I am the least knowledgeable person on stage and yet I still get to make all the decisions about who gets points and gets to win. So I'm Dave Shulman, a sleep medicine doc, but I'm here just as a moderator for these four brilliant individuals who I will introduce before we get started. So before we pardon the interruption, let's go ahead and pardon the introduction. Our first competitor is the wise guy, Buckeye, the best of the Midwest, hailing from the Cleveland Clinic, Dr. Shamita, your maker, Katri, thank you, and she does love lungs. Next up is the beast from the Northeast, pulling her weight in the Empire State, hailing from the Icahn School of Medicine at Mount Sinai, ladies and gentlemen, I give you Dr. Monica Arts and Crafts. Competitor number three, taking great pains to make great gains in the Great Plains, smack talk from the Jayhawk, hailing from the University of Kansas, ladies and gentlemen, I give you Dr. Mario Dadaia Castro. And last but not least, batting cleanup, she brings deep cuts from the land of peanuts, the Ranta from Atlanta, hailing from Emory, my own hometown, no bias herein though, Dr. Unyoung at Heart Lee. Round of applause, please, for all of our competitors. We will be led in later discussion by my colleague from the University of Rochester, Dr. Karana, Karana, Dr. Sandy, want to come up and take a little wave and let them know who you are? So Sandy will be taking some notes and will be helping us to moderate a later conversation when it comes to the Q&A portion of the session. Here are the rules of engagement. I've briefly reviewed these with the competitors, but I can arbitrarily change them at any time at my whim because that's who I am and what I do. We will get to all of the topics we can. They have seen the topics in advance. As brilliant as they are, I did want to give them some prep. For most of those topics, I will select the speakers in a random order. Comments under one minute, please. I get bored easily and we will move on if that's the case. The way I encourage you to speak is loud, funny, and then somewhat accurate. The last is that order is important. I reserve the right to cut people off, but you will see them cut each other off and that's what we hope is going to happen here in today. If you're particularly annoying or unfunny, I have a buzzer that I can use to cut you off as well. For each topic, four points are available per contestant, two for data, two for attitude, and if you are boring or if somebody actually gives you attitude, I can take points away. You can sass me if you like. I welcome it. That's worth plenty of points, but I will sass back, so make sure if you come, you come strong as they say in basketball. For you all in the audience, a couple of things to be aware of. Many of you have chosen to get within these paddles. If you like what a speaker is saying, please show me a thumbs up. The audience can grant points as well. If you don't like what they're saying or you think they're full of crap, please go ahead and give them a thumbs down and I will take away points for that. Yes, I am full of crap. You're right. I already got a thumbs down. I would give you a point, but you're not on the scoreboard, so well done. See me after class. We'll send you something. Lastly, for those of you who want to get some follow-up questions, it is a lot of stuff coming at you, so if you see something that you want to hear more about and you are on Twitter, please go ahead and tweet using the hashtag ChestPTI and I'll be keeping an eye on that and I will ask Dr. Karana and maybe our speakers to clarify some of the things after the game. All right. We're ready to go. Social media. Competitors seem ready. It's go time. First topic is fuzzy biologic. What is the best biologic for severe asthma in a patient with allergy and elevated eosinophils? Let's start with Dr. Khatri. It depends on, really, not just their phenotype, but also what their clinical history is. It's not just pick one. It's not just an algorithm where you go here and here. You have to really listen to the patient's story. If high eosinophils and allergies and allergies are the trigger, then you think about something like omelizumab because maybe it's seasonal perennial allergen, but if it's more non-allergic triggered, then you think about something that's more eosinophil activating against eosinophils. There are several options now for eosinophils, which is very nice. You can really, really think about the clinical history and how they're feeling and what you want to intervene on. Basically, don't just go with the one that the last drug rep has come and peddled to you. Is that what people do, you think? Just go with the drug rep? There is a fear of that. I think there is bias, no question, because it is our responsibility, I think, to really manage the cost of medication because healthcare is just getting more and more expensive and just giving a biologic is not always the answer. Dr. Castro. Anyoung wants to come in. Go ahead, Dr. Lee. Do you think that there's any benefit in those patients who have allergy and eosinophils to kind of go with dupilumab because of the fact that it inhibits the IgE formation as well as have all these other effects in terms of the IL-13 pathways? Would you really go to omelizumab or would you really try to stick with dupilumab in those patients? I like that idea, but I'd like to know what the pheno is. If the pheno is up, that would help. Exactly. Sort of figure that out. Exactly. And then, do you think allergy is the driver? Is that really the big driver? Perhaps. And so that would kind of help you with the omelizumab question. Yeah, I think so. David, I think they're all wrong. I don't know what you think, but I'm giving you a point just for saying that. It's whatever the payer is going to let us prescribe. Okay? The audience, those of you at home who can't see this, the audience did like that comment. But we have to fight back. Well, yeah, that's the point. Yeah, you have to be advocates. Why should the pairs decide what our decisions are? And more importantly, I agree with the broadness of Dupilumet, however, I think that we also have to think about why go broad so quickly. Let's think about more... Sumita, but you know that pair is an OBGYN that you have to convince to... Yes. There is no brain. And who has time for a peer-to-peer? I mean, they try to schedule it always when you're seeing patients at clinic and you don't have time. I love peer-to-peers. We talk about movies and... Exactly. The doc in the box, you have to convince them that your patient needs this particular biologic. So I know that's the problem. That's the problem. It's a problem. I'm all for what you're saying, but then there's the reality, right? There is a reality, but we can't give up. Why aren't they taking control? I agree. I agree. Moving on. Related topic. Is it working? What objective data do you look at either singularly or as a profile to call a certain biologic effective? Dr. Lee, we'll start with you on this. Oh, well, I think that you look at the multitude of different things. I mean, the endpoints of a lot of these studies basically looked at FEV1, decreased exacerbation. So we look at all of those things, which are important. But I think it's also important to ask the patient, how do you feel? Do you have increased exercise tolerance? Do you feel better? Are your symptoms better? Do you have less sputum production? So those things are really, really important. So it's a composite of multiple different things that I think you have to look at. It's not one single factor that determines whether a biologic is effective based on, you know, just the endpoints of the studies. Dr. Graft? Yeah, I agree. And sometimes you have to decide for a given patient what is really causing their asthma or what's really driving their asthma symptoms. Is it exacerbations? Then you've got to wait a while to decide if a biologic is effective. It could be six months or even longer. If it's symptoms and lung function issues, you can really figure that out earlier. Quality of life, those types of things. So I think you have to figure out what are the major drivers of that patient's asthma and then be able to kind of assess over a period of time, four to six months, ideally. Is any one of them sufficient? I mean, there are going to be a panoply of potential things that you can assess. Yeah, because this is where the patient comes in. This is where the patient comes in. A lot of this is shared decision to a certain extent. What really matters to them? Do they want to be active and they don't mind a little bit of steroids or do they want to be off steroids altogether? You know, it's a shared decision to a certain extent. That's why you go back to the peers and advocate for what's causing it. Yes. Well, also, how often do they want to give themselves shots, right? Sometimes I've got patients who do not want to do every two weeks. They'll do every eight weeks. And so that often has to go into the mix as well when you're deciding and then deciding if it's going to work for a patient. But is any... I think the only other thing to add is steroids. Patients hate steroids, right? And we don't like giving them, but exacerbations are driving our steroid use. So I would say, you know, this is the most important thing for a lot of my patients is can I get them off steroids? Can I avoid steroids for an exacerbation? So what I'm hearing... So I think we're bleeding a little bit into whether we want to continue an agent, but the question specifically is asking, how do you deem it's effective? So if a patient says, I feel better, but the objective data do not validate that statement, would you still consider that an effective intervention? Well, if that is true that they're feeling better, it would be reflected in an asthma control test or a quality of life questionnaire. You need some metric to follow. Yeah, you do. Like feeling like, okay, there's also a placebo effect, right? I'm getting an expensive medication and so you really have to, you know, separate the wheat from the chaff. The ultimate issue is, do they feel better? Are they getting what they need? You don't think that placebo effect could bleed into one of these objective questionnaires? It's possible. It's possible. Oh, definitely can. And then I think over time, after they've been on it for a while, then actually the placebo effect wanes. Yeah, the honeymoon. If a patient says, I'm doing better, I want to start with coming down the line on young all the way back to me. If a patient says, I'm doing better, but there are other than maybe the subjective tests, there are no objective data validating that. Continue a medication, assuming it's not causing side effects. Dr. Lee? I would continue. Dr. Castro? I would switch class. Okay. Dr. Kraft? I would switch. Dr. Kachri? I may continue. I love it. Two and two. I've chosen a good question. Excellent. Next topic actually bleeds into one. Dr. Kraft went to a middle. You go first. I'm listening on the clock. How long do you continue a biologic for severe asthma before you consider a change in management? Dr. Kraft? Right. Well, you know, you don't want to continue an expensive med longer than you need to. And so, you know, we use this four to six months, but it depends on what you're looking at. If you're looking at exacerbations, if they've had a couple a year, you might need at least six months to really assess a change or longer. If it's other types of outcomes, then you can get a sense early on, especially lung function and symptoms early on. So I sort of do it as a spectrum, you know, sort of, but I look at depending on what's driving that patient's asthma. Dr. Kachri? Yeah. I would say that it depends on the patient. Again, if there's a patient who's been on steroids for a long time and they are new to biologics, but you're having a little bit of hesitation that they may not get better, I'll actually talk to them ahead of time and say, normally I do wait six months or a little bit longer because success breeds success. But in your case, yours is so severe that I would switch at three months if this is not actually working for you. So again, having these conversations at the get-go is very important. Three months. That's pretty low. I mean, that's pretty quick. That is quick. Yeah. I mean, I went through all that paperwork to get it authorized. Do you think I'm going to change at three months? Your staff will be upset. I've got people, Mario. I've got people following. Are they going to do another prior op? They'll do it. They'll do it. It's not common, but it's happened. You know, but there are other things like, for example, I mean, with benrolizumab, you see an effect very early. Those patients, if they're going to respond, they seem to respond pretty effectively because of the loss of that terminal cell type that you see in the blood and probably in the airways. But other biologics like dupilumab, and we don't know much about, you know, in terms of TESI, aside from the trials that they say, oh, you see these responses. It's like when you look at the curves, it's like three to six months that you start seeing these curves and these changes in the patients who are going to respond. But with DUPI, what I find, or dupilumab, what I find typically is that the IgE levels don't fall in those patients until later. I know that that wasn't their end point. And so it may take a little while for those upstream mediators to actually have an effect immunologically in those patients. And so, you know, you might want to think, you know, I agree, you know, it sounds reasonable to do four to six months, but in some of them, depending on the biologic, you might want to choose a little bit longer, like you said, in terms of two exacerbations a year, you know, is six months long enough? Right. I agree. I agree. We've reached a somewhat of a consensus. Let's move on to rule the taper. Should other control room medications be tapered when a patient is doing well on a biologic for asthma? Let's start with Dr. Castro. Well, definitely. I mean, I think I tell patients, let's get rid of the steroids first. And once we're able to get rid of the steroids, their oral steroids, or to get them to a low dose ICS, then ultimately I switch them to smart therapy and try to minimize their steroid exposure. I tell them, don't stop it altogether, because then your insurance may stop paying for this biologic that worked very well for you. So, you know, I think that's the ultimate goal. Okay. Everyone wants to stop steroids. What about the other controllers? Are there other things other than, no one does not take a rocket science. We should minimize steroid dose. What are the other controllers? Oh, I've already gotten rid of all the other worthless medicines, like monolucast and, you know, all these things that they've thrown on. Yes, they're not working. Exactly. And the only problem is, what do you do when it's time to renew? Because, you know, my patients sometimes will stop their controllers whether we talk about it or not. And so then it comes time to renew, and the carriers have figured out that they're not renewing their ICS. So then what do you do? Yeah, then it becomes a very expensive controller medication. Yeah. And that's, again, something that we have to be responsible for. I mean, hopefully one day we'll find that biologic that's a disease modifying. And sure, you can get a shot and keep going, but this is like the price of a car, at least one, you know, a really nice car per year. So we need to think about the cost of this. And I would also add, from a phenotypic standpoint, if somebody's on an anti-eosinophilic but they've got some nasal polyps, I would consider that they should still be on a leukotriene receptor antagonist. And also, do we really know what happens? Have we really studied what happens when, okay, you've targeted IL-5, but you haven't really made sure that the airway inflammation and remodeling has been managed with the ICS? So I like the smart therapy idea, but I'd like it to be a little bit more... I don't know. I used a leukotriene receptor antagonist for years and never made a polyp go away, like I had with dipolimab and other drugs. You know, there's a certain phenotype of asthma, that is that tightness. It's not necessarily the wheezing and the mucus production. I see it a lot in these women who are postmenopausal, perhaps a bit obese. They come in and nobody believes they have asthma. Nobody believes it until you do a methacholine challenge and then you see under the conductions and resistance that this is high. And then you give them like azithromycin or an anti-leukotriene and they feel better. And you know what? I'm so done with women being ignored after menopause with their asthma. Absolutely. Thank you. I am done with that. Yay! I'm with you there. You know what I'd love to see, though? I'd love to see some data on tapering controllers in the setting of biologics and see what can be done really safely and getting some data, right? So that we can go to carers and say, hey, we've got something. This works. It's safe. And it's a lot better regimen than a steroid for decades. So let's get some data. So I guess the question is, you know, if you have two drugs that act on the same target, which is essentially what we're saying, right? Inhaled corticosteroids are affecting some of the T2 cells as well as the biologics. Should you be using both of those medications to, it's like basically having, you know, a machine gun and something else that you're basically attacking that pathway. So is that absolutely necessary? So it makes sense to pull it apart, right? To take, to pull some of the other drugs away. But so let me ask you this other question, Dr. Castro. So you said you would take, you know, Monteluk as it's totally worthless, but how about AERD? You would take it away from those patients too? Well, I mean, I think that's a subset that you potentially would help if it, if they responded to it. I mean, I can tell you that a lot of those patients, right, have not, have been on the drug and are left on it for years without really showing that it's effective. And, you know, I've had colleagues on my allergy side use, you know, high dose aspirin therapy for AERD and patients hate it, right? And so now we have biologics that are very effective for upper airway disease and my ENT colleagues are using it as well. So I think that's, it's been, the patients tell us what's working, right? And ultimately that's a good thing. I grew weary. Let's move on. Modeling agency is the next topic. How can we measure airway remodeling? Is it modifiable? Dr. Lee, let's start with you on this. I think airway remodeling is like pornography. We just don't know exactly how to define it, but we kind of understand when we see it, right? So like airway remodeling is like this whole concept of cells, epithelial cells and the constituents of the cells actually kind of, you know, composition and everything else changing, right? The molecules in there changing. That's what we anticipate. I think she just said I do pornography every day because I look at CT scans and I look at... We're on the internet, folks. Let's take it easy. Let's take it easy. She's back on the pornography references. Okay. Dr. Lee, back to you. So, you know, I mean, what is airway remodeling? So I kind of ask, what is the question, right? How do you define it? It's been so hard. Is it epithelial cell changes? Is it basement membrane changes? Is it angiogenesis? Is it, you know, the fibrosis? All of the above. Yeah, exactly. So then how do we measure it? We don't have good biomarkers to measure it, but we kind of say, well, is it lung physiology? Like, you know, increased air trapping? Fixed airway. Yeah, fixed airway. And then some of the patients get better when you treat them with steroids or some of these new, you know, biologics. Have we remodeled them? I mean, that's the question. Well, we were talking about this today. I did a session before this and a gentleman came up to me and said, you know, when are we going to have those studies where we know... Because I got a question about the role of the smooth muscle in the airway. Of course, a big role in asthma. But then at the end of the day, will these biologics target that? That particular part of the airway. Exactly. How are we going to know? And so I think we need to do the bronchoscopy studies at the time of biologic administration and then keep them on for a long period of time and do it again. Well, does it matter? We don't have those studies yet. Does it really matter is the question. Like, airway remodeling is happening and we know it. I love the idea of imaging and maybe targeting something like bronchial thermoplasty, which I do believe there's still a role for, to be honest with you. But why can't we make it easier? We're kind of pontificating on what cell is it. But why don't we make it easier, like the Lancet Commission suggested? Let's make it into phenotypes that people understand. Airflow limitation, airway inflammation, lower airway infections and impaired defenses. Because then we're going to be sitting back here wondering, what's remodeling? We won't know. Because like you said, we know it. But for the normal clinician, they need to think in phenotypes too. So if we can have something like imaging and we know what helps. I know remodeling is important, but then we have to think about certain targets. Like which, like tezapilumab looks promising. Yeah, I mean there was just a study presented at ERS showing that tezapilumab reduced mucous plugs. Something very easy to see on a CT scan. I think we as clinicians, as chest physicians, can look at a CT and tell whether or not a patient is improving in terms of their mucous plugs. I think lung function and CT scan is what I would use to measure remodeling. I want to know long term, do any of these biologics have this effect in adults? I mean I know they're being looked at in children, which is great to see if they're disease modifying. I think that's a huge issue. But I'd love to know down long term in adults, what's really going on at the airway level. So that we can sit here and tell our clinical colleagues about that. Because that might help in the decision making long term, which you want to treat your patient with. Let me ask one other question. So do you think airway remodeling has happened by the time someone walks into your office with lots of sputum production and having night time exacerbations and you're diagnosing asthma for the first time? We know there's some. Subepithelial basement membrane thickness is already there. It's there in pediatric asthma. But there may be a reversible piece. That's what I want to know about. And that would be related to remodeling. And you know the basement membrane is constantly, we always used to think it was just proteins that were laid down and that's it. But it's constantly changing. Proteins are coming down, breaking down. And they're constantly being made, they're being broken down. So it's constantly changing as well. So I think that those mesenchymal cells, those fibroblasts making that basement membrane, we're probably modifying that. And that would be really important to understand. We can get it with imaging too. I have no problem with imaging. I grow weary. Let's move on. Asila the Hun, can obese patients still have asthma without reversibility on spirometry? And is there actually a clinical role for oscillometry? Please. Dr. Khatri. Thank you. Yes, so I brought this up. I'm tired of, again, undiagnosed asthma. I'm tired of overdiagnosed asthma too. But underdiagnosed asthma where people have been suffering for years and years and years. And oh, well, this doesn't work. Let's try some more steroids. Well, let's try something else. Let's really decide what this is. So yes, I agree that we have very, very poor measures of lung function in certain people. And so I think oscillometry would be amazing. Honestly, I know it's very difficult to interpret. I know it's difficult to have some uniformity. You have to use the same machine. But I think in a lot of these panel studies that we're doing, we need to start doing it to see what is the resistance? What is the elastance? You know, it's not often in the large airways. It's in the smaller airways. Because, I mean, we see this now with COVID, right? I think it's pretty worthless. Oscillometry has been around for over 40 years. If Dr. Castro actually read the literature, he would know. There was a recent Lancet Respiratory Medicine paper. I know I was first author. A little self-serving. I get it. However, it showed oscillometry actually can predict exacerbations. And it actually negates the effect of the FEV1 when you put it in a model of other predictors of exacerbations like blood EOs, genus stage, and an exacerbation in the last year. I think there's a place for it. I agree. We used it in a pediatric study over 200 kids. It had really no predictive value. This was 773 asthma and 100 normal. The variability of oscillometry is huge. 200. That's not good. So why don't we use it? Why don't we use it? Is it resistance? We don't understand it. Yes. We don't know how to measure. It's really easy to measure. It's really easy to use. It's just we don't really understand necessarily the physiology as well as what you're really measuring. And so we just have to get that word out. We need David Kaminsky next to us. There you go. What did she say? We need David Kaminsky next to us. Exactly. But no, there's a couple of really good reviews out there on how it works. It's approachable. We can get there. We're smart people. We can do it. Patients like it better, don't they? Does anybody in the audience use oscillometry? Put your green thumb up or your brown thumb down. Now go to Europe, though. You guys should see in Europe it is really commonly used. So it's a difference in how we approach patients. It's a mindset. We can't be intimidated. Do you have to do prior authorization to get David Kaminsky to fly in? All right. Hung over the counter is the next topic. Given that primatine mist is over the counter, should budesonide 4-motorol move to over the counter to improve access? Dr. Kraft, you're not volunteering for this one, so I'm going to go right to you. I actually testified in the front of the Senate committee on this issue because the company Armstrong wanted to move their HFA, primatine HFA, to over the counter. And so it had been off the market for a while until the HFA was actually available. And albuterol isn't even over the counter. So we were arguing, let's get albuterol OTC. That would be a great first step. And actually, I don't really actually have an issue with budesonide 4-motorol being over the counter. But what's the price going to be? Right? The over the counter drugs aren't necessarily less expensive. And then they don't, they're not covered by insurance. So that's my big hesitation with it. But albuterol's got to be over the counter. A hesitation has left us with primatine mist. Exactly. So I say just put it out there. Yeah, you know, I will worry about the cost later. There'll be coupons, et cetera, ways to work through, you know, good RX, et cetera. But honestly, knowing now that we need not just a beta agonist, but inhaled steroids. I mean, it's actually a crime what's happening. This is a wholesale crime. And the drug companies have us over the barrel. Have there been any deaths with primatine mist? Like someone overusing primatine mist? Yeah. Absolutely. So why is that over the counter? Exactly. It's historical. It was actually put out there in the 50s. It's been there forever. And albuterol isn't, so it's crazy. Well, David, my panel is a little behind the times. Budesonide 4-motorol should be out there, first line. It is on the international guidelines. And the reason it's not here in the U.S. is because we're behind the times. I agree. I agree. But we have change in the FDA. But we've got some arrogance. Now we can do it. Well, isn't there arrogance, a bit arrogance on the medical profession that only we can give it to you? And there has been that concern that people are going to misuse it. But fluticasone, claritin, these have now gone over the counter. And you don't have to give the high doses where you worry about, you know, bone density issues. But really, just at least get them better. I think we're saying the same thing. You know, the reason patients use albuterol is it makes them feel better, right? And so the whole thing behind Budesonide 4-motorol is make them feel better with a 4-motorol. Oh, by the way, you're going to get some inhaled steroids. I'm for it. Just price it so patients can actually get it. They can access it. That's all I ask. I agree. All right. Sorry I lied is the next topic. Do macrolides have a role in treating severe asthma before or after a biologic in patients with severe asthma uncontrolled on ICS-LABA? Yes, yes, yes. Let's start with Dr. Castro. Dr. Kraft has shown me that she is like the person in the front of the class who's like, And I'm like, no, we're not doing that. No, I was usually in the back of the room. Dr. Castro. Well, Dr. Kraft, we did do a study in ACRN called the MIA study, macrolides and asthma. And I think Ran Sutherland was the primary on that one. And we proved after many years with macrolides and asthma, they don't work. Well, Mario, again, you really need to get to the literature because if you'd read the Brucell and Gibson papers on macrolides for both eosinophilic and non-eosinophilic asthma actually makes a difference. So it's too bad. Was that the primary endpoint in that study? No, it was not the primary. It was post hoc. Oh, wait, I can't say that. Brucell was post hoc. Gibson wasn't. That was prospective. The AMAZE study. The AMAZE study. And you do know that. You're just very artfully omitting that fun fact. Oh, it must be the neutrophils. Oh, yes. Let me ask Dr. Craft and Dr. Castro. So in this day and age, would you still use macrolides with all the biologics that are available? I mean, those studies done prior to the real use of biologics in the community. So I just want to throw that out there to ask you that question. Honestly, let's think about also as you're phenotyping someone, if somebody has among their treatable traits this whole impaired airway defense issue and they're making a lot of mucus, wouldn't it be nice to know if you do that intermittently that they'll actually be better without being on a very expensive medication? And if you're better than, you know, again, I keep saying that stability breeds stability. So I would do it before. Potentially, if it is that mucoid type of asthma, I would try that to see if they respond, number one. And if they don't, then you obviously let it go. Knowing when to stop is what's important. Right. And I think of it as kind of a pre-biologic, if you will, right? So you want to make sure you don't have any, you know, microbe resistance. You want to make sure the QT interval's not prolonged. And if they have GERD, it's a promotility agent. So you've got some benefits there in addition to, oh, yeah, check the hearing, right? And anti-inflammatory effects. So I think there are, in certain patients, it can be quite beneficial. It wouldn't preclude the use of biologics, but I think as you're sort of marching down your path, taking care of patients, it is an option. And some patients are scared of biologics. There's one who's absolutely a great candidate, and she just doesn't want it. She's just afraid. You know, even you talk about the chances of this and that. She's just too afraid. You're not going to force someone. So this has been the alternative. I think my panelists are just creating antibiotic resistance in the world. We should never use this antibiotic for years. Audience, hot take. Just thumbs up, thumbs down. Do macrolides have a role in treating severe asthma? Please use your paddles if you have them. Yay. Thank you. I would say 75% say yes. Do you have anything to say to them, Dr. Castro? This crowd may have turned against you. I'm in Dr. Castro's camp on this one because of the fact that, you know, I wonder if those patients really have some underlying infectious etiology that we haven't really documented. And the bottom line is we never check sputums on all of these patients prior to starting. Oh, I do. Okay. Well, maybe she's kind of the exception. But if we do the panelists here in the group, how many really check for all the different viruses, all the different bacteria, all the different fungi in terms of what's in the airway? Well, that's pretty hard to do. That's pretty hard to do. Although I will tell you there's a great technology coming online. There's a company out of Denver that's gonna look at next-gens, that's looking at next-gen sequencing to look at inflammatory cytokines and phenotype and microbiome. And I think it's absolutely necessary. That would be great. And let's not forget our friends who have bronchiectasis and asthma, too. So there's a role for that as well. You know, we can't forget them. They keep coming up, just like. Dr. Castro, I don't know if you were referencing your own paper earlier, were you? The MIA paper? No, that was the. Okay, you said we had done a study, I just didn't know if it was yours. I will forewarn the panel that yesterday we had a competitor, former ATS president, Atul Malhotra, who kept referencing his own papers. And we did start taking points away for it. So just be cognizant. It's not my paper. You are welcome to reference literature and gently your own. What's that? We were both on it. I'm just saying, I'm just throwing it out there. This is not about ego, this is about the good of public health. So just be careful, tread lightly in self-aggrandizement. Okay, next topic is adhere and now. Should biologics be offered to the non-adherent patient with life-threatening severe asthma? Start with Dr. Lee. I go both ways on this, but I'm gonna say yes. Because I think society, if this patient costs society a ton of money, right? So they're non-adherent, they're in the hospital. I've had a patient who was on ECMO because he was young and he had this. Therefore, what were the options? He couldn't get these other meds, he wasn't adherent. So I said, we gotta do the best we can to keep him out of the hospital. It saves society more money by doing this for some of the patients. Not all of them, but for some of the patients. So I think that we need to fight for that. That's one stance. I'm in agreement. I think the pharmaceutical world has really shied away from this. And they have done the typical trials with adherent patients, right? What if we gave them a biologic, identified they had eosinophils and gave them biologic when they hit the emergency room and we prevented subsequent hospitalizations and potentially mortality from this disease? I think those studies have not been done and those are the important studies to do. And I would say put them on smart therapy as well because then they can just take meds when they feel like they need it and that'll actually help them get some ICS on board. Well, how are we gonna practically do this? We're gonna have to come up with some health information, health implementation studies to do it, right? So I've been thinking about this a lot, but I'm a little concerned about just going with the biologic because we really just don't know what is going to be the reaction when they're not on other controller medications. But that is, again, arrogance on our part, potentially. But something where we make it easier for them. Where can they go get direct observed therapy, right? Similar to tuberculosis. Can they come and we know you're busy, we know you're trying to get your paycheck and you can't come to the doctor. We are so hard to get to that we need to come up with these areas. Maybe even these pharmacies where at least they can check in with a nurse practitioner or a PA and get an ACT. At least there's some follow through 24-7 or somewhere because what we're doing isn't working. But then just saying, come, we'll just give it to you is also a bit irresponsible for us. I think it's a partnership. And so I've had patients who once they start the biologic, they stop all their controllers and we have to have our little talk about that. And if they're doing well, that's one thing. But sometimes they're not always doing that well. They just don't want to take the inhaled meds. It's not a panacea. So yeah, so we have a kind of a partnership and we actually strike a deal. Like look, especially folks who are smokers that you're thinking about starting a biologic. That's a real big ethical issue, right? So you'll say, look, I want to get you feeling better. This is what we need to do. And we really kind of strike a deal together. And I've had some success in that. And again, it's about that whole partnership with your patient and really advocating for them. So I want to ask one question. So if, let's say, at some point in the not too distant future, biologics come down in price, right? So then they become comparable to the ICS or the controller medications that we have. What would your go-to be, right? I mean, would you choose something that you give dosing once a month, once every two months, once every two weeks? Or would you ask them to adhere to a medication that they need to take twice a day, once a day, in terms of that, assuming that the price is the same, right? So. I'll think about that for about two seconds. Yeah. I think that's a no-brainer. If the price came down, I think then if you take that off the table, then they would let me know. My panelists have not read the question here. Let me tell you. It says life-threatening severe asthma, right? These are patients that are at risk. And we're just gonna give them an ICS out the door from the emergency room. I would love if they came into the door, had EOs of 400, 500. I would love to give them an anti-L5, wipe out those EOs, and potentially get them out. Yeah, there was one easy study, right? Yes. There is. Let's just talk about that. We know how well our ERs manage anything chronic, so it's just giving that up. But somewhere where you can have them go get some assessment would be fine. I think it would be reasonable. But I also don't really know whether they'd need the biologic forever. After some control, would they be able to do smart therapy? Wouldn't that be nice? Severe fatal asthma after maybe the remodeling gets a little bit better? I mean, I'm thinking futuristically. Once you're on it, are you really gonna be on it forever? And these are often young people. Are we gonna basically commit them for decades of biologics? Because I just can't see wanting to do that myself. I think that's the question. What are the long-term side effects of these biologics? What happens to children when you keep them on IL-4, IL-5 antagonists for a lifetime? I mean, clearly, the IL-4 receptor is on multiple cell types. It's also involved in germinal center reactions in immunology, so would it affect vaccine responses are some of the questions. And we published that patients who are on biologics basically have decreased COVID vaccine responses. The other thing is IL-5 receptors are also, that receptor is on long-lived plasma cells. Therefore, will this have long-term effects that we just can't measure? So you're agreeing with me that we should do some bronchoscopy long-term. You're saying it, you're saying it. I knew you'd come around. You always come down. All right, moving on. As we move into the next topic, just a reminder to all of you out there in internet world, if you wanna hear more on any of these topics, some follow-up questions, please go ahead and tweet at the hashtag ChessPTI. We'll be having about 10 minutes at the end for discussion. Moving on, going up. Should we up titrate inhaled corticosteroid dosing in patients with good asthma control, but persistently high pheno? Dr. Castro, let's start with you. Well, we did do a study called Basalt, where we actually- Who's we? Again, you or somebody else? Is this the royal we? We as on the top. My lead colleague was on that was Bill Calhoun. And in Basalt, we basically tested three different strategies, symptom-based therapy, pheno-based adjustment of ICS versus physician assessment of guidelines. And we proved there was no difference at the end of the year between those three algorithms. Yet at the end of the year, the patients on the pheno management were on twice the amount of steroids and had received it. So I don't think it has a role for that. I do think I have individual patients where I do use it that way, mostly to assess whether or not they're gonna respond to a biologic or not, how I use it. Well, I'm a pheno, phenomenal. Phenomphana. Well, point for alliteration. Yeah, I tried to up my game for you. So there was a recent ATS single-question guideline, and I was on the study with 19 other people. So it was a guideline, it was a single-question guideline about pheno and whether treatment should be used it for when treatment's being considered. And it became a very much like a gold guideline kind of rule because you have to look at the clinical picture as well as the pheno, and it depends on whether you're going on sensitivity or specificity, how you wanna manage it. So again, if the patient's feeling fine and the pheno's high, I'm like, well, great. There's NO in there helping you bronchodilate a little bit. You may need that, actually. Whereas if it's high and they're not well, then you use it again to try and, first of all, see why their pheno might be high. Are they adherent, et cetera? And then have that conversation before. So in and of itself, you would not step up dose-based just on a high pheno? Correct. Yeah, and I would worry. I mean, you can recommend all you like because you wanna treat that number. But if patients are feeling well, are they gonna do it? I actually think they probably, they may not. And since I was on that basalt paper too, I'm a fan of symptom-based approaches. Okay, moving on. Thermoplasty of Paris is the next topic. What is the current role of bronchial thermoplasty and what phenotype seems to do best? Why are you in Paris? Don't we do this in the United States? It was a plaster of Paris joke. One person does. Mario Castro loses a point for not recognizing my efforts to try to be clever in every topic. Dr. Kraft, let's go with you first, please. All right, so I know my colleague to my left here loves BT and is a big fan, has done a lot of it, so I respect that. The problem is who are the responders? I was just talking about you today in a session I did with Dr. Picario here about how, is it about the posigranulocytic subphenotype that's failed other biologics? But you published that the eosinophils actually predict response to BT. So what is it? And should we just scrap the biologics and everybody gets BT? What do you think? So, have you read the literature yet, please? The Blue Journal or any, a chest or anything? So we showed that these patients with high ventilation defects on xenon MRI where we gave targeted therapy, we could do one bronchial thermoplasty and be done. And they worked just as well and improved their quality of life at the end of the year. So it's out there. Now, unfortunately, the company's not gonna support BT in the future. So it's not gonna be a long-term solution for us, unfortunately, until, unless somebody else picks it up. I'll be honest with you. I'm sad to see BT. I know that it was really a place for a lot of hope when it came out. And many people did benefit from it. And you had to be very careful that you weren't promising the moon and then have these honest conversations. But I also know that we did BT and many people went on for biologics. But I'm wondering, for those people who are doing okay with biologics but not great, what are those ventilator defects? And we need to do better evaluation of ventilation like with those xenon MRIs and the remodeling to say, okay, if we targeted that area, it's like surgical precision. Using precision instruments that we have as well as biologics. Well, I do agree with Dr. Khadram. There's a lot of these patients we've used both bronchial thermoplasty and biologics. No, I like that idea. And you know what, I'm a little frustrated too that it has just gone away. It wasn't the greatest thing since sliced bread, which is what it was hailed as, okay? But it got me rehired at the Cleveland Clinic, so I'll go with that. So you're now employed because of BT. That's good. Well, I'm employed because of being a good asthma doctor. And but then the second thing is, but why do we have to make it so difficult? I do believe it needs to be in specialty centers with registries so we know what happens long term like the BT10 study, et cetera. And I don't think it should be like, I really felt that all of a sudden the company wanted people to put up a shingle and say, BT available here now, walk in. And it was just very frustrating because not just anybody can do it. And I think people who treat asthma are the ones who should be very involved in that. There was a lot of being done in the community and not well. Exactly. Oh, disastrous. Dr. Lee. So could it have a role in some of the patients, like you said, Dr. Kotter, regarding those who are on biologics but just not doing great, they're doing okay. And perhaps we biopsy them just like in some of the studies to see if there's increased maybe smooth muscle hyperplasia or increased mass. And then in those patients, should we target them? Just like you are saying. So is there some other role for that? Right, and you can show that the inflammation is being targeted, so that's good. So that's off the table. So you're left with just a structural change. I don't know, I disagree with my panelists here. You seem to disagree with your panelists an awful lot, Dr. Castro. That's okay, that's okay. You told me I was supposed to. You are supposed to, I love that about you. Hopefully there's some facts underlying the disagreement. The problem with biopsy studies is there's a lot of variability with biopsy. We did a study in the Severe Asthma Research Program, did a lot of biopsies, two variable measure of smooth muscle remodeling. So I really advocate that imaging is much more reproducible. Why not both, why not both? Because I think you can do stereologic techniques and morphometry to really get at the, to try to harmonize the biopsies. That's not gonna help my colleagues out here in the community. They're not gonna do, how are you gonna do that? I say we do it, then we figure it out, and then we can disseminate the info. Isn't that how you do clinical, isn't that how you do studies? I don't know. Imaging is a lot easier. I'm sorry, these studies things, I don't know what you're referring to. All right, two topics left before we have a final closing topic. Mind the Gap is next. Intermittent ICS and rescue fast-acting LABA-SABA is a recommended therapy, but not broadly used. How do we close the gap, Dr. Khatri? Well, use it more and socialize it, number one. Fight against companies that won't allow it. And in the long term, even insurance plans might find that they're having to pay less for it because they're using it intermittently. So work around, for your own employee health plan, for instance, just advocate for it. They weren't paying for Pheno even. I'm like, what are you thinking? We wrote the guidelines. Same thing for smart therapy. In fact, I'm on the NAEPP coordinating committee now, and when I hear about what an amazing benefit it is- So why did they stop short? Well, why, well, listen to this. Right, because they- Because the FDA has not approved it, but the coordinating committee, even the kids in the schools, that single inhaler has helped, but the problem is it's often not covered. And then having it as a ICS after LABA or after SABA doesn't work because then it's not a single therapy. So the problem is because they never went through the process of doing whatever is allowed for that to be approached. But I think if we do advocate, we are all advocates. We've all been able to be advocates. Well, I wonder though, don't you think smart therapy has the advantage right now with ICS-LABA? So it's kind of out there. It's been in Europe a long time. Now it's coming to the States. It's almost like we've missed the- Maybe making it over the counter is the answer. And we sort of missed the ICS-SABA window because we've got the ICS-LABA approach now. And everyone wonders, you know, GINA versus NAEPP. And in fact, my colleague who's on the mix-up writing committee, he's like, so which one do I use? I said, you put both because really we all like smart, but we have to- Well, I think NAEPP should have been braver and said, you know, ICS-BNES-SNIPE for Motorol was okay. I think there's gonna be a different future for NAEPP. Just saying. Yes, they should have. I think guidelines should be with the societies now. So this is probably, because we need to be agile in our ability to do that. Okay. Last formal topic. Case management. A patient with severe asthma with frequent exacerbations has a history of allergy of pheno of 50 parts per billion and peripheral eosinophils of 6,000. Why are you smiling already? Oh, because we were talking about this scenario at this meeting. Did you get advanced look at the materials? Yes, you did. Okay. What is the appropriate treatment? Dr. Lee, you're the one not smiling and looking at me, so I will call on you. Well, I think that when you're looking at a patient like this, the first thing that you need to do is make sure that they don't have any other major causes of the peripheral eosinophilia. So that's the first thing. So you rule out parasitic infections, you rule out eosinophilic leukemias, you rule out the PDGF flip mutation, you know, translocation mutation. You have to rule out a bunch of other things that are commonly done. So once you do that and you make the assessment in terms of they're having frequent exacerbations, you wanna make sure there's not like chronic eosinophilic pneumonia or cardiac etiologies or something else. Or parasites, right? Yeah, so that's the first thing I said in terms of ruling it out. So just making sure all of that. And then typically the first line that I'll go to for this patient who's having frequent exacerbations is I gotta get that under control while I'm getting the approval for the IL-5 inhibitors, right? So you'll start with the steroids in terms of putting them on something to get them absolutely under control. And then after that, I keep them on it until I start the anti-IL-5s, you know, typically mepolizumab or benrolizumab in terms of starting those therapies because it takes time, right? And so that's what I'll typically do. But you know, we've had cases of people who presented like this making sure they don't have eGPA, other sorts of things in terms of sinus disease and elsewhere. But you know, we had a case of peripheral T-cell lymphoma that presented to the hospital like this. And so if you don't do that other workup up front, you will miss that. And you don't wanna be sitting there saying this is all just asthma. You have to keep your eye on the ball, right? And you have to use your consultants properly, your allergy immunologist, your rheumatologist, your ENT people. And it becomes very, a good opportunity to do this multidisciplinary care. And then you're playing off of each other and creating more relationships for these patients. And then you're not missing something. Yeah, the malignancy really worries me too. Well, a group of us did a paper, and I'm quoting my own paper, but I was with a group. And it's in Jackie in practice. It has an algorithm for this. And it's really, I actually find it helpful. We actually talked about it in our last session. 1,500 really was the cutoff we used. But some of us feel like even 500 to 1,000, you're starting to pay attention to those EOs and really kind of going down that path that Dr. Lee very nicely described. So, and I found that helpful because I think we know with DUPI that EOs can go up transiently. And so therefore, in someone who's got high EOs, even in a setting of hypheno, you may wanna tackle the EOs first. I don't know, I would've pulled the trigger a little bit faster. I would do that diagnostic work that Dr. Lee nicely did. But I would start them on anti-L5. I would pull out Benra from my drug closet and give them a dose. You have a closet at home, is that what I said? No, closet in the clinic. I give them that first sample, and then I say, okay, we're gonna do that pre-authorization. Yeah, we don't get samples. Exactly, we don't have them. I've had a patient just like this that was in and out of the hospital three times and never got a biologic. We're not allowed to have any samples at all. We don't have them either. Samples. All right, well, I was gonna say these are the final scores, but you know what? It's close, and there's actually something else I wanna do. So first of all, before we continue, please, a round of applause for our folks on our panel. We got through all 14 topics. We have about 10 minutes left. I'm gonna bring up Dr. Karana to speak about a post-game analysis. But I actually do have one more task. So you all have a piece of paper in front of you. You have a pen. While Dr. Karana speaks a little bit, so come on, join us. You're welcome to join us at the other podium. I'm gonna ask you, you have about eight minutes or so. We'll award up to five points. Write me a haiku about albedo. So just to review, a haiku, as just everyone knows, it's a three-line poem, five syllables, seven syllables, five syllables. Write me a haiku. It could be funny. It could be a little waxing, soporific, or whatever you wanna do. I will read them to the audience anonymously, and then we'll judge how many points each one is worth on one to five. So you have 10 minutes. Write a haiku about albedo. Dr. Karana, take us through a post-game analysis. I'm gonna look on Twitter and see what's going on. This was great. I actually had so much fun. So another round of applause. I think this, and in the spirit of competition, I think this PTI, Dave, is gonna be better than the sleep and any other PTIs. Wow. We'll see. All right, so just a few things. The first topic was selection of biologic for patients who have allergy and eosinophilia, and I think that is the most confusing question at hand currently for us. So I would look at the GINA guidance. They actually have a really nice guidance on how to select biologics with predictors of response. So if you wanna fact check our panelists here, go to the GINA severe asthma guidance, and also there's a NEJM paper that's a nice review. But I think for that patient in question, dupree, omelizumab, or tezepilumab could have been considered. And in addition to the pair deciding, we also have to ask our patients and also look at other comorbidities that could guide us in terms of the biologic selection. So that was my thing. Now, the other question was do you continue or switch if there's only improvement in symptoms but no other objective improvement? And I would say if there were only symptomatic and that's what got them on biologic or they had two exacerbations in a year, like Dr. Kraft said, then you need to go longer. So assess at four to six months, that's what the guidelines say, and then extend if you're not sure, and switch if you're sure they're not responding. So four to six months, I think, would cover pretty much all the available biologics to know whether, that would probably be a good timeframe to just check in again with your patients to see if they're doing well or not. What about tapering controller therapy when they're started on biologics? It doesn't matter what we think because our patients are already doing it. So I have so many patients who come and tell me, Doc, was I supposed to continue that, you know, whatever, name your ICS LABA? Oh, shoot, I haven't. And I haven't filled it in a couple of months. And so this is happening, and I do think, I think if we can get them on this, as needed, ICS for motor oil, at least we know that there's a safety net. Because I do worry sometimes, what happens if there's an interruption in the biologic therapy? You know, if they can't get it, if they're in the hospital, and nobody puts them on an ICS LABA, while they're, you know, they can't get their biologic, while they're admitted, are they gonna start exacerbating? So I do like this, as needed, ICS for motor oil approach. But doesn't matter what I think or we think. It's really the pairs that will decide. I do like oscillometry, but honestly, I still haven't gotten comfortable in interpreting it. So I think that is the gap with using oscillometry, is for all of us to kind of just get it out there, get educated, know, it's not intuitive. So I think that is something that we all have to get our, just get comfortable with using that technology. It's really easy to use. We are actually using it in a research setting with one of our fellows. I have some equipoise on the azithromycin question. You know, if you look at the AMAZES data, that Peter Gibson was the first author of the Australian study. These were patients who had moderate to severe asthma that was uncontrolled on ICS LABA. So very similar to what the type of patients that are enrolled in the biologic study. They were not selected for their use in a full count, and it showed a 50% reduction in exacerbations. Very similar to the biologic studies, right? So here you have an intervention. It's oral, it's available, it's given three times a week as long as the patients don't have any of those QTC hearing thing, and there's a 50% reduction. So almost equally effective to a biologic, and when they did subgroup analysis, eosinophilic, non-eosinophilic had a similar response, bacteria positive, negative had a similar response, and the long-term studies have shown that although there's decreased microbial diversity, it didn't really give a signal for one of these commonly seen MRSA, pseudomonas, you know, those bacterial resistance to develop. So I think in some patients where, you know, if they don't wanna get biologic, because biologic is also a long-term commitment, why not put azithromycin in there? You know, we have good data, and I think the evidence is there. And then I think the last thing that I'm gonna leave you with is that the mind the gap, because I do think that we gotta get this isosformoderal as-needed strategy, whether it's for the step one and two with just as-needed, or three and four of GINA with SMART, maintenance and reliever therapy. You know, FDA will get to it when they get to it, but I think if we can push and advocate, and I think this is a great place for advocacy, for generic, get that generic fluticasone, salmeterol. Why is that the preferred sort of formulary for almost every place? So let's put the isosformoderal, let's educate our clinicians, let's educate our patients. I say put it over the counter, put it behind the counter. Get it to patients so they can use it, and then FDA needs to come around to it. So I'll stop there. Thanks, Dr. Khurana, appreciate it. All right, so our competitors, please put your name on top. I'm not gonna disclose the name as I read them to the audience, but just so we know what we're playing for, this bling right here, folks, is the champ, whoop, and it just broke him. I think it's referable. So this bling right here, oh, apparently it is. It has a little cheap plastic clip-on that I will immediately fix. But this is what we are playing for, and you will get to leave, and I think you are obligated to wear this for the rest of the meeting. So fortunately I have three of these, so even if I can't fix one, which I'll do it later, I have another. Please don't break this one, because I think I only have one more after this. All right, so I'm gonna come around and pick up your, so again, you've chosen, you didn't know this was coming, you all wrote your haiku in real time. Thank you. It's messy. It's messy, it's okay. Artists are messy. They can always get a pharmacist to come read them for us if we have no other ability to do that. Okay, so I'll put these, again, I would ask that I have some chair prerogative, but I ask that the audience give me, for those of you with panels, thumbs up, thumbs down, if you like what, and you can like it because it's funny, you can like it because it makes you, again, think very optimistically for the olden days when Albuterol was all we had. Whatever you choose. Okay, so I will pick these in a random order. Please, as I read yours, do not try to get curry favor with the audience. You will be zeroed out for points. I don't do that. Okay, so let's start with the first one. Oh, sorry, let me get it right because I don't want to miss, the syllables are perfect. I love Albuterol. Ooh, that's six in the first one. I don't know. Oh, it is, oh, sorry. I love Albuterol. Oh, it's so bad for me. Yes, give me labaroids, please. That's the first one. I may take off a point for not having the correct number of syllables in the first line. Albuterol, I love, that's six. All right, so thumbs up, thumbs down, what you thought about that one? Not a lot of enthusiasm for that one. Very modest in the audience. Okay, all right, so I will give that one three points. Next, changing leaves from trees, chest pain, shortness of breath, help, Albuterol free. That does meet 575. It sort of makes you think of nature. Audience seems to like that one. Nothing, any thumbs down. And oh, it's a uterine, that may be, that's going to be a four or five point. That's a strong one. Next one is, Albuterol, yes, chest tightness and wheeze are gone, but not for long, bummer. It's so good, but not for long, bummer, has six syllables, but it's otherwise great. What does the audience think of that one? I do love that one. You could lose a point for that, but not for long, bummer, but not long. Could have just lost one syllable on that, would have been perfect. All right, last. Okay, this is, there's not a lot so much good syllable counting on this one. Albuterol is not the best. That's got eight in the, Albuterol is not the best. Other meds need to handle the rest. Let's find out, sorry, let's find what's better next. So it rhymes, but technically not a haiku, but I take input from the audience. Oh, so audience is split. Some thumbs downs on that one. There are a lot of syllables in that one. All right, so that last one belonged to my friend, Dr. Khatri. So Dr. Khatri, I can only give you one point on that. Sorry. Even that I'll take. That you'll take, okay. Albuterol, yes. Chest tightness and wheeze are gone, but not for long, bummer. Fantastic, only missing one syllable, Dr. Kraft. That is four points for you. I don't know that you're catchable at this point, but let's keep going. Dr. Lee, changing leaves from trees. I love the sort of the look at nature. It was beautiful. It did hit the level. So four points for you. And lastly was Dr. Castro. I love albuterol. Oh, it's so bad for me. Yes, you were just trying to get the seven syllables with that. I'm gonna give you two points. Folks in the audience, folks on the internet, your winner, Dr. Monica Kraft. Round of applause, please. Thank you. So again, thank you to all of our panelists and to our winner once more. Here is, this is an unbroken chain. Don't handle it too harshly. I don't know how much resilience it has for you. Congratulations. Thank you. Wear it with pride. I'm honored, wow. Yeah, that will actually get you into anything at chest. You can get rid of any badge. That will actually get you into anything. I guess it goes, does it work? It does, it works with the option for fleet. Folks, thanks for attending. If you liked what you saw this time, let us know. We'll try to do it again next year. Go enjoy the rest of chest 2022. Thank you. Thank you. Champion.

severe asthma

biologic

change in management

airway remodeling

oscillometry

macrolides

eosinophilia

as-needed ICS

individualized treatment plans