This webinar was recorded on Tuesday, July 26, 2022

Dr. Vickram Tejwani will give us an in-depth look at the unique characteristics of chronic obstructive pulmonary disease (COPD) and discuss management strategies.


  • Dr. Vickram Tejwani

Transcript: This transcript is automatically generated. While this transcript is believed to be accurate, errors sometimes occur. It remains your responsibility to evaluate the accuracy and completeness of the information in this transcript. This transcript is not intended to substitute for professional medical advice.


Welcome to today’s webinar on COPD phenotypes. This webinar series is sponsored by the American College of Allergy, Asthma and Immunology and we work together to share the latest information and advances in allergy and asthma with you. This is Sally Schoessler, director of education for Allergy & Asthma Network. Today’s webinar helps Allergy & Asthma Network live out our mission to end the needless death and suffering due to asthma, allergies and related conditions. Through outreach, education, advocacy, and research, we’re pleased to welcome today’s speaker, Dr. Vickram Tejwani. Doctor Tejwani is a physician in the asthma and COPD centers at Cleveland Clinic, where he joined after completion of a pulmonary and Critical Care Fellowship at Johns Hopkins University.


Doctor Tejwani is an active scientific investigator in both asthma and COPD and an assistant professor at the Cleveland Clinic Lerner College of Medicine. He is passionate about patient education and translating nuanced evidence and data into actionable recommendations. He has enjoyed partnering with Allergy & Asthma Network on numerous patient centered and academic endeavors. Thank you so much for being with us today Doctor Tejwani and for sharing your insights on this important topic about COPD.

Thank you for the kind introduction invitation both to you Allergy & Asthma Network and the American College of Allergy, Asthma, and Immunology. I am very excited to be here and speaking about this topic that’s certainly very dear to my heart both from a research perspective and clinically with the patients we’re seeing.


So in brief, what I’m hoping to address today is most importantly raise awareness of the established and some kind of established COPD phenotypes. A part of this will border on things that are emerging and developing evidence, and a part of it will. Center around true established kind of consensus, agreed upon phenotypes and I think. A part of that will hearken to future directions, but my second or am hopeful learning object from this is a true practical takeaway of just what are when you have a patient that is experiencing COPD or suffering from COPD in front of you, what are some traits or aspects of the phenotype that are will lend themselves to specific therapy or kind of moving into this era of precision medicine where not all COPD patients get the same treatment.


There are some treatments that work for all, but other treatments that will work if only they have a specific trait? So I always find it helpful when reviewing any disease and in particular COPD just to understand how we came at the definition of COPD, which is based on spirometry. I’d like to make the case to all of you listening that COPD is a heterogeneous disease. It’s a single term used to define a very heterogeneous disease. And then really the main focus of our talk which will be the COPD phenotypes and what we can expect moving ahead.


So without going too far historically and you could really go back on this with COPD just being described as people suffering from cyanosis, fatigue and before kind of the era of pulmonary function testing and spirometry. But where we got to our contemporary definition of COPD was. Based on spirometry testing, where we have a patient blow out as hard as they can and we measure the amount of air that comes out in the first second, which is defined as the forced expiratory volume of one second or FEV1 And the amount of air that comes out as they continue to blow, which is the forced vital capacity.


And the initial definition of COPD was actually that you would not get that. You would not even get 80 % of your air out in that first second, which is this FEV1 over FV C of less than 80 %. And in 1985 actually there was a very large study where they looked at all these ratios and they found these were all individuals with smoke that smoke cigarettes at the time and that a cut off of 70 % of your FEV1 to FVC ratio would have the greatest power to detect individuals with a subsequent decline in lung function.


And I just emphasized that to say that it’s not necessarily that this was people that had disease or didn’t have disease. This is kind of something that there’s been prior evidence for and really that cutoff was chosen based on who was likely to have a decline in lung function. And this study from the mid eighties was, subsequently excuse me, adopted by the American Thoracic Society and gold organizations for COPD and actually to this point despite some a little bit of controversy which we’ll touch upon in the next slide. That’s not changed at all. The controversy from this comes that if you use this cutoff over age there are three things that influence pulmonary function test which is age, sex and height.


So as one ages the expected values for them go down. So there’s been some conversation around using the lower limit of normal of this ratio as opposed to a fixed cutoff such as 70 %. And right now, the community is still generally using the fixed cutoff and this graph really exemplifies why. So this is the fixed cutoff of 70 %. And you could see that as we age starting here at 30 years of age on the X axis, what you expect that ratio to be declines with age.


So for example, somebody who’s 70 years old, 68 % may actually be normal for them even though it’s below the, our established cutoff of 70 %. The reason we’ve ultimately elected to stay at 70 % is that we find it’s better to detect disease earlier, particularly in a younger population. So this person would, if you used a cutoff, might of the lower limit might be considered normal. But if you 70 % they wouldn’t. So using that cutoff or excuse me, I flipped that. So if you use the lower limit of normal, they would be diagnosed. Umm or not diagnosed with COPD, but they would be at 70 %.


So essentially using the cutoff of 70 per 70 %, we are choosing to. Err on the side of picking up more disease, including in our older population, but that’s thought to be better because it raises awareness, potentially initiates monitoring and specific therapies for any symptoms that they might have. And then there’s been additional efforts to see, to revisit this possibility of if 70 % is the best cut off or not. And this was a study done in the Mesa color where they looked at different cut offs, 6566 etcetera onward and looked at what cutoff led to the best identification of developing symptoms, respiratory symptoms and COPD flares which is on the Y axis and you could see here replicating essentially that.


Higher study from the mid eighties seventy or technically seventy one percent % best efficacy at identifying individuals that would have COPD symptoms at the present time and develop COPD symptoms in the future. So this study which was from 2019 essentially reemphasized the current consensus diagnosis which is an FV one over FVC ratio over 70 % the thing that i will or less than 70 % to diagnose COPD. And the reason I again just want to talk about all this is that is that is a true definition, it’s what’s kind of established for all of us to use.


But you can see that even 7273 %. So these are people that technically would not meet the quote, unquote diagnosis of COPD because their cutoff is above 70 %, but they still do develop some symptoms in the future, they still develop potentially exacerbation, so. I just say that I think for any disease definition, particularly as we look at clinical trials and epidemiologic data, we need to have an agreed upon definition, but it’s not exactly a. Perfect cutoff there are there’s a spectrum of disease and preclinical disease as well above that cutoff that could still be of relevance.


So next, moving on to COPD as a heterogeneous disease and COPD is a heterogeneous disease. This is really from conception to development. So these two pictures are from 2 recent reviews. Well, one more recent review article and one review article from a few years ago on the left. I really like this picture on the left because it emphasizes, I think in the past we’ve thought of COPD as a disease that smokers get. So basically, you’re you, you’re born, you live life. You aren’t not at risk of COPD. Then you start to smoke and then you develop COPD, and we’re starting to understand that it’s much more complicated from that than that.


One aspect that might not surprise you all is that genetics play a role. There is a genetic cause of COPD, but there’s also seemingly genetic predispositions to developing COPD. And in fact, not only genetics, but what you’re exposed to in-utero as a fetus can actually influence the development of later respiratory disease. So it really starts even before you’re born as far as the possibility of developing this. And then as we get into adolescence years, you’re. Getting sick recurrently can do it. Your work can play a role and then you get into your more traditional risk factors which are smoking, certain occupational exposures and also cooking exposures, particularly in the developing world where biomass or other indoor wood form of cooking is used.


So and that’s essentially summarized here in this, in this figure on the right that you start in with early life exposures. There are other noxious exposures such as yourself smoking others. Other smoking around you occupational exposures and then individual and social risk factors which particularly in the last couple of years or last few years, we’ve started to have increased attention to their role in COPD among many other diseases and then the environment you’re in more broadly.


And starting to become more and more relevant, particularly with some of the records that have been broken this summer. The humidity, heat changes can all exacerbate and flare people’s diseases. Some of these are a little bit less causative of COPD and more so aggravate them. I think over here you’re really looking at more of the causes when you get over to individual and social factors as well as the environmental factors. You’re looking at things that lead to worse disease severity.


And then as we mentioned, all people that have COPD by definition have an FEV1 over FVC ratio of less than 70 %. But beyond that, the manifestations of COPD are quite varied. This is a really classic image from Frank Netter who’s one of just a fantastic medical illustrator and showed kind of the original pink puffer and blue bloater of COPD. But this is and those two phenotypes still do exist that’s on it from a clinical perspective. We’ll discuss the next slide that some people with COPD will exacerbate more than others and then also some people with COPD will have emphysema which is a chest CT. Finding and others won’t.


So you could have obstruction on spirometry or COPD like this or you could have true emphysema such as this, which we’ll talk about in our COPD phenotypes as well. So COPD can be caused from different etiologies. It can present clinically in a number of different ways. It can progress in a number of different ways. So each of these 4-4 bar graphs up here shows a change in the lung function of individuals with COPD. And you’re seeing that and this is actually bracketed out by their lung function and you’re still seeing a very big spread some participants will decline in their lung function by.


Fifty sixty seventy milliliters of FEV1 per year, whereas some will stay relatively flat and won’t lose function at all. So it’s really a very diffuse progression of disease and then. In a cross section, there are patients that have frequent exacerbations and frequent exacerbations which are flares of disease that typically require steroids and or antibiotics have their own consequences in terms of higher mortality and poor quality of life.


So the gold organization for COPD has recognized this. And this box in terms of clinical management of just a COPD patient independent of phenotypes is probably the most critical box. So on the X axis, you’re determining how bad their symptoms are with two COPD questionnaires and on the Y axis going from A to C or B to D, how often they flare and essentially where an individual falls into this box. Will be good to determine how you treat them outside of the specific phenotypes that we’ll begin talking about next.


So before we begin speaking specifically about the phenotypes, I just want to ensure we’re all using the same language. So phenotype scientifically was a part of language around genetics where you have the genotype, which is the change in genetics and the way that it manifests in the world is the phenotype. So that really is what it means originally. That’s not quite the way we’re using it medically and certainly not the way we’re using it in the context of COPD. So this was from an article in 2010 just to and that also kind of underscores how long this idea of trying to phenotype COPD and look at specific therapies has been going on.


But the proposed COPD definition of a phenotype is a single or combination of disease attributes that describe differences between COPD’s as they rate relate to clinically meaningful outcomes and I think that clinically meaningful outcome, it’s really a broad term, it’s intentionally a broad term. Exacerbators is a perfect example of this. It has both symptoms. It also means that they’re going to develop worse disease, so that has a rate of disease progression. And then there are also specific treatments for individuals that respond that have frequent exacerbations.


So the second definition is a little bit more of a practical definition than the first, particularly within the context of COPD. Sorry, I believe there might be a timer on my slide. So I think they’re popping ahead of me. The third one. And this really gets to being very practical to a clinic patient in front of you or a hospitalized patient in front of you, which is a trait and a treatable trait. And this would be something like eosinophilia. If a patient has eosinophilia, that’s a trait and that means we should start an inhaled corticosteroid and that’s just a very, that’s I think the ultimate goal of all of this.


Of the phenotype which is a little bit more in the research and scientific realm to bring it to the bedside to just say OK, if they have this particular trait that means I should start this particular therapy in this individual. And that’s really I think what we’re all moving toward and trying to get to within COPD and the foundation for that is really this recognition and hopefully the case that I made to you all today that it really is a heterogeneous disease. So it wouldn’t be appropriate to treat such a heterogeneous population the same, because we’d probably be missing some treatments that might benefit particular individuals.


The kind of gold standard of this and the only example that we have in COPD is alpha one antitrypsin deficiency is for an endotype and endotype is when you have the you know the specific cause of something, you know what that cause leads to and you treat that cause. So that would be, we know the exact gene abnormality that leads to alpha one antitrypsin deficiency, we know that it causes deficiency of a protein.


Called alpha one antitrypsin. And we know that if we in some part, some individuals, select individuals, if we treat them with that protein or augmentation therapy, they’ll get better. That would be ideal. Unfortunately, in disease, in real life is not always that clean at least with the technology that we have right now. So but i think we kind of want to take things from number two which is where we’re where we are currently just trying to identify these phenotypes, characterize them, understand that they might be associated with different symptoms, different progression and translate them into traits that we can treat and ultimately hopefully find upstream what the cause of the different.


Unit type sets. So my next slide just shows a picture of emphysema. So we had touched upon this in the various radiographic images. So emphysema is airspace enlargement, it can occur with noxious stimuli, it can occur with alpha one antitrypsin deficiency and all the different kinds of ideologies that we talked about before. So when you see a CT scan like this with your patient, there are a couple of things that we can think about.


One is that we do know that patients with emphysema. Particularly if there’s progression of emphysema, there’s higher mortality. So this would be something whereas if you’re counseling your patient and a common question I get is, you know, what does this mean for me that I have this diagnosis, this would be something that you could say the disease might progress a little bit more quickly and you just given unfortunately the presence of this airspace destruction on CT As we get into the treatable trait part of the emphysema, I really want to underscore this image on the left and I chose this image intentionally. You could see here that it’s very upper low predominant.


So in the early two thousands there was a net study or the national emphysema study where they looked at surgically removing this. Damaged lung or this emphysematous lung and what we’ve kind of taken away from that and now we’re there are some ways to do that bronchoscopic we as well which is a little less invasive is that individuals that have an upper lobe predominant disease might be candidate they do better with this. So if you’re seeing this upper lobe predominance of emphysema. That would translate from just being a phenotype into a treatable trait and that would be someone that you start to think about lung volume reduction surgery and or bronchoscopic volume reduction procedures and to remove this disease lung.


If it’s emphysema like this, where it’s kind of scattered throughout, there’s unfortunately not a lot procedurally to do because it’s so diffuse that you can’t really just remove the one part of the lung that has experienced the damage or the emphysema. Another progression of this or another separate phenotype is CPF E, or combined pulmonary fibrosis and emphysema. So a lot of the same risk factors that cause COPD and emphysema can also cause lung scarring or fibrosis. So there ends up being a subpopulation of individuals that develop both pulmonary fibrosis and emphysema.


And the way this typically manifests is with emphysema in the upper part of the lung and fibrosis or scarring in the bottom of the lung and because they have. Lung volume expansion from the emphysema. Their vital capacity is increased because they’re retaining air. But then they have restriction or lung volume loss from the pulmonary fibrosis or scarring. You end up seeing a normal FVC in them. There’s nothing if you just see this on a CT scan, there is no specific treatment to offer. But if they have CPFR combined pulmonary fibrosis emphysema and they also have pulmonary hypertension which can occur from the low oxygen that occurs with these individuals, you could use a pulmonary hypertension medicine called inhaled treprostinil which is specifically helpful in this population.


So if you see the kind of practical translation of this would be. So you see this CT scan where you’re seeing both scarring and emphysema, pulmonary fibrosis and emphysema. You would think about getting an echocardiogram to then evaluate or an echo of the heart to evaluate the right side of the heart to see if pulmonary hypertension is present. And this was the study that showed that inhaled treprostinil even in. It was just a study for pulmonary hypertension in general, but there were 17 individuals within it that had combined pulmonary fibrosis and emphysema. The next two phenotypes are a little bit more well established and fortunately have more specific therapy. So chronic bronchitis, which is defined as making sputum every day for at least three months out of two consecutive years.


It kind of tells us that there’s a little bit more inflammation in the lungs. And fortunately we know that if that is present that roflumilast which is a phosphodiesterase inhibitor can, will benefit these patients. And what it actually can do is both reduce their symptoms and reduce the likelihood that they have flares of disease. So when you have a COPD patient in your office that’s something you always want to be asking about is do you have a daily cough and do you make sputum daily and if the answer to that. Yes, then you can use roflumilast therapy. Some of the practical challenges with this is that it’s not well tolerated from a GI adverse effect perspective, but hopefully they’re able to tolerate it and derive some benefit from it.


Chronic bronchitis as well, like many of these phenotypes is associated with more progression of disease or symptoms, so generally speaking, worse disease. This is something you could counsel your patients on, but it’s something that they’re actually already experiencing, unfortunately, because they’re having this cough and sputum production every day. The next phenotype is the exacerbated phenotype. So this is really a very, a phenotype of a lot of focus because it leads us to a lot of patients. A major disruption in the quality of life because they’re coming to the emergency department, they’re needing Prednisone and dealing with all the consequences of the Prednisone. Because of these recurrent exacerbations, they will also have a faster decline in lung function.


So this is really a very disruptive phenotype. Again, there is a therapy that if they’ve had at least three in a year or two in a year, excuse me, you could use azithromycin, which is an antibiotic so frequently used for COPD flares, but in this case you would actually just use it daily. As more of an anti-inflammatory than an antibiotic and that has been shown to reduce exacerbations in this group. There’s a current study that’s ongoing. It started actually just right before COVID and early 2020 So it’s had some challenges recruiting but called the reliance study or the reliance trial, which is looking at comparing these two roflumilast and azithromycin to see which one might be better because we’re using them in a very similar population.


But until we have guidance from that trial or another, the general approaches, if there’s chronic bronchitis, just on Roflumilast and then if they’re.needing frequent zithromax, we do have a small number of patients that are just very severe and you end up using both. There’s not a lot of evidence to support that. That’s usually just you’re kind of running out of options and we’re just trying to use what we have in our toolbox to hopefully get them feeling better. The next phenotype which? I think we all had a lot of hope for was the eosinophilic phenotype of COPD. So one thing that remains true about these individuals is if they’re eosinophil count is over 300 they should definitely be on an inhaled corticosteroid.


So most of your COPD patients will be on a LABA or LAMA or a combination of the two. But if they have it’s an affiliate they should also be on an inhaled corticosteroid. So this the biologics are and asthma or drugs that target T2 immunity such as interleukin fiber, interleukin 4, which showed a lot of promise and or a lot of benefit in asthma and are being used widely. There are some encouragement around possibly using these in COPD as well, particularly those with eosinophilia because that might imply that they have a little bit more of a T2 immune phenotype.


So this was a study published in 2017 for Mepolizumab. So they actually did two randomized controlled trials and. Included in one publication. So this is the intention to treat with an eosinophilic phenotype. So you could see here that there’s the group that live received placebo and then the group that live received mepolizumab and you do see a reduction in the exacerbation frequency in those with mepolizumab. This was the other arm or the other study that was published in that same, including that same publication.


And although to the eye these actually might look different, this technically did not mean statistical significance. They did exclude individuals with asthma in the study. But it was just by asking, do you have asthma? Have you ever had asthma? So there’s certainly a possibility that individuals with asthma were still included in the study. So given there is one positive study, one negative study and then some limitations with the design of this study. Matt Lesniak was applied for FDA use and eosinophilic COPD after this study, but it was not approved, just given kind of equivocal evidence.


So I think using eosinophilic COPD still represents a phenotype. It is a treatable trait in that we can use to inhaled corticosteroids in it. But unfortunately they’ve been at least so far too and I’ll show the next one on the next slide. Studies of biologics and eosinophilic COPD and both have been negative. The other medication that was tried was benralizumab, very similar structure. Looking at eosinophilic COPD, excluding individuals with the history of asthma. They did use different doses just to see which one might be effective. One of the studies was galathea. One of the studies was Terranova, again both published in a single publication in the New England Journal and some of the.


Basically, to kind of sum this all up, there were some benefits and some doses, but not benefits and. Other doses, so just given again some positive findings and some negative findings, it was not thought to be fully beneficial in individuals with the SN Phillips COPD. And again those individuals were specifically asked about a history of asthma and excluded if they had a history of asthma. So that is eosinophilic COPD, which is just COPD, no features of asthma or anything like that.


But they have peripheral use and affilia. The next phenotype which is appropriately receiving a lot of attention is the asthma COPD overlap. So this was kind of first recognized in 2005. Well, first formally recognized by the. Governing bodies in 2015 the G9 gold for asthma and COPD respectively that published an update on asthma COPD overlap syndrome. In 2017 that was updated to asthma COPD overlap and now it’s really just a Co which is asthma, COPD overlap of it’s a descriptor. It’s not as much of a recognized, as much of a syndrome anymore, but it’s just a way to characterize people that have features of both asthma and COPD so. Given this is in the context of a COPD talk, so if you’re approaching your COPD patient and your clinic and they say I have these symptoms that come and go.


You might start thinking about a possible asthma overlap component there. If it started very early and if they’re not alpha one anti trips and deficient that might be another potential ideology. And then a lot of this; and this is a really nice graph that you could see here or figure that a lot of the things that cause COPD also cause asthma. So it kind you would it begs you know it’s a natural extension of that some of those ideologies that lead to separately asthma and separately to, could then cause both the asthma COPD overlap. The relevance of this, and it’s certainly clinically relevant, one thing is that the individuals with asthma COPD overlap tend to be younger.


They tend to be, they’re more likely to be women. They’re comorbid conditions with asthma, they’re comorbid conditions with COPD. And we find that in asthma COPD overlap, those comorbid conditions are very pronounced. They’re higher than in either disease alone and again not surprisingly since you’re dealing with essentially an overlap. To separate diseases, there’s higher healthcare utilization, more emergency department visits, more flares of the disease. An embroidered, distinct therapeutic feature of this is much like the eosinophilic COPD is that the mainstay for cornerstone and management of COPD alone is a lab or Lamar bronchodilator therapy.


But if there’s eosinophilia or features of asthma, you want to make sure that individual is also receiving an inhaled corticosteroid. So the last I guess phenotype, we’ll talk about some other kind of comorbid conditions, but the last true phenotype will we’ll discuss there is an endotype which is alpha one into trips and deficiency. This is kind of a schematic of what the alpha one antitrypsin protein does. So typically in the lungs it binds to something called neutrophil, elastase, neutrophil elastase can destroy the lining of our lungs, the elastin that things that kind of keep it from snapping back and the destruction of that.


Can lead to emphysema. This protein is probably more important than we think in other parts of the body. So one other thing. To think about is the protein builds up in the liver because it’s not secreted out from the liver into the lungs. So most commonly these patients can develop cirrhosis as well. So and every patient with COPD and alpha one level or and genotype should be tested once. If it’s normal, you don’t need to. It’s nothing that needs to be monitored seriously. It’s just a test that needs to be done a single time. And so the last couple of quote unquote phenotypes, I’ll talk about, I’ll say quote unquote they’re not true phenotypes necessarily, but there’s at least so far, but there’s a recognition that these.


Distinct individuals exist and there’s certainly some clinical relevance to them. So one is that COPD. Although it’s a disease that begins in the lung is a systemic inflammatory disease and a lot of the systemic inflammation that causes problems in the lung can lead to skeletal muscle weakness. It kind of hearkens back to that picture that we saw that Frank Netter drew, but of the individual sitting very wasted away, it can lead to heart disease, diabetes and psychology psychiatric illness, which we’ll talk about in the next slide. So part of two major parts of these comorbidities are.


The muscle weakness and sarcopenia that can occur and that can then lead to deconditioning and then lead to worsening respiratory status because they’re not as mobile. And then as not surprisingly, hearing about, you know, how this disease is, there’s a bidirectional relationship with mental illness. So when you have COPD, there’s an increased rate of depression, anxiety related to the disease and then that mental illness, the presence of that can then worsen the disease itself. So because of the depression,  and anxiety, there’s higher risk of flares of disease, there’s increased tobacco use, likely as a consequence of the mental state.


So all these things feed into each other. It’s not, they’re not always things you can address within the context of your visit with them, but it’s at least things to be aware about and ask about. So if you can address it, then they’re able to be referred to the appropriate specialist to help manage the comorbid conditions and really it’s a part of the care. In a way of the COPD.


Because if you know this person for example, is able to get the appropriate psychiatric support, whether that means starting an antidepressant or counseling to help better control the mental health disease, that’s going to lead to better control the COPD as well, and hopefully smoking cessation if there’s still a current smoker. So there’s some other considerations that i did not discuss in detail and I think that’s because they’re outside of the scope of what I would consider a phenotype. But outside of alpha one antitrypsin deficiency, which is a very well defined endotype, there are other genetic variations that and minor snips or single nucleotide polymorphisms that seem to be associated with worse disease.


We don’t quite know what to do with these yet, other than that they exist and they may play a role in a particular individuals risk of developing. Disease and their severity once they have it. Environmental exposure. So this is not just limited to smoking, it’s while smoking, secondhand smoke exposure, factory exposure, biomass exposure, cocaine exposure. So there are a number of kind of contributors there, socioeconomic influences, which again particularly can develop or influence the severity of disease. It might be as simple as somebody not able to enforce an inhaler, which the cost can be quite buried above. There’s increased attention, a lot of the studies. From years ago or predominantly done in men or from decades ago or predominantly done in men.


So there is increased attention around gender differences and Airways disease or diseases more broadly. And along with that there might be hormonal change influences on the disease. Dietary influences. So certainly an anti-inflammatory diet one would think would offer benefit. There’s been some studies on fish oil and vitamin D none of them have proven positive but there are still kind of , some biologic evidence that suggests it might play a role.


And then I think you know the thing that continues to excite me and hopefully keep us all moving is that there’s more to discover more to figure out a lot of this I’ve kind of summarized you know 20 progression over 20 to 30 years. So optimistic and excited to see what we can kind of continue to develop over the next couple of decades and I think what the future direction is. So one is just. whenever you start talking about precision therapy, you really are phenotypic therapy. You really need to have consensus because if I say you know the emphysema phenotype is this and somebody at another center says the emphysema phenotype is this and we both do a trial owner emphysema phenotype patients.


We can’t really compare our findings. So I think consensus around definitions using the same cut offs whether it’s for an easing uphill count, whether it’s for some degree of emphysema on chest CT. That part is in order exacerbation cut off. That part is really critical because it kind of influences everything that builds upon it. And then the next thing is i do believe more narrowed research studies and. When I say narrowed, I mean not COPD generally see like we saw with the SNF like COPD studies where you use COPD plus some treatable trait and only individuals like that are included in a trial so that you are able to develop them precision and focus therapy for those individuals.


So as far as the key take home points from our talk and I think if you walk away with everything on this slide that would be in my view of fantastic accomplishment. So COPD’s heterogeneous disease really in every aspect and this is from etiology mechanism, how it presents the Natural History. Some people exacerbate, some people don’t exacerbate, but have really bad lung function decline.


It’s just a very heterogeneous disease. Every patient you see with COPD you should get a CBC with a differential on them for an SNFL count. Eosinophil count can rise and fall so there is some variation to that and then an alpha one antitrypsin level and genotype. This just needs to be done once there is some variation with the level, but the genotype will never change and then beyond using that gold ABC D box criteria for. The cornerstone of your COPD management.


You also want to be looking for these treatable traits and also assessing for these other comorbid conditions that might be influencing their treatment and presentation. And as far as what we have currently in terms of just very practically what can we offer individuals for certain phenotypes. So if they have an elevated eosinophile count or they have asthma, COPD overlap, they should be on an inhaled corticosteroid. If they have chronic bronchitis, they should be on roflumilast. If they exacerbate frequently, they can be, they should be on azithromycin.


Excuse me. And if they have alpha one antitrypsin deficiency and a certain impairment and lung function, so that’s it’s not that all individuals with alpha one anti trips and deficiency will benefit from this, but some will. You could use alpha augmentation therapy for individuals with CP Fe or combined pulmonary fibrosis and pulmonary hypertension. They can use treprostinil and then when they have emphysema and it’s upper lobe predominant as we show in that example CAT scan earlier lung volume reduction. Surgery may benefit them. So I hope as we continue to give this talk that this fourth column will become longer and longer and we’ll have additional therapies and additional specific therapies to offer individuals.


But I think for now we’ll hopefully deliver all this to those that are candidates and to enhance the care of our patients. With that I’ll thank you all again for your attention and the opportunity to speak and I’m glad to address any questions. Thank you so much, Doctor Tejwani. That was really I, you know, going over all those different phenotypes really was great information. Thank you. Our first question is how do you change diet to improve COPD? Yeah that’s a good question I think.


So, unfortunately the data and it’s hard with questions like this just generally because it’s very hard to do a trial to do it. But what I recommend my patients to do and i will say I don’t do this as a part of my practice not there be wrong with it but it’s just people that ask me is to just you know you could search now what is defined as an anti-inflammatory diet and I think it just begs to kind of like reasonable if the disease generally is a very inflammatory disease in the lungs, painful stomach only that if you eat foods that are anti-inflammatory nature that at least could help with the disease. That’s certainly should not be harmful barring anything very expensive or anything like that. So I would say like in general an anti-inflammatory diet. Vitamin D supplementation may help. Again, probably not harmful unless you’re over doing it, and then same with fish oil. Probably not harmful unless you’re overdoing it. I do suggest to my patients not to spend too much money on any of these things though, because there are, I think, some. Websites and other places that will charge a lot for different things and I don’t the evidence it just isn’t there for spending that much on it.


Ok. Thank you. Our next question, is there an ideal heat and humidity for COPD? Yeah, that’s a good question, so. Umm,, I’d say. I guess I’m thinking through some of the studies on this as well. So I don’t think there’s an ideal temperature. Generally speaking it seems cooler is a little bit better. I would say humidity wise no humidity is ideal. There is no benefit of humidity. It only seems to flare disease. So there’s no humidity would be ideal and I think kind of what we would all find comfortable temperature wise generally speaking is appropriate which is like high sixties low seventies Fahrenheit but no humidity generally seems to flare disease and we’re seeing that a lot this summer.


I’m thinking about this summer with all the heat and. Community, this is probably very hard on people with COPD exactly. Ok. Next question I’ll take is, are the slides available or are recording to review later? Because this is for CME and CNE we can’t make the slides available, but there will always be a recording available and it’ll be on our website within about 48 hours. You also always get a follow up email from us following a webinar and it will give you the direct link to the recordings and other resources as well.


So someone wants to know, is the difference between chronic bronchitis and exacerbate or phenotype, the amount of sputum they produce, or the duration of sputum? Yeah, that’s a good question. I think that’s a great question because that kind of. That general question is underpinning why we’re doing the reliance or the reliance study is being done to compare those two medications roflumilast in azithromycin because these frequently overlap. But so one somebody can have both, you can have both, you can do both a chronic bronchitis and exacerbate or phenotype.


But chronic bronchitis definition is really based around the sputum. So it’s not as much the amount but more so the frequency. Do they produce it most days or every day for at least. Three months and two consecutive years. So that’s kind of the technical definition and this goes back to us all speaking the same language. For the patient that’s sitting in front of you in clinic, it’s very practical to just say do you cough every day? Do you make is it, do you make sputum every day? And once you see those folks, they, before you even finish the sentence, they’ve said yes, yes, I’m bringing it up.


Sometimes they’ll even bring it up in the visit. Separately from that is the exacerbate or phenotype. While they will have at least two to three exacerbations per year requiring Prednisone or an antibiotic. So they can have both, you can, you don’t, it’s not necessarily that you have. One or the other. Ok. Thank you so much. Our next question is since you mentioned environmental exposures, what are your thoughts in regards to allergy allergic triggers, indoor and outdoor and testing for allergic triggers and COPD since this can add to inflammation and then focus on targeted exposure reduction.


What are your thoughts on that? Very supportive. So I think it’s a great question and I think particularly it and this gets a little bit to that asthma COPD overlap, it’s maybe not quite an asthma. The overlap, but kind of a COPD allergen overlap. So frequently if I’m getting kind of an episodic story from my patients or if they, let’s say, they left their, you know, home and went somewhere for a few days and felt much better or something or didn’t have a flare, it would be very reasonable to check an allergen profile either blood or otherwise and then target that.


And then on that there’s been a recent study where they did indoor air purifiers in individuals. This was just published last year and that actually showed a little bit of a trend toward a benefit too. So I think my thoughts around your comments on your approach would be very supportive and I think it’s a fantastic thing to do and. Really should be a part of our history of like are there these other exposures because they have their baseline disease. But I think what you’re getting in is can we figure out what is triggering them to get worse on top of that? And I think anything we could do to address that and figure that out is very excellent.


Ok, great. Has pulmonary rehab been shown to be more effective in certain phenotypes? That’s a good question not that I know of. So you would think it would be more beneficial in that sarcopenic or cachectic phenotype. I think that’s a patient you definitely want to refer for pulmonary rehabilitation generally speaking , I really can’t say enough positive about pulmonary rehab. It really improves quality of life and improves functionality but I’m not to my knowledge and I to my knowledge I don’t know that there’s any articular phenotype or subgroup that it’s been more beneficial in, although the individuals that are sarcopenic and have cachexia definitely should be referred more proactively just because that’s a bigger part of their comorbidity issue. Thank you. Our next participants is a fantastic overview and one says from the patient perspective, what are the main barriers for patients to best manage their COPD? Yeah, that’s it. Thank you for the comment. That’s a great question. I think we’ve touched upon some of them.


So there is really this mainstay of just making sure you’re on the right medications which is what the majority of my talk was centered upon. But then there are these other things that have started to come up in the discussion which is and i tell my patients this is a little bit more so the asthma, but even with COPD you know these air quality alerts now that we have is if there is not a critical need to be outside particularly in some of the more humid weather we’ve been having. Instantly it might be better to try to avoid it or be a little bit more indoors trying to figure out if there is a superimposed allergy, asthma on top of it that can be addressed and avoided.


Maybe the anti-inflammatory diet. Again, I don’t think it would be harmful and then just being, you know, making sure you’re regularly taking the other medications, you should be pulmonary rehab, I think that’s a lot and then a lot of it is just avoiding bad things. Which is easier said than done, you know, be it secondhand smoke exposure, pollution, those types of things that are easier said than done. But I think that’s a lot of it. Thank you so much. Our next participant says how does our guests see the effects of climate change including wildfires impacting COPD? Yeah, that’s a great question.


So i think the climate change we’re starting to see a little bit in real time. You know the humidity of this summer has come up the wild, I’m not you know practiced in California or the Pacific Northwest side colleagues there. So I mean I can only imagine just naturally that all the smoke coming out from the wildfire would trigger. The COPD, we definitely know that there’s been a recent publication, this was now two years ago, that changes in the ozone are leading to more COPD severity. So i think the way I see that generally is at least so far I there’s not a lot of evidence that it’s going to cause COPD, but there’s definitely very good evidence that it’s going to worsen the control of COPD, it’s going to worsen exacerbations and cause progression of lung function decline.


And for people that don’t have COPD might lead to kind of like a pre COP maybe that part is yet to be determined but i think it would make sense that it would unfortunately. So you don’t have too many wildfires in Cleveland, so just quick our next question says what is the role of oxygen therapy in the phenotypes? Yes, so that’s a great question.


So oxygen. I wouldn’t. I don’t think hypoxemia or low oxygen is a specific phenotype, which is why I didn’t touch upon it because many of the phenotypes that we went over can ultimately lead to that. I think it’s very critical if you have COPD and pulmonary hypertension because low oxygen can be particularly deleterious when you have pulmonary hypertension. But outside of that oxygen kind of falls into the pulmonary rehab and the LABA and LAMA component, which is that or territory which is that if you have COPD and you meet the other. Criteria for it. You should use it. Ok. Our next question says is any phenotype or trait treatable regarding LVRS versus endobronchial valve therapy? Question so what you’re generally looking for with those two is localized emphysema.


So LRS is particularly useful in the upper lobe predominant even with bronchoscopic. What you do is you deploy valves that essentially prevent air from getting into that bad part of the lung and it basically closes off. So even though you don’t technically remove it, you functionally remove it. So the most important thing as you’re starting to evaluate those individuals is looking for localized emphysema. Because if it’s everywhere, you just, you can’t do anything about it because it’s everywhere and you can’t remove the entire lung. So that would be one with bronchoscopic therapy. This is getting a little bit into the weeds here, but there’s connections or pores of cone between our lungs and the fissures.


And there’s ways to check if that’s intact or not, so I think as an initial screen, just is it localized. Is the emphysema localized to a particular lober too in the lungs? Ok. And we only have time for one more question and that one will be what defines an exacerbation of COPD? So there’s a mild exacerbation which is just using more albuterol than usual, a moderate exacerbation which is needing Prednisone or antibiotics or a combination of the two, and then a severe exacerbation as if you have to go to the emergency department, go to the urgent care or be hospitalized.


Well, thank you so much, doctor Tejwani. We totally appreciate you taking all the time to answer these questions, but also for a great presentation. Thank you so much. Thank you, Sally. And I would like to thank our listeners for being with us today. So what I’d like to do at this time, if you want to download your certificate of attendance from your control panel, please go ahead and do that right now. If you have any difficulties, you can always email us using the link in your emails. Please join us for our next advances in allergy and asthma webinar as we discussed the basics of biologic medications and their connection to type 2 inflammation.


We’ll look at the latest information and gather insight into this health issue with Doctor James Tracy. The webinar will be on August 25 at 4PM eastern. You can register for this webinar on our website at Scroll to the bottom of the home page to webinars. You can also view our recorded webinars on this page. On our website. On the next slide, you’ll see some web addresses.


Please visit our website for quality guidelines based resources on allergy and asthma and also access important medical information on allergies and asthma from our partners, the American College of Allergy, Asthma and Immunology and Allergy and Thank you again for joining us today. Please stay online for two to three minutes to complete the evaluation survey. This is Sally Schoessler for the staff at Allergy & Asthma Network, thank you for exploring this phenotypes of COPD with us today as we look forward to having you join us next time on advances in allergy and asthma.

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