Chapters Transcript Video COPD 2023 OK. Well, welcome back. Our second topic uh similar to the first is on lung disease. Um And uh this is a picture in the background of M US C is this cancer that keeps growing across all of downtown um that uh builds a new building every year. But uh we think it's uh the Genesis of the Atlantic Ocean where the Ashley and the Cooper River is just uh are the center of the universe. And so we have a little bit of intrinsic biases there. But uh I think it's a nice picture. Uh My disclosures are the same and if you remember last lecture on asthma, we recognize asthma is this uh disease that you can use bronchodilators and get normal lung function. And what that does is it leaves COPD is everything else. And the numbers of patients with COPD in America and the number of people with asthma in America are almost identical. It's about 7% of the population with each uh disorder. We have a lot of misdiagnosis, a lot of under diagnosis and uh and COPD that um probably is not quite as common in asthma. We recognize that there are people that have chronic bronchitis. And if you happen to get a chest ct scan and see some holes in your lungs, the definition of emphysema, some of those people actually have normal sperry. So, uh there are some parts of this VIN diagram outside of the box. But the point is that spirometry uh makes the diagnosis of COPD much the way in A one c makes the diagnosis of diabetes just the same way that um many of our uh diagnoses have tests. Um So let's kind of talk about what we can do and what we can't do about COPD. Um There is uh in this picture of the alveus emphysema is a disease that has holes in the lungs. And so we only have 300 million vo I in our lungs. And what happens when we break down that little inter Alvear septa and you have two V I become one is that you start getting air space enlargement. And so in this diagram, we're losing the connective tissue matrix of our alveus and we get holes and then some of the holes then coalesce and make big bigger holes over time. But by losing that connective tissue matrix inside the lung, what also happens is we're losing the connective tissue that helps hold open our airways and our small airways when we exercise, get some lateral pressure on them and will collapse. And when they collapse, they trap air inside of our holes in our lungs, emphysema. And the point is that we don't have any medicines that fix airways collapse. This is the unfixable part of the fixed obstruction associated with the emphysema phenotype of COPD. And so sometimes they explain to patients why aren't these medicines working well? You, you can kind of go into, uh, there's some parts of this where we've damaged our small airways in addition to the emphysema. Uh, but it's really an airways disease that causes obstruction, whether it be asthma or COPD. The alternative diagnosis to emphysema is chronic bronchitis. And what happens here is that we have little cells in the airway called goblet cells that make mucus. Uh There are also some submucosal uh glands and after smoking for 20 years, uh you proliferate your goblet cells, the mucus glands grow and the minute you put down your cigarettes or any other chronic airway injury, the cells don't go away. You are a mucus hyper producing patient for the rest of your life. So, there's part of that that we can't fix. Although over six months to a year after smoking cessation, we do see the amount uh the volume of mucus decreasing. So, uh I would mention that we really don't have great therapies for mucus. Um And so it's a new topic and there's a lot of interest in trying to figure out if we can do something other than uh therapies, uh such as Gin Mucinex and others Mucinex. You take thick globby mucus inside of a test tube. And you add it, it makes it thin and watery. But in the airway, what that means is you actually increase the volume of your mucus while at the same time making it less thick. And so we'll sometimes turn on these therapies. We just don't leave people on these therapies because now you get the cough from excess mucus uh volume that happens as a result of all of our current mucolytic therapies. And I'll show you in the end of our talk, some of our strategies that we're thinking about how to decrease the goblet cell number uh and hopefully treat chronic bronchitis, predominant patients a little bit better. Ok. So what does COPD look like? Um We recognize that um we're, we've fallen from the third leading cause of death to the sixth leading cause of death. COVID beat us out these past few years. Shucks. Um But we're still up here pretty high cost. Uh New cost SS are heading towards $75 billion a year that we spent on this disease uh very prevalent even though smoking has been more effective. And all the great news about only 12% of Americans now smoking that came out this past month, we still have the 30 year tail of this. That means we're going to keep on having COPD at least be stable for a long time because once the onset of COPD is diagnosed, we usually have 20 more years with this disease, which makes it one of our favorite diseases in the claim to treat because these are your lifelong patients. They're coming to see you all the time and just like our chronic pain, uh speaker less than two hours ago, uh, you really can help these uh people and some people uh really embrace the whole COPD patient population, others, uh, the patients kind of tell those move on if you don't have anything to offer them. Um Yep. So uh it is a disease of the aging lung. And what that means is that our prevalence increases as you get older. So we think that's about 9% in the 45. Uh You're an older group for the past 20 years, women have had more COPD than men by a fairly sizable uh number. And we think that's because women's lungs are a little bit smaller and therefore the effects of cigarette and other airway particulates uh will have a disproportionate impact. Um This number has been very stable for a long time. This is 2020 data out of our CDC behavior risk factor surveillance study. But 25% of those of COPD have never smoked. And so if you're using smoking to think about COPD or missing a quarter of the patients, as opposed to using spirometry, the diagnostic test to think about COPD in which case you'll be accurate. Um Yeah, less than half saw a health care practitioner. And because this is a disease of the Aine Lung, the most frequent uh male practitioner, they see as the urologist rather than the, uh, than you. Uh And so the point is that this crosses all disease states, all different subspecialties. Uh, and the undiagnosed burden of COPD that it's 30% of all patients is really quite high. And then what does that mean? Well, people show up in the emergency room all the time with an acute exacerbation, but don't really have a diagnosis of COPD written on their chart and when it is on their chart and they haven't had spirometry. A third of the patients are undiagnosed. A third of the patients are diagnosed inappropriately, which means we appropriately diagnose about a third of the patients with COPD. It's really pretty dismal when we do our epic chart reviews and those sorts of things. So it's just using spirometry a little bit more. Uh, we showed this last hour kind of the types of service. And when we kind of look up here at our older group, 65 years and older, we spend a lot of money for lung disease. And here come the, the um, chronic Obstructive Pulmonary Disease is this button right here where most of the care is actually for hospitalization, but we still spend a lot of money on medications as well. So, uh the point is that uh we have a few kids with COPD, we increasingly recognize that there are a group of kids that uh graduate out of the neonatal intensive care unit or had a lot of respiratory infections through childhood that never achieved their normal lung function and their airways are collapsible and they have some COPD in their thirties and forties. That's that little red bar right there compared to all the predominance of older individuals in the COPD group in COPD. Most of our costs are inpatient costs. That's the yellow for the past 20 years. Here come the prescribed pharmaceutical cost heading on up to try and match that now. So we are equally uh spending our dollars and would hope that our inpatient costs would go down, which is that we really haven't penetrated very well. These very co morbid patients that have a lot of things wrong with them that show up with CPD exacerbations in the hospital. COPD prevalence is uh really heavily influenced by where smoking happened the worst here in South Carolina. Uh it, it's all over. It's not as bad as uh some parts of Appalachia, but uh there's a lot there. And if you talk about cigarette smoking related disease, remember that we have three big diseases there. They are lung cancer and a whole new topic of lung cancer screening where we find about uh a third of those patients have COPD. Um ischaemic heart disease. Number one killer of men and women in America. And number three on the list is COPD. And it's interesting that if you smoke a pack a day for 40 years, uh, no more than 20% of patients develop COPD. So, just because you smoked doesn't mean you have COPD. And we don't fully understand why 80% of patients are protected from this disease. Of course, they can have a stroke and heart disease and lung cancer and not have CPD. But this whole, just assuming that somebody smokes and they're short of breath and have cancer and have CPD is not by any ways the way to make the diagnosis. And then you've got all the non smokers that have CO PD as well. So, uh so it's a very important statistic that we don't fully understand. Um just because we mentioned it, uh remember that lung cancer screening, uh So mammography screening for appropriate aged individuals uh is embraced by primary care at about a 80% level lung cancer screening. This past year, 5% of eligible patients got their lung cancer screening. And so, uh I know this is a pharmaceutical comp uh conference. But what has happened is it been that the US Public Health Service has lowered the age to age 50 to 80 with uh any smoking within the past 15 years. Uh And uh you have to have 20 pack years or more to increase your risk for lung cancer. And that's a once a year chest CT scan, low dose at a, at a license center, um MESC and others license for this. Um But uh the uptake of this is abysmal. But remember these are people that smoked even though the surgeon general said not to. So where they're gonna follow health uh recommendations or not is a little bit different piece uh compared to the uh average patient that's out there spirometry diagnosis. Uh And the way we deal with this in the obstructive side is that we look at this ratio of feb one to FEC if less than 70% of the air comes out in the 1st. 2nd, then you've got an airways disease and then we quantify it by looking at the percent predicted fev one uh as mild disease greater than 80 moderate, 50 to 80 severe or the very severe patients. When we look at first diagnosis of COPD in America. Today, the average fev 1% predicted by the time they get to a diagnosis is 60% predicted you've lost 40% of your lung function before the diagnosis is made and we have uh opportunities there. Um The global initiative of Obstructive Lung Disease are our de facto guidelines here. They update every six months. They kind of characterize this stage 123 and four disease. Um But recognize that sperry doesn't really risk stratify as well as some other things. Uh And we'll talk about that part in a minute. I've shown this slide for lots of years. Uh just to make the point that um hypertension, 10% of the United States population uh may be a little bit higher. Doctor Basil will come and talk. Uh, here COPD similar uh uh prevalence in America. How often do we screen for hypertension? Every single busy you get a blood pressure. Um And do you really care what the blood pressure is today? No, you don't care. You care if you don't control it that they're gonna get kidney disease, a heart attack, a stroke, 10 or 15 years from now. So, in a similar manner, do I care what your fev one is today? No, I just want the diagnosis because if I can turn on the preventive measures for COPD, I'm gonna prevent you showing up in my intensive care unit, 10 or 15 years from now with respiratory failure. So if you think about hypertension screening is a blood pressure, uh I think about COPD screening is a spirometry. Let's put on all the spirometry, uh hats and kind of make the early diagnoses because it changes lives. And so that's the only reason to compare the two diseases that we do such different things in. And I get it. Uh one millimeter change in blood pressure correlates with meaningful outcomes and hypertension. We don't have that same data set uh in COPD and, and we understand however, we horribly under diagnosed COPD. And this is uh one of my friends David Menino, who lives in Kentucky and worked at the CDC at the time. And as part of their CDC surveillance, uh one year went out and knocked on doors of patients all across America unselected and pulled out this magic tool called the SPE and did the spry in the household of patients uh across the spectrum of age. And uh the COPD, the diagnosis rate at the time was about 5% of the US population. And this is those individuals diagnosed with COPD showing this green bar age association. But when you actually look at the spirometry, this is age greater than 65 20 to uh 20% of the population has COPD. And this is older. This is 2002. Data smoking prevalence has decreased since that period of time. Uh But the point is that this uh association of undiagnosed COPD in the elderly is really quite high. Uh and uh should be kind of thought of as being there if you have risk factors, which are our current algorithms. Um We tried to do the same thing in asthma with COPD with a capture instrument. It's been through NH trials. It actually works. It's not quite as uh detailed as the act, but the things that make a diagnosis of COPD more likely are some things you might not expect, which would be like, have you ever lived or worked in a place with dirty or polluted air secondhand smoke or dust? And so just recognize it's not all cigarette smoke here. It's, it's any particular exposure. Um, do your breathing change with seasons, weather or air quality? Well, traditionally we thought of that as having an asthma pre election. The point is that happens also in COPD does not differentiate between the two diseases. And, uh, if you ask a group of patients that have COPD, are you short of breath? They'll say no, I'm sitting here. But you say, well, can you carry two bags of groceries up your stairs that are 20 ft tall and they'll, they'll be uh no, I can't do that. And so it's really quantifying your exertional tania with some exercise capacity. And it's hard to get at that in questions about how much exercise people do. We have a lot of couch potato patients sitting in our uh in America today and this last one was a little bit unexpected when this tool was developed and it's all about fatigue and tiredness. How many of our us have patients that have fatigue. It's like every, every patient and we know that lots of diseases can do that. Um But fatigue actually ended up out of the 200 questionnaire, associating so strongly that it made its way into the five questions that help you make a diagnosis of CPD when you can't breathe. Nothing else matters. And fatigue is one of those symptoms and then the standard of missing work and the exacerbation burden that comes with COPD is certainly there. Um we have thought a lot, a lot about how to make this easier for primary care. We just can't do it. Um, we have so many different types of COPD, we'll have if we did AC T scan and everybody in America we'd be able to sort out who has COPD and who doesn't, but that's not gonna happen. Um, and we've add up spirometry and symptoms and, uh, and the exposure histories, but increasingly as smoking decreases, we have just as many if not increasing western wildfires and global warming in particular air quality issues um that are gonna be driving COPD for the foreseeable future. So that 25% number is likely going to rise as a percentage of COPD. And so it's really trying to capture symptoms of Disney and figuring out what disease it is. And the problem in pulmonary medicine is we only have 500 diseases. Uh We have all these interstitial lung diseases and it's the reason I went into Pulmonary in the first place. But it, oh it makes it so hard for pharmacists and uh and family doctors and any sort of primary care to really sort through all of these. So we're, we're working through all this, but we do believe that uh we'll have different definitions of COPD but they're still gonna have spirometry is an important part of that uh into the future. I do work in a genetic disease, Alpha one A trips and deficiency in this room. Um there are 3% of individuals that have an abnormal gene for alpha one. And it just so happens if you marry somebody also with an abnormal carrier state gene, then you can have two bad genes and present with your uh emphysema at age 35 and need a lung transplant at age 40. Um So that disease uh at this classic stage was uh took lots of different diagnoses uh from different doctors and visits. Everybody thought she had asthma or they're 35 years old and wheezing. And so we recommend uncontrolled asthma and all patients with COPD, get a once in a lifetime alpha one test that costs $17 in your hospital laboratory. And how many times you get a CBC? Uh And so it's a once in a lifetime because your genes don't change a low alpha one level uh then generates actually a geno type to learn your alpha one letters. It's on 23 and me and lots of gene panels. So we actually end up diagnosing families with alpha one. So if somebody comes to you and says my family member got diagnosed with alpha one, just uh just tell them, do what they said, which is to go ahead and get a test and it's cheap enough and you can figure it out. Um If you have alpha one, this is what it looks like. We have cigarette smokers in blue and non smokers in red. This is your age from 30 to 80 this is your FEV one. And here's this classic description of these people with really low fun lung function at early age. But here's the guy who smoked uh with their alpha one and has 100% lung function at age 75. So we have a whole lot of heterogeneity in here. Um And just recognize that just because somebody smoke three packs a day and has normal lung function, uh doesn't mean they don't have alpha one. We only treat with our expensive medicines. The patients who have progressive obstruction and, and more severe disease. And so we don't let people without symptoms get these $100,000 a year therapies for alpha one. Um And yet, uh there's a lot of fear for having a genetic disease you might pass on to your kids. And so it's our only genetic cause within COPD that we do anything about. Um because we have a medicine that takes your low alpha one level and then restore it to normal. And then we've got all these new and coming gene therapies and uh there's a lot of research going on because the other disease is that your alpha one as it's produced in your liver to go out to the bloodstream misfolds and causes liver disease. So we have a second burden of liver transplant that happens in these patients from the ages of 50 to 70. Um And so uh just to recognize that we've had recommendations for once in a lifetime Alpha one testing for everybody with COPD in place since 2003. Uh It's done about 5% of the time. So that leads us to the blood test. Uh an alpha one, a trip level, $17 A CBC with differentials. You got a whole lot of in there. It means you're more likely to have asthma, um and an IgE level, which means you're more likely to have asthma. And so uh it kind of just helps us rest our patients and into two big buckets that we talk about. Ok. Well, let's turn into therapy and we're gonna spend most of our time talking about our medication therapies here. We're gonna use the same abbreviations we did before Sabas and Sama and Lava and llamas and I CS s because it's the language we talk in. And importantly, when we start having all these new inhalers, I'm gonna show you in a minute if you don't put them in the right bucket of which uh and the words are too long. So it's worth learning these little abbreviations for all of our respiratory diseases, smoking cessation we're not gonna talk about today. Um A lot of good data that says we really have interventions that make a difference. Um And whole different one hour lecture, we begin with bronchodilator therapy. And the second thing we do is prevent exacerbations, which is where all of our hospitalizations and where all of our cost is spent, uh, during, uh, COPD care. Um, we'll talk a little bit about targeted therapy. If somebody walks in with an exacerbation, uh, what to do? And we think that if you're coughing up green or yellow stuff, you can have an antibiotic. We have a little bit of data that antibiotics make a difference. We tend to keep them short sweet. And, uh, and of the Azithromycin or Doxycycline world rather than expensive uh uh loans and other things. Uh If you're just coughing up a lot of extra white stuff, we can do the little muco mucolytic specter for a week or two. And we know that steroids work for all patients. And so if you go to Europe, then almost everybody gets a little steroid burst for five days without any of the above uh antibiotics or mucolytic as their way to get through this event. And increasingly in America, we're using less antibiotics, more uh prenazone for really short course therapy for exacerbations. Uh We're not gonna talk a whole lot about the expectant therapy. We can take questions on our vaccination strategy now that we have uh new pneumococcal vaccination recommendations every year for the past five years. That's, that's a burden for all of us. But uh uh we have those out there. We have the new RSV vaccine that was approved just last month and how to fit all those into our mentum of vaccinations, uh, with all the COVID vaccinations and all the vaccine hesitancy out there is a whole another hour talk too. Um, and then I'll just show you some of the cool things we're doing, uh, in the talk about the other things. Um, this number, this is the 2021 numbers. I went and looked at the 2022 last week and they haven't changed. Uh, we're still, we're not in the straight F column in the American Lung Association smoking cessation report card because we have the state law that mandates pharmacys cover smoking cessation therapy that brings us up to A B. Um But uh even though we increase our cigarette taxes and other things, uh it's still pretty abysmal, uh we're not the only state in the almost straight FS column. There are still about five of them that have straight Fs without the B in the middle of it. And four out of five FS uh is, uh including youth access, uh is all on the A L A website by state. And it's uh obviously what they use as their playbook when they're talking to politically active constituents. Ok. So we, let's get the big overview in place. So we sp meric confirm our diagnosis. We figure out if you're in the greater than 80 or less than 30 group by looking at your FEV one. But then we draw a pretty hard line here on what we're gonna do with medicines. And this whole category here that used to be the ABC D category has two axes. This one's symptoms, if you have mild symptoms, then we give any bronchodilators for the A S and we can advance and do more broncho for the bees. But our Y axis is the exacerbation frequency and it's exacerbations, lead cost, lead hospitalization, lead quality of life indicators and lead mortality. Then we've got to target exacerbations as the most important aspect of COPD care. So we define this as more than two exacerbations in the past year or one that required hospitalization. And if you have those, you end up being in the C and D categories, this made it a little, we had very few C patients. Most people have persistent symptoms and then get their exacerbation. And so what happened here was the new guidelines that came out in January just changed it to e you have exacerbations, you're a, you're a gold category E patient and we're gonna treat exacerbations. We're going to try and prevent exacerbations uh rather than do the ABC D thing anymore. And so all of our treatment recommendations now come out of this uh algorithm of A B and E. Um And you've seen this slide before last hour, it's the same medicines uh except that when we start getting to the combinations, uh We have a lot more controversy. This is one of these charts I have in my office. How many people have, have one of these in their office, it's free. Um, and they help, I mean, you'll find patients up there and, oh, I got the Greenwood, I got the, you know, it, it, it helps them because what it does, it puts everything, uh you know, in the combinations you kind of get all the I CS lava in one group, all the LAMAs in another. And so now you figure out that you're actually, uh you can actually figure out what people are taking. There are as y'all know drugs from Canada coming in, people give uh um samples off the shelf. It's one of these deals where uh the allergy, the chest foundation has supported this. I think everybody's trying to build the same tool kit that we all can get to the medicines and make sure we're not having overlapping medicines in different categories and making rational thoughts about our short acting and our uh longer acting and our combination medications and particularly these days when your insurance company makes you switch from one to the other every other uh visit it, it makes it particularly difficult to kind of understand because each of these are devices that are a little bit different. This one includes the biologics down here for asthma. It also includes bronchial thermoplastic that we mentioned last hour. Um And um, and so, uh it's, it's out there, it's available and I like it, it helps patients. Uh It comes as a PDF, you can send to patients if they ask for it, if, uh, if they want it. Um, but the buckets here are I CS Lava and llama la. Um, we'll show you where they fit in a minute. Uh One of the laba llamas came off the list last year because they didn't have enough US sales, uh, still in place in Europe, but we have three of the Laba llamas, uh, that are out there. Um And you'll see in just a second that these drugs have emerged to be uh recommended higher levels than the I CS Lava in our more current guidelines. That's a little bit at odds because these are all still proprietary and therefore higher cost than some of these that end up having now generic options. And so, um, much of this transition to llama Laba has been that when we compare these two groups of medicines in our C FTP population, we get about another 100 mL of fev one which translates to being able to walk further and do more with the LA LA than we do with the IC Lava. And then we have the added burden of the inhaled corus pneumonia conundrum. Uh That comes if we have a patient with frequent exacerbations, then our inhaled Custer s are our drug of choice. Um And that transitions into a patient who has more pneumonias but less exacerbations. Does that make sense? Yeah, it's one of those paradoxes that we don't fully understand, but every study for the past 10 years has shown it. And so increasingly we're gonna be using the I CS containing inhalers for people with frequent exacerbations. The big E category and laba LAMAs as we move up and people aren't fully uh, are still having dysnea that's uncontrolled. Uh, as we move from llama or lava monotherapy in the group A S to the group BS that have the combination of llamas and lava. So the group e that end up with an I CS lava or ice, we don't yet have one but one's coming soon of an I CS llama or A triple therapy inhaler up here. So when do we use an inhaled steroid in asthma all the time? When do we use an inhaled steroid, contain inhaler and COPD? Well, some of the time and this is the difference between the two diseases and against use to be repeated pneumonia events. And looking at that blood ey level when it's low, it's very unlikely that the inhaled steroid is gonna make a difference where if you have uh more than 300 cells per microliter on your CBC on this side, strong support and we can decrease exacerbation frequency much more briskly in the groups that have an hylic component to their disease. And we recognize that there are people that have asthma for 20 years. Now, they transition into fixed obstruction, usually with some cigarette smoking and we call those combination patients or um overlap patients of asthma and COPD. And so we, we continue to inhale steroidss in most of those patients. But I think the point is the same drug for all these diseases isn't gonna fly anymore. And so we need to uh begin to stratify the two diseases. So, um so that's the I CS statement. So our first question, you have inhaled steroids and COPD is associated with, please answer now, improved in fev one slower rate of decline of fev one more pneumonia, more exacerbations. All right, 85% of people got it. More pneumonias. And then what percent of COPD patients if you follow them for a year? Get a pneumonia on an I CS. That number somewhere different studies between 2040% of patients. So is pneumonia treatable and does it lead to mortality events? And the answer is yes, it's treatable. There is no difference in the mortality between the patients who get pneumonia with an I CS and those that don't get pneumonia with an I CS. So we think that most of these are rather mild events if pneumonia can be called a mild event and the elderly. Um, and yet, uh, it, it's a burden of disease and so that's, we don't want to scare people away from inhaled steroids because they do decrease exacerbations and the mortality benefit associated with the decrease in exacerbations over weighs the mortality increase associated with the pneumonia. Uh, if there is one. So this pneumonia recognition is kind of scary. People read about it and it leaves people away. That's the reason to use llamas, uh, cost and other things. Get in the way of that sometime and just pay attention to the pneumonia events and treat them early in your patients that are a little bit more fragile with some baseline COPD to decrease exacerbation numbers. Ok. New kids on the block. we have two triple inhalers now available for COPD. Um They are the astrazeneca drugs uh and the GlaxoSmithKline drugs. Um And so you'll notice here that when you go up this ladder of Brio and Neo and trilogy. Similarly, on the other side, Symbicort and Beth and Bre Tree are to they, when you compare these two studies, one of them 10,000 patients and one of them 8000 patients, it's amazing how similar these outcomes are there, these were done in exacerbating patients. So there is this uh support to not just throw everybody with COPD in these studies, but if you're failing your therapy and still having exacerbations, that was the entry criteria for both of these studies. And there was a small but sally significant mortality benefit associated with triple therapy compa compared to either of the combination uh dual therapies. And so, you know, whenever we get a a mortality benefit with any drugs, you get a 1% mortality benefit my infarction, it's like magically everybody in the world switches, that drug and COPD. This has been one of these events, this kind of, uh because it wasn't the primary end point of the study. It's just that, you know, it's only 10,000 patients, it's not 30,000 patients, uh becomes part of the conversation. Um, but we've not had drugs that decrease mortality in COPD ever. So, for us, this is a big event when we have a medicine in the frequently exacerbating patient that uh decreases exacerbation frequency, which is the graph, not by lots, but because you have so many people, uh the P values and statistical significance is strong and was reproducible uh in the uh ethos study uh with similar sorts of medications. So these are out here um retail, they sell for about $800. Uh if you're an integrated health system and you can decrease one exacerbation in your patients that cost about $50,000 to get hospitalized. Yeah, it makes sense. And we can show um reductions in overall costs and numbers of downstream exacerbations uh pay the way. But these often in America's fragmented health system come out of different pockets. And uh and it's really just part of the uh travesty of our health care system where we have such fractured care. So that's the whole piece around this group of medicines. There are major companies, Blue Cross Blue Shield that ends up for instance, paying for these as part of formulary because they recognize that they're also gonna be paying for the hospitalizations downstream uh for the appropriate patient. We still want everybody with COPD to be prescribed a triple therapy. Uh knowing that uh not everybody needs these. Uh as we move forward, this is the uh mortality reductions uh associated uh with a year of care. Uh So, it was a 2% mortality compared to 2.9% with the dual bronchodilator. Um And so, uh what that led the guideline committee this year to do was go to the initial pharmacologic treatment by ABC D group that now has changed to the A be group. And any bronchodilator works for group A. Uh these people, you give them a bronchodilator early in their course of COPD. They feel better in group B. We think that you need a long acting a lava or a llama and group E laba plus llamas are preferred initial therapy. And then what happens on the next visit when either they have another exacerbation or their, this is incompletely controlled is that you can go up the ladder from there to your next therapy. So that's the recommendations of the Gold Committee. Part of this focus on exacerbations is just focused on how bad these are for your patients with COPD. And uh this is uh a study that was done um back in 2012, but it's basically looking at the mortality rate if you show up in the hospital with an exacerbation and you have 11% of patients die within 90 days of that first hospitalized exacerbation. So these are not just uh events that you pass off as uh nothing. And then this is the median survival of patients who received their first hospitalization for an exacerbation of COPD with a median survival of 3.6 years. Um And so what does that look like? Well, what's the median survival of the first patient that gets lung cancer? Breast cancer? It's about the same. So think about these first hospitalized exacerbations of COPD as similar to a new diagnosis of acute myocardial infarction or a new diagnosis of cancer because the disease state means that this patient is destined to really do poorly over the course of uh the next few years unless we can turn on uh therapy. Uh been a part of a few of the initiatives that have actually taken every hospitalized patient and prescribed a triple therapy at the time of first hospitalization. And what happens is time till your next uh exacerbation decreases uh dramatically. And so, and for every 30 day delay in getting to triple therapy, you actually add a new exacerbation events uh in 6% of the population. So this is every month that you don't uh prescribe triple therapy, leaving the hospitalization. People that benefited the most are the ones with the most co morbidities. The ones that have had a stroke, the ones that have had a myocardial infarction, the ones that have uh uncontrolled hypertension and congestive heart failure are the ones that benefit from triple therapy the most. Um at time of hospitalization, that's different from the guidelines. This is in the hospital care. Um And so as we transition our hospital formularies who don't want to carry the triple therapies to recognize this is gonna end up being preferred, pay for every patient who's hospitalized. Uh is the, um is the conversation we're having right now? Otherwise you can build a triple therapy and you do that by giving an I CS lava and then a llama medicine. Now, they're on two inhalers. We call that open triple therapy compared to closed triple therapy. The laba llama I CS all in one inhaler. So there are a lot of options there. They'll all align if you kind of go through the big chart of all the different inhalers to get one of each of those categories out of there, a laba lama plus a standalone, inhale, steroid, do the same thing. So those are called open triple therapies. Uh If your formula area is not carrying the ones you need. Ok. So if you've had an exacerbation, they come back to the office. What are you supposed to do? Well, for the next year, you ought to be able to prevent the next one. And all these, uh, decrease your next exacerbation on this list are influenza pneumonia, vaccinations, pulmonary rehab, having a self management support system with the nurse coordinator, smoking cessation. On this list, we have a lot of these that are non pharmacologic as well as uh taking uh our medications that all decrease exacerbation frequency as well. Uh There's a very complicated, uh in our guidelines statement of, if you start with a Laba llama, uh for dyar exacerbations, what happens if you have a next event or if you add extra eys and whatever. But the final common pathway for all of these is a llama plus a laba plus I CS triple therapy. So we're kind of heading towards triple therapy depending upon the conversations with your patients much of the time. And then if you are on triple therapy and still are having exacerbations, then the next step is to add a pill or add the, the daily Azithromycin 250 mg a day for a year that decreases exacerbation frequency by 17% in our randomized control trials. So we often will take the Zithromycin and uh translate that data into more uh hearing friendly versions of Azithromycin three times a week as opposed to daily for this group of uh frequently exacerbating patients just knowing how bad exacerbations are. And then on the front side really got through on its exacerbation reduction. Uh But this was a time when we really didn't have any new drugs for COPD about uh six or eight years ago. And I think uh the FD was kind on the data set. Our, our inhaled medicines make a bigger difference than this pill. People would rather take a pill than an inhaler. Uh We get that, but this is kind of an add on therapy at least by guidelines after you've gotten to triple therapy. Ok. Next question. Triple inhalers. Laba llama I CS are associated with fewer exacerbations. Guidelines suggest they should be first line therapy FDA indications for asthma but not COPD or decreased risk for pneumonia compared to other I CCS containing inhalers. Please answer now. All right, y'all are smart group getting it every time. Maybe let's talk it out too much up here to give you the answers before the question. Uh Good job everybody. All right. So we're just gonna end up talking for the next uh five minutes about the other things we do. And we recognize that even though this is a Pharma conference that a lot of times our care for COPD when y'all send somebody to see me, uh 90 95% of the time they're already on triple therapy and all sorts of good medicines. And so what do I go to? This is my playbook of what I'm talking to patients about. And part of the translation is that you can too. And so we have Medicare guidelines for oxygen that are out there. I'm gonna talk through those for just a second. Uh We have chronic noninvasive ventilation for everybody with a P CO2 on a blood gas at steady state greater than 45. So this is a lot of patients that don't have, aren't using chronic noninvasive ventilation to rest their respiratory muscles at night so they can function better and do more during the day. Um, pulmonary rehab is a formal process that shut down during COVID. All the centers are now back open for business. As part of your Medicare benefits, you get 36 sessions of pulmonary rehab, two hours a day where you get and let our respiratory terrorists pull out their black whips and get you rolling on the, on the treadmills and get you exercising to improve your leg muscle uh strength which improves your oxygen utilization. And as a result decreases your CO2 production. So you don't have to breathe as hard when you climb the stairs or walk through Walmart. And so it's a quality of life improvement by getting your leg muscles strong with pulmonary rehab. 36 sessions looks like three times a week for 12 weeks. That's three months where you go into the exercise center and being supervised, you can learn how to turn up your oxygen. And so how much during your exercise, if you're unsteady on your feet, they'll bring in the physical therapist and kind of get things going. It's really a wonderful program. Usually a waiting list is involved, but they are great centers throughout South Carolina. Uh and around if you come from out of state Um And uh if it's been estimated that if we took every patient eligible for pulmonary rehab, it takes about 480 years to get everybody through the program. So it's a way under utilized program is the point because we have uh a shortage of centers. Um We're gonna talk, I'm gonna show you some of our cool new devices for COPD that are coming and then we have lung transplantation at the end about, I'm gonna talk about oxygen for just a second because I see in primary care, this one being a little bit um schizophrenic and everybody kind of knows in a hospital system that we want to have oxygen saturations, uh 90% or higher, 88% or higher in different hospital systems. And we do that really for patient safety. Um What we now know though is if you take somebody that's 92% at rest and run them down the hall, almost everybody will desaturate. And so historically, we've started cranking up the oxygen to keep them from having oxygen des saturation. And what that does it improves your exercise performance. You can walk farther. Uh Five years ago, the long term oxygen therapy trial was done as an NH study and it randomized patients to oxygen or no oxygen for a year with a whole battery of neuropsychiatric testing, cardiac function testing, lung function testing, finding no difference in this group of patients who start with normal sats and desaturate down as low as 82%. So the uh you'll see when you give grandma oxygen, the whole family uh puts the oximeter on her every time they, she walks down the street and it's this whole deal about keeping your sats up the same way we do in a hospitalized patient population and there's no data to support that. And so we freely let people desaturate. What happens if COPD you get down to 83% you short of breath, you stop, that's come right back up in 35 seconds. No harm done. And so what oxygen does is it helps you exercise, it helps you in pulmonary rehab, achieve your muscle strength and be able to do more and improve quality of life over time. So this whole focus on oh your oxygen is less than 88 is is really a little bit mis founded. Uh We do have mortality statistics. If your oxygen saturation is less than 88 which is where the Medicare guidelines set it persistently at rest. Then there were some mortality studies done in Colorado and other places that showed that oxygen, there makes a difference in mortality, but that's not what we're talking about most of the time in our COPD patients. Uh Let's move on ahead to our devices. We now have a group of devices that um um cause lung volume reduction. The process here is that with emphysema. What happens is that the holes in our lungs, trap air. So we breathe air and it goes into the holes. We exhale, it doesn't all come out of the holes. So we start climbing a flight of stairs and our lungs get bigger and bigger and bigger and bigger. A thing called dynamic hyperinflation. And what happens if we can shrink your lungs is that your diaphragmatic curvature remains and you can keep ventilating even at the top of the stairs, instead of having your diaphragm being flattened with progressive hyperinflation. So we go into the lungs and put these little one way valves into our airways and we target the lobe of worst emphysema. These little valves let air and mucus out, no air in. And so the worst lobe of emphysema will then collapse like a pancake and it'll move your diaphragm up and the heart shifts over and decompresses the other lung as well. And what happens is that I go back. And so what happens is that patients can ventilate and keep going. Quality of life. Improvement in all of our quality of life scales is about four times. The improvement with bronchodilators is a medicine uh to do this, you have to have an intact fissure between your lobes have to have AC T scan. You have to be hyper inflated on our, some of our uh pulmonary function tests. So it's a big deal to kind of figure out if you qualify for this. If you take everybody with COPD, it's about 20 to 30% of people that qualify for these uh if you have really low lung function. So, um big centers, uh Greenville Columbia and Charleston are all doing these. So don't be afraid to uh transition your emphysema predominant COPD patients to see if they qualify for uh any of these therapies. Next, therapies are experimental right now, but we don't really have a good way to uh treat mucus. And so mucus is caused uh by our muscarinic nerves that run on the outside of the airways. So we take a long acting muscarinic antagonist medicine. It actually decreases mucus production in our airway. And so what would happen if we instead just zap these nerves and killed the muscarinic nerves, we would have a persistently bronchodilate airway and it wouldn't make mucus anymore. So this is a catheter designed to do that. Uh We don't want to hurt the airway. So this electrode that gives electro mechanical energy to kill the nerves on the outside of the airway has ice water infused during the time of activation. Then you rotate around and you hit both of the main stem bronchi here and here and now your lungs are persistently bronchodilate without any medicines. Uh Patients hate medicines. So why not? And so this trial is be finishing in a few months. Uh And we'll see if uh it makes its way through the FDA soon. And likewise, for chronic bronchitis, we've used liquid nitrogen to kill all sorts of cells on our skin forever. Why not go into the airway and kill some of those goblet cells making mucus. So this is a liquid nitrogen uh application to our airways to kill goblet cells and it injures the respiratory epithelium for about a day. But those cells grow back, the goblet cells get injured and die. And so lots of mucus to no mucus quality of life improvements is the goal of uh this trial probably about two years before it makes its way to the FDA. So, uh leaving us eight minutes for questions. We're just recognized that we've got a big uh integrated Armamentarium of all the things we can do for COPD. And, you know, on the front side, there's the smoking cessation. Everybody does so well. Uh But uh we don't do so well in referrals for uh pulmonary rehab, uh and exercise in particular. Uh We've got lots of good uh pharmacotherapy that is emerging and we see new agents all the time here and then all the assessments and education that has to happen in the office and in pharmacies for adherence uh issues, uh which are fairly dismal in, in all of our COPD medications as we talked about before. Uh this whole process and focus on exacerbations is something when patients don't think these inhalers help them at all. What do you do? Um And that's kind of educating them about, we can prevent an exacerbation that if you end up in the hospital and it costs $50,000 far exceeds any. And the health uh uh deterioration associated with that and quality of life is huge. And so that's the conversation, you have to have not all patients receptors that if this inhaler doesn't really, they don't feel like it helps them very much. But you know, that this is an inhaler that is associated with decreased exacerbations. And sometimes we force that all along as much as they're willing to take it as long as you can give good rationale and build trust with your patients. We think that makes a difference. Uh regular practitioner contact makes a difference. These are patients that are gonna have their COPD for 15, 20 years. Um get to know them, get to know their families. They, these are some of your most endearing patients, we can help them along with good inhaler therapy and improvements in quality of life. It does take a community to do this disease. Um But hopefully, I've given you some tools to make their life journey a little bit easier. So, hospitalizations are the most costly aspect. Uh Let's try and decrease those by decreasing exacerbations. Um We heavily stratify eys, non eys asthma chronic bronchitis as to which kind of medicines we use for those patients. That part is not easy to navigate. Uh but don't be afraid to try some medicines and take them away as long as an insurance company is willing. And then these non pharmacological therapies are just as important as the drugs to improve good outcomes. And so let's pause there and see what pops up in our question list here. So, um are there any updates on approval of non antibiotic macrolides? And instead of turning to a zithromycin inducing resistance? So, in that original study, a Zithromycin 250 mg a day for a year versus placebo to decrease exacerbation frequency. Uh We actually had 57% of respiratory isolates, be resistant to Zithromycin. After that, uh 27% of people had some hearing impairments. So if I'm gonna turn to macro or chronic antibiotics to decrease exacerbations, I wanna make sure I'm already on triple therapy. I'm doing everything I can with rehab. Uh We sometimes if people have frequent exacerbation will turn on some hypertonic saline solutions. The point is that antibiotic, I, this is the one I turn to least frequently in the whole algorithm I showed just because of these resistance issues. And usually people haven't been to pulmonary rehab, they haven't. Uh and they don't have a good airway clearance regimen by which you get some hypertonic saline and exercise and get all the mucus out and buying away your salty 7% saline in your airways ends up killing the germs that are there uh as well, if not better uh than an antibiotic. So, um so the point is that none of the number of patients needed to get an FDA approval for exacerbation reduction is about 10,000. Um So to do these trials, none of the trials of any of the new antibiotics have done that. And so it's all just uh opinion based stuff and I tend to use antibiotics least frequently compared to all the other interventions on the list. I probably have two patients out of my large panel that are on chronic antibiotics. The, that's different than the group that have chronic mycobacterial disease and, and other chronic infections as well. Could you comment more on the use of gin chronic versus pr N uh use in dosing? So, you know, it's, it's really hard when somebody comes in doing everything you say and they still have bad symptoms of chronic bronchitis. So we get it that we need therapies. It's just that there are no randomized trials that show significant benefit with wain or any other mucolytic therapy. We can show it in the test tube. It just doesn't make a difference. We always want to do something. Uh patients use it. Um And then they uh what will happen often is that they'll kind of uh when they come in and see me, I'll end up stopping half their medicines and usually don't make much of a difference. So, so I think it's one of uh these uh chronic uh use, I avoid acute use. I and do if you're gonna start it, we'll do it for 10 days. Around exacerbation is the way I practice that, but we really don't have very much good data. And I think it's the last bastion, we don't really have good mucus drugs and COPD, hence the liquid nitrogen study and other things to try and really decrease uh the mucus burden and build new tools for that subgroup of disease that we don't really have right now. Um The what is the niche for the I CS llama you alluded to. So uh I CS for is first line with asthma and laba lama is first line with COPD, but both progress to triple. I think that's true. Um If I have a single monotherapy to give in that group a of patients, I actually pull out the llama over the lava because it has an effect on mucus production and that an colergic effect uh and kind of visualized by that uh the airway that's getting zapped with uh with our new devices will not only give you bronchodilation but also down regulate mucus production. So if you have a mucus producing patient, they're not on a llama and they're on monotherapy lava, that's the switch that you'd make. And so I tend to use my, more than my la uh as first line therapy and then build from there. So the therapy behind a lot, the rationale behind a lava I CS is that you would get the exacerbation reduction and decreases in mucus uh at the same time and they'll probably be the same as, uh I CS LA. But as you know, if there's an empty space, some uh, company will fill it and will make our chart even more uh complicated than it already is. All right. So, um, the last one and then we'll, uh, with one minute to go will end on time. Doctor Strange. When should spacers be used in patients with COPD and, or asthma? And our spacers, uh when medicines come out of a nebulizer, they come out or out of a meter dose inhaler, they come out in a variety of sizes. And the big ones, big particles that come out of a, a puff of a MD. I are the ones destined to fall out in our mouth and our hypo uh hypo, the small particles are the ones that make it down to our small airways that contribute to bronchoconstriction and where all the effect happens. So if you put a spacer, the big particles fall out in the space or rather than causing dysphonia or local um production, all of our um current I CS S they go in there are, if you swallow them are first past metabolize for the liver and don't make it to systemic circulation very much. And so it's the patient that has a lot of local symptoms that we put the spacer in. It's actually over time. Uh randomized trials of spacers haven't shown to be very effective in improving asthma control or COPD control. So it's really all about symptom control in the upper airway. You gotta remember that none of these medicines go through with the spacer uh in line with FDA trials, except there is a very old uh uh try and inhaler that had the built in space and the, and when it went and went out of the market, nobody used it. So all of them just kind of fell off after that. So uh that's the spacer and then shared clinical decision making, individualized care. That's what we're all about here and this and many of our other diseases. Thank you all for having me. I got one last question. You did not mention oral steroids except in the context of acute exacerbation. But we all know that many of our bad patients are in fact on long term oral steroid therapy. Yeah. So the question is around oral steroid therapy and COPD and we know it happens, we try and keep the doses as low as possible. Uh We try and build our other therapies and if you get patients into pulmonary rehab and all, then there is this dependency and the current trials, all of our biologics for asthma are now happening in COPD. And so whether these some of these patients or asthma see a pretty overlap patients or not, uh that are benefiting that might benefit from other biologics. Look at the ESN numbers I check an IgE on all those patients to get stuck on steroids, prednizone decreases your IgE level. And so trying to figure out if is this really the hidden asthmatic that we're not optimally treating for their asthma is another tool that we use to try and get people off steroids. Good question though. OK. So uh thanks for having me. Published Created by
