Episode #4: Screening for Pulmonary Fibrosis with Dr. Anna Podolanczuk

Foresight Medicine Episode #4 TranscriptScreening and early intervention for pulmonary fibrosisRobert Rogers: I’m Robert Rogers, host of the Foresight Medicine Podcast at the Foresight Medicine Substack, where we are envisioning the future of preventive healthcare as a systematic and whole-body framework for leveraging new technologies to maintain health for as long as possible.In this podcast series, I interview leading experts at the forefront of prevention and early intervention across medical specialties. Today, we will be focusing on the lungs and interstitial lung disease and pulmonary fibrosis. I’m very honored to have as our guest today Dr. Ana Podolanczuk. Dr. Podolanczuk is Associate Professor of Medicine at Weill Cornell, and a nationally recognized expert in interstitial lung disease and pulmonary fibrosis.She is a pulmonologist, critical care physician, a major contributor to the current clinical trials landscape, testing new therapies in interstitial lung disease, and a leading investigator of the earliest detectable stages of this disease. And it is in that capacity that I am most excited to speak with her today. Her work spans imaging, biomarkers, environmental risk factors, and the broader question of how we might identify interstitial lung disease earlier at a stage where intervention could potentially alter outcomes. Anna, welcome.Listeners should note that we are recording this on Thursday, April 23rd, 2026, and as always, this conversation is for general informational purposes only and does not constitute individual medical advice.So, Anna, I’m really excited to have you on today, and one of the reasons is because in some previous episodes of Foresight Medicine, we have had discussions about diseases where there’s really a quite well-established paradigm for what preventive or early intervention care looks like. And when it comes to the lungs and the diseases we’re going to be talking about today, I don’t think there’s an established paradigm, but there’s people who are working on that, and you’re very much one of those.And so this is an exciting new frontier for us. And so, kind of the first question I want to just start out with, and it’s always my first question to our guests is, what inspired you to focus on this area of lung disease? How did you get here? But in the course of your answer, for our listeners, let’s just level set with a couple of important terms. When we say interstitial lung disease, what do we mean? And when we say pulmonary fibrosis, what do we mean?Anna Podolanczuk: Sure, thanks so much for having me, and this is something I feel very passionate about and happy to speak about it. So, let’s start with the definitions. When we’re talking about interstitial lung disease, we are talking about diseases of the lungs that affect the lung parenchyma, the little membranes in the alveoli, where gas exchange occurs. And so that separates those diseases. They’re separate from things like airways diseases, like asthma and COPD, or from vascular diseases like pulmonary hypertension. And so pulmonary fibrosis is a subset of interstitial lung diseases, where there is scarring of the lung interstitium, of the lung parenchyma. And so that makes it really hard for oxygen, to get into the body, and leads to progressive usually progressive symptoms, like shortness of breath and cough,and worsening quality of life for many of our patients.And so, really, it’s that presentation that inspired me to go into this field, because even when I was in medical training as a medical student, as a resident, we saw many patients with pulmonary fibrosis being admitted to the hospital, or I would see them sometimes in clinic, and the thing that inspires me to do what I do now, which is focusing on early detection, is that many of those patients used to present very late in their disease course, and usually by the time they presented to the hospital or to clinic, their disease was very, very advanced, and there was very little that we can do. The thing about pulmonary fibrosis or scarring in the lungs is that it’s not reversible. Or currently, with our current treatments, there’s nothing to reverse it.And so, that makes it very challenging to intervene and to improve quality of life. And so all we can do, if we can diagnose disease earlier, we can hopefully have the biggest impact for our patients in terms of actually improving their quality of life.Robert Rogers: I really like that answer, and there’s two threads in that answer that I want to pick up on. First is you started to already kind of lay the foundation for why we might be interested in early intervention and early detection of pulmonary fibrosis, because when patients present clinically and it’s quite advanced, their prognosis can be challenging. But also, in the course of your answer there, in explaining what interstitial lung disease is, for our listeners, I just want to explain why, among all lung diseases are we focusing on this in this episode of prevention. And I think it’s fair to say, you know, in a pulmonologist’s office, there’s many different diseases you see, but probably the single most common, right, are those diseases of the airways, asthma and COPD. And I think that we sort of have a preventive care paradigm for those airways diseases. For COPD, it is so much dominated by the risk factor of smoking. Really, prevention consists a lot of smoking cessation, and for asthma, asthma is very much a disease where the whole care paradigm is about preventing exacerbations. Another disease that we see a lot in the pulmonary clinic is when people have nodules on their lungs, and we’re concerned if they’re cancer or not. And we had an entire episode of that on episode 1 of this series, and I encourage our listeners to check that out. So I think interstitial lung disease is really, among the pulmonary diseases, one that’s really ripe for our discussion today.So, picking up on what you said there about how, you know, when patients with pulmonary fibrosis present to the hospital, or present clinically, it’s often quite advanced. Let’s just outline a little bit what are the current treatment options, because of course, the logic of intervening early depends very much on what treatments can we offer.Anna Podolanczuk: Yeah, for sure. And so, you know, just to add to a little bit to what you were saying, it’s absolutely right that airways, diseases, nodules, you know, those are common, and those are pretty, you know, significant diseases as well, but what makes pulmonary fibrosis so challenging is that they are some of the sickest patients that we see in pulmonary Clinic are those patients with pulmonary fibrosis. And one of the challenges in taking care of those patients is that treatment options are very limited. Like I said, there’s nothing that reverses lung fibrosis. There are currently, 3 approved, what we call, antifibrotic therapies. And all 3 of those therapies slow disease progression. But they don’t even stop it from progressing. They, you know, at best, they slow the disease, the decline in lung function over time. They have limited efficacy. They don’t make anybody feel better. Two of those drugs have been around since 2014, and the latest drug, was just approved, a few months ago, and all of those drugs have side effects. The newer one has fewer than the older ones, but they all have, you know, they’re challenges with tolerability for patients, they’re difficult to take, they’re pills you have to take every day, and there’s not even a good way of knowing if they’re working, because most patients at some point are going to progress with or without therapy, they just progress a little bit slower without those drugs. And so the only other treatment that we often discuss with patients is lung transplantation, right? And so pulmonary fibrosis is actually the leading indication for lung transplantation.And it’s because it’s such a severe disease with so few treatment options. But lung transplantation is not a cure. Takes care of their fibrosis, when successful, but you’re trading one disease for a set of complications, including the risk of rejection, the risk of infection, and so there’s challenges. And then other things that we use to help patients feel better are things like supplemental oxygen, but again, those are, you know, comes with a quality of life, challenge where patients have to lug oxygen around. It may help them feel better, but it also significantly impacts how they feel and function in the world. And so, it’s just very challenging and we’re constantly doing clinical trials and research to find better treatments for patients, but so far, we have very limited options.Robert Rogers: Yeah, and let’s just double-click a little bit more on those antifibrotic agents, because as you’ve pointed out, they are far from perfect, they are not cures for the disease, they are not medicines that reverse the disease. But they do slow the progression of the disease, but they do that at the cost of certain side effects. And maybe just talk a little bit about, with the current standard of care, how you see the benefits of slowing the disease down versus the side effects you see the patients incurring.Anna Podolanczuk: Yeah, so it’s always a balance, and whenever I see a new patient with a new diagnosis of pulmonary fibrosis, we spend a lot of time talking about those risks and the benefits of when to start therapy. The antifibrotic therapies all have significant gastrointestinal side effects, and so many of them can cause diarrhea, nausea, stomach cramping, weight loss, poor appetite. Again, the newer drug is a little bit better, but none of them are perfect. And so for many patients, they don’t want to start therapy if they’re feeling okay when they still have very early disease. But the challenge there is that if you’re going to wait for the development of symptoms, you can’t go back in time and get that lung function back. And so for me, it’s always talking, monitoring patients very closely, even if they’re diagnosed early, and diagnosed before they have significant symptoms, to see if we can predict when they’re going to start progressing, or if we can find a way to identify early progression, then it might make sense to initiate early therapy to try to preserve as much of the lung function for as long as possible. These antifibrotics generally slow lung function decline by about 50% and so what we can tell, from clinical trials, that on average, the way we measure lung function and progression of disease is through something called FVC, or forced vital capacity. It’s a measure of lung volume on an inhaled lung volume on a breathing test.And so patients with IPF [Idiopathic Pulmonary Fibrosis], on average in trials, tend to lose about 200 milliliters of their lung volume, of their FVC per year. And the antifibrotics and trials have been shown to slow that down by about 50%. So instead of losing 200, you may lose 100 milliliters as opposed to 200 milliliters. And so again, the challenge of when to start that. I tell patients, if we started something earlier it might actually have a benefit and make you lose less lung volume over time, but it comes with the cost of the side effects. And every, you know, every patient’s different, and it’s always an individual decision for when to start these therapies.Robert Rogers: Yeah, and just for our listeners, IPF is the acronym for idiopathic pulmonary fibrosis, which is the single most common form of pulmonary fibrosis, but there are many others. I appreciate you bringing in this important measure that we think about a lot in lung disease into our conversation called forced vital capacity. The way that I tell people to think about this, and actually how it’s defined, is imagine taking in the deepest breath that you can, fill your lungs up all the way, and then blow all the air out as far as you can. And how much air you blow out there, that’s your forced vital capacity. And, so let’s just say, to make an easy round number, what’s normal for a person depends on their age, and their sex, and their height and personal factors, but let’s just use a nice round number. Say a normal person has 4 liters of that, and let’s say if you get down to 3 liters, you might come to your office to see you and complain, and let’s say if you get down to 2 liters, you might be in real trouble, right? You might be really, really sick. And so, what you’re saying is, is that with our current drugs, if people are gonna go down by 200 milliliters per year, they could maybe slow that to more like 100 milliliters on average. And so what you have to spend a lot of time thinking about is how early to start using those treatments, because they have some side effects. And so, the question that I really want to ask you that that brings up is, you know, how much fibrosis can actually accrue to the lung before a patient will present to you clinically, and how long can that period of time be?Anna Podolanczuk: Yeah, so that answer is different for everybody. I give a lot of talks on pulmonary fibrosis, and one of my first slides is always that it’s a disease that develops over years to decades, and it’s not something that happens overnight in most patients. Unless they had some acute hospitalization or something else that caused other types of pulmonary fibrosis, or injury to their lungs. But for most patients, there’s this long subclinical or early preclinical phase, where they don’t really feel any different, but there’s microscopic injury, and scarring that is developing in their lungs.It is slowly progressing over time. And then, when someone develops symptoms, it’s kind of dependent on their general activity level, right? If somebody’s a marathon runner, they may feel some limitations to their exercise capacity earlier on than somebody who’s more sedentary or not very active. I see patients who lose 30-40% of their lung volume, and are not too symptomatic, and sometimes I see patients who lose 20% of their lung volume and start feeling symptoms. But kind of like you said, it’s, you know, somewhere in that, you know, you lose 25%, 30, 35, or 40% of your lung volume, you’re going to start feeling something. But that’s a lot of lung volume to already lose through scar tissue. And again, that’s not something that we can reverse, and so we’re always trying to identify this disease early to try to preserve as much of the healthy lung as possible.Robert Rogers: It’s really somewhat of a blessing and a curse that we are born with much more lung capacity than we need for our daily lives. It’s a blessing because we can lose a lot and still do fine. It’s a challenge because a lot can be gone before you know that there’s any problem, and then you can be in trouble. And so let’s take a step back for a second. How should an average person think about what the overall risk is of developing pulmonary fibrosis? Certainly, it’s a lot less than things like coronary artery disease, but what is kind of an average person’s risk? And then maybe talk us through what are some of the environmental and genetic and other risk factors that increase that risk?Anna Podolanczuk: Yeah, so pulmonary fibrosis, especially the idiopathic pulmonary fibrosis that we just mentioned, which is kind of the most common idiopathic form of pulmonary fibrosis, is a disease that’s related to aging, and so it’s not something that develops in younger individuals, in people in their 30s, 40s. And rarely in their 50s. It’s something that we start seeing as people get into their 60s, 70s, and 80s. Now that people are living longer, in many cases, we are seeing more and more individuals with pulmonary fibrosis, because they are being identified, you know, into their 80s, and sometimes even 90s. So, the average person’s risk really does depend on your age. I do a lot of research, and I study, research cohorts, and we’re generally looking at individuals who are middle-aged and older. And there are some epidemiologic studies and data sets that show that, idiopathic pulmonary fibrosis affects about 1 in 200 individuals over the age of 65. That is from a Medicare data set. So in that population, it’s… it’s kind of rare, but not that rare. 1 in 200, you know, I mean, we all know, a lot of individuals, and so chances are that at some point, you’re gonna meet someone who is affected by this disease, but it’s usually going to be older individuals.Now, that risk, changes dramatically when we are talking about genetics and exposures. So idiopathic pulmonary fibrosis and other types of pulmonary fibrosis, have a very strong genetic risk. The genetics are not sufficient. It’s not like other, like, diseases, like cystic fibrosis, where there’s one gene, and if you have that you’re gonna develop the disease. It’s a multi-genic disease, or polygenic disease, where there are multiple, genetic factors that contribute to disease risk, and there are both common and rare genetic variants that contribute to risk. But there are a set of genes that run in families, and about 20% of the patients that we see have what we call familial pulmonary fibrosis, where there are multiple individuals in a family, that are affected by this disease, and in those cases, there’s often a strong genetic linkage, and some of those genes are related to premature aging and, pathways, things that we call, like, senescence and telomere function, and so individuals with those specific genetic risk factors are kind of one type of individual that suffer from pulmonary fibrosis. And then there are other genetic factors that are much more common in the general population, but are also strongly associated with disease risk. And generally, if you have those more common genetic factors, then there’s a strong link towards exposures, and so you need that genetic factor plus kind of an accumulation of exposures over your lifetime that cause injury to your lungs to develop pulmonary fibrosis. And in those cases, we still think of the disease as being a disease of premature aging, where the lung kind of exhausts its ability to heal itself when it’s exposed to ongoing injurious factors. And so those exposures are things like smoking, air pollution, many other environmental factors. There are some types of pulmonary fibrosis where exposure to things like mold and feathers can trigger a reaction and injury to the lungs that then leads to scarring. And then there are some intrinsic factors. We think that maybe acid reflux, may contribute to ongoing injury to the lungs that then causes pulmonary fibrosis.Robert Rogers: Yeah, and so you’ve brought up the complex nature of the pathophysiology of pulmonary fibrosis, both genetic and environmental contributions, and when we think about the genetic side of things, on foresight medicine, we discuss genomics a lot as sort of this general-purpose technology that’s gonna inform targeted prevention and early intervention across many diseases, and so there are many healthy people who might be considering getting whole genome or whole exome sequencing. How would you advise such a person to think about the benefits versus the costs and the risks of characterizing their genetic risk for ILD?Anna Podolanczuk: Yeah, I think that’s a challenging question, because we know so little still in pulmonary fibrosis, but we also know a lot. Like I said, there are multiple genetic factors that have already been identified, and when I see patients in clinic, I have the option of sending, you know, targeted genetic panels, but there’s also been research studies that have looked at whole genome sequencing and its utility. And there was a really great study that was done by David Zhang and Christine Garcia out of Columbia University that looked, actually, at the utility of whole genome sequencing in patients with both sporadic pulmonary fibrosis and familial pulmonary fibrosis. And they found that in about 25% of patients, you could find actionable or risk-related variants or genetic factors when you do whole genome sequencing that inform their risk for disease, and can tell us, you know, potentially why the patient developed that disease, but may also have implication for those patients’ family members, and can, help inform their family members’ risks. And we know that in families where there are one or more people affected by pulmonary fibrosis, their first-degree relatives have an increased risk of the disease, and that risk is about 1 in 4 individuals, so about 25% of first-degree relatives of patients with pulmonary fibrosis will have some sort of abnormality on their CT scan that may often be an early manifestation of pulmonary abnormality on CT scan. And so, when you take that, and then you think about whole genome sequencing,if you know that a certain genetic factor or certain variant runs in your family that is strongly linked to pulmonary fibrosis, whether you carry that variant or not may inform how closely, you look at your own symptoms, when you get screened, with a CT scan for pulmonary fibrosis, and how you approach some of those medical decisions. So I think there is utility to it. I wish there was more data, or we had better results with using some of those genetic findings to inform treatment decisions, and with that, we’re just not there.Robert Rogers: Right, and we don’t have anything as of now that can specifically mitigate a specific genetic risk factor, it’s more that it would clue you in to be perhaps more vigilant, which we’re going to talk about in just a little bit, how one might be, quote, more vigilant. Perhaps you could say, would it also make you extra motivated to avoid certain risk factors? Like, you would know extra to not smoke, or similarly? So before we get there, though, kind of one last question that I think is a challenge for the idea of early intervention in pulmonary fibrosis, and that is, you touched on this at the beginning, but could you say a little more about what the different clinical trajectories are of patients with pulmonary fibrosis? How some people will really not progress, some people can progress quite rapidly, and there’s really quite a large spectrum in between. And so, how can we think about predicting whose disease will progress and how rapidly?Anna Podolanczuk: Yeah, yeah, so it’s certainly a heterogeneous group of diseases where the trajectory is very heterogeneous, like you mentioned. Some people can stay stable for many, many years. And some people progress very rapidly. And we have very few ways of predicting, who will progress when. This is why we monitor patients very closely with serial PFTs. I see my patients with pulmonary fibrosis in clinic, every 3 to 4 months with pulmonary function testing. We image them at least, every 1 to 2 years. You know, we certainly assess symptoms. There are a few biomarkers that have been looked at, as being associated with progression. I think the one that we are talking about the most currently is something called telomere length, and some of us are sending that blood test that measures the caps on the DNA called telomeres, and patients who have short telomeres have a much higher risk of disease progression. It may actually inform some treatment decisions. They may respond differently to different therapies, like immunosuppressive therapies. And, it also impacts their risk of disease and their risk of progression. That’s probably the most promising biomarker that we have, but other than that, and aside from those genetic, you know, if there are known genetic factors that are linked to familial pulmonary fibrosis, that is also known to be kind of a more progressive phenotype of patients. There’s very little that we can do. So we just, you know, we kind of end up monitoring patients very closely, and what I tell patients that even if you’re stable for many years, you still need to be monitored, because I have patients who are stable, stable, stable. Eventually, patients fall off a cliff, and what I’m constantly trying to do is find patients before they’re falling off that cliff, and then they end up having a very rapid disease progression at that point.Robert Rogers: It’s very interesting the trade-off that you described that derives from the great heterogeneity of how patients can progress, And something that I think back to when I think about screening in the lungs is, you know, go all the way back to the original, that foundational paper called The Principles and Practice of Screening for a Disease in 1968 by Wilson and Junger, right? And it sort of lays out these principles that anyone who’s interested in early early detection and early intervention should take to heart, when does it make sense to screen for something? And one of those principles is that, you know, the natural history of the condition, including its development from latent to active disease, should be adequately understood. And I think what you’re pointing out is that, we don’t have a fine mapped understanding right now, actually, of being able to predict, you know, who’s going to progress. We have some clues, but I wonder if that is a little bittoo pessimistic a take on what we really can do in this realm? Because, like you said, you don’t have to necessarily predict at the outset. You can monitor patients over time, right? You can observe these patients every 4 months or every 6 months and decide when an individual patient is progressing. And so that’s a much more answerable and personalized question than this generalized question of, can we predict progressors? Is that how you actually think about it in practice?Anna Podolanczuk: That’s exactly right. I mean, to me, knowledge is power, and knowing that you might have an abnormality where we can be vigilant and intervene if it progresses, even though we can’t predict exactly when it will progress, is powerful, because, we do have drugs that can modify that disease course, even though not perfect, and so, exactly right, we can monitor patients and intervene early, as opposed to waiting for so much of the lung to be damaged, and that symptoms are developing, and we can’t go back in time.Robert Rogers: Great. So, pulmonary fibrosis is a disease that initially is largely diagnosed with CT scans, and tell us about this relatively new entity that you and others have been working on, defining what we call interstitial lung abnormalities. What is that? What does that look like? What does that mean?Anna Podolanczuk: Yeah, so this is an idea that, we can identify early stages of pulmonary fibrosis on CT scans, on imaging, often before they become symptomatic. And this has been looked at in a lot of research cohorts and kind of a lot of, large studies where patients underwent CT imaging, CAT scans for other indications, like to look at their coronary calcium, for example. And many of them, roughly 7% of the middle-aged and older adults, will have these, often early features of pulmonary fibrosis. And many of them will progress, even though they progress very slowly. But, you know, in that context, we call it an abnormality. We don’t know yet if it’s a disease, if it will impact somebody’s quality and quantity of life, and so it’s just something for us to evaluate and monitor over time, and so this has been a concept that’s been recognized for many years now, but we formally kind o defined an approach to evaluation and management of those patients with these incidental abnormalities. In this recent document, we came together with 40 individuals from across the globe to recommend who should be screened for these abnormalities, and how individuals who have these abnormalities should be monitored and evaluated.Robert Rogers: Yeah, great, and so you are, in fact, one of the leaders of that effort, and the first author of that document from the American Thoracic Society about the approach to the evaluation and management of interstitial lung abnormalities, and so I’d love for you to tell us, kind of how you approach both of those questions. What’s the current standard of care for someone who’s found to have these radiographic findings?Anna Podolanczuk: So, what we agreed on in this document is that these individuals should be evaluated for the presence of interstitial lung disease. And so, one of the things we did in this document is try to come up with criteria for what differentiates an abnormality from a disease. And these are things like having abnormal breathing tests, having symptoms that can be attributed to lung disease. Or having certain features on a CT scan that are known to be associated with a high risk of progression, and those are fibrotic features, so things like what we call traction bronchiectasis and honeycombing. They’re just aspects of a CT scan that are known to be strongly, associated with poor outcomes in patients who have these abnormalities. And so, if people have these abnormalities, any of these things, they should be considered to have a disease, often early disease, but a disease rather than just an abnormality, and at that point, they should be evaluated by a pulmonologist, and monitored, and assessed for potential treatment of that disease. If they don’t meet any of the criteria for interstitial lung disease, if they just have an abnormality.They should continue to be monitored, in a pulmonary clinic with, CT scans every 2 to 3 years, and with, mitigation strategies, so things like, risk reduction strategies like cessation of smoking, any other harmful exposures, you know, age-appropriate vaccinations, all of these preventative strategies that we know can help people decrease the risk of progression.Robert Rogers: So that’s great, so there’s a lot of rich material there. So basically, you know, you said if you went out into the community and did these CT scans for whatever reason on 100 70-year-olds, you know, 7 of them, on average, would have these abnormalities, and then if you catch these abnormalities, the standard of care is now to figure out, is this just a radiographic abnormality, or do they actually have disease? And either way, they’re going to be followed now from now on, but the intensity of that following, it sounds like, differs very much between whether it’s just an abnormality or whether they have the disease. Maybe taking one, just pushing that one step further, should anybody currently be screened for interstitial lung abnormalities even before they’re known?Anna Podolanczuk: Yes. So, in the same document, we had a lot of discussions, and we reviewed the current state of evidence for which groups of people are at risk, at higher risk for having these interstitial lung abnormalities. And there’s several groups that we recommended screening in. The first group are individuals who have family members with pulmonary fibrosis. And we specifically said, individuals, first-degree relatives of patients with familial pulmonary fibrosis, where there are two or more individuals with pulmonary fibrosis in a family. Those individuals have a high risk of having an abnormal CT scan. About 1 in 4 will have some abnormalities, and so we recommended a screening CT scan starting at the age of 50 in those individuals, in the first-degree relatives. Two, we recommended screening in individuals who have what is known as connective tissue diseases. These are, autoimmune diseases, so specifically scleroderma, rheumatoid arthritis, mixed connective tissue disease, myositis, and Sjogren’s syndromes. These are conditions that are, have a high risk of also having interstitial lung disease. These individuals, in our, analysis of the existing data, there’s about, somewhere between a 20% and a 40% risk of having an abnormal CT scan when you look at the data. And so we said everybody who has those conditions should get at least one baseline screening CT scan to evaluate for the presence of interstitial lung abnormality. And finally, we looked at smokers. We know that smoking is a risk factor for pulmonary fibrosis. The data on smokers, the prevalence of interstitial lung abnormalities in smokers, is about 7-10% of middle-aged and older adults, so it’s not that different than the general population. And so we said that’s not enough to justify recommending a screening CT scan for all smokers. But, in patients who are a smoker, lung cancer screening CT scans is already recommended. And so those individuals who are undergoing CT scanning for lung cancer screening, those CT scans should be formally assessed for the presence or absence of interstitial lung abnormalities or interstitial lung disease. That should be formally reported on the CT scan.Robert Rogers: Right, so it sounds like there’s evidence to support screening in those three high-risk groups, patients who have a family member with interstitial lung disease, patients who have certain autoimmune diseases that predispose them, and patients who are already getting CT scans because of their smoking history to look for lung cancer. Are there any other groups who were, quote, on the bubble who you considered putting into that group, or who you could see evidence emerging over the next, say, 5 years, that if we had this discussion 5 years from now, they would be included in that list?Anna Podolanczuk: Its that family history. We had two kind of two subgroups. One was where there was two or more individuals, and one when they were their family members, when there’s only one individuals with pulmonary fibrosis. And in that group with sporadic, you know, it’s a patient who has IPF, and their children or their siblings are interested in screening, the data shows that the risk of pulmonary fibrosis is still elevated in that group, but there’s just less data in those patient populations, so we really couldn’t reach consensus for sporadic IPF, or idiopathic pulmonary fibrosis on screening. And so I think many of us are approaching it on a case-by-case basis and individualized discussions. But I think as we see more data emerging in that patient population, we may modify our suggestions.Robert Rogers: And so when we think about the benefits and risks and costs of screening and early intervention, we always have to weigh several factors, and one of those factors is patient anxiety, this worry that now you’ve been told you have an abnormality or a disease, and you may not have any symptoms of that. I’m curious, in your clinical practice, and to the extent that there’s research on this, how are patients reacting to learning that they have what, to them at this time, is asymptomatic interstitial lung abnormalities or disease on their CT scan.Anna Podolanczuk: Yeah, that’s a great question. I haven’t seen any studies in this specific patient population, but it’s certainly a concern. Most of my patients, when they come to see me because they had this incidental finding on their you know, a lung cancer screening CT scan, or their coronary artery calcium CT scan, and they look it up on the internet, they get very scared, they get very nervous, and so I have to do a lot of education to put this in a larger context, you know, this is not the same as being diagnosed with idiopathic pulmonary fibrosis. This is an abnormality, and so the anxiety is certainly real. At the same time, especially for individuals that have family members who have suffered from pulmonary fibrosis, I think there is interest in trying to identify earlier stages and tryto intervene earlier, because many patients have seen their family members get diagnosed late and have to go through a lung transplant, and so I think it can be very empowering to get screened. But it has to be an individual decision, and it has to come with a lot of education to put everything in context, because the prognosis is highly dependent on the disease stage. Patients who are diagnosed with early disease are gonna live a lot longer than patients who are diagnosed with very advanced stages.Robert Rogers: Yeah. So, let’s, imagine for a second, hypothetical situation. Imagine that we had some sort of widespread screening program, to give middle-aged or older middle-aged adults, chest CTs, in the population at large. It extended beyond those, those three groups that you, have already mentioned. What do you think that would look like at this point in time? Would the risks of that, of overdiagnosis and false positives and things, outweigh the benefits? Would there actually be great benefits? How do you think something would pan out if we did that with today’s tools and technologies?Anna Podolanczuk: So it’s interesting, because actually this is done in some other countries, like in Asia, and a lot of the research comes from Korea and some of it from China, where health screening with CT scans is much more common, and so it’s not just a theoretical discussion. I think the approach to education is different in those countries. I think here, there is, hopefully, a lot more education that would happen. Because I think, from my perspective, it has to be a risk-benefit discussion, and it’s not right for everybody. I think patients need to be aware of their choices, they need to be provided with some sort of guidance before they decide to undergo screening, on whether it’s right for them and what to expect from screening. I think the power of CT scans is that there’s so much now that we can detect on CT scans. Obviously, we’re talking about pulmonary fibrosis, but you get a CT scan, you can identify nodules, you can identify, you know, coronary disease that was previously unknown, you can identify things like emphysema, there’s so many incidental findings, some of them are meaningful, some of them are not meaningful, some of them are actionable, and some of them are not actionable, and there’s certainly a risk of a lot of procedures, and there’s a potential for harm with screening if it’s not done in the right context. And so, I don’t know about the role of just widespread screening. To me, screening and targeted population, where we know there’s an unknown risk, an increased risk, where there’s a higher likelihood of having a true positive as opposed to a false positive, makes more sense than just having this broad, broad screening. But certainly, you know, that should be a risk-benefit discussion with individual patients.Robert Rogers: Very good. What is one development or advance, could be at the level of tools for diagnosis, or treatments, or even policy or systems-level changes, that you think would most advance the field of early intervention for pulmonary fibrosis?Anna Podolanczuk: My dream is to have a blood biomarker that would, be a sensitive test that would inform who should then undergo screening. And so having that first tier, kind of, kind of like a D-dimer, you know, I don’t know, are we still doing D-dimers? But, you know, something that…Robert Rogers: We’ll just explain for our listeners a D-dimer is a specific blood test, and the way that it’s used clinically in medicine is to rule out the presence of a blood clot in the lungs. So people come to the emergency room, one of the things, if they’re short of breath, one of the things that could be causing that is a blood clot in their lungs called a pulmonary embolism, but we don’t necessarily take every patient in the emergency room who’s short of breath, and do a CT scan to determine that, because we have this easy blood test that tells us, you know what? This blood test is so low, we don’t have to worry about blood clot, and we can skip the whole CT scan. And so what you’re saying is you want a D-dimer for pulmonary fibrosis, basically, and then you wouldn’t have to screen all 100 of those people in the community to find the 7 that have interstitial lung abnormalities. You could just screen, you know, the..Anna Podolanczuk: 10 or 20 or whatever, yeah, exactly. I think that would be life-changing.Robert Rogers: And you mentioned one such biomarker that you’ve studied, and that is being used increasingly in advanced clinical practice. Maybe just say a little bit more about that, and what are some other potential biomarkers that might emerge?Anna Podolanczuk: Sure, and you’re talking about the telomere length testing? Yeah, so again, this is not available in every clinic, because it is, a test that is, only run in certain in very limited number of facilities, and is not often covered by insurance, but I find it useful for many of my patients. And again, this is a test that is measuring the caps of the DNA, and as people age, those caps, the telomere lengths, get shorter, and that’s associated with aging, but in people who have extra short telomeres, it’s associated with premature aging and some of those things that are, some of the diseases that go with that, including lung fibrosis, but also liver fibrosis, and also potentially cardiovascular disease. And so I find it useful. It shouldn’t be a prerequisite in screening. We actually addressed this in our document. But it is something that can be an adjunctive test to help make decisions for our patients.Some of the other tests, you know, we’ve published and others have published on monocytes. These are a type of cell in the blood that is an inflammatory cell, and having elevated monocyte counts is associated with interstitial lung abnormalities and progression of those. So I look at those sometimes, kind of, in the overall, my overall approach to the patient. I don’t make any individual decisions just based on the monocyte count, but I take it kind of as in the overall evaluation of the patient. What I’m really excited about in the future is the role of genomics and proteomics specifically, in helping to guide individual risk of progression. There’s some really great work being done by Justin Oldham out of Michigan, looking at proteomic biomarkers. Now you’re taking, a set of proteins in the, in the blood, and he’s developed predictors, classifiers, using, the levels of certain proteins, and, he’s shown that having a certain level of proteomic biomarkers, having a high-risk proteomic signature can discriminate people who are at high risk for progression of pulmonary fibrosis, and so I think that’s, again, that’s still in the research stages, it’s not available clinically, but I’m excited about that potentially being available in the future.Robert Rogers: Great, and final question, on foresight medicine, we focus on having a comprehensive disease-oriented framework for prevention, and I’ve learned from your work recently that you’ve been studying a lot of the shared risk between both interstitial lung disease, what we’ve been talking about today, and also another disease that we’ll talk about shortly in the future, coronary artery disease and heart disease. Tell us what you’ve found so far.Anna Podolanczuk: Yeah, we’re talking specifically about atherosclerosis, or, that’s another name for coronary artery disease or cardiovascular disease. And what atherosclerosis is, is fibrosis of the blood vessels of the arteries, right? And so it’s just another fibrotic disease, and there is a strong link, epidemiologically, between the risk for pulmonary fibrosis and having elevated coronary artery calcium, having a higher risk of things like angina or myocardial infarction, of heart attacks, and so I think there’s a certain, group of individuals biologically are predisposed to scarring in the lungs, as well as scarring in their arteries, and we’re trying to better understand what that predisposition means. Is it genetic? Is it some combination of exposures? The predisposition seems to go beyond smoking, beyond lipids, although lipids seem to, seem to play a role. Like, for example, I found that having high levels of HDL cholesterol, which is the good cholesterol, is protective. It’s known to be protective in cardiovascular disease, but it also seems to be protective against pulmonary fibrosis.And certain protein components of the HDL seem to be the most important and most protective, and that’s something called apolipoprotein A1. And so we’re trying to better understand what that connection is between those two fibrotic diseases to better identify if there are specific drug targets that we can identify that would work, both for pulmonary fibrosis or cardiovascular disease, or if we can learn from each disease and better identify better treatments for them.Robert Rogers: Very fascinating work. Dr. Ana Podolanczuk, thank you so much for joining us on Foresight Medicine. Learned a lot from this conversation.Anna Podolanczuk: Thanks for having me. Get full access to Foresight Medicine at foresightmedicine.substack.com/subscribe