Good morning, everybody. My name is Jack Buckley, and I'll be introducing our speaker today. But before I do that, I want to cover a few announcements. If you have not already downloaded the CHESS app, I would suggest you do that. In addition to having, you know, a full list of the entire schedule, it'll give you access to the audience response QR codes. So a number of lecturers over the course of the meeting will have opportunities for audience response, and you can answer that. Dr. Baig has some in his. So if you haven't already downloaded the app, please do. There'll be a QR code that pops up. You can load that to help address the questions. All sessions are eligible for CME. Claiming those opens up on Wednesday. It's not quite open yet, and you have up to, I think, a year to claim CME for the meeting. And much of that also includes MOC points towards the board certification. And those are most of the announcements. It is my pleasure to introduce today's lecturer, for the Thomas Petty Master FCCP Memorial Lecture, Dr. Barry Maig. This honors Dr. Petty, who trained hundreds of physicians in COPD, oxygen therapy, and spirometry. The award is conferred to a CHEST fellow known for their work in advancing the understanding of COPD pathogenesis and or treatment for exceptional mentoring and clinical instruction skills. This year, it is my pleasure to present the award to Dr. Barry Maig. Dr. Maig. Wait, there's more. Dr. Maig is currently the co-director of the COPD program and director of the Pulmonary Rehabilitation at National Jewish, as well as professor of medicine at the University of Colorado School of Medicine. He specializes in COPD and pulmonary rehab, and has a personal interest in utilizing personalized medicine. His involvement with CHEST began during his fellowship. He was a founding leader of the International Conference on Home Ventilation, sponsored in part by CHEST. Most recently, he was a member of the Medicare technical panel report sponsored by CHEST to inform Medicare on policies to ensure access to non-invasive mechanical ventilation. Dr. Maig has published many manuscripts and most recently participated in the Medicare report on the on-map technical expert panel on optimal non-invasive ventilation Medicare access promotion. For his advances in medicine and contribution to CHEST today, we honor Dr. Maig. Please join me in welcoming Dr. Maig to present the Thomas Petty Award. Thanks so much, Jack. It's my pleasure to accept this award, mostly because we all knew Tom Petty well, but I knew Tom Petty well. So the first time I didn't meet Tom Petty was when I went to Denver for internship interview. And people talked about Tom. I said, oh, I want to meet Tom. Of course, Tom was busy. But I also did not get accepted to internship at the University of Colorado. So then I tried again to try to do a fellowship at the University of Colorado. And I met Tom, and I didn't get to be a fellow. But then when I moved to Denver, Tom became a good friend. I reminded him of all the stories over the years when he turned me down. He was very apologetic about that. So the question is, what would Tom Petty think about COP today? And I'll tell you a little bit about Tom Petty. Here's my disclosures. Here's the QR code for the audience response and the evaluation of the speech. So the question is, for the older people, the older people, of course, will not know this, who is Tom Petty? So Tom Petty was actually all these people. He would count himself most as a fisherman, which he loved to do. And many around the world went fishing with him, mostly in Colorado, which has great trout fishing. But he was also a rock star because he was able to do all these things simultaneously. And his students, who were not only the pulmonary fellows but the nurses and the medical students and everybody who saw him, even the other attending physicians, everybody learned from Tom. And you know, when I first went to Denver, I said, well, Tom does all these things, but I suspect that when there's a grand rounds, you know, we do medical grand rounds or pulmonary grand rounds every week, he won't be good at evaluating patients. I was totally wrong. He blew me away as he did everybody else with his expertise in clinical care during pulmonary grand rounds. Like he always got the case. He was the only one who always got the case every time and guessed the case. And the fellows would try to stump him and they never could. So he was an expert clinician as well. The jokes, I won't tell many jokes because I don't have time. And a lot of them are off color, so I don't ever tell them. But I think Tom was known also for thinking outside the box. And as I show you in the next slide, some of his articles, he did a wide variety of things and was the first one to do them. He was kind and caring to his faculty and his fellows as well as his patients. He had 153 publications on COPD. You know, today with team science, many people have more than that because there's a whole bunch of people to get together and write articles all together on some study. And in fact, his earliest research was on experimental emphysema. Most people don't know him for that. What they know him for is for ARDS at the bottom left here. He published the article looking at the definition of ARDS when he was an assistant professor. And it made it into Lancet, turned down by JAMA and New England Journal of Medicine, published on Lancet. Most people don't recognize him for that. And these other two landmark papers on COPD, the long-term oxygen trial down at the bottom right in 1980, he was the founder of that study and he was the driver of that study. And even today, physicians in Denver say, well, because of Tom, I'm putting all my patients on oxygen. I don't care what the lots study and others show. My patients need oxygen because Tom told me they needed oxygen. And so I think some of his legacy in Denver is not necessarily appropriate. Too many people are on oxygen in Denver because of Tom. So what we're going to do today is talk about not COPD as it's usually termed, but some other definitions. What is pre-COPD? This is a very confusing area. What is PRISM? What is NOCB, non-obstructive chronic bronchitis? What is gold zero? These are terms that people don't understand. So I will try to sort of inform you from what we know about the literature and about our own studies in these different things that are sort of semi-COPD. And I think we have to look to Tom to say he was really a proponent of spirometry for the diagnosis of COPD and the diagnosis and recognition of patients and evaluation of patients. And things that these have in common is the lack of a lot of pulmonary function testing to define these interestingly. So this is the usual gold definition you all know, but I just want to highlight that the most important thing here is non-fully reversible airflow limitation, which these other terms I'm going to talk about do not have. So my question for you is, is this current definition of COPD, and it's a definition proposed by GOLD, the Global Obstructive Lung Disease Initiative, as you know, is this satisfactory, this definition, not the new terms we'll talk about, but this definition, is this satisfactory for you, your patients, and Dr. Petty? So is the definition satisfactory? It's supposed to be yes or no. Okay, forget that question. Oh, there it is. Okay, the answer's there. Oh, yes. Oh, everybody says probably. Yeah, so, you know, you're all very good at taking tests, right? And everybody knows, well, the answer probably isn't definitely yes and definitely no. It's somewhere in the middle. So that's where people are, in the middle. So the question I would have you think about this as we go through this is, well, why probably not? Or why only probably? What's wrong with it? What should we change? Well, the GOLD group in its wisdom and its evidence base says we're not changing the definition, but we may add some things around the edges. So we'll talk about the edges. So this is Tina. Does Tina have COPD? Well, a youngish woman, at least by most of our standards, so certainly not 65 or older, not elderly, not 80, who comes in and has what looks like a typical COPD, short of breath, cough and phlegm, can't catch her breath. And so she has a little history of having similar kinds of things, but they don't get treated. She hasn't seen a physician for it. When you ask her carefully, and of course the residents don't do this. The pulmonary attending had to do this. Well, what about your usual state? Do you wake up in the morning and have cough and phlegm? Oh, yeah, I do, but it's a smoker's cough. I've had it for years. Even when I stopped smoking, it persisted, but it's not a problem. So she's a cigarette smoker. She'll attack her cardiac and tachypneic as wheezing, but nobody thinks she has heart failure. And in fact, her cardiac echo is normal, but they don't do spirometry, do they? No, but they do an echo. And they treat her for COPD, and she gets better. And so she's discharged, but she has to go see her physician. Physician does spirometry later, and the interpretation of the spirometry is FUNFEC ratio. Above 0.7, FEC greater than predicted, 82%. Go to some other sessions. We'll talk about spirometry interpretation and racial issues. FEV1 is a little low, but it's interpreted as normal spirometry. So by definition of COPD, she does not have airflow limitation. So I'm going to talk a lot about the COPD gene study. Now, there's a lot of studies in the form of the definitions I'll talk to you about, but we know COPD gene best because it's run out of National Jewish. We actually just got our grant for following these patients for a 15-year evaluation. So we have over 10,000 subjects funded by the National Heart, Lung, and Blood Institute and over 500 publications in 15 years. It's been very productive. So I'll talk to you a lot about this group of patients who, although we call it COPD gene, interestingly, not everybody smokes, but not everybody has COPD. As you look in the gold spirometry grade here, 44% of our patients have normal spirometry. That is, they do not have airflow limitation. So this study informs not just COPD, but the history, natural history characteristics of patients who smoke, whether they have COPD or not. Equal male and female. And race is self-identified. Our goal was to have one-third African Americans, and that's what we achieved, and that was fantastic. So this is the spirometry graph, and there's four quadrants. You all know how to interpret spirometry. So at the top right, FEV1, FEC is above .7. FEV1 is greater than 80% of predicted. So in the top right, purplish, you know, a lot of different colors here. I don't know what to describe these colors. So it's the top right. The top right is no COPD, right? And the bottom right, in orange, that's gold one, and you have gold two, three, and four in the bottom left, and some other interesting group in the top left. Now, COPD gene was not the first to discover these patients, but, you know, we enrolled patients just because they had a smoking history, and there's a lot of patients in the top left there, too. So we call that prism. But if you take the first cut at this, the patients above the horizontal line of .7 have no COPD because they do not have chronic airflow limitation. Everybody below that line has COPD. So what we're going to talk about today as we define these terms is the people with no COPD here. Who are those patients? They smoke, and they smoke rather heavily. The average pack years of our population was like 35 pack years, so this is a heavy smoking history cohort of patients. So these are the terms, again, we're going to talk about. Nonobstructive chronic bronchitis, that is cough and phlegm with no airflow limitation, sometimes called gold zero. There's two terms, and we'll define all these a little bit more. Prism, that group in the top left I showed you, and pre-COPD. What's in a name we'll talk about. Why is it called pre-COPD? Should it be called something else? But everybody else who is at the top of that line, top of that graph, they don't have a name. So the next question is, do you fully understand these terms? Yes, no, or partially? Now, of course, I know you're all smart, you recognize that I'm here, so I've got to tell you something new, so nobody's going to answer yes. Of course, nobody wants to say no, and nobody would raise their hand if I asked them, they wouldn't say no. But on this, I have no idea who's answering, so that's the advantage of ARS. We don't have to worry about HIPAA here. Everybody, this is confidential. So most of the people, partially. I think I would put myself in that category, so I think that's fine. So what is gold zero? We'll talk about that, because that's actually an old term. At the bottom right here, gold first defined this in 2005, and then they got rid of it in subsequent iterations of the gold document. So gold zero originally was a history of cigarette smoking with cough and sputum, but no airflow limitation. Well, so why is it a gold category at all? Well, to gold zero, it's not a gold category, it's not a gold one, it's a gold zero. So that's what they called it. And why would they even pick out these patients as being important to identify in the first set of gold guidelines? Well, because initially, one of the purposes of gold was to raise awareness of COPD and raise awareness of the importance of smoking and lung disease. It was a public health document as well. So they wanted people to recognize that people had cough and phlegm, but didn't have airflow limitation. But in addition, they felt that at the time, the cough and sputum preceded the development of COPD. Doesn't always, but that's what they thought at that time. So that's why this term gold zero existed at all. So in COPD gene, we had over 1,000 of our first patients with gold stage two to four out of our first 2,500 COPD gene subjects, we wanted to see who had chronic bronchitis. And the definition of chronic bronchitis is here, it's a longstanding definition proposed by the ATSDLD respiratory questionnaire that dates back decades and eons. And we had 290 patients with chronic bronchitis and 771 without chronic bronchitis in this first group that we identified. So we said, well, what's the importance of chronic bronchitis? And again, what I'm showing you are studies from COPD gene, but there are multiple other studies that show you similar things. So they had worse shortness of breath. They had worse health status by SGRQ. And their BODE score was pretty similar, but actually that was a tiny bit increased as well. So these patients who had non-obstructive chronic bronchitis still had problems. And exacerbations were almost twice as frequent if you had chronic bronchitis compared to if you didn't have chronic bronchitis. And the percentage of subjects with severe exacerbations, hospitalization was higher if you had chronic bronchitis, the CB plus in the left column compared to CB minus, those without chronic bronchitis. So significant symptoms, significant impact of the symptoms on their daily lives and their shortness of breath, and also their exercise capacity by a six-minute walk and hospitalizations. So then we had the opportunity to look at non-obstructive chronic bronchitis. Who were the patients who had non-obstructive chronic bronchitis, cough and phlegm with normal airflow? If you look at those patients, non-obstructed chronic bronchitis, no non-obstructive chronic bronchitis on the right. And those with chronic bronchitis and who had chronic bronchitis and non-obstructive on the left, they had worse health status. And this was a significant score. So this is a difference of the SGRQ from 36 to 15. The minimal clinical importance of the SGRQ questionnaire for quality of life is four points. This is a huge difference. So this impacts these patients a lot if they have cough and phlegm compared to no cough and phlegm, even if they don't have airflow limitation. So what is PRISM? That group I showed you at the top right. I'm sorry, top left. PRISM is up here. A normal FE1, FEC, no airflow limitation, but a low FEV1. So the definition is based on spirometry. It's not based on anything else. But in our population and most populations, we're talking about only smokers here. Classically, these patients may be said to have restrictive disease, but we did CT scans and they don't have any interstitial disease, no chest wall problems. So nothing that smacks of interstitial disease. So we looked at these patients, as many other studies have, and 12.5% of our patients have PRISM. I mean, that's a lot of population. We're going to miss these patients if you only do spirometry and think about the classic spirometry. We need to think outside the box, as Tom did. What are these patients? Who are they? And what is this spirometry pattern? Well compared to patients without COPD, the PRISM patients had more shortness of breath, worse walk distance, more chronic bronchitis. They also had more CT abnormalities in terms of greater wall area of their wall thickening on their CT scan. They did have more diabetes and they had slightly higher BMI, but we had groups, we had a subgroup that did have a higher BMI and subgroups that did not have higher BMI compared to not PRISM. So we don't think that this is important. But they had less emphysema, interestingly, even though they had more airway disease. They also have a higher mortality. So when the left is all-cause mortality and the prison group is an orange and normal spirometry is black. I don't know if you can see that, but the orange is higher than the black. So these patients have a higher all-cause mortality. And this was not just from COPD, but Emily Wan looked at COPD gene plus other cohorts. So this is combined multiple cohorts, not just COPD gene. And on the right is respiratory-related mortality. And compared to the black, which is normal spirometry, orange you see has a higher mortality because that's PRISM. And people with obstructive disease have even a worse survival and higher mortality. So what's the causes of the mortality? On the left is cardiovascular mortality. And you can see that's higher in PRISM as well. And on the right is respiratory-related hospitalizations and mortality, higher than people with normal spirometry, but not quite as bad a people as people who have definite airflow limitation. So these patients have problems. PRISM is an important group to represent. People have criticized PRISM because they say, well, this spirometry pattern, which is really the definition of PRISM, is not stable over time. And so this is, again, a paper from Emily Wan, who's in COPD gene, our guru on PRISM. And you can see that in the middle panel there of each of these, the blue getting to darker blue as you go left to right, 51 percent of patients in phase one of their study, compared to phase two five years later, compared to phase three on the right 10 years later, you can see 50 percent of those patients stay in PRISM. Some of them go to gold zero. They don't have that spirometry pattern. And some get airflow limitation, too. About 25 percent go from PRISM to definite COPD and airflow limitation. So the pattern may not necessarily be stable over time, but I think the importance of PRISM is not just what happens over time to the spirometry, but what happens else to them. So this is information from the Copenhagen City Heart Study. It was published in 2021. The verbal description on the right is PRISM, even if they had recovery of the PRISM pattern in the Copenhagen City Heart Study, they still had a high mortality risk. They had a higher mortality risk compared to people with normal lung function. So even if their pattern changed over time, if they were identified as spirometry by PRISM at any time, they still had a higher mortality, even if that pattern changed. These patients are at risk, no matter what happens to their spirometry. So identifying them at any time is important. Well what is pre-COPD? Well, pre. So to me, pre would mean, well, this is going to get to COPD at some time. Well, we don't necessarily know that either, and we'll talk about the terminology, but it's defined as no classic airflow limitation by spirometry, a normal FV1-FVC ratio with either respiratory symptoms, cough and phlegm or shortness of breath, and or structural abnormalities on CT scan. Now one of the advantages of the COPD gene is everybody had CAT scans. Clinical practice, you don't do CAT scans on everybody, but maybe you need to think about that. Even in people that don't have COPD, it may be more important than people who do have COPD to look at CAT scans. And or physiologic abnormalities, they could have prism, but they may have other abnormalities. They may have a low diffusing capacity, they may have air trapping. So pre-COPD are smokers without classic airflow limitation, but other problems in their lungs that you really need to search for. So who are those patients on our graph of spirometry? You know, I hate to keep going back to spirometry, but that's what everybody does. They use spirometry. So, that's why I'm using this as a highlighted here. So, in the top, those without COPD, some of them could have pre-COPD. Even prison patients, well, in some studies, prison patients are called pre-COPD as well because they do have some pulmonary function abnormalities but not classic airflow limitation. And the patients with chronic bronchitis, they have symptoms, no airflow limitation. That's also pre-COPD. So, we're getting more complicated here. As we look at these terms, they're not totally independent from each other. There's a lot of overlap. So, when you use the terms, you need to carefully think about who you're describing in your practice. So, there are two, I think, major publications about pre-COPD. The first, of course, is from COPD gene. Now, the people who are in the spiromic study, another NIH cohort of observational study would say, oh, the prison, these patients are better described, smokers without airflow limitation, in the spiromic study than COPD gene. And we always battle each other who's got the best paper. We all find similar things in both these large NIH-funded studies over time. So, our paper is called Clinical and Radiologic Disease in Smokers with Normal Spirometry. I'll tell you what title we wanted to choose. I'll tell you what journals did not accept it. But anyway, it was published in JAMA Internal Medicine. And we looked at GOLD0, because pre-COPD was not defined at that time. But GOLD0 is part of pre-COPD. And we looked at, compared those patients to patients who had GOLD Stage 1 spirometry COPD. And you can see, you know, pretty similar. Chronic bronchitis in both populations. SGRQ greater than 25, pretty big quality of life. MRC dyspnea scale. So, these patients had a lot of decrements. If you look at them, similar to patients with GOLD1 COPD, even though you call them GOLD0 or smokers without airflow limitation, whatever you want. So, we came up with a definition of impairment. Now, these patients we felt could be impaired and have problems in terms of symptoms, in terms of structural abnormalities on CT scan, because we did that in everybody, in terms of functional issues like low walk, or people who had acute respiratory disease. Now, you can't call it COPD exacerbations, because they didn't have COPD. But it's a COPD-like exacerbation. They have acute respiratory illnesses that if they had COPD, you called it an exacerbation. So, our definition of impairment is one or more of these issues. And we found that 54% of patients were impaired. They had some abnormality in one of those areas. They had symptoms, impaired health status, they had hospitalizations, they had radiologic evidence of lung disease, and they were receiving respiratory medications. Well, it's your population and how you collected it. That's why they were on respiratory medications. They don't have lung disease. How could they be on bronchodilators? Well, I remember I told you that Spiromics had a similar paper published in the New England Journal of Medicine. That somehow they get better billing than we. And in their population, 42% use bronchodilators, even higher than COPD gene. So, the physicians were smarter than spirometry in these patients. Patients had symptoms. If they have symptoms, their physician said, well, I have to try to treat them. What do I have available? The only thing I have available for lung disease is bronchodilators. So, I'll put them on bronchodilators. Question, of course, is does bronchodilators help? What we wanted to call our study was the myth of the healthy smoker. And the journal would not allow that. So, we didn't call it that. But I still like that term. You need to think about people who have a history of cigarette smoking, whether they're smoking now or smoked in the past, they are not healthy and we have to find that. Now, what's in the name? What do we call this group of patients? Well, the patient I presented to you may have had early COPD, but that patient didn't have COPD because their spirometry didn't show that. Although it showed prism, it didn't show COPD. So, is this early COPD? Is it young COPD? Is it prism? Yes, some have prism. Is it PDS, pulmonary disease and smoking history? We'll come up with some new terms. Is it no POD, non-obstructive pulmonary disease? Is it pre-COPD? Well, in its wisdom, the Gold recommendations call it pre-COPD. And that is an FEV1-FEC that's greater than 0.7, no air flow limitation. And this is a diagram from Milan, how I was first author of this paper. So, Gold's pretty smart. So, before the Gold 2023, they published this paper by reference here talking about pre-COPD. So, they can then cite it in the recommendations and say, oh, here's the paper that talks about it. So, that's what they did here. And you can see they defined COPD, pre-COPD, again, as symptoms, structural abnormalities or functional problems. So, again, here's our new terminology. Let's go back to spirometry and see where we land here. Well, it gets more confusing, right? So, prism is still prism, top left. But what is no COPD? Well, it's still all those patients above that horizontal line, they don't have air flow limitation. Pre-COPD, these could be considered all pre-COPD. Is it non-obstructive chronic bronchitis? Well, some of these patients also have non-obstructive chronic bronchitis. So, you see these terms overlap a lot. And you need to know what term you're using, who you're describing when you have a particular population in your clinical practice. It may be hard to distinguish these because you need to spend some time figuring out. You need to have a CT scan, symptoms, spirometry, diffusing capacity, maybe. Talk about, what are their symptoms? Are they short of breath? Do they have poor exercise capacity? Do you need a walk test? So, this is not an easy group of patients in our practice to sort of find, figure out, and label them with a term. And labeling with a term, often you need to figure out what the diagnosis is in terms of deciding a treatment. So, now we have the what. The what is, what are these problems? We have the so what. People that have these definitions and diagnoses have problems. But now, now what? How do we treat them? Well, I don't think we know. I don't know how many of you remember this slide from the American Thoracic Society published in 1995. One of my other mentors, Gordon Snyder, as well as Tom Petty, was very instrumental in this. So, here they're describing COPD. In the top left in that purple circle are patients that have cough and phlegm. Top right are all the patients that have emphysema. They didn't have CT scans then, but they did have diffusing capacity. And the bottom blue is asthma. So, what is COPD? Well, first thing, the airflow limitation. So, that dotted line box is everybody with airflow limitation. But you can see that there are patients who have chronic bronchitis who do not have airflow limitation. Patients with emphysema do not have airflow limitation. So, those patients, they knew existed even back in 1995. So, I would change this slide a little bit today. Okay, when we're talking about pre-COPD, I would say those patients with respiratory symptoms, including chronic bronchitis, without airflow limitation, the shaded purple, that's pre-COPD. People who have CT abnormalities, not just emphysema, in the top right, the shaded yellow, that's what we're talking about in terms of COPD, pre-COPD, not real COPD, but pre-COPD. So, there was another paper that I really like from COPD Gene, and this paper said, well, if we have all these problems, we can categorize patients a little more in terms of what their problems are and look at what change they have over time in spirometry and their mortality. That's one of the advantages of COPD. We're collecting deaths and cause of death. We have an adjudication panel to adjudicate the cause of death. So, we're really interested in long-term progression or prognosis and not just what's happening to the patients at a single point in time. So, we have this diamond that we came up with. On the top of the diamond is exposure. Now, all our patients were smokers, so everybody has the black characteristic. Some patients have CT scan imaging problems, which we defined as more than 5% emphysema, more than 15% gas trapping, or airway thickening. That's in the blue on the left side. On the right side of this diamond is symptoms. Shortness of breath or chronic bronchitis. And the bottom is spirometry problems, which may be air flow limitation or may be prism. So, patients may have one or more of these characteristics in this diamond. And we like the diamond better than gold. So, we said, maybe in the future, there'll be COPD gene diamond rather than COPD gold. So, we're hoping that that'll catch on someday, maybe. So, if you look at those characteristics again, okay, exposure, everybody that was a cigarette smoker in the top line, exposure in CT abnormalities, exposure in CAT scan problems, exposure in spirometry, and you start combining them, you come up with these different categories. Now, nobody should know these categories. You don't need to, because this, again, is COPD gene. We need to take this to the community and try to operationalize this, which is what we're trying to do. And we called the patients in the top there, B, C, and D, possible COPD. I'll show you why in a minute. The middle two categories, F and G, probable COPD. And H, people had everything we called definite COPD. And the reason we did that is we were able to look at the odds ratio of the FEV1 change by more than 350 ml over five years. Or the hazard ratio for all-cause mortality. And you can see our reference population with those patients with no COPD, just exposure history, it's smokers only. As you go down, you see that the odds ratio of FEV1 decrease over time increases, and the hazard ratio of all-cause mortality increases. So these patients with pre-COPD, they do get more airflow limitation, and particularly they're at risk for death. So we feel that these pre-COPD patients are really important to think about, and characterizing patients with all these things in the triangle are really important. That's why we decided to call them possible COPD gene 2018 diamond, or probable COPD gene 2018 diamond, or definite COPD. We have three categories to lump these patients together. So here's our diamond, and I would have you think that what we've talked about today includes all these things to assess in patients who come into your office and have cigarette smoking, whether they have COPD or not, actually. How much exposure do they have? What are their clinical symptoms? What's their CT imaging? Do they have abnormalities? And what's their spirometry? The better-defined disease than spirometry alone. You see we're moving away from spirometry, okay? The world is doing that, COPD gold, COPD. They need to catch up with the rest of the world. You know, they're so entrenched in defining COPD in this particular category, and that's fine, but you need to recognize there are more people out there who have a history of exposures like cigarette smoking and major problems that are going to impact them. So how do you operationalize this? Well, I had a companion paper in the Journal of COPD Gene, and to summarize it, I said, well, you need to think about people that come into your office in terms of exposure, symptoms, spirometry, of course, and CT imaging to identify where patients fit in this diagnostic paradigm, in this new diagnostic paradigm, and what would you label them so you can, as future papers come out and tell us about treatment, figure out what to do for them. And there needs to be a lot more in terms of treatment. The only treatment trial is one that was published in 2020, Fernando Martinez and Milan Han were the primary investigators, and they said, well, in this group of patients with pre-COPD, what do we have available? Let's use a dual bronchodilator and see what happens to the patients. Well, the article was published in the New England Journal of Medicine, and one of the things you need to remember about the New England Journal of Medicine is not just that it's high impact, but why is something accepted into the New England Journal of Medicine? Well, they have a policy that says it has to be impactful for clinicians, has to be paradigm changing, has to be something that's new and novel and different and has clinical impact. So treat this group of patients without COPD with bronchodilators, well, that should have a lot of impact whatever they show, right? Okay, doesn't necessarily mean it was a positive study. In fact, it was a negative study. So bronchodilators in tobacco-exposed patients, on the bottom left, change in SGRQ, there was a little difference, but not statistically significant. In the transition dyspnea index, which is change in shortness of breath, not a difference, and change in CAD score, COPD assessment test, test of patients with COPD, what is their quality of life, no change in their main outcomes with dual bronchodilator. So does that mean we shouldn't treat these patients? Well, I would say there's probably patients buried in here who did have a response, as well as patients who didn't. We need to find those patients, we need a lot more information. Of course, what are we looking for? Well, if these patients have more airway disease, maybe we need a different airway-specific medication, which doesn't exist yet. And maybe in COPD gene, as we do metabolomics and proteomics, as well as genetics, we will find markers that tell us what kinds of medications we need to develop to prevent further airway inflammation and reduce the airway inflammation that's present. We don't have those medications yet, but it's an area that's ripe for clinical investigation with the right medications, which hopefully a pharma will be able to help us develop. So the so what, we really don't know yet what to tell you about that. Fernando Martinez wrote an interesting article a couple years ago in the Blue Journal looking at therapeutic proposals for what he defined as either early COPD, he said this is people who are really young, or pre-COPD, as we defined it, and agreed that the goals for treatment should be to improve mortality, because these patients have a high mortality, improve their lung function, but more improve their symptoms and exacerbations and structural abnormalities. Again, medications we do not have available yet. So I'd like to thank the COPD gene investigators, many of whom, but not all, are on that list, and I added Dr. Petty, because of his landmark studies that he's done leading us to investigate this disease a lot more in a lot more depth over time, and telling us about some important things in terms of treatment, pulmonary rehabilitation and oxygen therapy. So I hope that with this expanded paradigm definition of COPD, that you'll emulate Dr. Petty. And what I remember Dr. Petty for was first his patient-centric evaluation and treatment. Treat each patient as an individual. And so you need to evaluate each patient as an individual, determine what their particular issues are, evaluate them in depth. With the history of cigarette smoking, including the things we talked about, how much cigarette smoking, what are their symptoms? One of my favorite things I talk to medical students about is that, well, I'll play the patient, you play a physician, ask me if I have cough and phlegm. It's not easy to do, right? So the student says to me, do you have cough and phlegm? I say, no. I said, why did I say no? Because you asked the question wrong. So do you need the ATS definition to say, do you have cough and or sputum for more than three months out of the year, for more than three years? Well, what do you mean cough and phlegm? Sure I got cough and phlegm, and all my buddies that smoke have cough and phlegm, it's normal, isn't it? So we need to know how to be patient-centric in our evaluation, simple things like medical history for these patients as well. And look for structural abnormalities on CT scan, and do spirometry and be really careful about how we're interpreting it. Recognize and prevent that there are poor outcomes for many of these patients. And as you saw, patients with PRISM also have poor cardiovascular deaths. So evaluate them for not just their COPD, but for other problems, particularly cardiac problems, which may be their eventual cause of death. So this new terminology, non-obstructive chronic bronchitis or GOLD0, PRISM and pre-COPD. So the question is, will you employ these in your practice? Yes or no? Well, I don't think I've ever got 100% on any question I've asked. So that means I asked the question right, no. It means that, thank you for listening, and to end this, so they understand there were some fireworks here the other night, and because everybody got 100%, we'll have fireworks at the end here. So Dr. Tom would endorse the recognition and management of these patients who had a smoking history, and here's my favorite picture of Tom, because he really enjoyed fishing so much. But Tom would also tell you to smell the roses. This is an oxygen bar I took a picture of in Las Vegas last time I was there. So he might say smell the oxygen as well as smell the roses. So thank you very much. We have some time for questions. Yes, sir. Thank you for a very good discussion of this topic that's become more and more prominent. There's several papers on the same thing, one recently from San Francisco, where they talked about the smokers exposed with supposedly normal spirometry. But as you're reading the PFTs, what kind of advice are you giving the people that are gonna look at this, the non-pulmonologists, the family practice, the internists, what do we do about those women who are obese and have respiratory symptoms and that the other diseases will kill them, or maybe the respiratory. So I think some of the studies that have shown pre and post, and they've been following them, the ones that get better, someone was involved. Someone made them stop smoking. When I do a retrospective evaluation of my patients, they got better because we intervened. We stopped smoking, we did other things, we made them lose weight. How do you approach that? So I think there are four questions there. Maybe there's more, I can only count four. I only have five fingers. So the first question is how do you interpret spirometry if they have a prison pattern? Well, you know, I think our classic interpretation of pulmonary function is horrible because we interpret the numbers, but the numbers have to be taken in concert with the individual patient, and that's what Tom would say. Numbers don't mean anything by themselves. We need to look at the whole patient, and that's why these other things I talked about, symptoms, quality of life, respiratory symptoms, eventual mortality, other diseases they may have, structural abnormalities in their function is really important. So I read pulmonary function tests, and I go back and forth with myself all the time and my colleagues at National Jewish. How should we read prison spirometry? Well, first, you don't know if the patient has an exposure history, okay? And second, as David Menino in the audience likes to say, well, these patients could have a restrictive problem. It depends what the viral capacity is and everything else, and is the FEV1-FEC high? You don't know what they have, but you interpret it as the FEV1 is below normal, right? FEC is normal, ratio is normal, they don't have airflow obstruction, and then you can say if the patient is a cigarette smoker, I mean, it depends how far you wanna go. If the patient has exposure history, maybe they have prison, or if they're obese, maybe it's related to obesity or a structural problem of their chest wall. So you don't know. It depends how far you wanna go in interpreting pulmonary function tests. I could take any spirometry and spend a whole page interpreting it and provide references at the bottom. Unfortunately, we don't usually do that, but maybe you should see a pulmonologist. So I think that's one complicated answer to spirometry interpretation. And of course, we need to think about racial issues as well, and I have a talk on this and there's others at this conference. So go to the sessions that talk about racial values and using race-specific or non-race-specific, non-race-adjusted pulmonary function test interpretation as well. And then what do you do for these patients? Well, I think one of the reasons, and I didn't focus on this, but it's important, is if these patients have an exposure, you wanna stop the exposure. We know we don't want them to smoke, and if they already have some abnormality, even if it's not COPD, which puts them at a higher risk for progression or for mortality, make sure you double down on smoking cessation. And if they are obese, make sure you control that, and that could be precipitant for their shortness of breath. And they have cardiovascular disease, evaluate that as well. So I think we just stretched the surface in what I think physicians should think about in these patients. Thank you for your questions.

COPD

non-obstructive chronic bronchitis

prism

pre-COPD

airflow limitation

spirometry

CT scan

treatment approach

Chronic Obstructive Pulmonary Disease