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Uh Hi, Francesca. Um uh it's, it's really good to, to see you today. Um, and um uh we're going to talk a little bit about about 80 s. Uh and what the, um, what the kind of major updates were from the, from the conference. Um First of all, I wondered whether would, would you mind maybe giving us a quick introduction to you and, and, and who you are and maybe a little bit of your background and then we'll dive into some questions about 80 s from your perspective. Sure. My name is Francesca Palmerino. I was born and raised in Italy. I did my medical school in Italy, I Naples and then I moved to uh my or kind Spain to do some part of. And then I ended up at the Brigham and Women's Hospital, Harvard Medical School in 2010 where I spent almost 10 years I did my phd there uh in the Pulmonary Critical Care Division. Um I became a faculty in 2017. And then, um after a brief period, the University of Arizona where I was recruited to set up a COPD research group, I moved to Baylor College of Medicine, where now I am an endowed Professor of Medicine in the Palmer and Clinical Care Division. And I ran the COPD research group here at Baylor College of Medicine. So I am an MD phd. I see patient's uh as well in a county hospital. And um my uh main interest is in the COPD pathogenesis and early origins of chronic careful limitation. Great. It's really great to, to, to have this conversation today. Um I'd love to know from, from your perspective. Uh what were the kind of major trial results or the key, the key trials that were discussed at 80 s this year? Oh, for COPD. That is this year. It was all about the trial that was just published in the New England Journal of Medicine where they were, I'm sorry, where they used the pill a map which is a monoclonal antibody that is currently used like Dupixent, which is the diploma uh which is produced by San Office less Regeneron. This drug has been extensively used successfully in asthma. Yeah. And now it has been shown to um it has been used in Syria, tried in COPD with using a pill component and uh has been shown to greatly ameliorate, not only the symptoms but also the F E one. So all the primaries the first time honestly that I've seen a drug that ameliorate. It's both the primary effects so deeply, both primary and secondary endpoints when it comes to symptoms F E one and all the rest. So this 80 s has been really um smarck by the success of this trial with Dupixent in COPD. Uh brilliant. Do you mind me telling a little bit more? So, um uh when are we, when are we most likely to, to make a treatment decision in, in this space? What, what are the kind of key indications? What, what uh what does, what does a clinician need to know about, about when to prescribe? So, Dupixent is a monoclonal antibody that blocks in there looking for and to look interleukin 13. Right now, I was just used in allergic asthma eczema um in particularly in uh all the asthma without using the fill component. So what I still have to dive into the paper um much. But what I can tell you is that uh from now on it is recommendable to uh well, usually, you know, when you talk about COPD and using Ophelia, it's all over the map. People don't know exactly how to handle that. But now with this trial, we do know that the eosinophils is a component that needs to be taken into account when designing a treatment strategy for the COPD patient's. In fact, um as I said, um the this this monoclonal antibody has been shown to work greatly in a patient with COPD without using the field component. So uh to make a long story short, it will be recommendable to just measure the using the pills in blood. And if there is a using a field component as as we do in asthma, uh This patient is a good candidate for uh to fix it super. Um And in terms of other key results, um any other papers that were kind of really interesting 80 s from your perspective, I cannot tell you about papers, but I can tell you about the topics that were predominant uh COPD word. Uh This 80 s was really the 80 s of integration of multi ah mix. When I say integration of multi ah mixes that now uh the single cell RNA sequencing is becoming very prevalent in the study of COPD. After a couple of papers, the major papers that were published where the ATLAS of the COPD LANG was made available. Everybody now is jumping into the single cell RNA sequencing. But then from the single cell RNA sequencing, I mean it's as good as you can get right now. So everybody's doing that. Although it's you know, if you have the pockets, you can do that. But now the field is moving towards towards something that is called spatial transcript onyx where basically you can have the single cell data with the spatial resolution on tissue slides, which is something that has replaced the laser capture micro dissection. And then from there uh this the people as myself and other other investigators in COPD are trying to integrate these transcript Tomic data with the radiology, meaning that we look at the city's kind of these individuals. And we try to see if there is any correlation between that the Radionics, the radiological features of these lugs with the biological features and the nature of the immune um environment that we see in the lungs. So you know these 80 s was all about integration all multi ah mix, meaning that everybody is talking about single cells, special transcript ah mix and radiology. The three things are about to be to be merged. Um People are working hard to try to integrate this uh this high triple data into one data set that can better define the COPD lank. Like just looking at the CT scan, you'll be able to predict without the biological features of the lung of some individuals, which one's which is one step forward towards the precision medicine precision medicine approach in COPD. Super interesting. Um How far away do you think we are from that kind of precision medicine approach? How many, how many years or how close are we? Well, we are not that close and not that far is the problem is that? So the concept of COPD is evolving very fast in the last couple of years. You know that for many years, we define COPD with only with the spire a metric obstruction with the gold recommendation. And this is this God that stuck uh for many, many years because we were stuck with this paramedic obstruction. But now thanks to a couple of uh papers that were published first, the, the Lancet, the lancet um um paper where they redefine completely the COPD and they are not talking about one kind of COPD anymore. Now, we're talking about different types of COPD that have different causes that they have called Xia types, which means different causes of COPD. So now we know the COPD is not just the disease of the old people that are self inflicted disease of the old people that have been smoking. Now, we know the COPD is me has many faces. One for example, is alpha one antitrypsin. Another one is COPD of people who were asthmatics. And then the asthma chronic sized into COPD, even in absence of cigarette smoke. Another type of COPD S to one of the premature kids who were born premature. And the long you know, these individual, they were dying before. But now all these individuals are alive because we have the surfactant. So more and more we see in clinic, all these people who were born premature and they have never smoked, but they were just born with a low lung function and they meet this paramedic criteria for COPD. So we know COPD right now or for example, we know that infection, such a respiratory RSV infection in childhood or adenovirus infection in childhood, lower spiritual tract infection can affect the lung for the rest of your life. They can determine um the onset of COPD very early in your life. But as you can understand that this is not the COPD. As we used to think, this is not the COPD that is associated with cigarette smoke. This is just a COPD as relates to this paramedic obstruction, but maybe in this individual lab, Allama will not work. This is why we need a position medicine approach where we need to understand that the cause of the airflow limitation in order to tackle these causes. And but we unfortunately, right now, we need biomarkers and clinical trials in order to target this subject of individuals. And where, where are we on that biomarker front. So that's really, that's a really interesting next step, right? Where, where are we in, in that research? So we have been trying to, we, I mean, the COPD feel that been trying to look for biomarkers quite a lot. Um The problem is the blood biomarkers are difficult to find. But for example, previously, that microalbuminuria, for example, can be a valuable biomarkers that is associated with the systemic endothelial dysfunction in COPD. And I know that there are trials that are tackling individuals with microalbuminuria or we just published a study where we show that uh given Metformin, which is a anti diabetes drug to patient with COPD can actually also help Ameliorating um the uh a subset of individual or what we do in the lab. In my lab, we target individuals with emphysema predominant COPD that I've uh um of targeted. Yes. And we um we, we, we believe that uh monoclonal therapy and biological therapy, targeting B cells could be beneficial in this substance of individuals. So the field is moving forward now, I think it's gonna move a lot faster now that we have established that COPD is not just the disease of the 70 year old smokers. So now the field is gonna move a lot faster. And what does that mean for treatment? So were there any kind of major, major trial updates or findings about what that means for treatment? So if we're gonna split this into lots of different subsets, what does the treatment look like in terms of each of those different subsets? And how does it differ? As I said, the only trial that was positive uh that, that is going to have a big impact in COPD is the one with Dupixent. But what I can tell you is that there have been trials, for example, they had did a trial with an understanding receptor blocker and COPD because we have shown previously, we and others have shown previously that there is endothelial dysfunction in COPD. So they gave angiotensin receptor blockers with people with COPD and the trial was negative. But the caveat is that you cannot just give one drug to all the people with COPD. You have to identify the subset of these individuals that might need for example, with endothelial dysfunction that might need this drug. And this is we, you know, we published an article last year, it's called the selection of the right patient population, the achilles heel of clinical trials. So the selection of the patient population is really the achilles heel, the weakness of all these clinical trials that are coming out. And when I say the weakness is because um we, we do understand that the COPD has different phases, but we keep doing clinical trial by targeting the entire COPD population selected solely based on their spiro metrical Spira Matic obstruction, which is a major weakness of all the clinical trials that have been coming out so far. So most of the clinical trials where they've been trying these alternative drugs in COPD have been negative. But for my perspective is just because the right patient population has not been selected yet. Super interesting and then looking, looking forward, where do you, where do you think, what, what are the most exciting ongoing studies right now? In, in CVS, we've talked about some of the really big published results from, from 80 s. But obviously, there's lots of really interesting research happening in the field right now. What, what, what are the, what are the studies that everyone's talking about? What, what, what, what uh what, what results are eagerly awaited and, and, and, and what should we, what should we know about those trials? Honestly, there are so many, there are so many trials that are ongoing right now and there is nothing specifically specifically that is popping out or that is coming to my head right now. Um I know that one big thing right now is the repurposing of drugs. For example, there was a session very, very well attended session at the 80 s where we talked about repurposing of drugs that are used for other diseases in COPD. Just because we now know that COPDs are met about this metabolic component with an accelerated aging component. So we are trying to repurposing drugs from other diseases, such a Metformin or Enalapril or ace inhibitors that are used in other diseases such as diabetes or heart failure that have the same nature of accelerated aging and this metabolism. So we're trying to repurpose these drugs into COPD to see if uh obviously this is not very palatable from industry perspective because you know, we're repurposing industry. I mean pharmaceutical company don't make much money. But uh it's something that is um it's a viable option that um a lot of groups are trying to investigate right now. So what I can tell you is that we're moving away from the lab, a llama and more bronchodilator because I think this is as good as you can get. We tried all of them combination triple therapy, mono therapy, which tried all possible combination. They still work, they still have an impact on the uh symptoms and progression of COPD, but they're not um changing the course of the disease. So we're moving away from the lab Alumai CS. And we're trying a different strategies such as, for example, targeting the inflammation, like the diploma for targeting the metabolism that concern Metformin. So, alternative strategies really interesting. Um and in 10 or 15 minutes, that is a really great insight into what was happening at 80 s. So I'm really grateful for, for your, your time full of, well, you know, um and um and, and thank you for kind of sharing your, your updates with the kind of global, global community, really great to get your insights and really appreciate it.