93. Guidelines Series: GINA Guidelines – Asthma Diagnosis and Assessment

[Music] Everybody, welcome back to Pompi. We took a brief hiatus over the holidays in the New Year to rest in recover and we hope all of you guys had a great new year in restful time and we are back now with a bunch of great new Pompi features coming up in the next few months. We'll be continuing to do our journal clubs with our fellow's case files, some top consults episodes, but we're also adding a few new features that you maybe have not heard before. Some real in-depth discussions of different disease processes and some review of some guidelines which is what we're going to be doing here today, but we're very excited to be back with you all and hope everyone's doing well. Christina, great to be back in the proverbial studio. How are you? How is your new year and holidays? Hey, for, yeah, so glad to be back with you. I feel like I missed you over the last few weeks. Always one of my favorite parts of the week is when we get to do this and get to record. So doing great though, I feel like the new year is already going by very quickly, but as you mentioned, a lot of great things that we have to look forward to and really excited to introduce our latest series which are going to be guideline series and we have a couple of new additions to the team that are going to be helping us out with this which will introduce shortly, but I think this series was actually developed with working with some of some fantastic trainees. So getting excited for that part, but what we're going to be doing as this new feature to pull on peeps is diving into major guidelines that really shape pulmonary and critical care medicine. There's so many guidelines that exist and we thought how can we actually break this down into more bite-sized pieces. So in each guideline series episode, we're going to break down a specific topic or guideline and to really practical, easy to follow steps that you can incorporate into your daily practice. Or at least that's our goal, which I think we can be successful with. Yeah, we'll see how we do achieving it. Yeah, I feel like with guidelines in medical education and your progression, the goal full circle. You start by reading the guidelines to say what you do. Then you start delving more into the individual literature, you're shaping your practice and then eventually you get back to the guidelines and saying, do I actually adhere to this, but also do I think that this is appropriate. You start meeting the people who are writing the guidelines and thinking about how they're going to shape the next ones and what's going forward. But these are all out there. I think they provide unbelievably great guidance about caring for disease processes. And I think we're often practicing without having to full grasp of them. So we're trying to make them more accessible and help people get their hands around them and very excited for that. And to help us do this, we have a couple new faces joining poem peeps that we'd love to introduce. So our first new team member is Tom Deventonio. He is originally from New Jersey and attended medical school at Rutgers, New Jersey Medical School in New York. He then completed his internal medicine residency at Wheat Byle Cornell, where he also served as a chief resident. He currently is a second year pulmonary and critical care medicine fellow at Johns Hopkins. And he's passionate about caring for critically ill patients, how we approach the management of pulmonary embolism and also about medical education of trainees to help them be more confident in patient centered in the care they have going forward. Tom, thanks for your help with this and thanks for joining us. Very excited to be here. Good morning everyone. We're looking forward to this series a lot. Awesome, Tom. So glad to have you be joining us. And our second new face to poem peeps as our newest team member, a addition to Tom is RuPaulie sued. RuPaulie grew up in Las Vegas, Nevada and made her way over to Baltimore for medical school at Johns Hopkins. She then completed her internal medicine residency training at Massachusetts General Hospital. Before returning back to Johns Hopkins, where she is currently a second year pulmonary and critical care medicine fellow alongside Tom. RuPaulie's interests include interstitial lung disease, particularly as related to oncologic drugs. And she also loves bedside medical education. When not working, you can find RuPaulie and Tom, Paulie together thinking about great things and educational initiatives at local coffee shops, the hiking trail, and she loves to do yoga as well. So hopefully get to do a yoga class with you RuPaulie. And we'll say just Tom and RuPaulie just great educators have really been instrumental in doing some sim sessions for resident trainees as well as procedural office hours, which they offer. So glad to have you both joining in RuPaulie. Welcome to Plum Peeps. Thank you so much, Monty. Good morning, everyone. I'm really excited to be here and be a part of this Godline series and happy to get started on this. Yeah, absolutely. I love that intro because it's like when they're not working, they're thinking about work and to like explore, it were different environments. Great. So before we dive in, just our standard disclaimer. As a reminder, this podcast is not meant for specific medical advice and the views we expressed today may not necessarily reflect those pinning your policies of our respective employers. Yeah. And excited today to be going over Gina guidelines and covering asthma. If I think if anyone attempted to read the series, it would take you a little while to go through it. So we're hoping to do more kind of bite-sized teaching of the guidelines over three to four series within asthma itself. But RuPaulie, can you tell us what the roadmap is for listeners for today about what we're going to be covering? Definitely, Monty. So today we're going to tackle the most recent Gina guidelines with a few different topics. So the first thing we're going to focus on is the diagnosis of asthma and talking both about the definition and just an overview of how we define asthma. Then we'll get into some of the key features of asthma as well as how we think about genome-type asthma. And then last, then we'll talk about some adjunctive diagnostics in terms of things that can be helpful in that diagnosis of asthma. And then we'll end with an assessment of asthma and clinic and how we think about patients that are returning to clinic and assessing their asthma in a reiterated process that occurs over time. With that, we will always like to have a case for reference. So Tom, maybe I could kick it over to you to start diving it. Yeah, of course. I've always found it so much easier to think about how we care for patients with another with a particular patient in mind. So I want to share with you a case that I saw fairly recently. And I think it's a pretty typical case that a lot of us will recognize both within pulmonary and critical care, but also internal medicine, pediatric. This was a 28-year-old man. He was coming in with intermittent shortness of breath, wheezing and dry cough for the past six months. His symptoms were worsened with exercise, activity, and particularly as we went into the winter seasons with cold air. He noticed a pretty significant increase in his symptoms. He had a family history of allergic rhinitis, but he didn't carry any diagnosis of asthma. No one ever told him as a child that he had asthma. And he was coming in to see me for a first-time evaluation. His physical exam was normal. He had no wheezing either during inspiration or expiration. And that's the situation that we were presented with in clinic. Thanks, Tom, for sharing this. I agree. This is a really classic case that all of us see from first year fellows on our first day of clinic to the season's physicians. We definitely encounter patients just like this. So great clinical case. And we are thrilled in this series to use this clinical case as a framework and dive into the 2023 and 2024 global initiative for asthma. Regina Guideline is our primary reference for this series. Yeah, absolutely. And agreed. This all sounds very familiar. There are times when you can make a diagnosis off the bat when someone's telling you something. However, that's not the core of what we think of for diagnostic criteria. And so you really have to start at the basics as you have a good familiarity to start at the basics. A reply to hope you can tell us how the Regina Guidelines define asthma. What are the key characteristics and how are we distinguishing this from other chronic diseases? That's a great question, Dave. And I think a lot of us have an idea of what we think asthma is defined of. But the Regina Guidelines are a really nice job of giving us some concrete symptoms and then categories to go off of. Asma is really a heterogeneous disease. It's characterized by recurring pulmonary symptoms. These symptoms include breathlessness, wheezing, which can be appreciated on physical exam, cough often dry and then chest tightness. Oftentimes, there are triggers that these patients report as did Tom's patients. And I really describe these patients when I'm describing these symptoms to patients. I describe them as being variable symptoms that can either just go away on their own or will improve when patients use certain treatments. Though sometimes it can be, these symptoms can be incompletely reversible. However, a key point for us to remember is that variability seen in this condition is something to highlight. That's what really distinguishes asthma from other forms of obstructive lung disease is the variable airflow limitation. The importance of these symptoms is also really highlighted in the new 2024 Guidelines where they actually block it asthma into different phenotypes that are now recognized within the scope of asthma and based on symptoms. These include allergic asthma, non-allergic asthma, cough variant asthma, adult onset asthma, asthma with obesity, and asthma with persistent airflow limitation. Monty, I'm really interested to hear how you think this variability in the disease impacts our patients. Thanks so much, RuPauline, for going over a great baseline definition for us to continue the rest of the discussion with. The variability is such a great point to highlight. I think we often see this. Some patients are going to feel perfectly fine one day and the next day they may struggle a lot with symptoms. I think as Tom alluded to earlier with the patient that he was referring to, really how important the environment or exposure to specific triggers can exacerbate symptoms. I know where it is the season right now. I think it's single digits in a lot of different states. There is definitely triggering these symptoms for a lot of patients. So I think it's just important to understand really how both clinical and environmental factors can impact asthma and how we are going to guide and treat patients. And exciting on this a little bit further, we probably mentioned a great framework for the guidelines. And I really like the 2024 guidelines, how they actually mention what specific symptoms and patterns really help support the diagnosis of asthma, which can help with my framework about how I'm thinking about patients. Specifically, the new patient that you may be seeing, asthma is going to be on the differential, but you obviously don't want to miss anything. I'm going to highlight a few key points, right? Everyone's going to, the gene guidelines are available online, so anyone can reference them at any time. But a few key points I hope those nurse can remember from today are the presence of more than one respiratory symptom is going to be supportive of asthma. So they actually mention cough as the only symptom is unlikely to be asthma. Maybe we should broaden your differential, but if you have more than one respiratory symptom that can help support the case, the second highlight I want to mention is that symptoms are often going to be worse at night or upon awakening. So as you're getting that history, those are going to be really important things to look for and ask. And the third one is asthma, maybe more apparent with the concurrent viral infection. I tell the teams right now, it's the season. There's a lot of rhinovirus going on. I've read non-COVID-URI infections, RSV, influenza. I know a lot of recent hospitalizations with that. It's just understanding how there may be variation and seasonality as well with symptom presentation. And I also tell them, I appreciate how you commented on the physical exam in your patient earlier, because often in asthma, the exam can be normal. Or if you're seeing someone in clinic, you may hear wheezing on force expiration, but a lot of times, you may not notice any pulmonary abnormalities. So I think with that, we have a good framework for what the diagnosis of asthma means. This is really important point of variability, because we, as we said, we want to get the right diagnosis and we want to avoid missing alternative diagnosis, because that's really going to impact how we're going to treat patients. And Tom, I'm hoping you can walk us through when you're thinking of the diagnosis of asthma. What key test and clinical factors really help you solidify and confirm the diagnosis? Yeah, absolutely. I think the big takeaways here to think about are that clinical history is key. And then also the presence of variable airflow obstruction and airflow limitation. Those are two central things to the diagnosis of asthma when we're formally making it. We learned this in medical school, but this is very true here. History is essential. It's going to give you most of the diagnosis in this case. And it's important to, there's a saying I remember learning when I was either a medical student or a resident that not all that weasers is asthma, weezing can present from a variety of different causes. And as Christina was alluding to, it's really important to keep a broad differential diagnosis. So we're going to, when we're taking our history from our patients, we're going to hit many of the topics we've already discussed. When do these symptoms occur? What symptoms are they having? What make them worse? Particularly looking for triggers, further worsening of their symptoms, things like cold air. Patients will tell you that when they, they walk into a room where someone's wearing really strong perfume or cologne, it could cause them to have a flare of their symptoms. And then what are the things that make it better? Many patients have been prescribed a bronchidial later in the past. I'm curiously, has that made them feel better? Does getting away from the trigger make them feel better? So with that clinical history, we go into doing particular testing to move our pre, to move our post test probability of diagnosis. And the diagnosis of asthma really hinges upon the confirmation of variable air flow limitation. Ideally, this is done before someone has started on asthma therapy, but that's not always possible. And we probably will talk a little later about how do we navigate that situation? The classic way that we look for variable air flow limitation is with spirometry. Now, someone who is not in an asthma exacerbation likely will have normal spirometry. But the things we are going to do are bronchidial later challenges. And for that, we look for a response in the patient's FEV1 by 12% or more than 200 milliliters. That bigger the response, the more suggestive it is. But the Gina guidelines, particularly the 2024 guidelines, highlight that not all places have ready access to spirometry. So there's other ways to make that diagnosis a variable obstruction. You can do it with peak expatory flow monitoring over several weeks. You can give someone an empiric treatment of a inhaled corticosteroid containing medication and look for improvement generally over this span of about a month you're looking at a minimum. And then you can also do provocational testing like methodcalling challenges to really try and demonstrate that there is some airway hyperreactivity that's central to the diagnosis of asthma. I think it's really interesting the way you point it out. Again, they mention specifically that a higher threshold for improvement in FEV1, like 15% or 400 milliliters is more sensitive for the diagnosis. And I think it's always just helpful to keep in mind that the diagnostic criteria we're using both clinical and testing are all about this sensitivity. Having an empiric treatment mentioned there in the diagnostic guidelines is an important element. I can think somebody has a disease, or some of you have limited, or the patient is limited in their ability to be able to get this confirmatory testing. And in certain circumstances, that shouldn't stop you from doing the treatment because again, we're all thinking about our pre-test probability and our sensitivity going forward. So just a really interesting point. And then I also just want to both you and Monty mentioned the symptoms being worse at night. And I think this is, we can have a whole other episode about why asthma symptoms are worse at night. And where the guidelines really help to still down a lot of our old physiologic understanding, they don't maybe always dive into all the mechanisms. And I think they're really interesting. Circadian and hormonal and trigger related and muscle tone related mechanisms behind asthma being worse at night. But I think it's just, they give us this sink to description of everything. And such a great point, Dave and Tom, is that a lot of times we don't have the perfect, we can't put patients in these boxes and say check they have pulmonary function tests that show very well airway obstruction. And then they have all the symptoms. So it's sometimes we're stuck with thinking about how likely do we think it is that this patient has asthma based under combination of all the symptoms that they told us about. And then we are left with how do we establish that they have this variable airflow obstruction. And what one of these scenarios that Tom described is that nowadays we have many different things that we can provide to patients. I really like the peak expatory flow monitors that patients can take home with them. Our patients are really good at knowing when they don't feel well and being able to provide us with that information in real time is super helpful because often in the pulmonary function testing clinic, we know we're not capturing patients at that time. And so I always tell my patients that when they come to clinic and they have symptoms that are suggested that asthma with a typical history, even if their pulmonary function tests are normal, that does not mean that they do not have a plasma. I think that's a key point to highlight here. And one of the things that Tom mentioned is oftentimes our patients now are started on therapies empirically, whether that be by a provider who's seen the patient before they've reached our clinic or someone else is they often come to us already on some sort of either bronchoc dilator or potential at male corticosteroid as well. And the guidelines actually do suggest that this is a very common scenario and give some guidance that in this scenario, it is sometimes worthwhile thinking about even potentially decreasing the element of therapy that they're on. So it's not an inhaled corticosteroid in that their symptoms are stable. Maybe think about stepping back that dose of inhaled corticosteroid and then doing some bronchoc dilator testing and seeing how they respond or doing some of that peak excitatory flow monitoring just to see if you can find that element of variable obstruction. However, really good to know that a lot of our patients are empirically being treated and that helps with the diagnosis of asthma in many of these situations. I think it's a great point. I think we'll get into treatments later, but you should always be considering stepping down therapy, which is not something we always think about. But then also if you're not 100% sure on the diagnosis, how you're going to influence that going forward and how that can help you to best manage a patient. And then we do get this so common that it's also worth mentioning that we, I definitely step this down to see there's also we always have to consider look with draw effect of some of our medications, especially like inhaled corticosteroids and just planning appropriately for that. And so it's just a consideration to take when you're interactive with the patient for that who's already on it for the first time. Such a great point, Dave. And I think we spent some time talking about the diagnostic approach of asthma. And I wanted to transition a little bit to thinking about how precision medicine is reshaping asthma care and is further driving care. Dave, I know you've done some really interesting fascinating work on COVID-19, a key respiratory distress syndrome, subroping them. Could you share some insights and the benefits and clinical utility of understanding asthma phenotypes and how you think about them? Yeah, look too. I think phenotype being in general is obviously a huge push in all fields of medicine and having precision medicine and more focused treatments. I think we now sometimes tend to think about phenotype being is this very ultra complex using multiple assayist, put things together, but we do phenotype in all the time, right? You see a patient who has asthma and they seem to be a personalized more allergic type asthma. They only have it in the spring time when they also have. allergic rhinitis and we call that sort of an allergic phenotype asthma and maybe changes the way that we treat. And so I think we've really honed in on these phenotypes and they can help distinguish our diagnoses for two main reasons. One is prognostically how we think somebody is going to do and the second is to influence treatment, right? So these are the main end points that we're gonna end up thinking about. And so the genoclycline is used multiple different ways to think about different phenotypes. You mentioned that they had all those different categories, obesity is associated, so you'll see it be overlap, allergic, airway responsiveness. So those are phenotypes in and of themselves. They also have certain measures on spyrametry that they use as phenotyping and certain serologies that they use as phenotyping. And so I think the key ones that we're often talking about in asthma is about the elemental reversibility, which is part of the diagnostic criteria. And then also about the level of allergic markers. So eosinophilia is to become a main, mainstay of asthma treatment and helping determine how much they may respond to different treatments. And that's a phenotyping method itself. And so just to focus on one of these, the asthma COPD overlap is something that can really complicate the management of asthma and that we see all the time. And we have patients who have features of airway reversibility, but also have this persistent, this smoking history when they get PFTs that always seem to have some airflow obstruction that's not fully reversible. And so then you're left wondering, but not the hip-COPD and asthma or asthma or both. And it matters because the treatment is different, right? So inhaled corticosteroids are the cornerstone of asthma treatment. Now for general COPD treatment, we usually don't start with a inhaled corticosteroid. We start with a long-acting betaagonist and muscarinacantaginist. And so we think about the drugs differently. And so the gene of violence has helped us phenotype these people a little bit more by saying you're going to look for the clinical history that could be consistent with a COPD type picture. You're going to look for airway bronco-niallate reversibility because that may end up putting you in this overlap category. You have a fixed obstruction, but it also reverses. It just doesn't correct to normal. And then we can use things like a blood-easy NFL level to further hone in and say, you have a persistent airflow obstruction. You seem to have reversibility. And you have ESINFL is great in 300. Maybe you really have an asthma COPD overlap that can benefit from more directed therapy as opposed to someone who just has really COPD. And would have a different treatment paradigm. Yeah. And that really is a great way to help me think about how we approach treating patients. Really personalizing the care that we're giving to our patients, thinking about who that person is individually, how their disease is affecting them. One thing that I've really learned in my time as a pulmonary and critical care fellow is really focusing on what that individual patient's phenotype is. I think we're very fortunate to have very thoughtful attendant physicians and clinic who challenge us to think about, is this person in a high ESINFL? Do they have high ESINFL like asthma? What's their IgE levels? What type of inflammation do they have? And then providing about a best care to our patients. I think what they're really getting at with a lot of that is distinguishing between what is known as type 2 versus non-type 2 type asthma. And it's an important distinction to make because as we'll see later on in this series, particularly when we get into the world of biologic therapies, those are, it's an important distinction to make. Christina, are you able to tell us a little bit more about those key differences between what is type 2, what is non-type 2, and how we should think about that? Yeah, Tom, such a great question. And I feel like great type tube inflammation for those of us that were at ATS a couple of years ago. I feel like that was a Wi-Fi password. So definitely big in pulmonary and critical care space. I know they changed the password every year. I don't feel bad for disclosing it. It'll be a different one. So we'll see what it is on a few months. But I just think that brings the importance when you're thinking about different pulmonary disease states. How important it is to really differentiate between this type 2 inflammation versus non-type 2 inflammation. And for me, I really try to break that down. Some great points in the newest gene of guidelines that extend on us a little bit further. But I feel like I understand things in a very basic and simple fashion. So really understanding what are the five features that are going to be different between type 2 and non-type 2 and inflammation. And really the five that I try to, the buckets that I break it down to are going to be what inflammatory cells are present. What biomarkers that we have regularly available and non-invasive can we use to differentiate the two? What trigger types are going to be important? I think one of the really important is going to be like, are the patient's steroid responsive or not? And as Tommy just mentioned, this advancing world of biologics, what treatment responses and opportunities are going to be available to these patients? I think as we talked about earlier, if we can perform these diagnostic testing off a systemic corticosteroids, that's going to be the best. But I know that sometimes that's not always possible. And delving this until a little bit further, those five features that I mentioned. And when I think about type 2 and inflammation and really think about the key players, Tommy note your prior wrestler, I feel like I played basketball, so trying to do a sports analogy. So like the type 2 and inflammation, I feel that the starting lineup for the team, as far as inflammatory cells go, are really going to be the asynophils. And for a few, just mention that as well. Right, so this is going to be obtained by just doing a CDC with diff is going to be important. As far as biomarkers go again, this is a phil's and then having a high fractional in having a high fractional excelled nitric oxide. And we're going to get into that a little bit more in depth, but really just understanding that in type 2 inflammation, the levels are going to be high. The trigger types are going to be allergens. We mentioned some of this earlier that the perfume that we mentioned the cold air, just to name some examples. Stereoid responsiveness is going to be high in type 2 inflammation, having a patient trial and in held cortical steroid that's likely going to show some improvement. And then as far as treatment goes cornerstone is ICS and as well as biologics and we'll have a whole episode on how to determine biologic therapy and which one is going to be we should start out on our patients. But when I'm thinking of the starting lineup for type 2 inflammation, those are going to be the key players alternatively when you think of non type 2 inflammation. It's going to be a little bit different, right? So what's going to be their starting lineup? So as far as inflammatory cells, it's really going to be more neutrophils. So we're not going to be seeing high eosinophil levels as far as biomarkers go complete the opposite of type 2. So we're going to see low fractional exhaled nitric oxide as well as low eosinophil levels trigger types may also differ in non type 2 inflammation. We really think about these infections, which are going to be viral or bacterial infections. There may be some overlap as far as irritants and allergens. Another key distinct feature is going to be the steroid responsiveness. So it's going to be poor. So you may start a patient on an in health core, go steroid and you don't see benefit may make you think, well, it's probably isn't a type she responder. And then as far as treatment goes, the biggest different distinction is going to be bronchodilators are going to be more used in the setting and some recent studies where there's actually some benefit for macrolite therapy. So I think we'll get into this by thinking having a good framework when you're thinking about a patient and clinic for the first time doing some non invasive testing, the CBC with diff. We can also talk about potentially doing an IGE level and the guidelines also mentioned in a specific patient population based on history and context, whether or not you want to get rast panels, which I know there may be some institutional variation on what's ordered and what allergens are tested, but that's going to be testing IGE levels to a variety of different allergens. For if anything to add on how you think about type two versus non type two inflammation. Only that I think we should get some Jersey, this is Popeube's Jersey is for the starting five on the back. At me, it's enough. No, no, it's great. I think that's exactly how we conceptualize that these two different big buckets of patients and I really want to talk more about these diagnostics and fractional exhale, metric oxide is one of the easiest, most available metrics we have for this as well as syramia synafile levels. But before we go into there, I just want to take a brief detour that none of the things you were mentioning and this phenotype in her diagnostic had to do with imaging features in as well, which is really unique for us as pulmonologist. I think like most of our diagnostics we really get this early. I was seeing an asthmatic patient the other day and I was like, oh, right, what was your last CT scan she had never had one. I'd been seeing her for three or four years and I just never needed one in her diagnosis. She never met any criteria to automatically get the scan and that should be the way that we practice medicine. But there may be times when imaging can be helpful mostly for sort of mimics of asthma or thinking about different phenotype groups for this. So we're probably just hoping you can share if they're before we go into some of these more diagnostics that are more common. If there are times when we should think about if we should incorporate CT imaging specifically into this diagnostic workup. Sure, Dave. I think I've thought a lot about when to get imaging as purely as a patient is an adjunctive diagnostic. Some of my patients say come to clinic they've had imaging and so I don't have to think that hard. I just look back and I'm able to assess that but sometimes imaging can be helpful depending on this scenario. The CT chest can sometimes be helpful in asthmatic patients when we're looking for certain colomorbid conditions that can complicate the clinical picture and our further treatment with that patient. These include bronchiactasis. or even emphysema in that asthma COPD phenotype overlap that you had mentioned before, that would be helpful. And I might consider obtaining a CT in that setting to evaluate the poryclumal changes that are associated in that asthma COPD phenotype group. Additionally, if I'm concerned about a specific disease process, it caught ABPA or allergic bronchocommonary aspergillus related disease, then I might consider getting a CT scan to evaluate for bronchiactasis. This can be really helpful to fold. It can help me assess bronchiactasis and look for certain things associated with that certain disease process, including the distribution of bronchiactasis, and formulate my further care of this patient a little bit more. So I found it helpful in those two scenarios to really think about obtaining CT chest imaging in those scenarios. Similarly, I have had patients come to me who report a lot of different sinus problems, and can come in with some of the asthma symptoms that they're discussing with me. And they report maybe a history of having sinusitis in the past and receiving frequent antibiotic courses. In those certain clinical scenarios, I often sometimes will think about whether a TINI-CT sinus may help me further define this patient. Again, that allergic phenotype that we're thinking about, but may also be helpful in obtaining imaging before we refer our patients to see your no-stroke specialist and think about concurring conditions that can be associated with asthma, and that includes nasal polyps. Very important because it's like we mentioned, a lot of asthma is coming down to phenotyping patients, and with newer and newer drugs available, it's helpful to know about some of these other conditions that can be examined with imaging because they will tend to guide further treatment selection and specifically nasal polyps. Sometimes we think about concurrent biologic. So those two scenarios are where I like to. Three scenarios are where I like to think about imaging is if I think someone may have ADPA, they may have a COPD asthma phenotype overlight, or they may have chronic sinusitis, and I'm interested in looking at those sinuses. - Yeah, thanks for sharing that. - And I think it's important to highlight that mostly that we're thinking about either you could use the word mimics or like more complicated versions of asthma, right? So even nasal polyposis, you may start your starting to border along on somebody has an EGPA type picture, or somebody has an aspirin-hob related allergic response and disease, right? And so when someone is just really not improving or fitting one of these buckets, I think it's important that we expand our differential to some of these disease processes that have asthma as a feature but might require some more consideration. Tom, can you shake us through some more of the standard diagnostics that we think about and that the gene guidelines specifically mention and some other guidelines might refer to as well? - Thanks Dave. We talked about fractional exhale, nitric oxide a little bit earlier, FENO, and how it can be helpful in phenotyping some of our patients, particularly those patients with a type two inflammation. Christina, can you tell us a little bit more about when you would think about using FENO testing and some of your patients? - Yeah, sure, I would love to, Tom. And I think it's been really an important point to talk about. Before I get into that more, though, Ferf, I just loved, as you were talking, I was like asthma mimickers, like we should have a whole episode on asthma mimickers. Something else to look forward to in the future. And I'm obviously struggling today with saying fractional exhale, nitric oxide more than once. So FENO, Tom, as you mentioned, is something that can be done. The genocyanolins actually mention, and we're really helpful, right? So it's not gonna be, we just do this one test and we're gonna diagnose someone with asthma. It's really an adjective supplementary test that we can use, especially helpful for patients who have frequent exacerbations, signs of type two inflammation, which we've already talked about. And just really when the patient's symptoms don't really fit into a clear bucket that RuPauli talked about earlier. And when I was first learning about FENO testing, I was like, "Why is this even helpful? Like, why are we doing this?" And there's just great work and studies and other papers at that reference list. But nitric oxide is a marker of isynophilic airway inflammation. So it naturally fits into being able to do a non-invasive and quick test. What I typically tell my patients, so I guess it's not much different from doing PFTs, but as I'll tell them this is gonna be done in a lab, there's probably some institutional variation on how often this is gonna be ordered, is it readily available or not? But it's something that can be done in many PFT labs or adjacent settings. But when I'm telling my patients, it's a quick test, it's not invasive. Basically, I tell them, you're gonna just take a deep breath in, you're gonna have your lungs filled, similar to if you were gonna be performing a PFT. And then you're gonna actually just do a slow exhalation, steadily into a mouthpiece connected to a nitric oxide analyzer. And that analyzer actually measures nitric oxide levels in the breath. And that's gonna be reported typically express in parts per billion. An FENO level of 50 parts per billion are higher, strongly suggest type two inflammation. As we talked about today, it can be important in how we're gonna actually decide to treat our patients. As I mentioned earlier, not something that we're gonna use on its own, but can really work and complement spirometry and clinical evaluation to help us get a better picture of maybe what's going on. I think this is one additional test that can be considered. And again, as I mentioned, may not be readily available at every institution, or outpatient clinic that you may be working in. And I know that there are some additional testing that can be considered. And Tom talked about this a little bit earlier today when he mentioned met the colon challenge, but it's really this testing of bronchopropication test. And for if I'm hoping that you can share your approach on when you consider including this additional testing, who are you, what patient population are you gonna really try to consider this and then what do you tell the patients when you're discussing this as possibility for diagnostic evaluation? - Yeah, absolutely. I think that is the key question is which group of people are you gonna use this in? To talk just logistically first about bronchopropication testing. Generally, these are patients where the diagnosis in question and we are looking for airway reversibility. And so we mostly do that by trying to reverse their airway obstruction and measure that with your bronchodialaiders. However, we can do it the other way and we can give people agents that we know are irritant to all their airways or most are all airways and see how they respond. So we can use pharmacologic agents like metacoline or manateal. If someone really has like exercise induced asthma, we can actually do exercise and exercising a lot of patients will make it slightly worse but we can use that as a diagnostic of exercise induced airway reversibility. But the metacoline challenge is the most commonly used. The patient in hails metacoline at different concentrations and we get a metric at each concentration. And then we end up seeing looking for a drop in their FEV1. So I'm really looking for a 20% drop at a low concentration of metacoline, typically less than eight milligrams per milliliter. And manateal is similar. We're looking for a 15% drop in FEV1 at a certain concentration. And that just helps us say you have abnormally responsive airways. Now, if you give enough metacoline or manateal to anybody, their airways are gonna constrict some. And so we see this when we look through the charts that we get of someone's FEV1, but we're really looking for the meet this threshold that they have airway hypersponsiveness. So then the question becomes, when am I gonna do this? So first of all, this is not a pleasant study. Right, the patient is breathing. I was already someone who has respiratory complaints and they are breathing in something that we know are gonna trigger it. And so I really talked to my patients a lot in advance of doing this. I also think that it's very standard practice and should be that any PFT lab doing this only does it in people with a preserved FEV1. Some certain cutoff of that VV1, you probably don't wanna get metacoline to someone's FEV1 is one-leager. And then usually that there is a physician around to help manage something if that goes wrong. But I really consider in people where I think asthma is plain or it's on my differential, but we've had issues proving its conclusiveness. Right, so I love fractional tailed nitric oxide. I think that makes a lot of sense to me. IL4, IL13, the things that trigger type to inflammation, lead to nitric oxide being produced in your airways to try to bronchodilite them and we can measure that. And so I think is a much better next step after your initial spirometry. But if you've done that and you're still not sure, then this test can be helpful. So I will just share that the one patient I've done this on in the last 12 months, had a huge workup was really having issues with ongoing cough and short as a breath, had been tried on multiple different therapies before even coming to pulmonary clinic, had that imaging and all of this. And then had been escalated to even a biologic for asthma therapy with minimal response. And so then the question was, do we have the wrong diagnosis or are we just still not adequately controlling this? Are we still just not treating this appropriately? And so that's a person where this diagnosis really made a difference and stripped down the medications, did one of these proved to be positive for asthma and then escalated to a different biologic regiment which ended up being successful. But you could see a picture where someone might really be going in a different direction and you might have had the wrong diagnosis. The thing that I will say is the most helpful for these is that when somebody has a negative result for this, you get to high doses of metacoling and they're still not having a high responsiveness, you really rule it out as a trigger. That doesn't mean they don't have use in the philia, doesn't mean they don't have inflammation, there's a cause for it, but they don't have what classically sees as asthma and we have to think about other conditions that could be causing it. Yeah, that is a, I think Dave, you just, where you just highlighted is what we're gonna transition to next but the way you describe the continual assessment of that patient, trying to nail down what this diagnosis is, constantly questioning, do we have the right diagnosis? And then using different adjunctive therapies is really at the crux of how, I think, we all practice in our assessment of asthma, but also has the guidelines recommend that we assess asthma as well. The most recent guidelines actually highlight that the diagnosis of asthma and the management of asthma is not a one and done deal. You don't make the diagnosis started in hailer and move on. Every time you see that patient back in clinic, you're continually repeating this cycle. And the three things they highlight are that you are every visit you're assessing. So you are assessing their symptom mythology, how well they're controlled. You're assessing any comorbidities, particularly things like post nasal drip, asic reflux, other things that could be confounding your diagnosis and management. You're going to assess inhaler technique. That's a very common pitfall for us. Every inhaler is a little bit different. And some patients might have difficulty with coordinating. Maybe they have arthritis and aren't able to use their inhaler correctly. So is assessing if the reason their asthma is not controlled is because of technique. And then you're always going to assess what that patient's goals are for achieving management of their asthma. Once you do that and you have a sense of where that person is, you adjust your therapies. You treat modifiable risk factors. You provide education and skills training for your patients. And then you come back and review how have your changes made an impact on the patient's symptoms? Are they having less exacerbations? Has their lung function changed? And this is a continuous cycle that we go through. And just like with your patient, we always need to have a diagnostic pause and say, is this the diagnosis? When things aren't making sense, we need to assess if our diagnosis is correct. So we can pivot if needed. Figging about how we classify asthma and make decisions on it. I remember when you're in medical school, you're classically taught to call asthma intermittent or persistent asthma. And then we give it this categorization of mild, moderate, or severe. That's what I remember learning. But as asthma therapy has changed, the guidelines have actually moved a little bit away from that. And there's a couple of reasons for it. One in particular is that the diagnosis of mild asthma can only be really made retrospectively. When you're looking back, how did the patient respond to therapy? How much inhalers did they need to get their symptoms under control? But potentially even more importantly, is that mild seems like it's not a big deal. Mild seems like it's not a big deal, and mild intermittent sounds like it's really not a big deal. But in reality, even patients with mild symptoms, even patients with intermittent symptoms can have severe and even fatal asthma exacerbations. So the most recent guidelines actually move away from using terminology like that. And in some ways, we're moving more towards defining patients asthma based on the level of controller that is needed for them, whether it's step one, step two, step three. That said, even though guidelines are changing, and the way we're thinking about asthma has changed over time, particularly with the use of anti-inflammatory relievers and thinking about where patients fall in the different steps of asthma therapy, the terms mild and to mid-in severe, those still are very much in our vernacular. Rupali, can you tell us a little bit more about how we could think about those terms in how we assess our patients asthma? Definitely, Tom, and something I've definitely found confusing is if I'll or reading those words, trying to figure out where the patient falls and what these words actually mean. And so a nice little acronym that I heard as a resident was 2, 4, 7, and every day gets worse. And this helps us really think about the symptoms and how frequently the symptoms are occurring for our patients and then bucket them into these categories. So 2 is generally intermittent classification, and that means that symptoms are occurring less than two days a week, less than two nights a month, and that inhaler use, specifically short-acting the agonist generally in inhaler use has less than two times a week. So that's intermittent. We get to 4 and beyond, we're in the persistent category, meaning symptoms are more persistent. So 4 stands for symptoms occur more than 2 days a week, but not daily, so that's 4 and it's classified as mild persistent. 7, which is classified as moderate persistent, is just every day symptoms, so that's 7 days in a week. So daily symptoms, weekly nighttime issues, and then the everyday gets worse is severe persistent, and those are patients who are experiencing all day symptoms and very just frequent nighttime awakenings ongoing. So that's how I think about it is 2 is intermittent. Beyond that, symptoms are considered persistent and then mild moderate severe. It's just based on how frequently the symptoms are happening. So that's a nice way that I found to think about it quickly, clinic when reading these in the one-liners. - Yeah, we have to keep a lot of things in our head and sometimes having those quick mnemonics to go to makes it so much easier. - Oh, Tom and Rupali, I love that the discussion, yeah, like easy framework to go to, but Tom, you mentioned some great, you highlight some great points on the guidelines and you know why it's an imperfect evaluation and going away from how we previously thought things and moving forward to it. I think one thing that you all have both alluded to are symptoms controlled or they're not controlled, 'cause this really is gonna help change management and understanding why they may not be controlled or not controlled, Tom's perfect question. Inhaler, technique, so important, we've talked about that before. We have a whole episode on inhalers where we actually had a pharmacist talk about correct technique and et cetera, which you can go back and listen to as well. But Rupali, in addition to this 247, everyday gets worse framework. I hear you say Rupali, I always use the rules of tools and clinic. What is that? And I'm hoping you can share a little bit about your framework that you apply when you're seeing patients weekly with those listening today. - Yeah, thanks, Monty. And I think as we alluded to you, is a lot of what we've learned about asthma is how often are they having symptoms? But the notches that it's just how well are the symptoms controlled? Because oftentimes we meet someone in clinic and we are, some of their having symptoms is soft and you start them on therapy, but then as part of this sort of creative process, we bring them back to clinic and then it's our job to figure out one. Do we have the right diagnosis? Are they on the right treatment? And that can be determined by the control that they're experiencing with whatever therapies they're on right now. So the rule of tools is a way in which we can assess whether asthma is well controlled or not well controlled, which is really what the guidelines emphasize as the cornerstone of what should drive our visits and should drive our next steps in terms of therapies. So what is the rule of tools? So the rule of tools is a simple way to ask three questions and then determine whether the asthma is well controlled or not well controlled. So the first thing is do symptoms occur more than two days per week? The second question is do patients have nighttime awakening so that happen more than two times per month? And the third question is a quick reliever inhaler or a short-acting beta agonist often use exceeding more than two times per week, excluding when patients empirically use it before doing exercise. If a patient answers yes to any one of these questions, then we determine the asthma to be not well controlled. And that's extremely helpful as we've been discussing because that level of control of their asthma is really helpful for us to discuss the next steps in terms of their therapies and to think about whether we need to think about confimit and diagnoses or other things that are important for this patient in terms of phenotyping these patients. So that's the rule of tools. Do you have symptoms more than two days per week? Night time awakening is more than two times per month or do you have to use your rescue inhaler more than two times a week? Answer yes to any of those questions. Makes me think that we could probably do better in controlling the asthma of this patient. - That's great. And like anything that keeps it simple is the way to go. So a rule of two is two, four, seven, and the things you didn't worse. I love both of those. I think we should at least mention that there are some validated questionnaires out there similar to the MMRC or CAT that we use for COPD. The asthma control test, the asthma control questionnaire, that if you have a way to give people a questionnaire in the waiting room or clinic, this can be really helpful way is to measure how their symptoms of control are doing. And then a huge plug for peak flow meters. Most asthma exacerbation plans are designed around peak flow meters. I, when I was in fellowship, the one thing that we had a million of was peak flow meters to give to patients. And I love nothing more than that. It's so simple. I wake up in the morning and they use a peak flow meter. The patients understand how to work use it, which is not a complicated device. And I've seen patients as they get better, be like, oh, I'm getting to, you know, the 700 every time now. And you're like, oh, that is amazing. We're so happy that you're doing better as we improve on this. So if patients can have a peak flow meter, they're pretty cheap at the cheapest ones. I think hopefully our pulmonary clinics can help provide them. That is a great way for them to monitor their symptoms. And then it can be the trigger for them to start an asthma action plan, which we'll talk about in subsequent episodes. Tom, go ahead. Yeah, Dave. I just wanted to, it seems like we've come full circle in some ways talking about sending patients home with these peak flow meters. It definitely is empowering for the patient to see what, you know, how their disease is improving with therapy. I think of you reading. But it's also providing us with a lot of diagnostic information because in some ways that's demonstrating reversibility in airflow obstruction. And it just really helps us confirm our diagnosis. 100% 100% and then especially when it pairs up with the patient symptoms and how they're feeling that day, it's very very satisfying and then really helps us to have a good sense of how to treat them. David, totally agree. I think like Tom was saying, nothing better than when an asthma patient comes back telling you that they feel better after you figured out what their phenotype is and gotten them on some therapy. So I really enjoy talking about all this with you guys. Definitely. Thank you guys both so much. This was a great first episode kicking off our guideline series. This is the first of a few in our asthma guidelines series and then of a broader effort to address some of these guidelines and package them. Be on the lookout for some accompanying infographics, some questions to help you guys solidify some of this information. And we're probably in time. This was great. Monte always a pleasure. We're excited to come back in a week or two and talk about some new topics. Thank you guys all for tuning in and listening and make sure you like or subscribe wherever you're listening right now. This episode was written and produced and edited by myself from Christina Montseweuer, the music's original music by Eric Rogers. And we'll see you next time.