All right, let's get started. I am Alejandro Diaz from Brigham Young Hospital in Boston, and I am a member of the editorial board of the Chase Journal. So we are proud to present today the Canadian Thoracic Society Guideline on Pharmacotherapy in Patients with Stable COPD. So we have here two authors of this guideline, two active participants of the panel, Dr. Erika Pins and Dr. Darcy Marcinik from USASCA. So let's get started with Dr. Erika Pins now. Good morning, everybody. It's lovely to see so many people out so early on Wednesday of our CHESS conference. My name is Erika Pins, and I'm really honoured to co-present the Canadian Thoracic Society Guidelines with my colleague and mentor, Dr. Darcy Marcinik. In the next hour, we're going to review the new guideline recommendations for pharmacotherapy of stable patients with COPD, and we're also going to highlight how to integrate these guidelines into the comprehensive management of COPD patients through a new pharmacotherapy pathway. As I mentioned, my name is Erika Pins. I'm an associate professor at the University of Saskatchewan in Saskatoon, Saskatchewan, and a co-author of these guidelines. These are my disclosures. The guidelines were co-published in September of this year in CHESS online, as well as the Canadian Journal of Respiratory Critical Care and Sleep Medicine. The print edition will be coming out in the next edition this coming month in CHESS, just for everybody's information. So why are these guidelines now relevant, or continue to be relevant? Well, as we all know here in this room, the burden from COPD remains immense. In this Canadian study just published this year, what we've seen since 2010 is a continual rise in admissions to hospital for COPD over this time. And this is even after adjusting for our growth in population, as well as aging. And this is also despite a declining trend in rates of admissions for all-cause hospitalizations. So the Forum of International Respiratory Societies published the Global Impact of Respiratory Diseases in 2021. And they also identified COPD, along with asthma, TB, respiratory infections, and lung cancer as the big five contributors to respiratory illnesses and mortality worldwide. And we see that COPD infections and lung cancer remain three of these diseases in the top 10 causes of death worldwide. And when you look at deaths from respiratory diseases worldwide, COPD accounts for 82% of these deaths. So going into our guideline, we included randomized control trials only for this guideline. Risk of bias for the trials was assessed by two individuals and then confirmed by the methodologist on our team using the Cochrane Risk of Bias Assessment Tool. Certainty of the outcomes were evaluated using a grade process and considered components like study design, risk of bias, inconsistency, imprecision, and indirectness. And then quality of evidence was also assessed using the Grade Pro Tool and rated as high, moderate, low, or very low. The strength of each recommendation was also determined based on the totality of the evidence. And when there was lack of evidence for this guideline, the panel indicated this, and then we employed an expert consensus opinion. So there was a comprehensive search for our three PICO questions, which I'll tell you about in the next slide. But this was basically for the first two questions, the first two PICO questions, our search was updated from our last guideline, so from October 2018 up until June of 2022. And then for PICO 3, which was a new question added to our guideline this year, our search extended from 1974 to June 2022. Ultimately, 203 studies were included in our quantitative synthesis and the meta-analysis process. So our PICO questions, we had three. Two of them were updates from our last guideline, Pharmacotherapy to Guideline in 2019. And then the third PICO question was, you know, how as clinicians do we choose appropriate maintenance pharmacotherapy in our stable COPD patients to reduce mortality? So we review both reducing symptom burden and improving health status in PICO 1, reducing the risk of exacerbations for PICO 2, and then mortality for our PICO 3 question. So outcomes that we considered, and I'll run you through them, were dyspnea, health status, exercise tolerance, physical activity, lung function, and adverse events. These were all assessed through our PICO 1 question, exacerbations for PICO 2, and then mortality, as I mentioned, for our third PICO question. And then we performed meta-analysis if there was more than one study which reported an outcome. And as I mentioned, only randomized controlled trials were considered for this. So in terms of our review process, we independently invited a formal review for this guideline by five external non-CTS content experts. We had two internal CTS members also review, and then we aligned our peer review process with both our Canadian journal and CHESS journal to obtain feedback and then incorporate suggestions over that time period. So in addition to the manuscript, which you'll see, we also have additional almost 300 pages included in appendices, which basically summarize the totality of the evidence that was reviewed for this guideline. And then just in terms of presentation of our recommendations, what you'll see is that we present for each PICO question along with any clinical marks in a table format, and we summarize the strength of the evidence, the certainty, and then where you can find that in terms of in the supplementary material pulled from the meta-analysis. So we're going to start with now the recommendations that we covered in this guideline. So for PICO 1 recommendation, in our COPD patients with low symptom burden defined by a modified MRC score of 1, a CAT score less than 10, or unpreserved lung function, an FEV1 equal to or greater than 80%, we recommend to initiate maintenance therapy with an inhaled long-acting bronchodilator. And we don't recognize any significant difference between a long-acting muscarinic antagonist or a long-acting beta agonist. So this recommendation is a change. Our prior recommendation in our 2019 guidelines was to initiate treatment with SAVA as needed. And our clinical remark that we have here is that basically the studies that we included in this assessment in this part of the PICO question, you know, were individuals obviously with spirometry-confirmed COPD, but not every study compared either LAMA or a LAVA monotherapy to placebo with every single aspect of these like we did in terms of FEV1, CAT scores, or MMRC. But we value the importance of having a precise sort of consensus working definition of COPD with mild symptom burden and what we've recommended as regular long-acting bronchodilator therapy. This is just to, I won't walk you through this, but just so you're aware in, as I mentioned, as complementary to every recommendation, are these summary of evidence tables as well as the forest plots describing the meta-analysis that supports the recommendation. So now in terms of those with moderate to high symptom burden and a low risk of exacerbation. So this would be an MMRC of 2 or greater, an FEV1 that would be less than 80% predicted, and a CAT score of 10 or more. We recommend to initiate now maintenance therapy with LAMA-LAVA dual bronchodilator therapy. Again, this is a change from our prior recommendation where we had previously recommended initiation with a LAMA or LAVA monotherapy. And our clinical remarks in this regard is basically LAMA-LAVA dual therapy is preferred over ICS LAVA combination therapy due to the significant improvement that we see in the studies in terms of lung function and also lower rates of adverse effects such as pneumonia. However, there's a caveat where ICS LAVA combination therapy may be preferred to LAMA-LAVA dual therapy in those individuals with COPD and concomitant asthma. So improvement in exercise capacity may not lead necessarily to, you know, the goal for us which is improvement in physical activity for our patients without adding an additional behavioral intervention. So we recognize that in addition to what we're recommending in terms of pharmacotherapy for this population. Okay, so how about those individuals with moderate to high symptom burden and a low risk of exacerbations who are already on dual LAMA-LAVA or ICS LAVA therapy? Well, we recommend stepping up to LAMA-LAVA ICS triple combination therapy. And this, in fact, is no change from our 2019 guidelines. And really we provide sort of the clinical remark that acknowledges the two additional studies that have been published since our 2019 guideline with ethos and impact where we were looking at individuals with COPD who, yes, of course, had high risk of future exacerbations, but they provided strong evidence in those trials where we saw improvement in dyspnea with combination therapy compared with the dual combinations. So we extrapolated to this population who are at low risk of exacerbations, but likely with similar symptom burden that we see in our practice. So then this is just to summarize some additional recommendations that we addressed with the PICO-1. So in those who were at low risk of exacerbations with a moderate to high symptom burden, if people were taking triple combination therapy, we suggest continuing with that therapy rather than stepping down to LAMA-LAVA dual therapy. This is actually not changed from our 2019 CTS guidelines. For patients who are on dual therapy with LAMA-LAVA, we do not suggest stepping down to LAMA monotherapy. And again, this was a change from our last COPD guideline. And then we do not suggest adding any oral additional medications to improve symptoms of dyspnea, exercise tolerance, physical activity, or health status to individuals in this population. So at low risk of exacerbations. So just to confirm, I'm going to move on to PICO-2 and PICO-3 next. In terms of how we define exacerbations, we, in this guideline, classified consistent with the other definitions that you see in other papers into low risk and high risk of future exacerbation to basically align with the individuals that were enrolled, particularly in the more recent ethos and impact studies. So low risk of exacerbations is defined as one or less moderate exacerbation in the last year, and they could not have been to the emergency room or hospitalized for that exacerbation. High risk exacerbations are individuals who'd had two or more moderate exacerbations or one or more severe exacerbations in the last year, which did require a hospital admission or ED visit. And we align the pharmacotherapy recommendations according to low risk and high risk individuals. So for choosing amongst pharmacotherapy amongst individuals with COPD with moderate to high symptom burden and low risk of exacerbations, we recommend starting with LAMA-LABA dual therapy as the initial maintenance therapy. So this is a change from our prior guidelines, and again, it aligns with what we've recommended in PICO-1, which is initiation of therapy for the purpose of reducing exacerbations in this population. We also state here that LAMA-LABA dual therapy is preferred to the ICS-LABA combination therapy due to significant improvements that we see in lung function and lower rates of pneumonia in the studies. However, again, ICS-LABA combination is preferred in those individuals who have concomitant asthma. All right. So for those individuals with COPD, stable COPD with moderate high symptom burden and now high risk of exacerbations, we recommend initiation with LAMA-LABA ICS triple combination therapy as initial maintenance therapy in this population. This is a change from our 2019 guidelines, and our prior recommendation in this high risk population was to initiate either LAMA-LABA dual therapy or ICS-LABA combination therapy. And our clinical remark here is that for individuals meeting this definition of high risk of exacerbations, that the two large studies impacted ethos demonstrated the benefits of triple combination therapy versus dual therapy in this population for the purpose of reducing exacerbations, and that's what really drove the recommendations in this case. Okay. So for, again, PICO number two, in those patients who are moderately high symptom burden and continue to have high risk of exacerbations, we do not suggest stepping down triple therapy, combination therapy to a dual combination therapy in this population. This is actually not changed from our 2019 guidelines, and really our comment here, the clinical remark is that withdrawing an ICS, in addition to possibly lowering health status and lung function, can be associated with increased risk of moderate to severe exacerbations. And this could be particularly important in those individuals who may have blood eosinophil levels greater than 300 cells per microliter. And then a summary here in terms of a couple other recommendations in this PICO two section is that those individuals with high symptom burden and who continue to exacerbate on triple combination therapy, we recommend the addition of macrolide maintenance therapy in those individuals with a normal QT interval on their ECG, no significant harmful drug interactions with other medications they may be on, and no evidence of an either indolent or active infection with atypical mycobacteria. This is not changed from our prior CTS guideline. And our clinical remark here is that really as clinicians we should weigh the benefits against the risks of microbial resistance, possibly hearing impairment, and even cardiac arrhythmia related to QT prolongation in chronic macrolide use. In those individuals who, again, continue to exacerbate despite being on triple therapy, we suggest now, so our recommendation is to suggest the addition of either riflumilast or N-acetylcysteine. So this was a change from our prior guideline. In our prior guideline we had recommended these two oral agents in those individuals, we now have downgraded that to a suggested. We do continue to recommend against the use of theophylline or systemic oral steroids for maintenance treatment in our COPD population here, which is not changed. And then, again, we state there's no rule for ICS monotherapy, and really ICS should only be used in combination with other bronchodilators in our COPD population. All right, so for PICO-3, this is, again, as I mentioned, a new question added to this guideline, and this asked around those individuals with moderate to high symptom burden and high risk of exacerbations. We now strongly recommend in our guideline the use of LAMA-LABA ICS triple combination therapy over LAMA-LABA and over ICS-LABA combination therapy for the purpose of reducing mortality. So this is new from 2019, and really what we see is the clinical remark here is the greater benefit that we see in our triple combination therapy over LAMA-LABA dual therapy as well as ICS-LABA is not only for reducing mortality, which was what we assessed in this outcome in PICO question, but in fact the benefits that we see with improving overall dyspnea and health status, lung function, but also preventing moderate to severe exacerbations, which is a major risk factor for morbidity and mortality in this population. And then you will just see we highlight here sort of the totality of the studies that were considered for this particular PICO-3 question. So in terms of when we look at the risk ratio for mortality, the inclusion was five RCTs, where we see a relative risk reduction of 0.71 in ICS combination therapy versus LAMA-LABA. When we look at the hazard ratio, we only had one RCT that reported that with a hazard ratio of 0.67. When you look at the triple combination therapy versus ICS-LABA combination therapy, we had five RCTs that informed this recommendation, looking at the relative risk ratio of 0.94 with a confidence interval over one, and also the hazard ratio of 0.95 in this group. So I'm going to hand it over to Darcy, and we can take questions at the end. Thank you. Yes. Thank you. Well, good morning, and thank you very much for the opportunity and also to co-present with Dr. Penn's, my colleague. This is my conflict of interest disclosure. So we've heard about the recommendations, and we know that there's about just shy of 300 pages of information, and it tells a story, but it's essentially a very long story. So one of our intentions was to consolidate the information into tools, and I'll show you some new figures, that make it easy for practicing clinicians to be guided to do the right thing for the right patient. And we had had prior figures and guidance in our past guidelines that had been well-received, but we've updated them with the new and, in some cases, very compelling evidence. I've shown here what GOLD2023 has for, on the left, is for the initial pharmacologic treatment for groups A. I have to be careful not to put a laser pointer in any of my colleagues here, for A, for B, and for E. And then, finally, the follow-up pharmacologic therapy for those with a predominantly dyspnea phenotype versus those with a predominantly exacerbation phenotype. And I think it's a bit complicated, and I think it's a bit hard to follow. And I'm not saying that in a judgment. This is a tough sort of field. But remember, GOLD is also a consensus statement. It's not a guideline. They do not perform a meta-analysis. And it changes from year to year, as much of our evidence does. So we've constructed something that I think, and hope, will be easy to follow. And it aligns with our PICO questions, and the evidence, and the strength of the evidence. So we've provided three sort of streams, mild, moderate, and severe, coalescing the moderate and severe. So the mild are individuals with COPD, so they have obstruction, but a CAT less than 10, and an MRRC of 1, so a low-symptom burden with an FEV1 greater than 80%. So it's very mild. For moderate and severe, those are categories with a CAT greater than 10, or equal to 10, an MRRC 2 or more, and an FEV1 less than 80%. And again, when you stratify the lung function, 50 to 80 would be moderate, 30 to 50 would be severe, and less than 30 would be very severe. In all instances, a short-acting bronchodilator should be used and utilized by patients as needed, as a package, in addition to their maintenance therapy. So again, for low-symptom burden, as recommended, as Erica mentioned, a LAMA, long-acting muscarinic antagonist, or a long-acting beta-2 agonist, as maintenance therapy. The implication being that all patients with COPD who are symptomatic, even if it's mild, should be on maintenance therapy, in this case with a long-acting beta-2 agonist. And that was a change from our prior where we, in fact, did start with, as needed, a PRN, short-acting bronchodilator. And that's because of the evidence in terms of improving those outcomes. And then for moderate, as was described by Erica, we've divided into those at low AECOPD risk and defined that, and high AECOPD risk, and we've partnered that with an increased risk of mortality. And you'll see that also in the recommendations. Because those are the individuals that are higher risk of mortality, turn that around, also likely to benefit from the therapy that has been demonstrated to reduce mortality, in addition to the other endpoints. And so for this, as Erica mentioned, combination, dual-combination therapy, long-acting muscarinic antagonist, long-acting beta-2 agonist, there's an asterisk here. I'll show you on the next slide the figure legend, because there's some descriptors to help guide. And then, if you still have unmet needs with persisting symptoms, you would go to triple-inhaled combination therapy. And we do have text preferring single-inhaler triple therapy over multiple inhalers, although there is some judgment left for that. And then finally, in the high AECOPD risk that is associated with increased risk of mortality, initiation therapy with triple combination, single inhaler, because it reduces mortality. So these would be individuals, for instance, going home from hospital who have had an exacerbation, who survived, who are being discharged. A quality indicator in this case would be they should all be discharged and receiving and adhering to triple-inhaled therapy. And then finally, if there are persistent exacerbations and so forth, despite that, we would add oral therapies and we provided a pathway for that. So this is our scheme for pharmacotherapy. We like it because it stratifies and it kind of aligns with what we see when we assess patients, symptoms, exacerbations. Secondly, we've eliminated the going back or pulling back from therapy because COPD is not a disease that gets better. And so if you're receiving benefit from therapy, we don't believe it's appropriate to pull back and see what happens and then increase and such. It's maintenance therapy, as long as it is initiated appropriately. Now we all have some patients where sometimes they're on therapy and they should never have been started, then you need to recalibrate and readjust as appropriate. So in that legend, it speaks to LAMA, LABA, single inhaled geotherapy is preferred over ICS-LABA, as you've heard, considering additional improvements in lung function, lower rates of adverse events such as pneumonia. But if there is COPD with concomitant asthma, then ICS-LABA might be more appropriate. Okay? And you're getting the benefit of ICS in that specific phenotype, that specific type of patient with asthma in association with significant obstruction. And then we do mention here that triple inhaled ICS-LAMA, LABA combination therapy should preferably be administered in a single inhaler therapy. And there is some text in the document that speaks to why with references and not in multiple inhalers, although we acknowledge some patients continue to prefer separate inhalers. But we know that we can sometimes help guide patients to the best therapy, to optimize the therapy when they become fully informed. And the outcomes are better with a single inhaler. So just from the pharmacotherapy, some important implications. Long-acting bronchodilators, be it LAMA or LABA, are maintenance therapy for all symptomatic patients with COPD. So we should not have patients who are symptomatic with COPD just walking around with a puffer in the pocket that they use as needed. They're not realizing the benefits of therapy. For individuals with moderate severe disease, CAT-10 or more, MMRC-2 or more, FEV1 less than 80%, with a low risk of exacerbations, that means they've had one or none without a visit to the emergency room without a hospitalization. Dual therapy is now indicated. And again, the evidence is pretty strong in terms of those symptomatic benefits and the appendices and the text tells that story. And then finally for individuals with moderate severe disease but who have had two or more exacerbations or visited the emergency room appropriately or been hospitalized, triple inhaled therapy is now indicated because of superiority in many endpoints, including a significant reduction in mortality. And we're able to coalesce all that data. So we didn't just look at one study and the conclusion, all of those studies. We've got tens of thousands of patients from multiple studies to demonstrate that. The meaning for individuals discharged from hospital, that would be appropriate therapy or two outpatient exacerbations that are managed. And then finally, if you believe this, and the data says we should, there's recommendations, strong recommendations, we need to think about targeted case finding for strategies to find these patients so that they can be put on appropriate pharmacotherapy, and I'm going to talk about comprehensive care in a moment, so that they can realize this benefit. So we know that there are many patients with COPD who have never had spirometry, 10, 12, 15% who actually don't have COPD. But we know there are many patients or individuals not diagnosed because COPD is underdiagnosed in about, whatever you believe, but about half of those patients have moderate, severe or very severe. They're experiencing symptoms or even being admitted to hospital and attributed to other reasons, but they're not able to realize the benefits. So we have to kind of rethink our case finding, our targeted testing in order to align the benefits with these individuals. Some known, some we don't know about, but we have to go looking for them. So pharmacotherapy is only one part of the picture for COPD. So we've also constructed a guide to make it easy to put together and partner, align the right therapy with what a patient's symptoms, but also their needs are. And this is, again, it's a variation of what we had in our prior document, speaks to the comprehensive management, and we've identified at the very top, and this is new, the goals of therapy. These are specific goals and they are all achievable in terms of alleviating, reducing dyspnea, improving health status, preventing exacerbations and reducing mortality. That's our targets. That's why we're doing what we're doing. We've also emphasized the importance of diagnosis confirmed by spirometry. As things get a little bit more progressed, to think about advanced care planning, and then finally, when it is appropriate, where the goals of therapy may change, end-of-life care. We didn't speak to that, but it's sort of a continuum there that we've provided reminders and it kind of parallels what we do in our clinical practice. At the base, at the foundation, we've again provided these clinical indicators. So lung function impairment for mild, moderate, severe, very severe. The MMRC, remember zero would be normal, so one to four. Health status, CAT score, and we've now implemented a CAT in our waiting room while they're waiting to see myself or my team. They do the CAT score. It takes not long at all and we follow it. It is responsive to interventions and over time and severity. It goes from zero, but less than 10 to 40. And then finally, the mortality risk, which is more of a binary where it's low, one or none, or high, two or more, or hospitalization, or emergency room visit. And I'll show you once we climb to the top how we put that to work. Everybody, so these bars, the yellow bar and the blue bar, are completely from left to right. So everybody should be receiving, advised, activated for self-management education so they become good patients. They know what to do. They know when to call for help. They know how to adhere to their medication and so forth. Smoking cessation, if appropriate. Exercise and active lifestyle. Vaccinations. And then inhaled short-acting bronchodilator therapy as needed on a peer and as needed basis. And then finally, blue links up with the algorithm I just showed on the past few slides for inhaled maintenance preventive therapies. So that's guidance for everybody. And then as disease severity increases, pulmonary rehabilitation and there's good evidence for patients with moderate, severe, and very severe. We don't know about mild because the data is just not there. But exercise helps everybody. It would be unusual for exercise not to help people with mild COPD as well. But we have pretty good compelling evidence for moderate, severe, and very severe. The benefits and a number of endpoints for pulmonary rehabilitation. I'm going to show you some data as well. Other pharmacotherapies and I'll define that in the legend in one of the upcoming slides here. But that's oral therapies, alpha-1 antitrypsin and so forth. Oxygen plus or minus non-invasive ventilation. We have guidelines. Canadian guidelines, ERS guidelines, ATS guidelines, when to implement that. And then finally, surgical or endoscopic therapies. We've provided some guidance that assessing severity in any of the four categories as the base of the figure, that's these ones, lung function impairment, MMRC, CAT, or mortality, guides the therapy by these very light gray bars which you probably can't see but I can. But it is not stepwise. We don't start here and then climb a step. What we do is we assess and you don't have to do all four at once. If you only do one, you kind of place a green here or whatever whereabouts are you and then you draw a line up. And our guidance is if this is low and this is medium but this is here, you take the one farthest to the right and you go all the way up and you consider those interventions which include both pharmacologic and non-pharmacologic. And in some of the CAT, the knowledge transfer, the implementation work about this, we have some case studies that provides guidance for practicing clinicians. And we have to remember, we don't see everybody with COPD. 80 plus percent of patients with COPD are managed in primary care. So we have to make this presented in such a way that they do the right thing, they're able to recognize what the appropriate intervention says, follow up and so forth. So in this regard, we've provided some guidance. So a long legend backing this in the text, and I've just summarized some of it, that the inhaled maintenance or preventive therapies include LAMA, LABA, ICS, and ICS monotherapy should not be used in COPD management. And we've learned there's a bit of repetition in the document because we've learned that sometimes people just extract the figure and put it into a presentation or just look at the figure and they're not going to look at the text. So we've made it harder to be misinformed by a bit of repetition. Other pharmacotherapies include oral therapies, as you've heard, azithromycin, riflumilast, and acetylcysteine. Alpha-1 antitrypsin augmentation therapy, there are other guidelines and situations for that. We did not address that in this document. And then finally, opioids for severe refractory dyspnea, we have prior guidelines, but that's also a changing, evolving field. We did not specifically address that. And then surgical therapies, and again, it's different where you are, whether you're recruiting for studies and such, but would include transplantation, lung volume reduction, largely now with endoscopic fills. So in terms of the comprehensive management, so we've talked about the pharmacotherapy and that was a specific intention, disciplined intention of the guideline, and we've provided all the evidence. But we did want to put it together so that clinicians are better able to deliver comprehensive care. So some of the evidence, and I've just abbreviated some here, this is a study Rich Cassabury published in CHEST in 2005. Individuals with pretty significant severe COPD and FEV1, 34% are predicted, who were followed for six weeks. And this is their endurance time on a treadmill, walking endurance time. At rest, after four weeks of therapy, after eight weeks of rehab, and then follow up to six months. And the intervention in this case was either a short-acting bronchodilator in gray, or a long-acting, in this case, a muscarinic antagonist deotropium in blue. And after four weeks, they then went targeted, goal-directed pulmonary rehabilitation, and then the end. So there's a few messages here. First of all, you know, more effective bronchodilation, blue is better than gray. Secondly, look at the lift in both, the pulmonary rehab. It allows people to have better lung function and then realize the benefit. And that alludes to the point that Erica made. You can improve exercise tolerance, but without behavioral and programs like pulmonary rehab, a patient may not realize the benefits. I can double someone's lung function, but if all they're watching on TV or their whole life is watching Netflix and White Lotus, that doesn't really, you know, allow them to improve how far they can walk. So that has to be partnered. But at this time, probably the most important benefit, learning, and this was for all of us, you know, we used to hear irreversible, not much we can do. These patients were walking nine or ten minutes, and then at the end of simple interventions, LAMA therapy, pulmonary rehab, you're up to 22 or 23 minutes on a treadmill. So that's pretty powerful. It can be done. Patients can realize the benefits with some of the interventions we've discussed. Similar with pulmonary rehab, this is a cohort retrospective, so it has lots of limitations, but it's interesting that in 197,000 patients in the United States who are admitted to hospital with acute exacerbations of COPD, survive, and we know the in-hospital mortality rate's about 7.8%, just like it is for acute coronary syndrome, discharged, that there's a difference in re-hospitalization rate for those who are participating in pulmonary rehab within three months, 90 days of discharge, versus those who are not, or after 90 days. So it's a pretty significant risk reduction. It's kind of interesting. It's also kind of interesting that in a cohort, similar cohort, about 200,000 patients admitted to hospital, survived, discharged, that there's a difference in mortality, an association for those who participate in pulmonary rehab within 90 days, and those beyond or not at all. Lots of reasons why this might be the case. This is not a randomized controlled trial, so it has limitations, but on top of all the other evidence that we get from pulmonary rehab, I think there's benefit here. And the last thing I wanted to speak to was multidisciplinary integrated care of our patients, so programs, healthcare system practices that put together, enable all of what we're doing. So Cochrane, this was published in September 2021, defining multidisciplinary as two or more healthcare professional disciplines and two or more components. So for instance, inhaled therapy, exercise, behavioral, all sorts of things, for at least three months duration. So this is the integrated disease management interventions for patients with COPD. And what they found when they put everything together, and Cochrane, they know how to do their work. Health-related quality of life was improved. Remember this St. George's respiratory questionnaire, lower is better. Four is clinically meaningful. They weren't able to do a responder analysis, but it's down 3.9 at 12 months. Improved quality of life. Exercise improved 44 meters at 12 months. And here the MID is 30 meters, so they're able to walk farther. Healthcare utilization attributable to respiratory-related diseases is reduced by about 36% over 12 months. All-cause hospital admissions, about 25% reduction over one year, with 2.27 less hospital days. And you don't need a calculator to say that's good. We don't want patients in hospital. We don't want patients, because that's a big pathway to mortality, to increased symptoms, to re-hospitalization, to more exacerbations and so forth, quite aside from saving money. And then emergency room visits are also down by 31%. So we know we've got pretty good, pretty compelling evidence that we have effective pharmacotherapy, effective non-pharmacologic therapies, and healthcare system practices that we can make a difference for our patients. So the bottom line is, for a disease that is the third most common cause of death in the world, COVID's played with this a little bit, but it's going to recalibrate. And the second most common reason for admission to hospital, and I'll add in Canada, the most common reason for being admitted to hospital in Canada is childbirth. That one I get. COPD I don't. And the chronic mental condition with the highest cost to our hospital systems, again, this is Canadian data, it's about 50% higher than heart failure, which is number two. So it's common, it's expensive, and a disease that causes so much suffering and disability, we know that. We see that in our patients, we live that every day as we're taking care of them. We do have many effective interventions and strategies, including pharmacologic, non-pharmacologic, and healthcare system practices, and I hope that our updated CTS guideline will further amplify, further assist that, inform that if we use it properly, targeting therapy with specific patients, and we've provided guidance how to do that, that we can improve the care and outcomes for patients with COPD. So on behalf of Erica and I, thank you very much, and we'd be happy to answer any questions. Thank you.

Stable COPD

Pharmacotherapy

Guidelines

Bronchodilator

Exacerbations

Symptom burden

Maintenance therapy

Comprehensive management