Aloha. My name is Don Mahler, and welcome to this session, Key Revisions to Goal 2023. What are the clinical impacts? So when you or I prescribe inhaled therapy for COPD, you have to make three discrete decisions. One, short versus long or both, the class of medication, and the delivery system. And one of the key revisions of Goal 2023 is to provide some additional information about inhaler selection. And I'm going to present that information, review what Goal discussed, and then amplify that with some of the literature. This is an interactive session, and I'd ask you to scan this QR code now with your phones because that will help you and help us see what responses you have to the various questions. I'll leave this up for 15, 20 seconds. Comes up later also. Another key revision in Goal 2023 is a recommendation for labalama for Group B patients. And Dr. Sandra Adams from University of Texas Health, San Antonio, Texas, will discuss this. And then finally, we all recognize that one of the key revisions to Goal was the elimination of Group C and D and replacing it with Group E. So Dr. Nick Anania from Baylor College of Medicine at Houston will address why have Group C and D been replaced by E, the rationale for this. And I'd like to point out that none of us are members of the Gold Committee, so we don't have any particular bias to support what is in the, what are in the revisions. So we're going to start with a question. Hopefully you've scanned the QR code. And it doesn't show on this screen, so I'm just going to move over here. So which one of the following statements is correct when patients with COPD use a handheld inhaled delivery system? One, the patient should exhale slowly and completely to empty the lungs before inhalation. Two, for a pressurized meter dose inhaler, the patient should breathe in quickly to catch the quick release of the aerosol. Three, for a slow mist inhaler, the patient should breathe in hard and fast to capture the 1.5 second release of the mist. And four, for a dry powder inhaler, the patient should breathe in slow and steady for as long as possible. Hopefully that's a very simple question for you. Hopefully you're marking your responses. Give you a few more seconds. So 77% said the correct answer, the patient should exhale slowly and completely to empty the lungs. In reviews of correct inhaler technique, this is one of the common errors reported in the literature. And certainly when I see patients, ask them how they're using, no one says, oh, frequently they'll say, no one told me to do that before using one of the handheld devices. So good response. So I'm going to discuss what are the key patient factors. Here's my conflict of interest slide. Point out at the bottom that nine years ago, I created an educational website for patients with COPD, family members, and caregivers. It's a free website. Check it out if you're interested. So my two objectives are to review the goal 2023 information on inhaler selection and then describe key patient factors. So we're all familiar with the four different delivery systems. I've included the dates when these first became available. And it's interesting to see how far back some of these different delivery systems go. One of the things that Gold points out is that there are 33 different inhaled medications alone or in combination in at least 22 different inhaler devices. So it's no wonder that some of us are confused about what to do. And it's clearly quite understandable that our primary care colleagues are totally confused about these issues. So our goal in prescribing therapy is to match the specifics of the inhaler devices, come on in, with patient factors. So one of those tables in gold is shown here. And I'm highlighting the second bullet. The choice of the inhaler device has to be individually tailored, depend on access cost, prescriber, and most importantly, patient stability. So they're emphasizing the importance of the patient here. I'm not going to read over those other bullets. So what are these important patient factors? And that brings up the next question for you to answer. Which one of the following statements on patient factors is most important when you prescribe a handheld inhaled delivery system? One, age, education, and cognitive function. Two, ability to use a smartphone, manual dexterity slash strength, and peak inspiratory flow. Intranet access, number three, to view videos on inhaler technique, manual dexterity strength, and peak expiratory flow. And number four, peak inspiratory flow, manual dexterity strength, and cognitive function. So please mark your answers. Again, hopefully this is fairly straightforward. So 91% said the correct answer, which is peak inspiratory flow, manual dexterity, and cognitive function. A few of you said age, education, and cognitive function. And clearly those are, you know, I can understand why that might be the answer. So what else does Gold say? The third bullet here, the number of different device types should be minimized for each patient. Ideally, only one device type should be used. And my response to that is to underline the word ideally. When those of us who work in the United States recognize that insurance coverage, insurance companies tell us what to do, we're struggling at times. But ideally, try to use one device. And the last bullet there, patient's cognition, dexterity, and strength should be taken into account. So how did they get that information? Well, Dr. David Halpin is the primary author of the information in the Gold document. He and I did a systematic review of different algorithms for selecting an inhaled delivery system in COPD and found nine algorithms for device selection. All of them were basically different, and none of the algorithms have been tested prospectively. What we found when we looked at the different domains in these algorithms, patient factors were mentioned 19 times, device attributes 10, and healthcare professional factors 7 times. So out of these 19 times of patient factors, we came up with these three, which you clearly identified. Cognitive function, manual dexterity, peak inspiratory flow. And as I mentioned just a minute ago, insurance coverage is obviously a dominant factor for those of us that practice in the United States. So what about cognitive function? First question, or not question on cognitive impairment, is an important patient factor for you to consider for selecting an inhaled delivery system. Why? Number one, the prevalence of mild cognitive impairment is one out of four patients with COPD. Two, most COPD patients with cognitive impairment can use a PMDI correctly. You just press and inhale. And three, most COPD patients with cognitive impairment can use a DPI correctly. Prepare the device and inhale. So please again mark your responses. Hopefully a very straightforward question with response. And again, majority of you answered the correct answer. The prevalence is about one out of four. Where does that information come from? So Johans in 2017 did a systematic review of 14 studies. Over 23,000 patients were included. And the pooled prevalence of mild cognitive impairment was 25%, with a range of 5 to 63%. So again, that doesn't mean that's true in your practice. But based on large population, most likely, close to one out of four of your patients has some degree of cognitive impairment. So I ask you, if in your office, if the patient has cognitive impairment, will the person be able to use an inhaled delivery system? And I've got the four choices here again. And fortunately, we have some data to address this question. Cognitive ability and inhaler technique was examined in 388 patients with COPD living in New York City and Chicago. Mean age was 68 years, slightly more females. 29% had limited health literacy. And 38% had a low score, 24 or less, on the mini mental state exam. And technique is shown there for the MDI, 67%, and 53% for the dry powder inhaler. And these investigators found that baseline cognitive ability on a global scale, using the MMSE, was predictive of correct MDI and DPI techniques. So to address that question, I ask you, in my practice, if the patient has cognitive impairment, I would say no to the handheld devices. And I would consider nebulized delivery system, particularly if the patient has a caregiver or family member to provide assistance. What about manual dexterity requirements? These are some examples, the pictures are some examples of what's required to use these different delivery systems. How prevalent is impairment in manual dexterity function in COPD? I present here a big question mark because my review of the literature does not answer this question. I don't think we know. The best estimate is found in the results of a survey that Dr. Anania is the first author of, involved 499 patients. This was an online survey, and the question was, what potential impediments do you have for optimal device technique? So 44% they had arthritis, 36% difficulty with fine motor activities, and 15% said tremor. So does this affect inhaler technique? Again, a search of the literature did not reveal any studies that examine the impact of impaired manual dexterity function on ability to use a handheld inhaler. So how good are you and me in evaluating some of these factors? And the best evaluation is from Dr. Brayman, Sid Brayman. Again, an online survey of healthcare professionals, and you can see in the orange box, physician screening for physical or cognitive impairments that could impact device choices was 53% and 16% respectively. So doesn't sound that great that we're doing the appropriate job in the office. Obviously, time is a factor, but providing optimal care should be number one. So what else does Gold say? Second bullet here, dry powder inhalers are appropriate only if the patient can make a forceful and deep inhalation. Check visually that the patient can inhale forcefully through the device. If there is doubt, assess objectively or choose an alternative device. So let's quickly review how does a dry powder inhaler work. We have the powder here are the black dots on the top left of the diagram. We have the open white circles are lactose particles, which are usually used as a carrier. And the patient has to create turbulent energy highlighted here by inhaling hard and fast through the resistance device in the DPI. So by doing that, the individual pulls the particle away from the carrier and then breaks up the drug particle into respirable size, five micron or less, and then inhales deep into the respiratory tract. And most studies in general show about 20% of what's inside the inhaler, the DPI, is reaching the lower respiratory tract. So we can estimate the turbulent energy by the product of peak inspiratory flow and the internal resistance of the particular DPI. In my practice, we would use an inspiratory flow meter shown here. I have no financial interest in this particular device. And I list here some different levels for peak inspiratory flow measured against R1, which is a low resistance DPI. R4 is a medium high resistance DPI. And I've listed three references down here on the bottom right, which suggests based on in vitro lung models that an optimal peak inspiratory flow is 60 liters a minute or higher. That would suggest that if you're below 60, it's suboptimal. And I recognize that some pharmaceutical companies state, based on in vitro models, that 30 liters a minute is adequate or reasonable to use their DPI, while another pharmaceutical company will say 45 liters per minute is acceptable for their particular DPI. So I'm presenting a concept here. I'm not going to get into individual types of dry powdered inhalers. So if someone has a suboptimal value, what are the potential clinical impacts? And because of time, I'm only going to show you results of two studies. This one was a randomized trial comparing two different LAMAs, teotropium dry powder inhaler and rivifenesin solution, also a once a day LAMA. And patients were selected or recruited by requirement that they have a peak inspiratory flow less than 60 against the R2 level. It was a double blind, double dummy study. And a preselected group for analysis were those individuals with an FEV1 less than 50% of predicted, and of course, a low or suboptimal peak inspiratory flow. The primary outcome was trough FEV1 at day 28. You can see by the brown bar with the dry powder inhaler, there's some improvement, but it's significantly higher with the solution. Similar results, better improvement in FEC with nebulization compared with dry powder inhaler. In this study, the delivery into the lower respiratory tract was not measured, but it is reasonable to assume that patients were able to get better drug delivery with the nebulized delivery system compared with the DPI and having a suboptimal peak inspiratory flow. A second study published last year looked at healthcare costs. It was done primarily in Europe. Cross-sectional, multi-country study, over 1400 patients with COPD, and all were recruited because they were using a DPI as their maintenance therapy for COPD. And one of their key findings was that those individuals with a suboptimal peak inspiratory flow had higher medication costs by 7% and higher total COPD-related costs by 16% compared with optimal peak inspiratory flow. Again, mechanisms were not investigated. So in summary, these are the estimated prevalences of impairment in patient factors. Cognitive impairment, 5% to 63% based on the systematic review. Manual impairment estimated by the online survey that Dr. Anania is first author on, and suboptimal peak inspiratory flow, 19% to 84% based on a review that I perform of six studies. So I'll leave you with the recommendation of gold, and I think there's at least one study to support the shared decision making. We see the different options here on the left. We have the patient on the right. And certainly shared decision making is a reasonable approach in helping you and the patient select the most appropriate delivery system. So I'm going to stop there and introduce again Dr. Adams, who's going to talk about Lama Labas for Group B patients. And hopefully we'll have some time for Q&A at the end. Thank you so much, and I really appreciate the opportunity to come here and speak. We're going to talk about Group B patients in particular, and talk about Lava Lama and that sort of thing. These are my disclosures. I too have a website for education, patient, and professional, White Diseases Foundation. And I want us to look at and kind of critique the gold recommendation for Lava Lama, and talk about why it maybe wasn't earlier than it is now, and why it just came out in 2023. So I'm going to start off with a question. I, hopefully, y'all have been able to put the QR code in. I'll leave it up there just for a minute for the few of you that have just come in. So, which scenario regarding a patient with spirometry diagnosed COPD is most appropriate to prescribe new therapy with dual bronchodilators with Lava Lama, plus a PRN reliever? Sorry. Huh. They did it. They did it the wrong way. Okay. Well, so they're doing the poll question after this. So y'all all got it right. Perfect. Wow. Aren't y'all smart? So let's look at these. So the MMRC of zero, no prior exacerbations, absolute EOs of 50. What group is that in? A, exactly. The MMRC of two, one outpatient exacerbation and low EOs is group B, the ones we're talking about. What about the fourth one? MMRC of four, so very symptomatic, one inpatient exacerbation and absolute EOs of 400. What would you do with that patient? Triple therapy. And Gold now recommends in a single device, if possible. What about the third one? Again, the if possible because of, you know, insurance and other challenges. What about the third one? MMRC of three, no prior exacerbation, absolute EOs of 300. So that one's a little trickier. Technically, if we go exactly by Gold, that patient's in group B because no exacerbations. And so we could, let me just skip through this. We could typically do a Labalama. But I'm not sure that we would be faulted for doing triple therapy because that patient's so symptomatic. But if you go strictly by the recommendations, it'd be Labalama. But with the high Eosinophils, maybe a little bit of asthma in there too, I don't think triple therapy would be necessarily wrong. So let's look at Gold. You know, they uploaded the wrong thing here. So it's not going to have any of the stuff that... Okay. Is there another file on here or was this it? Okay. All right. Well, we'll just move on. And I don't think the videos will actually work. I just uploaded and everything checked out in the speaker reader room. But anyway, when we look at group B, the Lomalabas, looking at symptomatic patients, and why was it that Gold took so long? Well, when you look at these studies, the SPARC trial, the ones at the top, on the Y-axis is the percentage of patients enrolled in those studies who were already on an ICS. And so it wasn't until the EMAX trial that it looked at Labalama in Gold group B, and they were not allowed to have ICS. So when we look at that, the EMAX study, they were 40 years old, symptomatic, very symptomatic, only one or no exacerbations in the last year, and certainly not an inpatient one. Not receiving, not only not receiving inhaled steroid, but not receiving Labalama either. And you can see moderate. And it was Labalama versus Lama versus Laba. And the Laba was salmeterol that was chosen. Primary endpoint was TROF-FEV1, but you can also see they looked at other things like dyspnea, symptoms, rescue medication use, quality of life. When we look at this, we can see, and if you had had my gorgeous slides, you would have seen that the P values are very significant versus the dual therapy versus the Lama alone, and very significant dual therapy versus the Laba. And this is TROF-FEV1 and TROF-FEC. When we look at dual versus monotherapy in dyspnea, the TDI score, basically it's a self-administered transitional dyspnea index score. And higher is improvement, unlike the St. George's where it goes down is better. And you can see at every week, the dual combination therapy did better than the individual. Well, what about things like quality of life? This is a different combination of studies. And we're looking at teatropium alone. And you can see that it's clinically significantly improved in quality of life. Again, St. George's down is better. And there's a statistical and probably clinical significant difference in the combination versus the initial single inhaler. When we look at reduction in overall symptomatic review, systematic review, I think I'm having the symptoms because these slides are not at all what I put up there. So the systematic review, it had nice arrows, nice everything. It was really, they're really pretty if you want to look at them sometime. So there was an 11% reduction in hospital admissions, a 20% reduction in exacerbations, and really no difference in adverse effects. So this one's not going to work because the video didn't, wasn't uploaded. But what we'll do is I'll kind of go through. She's Alexa's 54-year-old woman with GOLD3B. Last exacerbation was four years ago, and she's never had an inpatient hospital stay for exacerbation. She's on a medium dose ICS Labo through the MDI with a valve holding chamber. She's using her reliever two to three times a day, and her MMRC is three. Her CAT score is 14, so she's very symptomatic. Eos are low, and you ask her to show you how she's using her inhaler. So since she can't demonstrate, and I am doing an air demonstration, I'll show you what she did. She shook, great, for five seconds. She took off the caps. That's important. I know a lot of patients, you know, try to squirt it with the cap on. Put it in there. She squirted and put it to her mouth. Is that a problem with a valve holding chamber? It's not, because it's a one-way valve. So she squirted, put it in her mouth, inhaled, and exhaled. So the question is, with that, what would you do? Would you change her ICS, just making sure you're all seeing the same thing I am, change her ICS Labo MDI to a DPI with inhaler education? Would you increase her to high-dose ICS Labo, same mechanism? Would you discontinue the ICS Labo, change to a Labo Lama? Or would you de-see the ICS Labo and change her to triple therapy? Let's see if this will work. Okay, yes. First thing that'll work, yay. I'll give you a couple of minutes or a couple more seconds to vote. All right, let's see. So we had a mix of discontinue the ICS Labo and change she to Labo Lama or triple therapy. So I think that that's important. And the thing is, she's only had one outpatient exacerbation. She's a classic Group B patient. So that was four years ago. She's on a medium-dose ICS Labo, which we'll talk about is not the ideal therapy based on the current recommendations for somebody with COPD. And I'll talk about that data a little bit more as well. And her EOs are very low. So I'm not sure at this point that I would keep her on the ICS, especially if she's not sneezy-weezy allergic. She doesn't have, you know, family history or childhood history of asthma or anything like that, okay? So her issue and the way that I did this incorrectly is I didn't exhale. And then I didn't hold my breath. But the shaking and everything else and even squirting outside is really not a problem. So I would actually say that the third one is the correct one. Correct technique had a nice little video of her doing this, shaking, exhaling, you know, the whole thing. But those are the steps there. And I think a lot of people don't remember to hold their breath. And the other thing is, have you seen this? Anybody seen that? Okay. Well, I explained that the second dose is pretty much wasted. And for patients who really don't want to be wasteful and want to get their medicine, then once I explain that, they're like, oh, no one's ever said just like, just like he said. You know, no one's ever explained that to me before. All right. When we look at the therapy in COPD, these are two large registries that were evaluated. We can see that a large percentage of patients in both of these cohorts of the registries are on ICS-LABA. But despite that, a lot of them are still very symptomatic. With mild to moderate on the left, and with moderate to severe, or severe to very severe, on the right, you can see that a lot of them have MMRC scores of two, three, or four. When we look at dual bronchodilator versus ICS-LABA, so LABA-LAMA versus ICS-LABA, this was with accladenium versus fluticasone cellmeterol, accladenium for motorol. And you can see that this is improvement change from baseline and peak FEV1. And I see that the pointer, you all don't see the cursor, right? Okay. Then descriptions are good as well. So the top one is the LABA-LAMA. And you can see that even though the ICS-LABA, the bronchodilation occurs significantly more in the LABA-LAMA group, best bronchodilation. We look at exacerbations, LABA-LAMA versus LAMA alone, also significantly improvement in, actually this is reduced exacerbations with ICS-LABA versus LABA-LAMA. So the heading should be ICS-LABA versus LABA-LAMA. And you can see it every way. The top line is probability of exacerbations. Orange for those of you who are not colorblind. And the bottom line is the blue line, which is the LABA-LAMA. So you can see it every kind of step of the way, whether there are any exacerbations, moderate, severe, or even the severe were statistically different. How about moderate versus very severe COPD in exacerbations as well? And this looked at LABA-LAMA, teotropium oledaterol versus teotropium. Two, really three studies, one and two of the top one. And you can see that in every respect, it favors the LABA-LAMA. Again, a lot of those patients were on inhaled corticosteroids at baseline. And so I think that's why GOLD has lagged until EMAX came out of saying LABA-LAMA should be the deal for patients with group B. This is a cohort of patients who are followed for like 84 months. A lot of them had like bronchiectasis as well as their COPD and chronic bronchitis type of patients. But if you'll notice, I want to highlight that the biggest issue in the thing that is associated with pneumonia is ICS with low EOs. So again, if they haven't had an exacerbation, an inpatient or two or more outpatient exacerbations, and particularly if their EOs are low, we're probably not doing them a lot of service by leaving them on ICS unless it's for symptoms. So just to show you, ICS-LABA is not recommended anymore for patients with COPD, which is a problem because what are patients on? ICS-LABA. So a lot. And we don't have, other than buried in the text, great algorithms for saying what do we do with those patients? There are a lot of patients out there. They're doing fine. So what do we do? I don't have an answer. But the bottom line is what I'm clinically doing in my practice is if they do have low EOs, they haven't, you know, been having exacerbations and all that, I tend to switch them to a LABA-LAMA. I work in the VA as well as in the county system. So we're somewhat limited by the formularies as I'm sure every person in this room has issues with that. ETS guidelines are actual guidelines from 2020. And they're congruent. Basically, the LABA-LAMA rather than a LABA or a LAMA monotherapy for patients with dyspnea or exercise tolerance. So they're congruent with GOLD as far as group B. So my take-home points. I think proper inhaler technique and careful device selection is important. And hopefully this is like just an add-on to what Dr. Mahler talked about. LABA-LAMA combination for group B improves lung function, breathlessness, quality of life, and reduces exacerbations. And the LABA-LAMA combination even for group B, if you look, for patients in the top on group B, if they do not have high EOs. But again, if they're on LABA-LAMA and then they have an inpatient stay, then they tend to move them over to LABA-LAMA ICS triple therapy. With that, we'll stop. Thank you so much for your attention. Thank you, Sandra. Dr. Hanany is going to tell us why we have group B now. Thank you very much. Good afternoon, everyone. I know we're sort of getting the stretch of the afternoon and it's late based on where we live in the U.S., but hopefully you can give me 15 minutes of your time. I'll try to convince you why I don't serve on gold and I don't agree with everything they say, and I'll show some controversies here. But why did they remove E? And I agree with them with that one, and I'll show you why. You've seen my introduction. These are my conflicts of interest. I do clinical trials in asthma and COPD, none of which will really influence my discussion today, I believe. These are my ambitious learning objectives. I want to discuss the importance of assessing symptoms and exacerbation risk in general. But why is grade E now is the main predominant grade in those patients with high symptom and high exacerbation risk? And what is the clinical implication and how does that affect our choice of initial and subsequent therapy in that group of patients? I do have some questions. My questions are much easier than my fellows here, my fellow colleagues. You'll see, it's just short questions. So please scan this. But let's go back to square one. If you remember, and some of you have white hair like I do, and Dr. Mohler agrees with me, at the initial gold strategy in 2007, I believe, the stretch was we should measure lung function and classify gold severity for 1, 2, 3, and 4. And lung function was used to stratify treatment. Then in 2011, which I will show you in a minute, suddenly and correctly so, we started thinking, it's not enough to measure lung function. We actually need to assess symptoms. We need to assess exacerbation risk. And of course, the comorbidities also got in very correctly. So right now, assessment of COPD in 2023 should not just be based on lung function, although we do use lung function for staging the disease as gold 1, 2, or 3, or 4. But we grade COPD based on alphabets, based on symptom risks and exacerbation risk. Why is that important? Well, there are quite a bit of papers out there. I chose one clinical trial we participated in. And this trial was more to evaluate teiotropium over time and safety and mortality effect. But what I want to show you is that patients will report exacerbation in the past, even one exacerbation. And there, I may argue with gold, two or more. Where did these two come from? Because even one moderate exacerbation, definitely one severe exacerbation increases the risk of subsequent exacerbation. But not only that, symptoms are important. And in this study, we looked at MRC dyspnea. Anything MRC more than 2 signify high symptom burden increases risk of also exacerbation and even mortality in this large study. So that brings me to my first question. Let me see. Hopefully, it'll load. In previous gold strategy, a patient who has grade CCOPD is the one who choose one of these four, please. I told you my questions are easy. Let me see. So should I hit? OK, so high exacerbation risk, low symptom burden. Two thirds of you got it correctly. So that was what goal C is. Well, and actually in 2011, what gold decided to do is incorporate the lung function as well as symptoms. And you can see we had two y-axes. And it was very confusing. So it was less than 50% FEV1 was also incorporated as part of the algorithm in C. But C mainly showed less symptoms and higher risk of exacerbation. What do we know about group C? And that is one of the rationale why group C was dropped off. How common is it? Well, actually, if you look at epidemiologic studies, looking at group C based on the gold 2011 classification, it's very, very low prevalence. 5% in one cohort, another one is 7%. And even when you look at different longitudinal cohorts, the prevalence of group C, like how often can you see patients who have severe disease or have high exacerbation risk but no symptoms? Most of these patients probably, they do exist, but they're not too many. But most of them have poor perception. And is it harmful to have a grade C for them specifically? Nevertheless, they looked at, in other cohorts, they looked at mortality. And you can see group C patients have lower mortality than group B who have high symptom load, and definitely less than group D. So the mortality and prevalence based on gold 2011 for group C was very low. Well, in 2017, things changed. Here, the lung function was taken out, if you remember. So we staged the lung function, and then we grade strictly based on symptoms and exacerbation. So group C remained to depict patients who have high symptom load. I mean, low symptom load, but high exacerbation risk. Well, what do we know about the prevalence of that? When you take lung function out, in fact, the prevalence of gold C goes down even lower. 6% in one of these cohorts in Norway to 3% after changing in the gold strategy. So you can see the rationale of keeping gold C was not justified based on prevalence. And in our COPD gene study, when you look at the classification, the group C prevalence is also about 4% based on 2017 gold. So that is really one of the rationale not to keep gold C and to switch it to gold E. And the real rationale from gold is that, really, we have to focus on exacerbation risk. And that is really the main thing, whether the patient has symptoms or not, that we lump them up in group E. And so that's where group E came in mind. Let me remind everyone, why is it important to highlight exacerbation, or at least frequent exacerbation? Reminder, when we talk about group E, we're talking about one hospital admission or two moderate exacerbation. Now, I might argue that, and I was talking to a colleague earlier today, I think we should have a group H. Because hospitalized patients with COPD, I'm very convinced they're a different phenotype of patients. They're not the same as those who are needing antibiotics, steroids in the outpatient setting. In fact, the mortality of those patients hospitalized for COPD exceeds mortality from acute myocardial infarction. Yet, we undermine the seriousness of that group of patients. So maybe in the future iteration, they will add an H or something else to E. Currently, we're stuck to the two moderate, one severe, as classifying group E, whether they have high symptoms or low symptoms. Why? Because frequent exacerbation, and these are data from multiple studies, have been linked with increased risk of future exacerbation, mortality rate, decline in lung function, poor quality of life, and increased exacerbation. Well, that brings me to my second polling question. And according to GOAL 2023 strategy, the initial pharmacologic therapy for patients with grade E COPD, if you were paying attention to Dr. Adams, she gave it away, which one of these four? This is based on GOAL. Whether you agree with them or not, that's another story. Let's see. OK, well, here we have a split. Two-thirds say triple therapy, and about a third say LAMA-LAVA. OK, well, actually, I'll show you the data. But it is LAVA-LAMA is what they ask us to do. Let me go to the second question, and then I'll show you the algorithm. High blood isoflucon. More than 300 cells per cubic liter at baseline predicts. What do we know about this? Predicts risk of exacerbation. Identify potential benefit from ICS. Suggest underlying. Actually, this is all except. So you have to actually choose the wrong answer here. Sorry. I apologize. This is not me. I gave them the question, and they... So we had a very interesting session on ACO earlier on. And in fact, high blood isoflucon does not always mean asthma-COPD overlap. Indeed, we just completed a three-trial laborious study where actually we excluded everybody with any mention of asthma in the past or diagnosis of asthma. And yes, 20% to 30% of COPD patients, they don't have asthma, but they have what we call type 2 inflammation with high isoflucon. So blood eosinophil and COPD does not reflect underlying asthma. Although in patients with asthma-COPD overlap, they may have high eosinophils. So what do we know about eosinophil? Dr. Adams very nicely mentioned. A low blood eosinophil usually at least predicts patients who are not going to be responsive to inhaled corticosteroids. They may have a different sort of microbiologic profile. They may be at increased risk of pneumonia if you treat them with inhaled steroids. But in general, a high blood eosinophil in COPD patients is usually bad news because it predicts increased risk of exacerbation. But it also predicts improvement or response to inhaled corticosteroids. And possibly for biologics, we don't have any one of them approved. So back to the question, if you look at the previous gold with group C, they had LAMA, and then they had group D LAMA, or LAMA-LABA, or LABA-ICS. Well, the newest recommendation initially is LABA-LAMA unless the patient has high blood eosinophil more than 300. Then triple therapy is advocated. So LABA-ICS, like Dr. Adams mentioned, is no longer in the initial therapy in group E patients. Indeed, the statement from gold says that initial therapy should consist of a LABA-LAMA. Consider triple therapy in one inhaler device if possible if eosinophil count more than 300. Now, you may argue, why 300? Because there are clinical trials that show that blood eosinophil more than 150 or more than 100 can have increased risk of exacerbation. But currently, this is what the strategy is for initial. What about subsequent treatment? The previous gold, 2017, subsequent therapy was either LABA or LAMA initially, plus LABA-LAMA. But as you see, LABA-ICS was there, and then de-escalation. The new strategy now is to do what we call treatable approach treatment. So a patient with predominant dyspnea, who is group or grade E, you treat them with LABA-LAMA combination. Consider switching. We heard very elegant talk about inhaler devices, because not always that these patients are not responsive, because the drugs are not working, but maybe they're not using their inhaler correctly. On the other hand, if you have the exacerbator phenotype, the newer strategy, which is shown here, this is the previous one. As you see, very succinctly mentioned that LABA-LAMA-ICS, especially if their blood eosinophil is more than 100. So you may argue, why is it 300 there and now 100 here, more than 100? But definitely, if the blood eosinophil is less than 100, then you may look at other treatment strategies. And I think one of the things that drove this is the clear evidence of triple therapy in COPD patients, in high-risk group D patients with recurrent exacerbation. We've had landmark studies. I don't know if you're all familiar with the ethos and impact. These are two landmark studies. There are others, but these are the ones that at least were done in the United States along with other countries. No matter what delivery system you're looking at, whether it's an MDI here or a DPI, a triple therapy was superior in reducing exacerbation in this high-risk population, many of which have high blood eosinophil at baseline. But not only that, but there is actually very intriguing data, although these are secondary endpoints, on mortality reduction. In fact, for the very first time, GOLD adopted a table showing what can reduce mortality in COPD. And for the very first time, they mentioned triple therapy in this population in high-risk grade E population. So therefore, I think we are sort of shifting based on our knowledge about triple therapy in this disease. Now, let's not forget that, of course, group E patients, like it is with other groups, we have to keep in mind our non-pharmacologic approaches. Obviously, nothing has changed a lot in this field. Of course, pulmonary rehab, very important physical activity, and of course, the vaccination part. So my take-home message is assessing symptoms and risk of exacerbation is very important to not only classify patients, but to identify patients at risk of subsequent exacerbation. Eliminating grade E from GOLD assessment, emphasizing for us as clinicians the importance of identifying high-risk exacerbators, who usually, by the way, have also high symptom burden. I showed you the old grade C prevalence was very, very small. Maximizing bronchodilator therapy in such patients is the initial step unless they have significant eosinophilia. Triple therapy would be the next step if they have high blood eosinophil more than 100 and continue to have symptoms or exacerbation. And the use of ICS-LAVA as dual therapy is now discouraged and abolished from our treatment strategies. Thank you very much. Thank you.

GOLD 2023 strategy

COPD management

symptom burden

exacerbation risk

blood eosinophil levels

Group E classification

triple therapy

inhaler technique

pulmonary rehabilitation