ATS_BEP_05x_ALA_First_Edit
non: [00:00:00] You are listening to the A TS Breathe Easy podcast brought to you by the American Thoracic Society.
Eddie: Hello and welcome. You're listening to the A TS Breathe Easy Podcast with me, your host, Dr. Eddie Chen, also the host of the ICO and Podcast. Each Tuesday, the a TS will welcome guests who will share the latest news in pulmonary critical care and sleep medicine. Whether you're a patient, patient advocate, or healthcare professional, the ATS Breathe Easy podcast is for you.
Uh, joining team joining me today, I've got two very special guests. Anna Potamic, who is an assistant professor of medicine at New York Presbyterian, co-director of the ILD program. And then Joe Opal, who's an associate professor of radiology at Duke. Thank you guys both for coming.
Anna: Thanks for having us.[00:01:00]
Eddie: Absolutely. So, so today, uh, our topic of conversation is gonna be talking about ILAs, uh, or interstitial lung abnormalities. I think, you know, to start, this is a relatively new definition as far as like the history of medicine is concerned. Uh, Anna, can you help describe to me what, what, what is an ILA?
Just to set the stage.
Anna: Sure. So over the last, uh, decade or two, there's been increased awareness about trying to diagnose interstitial lung disease and pulmonary fibrosis earlier. And so there's been a number of research studies that have looked at subtle changes on a CT scan and individuals who don't have a known diagnosis of interstitial lung disease and they.
Undergone CT scans for things like lung cancer screening, or they were enrolled in a research cohorts like, uh, Framingham heart study and a number of studies have looked at their CT scans and found that there an. Quite a large [00:02:00] number actually, of individuals in those studies have changes that are suggestive of interstitial lung disease.
So those are things like reticular abnormalities or ground glass opacities, and sometimes more advanced fibrotic changes like traction, bronchiectasis or honeycombing. And so in 2020, the Fleischner Society formally defined the term interstitial lung abnormality, and then they, they define them as. Those findings of reticulation, grand glass opacity, traction, bronchiectasis, honeycombing, or architectural distortion that involved, uh, 5% or more of, of, of a lung zone.
Um, and in 2020, the iShare Society, they need to be said that they need to be found in individuals. Uh, they need to be incidental findings. So in individuals who don't have a known diagnosis of ILD, we recently updated that definition as part of a large, uh, committee of, uh, and an a TS sponsored document on interstitial lung abnormalities.
And we largely left. Retained the radiologic definition of [00:03:00] ILAs, but we did remove that need for the incidental findings and so allowing for ILAs to also be identified in screening population, like those undergoing lung cancer screening or those with connective tissue disease or those with the family history.
Eddie: Yeah, no, that makes a lot of sense. And and so much of this is dependent on a radiography because, you know, a lot of these patients don't have symptoms, Joe. Uh, do what, what kind of things do you have to add as far as like the radiologic definition? And then also can, can you gimme a little bit of your experience on what you're seeing as a the thoracic radiology?
Joe: Yeah, I would love to, you know, we've learned a lot about fibrotic lung disease over the last 10 years. Honestly, we didn't really know anything too specific before 2013. The medications really forced us to get really good at diagnosing interstitial lung disease. That was the first thing I noticed. And you know, now it's 10 years, right?
10 years since that and now we have gone back and looked at scans. One of my favorite things to do is to read out with a [00:04:00] fellow resident and to look at the earliest scan in a patient that we know has ILD, and not even just that chest ET, to go look at that abdominal CT for a renal stone and see if you can see any findings at the lung basis and see what the earliest form of fibrotic lung disease is.
And you know, I will tell you as we've gotten better at this and we're still learning and we're still trying to get all the radiologists on board with this, we really try to identify those first imaging findings that may get us to say there is subclinical fibrosis here. And so that's kind of been the journey with ILD first to really get good at diagnosing interstitial lung disease, and now to identify subclinical fibrosis by imaging.
Eddie: How you mentioned going back and looking at all the imaging, including even abdominal cts, how, how often would you say you might not have a number, but how often would you say that you're, you're seeing these things, the first representations of these interstitial lung disease show up on non-dedicated chest imaging?
Joe: I would say a lot.
Eddie: A [00:05:00] lot?
Joe: Yeah. I would say like there are times I've had to even educate some of the body people in our own medical center to be like, you guys need to comment on this 'cause this is a real finding. There are a architectural changes here that may impact this patient in a couple years and we want to get them to pull to potentially get P fts and look for restrictive physiology.
And so I would say we see findings very frequently on scans that aren't dedicated chest CDs.
Eddie: Yeah, no, that's really interesting. And then the can from a, I guess from a, like a pulmonologist perspective, you know, I also look at the, the chest imaging as well, how com at least compared to like what I'm used to seeing some of the, like these end stage ILDs.
How subtle can these changes be? Or am I looking for something or should it be something that's, uh, if you're used to looking at some of these chest cts should be obvious for you.
Joe: Yeah, I mean that's where we get into the weeds a little bit and where I get made of, made fun of by some of the people in my section.
'cause I'm over calling ILA, I mean. It's just the reality. Like we see subpleural [00:06:00] opacities when a patient is laying on their back on a hard CT scanner and it's when are you gonna make that call to say, Hey, this is interstitial lung abnormality. And I think really honing in on those imaging findings of reticulation traction, obviously honeycombing, to be able to say, no, this is true fibrotic lung disease or subclinical fibrosis.
But it can be very, very, very difficult. And we certainly don't wanna be over calling interstitial lung disease or subclinical fibrosis. And it's a fine line. And I would tell you those of us who are trained in thoracic radiology, we even have difficulty with it too. So I would tell you it, it is still very difficult to do.
Eddie: Yeah, no, that, that's really helpful. So the, so let's say we have this patient and the, the body radiology people, uh, find the, what they think of an ILN. The recommendation is to, to get them into, to pulmonary. Uh, and, and a how, how from like a, from a clinical side, how are we drawing the line between ILAs and ILD?
So what? Yeah, it's, what would you say? Say that difference. [00:07:00]
Anna: Yeah, it's, it's a, it's a hard decision sometimes and so we, in, in this document we recently published, we try to have the term ILA be kind of more broadly inclusive and so less specific. And a lot of individuals with ILA will not progress to true fibrotic lung disease.
And so we try to identify features in individuals with ILA that would make someone a pulmonologist or even a radiologist. Say this is not just an abnormality, this is early disease. And so we actually, as a committee, proposed a definition of ILD individuals with ILA and we considered, um, individuals with symptoms that can be attributed to, uh, to ILD as.
Having a disease rather than an abnormality, as well as physiologic abnormalities, any decrements below normal and F-E-C-T-L-C or DLCO. Um, and importantly there's a large body of data and imaging findings of fibrosis, and those individuals who have an ILA with. [00:08:00] Obvious fibrosis as having, uh, really high mortality rates.
And so, uh, important in this document we said that individuals who have honeycombing or traction bronchiectasis in the context of reticulation that involves 5% of more of the total lung volume should be kind considered as having an ILD rather than just an abnormality that that would. Usually be an early ILD if those findings are mild and subtle, but those abnormalities have been shown to be associated with higher mortality rates, uh, and as well as progression of abnormal of, of ILAs over serial CT scan or progression or, or decrements, or decline in p fts over.
Over time would also be considered a disease rather than just an abnormality. And then in individuals who happen to have a lung biopsy for, let's say a nodule resection, and if you can find, uh, a, an an ILDA fiber presence of fibrosis of a fibrotic pattern on biopsy, that should also be consider called an ILD rather than an ILA.
Eddie: So, so I, I liken a [00:09:00] lot too of this definition. You're talking about the, you have symptoms that can be attributed to the interstitial lung process here for the parallel in the critical care world is, is a RDS. Do you think, you think that it's not related to cardiogenic pulmonary edema? How, as a, what would you recommend to clinicians who are seeing these patients, um, in clinic?
H how far should they go to evaluate other causes of, of dyspnea, for example, um, before you're saying that this is gonna be attributed to i a, should I be getting their an, an echocardiogram, even if they're, you know, PFT is normal, they don't have orthopnea, or how, how far should I be going?
Anna: Sure, absolutely.
I think this is where, where the art of medicine comes in, right? And so if I'm seeing a patient who's coming in with shortness of breath for an evaluation, for a pulmonary evaluation, you know, I'm looking at their CT scan and I'm looking at the extent of abnormalities under their CT scans, and can that extent of abnormality truly explain that dyspnea or is there something else that we're missing?
Um, and so, you know, [00:10:00] if, if, if. If it doesn't seem like they're a combination of their pulmonary function and their CT scan, it really explains the extent of their shortness of breath. Then I am pursuing other things like an echo, even occasionally a co A C PED or cardiopulmonary exercise test. There's also some advanced imaging modalities that could be considered in those settings to try to really figure out why someone is short of breath.
I,
Eddie: my favorite test from pulmonary boards is, is CCP a. Absolutely. We, we've talked a little bit about, you know, ILAs and, and ILDs and when to call it, uh, Joe, I'm, I'm curious, are, are there features of a patient's thoracic imaging that may make you say where, what's the, where's the line between calling something an ILA versus ILD from a radiology perspective?
Joe: Well, this is still a moving target for all of us, and I would tell you, you know, initially we were, it was all about if the patient had imaging findings, if they were actually symptomatic. And so that's when we would shift gears from ILA to ILD and I, I promise you, [00:11:00] we have patients in our lung cancer screening group that have honeycombing that we are saying ILA.
I'm calling the clinician like, no, they're asymptomatic. And we're like, that's not even possible. And we're watching them progress over their annual lung cancer screen, right? It's a great patient population to watch true interstitial lung disease progress. And so, you know, when I see like true the features for me that slam dunk it are honeycombing and traction, really only restrictive physiology is gonna give you that appearance.
Architecturally within the lung reticulation is a little bit of a slippery slope, right? We've seen other things cause reticulation. But I, when I see those other two features, I really start to kind of, in my mind, push this from ILA to ILD. Obviously we, there's a lot of stuff that goes into an ILD diagnosis, and that's a very important diagnosis to make.
But for me, radiographically, those are the things I think about with true fibrosis.
Eddie: Yeah, that, that's really interesting. I think Bo both of you have kind of mentioned this following over time and, and who's gonna progress, I think e either Ann [00:12:00] or Joe. What, what kind of, what kind of patients are we looking for as far as those patients who, uh, you're concerned about their ILA progressing because, and please correct me if I'm wrong, my understanding is that some of these patients ILA will not progress and some of them will actually get better over time too with the, at least radiographically.
Anna: Sure I can start and then Joe can maybe add to it. So, um, back in the Flexner document, they define subcategories of ILAs and those subcategories are, are there because they're associated with different risk of progression. So there's a. Antifibrotic ILA, so that's pure ground glass. And even just reticulation as Jo, uh, Joe mentioned, it's, it's nonspecific.
So, um, those are considered non fibrotic ILAs. And, and in those cases, they're less likely to progress, but individuals who have subpleural abnormalities, um, so subpleural, non fibrotic ILAs or have a higher risk of progression. And then that presence of frank fibrosis, as Joe mentioned, that's, it's the same in, in, in my sphere, it's [00:13:00] presence of traction, bronchiectasis or honeycombing, or.
Know, occasionally, like it may not be frank traction bronchiectasis, but even more subtle traction bronchiectasis, um, is a, is um, a associated with higher risk of progression. And so those are the individuals that I'm watching more, more closely and monitoring over time with serial PFT as serial imaging.
Joe: Yeah. The only thing I would just add to that is yeah, specifically agree with ANA on the, on the. Architectural findings. Of course, in addition to that, anything clinically that our clinicians can give us that is even a, a whiff of this could be like true ILD and a connective tissue disease person or anybody with any type of history, familial history.
That's when I start to really start thinking these findings are more likely gonna progress and probably represent true for lung disease.
Eddie: Yeah, no, that, that's all that's really interesting. And, and kind of building off of this, you said. Talk about history and connected tissue disease patients with familial histories, and [00:14:00] you go, you mentioned lung cancer screening.
Are there, you know, not, it seems like everybody gets some sort of cross-sectional imaging at some point in their life, but a lot of these patients actually, actually don't. We see a, we see a, a select, uh, subset of patients here in the hospital. Are, are, are those, are there patients who should get screened?
Uh, even if we don't know that. They already have the ILA or otherwise.
Anna: Sure. Yes. Uh, so in our document we suggested screening for any first degree relative of family, of of individuals who have familial pulmonary fibrosis. Meaning those are individuals where there are two or more family members. Uh, any type of pulmonary fibrosis in a family.
Uh, and so we know that those individuals, their first degree relatives, uh, have roughly one in four risk of having at least an ILA, not early ILD. And so [00:15:00] we suggest that screening in that patient population once they reach the age of 50, um. There was some discussion about also screening an individual first degree relatives of individuals with IPF and just sporadic IPF.
Um, however, there's data that suggests that the risk is, uh, similar and sporadic and familial pulmonary fibrosis in terms of the genetic risk to their relatives. But the data in the sporadic, uh, patient population is just much more sparse. There aren't as many studies and so. We've thought there would be a large burden of scre potential screening population.
And so I think in those cases it should be an individual discussion. And if there's additional, um, PFT abnormalities or any symptoms, then I would consider screening also in that patient population. We also suggested screening in patients with connective tissue disease that are associated with, uh, with ILD.
So those are individuals with, with scleroderma, rheumatoid arthritis, myositis, um, mixed connective tissue disease. [00:16:00] Um, I'm not sure if I'm missing anything else. Um, and then lung cancer screening obviously is a large patient population, uh, and smokers in general. And so in that patient population, I think, uh, there should be a consent, uh, a concerted e effort towards reporting ILAs on those lung cancer screenings.
Uh, CT scans. We're still seeing a lot of, um, radiologists not. Formally reporting ILAs, um, when they're present. And so if there's someone's undergoing a CT scan, it should at least be evaluated for the presence of an ILA.
Eddie: You know, Joe, there's, there's so many different flavors of, of CT scans. It's so easy for me to say in clinic to one fellow that we can go ahead and screen them for, for an ILA.
What, what kind of, what would you, what would you recommend to us on the kinda ordering side or what kind of CTS tests are, are adequate or what would be the best possible? 'cause I know you have, we've talked about low dose lung cancer screening cts. There's normal CT tests. We do a lot of high res or like multiple physician where the patient gets [00:17:00] sent through the scanner multiple times is supine and prone inspiratory exploratory films.
What, what would be best if we're talking about the these, this kind of screening population?
Joe: I mean, the first thing I would tell you is now in contrast, no thoracic radiologist wants to have contrast, right? We start lighting up pulmonary vessels and lymphatics, and then I'm like, is that reticulation or is that contrast?
So first non-contrast. So if you have a patient that you're suspicious, maybe they went to the ED and got a PE study, that's probably not gonna be enough for us to be able to say in particular ILA. So they're gonna need a non-contrast chest ct. Outside of that, you know, honestly, the low dose lung cancer screening.
Images are really good. You know, there's enough contrast, there's enough attenuation difference between the pulmonary parenchyma and pulmonary fibrosis that we can see those imaging findings. So that is a pretty good study. If I was gonna shift gears and say, Hey, I'm on an abdominal ct, which is non-contrast, is this ILA, then I would just punt right to what we have as an interstitial lung disease [00:18:00] protocol ct.
And you know, for that, it's exactly what you said. First of all, I want intersection imaging. So non-contrast thin section imaging, they should be at least less than 1.25 images. I don't really wanna see greater than two or than 1.25, because you're gonna miss ILA. And then, yeah, when we get these subpleural opacities laying on their back, it's great to get prone imaging, in addition to supine imaging, to see if those things resolve and see if that actually wasn't even ILA.
And then also the expiratory imaging can be very helpful to look for airway centric fibrosis like HP or some other airway centric disease. And so that protocol is kind of built into many of these academic centers for interstitial lung disease. And I would tell you, if you don't have a really good non-contrast chest ct, which is good enough, I think to address these, these questions, then I would, I would move to an ILD protocol ct.
Eddie: Let's say we've, we've gotten to the point where we are, ILA, we said they have a radiology, a [00:19:00] radi, radiologic abnormality that suggests that they have ILA, but they don't have symptoms attributed to that. How, Anna, when you see this patient in clinic, how, how are you managing them? What kind of things are you going to be looking for, uh, and how are you counseling these patients?
Anna: Yeah, absolutely. So I. My approach is to risk stratify those patients with ILA and to to figure out if at what risk of progression they are. And so that's where all those other clinical factors come in. Like is there a family history, is there a presence, signs or symptoms of connective tissue disease? Um, are there other risk factors like smoking or reflux?
Other things that are associated with, uh, pulmonary fibrosis. So I'm doing, you know, I'm evaluating the patient as I would any patient potentially with, with ILD, just to look for tho that history, that clinical history, um, considering looking for autoimmune serologies and select patients depending on their, on their risk.
Um, and then doing a lot of, uh. [00:20:00] Teaching counseling on the genetic risk. On the exposure modification. Obviously if they're smoking, they should quit smoking. Um, we're looking for occupational exposures and risk factors for, for progression in terms of that. Um, and then I'm mainly telling patients if they have subtle, early abnormalities that they should not be ignored, that they need follow up.
And you know, as Joe was. Saying you can often look back five, 10 years and see people had set ups on their CT scans, and then you're seeing them in clinic five, 10 years later and counseling them about oxygen because they have end stage fibrosis. And that's really frustrating when something could have been done to intervene earlier.
And so I'm telling patients, come back and see me. In a year get an, get a breathing test. They should get a baseline breathing test and they should get a follow up breathing test just so we can trend it. Don't, don't forget to follow up, come back once a year to see me. If there are any new symptoms developed, come back sooner.
And then imaging depends, uh, on kind of where they, uh, lie along that [00:21:00] ILD risk. We sit in our document follow up imaging in two to three years for ILAs, but if they have more. Suggestion of a fibrotic process, then I might do a sooner CT scan like that a year.
Eddie: I was talking to some of my colleagues as we were preparing for this, uh, preparing for this episode, and you'd mentioned in a couple of times that there was a good review published by you in the, in the Blue Journal in July of 2025, called the Approach to the Evaluation and Management of Interstitial Lung Abnormalities and Official American Thoracic Society Clinical Statement.
And in that, you, as you mentioned, that there's. Uh, you, you screen PFT high risk every six to 12 months, low risk every two to three years. How, how did you and the committee come up with some of these different timeframes, um, for, for these different screenings?
Anna: So it, it's, we, this is an evidence-based document, so there was a large, um, literature surge and, and, um, and.
Evidence synthesis that [00:22:00] guided our, our suggestions. Um, and these are all suggestions. And so they need to be individual, individualized to, to practice settings and, and individual patients. Uh, but so, so there was a committee of 40 individuals from across the globe, and so the suggestion for follow-up would.
It was based on studies, um, in, in certain populations and for example, in a health screening cohort, um, out of Korea where they do routine kind of CT scans for, for just for general health screening. And they had a large long follow-up of individuals who underwent serial CT scans for, for, for health screening.
And they found, they looked at time to progression in that population and they found that time to radiologic progression in ILAs. Was actually median time was about three years, but median time to progression to UIP was closer to 10 years. And so it was really based on that data showing that, um, an ILA is something that can progress very slowly.
Now in individuals with a family history and in with some more fibrotic features, that [00:23:00] time to progression is shorter. And so in those individuals, that's why we suggested doing a shorter interval for follow up.
Eddie: Interesting. And, and Joe, from your perspective, you know, radiology can sometimes be this, like this time machine.
As you get to review all these different imaging studies over time, what, what is your, I guess, gut reaction to this, this timeframe? Does it seem like a reasonable timeframe from what you're seeing in your experience or otherwise?
Joe: Yeah, I think that's pretty accurate. What you know, it's great because in the lung cancer screening group, which is certainly one set of ILA and interstitial lung disease, we're able to kind of watch these features every year, right?
So you really get a perspective for that. Also, kind of looking at the different classes of patients that come to our ILD clinic and going back at looking at the images. Some of these architectural features are totally unchanged, right? And then some of them progress pretty rapidly, and so I think the evidence-based approach is really appreciated.
For following these patients.
Eddie: Yeah, that makes a lot of sense. I I, I have, I have one, [00:24:00] I have one more question I think for Anna before I wanna get both of you all's kind of closing thoughts on this. And, and, and you had mentioned, you know, talking about like genetic genetic risk. Uh, are, are these, are there patients or are there situations in which you would recommend genetic testing for different types of ILD variants that we have known?
Gene associations,
Anna: uh. It's hard because genetic testing is not. Yet broadly and widely available. So we know that there are variants, for example, in the Mach five B. It's a common variant that's strongly associated with IPF and with Ila actually, uh, there are also, um, multiple variants in genes that are associated with telomere length and telomere, uh, dysfunction that, um, are strong risk factor, especially for familial pulmonary fibrosis.
And so, and fa and, and. Individuals who have a family history, who have FPF, um, who have. [00:25:00] Diagnosed ILD, that there's, you could consider referral to genetics if that's available, but otherwise we're not routinely testing, um, those individuals for specific mutations or variants because there's also a lot of unknown.
There's a great study actually out of, um, group at, uh, at Columbia University that looked at the FPF population and, and individuals who have a known family. Uh, history. They found that in more than well over more than half of individuals, they could, they, when they did whole genome sequencing, they couldn't identify a specific variant that was related to their lung disease.
So there's still a lot of unknown about the genetics. Um. Tell your length in itself could be considered testing, and a lot of centers are measuring telomere length in individuals. Uh, some individuals with ILA and individuals with ILD, but again, that also depends on availability and cost of that test because it's not widely covered by insurance.
Eddie: That makes a lot of sense. Uh, this has been really enlightening to me and really educational, and I hope it's for the listeners as well. Uh, [00:26:00] I'd like to just see if there's there anything else that you'd like to leave our, our listeners with. I start, I guess I'll start with Joe first, and then we can close out with Anna.
Joe: Yeah, I mean, I think the biggest thing is we've learned so much about interstitial lung disease over the last 10 years. We've gotten really good as, I think as a group of thoracic radiologists, we've tried to impress upon the people. In radiology who trained before 2014 to really explain to them that this diagnosis is very, very, very important because there's treatments out there that didn't exist.
Now we're kind of shifting gears to kinda really pick out who are the people that have these subclinical features, right? Radiology is the gatekeeper, for better or for worse, sometimes I say for worse, but we're the gatekeeper for identifying these patients. And getting them to pulmonology. So it's really, really important to identify these imaging features and be able to say, Hey, this is ILA, let's get 'em to poem, and then we can see if they're actually gonna progress.
That was great. Joe. Anna, what
Eddie: [00:27:00] about you?
Anna: In the same vein as what Joe mentioned, uh, just please, uh, don't ignore findings. This is like what? This is what keeps me up at night is when I see patients coming in with end stage disease, and we could have intervened earlier. Not every patient with an an imaging abnormality or even early fibrosis necessarily needs treatment, but properly diagnosing them and monitoring them over time to decide when it is appropriate to intervene and to treat is the most important thing that I look for in my practice.
Eddie: I think, I think one of the important things for our listeners, as we already referenced, I think, and I think we can link in our show notes, uh, is to to go to the statement that was put, uh, put out by Anna and colleagues, uh, published in the Blue Journal. But I, I would like to thank everybody and for joining us for today's a TS Breathe Easy episode.
Please subscribe and show this episode with your colleagues. Uh, put it on your calendar. I think early registration for the a TS conference in Orlando in May has already opened. Go to conference thoracic.org today. [00:28:00] Members get a discount on the conference registration, so become a member to renew your membership or, and take advantage of the savings.
That's a good reminder for myself. To, uh, and we will see you next time. Thank you, Anna. Thank you, Joe. Thank you. Thank you.
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