as maintenance with a SABA. So again, pretty good data that we have showing that by using this approach and using the SMART therapy, there can be reduced and severe exacerbations in these patients. And then we'll pivot a little bit now to talk about some of the updates that we have that have come about, not necessarily in the last year, but in recent years regarding biologic therapies. And so these are going to apply to a smaller subset, maybe up to 10% of our pediatric patients who do have more severe persistent asthma. And these focus a little bit more on using phenotype-directed therapy for these children and adolescents. These should be agents that we're considering in patients who have uncontrolled asthma despite treatment with moderate or high-dose inhaled corticosteroids with or without the addition of nonbiologic agents into their medical management regimen. And so currently there's five approved biologic therapies in children 6 years of age and older. These include omelizumab, mepelizumab, and dupilumab. And then in patients who are 12 years of age and older, we have benrolizumab and tezapelumab are the additional two biologics. And there's been some really nice review articles and lots of studies that we'll talk about, but we'll talk about each of these in a little bit more detail now. So we'll go through each of these. Like I said, omelizumab is obviously not new. This is our first approved biologic and this works as an anti-IgE antibody. So it inhibits that subsequent binding of IgE to other cells that really propagates that asthma cascade. As you can see at the bottom there, in order to qualify for this medication, you do have to have a specific IgE range in order to receive treatment. When we look at mepelizumab and benrolizumab, these work against interleukin-5 within that asthma cascade. And this is a cytokine that's produced by Th2 cells that's really critical in eosinophil development. And so both of these, one is anti-IL-5 specifically, the other works against the receptor. But these are really useful in patients who have severe asthma, more so with eosinophilic phenotypes. And as you can see, again, you have to have a specific eosinophil range in order to qualify for both of these therapies. With dupilumab, this similarly is an option for those who have more of that eosinophilic asthma phenotype. But this targets anti-IL-4, sorry, is an anti-IL-4 antibody. Again, these are cytokines that are important in that T2 pathway that lead to IgE production and eosinophil production. And then lastly is tezepilumab. So this is the newest biologic therapy that's now available. This works as an antithymic stromal lymphopoietin or TSL antibody. And that TSL protein is a cytokine that is released really just in general in response to airway injury. And so as you can see, unlike the other treatments that we have in regards to biologics, there's no IgE range or eosinophil range that you need to have in order to qualify for this therapy. And when it comes to efficacy for these, there's been, as you can probably imagine, lots and lots and lots of trials that have gone into this. I'll focus a little bit on the pediatric-specific ones. So with mepolizumab, there was a trial that was done looking at mepolizumab as an adjunctive therapy for the prevention of asthma exacerbations in children who were age 6 to 17 years of age. And within this study, they found that there was almost a 30% relative reduction in the rate of severe asthma exacerbations, again, in that 6 to 17-year-old patient population. And then with dupilumab, there was a really nice pediatric-specific trial looking at the use of dupilumab in patients who were 6 to 11 years of age. This was a year-long, double-blind, placebo-controlled trial. And they had over 400 patients in this study who had moderate to severe uncontrolled asthma. And they showed that using dupilumab resulted in almost a 60% relative reduction in the rate of severe exacerbations in those who had elevated eosinophil counts above 150, and then in those who had eosinophil counts ranging over 300, they had a 65% relative reduction. So pretty nice efficacy for the use there. When it comes to benrolizumab and tezepilumab, the data that we have there is largely adopted from adult studies. The ones that are referenced here for benrolizumab, the study had over 2,500 patients. But within that subset, only 108 were adolescent patients. And then for tezepilumab, the Navigator trial had over 1,000 patients enrolled. But again, only 82 were adolescents in that whole subset. They still had good efficacy, obviously, in those trials in reducing severe exacerbations in the subset of patients. But hopefully we'll have some more pediatric-specific trials in the future. And then just to conclude a little bit about maybe what will be to come when we look at the pathophysiology of biologic therapies and management of asthma, certainly historically we've targeted a little bit more of these downstream effectors in this asthma cascade. So as you can see on the right, your free IgE, and then your interleukin 5 and 4. But now that we have tezepilumab working at that TSLP a little bit more upstream, there's new studies in the works now looking at biologics that target these other alarmin interleukins, as we call them, interleukin 33 and 25. And so hopefully, because these activate cells earlier in that asthma and inflammatory cascade, hopefully in the future we'll have some therapies that can actually target those fundamental pathobiologic mechanisms and really work to modify disease in these patients with asthma. And so to conclude, some new clinical updates from the last couple of years. Consider using an inhaled corticosteroid in those with intermittent asthma or mild persistent asthma at the start of asthma symptoms or illness. Using SMART as the preferred therapy in children four years or older who aren't well-controlled on low-dose ICS alone. And then using ICS famotarol as that preferred reliever in our adolescent population. Hopefully a nice review that you guys can take away on some of the biologics that are available, and hopefully we'll have some things coming up in the next few years as well. And that is all I have for you guys. Thank you so much for listening. So our session is going to conclude, actually, with me. I am going to be providing you a brief overview of updates in pediatric sleep disorders. My name is Sumit Bhargava. I'm a clinical professor of pediatrics at Stanford and the medical director of our sleep laboratory. And my interests are essentially in home sleep apnea testing as well as medical education. I have nothing to disclose. Our lesson objectives are going to be that I wanted to use this session to highlight the latest developments in pediatric sleep medicine, essentially from mid-2022 to now. I'm hopeful that we would be able to integrate the most significant findings and their impact on your practice of sleep medicine. And then as you listen to this and see what is actually happening in the field, perhaps you will be able to develop some research priorities or interests of your own. So I wanted to begin with epidemiology, which is kind of a traditional start to disease assessment. And this is the article that I actually wanted to highlight that was published in the February issue this year of Pediatrics. It is the clinical practice guideline for the evaluation and treatment of children and adolescents with obesity. And one of the key things that becomes important for pediatric for me and sleep medicine doctors is that there is a specific recommendation over here for the assessment and diagnosis of comorbid obstructive sleep apnea. Now this desire to investigate sleep apnea in obese children has made earlier appearances in guidelines from the AAP. It was published in the initial guidelines issued by Dr. Carol Marcus on the childhood management of OSA. It was reiterated in the updated guidelines in 2012. However, this is a specific recommendation from the AAP section on obesity. And what they're emphasizing over here is the need for a polysomnogram. And when you think about the fact that there is not a pediatric sleep laboratory in every state in the United States and that access to these facilities is limited, but the population of obese children is not going down, that leads to a significant discrepancy in what is now going to be considered standard of care. So one of the other things that the obesity epidemic in this country highlights is the gender and race and ethnicity-based disparities that exist. In this, I am actually going to take you through some interesting findings that kind of become apparent. One is that here on the x-axis, you can see that children are getting older from childhood all the way to adolescence. This is the AHI in events per hour. You can see that overall, as children are getting older, OSA is kind of increasing, which is the gray line. The other is the distinction between boys and girls. Boys are in blue. Girls are in red. Overall, you can see that the tendency in boys is for sleep apnea to be more prominent than in girls. If you are comparing obese boys and obese girls, you can clearly see that there is a huge difference in the severity of OSA, this being for obese boys. You can actually see those differences are persistent even in non-obese boys and girls. So I think that this is an important factor for us to realize that when we are looking at obesity and obstructive sleep apnea, we are also confronting something that is presenting disparities in healthcare in specific races, ethnicities, and in genders. This is just a map to show that there is not a single place in the continental United States where there is not a proportion of obese children. And this is where we are right now in Hawaii. So 16% of people in the island or children in the islands are actually obese. This is what I was talking about, about the prevalence of obesity aged 12 to 19 years by race and ethnicity. And there are some important things over here that I wanted to highlight. First is the left graph is essentially boys. The right graph is essentially girls. You can see that overall, the tendency for boys to be obese is much higher overall than girls. When you start specifically examining boys versus girls and you're looking at race and ethnicity, you can see that while the incidence of obesity in non-Hispanic white is quite high, it is lower than non-Hispanic black, much lower than Mexican-Americans. The same trend relatively holds true even for girls, although over here you find that non-Hispanic black are more than the Mexican-Americans. So this led me to kind of look up specifically health disparities in pediatric sleep, and I found this very nice article written by Dr. Lupini and Williamson in Sleep Medicine. And they looked essentially at individual child factors, family factors, school and health care system factors, and neighborhood and broader socioeconomic conditions, which in their opinion leads to disparities in pediatric sleep and health disorders, and then to child neurocognitive, social, emotional, and physical health deficits. So this is really a wonderful paper, if any of you have the time to read it and you want to understand this problem a little bit better, they really explain it very well. Their conclusions essentially was that black and Latinx toddlers and schoolchildren have more symptoms of sleep disordered breathing, that black youth have more severe OSA as compared to white youth on polysomnograms, that children from lower socioeconomic and low-income neighborhoods are more likely to experience sleep disordered breathing than those in higher socioeconomic states, and that OSA treatment with adenotonsillectomy is less prevalent in black youth as compared to white. So what I've done utilizing the first few slides and then coming to this is essentially shown that there is a problem with sleep apnea in this country being overrepresented in groups that do not actually have access to health care, that pediatric sleep medicine has come far enough that this data has actually accumulated that these trends can be seen by people who are sociologists and not necessarily medical doctors. So this is clearly a huge problem, no pun intended, for all of us to kind of confront and realize on a daily basis. So a few updates on diagnosis. This was something that has come up very frequently in sleep medicine, all the more on the adult side. I was able to find only two papers that talk about the application of machine learning and artificial intelligence. They were not published in medical journals, and I am not, in fact, an artificial intelligence engineer of any kind. I have absolutely no idea what is a multilayer perception model, none whatsoever. I do not actually know what is a 2.0 convolutional neuronal network. The key thing that actually stood out to me was this. They were using essentially very few sensors, they were correcting for a lot of things, and they were diagnosing moderate to severe OSA. Just earlier this morning, I had a discussion with a colleague who was interested in home sleep apnea testing, and we were talking about how great would it be if there was no EEG and no airflow sensors required. And so I think that this technology perhaps holds the promise of using less sensors to actually collect more data, but interpret it in a way that it can be clinically applied. So I wanted to be sure that at least you got a chance to see this. Here is the other very interesting thing that I found. The non-formal title of the slide is, How to Diagnose Sleep Apnea from a Stool Sample. So this is the one paper I found on gut and salivary microbiome and sleep disordered breathing. This is interesting to me because we are starting a complex sleep disorder clinic at Stanford, which will have a focus on morbid obesity and bariatric surgery, in addition to cerebral palsy and other clinical phenotypes of persistent OSA. So the gastroenterologist who is going to be working with me has, in fact, an interest in this. So here's what was discovered, that if you collect stool samples from 45 children who have obstructive sleep apnea, hypoventilation syndrome, which is proven on polysomnography, you actually find that as you compare it to the control group of normal children, there is definitely a change in some of the bacteria that generate short-chain fatty acids. So you can kind of see those trends represented over here. And this was just interesting because they're essentially talking about the fact that people would come to clinic, they would give a stool sample, and then you would call them to say, yes, you are at very high risk of sleep apnea. Now whether this means that they will go for a TNA or whether they will go for a polysomnogram, but this was just interesting because I'd never thought about stool sample as a way to diagnose sleep apnea, but people are doing that. So a brief update on infant sleep disorders. One of the things that pediatric primary doctors are constantly challenged by is when to take the premature child off of oxygen. And so most of us are turning to polysomnograms as a way to do it. As I already mentioned, polysomnograms are not easily accessible, and they are expensive, and they are uncomfortable, and people are not going to drive four hours with their premature baby to come and do a polysomnogram. So in this particular study, this group actually came up with a consensus-based algorithm that they are very careful not to specify in their paper because I'm assuming that they want to set up a company. They are essentially comparing this recorded oximetry to polysomnography. And this is the interesting thing. This is the Bland-Altman plot, which is usually used to compare two different measurements and see how close they are to each other. This means that the closer you are to the center line, the greater the level of agreement between the abbreviated testing montage, which is the recorded home oximetry, and the full polysomnography. So this is very significant. This is in very close agreement, which is also kind of represented over here in the regression analysis. This means that if you want to take a preemie baby of oxygen, maybe you just need an oxygen sensor and an iPhone app. But these people have not published anything beyond that. But I thought you should know that this too is actually coming up for this very vulnerable section of the population. Going to be closing with treatment, and this is essentially dealing with the approval of neurostimulation for Down syndrome children who are adolescents. This was one of the best papers that I kind of found that was kind of talking about it. This is talking about, at baseline, where was the AHI and where it went to when the neurostimulator was implanted. If you view a 50% reduction in events as being evidence of successful therapy, that was certainly achieved over here. In fact, the obstructive apnea index went down. The central apnea index went down. The proportion of time that was spent being hypoxemic or the proportion of time that was spent obstructing went down. Oxygenation improved, but there was not much effect on sleep architecture. In this particular thing, they are talking about what is important to parents. Did the children's quality of life actually improve? It actually did. On this OSA-818 instrument that is widely used, they actually reported a significant improvement in the quality of life. A few months after the neurostimulator was actually placed, there was also a decrease in what was perceived to be the daytime sleepy child. So in conclusion, it's very clear, based upon my limited review from June of last year to June of this year, that there is an active amount of research that is happening in pediatric sleep medicine, which very often used to not be the case. That new findings are there, specifically regarding health disparities and sleep disordered breathing in highly vulnerable sections of the pediatric population. That artificial intelligence can actually make diagnostic testing possibly more efficient and more approachable and less expensive. There are new treatment options for special populations with persistent OSA. And that you may actually be ordering a stool sample collection for the diagnosis of OSA. So thank you so much.

pediatric medicine

cystic fibrosis

CFTR modulator therapies

FDA approvals

inflammatory markers

lung health

pediatric asthma

National Asthma and Education Prevention Program

obstructive sleep apnea

CF