ILD Diagnosis, Screening and Monitoring Save

Hello, everyone. Welcome to Tuesday night rheumatology. It's ILD month. September is ILD month. I'm Jack Cush with roomnow.com.

I'm here for our final TNR webinar on ILD. Tonight, we're going to be discussing, ILD diagnosis, screening, and monitoring. I'm joined by four friends, four experts in the field. Let us introduce ourselves and then we'll get into it. I'm Jack Cush in Dallas, Texas.

Elena?

Hi, my name is Elana Bernstein and I'm an associate professor at Columbia University where I direct the Scleroderma Center. Happy to be here.

Excellent, Brian. Hi,

everybody. Brian England, rheumatologist, University of Nebraska Medical Center and co director of our autoimmune lung disease clinic.

And rheumatology's favorite pulmonologist, Shane, you're muted.

Hi there, I'm Shane Shapiro. I'm an associate professor at the University of Toronto and I run the ILD program from a pulmonology perspective.

Excellent. All right, so let's take a look program. At As you know, we've been doing these weekly for the last four weeks. Tonight, we'll be getting into screening and monitoring, especially throughout the month, a lot of content from a lot of really fabulous contributors. It still have content coming in.

We had two great articles on JDM and ILD in the last two days that are gonna be posted for you to look at. We've got great podcasts, a lot of good videos, a therapeutic update, which is all about the guidelines and the diagnosis of ILD. Again, a lot of content to consume, either by video, by reading, or on a podcast. Tonight, we're going to go over the results of a pre webinar survey that was sent to the RheumNow Rheumatologist HCP audience. We had back in one day, one email invite, two eleven responses, ninety two percent of whom were rheumatologists.

We have, again, a healthy number from both outside The US and inside The US. Four percent were advanced practice providers. And we asked a total of 11 questions on these topics. I didn't ask any questions on diagnosis of ILD. We've covered that in other webinars and other ways during the month, but I want to give our panelists an opportunity to comment on here.

Is there something that we're missing in diagnosis? Who wants to take a run at that?

Well, I can start the discussion there. I think, Jack, the important piece of the diagnosis is we spend so much of the time in the guideline efforts both the ACR, ULA corresponding one, and who do we send for testing, but that's the first step in this process right is who do we go with the testing to help us detect some of these abnormalities, but once you start to detect an abnormality that doesn't mean it's an instantaneous application of a new diagnosis, right? There's that next step where we have to continue to be very thoughtful about what we found that was abnormal, how that is combined with what symptoms, findings that you see on exam, and then discussing with other smart people that you can you can find like a pulmonologist or a radiologist to ultimately come through and establish the diagnosis. So I just you know, I think the big thing to me is putting a plug out there that it's not just about when do you order the tests, you're not done there, right? You have to interpret the tests and thoughtfully apply them before you make this diagnosis.

Brian's suggesting that it's not just one test and a diagnosis has had that maybe time is very important in making a diagnosis. Is that true for you?

So that's a very interesting question. So I'm going to sort of approach the question of incidental finding of ILD. And I think I'll get to an answer there. So when we're screening our patients for interstitial lung disease, our question is, you know, do they or do they not have ILD? So I'm not sure that I would say, if you find ILD on a chest CT, is that really an incidental finding?

Because you set out to look for it. And the gold standard diagnostic test for ILD is a high resolution chest CT. So I think if we see ILD on a chest CT, it's ILD. Now, the question though is, you know, what is the etiology of the ILD? So I agree there.

You know, is it the patient's underlying autoimmune disease? Could they have, you know, coexisting hypersensitivity pneumonitis? Were they misdiagnosed at some point with an autoimmune disease? And is it really idiopathic pulmonary fibrosis? So I agree that finding it on a chest CT doesn't tell you exactly what to do about it.

But I would say it is ILD, whether it needs to be treated is a separate question. And I do agree with, you know, conferring with pulmonologists and radiologists, ideally in a multidisciplinary discussion that we have at academic centers to figure out what the next step should be in assessing a patient's risk of severe disease of progression.

Shane, I want to give you a chance to jump in on this, but I also want to point out another thing. I think pulmonologists often see patients where ILD is really found because a chest CT was done for a shoulder injury and that's how they found incidental, not because they had a suspicion or whatnot. And I found the pulmonary literature on this kind of interesting. Do you wanna address that?

Yeah, that's exactly where I was gonna go, Jack. Like I think it's so interesting how we come at it from exactly the opposite end. I get a ton of patients from our local scleroderma clinic and our RA clinics, but we also have a whole bunch of patients who are found to have ILD or ILAs. And we're trying to find out if they have an underlying autoimmune cause because that completely changes our thinking around the case. And I find, we're always trying to find that balance between going fishing and actually finding useful and meaningful stuff.

And I think one of the places where we've evolved the most in my sort of ten or fifteen years at U of T is that we're starting to screen in different ways for CTD or SARD. We now do things like myositis antibody panels that we didn't used to do. And at first that seemed a bit fishy that we were literally just fishing for antibodies, but then we started to find that, hey, all these patients who had COVID six months ago, now they have organizing pneumonia and then we do a myositis panel and we find that they have an anti MDA five and we send them to the rheumatologist who's like, I don't care if there's not much else going on in the joints. If you've got organizing pneumonia and rapidly progressive ILD with a high tighter anti MDA five, that's MDA five disease and so, I I think we sort of come at it from the other line and and I think that's why it's so important that we all get in the same room so we can start to see how the others think.

Okay,

I'd just sort of add on to that, even though this is not a treatment discussion, but I think that's a great point. So, in the inflammatory myopathies, obviously we think about myositis as a key feature, but there are some patients, many patients who just have interstitial lung disease, and a myositis associated antibody, whether it's MDA-five or one of the antisynthesis antibodies. And these patients have myositis and their ILD is often very treatment responsive. So it's important for us as rheumatologists to sort of recognize that.

Okay, that's really helpful. I want to pause here and make two announcements. One for the audience, please, if you have any questions, ask them in the Q and A box, and we'll answer them real time with our panelists. Secondly, I want to acknowledge the sponsor of our ILD month, which is Boehringer Ingelheim. Thank you for all your support for this educational program that's going on throughout the month.

So our next, where we begin our questions, I asked the audience, again, mostly rheumatologists, who do you screen for an ILD? And the answers were in favor of SARS and that systemic autoimmune rheumatic diseases. In pulmonary, they call them CTD ILDs or CTDs, but ones who have risk factors or all SARs, twenty eight percent. And then being more specific and picky, only in my scleroderma, my myositis and Sjogren's, or only in my lupus and RA, or only with respiratory symptoms. So again, what's the right answer here?

We obviously see lots and lots of SARs. Should all of these that have been mentioned here all be screened in the same way or should you be more selective? Shane, what do you think?

Yeah, think that there is definitely a lot to slice there. Like, I really don't think that a scleroderma patient is the same as a lupus patient. We know scleroderma is gonna have a very high incidence of ILD whereas lupus is really not gonna have a lot of chronic ILD, maybe an acute pneumonitis at diagnosis, but not a lot of progressive fibrotic ILD. So I really think that we should be thinking about both the disease and within the disease, the patients who are the highest risk. So, a scleroderma patient, you could argue that basically everyone with scleroderma who you're gonna screen for pH, maybe you wanna send off, you send off the echo, maybe do that one time CT scan, Whereas in a rheumatoid arthritis patient, maybe it's not every young woman who has a classic presentation in that context, more the older men with risk factors.

So I think disease specific risk factors is important.

Brian, we're gonna get to Elan in a second.

Yeah, I would agree with Shane. The big picture is that you're not applying this to every person with all SARDs equally. This is going to be tailored based on the underlying SARD but there's a couple other pieces here. So one is that you know sometimes we like to boil down screening to like a one time event and that's very different right if you have an RA patient you make the diagnosis of RA that's time zero that's different than a scleroderma patient at time zero, right? We think of these prevalence estimates so often and we take those from studies where they have long periods of follow-up and we find that you know over the total duration of disease you know ten to fifteen percent of RA patients will develop clinically significant ILD.

And so then we think well RA ten to fifteen percent that's not at time zero. The average time for an RA person to develop interstitial lung disease is about seventy years into the disease course. So we have to remember it's very different you know the lifetime prevalence of a disease versus at diagnosis. The other thing is the risk factors and so we like to boil this down to be very simple for guidelines or questions where it's you know has a risk factor, but not all risk factors are created equal. One risk factor is maybe different than two risk factors and well if one risk factor is really strongly associated that may mean more than two really weakly associated risk factors and so we have to simplify this down but in real life we as clinicians don't have to, right?

We have our clinical expertise and knowledge that we can apply these on kind of custom de novo one on one fits. So we have kind of a framework based on risk factors, but when you apply it we'd like to do it a little more nuanced.

Alana, how's the view on this from the scleroderma side? Everyone's saying they all get screened.

Yeah, and I agree with that. I think every patient with systemic sclerosis should be screened for ILD, and that screening should include PFTs and a high res chest CT, I think for sure. Now there are some people who might say, well, if someone has limited cutaneous subtype and they're centromere positive, they have a lower risk of developing progressive ILD. And that's likely true, but that's still, that's not no risk. And there are certainly centromere positive patients who have gone on to lung transplant for ILD and not for pulmonary hypertension.

So I think, you know, given the prevalence of ILD in systemic sclerosis of over fifty percent, I think that diagnosis in and of itself warrants full screening for ILD.

So Artie Cavanaugh asked a question about, are we putting too much stock in autoantibody panels, especially for scleroderma and myositis? And especially in light of the fact that UR guidelines have come out and said the screening tool of preference is the high res CT, without much mention, I must say for autoantibody panels. So what is the importance of autoantibody panels?

Well, I think they are important because they do risk stratify people. People. So for example, in you know, as I just said it in systemic sclerosis, people who are centromere positive are less likely to have progressive ILD. People who are SEL seventy positive, or also called Topo-one, they're more likely to have progressive ILD. And I think that's very important.

When you're discussing screening with a patient, you're going to screen them, ideally regardless. But that's an important conversation to have about what people might expect down the line if ILD is actually detected. Same thing with myositis, you know, the antisynthetase antibodies obviously, are associated with a much greater risk of ILD than some of the other antibodies. MDA five is associated with rapidly progressive ILD. And so those are very important pieces of the puzzle for patients to have.

And for you as a rheumatologist or the pulmonologist to be able to discuss with the patient, I still think you should get the HRCT and you should get the PFTs. But risk stratification is important. And those antibodies too in scleroderma will tell you about other manifestations of a patient's disease, you know, outside of ILD that you might expect as well.

So Brian, Christian asked this question about, should we be doing high res CT in every RA patient? We probably never did that before, but we also probably under diagnosed lung disease in our RA patients. So where do you draw the line on ordering the test in RA?

Yeah, I don't screen every patient with RA with a high res CT. Instead, every person that I see with RA, I ask about symptoms and I certainly do a physical exam to see if they have crackles in their lungs and know those are not perfectly sensitive modalities but given the lower prevalence of having interstitial lung disease particularly right at diagnosis that's what I use. It's people who have other risk factors, so people who have severe RA, people who have other extra articular features, those are the people people smoking history those are the people that are then going to make me think about okay I should screen this person for ILD and it may not be a time zero right screening is not a one time event it's not you made the diagnosis you decide whether or not you're going to get a CT and if you choose no you can never again the rest of their life decide not to get a CT. CT machines will still exist and still can be ordered in five years.

Shane, Marilyn Solski asked this question about what is the relative importance of PFTs? It's easy to order when you're ordering a high res CT, but it seems like it's trumped in a major way by high res CT. Could you get away with not doing? Again, rheumatologists, we've always been in love with DLCO, but primary endpoints in the clinical trials are FVC change. So what's your guidance on that?

Yeah, this is where I have to say, I'm gonna be a bit controversial because I do not agree with the ACR guidelines on this. So ACR talks about doing both CT scan and pulmonary function testing for screening. EULAR on the other hand sort of says, should PFT replace CT scan? And they said no, but they didn't really comment on whether or not you should be doing both. In my experience, I think about what you're really trying to accomplish with a screening test, right?

A screening test is a test that has a relatively high sensitivity so that when the test is negative, you can rule out disease. And personally, I think that CT has that on its own, right? If you wonder is this patient got ILD and you do a good quality CT scan with prone images and there's no ILD there, what's the role of also spending money on a PFT to screen for ILD? I personally don't see it, I think you're much more likely to get false positive results where their vital capacity is low because they're overweight or because of their ethnicity and their diffusion capacity is low because of anemia or some other pulmonary hypertension. So personally, I don't find that PFT is a great screening test.

It's an absolutely essential test once you've identified ILD because it characterizes the ILD. But personally, I don't use PFTs as part of my screening, or at least I wouldn't if I was a rheumatologist.

Okay, let's get into some of the other questions here. Family history. Do you ask about family history in people who may be at risk for ILD and how does that play in? Of course, everyone in our audience said, yeah, you should do a family history because that's what you were taught in medical school. Forty two percent saying it's part of the routine thing that you're supposed to do.

And forty one percent says that maybe if you find a family history, it can portend a worse prognosis and maybe a genetic link and telomere issues. Fourteen percent said no, because it's really not gonna change my management. Who thinks the family history is really poor? And forget the fact that it's free, cheap and easy, but is it really important and predictive?

So I can jump in and say that I think it is important and I think it is predictive. And we're not talking about a family history of SARD, we're talking about does this patient have a family history of ILD? And there was a really interesting New England Journal paper, now I guess it's probably about eight years old, maybe longer, but they looked at this MUC5B gene mutation and we know that patients with IPF are more likely to have the MUC5B mutation. At the same time, what they found is that patients with RA who had the MUC5B mutation were more likely to get ILD and their ILD was more likely to be in a UIP pattern. So we know that MUC5B is a risk factor for both IPF and RA, it's not captured in the guidelines, but in my mind, if you've got a patient who's got RA but their father had IPF, that's someone who is going to be at quite substantially increased risk of developing ILD and a UIP pattern and you wanna find that early in their disease course.

So if there is a family history of lung disease, and I'm sure it's just like arthritis, I don't know what kind of lung disease, but my father and my uncle had that. What should you be doing about that? Should you be ordering MUC5B? Should you be doing telomere testing? What's the next step?

Brian, you have a suggestion?

Well, I was going to say that Shane's much better at taking a family history of lung disease than I am because Jack, my situation is much more like yours. You ask the patient, Anybody in your family have interstitial lung disease? And they kind of look at you like, What do you mean? Well, anybody in family have pulmonary fibrosis?

They

still give you a look. They're not quite sure. You say, Anybody in your family have lung disease? And they're like, Yes, I've heard of the lungs, and they had a problem there. And so I have not found it super useful for my screening.

Okay, it's funny because I'm the exact same way with the joints. Has anyone's joints hurt in your family? And you wouldn't believe it, like almost everyone has a family history of joint pains.

We have that same problem too, Shane.

Will say the pulmonologists take a wonderful family history and exposure history also for ILD.

Is there a risk calculator for ILD risk out there?

Not that I'm aware of. I think that this is a relatively emerging area, like really before ACR and EULAR guidelines, the concept of mass screening in SARD was not really something we even talked about so much. So I think we're, I suspect that that's gonna come, someone's gonna create this, a calculator that can give you a sense for each disease, but not currently. I think we need a lot more epidemiologic data before we can make those papers come out that give us meaningful data.

There are a few risk scores that have been proposed specifically in rheumatoid arthritis for identifying RA ILD A handful of those they're all fairly basic in terms of clinical factors. Things like looking at age or age of diagnosis, whether they're seropositive, whether their disease activity is moderate or high, whether they have smoking history, and then they all have kind of a little difference in terms of their weighting, how much importance they play on those, and they all have seemed to do a pretty modest job. None of them are perfect. There have also been some studies that have taken a look at genetic risk alleles and added those on top of clinical risk factors to come up with combined genetic and clinical risk scores that can help us risk stratify ILD. We do see that adding genetic data does give us a little increase in performance and discriminating those with and without, but again nothing that is ready yet to be implemented widely clinically.

I want to ask a question that I got from Tony Russell in Edmonton about ANA positive referrals in ILD patients. I always considered those to be just like an ANA consult. And yeah, got autoantibodies because they have lung inflammation and alveolar macrophages and IL-ten and whatnot. And it doesn't really mean anything unless you can find evidence of a SARD. But it's not quite that simple.

Those patients are called IPAF now. Who wants to take a stab at what do I do about an ILD patient with an ANA? Should I take it seriously as a consult? Elad, you want to try that? And then maybe then Shane?

Yeah, I mean, so, know, ILD plus an ANA doesn't automatically give someone I path, it needs to be a respectable titer of the ANA for it to count. But I do think that or a nucleolar pattern. But yeah, I do think that those consults should be taken seriously. I think it is, you know, reasonable to do, you know, a full evaluation of whether that patient has any other features going for a SARD. Because ILD can be the first, you know, clinical manifestation of a SARD.

Not as common, obviously, as arthritis, but it can happen. So doing an additional workup as you see fit once you see the patient is warranted.

So for our audience, IPAP is interstitial pneumonia with autoimmune features. It is to ILD what UCTD is to future development of scleroderma or lupus or RA. It's potentially a disease in transition. It's not just having ILD with an ANA, as Doctor. Bernstein says, you have to have other domains involved.

But identifying it as IPAF does put you in a whole new category because the outcomes on IPAF are scary. Shane, how do you handle this or what's your advice to rheumatologists?

Yeah, I think the IPAF story is sort of an interesting one that is still an evolution because I'm not sure, right now we have this giant bucket that we call IPAF but we don't diagnose people with IPAF. In our clinic, we'll sort of say you have unclassified ILD that meets criteria for IPAF because it's not really a diagnosis, it's meant to be kind of a placeholder, something that describes someone who kind of smells a bit like CTD but you're not really sure. And I'll say that, we are starting to see when we follow these patients over time, they don't all take the same course, they're not really, it's not the same as someone who's got a little bit of arthralgia but has a high titer rheumatoid factor and a high titer anti CCP where, think the vast majority of those people are gonna go on to develop RA. Someone who's got an ANA of one in six forty and has a little bit of achiness in their hands, a lot of those people are never gonna develop a CTD or an SARD. So for us, one of the big things that really matters is what's the radiographic pattern, right?

If you have a IPAF patient who has an NSIP pattern, an LIP pattern or an OP pattern, the vast majority of those people, we probably will treat like they have some sort of autoimmune flavor but if you've got just a UIP pattern and a positive ANA, even if you get some arthralgia in the mornings, we're still probably gonna treat that like IPF and we wanna make sure we don't remove the opportunity for those people to get on anti fibrotic therapy early by calling it, ILD that's from a SARD and then giving them hydroxychloroquine that isn't really treating the lung disease. So we gotta think about them as different buckets.

So this discussion reminds me of something I heard in an ACP meeting when I was a resident, how long ago was that? From Robert Bennett, the guy who described MCTD. And from the podium, he said MCTD, it's an autoantibody in search of a clinical syndrome, high titer RNP antibodies in search of a clinical syndrome. And that's kind of what we're talking about here. We're gonna get to biomarkers coming up soon, Evan, so hold tight.

Can I just add one thing about the IPAF story? We did find in our cohort that people with IPAF, I mean, is not shocking to anyone, But when comparing people with IPAF to other forms of unclassifiable ILD, those with unclassifiable ILD and IPAF had a greater risk of actually progressing to a definite diagnosis of SARD compared to those without Again, not shocking, but another reason why these positive ANAs in the setting of ILD should be taken seriously and evaluated.

All right, let's go through the next three questions kind of quick. What's the greatest risk factor for future ILD? Our audience was split on inflammatory SARD activity and tobacco use, less interested in family history and radiation. Which of these is, is there a right answer here, Shane? Greatest risk across the board.

Yeah. I'm I'm not sure. I don't know the actual relative risks of these. And I think one of the challenges is just, you know, we we don't have really great data where we can screen everybody and look for these risk factors. I I know these are both the two biggest risk factors along with high titer autoantibodies, particularly rheumatoid factor and anti CCP.

So I'm not sure if one of them is bigger than the other. I'll defer to my colleagues if they're aware of any data on that.

Okay. The second question, which is not associated, you're not supposed to ask questions like this, but I did, which is not associated with an increased risk of UIP? Is it shared epitope is what everyone chose, 60 two thirds, with about a little more than a third or forty percent choosing smoking males or seropositivity. Brian, what's the right answer here?

Well, think it depends on the context, right? So it depends on your population. If we say the base population is a group of people with RA, then your genetics, you know your genetic background for RA really doesn't influence your risk of developing ILD. So most studies have not shown shared epitope to tell us invaluable information about the risk of developing ILD and RA. Now, if you took that away, that population said this was all comers with SARD, then I would say, yeah, sure shared epitopes associated with UIP because shared epitopes associated with RA and UIP is the most common pattern in RA.

So it depends on the population you're testing.

Okay. One more question. Which antibody is associated with the greater risk of developing scleroderma or systemic sclerosis associated ILD? Doctor. Bernstein, the audience thought it was SCL seventy two thirds of the time and RNA polymerase three in twenty five, twenty three percent, less so for fibrillin and centromere.

Did they get it right?

Yep, absolutely. SEL70 is associated with an increased risk of ILD. Arne polymerase III, that one is associated with probably with a lower risk of developing ILD and at least less likely to have progressive ILD, although they can still progress. And RNA pol III, we typically think of in people, scleroderma patients who develop renal crisis, GAVE, rapidly progressive skin thickening and malignancy.

Do any of these autoantibodies and I'll throw into the mix there, CCP and RF and ANA, do any of autoantibodies behave as biomarkers for disease other than risk factors for disease? I assume they're just risk factors.

And Jack, I honestly don't think that RF and CCP are all that helpful as risk factor for RA ILD. I mean, the math just doesn't add up very well. If seventy percent of RA patients have RF or CCP, yet only ten to fifteen percent clinically have ILD, that's a pretty big difference in terms of the numbers.

Yeah. And I put those three in there because I learned at a recent ACR UR about the three S's being an increased risk of UIP and R. That's a Jeff Curtis, I think, abstract being smoking, sex, being male, and seropositive. If you had those three, I think it gives you a seven or seventeen fold higher risk of developing UIP if you already have RA. And that's why I throw those together.

It's something that I can remember clinically. So again, going on with screening, oh, I think I missed the Oh, here we go. So yeah, we're back to screening. So a patient with new active RA or scleroderma, what screening should be done? Half the audience chose a high res CT.

The other minority, about eighteen percent each said, only if you have risk factors, or I'll do PFTs and DLCO, or only if there's a good history. So does anybody want to reference the guidelines and what the right answer here is? Is it different between scleroderma and RA and you're considering screening for ILD?

I mean, would say no. Yes and no. So I mean, really, if you're screening for ILD, the gold standard, again, is an HRCT. So if you're suspicious enough, let's Brian, I'll defer to you. But I will say if I'm suspicious enough that an RA patient might have ILD, I'm going to get an HRCT.

I'm going get PFTs too. I know Shane might not, but I would. So I think HRCT for sure for both if you're screening. And I would do PFTs.

So and I think Shane agrees with that. But what's the deal? And what's the importance of the risk factors? We're going to see in a few slides, the UR ERS guidelines say that everybody gets screened, if you've got RA and Sjogren's, you don't get screened unless you have risk factors. Why is that in there?

Does anybody know the answer to that, Shane?

I wasn't on the guideline committee, so I can't say what their thinking was, but I think it comes back to what Alana was really saying that we know in scleroderma, the rates of ILD are very high. So we're really thinking that the vast majority of those people should be screened. Whereas in RA, it's not entirely clear, particularly when we're talking about early in the disease, like Brian has been mentioning. So I think it's more about saying that, some diseases we should have sort of tick boxes, right? You're gonna come to clinic and we're gonna make sure we do all the things.

Each visit we're gonna check, is it time for your echo? Is it time for a COVID vaccine? Are there all these things that you're supposed to be doing regularly each year? Whereas in other diseases, it's really gonna be more nuanced and the guidelines are really designed to give you the clinician, opportunity to use your spidey senses, right? These are not meant to be recipe cookbooks, They're meant to be guidelines so that you can kind of filter it all down.

And in the end, you're in the room and your Spidey says tingles and you're like, ah, this one needs a CT.

Okay, let's move on to the next question. ILD and IPF patients should be screened for a SAAR? This sounds like a question in the pulmonary clinic quite commonly. But rheumatologists are answering it. Sixty percent said, yeah, screen them by sending them to a rheumatologist.

I would say rather than send them, give me a call, and we could figure it out over the phone about what should be done next or whether I should be seeing them. Twenty five percent say if they meet SARD criteria, lupus or RA, eleven percent said with serologies only. What really happens in pulmonary clinic, Doctor. Shapira?

Yeah, so those who voted by rheumatology referral, be careful what you wish for, unless you're out of work and you need work. IPF is an uncommon disease, but it's getting to be more common. And if I send you all my IPF patients, you won't have time to see the actual people who've got joint disease that need you to see them. So I actually disagree that we should be sending everybody to a rheumatologist, but I do think that it's part of the pulmonologist assessment to be carefully asking. I think every single patient with IPF should be asked if they have Raynaud's phenomenon, they should be asked if they get joint stiffness in the mornings, they should be asked about other classic features and they should be examined for telangiectasias and do a quick skin exam and maybe just grab their hands.

Like to be honest, when my residents are in seeing patients, they all come back and they tell me that they have crackles and I'm like, of course they have crackles, we're in the ILD clinic. What I really care about is what do their hands look like? It's the only physical exam that matters in a pulmonary clinic if you've got ILD. So I think we should be screening our patients on history, physical exam. And I do think we should be doing screening serologies.

And I get it, I talked to a lot of rheumatologists who say like, don't go fishing, don't find me something I don't know what to do with, but the reality is that most pulmonologists are not able to take a really good history for autoimmune disease. And so serology is not meant to be a diagnosis. That's just meant to flag the people that those are the ones that you're gonna send to a rheumatologist because every once in a while they'll do some nail fold capillaroscopy and come back and be like, ah, how did you miss

Right. And then lastly, wanted to throw in a question about lupus. I think lupus has been kind of forgotten this month in ILD. Should lupus patients be screened for ILD? Brian or Elena, do you want to take a stab at that?

I think Jack, it's a tough question because the prevalence of ILD and lupus is pretty low. I think the numbers are five percent or less, but that doesn't mean there's not pulmonary pathology in people with lupus. I think there's less interest in whether we need to screen specifically for ILD, but certainly considering the other pulmonary manifestations, the pleural fluid that can happen, shrinking lung syndrome, other things like that. We have a few of those cases that we have in our autoimmune lung clinic, we shouldn't forget about the lungs and lupus, but I think we just approach it a little bit differently because the epidemiology of it is different.

And I will add, you know, there's a reason that lupus was not included in the ACR chest, you know, start ILD guidelines. Because people are with lupus have a much lower risk of developing ILD.

Right, right, right. Agree. Tony Russell says, you need to do more than just ask, do you have joint pain? Because then you're going to get lots of fibromyalgia and lots of other things. I think that we should co develop the seven point questionnaire on what do you look for in the hands of an ILD IPF patient, IPF patient that would clarify whether you need referral or further investigation.

And these are usually simple things like skin tightness, rainouts, periungle changes, mechanics hands, boggy synovium contractors. There's like 10 things or seven things that you could ask for that would go a long way, at least in my opinion. So, all right, let's move on to, and this is the screening as set forth by Anna Maria Hopin Vold who gave this presentation at EULAR in Barcelona, and just recently published this. These are the ERS UR practice guidelines for CTD related lung disease, aka SARD related lung disease. And they recommend screening in all patients with scleroderma MCT and myositis, and only screen RA and Sjogren's who have risk factors, risk factors being age, males, smoking, seropositivity, markers of inflammation or high disease activity like by DAS score.

But then over here on the right, this is from her slide that says you screen MCTD and scleroderma, no questions asked. And that's systemic sclerosis, preferably the diffuse kind. But they are asking about risk factors. Does anybody want to tackle the guidelines and whether they agree with them?

So I'll take a stab at it. So I agree with systemic sclerosis and MCTD. I think for the idiopathic inflammatory myopathies, it is a little more nuanced and perhaps that's why they've split it up. But I think realistically, the vast majority of patients with one of the types of myositis are going to get a chest CT, right? Even if it's for just as part of their cancer workup.

Because we can go to that question, should all patients with myositis have an evaluation for malignancy? And the vast majority do and get a CT chest abdomen and pelvis. So I think, and given that at academic centers anyway, the vast majority of chest CTs now are high resolution, yeah, we're getting HRCTs in the vast majority of patients with any type of inflammatory myositis. So that aside, I do think it's reasonable to get an HRCT in all patients with myositis. Now, there reasons why you might not, insurance coverage, things like that, cost, sure.

But I think it all comes back to shared decision making. And that was something that the ACR CHEST guidelines, you know, really emphasized. And so risk factors are helpful in that conversation too. Certainly someone with more risk factors, you know, is more likely to need to be screened than someone with no risk factors. But it's still a joint decision to be discussed between the rheumatologist or pulmonologist and the patient.

So the other thing in the guidelines was that bronchoalveolar lavage is not routinely recommended unless there's a suspicion for infection. Shaney, would you agree with that, I assume?

Absolutely, absolutely. And

then they did get into monitoring. By here we're talking, what are the tools that you use for monitoring? That could include not just high res CTs, but PFT six minute walk time, patient reported outcome measures. And so let's ask some questions about monitoring. How frequently should a SARD patient have their ILD status monitored?

I'd like to know each of your answers on this and then what you recommend. Do you recommend repeat high res CTs every four, six or twelve months? Alana, you want start on that?

Sure. I think it's hard to group all SARD patients together for this question. So let focus on scleroderma for a minute. So in my scleroderma patients with ILD who are at high risk for progression, so those are patients who are SCL seventy positive, or have the diffuse cutaneous subtype, I'm actually getting PFTs for the first few years every three months. So that's not even an option here.

And once they're stable for maybe a good three years, then I'll space out their PFTs to every six months. I'm certainly not getting an HRCT every four or six months. It is reasonable to get a repeat chest CT at one year. I don't do that routinely, but there are some people who do. And one could certainly make an argument to do that.

And I think also in, let's say, patients with an inflammatory myositis, let's say, antisynthetase syndrome or MDA-five associated ILD, I think it's reasonable also to get PFTs for monitoring every three months for the first few years.

Okay. Brian, is different in RA?

Yeah, I think it's a little different in RA. You have much fewer people with RA ILD who have a rapidly progressive phenotype. Know, the vast majority of RA patients have this slowly progressive phenotype and so the need to do Q3 months PFTs for a few years is probably more than needed. I'd say most of the time in RAILD you're repeating them at six months, and if over the first couple times you do that you don't see evidence of rapid progression or you see kind of more stable disease course you might even stretch it out every twelve months. The big key with monitoring is that you tailor it to the patient and you tailor it to what you're doing.

If you're changing a therapy because you think they have progressive disease and you want to understand whether or not they're going to have some response to that or not, you're going to repeat the PFT sooner than later. Our approach is we generally use PFTs as the primary thing that we follow over time, and then we use that CT in those situations where we really need additional information. Whether it's the PFT is not conclusive or there's discrepancy between symptoms and PFT findings and you need that tiebreaker of the CT or if you think the phenotype on the CT may change to where the direction that you're pushing immunosuppression anti fibrotic is going to differ based on what you're seeing, that's triggering us to get the CT.

Yeah, I want to underscore what we've heard. That is that you need to identify the rapid progressors And you can identify them with Q3, Q6 month PFTs and you're looking at a change in FVC because if they are rapid progressors, that's a whole new can of worms. Those people die and go to lung transplantation at a much, much higher rate than those that don't meet that categorization. So Shane, what qualifies as a rapid progressor? What amount of change in FVC would you be looking for?

Yeah, that's again a hard question to answer and I'll tell you why in just a moment, but I'll tell you that the textbooks would tell us that an FEC decline of about 10% over a time window that's probably about twelve months is significant. So if you're seeing a 10% decline in your three month PFT, that's scary, right? That's someone who's progressed pretty rapidly. So I think using a 10% drop in FEC is a useful marker, but the reality is that's not really how we identify the rapid progressors. The rapid progressors almost always are gonna end up presenting to hospital with their illness or they'll see me, I'll see a guy who was seen by a local pulmonologist, put they him on prednisone low dose and mycophenolate and they come to me and then I find their MDA five positive and I'm like, all right, they're fine, I'll see them back in three months.

Then they end up in EMERGE six weeks later, right? Like these people end up in EMERGE hospitalized on high amounts of oxygen in a short amount of time. So really the rapid progressors that you're really scared about are the ones that are either diagnosed in hospital or you're seeing early in their disease in hospital. And that's when you just kind of freak out and you start throwing everything at them.

Yeah, that's really helpful. What do you use in monitoring ILD? We've already discussed this. Think everyone says all of the above, but I think the right answer here is PFTs more frequent than chest CTs. What's the role?

I mean, I'm gonna ask the rheumatologists, do any of you do six minute walk time? Do you have the time for that? Can you bill for that?

No, I mean, we can order it and they're done in like the PFT lab. So I don't personally bill for it. It's not something that I do routinely. It's certainly something that our patients who have pulmonary hypertension have monitored on a regular basis. And that's often ordered by their pulmonary hypertension specialist.

I think for ILD, I think there is a role for like in the ACR chest ILD guidelines, we separated out six minute walk test distance from ambulatory, desaturation monitoring. And I think ambulatory, you know, oxygen saturation monitoring does have a role, in, you know, monitoring for ILD progression. But the six minute walk test distance has less of a role, especially because it could be confounded, you know, by cardiac disease, by musculoskeletal involvement of their, you know, systemic autoimmune rheumatic diseases.

So Shane, pardon my far side kind of humor. I used to think that when I walked by pain clinic that I should hear people screaming. So to walk by the pulmonary clinic and see a hoard of people usually with oxygen tanks doing a six minute walk seems like a far side kind of cartoon. How does this really work in pulmonary clinic?

Yeah, we do them as a group. It's like the Boston Marathon. We just put them all on one end and we see what happens, you know? No, I mean, I'll be honest. You know, it's always funny.

You use the tools that are at your your hand, right? And so like my office, literally, I have to walk through the aisle where they do the six minute walk test to get to where I'm gonna see them in the clinic room. And in our clinic, doing a six minute walk test is part of each assessment, but I appreciate that not everyone does that. It's expensive, it's very time consuming, it takes about fifteen minutes of a tech time, and so it really doesn't, it's cost negative, but we do it and we find it really helpful and I'm not disagreeing with anything that Brian or Elena has said, but what I find really helpful is that Elena mentioned that you can have these other factors that affect your walk distance and that's why the distance can be difficult to monitor. But what happens in a six minute walk is you basically, you have this long hallway, they go up and down in a very organized way.

And so the idea is you sort of standardized a whole bunch of parts, The ambulatory desaturation, the problem is you don't know, did you walk them a little faster that time? Did you walk them a little slower? And so we find that having those two elements, the distance walked and the oxygen saturation niter is helpful because if they walked a shorter distance, but their sats were higher, they're not limited by their ILD and it's probably their joint disease or deconditioning, but if they walk a shorter distance and their sats are actually lower than they were eight months ago, that really suggests that there is progression of their underlying ILD there. So it has value, but I get it, it's expensive and not readily accessible.

Let's ask a question about biomarkers. Is there a biomarker that confers risk of ILD and severity of ILD? Is it forty three percent said it's rheumatoid factor or CCP, thirty five percent, a third said row 52, sixteen percent said KL6, and a few people are familiar with WB telomere length. I'd like each of you to explain each one of those answers and their role. Let's start with Brian.

Yeah, so a lot of biomarkers are associated with ILD in the literature. And I think to me the big thing is there's a difference between an association versus something that is either causal or between something that is also clinically useful. And I think where we're stuck right now is a lot of information on association, not as much information on the causal or clinical utility perspective.

Okay, so there are associations for each of these. KL6, rheumatologists are not familiar with Doctor. Shapiro, can you explain that to us?

Yeah, so KL6 is a very promising biomarker in the sense that there's paper after paper that shows that it predicts progression. The problem is, as far as I understand, it is a really challenging test to perform. And when I first read about KL6 that I talked to one of my bench guys who works in the lab and I said, can you start doing this on my patients? And he says, God, no, don't make me do that. It's laborious, it's difficult to standardize.

And although I totally believe that it's a useful biomarker, I'm not convinced it's at least in the near term, it's not coming to gross clinical practice. So, I mean, maybe, I don't know, I work in Canada, so it could be different, but you guys tell me, are you using KL6 in your clinical world?

So it's not commercially available in The States yet. It's available in Japan. That's where, you know,

the test

was developed. But there have been studies that have looked at KL6 in The US, and it does not perform as well, nearly as well. It doesn't have the same predictive ability when it's, at least in more recent years, when it's been, assayed here, as when it's assayed in Japan. So I do think there's labs I think are starting to learn here. I'm hoping that at some point we can get this at sort of point of care.

Because it especially in SSCILD, it is a really good predictor of patients who will have progressive SSC ILD. It's really good. But when it's done in Japan. Time will tell.

Do any of you order row fifty two or telomere abnormalities?

So telomeres, I actually think are out of all of these, the one that I think is the one we're gonna be using in the relatively near future more than the others. I do think that short telomeres are helpful. Not only are they prognostic, but they're sort of an emerging sense that those are the patients who might do a little bit worse with immunosuppressive therapy, whether that's because it worse than cytopenias or what it is, who knows? And these are all associations, as Brian said, it's really tough to tease out an association from causation. But I mean, we know that our short telomere patients do worse and we know that they might do worse with immunosuppression.

So one wonders if down the line, will we be sending telomere lengths on our patients with UIP, RA UIP and saying, okay, well, that's one that I'm gonna treat with anti fibrotic first versus someone who I'm gonna treat with immunomodulatory therapy. I suspect that might be coming and we certainly do send people for telomere testing if they have other features suggestive of a short telomere system syndrome. So like premature graying in the hair, cytopenias, history of liver disease or family history of any of those things, because we wanna be looking for extra pulmonary manifestations of their short telomere syndrome as well.

So we do a lot of telomere testing at Columbia because we are a pulmonary ILD research group, that this is one of the things that they research. So they do a lot of that testing here. And I will say, you know, from what I understand, the data for telomere testing in patients with SARD ILD is less robust than say, telomere testing in people with IPF. And I think, you know, even when we have, let's say results of short telomeres in patients with SARD ILD, it's really hard to not offer those patients immunosuppression, especially when we're talking about, let's say, someone with SSCI LD or myositis associated ILD. I think we should certainly be aware of the potential complications when these patients are immunosuppressed if they have short telomeres.

But I'm not sure that we'll get to a point necessarily at anytime soon, where we're gonna say, all right, we're not gonna immunosuppress these patients, especially because of their extrapulmonary manifestations.

I agree with that comment completely. And I think that RA patient who has a UIP pattern who has quiescent joints is very different than scleroderma patient where we've got really robust data for immunosuppressive therapy to help with the pulmonary and extrapulmonary disease.

So I want to end with these two questions and we only have three or four minutes left. Does monitoring, as we've discussed so far, do you do it because does change therapy or because it can change outcomes? Or is it just for prognostic information? And then second question is, in patients that were managing with ILD, when if ever do we rethink the diagnosis? Other than in IPAP patients who are on their way to maybe some diagnosis, where that's mainly a research construct?

Who wants to take a stab at these?

Can I tackle the first one?

Yes.

We'll see if others agree or disagree. But I do think monitoring changes therapy and outcomes. And I think we monitor patients precisely because we want to know if the therapies that they're on are effective. If they're leading to stabilization of their disease, obviously, we hope for improvement, and that's possible in myositis, but less likely in the other SARD ILDs. But if someone is progressing on their current therapy, we need to change it up.

We can't stay with the status quo. And I'll also say that if someone continues to progress despite first line, second line, even third line therapy, we need to be thinking about referral for lung transplant evaluation. The sooner that we refer the better, because if a patient needs to be listed, we want to make sure all the appropriate testing is done so that patient can be listed. And, you know, many of these patients with who develop end stage lung disease in the setting of their autoimmune disease can be successfully taken through lung transplant. So I think, you know, if we're not monitoring these patients, we would have no idea that their disease is progressing, until it's too late.

Okay, Brian.

Absolutely monitoring will change what we do. I don't think we have really any idea if it's actually making anything better or worse. I don't think we don't have any data really showing a hard outcome improvement and even if you push us on a lot of the therapies that we choose to use, we don't have a lot of hard data showing that the therapies we use lead to market improvements. So, I hope that we're improving outcomes, but I think we're definitely just that the more you monitor, the more you change things.

So, before we get to our final word from our pulmonologist, I want to quote our pulmonologist from last week, Doctor. Toby Maher from USC said something really interesting as he was talking about these two pivotal studies we talked about, Fibronir and RECITAL. And he said when he started his career, ILD IPF bleak, horrible, ugly outcomes, no choices, no therapy. That's why he got into the sort of underpowered recital study of cyclophosphamide versus rituximab. But here we are now twenty years later, and we have therapies, and we have better research and biomarkers.

So as much as we know that there's a lot of unknowns here, that a lot has happened in a short period of time, and it's quite encouraging. So Shane, you want to close us out with some comments here?

Yeah, actually that's exactly what I was gonna say. I think there is still a lot of work to do. And as a result, there can be a bit of nihilism about why are we even bothering? But I promise you, I've got like, I got a job worth doing. I think that we are following these patients.

I think that we are learning more and more every year. And I do think that, particularly as more data comes in, Recital and Ever ILD and Inbuild and the FiberNeer trials, was a time where the best we could do is say, well, in an open label trial, it seemed that people stabilized. That was where we were for a long time, but there is actual data coming out in SART ILD that is prospective randomized and positive results. People don't realize things like the INBUILD trial of Nintendentive, that was actually the biggest prospective RA ILD trial that had ever been done. It had like, I think one hundred and sixty RA ILD patients and it was a positive study and different SARD ILDs didn't differ in their outcome.

So I think we have treatments that are effective, I totally agree, we need better data, we need better treatments, but there's no doubt that monitoring and finding diseases, whether they're inflammatory, fibrotic or both, giving people care beyond just pharmacotherapy, oxygen and other things and giving access to transplant, these things have a major impact on outcomes for our patients.

All right, this concludes our webinar. I wanna thank our panelists, Drs. Bernstein, Englund and Shapira for their SAGE advice, insights and perspectives. This was really, really helpful. I'll refer the audience to our four total webinars available as videos and also as podcasts.

Thank Boehringer Ingelheim for their sponsorship of this month on