Hi, everyone. Good morning. Just please remember to, on your apps, to mention the program and give us the advice. We can make it even better in the future. My topic for today is asthma in childhood, as like almost every other disease, asthma also starts in childhood. And if it is not diagnosed early in life, that's when you guys get into bigger trouble. So every severe asthma is our failure, and failure starts from us as a pediatric pulmonologist. So having said that, I hope it let me change. I know, but guys, the program is stuck. Yeah, let me get out of it and then come back. We have an IT failure. Anyone for the rescue? All right, it's all right. Yeah, I hope so. All right. So no financial relationship, no copyright infringement. All right. The objective of this talk is primarily to define the natural course of the wheezing in infants and young children, and to determine that who is at risk for asthma. And also, I then briefly mentioned the management of asthma in children, as per new asthma guidelines. As we all know, asthma is the most common chronic respiratory disease in childhood, impact up to 10% to 15% of children. And from infancy to adolescent, boys outnumber girls, and then the ratio changes. The race significantly impact morbidity and mortality, and atopy significantly affect the natural history. And every level of severity of asthma can be fatal. So before we go for our dream medications and all other ideas, let's have a view of where we stand now, in spite of all those wonder medications we have for the last so many years. We still have around 25 million individuals with asthma in the United States. One in every 10 children have asthma. About 80 billion are spent every year for asthma care. Still, we have more than 3,000 deaths every year, which is more prominent in minorities. And there are about 14 million missed school days and almost the same number of missed days at work. Even with all these medications, three in every five individuals with asthma still have limited physical activities, and about 70% of patients with asthma still don't know how to use their inhaler. And trust me, about half of the healthcare professionals don't know how to teach the patients how to use the inhaler the right way. And unfortunately, thanks to our healthcare system, one in five asthmatics still cannot afford their medications. So having said that, asthma is a chronic inflammatory disease. It involves multiple cells. It has significant structural issues, including a smooth muscle hypertrophy, goblet cell hyperplasia, basement membrane thickening, airway remodeling, and even fixed airflow obstruction with fibrosis in some. Structural changes are secondary to persistent inflammation and airway obstruction. Now, everyone with asthma starts with wheezing, but not everyone who wheezes eventually develops asthma. So there is a little distinction, especially in pediatric age group. So you have to define which of the wheezers are asthmatics and which are wheezing just for fun after they get a rhinovirus. So the risk factors for recurrent wheezing include, and most commonly, viral upper respiratory infection, early atopic sensitization to environmental allergens, family history of asthma, especially in parents that describe genetic predisposition, prenatal and postnatal exposure to smoking, especially maternal smoking, acid reflux, aspiration and environmental pollutants, prematurity, and being a male itself is a risk factor for wheezing, just like it is in many other conditions, and structural airway anomalies, and so on, and the list goes on. And the wheezing itself is a very common problem. If you look at its prevalence, some studies have suggested that even 30% of infants and young children do have often on wheezing when they are little, and with a strong association with viral bronchiolitis. As kids go more often to daycare centers compared to adults, so those who go to daycare centers are more prone to develop recurrent wheezing because of their increased exposure to viral infections compared to those who do not go to daycare center. But I do like to mention one thing, that it doesn't mean that those who go to daycare centers are at increased risk of developing asthma. Those are two entirely different phenomenas. Now, at least 20% of children during the first year of life do develop low respiratory infection, and of them about 70% it is associated with viral infection. Similarly, severe viral infections like rhino do increase the risk of developing asthma later on in life, and those who get early sensitization with the environmental allergens, especially in less than two years of age, there's an increased risk that when they get the milder, even milder viral infections, they continue to wheeze for many years after that. Now, if you look at the association between allergy and asthma, there is a significant literature which suggests that those who are sensitized to perennial allergens, those allergens which are there throughout the year, that is more associated with risk of asthma, and those includes dust mites, indoor fungi, cockroaches, and so on. But the sensitization to the seasonal allergens, like pollens or ragweeds and so on, are more closely associated with risk of rhinitis. That is not exclusively, but that is more commonly seen. Now, if you look at the natural history of wheezing in children, that story will not be done without mentioning of a Tucson study. In this study, they enrolled many kids when they were born and followed them over the period of time. Currently, they are about 20 to 25 years old, and the last study on this cohort was when they were 22 years old, a couple of years ago. This is their first study which I'm mentioning. At that six years of age, they were about 800 children in that cohort, and by that time, they were able to define this cohort into four different subgroups. About half of them never wheezed, so they never developed asthma over the period of time. About 20% of them start having wheezing by the time they are one year old, and they were wheezing by two or three years old, but by three years, the wheezing stopped and they never wheezed again. Those were the children who were born to the mother who had a smoking exposure, had viral infections, and so on, and none of them were associated with asthma. Then there were persistent wheezers who started wheezing by the time they were one or two years old, but continued to wheeze at the time when they were six years old. Over the time, about half of them became atopic, half of them were non-atopic. Those who were non-atopic did not develop asthma. Those who were atopic, some of those did develop asthma with the time, and the last group was the late-onset wheezers in which they did not wheeze during the first three, four years of life, but they were wheezers around six years, and they developed atopic sensitization, atopic asthma, and many of them developed asthma from this group. So this just briefly describes how the wheezing is looked at in pediatric age group, but I do like to mention that if you just look at this study, at least 50% of infant and children do wheeze at some time during either during the first few years of life or by the time they are five years old, but you can't put 50% of the population on inhaled steroids without knowing how long you want to give that medicine and when to stop, when you don't even know that they were going to develop asthma or not, or at least 50 to 70% of that subgroup will not going to develop asthma. So, and high-dose inhaled steroids do have their side effects also, so that's the dilemma the pediatric people do face. So if you look at the older studies, it's very clear that at least 70% of those who develop asthma do have wheezing by the time they are three years old, and only one-third of them develop wheezing after three years of age. So we have most of the wheezer, most of the asthmatics being symptomatic by the time they are two, three years of age. And why is that important? To diagnose them early, because the studies have shown that most of the morbidity from pediatric asthma is during the first five years of age. That's when they have the most hospitalization, the most emergency room visit, the most weird flare-ups, the school day, the work day is missing, and the parents getting nervous and all that stuff, and that's when the medications need to be started to avoid that morbidity. By the time their medication started, if you look at after five years, slowly the morbidity keep on decreasing. And there's another reason also. If you look at both the pediatric and adult studies, it clearly shows that the more is the time spent with the symptoms without therapy, the less is the recovery of the lung functions over time, which means if you look at the pediatric study, which was an agar-toft study, if the duration of symptoms were more than two or three years, the recovery of the lung functions was significantly less in those individuals compared to those in which the therapy was started early in life. And similar is the cellulose study in adults. So what that means, it means that these kids need to be identified early, start on medications early, and their symptoms need, asthma need to be controlled early, so that they do not develop a fixed airflow, airway obstruction, and don't end up with the early COPD or other problems when they are older in life and when you guys see them. So based on the Tucson study, there was an asthma predictive index developed. I think this was done by Castro, later on a little bit revised by Gilbert, which shows that if someone have three or more episodes of wheezing in a one given year, and at least one of them is also confirmed or diagnosed with a physician, so it's not a parent's perception, then you look for two things. Do they have a major criteria or do they have a minor criteria? And that defines what is their risk of developing asthma. Major criterias were paternal asthma, sorry, parental asthma, not siblings or cousins or grandma or any of those things, but parents, mother or father. And if they have a physician diagnosed eczema, which shows allergic phenotype early in life, or if they are sensitized to the environmental allergens early in life, which includes the cockroaches, dogs, cats, moles, pollens, and so on, or they have two minor criterias, which is the wheezing without a viral infection, eosinophilia, and allergic sensitization to food allergens. If that criteria are present, then they are called, that means they have a positive index. Positive index means by the time they will be six years of age, there is about a 65% chance they will develop asthma. But even more important is that if they do not have these criteria, they have what's called negative index. It means that there's a 95% chance that those are the kids who will never develop asthma, and with the time they will get better. So that's how you can identify those eta increases much early in life and start them on therapy much early to decrease the morbidity. All right, so in brief, the natural history is that you have a smiley face, a child who get exposed to viruses or early sensitization to the allergens, started having wheezing. If there is a genetic predisposition, such as the family history of asthma or the early sensitization to the environmental allergens or eczema, those are the subgroup which is at increased risk of developing asthma. So either they can go to remission or they can continue to have symptoms, and there is a small subgroup which develops early. So in brief, if I have two, three minutes, I could just briefly mention that what is the new in asthma guidelines. Now, the most important part of new asthma guidelines, no matter which guidelines you look at, is that if your patient is doing well on current therapy, please leave her or him alone. Your desire for perfection is not as important as the patient's safety and patient stability. So only go for the change if someone need a change, not you want to practice the change. So briefly, in kids in zero to four years of age, the only change in the guidelines is that step one, which is the intermittent asthma, in which we just used to give albuterol only when someone needs it, which is about 50% of the patients. The new guidelines says that, well, with albuterol, give them five or seven days of inhaled steroids at the same time, because that decreases the severity of the flare-ups need for the oral steroids much better than with the albuterol alone. But remember, these are the kids who have intermittent asthma. So if someone needing a week of inhaled steroids, two, three times a year, which means that that is no longer intermittent asthma, and those kids need to be on daily steroids, not just the as needed steroids for a much longer period of time. Now, there are no such preparation which is FDA approved yet, which is a combination of inhaled steroids and albuterol. But these kind of preparations will come to market very soon. They are already in Europe, which means that they are trying to make sure that the inhaled steroids become a part of albuterol also, as it is a part of long-acting beta-2 agonists now. Other than that, there are no changes. In little kids, we don't start lab us very fast. We go with the low-dose inhaled steroids. If they don't get better, increase to the medium-dose inhaled steroids. And even if that is not working, then we think about the long-acting beta-2 agonist or other medications. In kids from five to 11, we do not use as-needed inhaled steroids in intermittent asthma. It's not recommended in that age group. The only new thing which is recommended is to do the smart therapy at step three or four, if the low-dose inhaled steroids are not working. But to use a smart therapy at this age that have its own issues, and I'm not sure that everyone is practicing it yet. There are a lot of reservations. But that's a topic for some time later on. Now, in the older kids, 12 years or above, just like in adults, the recommendations, of course, if the low-dose inhaled steroids are not working, then in step three or four, go to the smart therapy. And in step five, add the LAMA into it. Or if in certain cases, add the biologics, depending upon the phenotype, and so on. The rest of it is still the same. So the last conclusion, if the patient is still having issues, look for the comorbidities. Acid reflux, chronic rhinosinusitis, obesity, sleep apnea, ABPA, VCD, anxiety, depressions, and, of course, the adverse health care choices like smoking, alcohol, drugs, and so on. And with that, I will stop. And thank you very much for your patience. And I think our next speaker is Dr. Soti. Please. Thank you, Dr. Sheikh. So I would like to now call upon Dr. Amik Soti. She is the Medical Director of Critical Care Services at University of Wisconsin. All right. So I'm going to talk about hormones and asthma. And as you all can probably imagine, this is a huge topic. Some of which we understand, and some of it is up and coming and kind of new data. So I'm going to try and distill this down to a few salient points that I think are relevant. And so here's what I'm going to try and cover over the next 15 minutes or so. So we'll start out with, what do you all think the effect of hormones is in asthma? What do estrogens do, or what do androgens do? And so if you can look at these A, B, and C, and D. OK, so I'm going to try and convince you of one of these and try and sort of convince you that estrogens do play a significant role in potentially exacerbating asthma. So there are clear sex disparities in the prevalence of asthma. Before the age of 13 years, boys are more likely, and asthma is more prevalent in boys. But around puberty, there's a switch, and asthma becomes much more prevalent in girls and women. Because this switch occurs at puberty, the thought is that sex hormones likely play a role in asthma prevalence. There's also sex disparities seen within asthma phenotypes and endotype clusters, where females form the majority of less atopic, less corticosteroid-responsive asthma. When we look at population-based data, over the last 20 years or so, this is data from the United States, there has been an increase in prevalence of asthma, mostly noted in girls and women above the age of 12. During the same time period, so about the last two decades, there has been overall mortality decline in asthma in both men and women. But as you can see from these graphs, there still exists a mortality gap, with girls and women above the age of 12 having mortality that's about twice that of boys and men. So what does this really mean? And I put this graph up here to sort of show you, not to walk through all of this, but to show you how complex the interaction between sex, which is an anatomic and a biologic construct, and gender, which is a learned social construct, interact in the development, and then exacerbation of disease. So things like socioeconomic status, your value systems, and beliefs, health behaviors, exposures, all combine to determine how disease occurs and how prevalent it is. And then biologic things that are dependent on hormones modify that disease based on genetic factors and interaction, and can lead to, again, disease severity and disease control issues. And then within asthma, there is a lot of interaction between age and gender. So at any point in life where there is a significant change in hormonal levels, for instance, puberty, or menstrual cycle, or pregnancy, or menopause, there is a change in how asthma control is and what asthma prevalence is, again, suggesting the role of sex hormones. Sex hormones also interact with genetic factors and environmental factors to modify and modulate inflammation, which then eventually also changes asthma severity and control. There's also an interaction between fat distribution and gender and asthma control. And then in the elderly, there's lung aging, immunosenescence, treatment failures, treatment compliance issues that may all lead to a different asthma prevalence as well as control. And so understanding the interactions between sex, gender, and age is important in understanding the pathobiology of asthma through the lifespan. So one of the curious things that occurs in asthma in females is this perimenstrual asthma. And before I talk about perimenstrual asthma, I just wanted to refresh everyone's memory on the menstrual cycle. So here's a menstrual cycle that's been normalized to 28 days. First half of the cycle, the follicular phase is characterized by an increase in LH and FSH, leading to an increase in estrogen, leading to ovulation. And then the second half of the menstrual cycle is the luteal phase, where with the development of the corpus luteum, you get an increase in progesterone levels. And if pregnancy does not occur, progesterone levels fall, leading to menstruation. And so what is perimenstrual asthma? It's essentially the cyclical worsening of asthma symptoms, control, perhaps lung function in that late luteal perimenstrual phase. So the last couple of days of the luteal phase, extending into the first few days of menstruation, is when most patients with perimenstrual asthma will say that their symptoms worsen. And depending on how this is defined, it can be fairly common. So when patients are asked to keep daily diaries and talk about their symptoms and their inhaler use, the prevalence of perimenstrual asthma seems to be about 40% or so. When more objective means are used, so use of peak expiratory flow rate reductions, then it's about 10% to 20%. Regardless, a big percentage of patients with asthma will have this perimenstrual worsening of their symptoms. And there's been some studies that show that there is potentially increased bronchial hyperreactivity that occurs in this phase. When methacoline challenge tests are done, there's a correlation and an increased risk of bronchial hyperreactivity. In that late luteal phase. And what's noted is that this increased bronchial hyperreactivity is actually seen in both patients with and without asthma. And so what that means is this cyclicity that's preserved in patients with and without asthma would again suggest that there's an underlying hormonal effect that's unrelated to the actual disease. The effect size is, of course, much worse in patients with asthma, but it occurs in both with and without asthma. And I put this graph up again of the menstrual cycle. And you'll note that towards the end of the luteal phase, you have a rapid decline in progesterone levels. And it is thought that this rapid decline of progesterone levels is what leads to degranulation of mast cells in the endometrium. The degranulation of mast cells is potentially also linked with an increased local and systemic inflammation, potentially leading to further degranulation in other tissue beds where activated eosinophils and mast cells may already be present. This is one potential mechanism that is thought of. We do not know what the exact mechanism of perimenstrual asthma is. So this is a cartoon depicting the two major pathways that are active in inflammatory cascades in asthma. On the left-hand side of the screen, the type 2 pathways that are characterized by innate lymphoid cell 2 and Th2 cells, leading to the increase in IgE and activation of eosinophils. And then on the right-hand side, the non-type 2 pathways characterized by neutrophil infiltration with increased interferon gamma and IL-17A levels. Both of these pathways are modified by sex steroid hormones. Very simplistically speaking, estrogens tend to worsen both type 2 and non-type 2 pathways. And androgens tend to attenuate both pathways. The effect of progesterone is a little more complex and not fully understood. There seems to be some interaction between the levels of estrogen and progesterone, and especially as the levels of progesterone change. So it's not a very simple ability to sort of say what progesterone does to the inflammatory cascade. So here's a summary of some of the animal study that we have available on the effect of sex steroid hormones in asthma. As you can see, estrogen, working through the ER alpha signaling, increases both type 2 and non-type 2 inflammation. Curiously, estrogens working through ER beta signaling receptors actually downregulates or attenuates type 2 pathways. Androgens, working through androgen receptors, attenuate both type 2 and non-type 2 pathways of inflammation. So it's all well and good to say, hey, this is what the animal studies show, but what do we know about in humans? So we have a little bit of epidemiologic data that can help guide us. Epidemiologic studies have shown that decreasing testosterone levels in men more than 45 years of age may be associated with increased asthma prevalence. In a large study of more than 7,500 patients, both men and women were found to have an association with increased testosterone levels and decreased asthma prevalence, and this was dose dependent. In another large study from the United Kingdom of more than 200,000 patients, increased free testosterone levels were associated with decreased asthma symptoms and decreased hospitalizations in women. So while this suggests that there is a link between androgen levels and asthma, these are all cross-sectional studies. And so we really have to put aside the question of causality, because that cannot be determined from these cross-sectional studies. This is data from the Severe Asthma Research Program, where they found that testosterone levels above the lowest quartile was associated with decreased odds of developing asthma in both men and women. In addition, women with the highest testosterone levels within the highest quartile of testosterone levels were found to have lower odds of more than one hospitalization for asthma. Also, there was a positive association between androgen receptor expression and percent predicted FEV1, FEV1-FEC ratio, as well as total asthma quality of life questionnaire score. There was also a positive association between androgen receptor gene expression, and this was on bronchial epithelial cells, and exhaled nitric oxide levels, and inducible nitric oxide synthase 2 levels. Again, suggesting that androgens work to attenuate some of the pathways that are active in patients with asthma. And all of these were seen in both men and women. So what about exogenous sex hormones? Before I go into some of the data, this particular area is where the most conflicting data exists. And when we're talking about exogenous sex hormones, we're talking about contraception and hormone replacement therapy. And so I'm going to preface what I'm going to say by saying that there is conflicting data out there. For hormonal contraception, the majority of data suggests that use of combination hormonal contraception reduces asthma incidence and potentially reduces severe asthma exacerbations. However, the Nurses Health Study from the United States showed the opposite association. So any previous use of contraception was associated with an increased risk of asthma. And hormone replacement therapy has the same problem. There are reviews, as well as a Danish nested case control study, that suggest that hormone replacement therapy is associated with an increased risk of asthma in women. And then there's data from the United Kingdom over a 17-year longitudinal study that suggests the opposite. So some of the different results are potentially related to the fact that the way asthma was defined and the way that contraception and hormone replacement therapy was identified was different. And so potentially, that's what's led to some of the conflicting studies here. There also does appear to be an interaction between BMI and hormone replacement therapy. For instance, in the Rhine study, patients who are on hormone replacement therapy had an increased risk of asthma if their BMI was less than 25. But if their BMI was more than 25, then that association was not seen. And then finally, asthma in transgender patients. There is very limited data. This recent sort of abstract talked about and looked at a large database and found that there was a significantly increased incidence of asthma in transgender patients, with the highest risk being in male to female transgender patients, either those with gender identity disorder or those undergoing gender-affirming surgery. Having said that, there was still an increased risk in patients female to male that was above that of the general cohort. So we certainly need more data and more understanding of why this might be occurring. And so in summary, I hope I've convinced you that there does exist sex disparities in asthma and that estrogens tend to exacerbate type 2 and non-type 2 pathways, and androgens tend to attenuate it. There are mixed results for contraception and hormone replacement therapy and their effect on asthma. And then we do have increased risk, especially for male to female transgender patients that, as practitioners, we need to be aware of. Thank you very much. And I'm going to invite Dr. Navita Ramesh to come up and give her talk on stable asthma. Dr. Ramesh is the critical care program director at UPMC Harrisburg and actively involved in the Airways network here at CHEST. Thank you for this amazing talk, Dr. Sodhi. So in the next couple of minutes, we'll go over asthma and pregnancy, specifically stable asthma in pregnancy. I do not have any financial disclosures. As I mentioned before, I will talk a little bit about the epidemiology of asthma and pregnancy, what are the physiological changes that happen in the body, the maternal and pediatric outcomes and the implications, management of stable asthma and pregnancy, asthma, pregnancy, and pandemics, very briefly about that, and managing the exacerbations of asthma and pregnancy. So to start off with, in the United States, about 5% to 8% of pregnant women have asthma, and that prevalence is increasing. Worldwide, asthma affects about 2% to 13% of pregnancies. And it's most commonly seen in the second trimester, but asthma can occur, exacerbations can occur in any trimester. And asthma is actually the most common respiratory condition of pregnancy with increased health care utilization and increased health care cost. So briefly, to go over the cardiovascular and the respiratory changes in pregnancy, as we know, the heart rate increases, stroke volume increases. Hence, the cardiac output also increases in pregnancy. The systemic vascular resistance decreases, and the blood pressure decreases. So it's important to put the cardiac changes in conjunction with the respiratory changes that occur during pregnancy. In the respiratory system, the respiratory rate may increase. However, the tidal volume increases, and hence, the minute ventilation as a product of the other above two, the minute ventilation increases during pregnancy. To go a bit more detail on the respiratory changes, as we know, there's elevation of the diaphragm due to the enlarging uterus. It's usually 4 centimeters above the usual rest position. And hence, when you look at the lung functions, there's decrease in FRC, decrease in the ERV and the RV. However, this FEV1 remains stable. And hence, there's not a significant change in the FEV1-FEC ratio throughout pregnancy. So in addition to the cardiovascular and the pulmonary changes that happen, there is changes with the blood flow that happen during pregnancy also. The uterine artery blood flow is maximal. And also, the maternal oxygen content needs to be improved in order to help the fetus. So there's increased maternal cardiac output to enhance the maximal utilization of the maternal oxygen saturation. Also, physiological changes that happen during pregnancy in the upper airway, that's also important to consider in asthmatic patients who are pregnant. There is mucosal and laryngeal edema, which could be mediated by estrogen hormones during pregnancy. And this edema sometimes is associated with rhinosinusitis in about 20% of asthma patients. And also, there is a shift sometimes from the T helper cells, from the T1 to the TH2 type immune response, which is thought to be sometimes mandatory for the fetus to survive. And so this TH2 upregulation also causes some changes in the bronchial hyperreactivity during pregnancy. You may have all seen this before, the rule of thirds in asthma, where if you have a patient with asthma and they get pregnant, a third of them, the asthma symptoms get worse. A third, the asthma symptoms remain stable. And actually, in a third of patients, they actually feel better, it gets better during pregnancy. So when you look at the maternal outcomes, there is increased risk of preeclampsia, placental abruption, placenta previa. They often lead to obstetric hemorrhage. Increased heart rate, increased rates of cesarean section delivery, especially in those with severe asthma. Increased risk of spontaneous abortion. And for the mother, there's increased risk of gestational diabetes and also pulmonary embolism. The pediatric outcomes, the babies could be low birth weight, small for gestational age infants, and increased prevalence of some minor congenital malformations, and also asthma in children during their childhood. So when you look at, this was interesting because when you look at the neonatal hospitalization rates maternal asthma was associated with increased risk of neonatal hospitalization. So now when we come to the management of asthma during pregnancy, our goal is to prevent the chronic day and night symptoms for the mother. Maintain the optimal pulmonary function and normal activities. You don't want them to be sitting down the whole time. They have to maintain their normal daily activities. Prevention of exacerbation using maintenance therapies. And also maintaining the fetal oxygenation by preventing episodes of maternal hypoxia. So I've just divided this management into five subsections and we'll go over each of them. All five are equally important in the management of stable asthma in pregnancy. So the first one, monthly assessment of asthma. Asthma patients who become pregnant, they should be assessed on a regular basis, monthly if possible. Structured asthma history using validated questionnaires should be used. Monitoring the lung function by spirometry or expiratory flow. And also fetal monitoring should begin after 32 weeks. So now the ACT score, I'm sure all of you have heard about the asthma control test or ACT score. And this has, this study is from Brazil where they use the ACT score to see if it's validated in the pregnant population. There was a small subset but the conclusion of the study was the ACT score could be used to discriminate between the controlled and uncontrolled asthma. And it was responsive to the symptom improvements during pregnancy. So you can use the ACT score in your pregnant patients. This study used the ACT score but the patients were not seen face to face. It was a telephone study and the ACT score was administered via the telephone. And the conclusion of this study was basically this had good internal consistency, and telephone administration was reliable and can be used to evaluate your asthma patients when they are pregnant. So the assessment of asthma as spirometry, we use spirometry in non-pregnant patients the same way we can use this spirometry FEV1-FEC. As I said, you should not expect a significant change in FEV1-FEC during pregnancy. So it should be near their baseline. Peak flows can be evaluated, and it's important to maintain 80% to 100% of the personal best levels. However, methicolene challenge test is contraindicated during pregnancy. So now looking at the exhaled nitric oxide and asthma in pregnancy, so the study listed below is a double-blind study where a group of patients who are pregnant were put on inhaled corticosteroids based on their exhaled nitric oxide level, and the second group was based on their symptoms and not based on the nitric oxide. And the graphs below show that the lower graph, the lower bar with the triangles, that's the pheno group. So the pheno group had decreased exacerbation and also had a decreased amine inhaled corticosteroid dose when the patients were treated based on their pheno level. And the number needed to treat in that study was six. And also, these two studies also showed that the pheno or exhaled nitric oxide-based management showed less infant bronchiolitis and childhood asthma. If the mother was treated based on pheno, the infant had less bronchiolitis and childhood asthma. So now telehealth and asthma in pregnancy, very briefly. Management of asthma with telehealth, the mastery study showed that even if you use telemedicine, to monitor your patients, it improved the asthma control and improved the quality of life in pregnant women. They basically had a handheld respiratory device and a smartphone which transmitted the data, and that's how they were able to follow the patients. The second part is patient education. Again, patient education, regardless of whether they are pregnant or not pregnant, patient education is very important. So continue to talk to your patients about the importance of their asthma control. The medication discontinuation during pregnancy is an important consideration. It's always important to partner with the obstetrician when you're treating your asthma patients who are pregnant. They tend to listen more when the obstetrician tells them it's okay to take your inhalers, you can continue to take the inhalers. So it's important to partner with them as well. Just like non-pregnant patients, the triggers and environmental agents need to be monitored and controlled. As I've listed here, identify the perineal triggers or the seasonal triggers and control them adequately. Comorbid conditions, again, just like non-pregnant patients, comorbidities have to be actively looked for, assessed, and managed appropriately for adequate asthma control during pregnancy. Pharmacotherapy is inhaled corticosteroids are the backbone for management for asthma. We can also use short-acting beta agonists as needed. And I'm not going to go into the details, but it's similar to the management of asthma in non-pregnant patients. If they were using biologics from before, you can continue, but you usually do not initiate biologics when they get pregnant. So this slide is just to show you mild, moderate, severe, persistent asthma. What are the medications you use? It's same as the GINA recommendations. Again, this slide is just to show you that allergy immunotherapy and monoclonal antibodies should not be started during pregnancy. So this slide is a summary of all the five points. And we have to make sure all five are followed in order to appropriately manage your asthma. So, preferred controller medication, as you all know, is inhaled corticosteroids. Reliever, they can use short-acting beta agonists. Systemic steroids should be used as you would use in a non-pregnant patient. Because again, you do not want maternal hypoxia, which will impede the fetal blood flow and hence affect the fetus. So maternal hypoxia needs to be avoided. If anesthesia is needed, as I mentioned in one of the slides, there's increased risk of cesarean sections and increased risk of cesarean section delivery. If anesthesia is needed, regional anesthesia is preferred. Other approaches, these two studies looked at pharmacist-led asthma management and nurse-led asthma management or asthma monitoring. Where the first study, the pharmacist continued to follow the patients. The second one, the nurse did. And both of them did show that their close intervention did decrease asthma exacerbation in pregnant patients. So this study looked at the effects of asthma severity, exacerbation, and oral steroids on perinatal outcomes. So basically, the low birth weight. That's basically what they were looking at. So increased low birth weight with more asthma exacerbation. So basically, don't wait until your patient goes to an exacerbation. Continue their controller medications, work with the obstetrician. And if needed, give oral steroids, just like how you would in a non-pregnant asthmatic patient. Acute exacerbation, again, it's a whole topic in itself. But maintain your bronchodilatation, avoid hypoxemia, that's key. Continue to monitor the fetus. Systemic steroids without delay if you think your patient's exacerbating. You can use adjunct therapies if needed, magnesium or terbutaline. Early and expert intubation and mechanical ventilation. However, you do not want hyperinflation of the lungs. And in extreme situations and experienced centers, early initiation of VV ECMO can be considered. With that, I want to conclude by saying thank you, Dr. Sodhi, for having this session. Yeah. Next, I would like to introduce Dr. Khurana, who is the Director of the Asthma Center at the University of Rochester. Good morning. And thank you, Dr. Sodhi and Ramesh for this invitation to speak. So, as, you know, over the next 15 minutes, I want to just review how's asthma managed and approached differently in our older adult patients, the elderly or geriatric asthma. And as I was putting this talk together, I kept thinking about the 87-year-old female that I first met when I was on inpatient consult service, who had been admitted five times in the past five months and treated for heart failure or COPD exacerbation and discharge and would just get readmitted. And when we went back and looked at her eosinophil count on admission, you could see that every time she would wheeze, her eos would go up, she would get better with steroids, a little bit of diuresis until a few weeks later. So my really aim, this is sort of the outline, is to really review the burden of asthma in the elderly. Is the pathophysiology of asthma in the older adult different than the non-elderly? Specific challenges of asthma in the elderly and just a brief overview of evaluation and management. And I want to start out with just this really interesting graph about the population age and gender structure and what is anticipated by 2050. And on the y-axis is the age and these are the two genders, male and female. And as you can see that we're going to have a lot more older adults as we approach 2030 or 2050. Currently we have about 46 million people who are over the age of 65, but by 2050 that is thought to double to 90 million. Also by 2030 it's thought that one out of five adults in the U.S. will be over the age of 50, I mean 65. The prevalence of asthma in the elderly is about 8%, but we believe that this is an underestimation because often asthma is underdiagnosed in the elderly. It's usually mislabeled as cardiac disease or it's just I think the core morbidities take over and we miss the opportunity to treat asthma in this population. And within this age group, women have higher prevalence of asthma than men. Older adults are also more likely to require hospitalization. So if an older adult with asthma presented to the ED with asthma exacerbation, the risk of hospitalization or the likelihood of hospitalization 25% compared to 8% for all ages. Older adults are also more likely to have a fatal asthma event, a five-fold increased risk of overall mortality compared with their younger counterparts, even after adjustment for comorbidities. And then within that age group again, women seem to do worse than men. Now this graph is just hospitalization rates in the U.S. and as you can see, apart from the zero to four-year age group, so what Dr. Shaik deals with, the older, the elderly or the geriatric population, as I'm getting older, I feel like I don't wanna use that term anymore, but the older adults seem to have more hospitalizations. And then within that age group, again, females did worse than men. And this is sort of the population. As you can see, men, women, a lot higher hospitalization rates in women compared to men. This graph is just projecting the mortality trends for asthma by age groups. And we've kind of felt that the mortality, fortunately, mortality in asthma is extremely low, but it's not zero. And since the introduction of inhaled steroids and more effective therapies, the mortality went down quite a bit and then has plateaued. But as you can see here, this is the 65 plus age group. And it seems like most of that mortality benefit, I mean, the rate of mortality has decreased at the fastest rate for this age group, which is really great. And perhaps that has to reflect with better identification, more multidimensional assessment and more effective management of comorbidities. But what was sad to see within this age group, which Dr. Sodhi mentioned as well, that women still seem to have twofold the risk of dying compared to their male counterparts. And I think what was even more disheartening as I was putting this together is if you separated it out by race or ethnicity, the top line here is African-American women. The bottom line here is non-Hispanic white men. You can see the separation. The disparities are there and they're not sparing any age group. So they're there across the entire spectrum. The pathophysiology of asthma in this age group gets a little complex because we have aging-related changes in the lungs and then you superimpose on it additional asthma-related inflammation and airflow obstruction tends to be more severe. So normally as we age, you lose the elastic recoil, the alveoli, they get bigger. So you develop the senile emphysema. And then you also have decreased respiratory muscle strength or sarcopenia. There's also immune changes or what we call immunosenescence where there is more of the memory B cell. So the naive sort of population is not able to create more new sort of immune protective mechanisms against exposures. And then there's just what we call inflammaging or just low-grade chronic inflammation that occurs. It was a really nicely done study, three groups, young asthmatics, elderly asthmatics and elderly non-asthmatics, 50 patients in each group. And they found that the airflow obstruction, so these are your elderly non-asthmatics, I don't know how well it projects, worse lung function, higher sputum neutrophils in just older people, whether they had asthma or not. And then when they looked at some of the systemic markers of inflammation, elevated CRP, CC16, this is an epithelial sort of marker. And then your sort of leukocyte, the CCL18 were all elevated. So there seems to be both worse lung function, increased neutrophilia in sputum and eosinophilic inflammation and systemic inflammation. And then if you look at phenotypes in asthma in the elderly, again, they're very similar. So you do have the atopic, so patients who have had asthma lifelong, they were diagnosed in childhood, will have more of the allergic. And if they had allergic sensitization, they seem to have worse airflow obstruction. Then you, of course, can have non-allergic asthma, which is the more eosinophilic, tends to be more late onset. And then the asthma COPD overlap or just irritant exposure, indoor air pollution, smoking related, and then obesity associated. And cluster analysis have been done within this age group and correlated with exacerbation risk. And this was actually a Korean study of 872 elderly asthmatics. And when they looked at all the clusters, patients who had the longest symptom duration and myoct airway obstruction, this cluster one seemed to have the worst outcomes in terms of exacerbation. So what are the challenges that are specific to asthma in the elderly? I think I'd already mentioned that it's often misdiagnosed, just underdiagnosed or misdiagnosed. And less than 50% of patients in this age group with asthma actually receive a spirometry. There's also this paradox of well-being. I don't know how many of you know, I just think of my grandparents. It didn't matter what adversity they were seeing, they just seemed to have this sense of well-being. And I think that can be a problem as in they don't perceive their symptoms well and they may not seek care or even complain. There's also, especially in the octogenary, like once you get into that 80 plus, there's concerns about motor skills and cognitive impairment and whether they'll be able to even adhere to their or take their medications and use their inhalers correctly. There are a lot of comorbidities in polypharmacy, so the drug interactions and perhaps the risk of more toxicity or intolerance can happen. And then just social isolation, the psychosocial, we understand the psychopathology is a huge comorbidity in asthma and it may be even more prevalent in this age group. And then we just don't know how to manage them because if you look at, they're just underrepresented in clinical studies of asthma. In terms of evaluation, I would stay away from, the reference values show that the FEV1 to FEC ratio decreases with age. So if you're in this age group and you're using this cutoff of 70% FEV1 to FEC ratio, which is what GOLD is using still, then you are at risk for overestimating degree of air flow obstruction. So just try to use the lower limit of normal or their age reference Z-scores. But I think the phenotyping and endotyping is gonna be very similar to younger adults. Again, beware of the comorbidities and partner with your geriatric colleagues, geriatrician, sorry, colleagues, and see if they can get involved because a really comprehensive assessment of frailty and cognition is really helpful here. So the treatment's really multidimensional assessment, objective evaluation and monitoring using geriatric specific tools to screen for any impediments that can interfere with effective therapy. You know, address their comorbidities while we're seeing these patients so that we're treating them as a whole. And then, of course, education deterrence, things that we would normally do but just on steroids, a little bit more, just a little bit more close attentions. You know, if you have, if you're seeing an elderly patient in your office, you know, in addition to demonstrating inhaler, just have them show it back to you. And also, like sometimes the coordination is a problem, so give them that spacer or perhaps a dry powder inhaler that is low resistance inhaler that they can self, you know, breath actuate might be better for some of these patients. I just want to leave you quickly, I know we're almost out of time, just to show you the SAMBA study that actually showed that multidimensional assessment and treatment is actually effective in this population. This was a New York City-based study. They looked at a very multi, sort of multidimensional screening and assessment and intervention led by asthma specialists, both in a primary care office setting in their own homes and compared it to usual control. And the outcomes they looked at were these, ACT score, AQLQ, adherence, MDI technique, and ED visits. And what they showed was that this intervention actually improves everything. The asthma control got better, the quality of life got better, there was improvement in inhaler technique and adherence, and the number needed to treat, to achieve a minimal clinically important difference, improvement in asthma control and quality of life was really low, it was nine. And five, for asthma control, nine, quality of life, five at six months. Increased a little bit as, you know, at 12 months, so perhaps a more sustained or repeated, you know, more frequent interventions might be indicated. But what really just impressed me was that this intervention actually halved the risk of ED visits at one year. So really, you know, we talk about 50% reduction with all the biologics, and I can get on my soapbox here, but in this intervention, it decreased need for ED visits by 50%. So I just want to summarize that, you know, just recognize that burden of asthma in the elderly is high. Women seem to do worse than men, and then the health disparities are significant. And when taking care of these patients, it's really important to have a multidisciplinary approach and a very multidimensional assessment to take care of our patients effectively. So thank you for your attention. I'll stop here.

asthma in childhood

asthma in pregnancy

asthma in elderly patients

early diagnosis

wheezing in infants

racial disparities

socioeconomic disparities

inhaled corticosteroids

multidimensional assessment

SAMBA study