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Dr. Amy: All right, so welcome everyone. So we are going to be doing our series on what you missed at ATS 2025. In particular, we're gonna be focusing on the clinical year in review, which is a really exciting there's a number of topics that were discussed this year and we're so excited to kind of summarize them and think about the broader implications.
So I'm here with Dr. Sara Auld. So she is an associate professor of medicine from Emory and has extensive experience in research related to tuberculosis and global health. And she was one of the speakers last year in the clinical year in [00:01:00] review, and this year she got to help organize the clinical year in review.
So we're gonna be talking about some of the topics and kind of maybe go a little bit into how you got started at ATS, how you've kind of had the journey. To become the organizer of the clinical year in review. Yeah, thanks so much for inviting me. Great to, so we're so excited you're here. I noticed I have a lot of interest in like the asthma COPD related topics.
There was for asthma, again, there was a lot of really exciting to things coming out about biologics. And I think the one was about switching biologics, which I know. That's something that as clinicians we're always a little bit worried about if how they'll do, if we try to switch from one to another or how their outcomes will be.
That I thought that was a really exciting one. And then also the biologics for exacerbations. I thought that was really exciting. And it also, that that study had asthma and COPD [00:02:00] patients,
Sara: right? Yeah. So Lauren Eggert from Stanford was our speaker for asthma, and I think she did a great job as the first speaker for the clinical year interviews series for this year.
And these two studies that you highlight, both of them had Benralizumab which is one of our anti IL five agents. And. For the first one where you talked about switching, it was really, I think, reassuring for her to share that both patients who were biologic naive and patients who were biologic experience.
So again, those patients who would've been switching had benefit after the switch. It was less in those who'd been on previous biologics, but they still did have some benefit. So I think it certainly. It gives people permission, if not an obligation to think about switching some of your patients to see whether they might have benefit mm-hmm.
With one agent versus another. And then, like you said, the asthma COPD study. As someone who doesn't specialize in this space but takes care of inpatients and works in the [00:03:00] ICU setting and has people coming in with asthma and COPD exacerbations, I thought this was a really great study because as Lauren pointed out for so long.
Our treatment and management of exacerbations is really very rote and formulaic and hasn't changed in decades. You know, we give people steroids, we give them bronchodilators. We sort of let them settle out, and so with this study. They took people who had high eosinophils above 300 at the time of their presentation for an acute exacerbation and found that those who were given the benralizumab a biologic at the time of exacerbation they did use higher doses about three times.
What would I. Be used for sort of a maintenance dose, but this one time dose they had better responses after the exacerbations and so fewer treatment failures improvements in symptoms. And so looking ahead, I think it's exciting to think that we might have another sort of tool in our toolkit to [00:04:00] use against those acute exacerbations.
Dr. Amy: Oh yeah, absolutely. And the fact, so they also had COPD patients in that study. And also that was, it was such an exciting study that I, I remember it was presented at the asthma year in review and also the COPD. Yes. Year in review. Everybody wanted a piece of it. Exactly. But I really do, I think that the outpatient management for COPD can be very nuanced.
But when we're inpatient, I always felt like we're, there's, I feel like there's, there's more we could be doing and maybe trying to get at that anti-inflammatory pathway in a way that is not have all the side effects and complications of steroids. So, I know is, you know, I think there's so much exciting, um research coming out in that arena for asthma and COPD.
So, and then there's a biologic I guess, that we can use twice a year. I think that was the
Sara: other finding for asthma. Yeah, it's kind of mind blowing thinking of how far biologics have come over the last decade. And so it's. DEPA. Mm-hmm. De yeah. Which Lauren? [00:05:00] Thankfully shortened for all of us. And so this is an ultra long-acting anti IL five agent.
And so thinking about having people who can come in twice a year, and they, as with all the other studies of biologics and asthma had. Significantly lower exacerbation rates and all those other things you would want, but to only come in twice a year. You can imagine what a, um how much more bulk node would be from a patient perspective.
Oh yeah,
Dr. Amy: absolutely. I think that was when we had our previous podcast with Dr. Monica Kraft. She was always talking about how the, you know, the burden can be a lot of times and what patients can do, like how, you know, that is not impacting so much their life. So having a biologic twice a year, I mean, it's, it's mind blowing to me.
But
non: did you miss the ATS 2025 International Conference in San Francisco? We've got you covered with the ATS conference Highlights package. You can access inspiring presentations as well as valuable clinical insights from pulmonary critical care and sleep [00:06:00] sessions. Members get a discount, so be. Come an ATS member or renew your membership to take advantage of these savings, go to conference.thoracic.org today.
Dr. Amy: So yeah, I think really exciting year for asthma and again, had COPD in there as well. So kind of moving on, so there was the pulmonary function testing section also had I think really interesting studies coming out. And I think the, I was trying to kind of put it together, so it seems like we're trying to move away.
From our standard way that we think of pulmonary function and kind of using other other ways to diagnose, um lung disease. Like they, there was one there, real emphasis on the race. Neutral P fts, oximetry, FEV one Q. So a lot kind of moving beyond what we think about in our standard way that we interpret PTs.
Sara: Yeah, was, I think this is an area where absolutely the [00:07:00] field is shifting and I think for many of us who've been practicing for longer, it's gonna be hard to let go of the things we learned in training. Right. And you know, the standards that are built into much of the software we use, but we were really lucky for the PFT topic to have Sanja Vic, who's from Dhha University and has led a lot of this work, was first author on some of these really seminal publications that have come out.
And as you mentioned, I think the biggest shift is sort of across the board moving towards. Using Z scores instead of percent predicted values. And then also the race neutral. And I really appreciated the way she described the Z-score as sort of a distribution of normal. Mm-hmm. As opposed to the sort of firm cutoffs that we're used to using, with percent predicted.
And so it just helps you get a better sense of where your patient might be within a spectrum. Of someone who compares to their range. Mm-hmm. Rather than I think a lot of people hear Z-score and they kind of shut down 'cause they think it's about some fancy statistics and they don't wanna look like they don't understand it.
[00:08:00] Mm-hmm. And so I think in as many fora as we can, trying to sort of push this message out that. Really as a field we wanna move towards Z scores where it's been shown to be more predictive of the clinical outcomes that we care about. And so that's really the impetus for changing this. And then also the race neutral, where we found that, you know, race is sort of a biologic construct, doesn't exist in the way that we thought it did.
Mm-hmm. And that moving towards these race neutral equations, again, are also gonna be more clinically relevant for our patients and sort of more accurate.
Dr. Amy: Mm-hmm. Yeah, I remember. So Dr. McCormick and Dr. Bre, we had a, a podcast on that a couple months back, so it was great to see that paper from Dr.
McCormick's group validating what they had talked about in their workshop, the ATS workshop on race neutral PFT. So I was really excited to see that included. And I do so Z-score. And if if, if I think of it correctly, it's what we [00:09:00] use for when we have a bone scan, right? Like a DEXA scan. So I think we're all, we've used z-score before, so I think it's something that, you know, we can may just need to get a little bit more used to, but it's something I think that we've already been using in clinical practice, so,
Sara: yeah.
Yeah. And then you'd asked about some of these other measures that Sanja also brought up and sort of reviewed, and I think these are. Not gonna probably take the high level billing that the Z-score have, but I think are really interesting. The FEV one Q, which is sort of a quotient, and what that does is it compares the patient's PTs instead of against a normal like you see with the Z-score, but against the sort of minimum.
Volume that one would have to be able to survive. And so it's instead of how close are you to normal, it's how close are you or how far are you from survivable? Mm-hmm. Right. You know? How far are you from the sort of low threshold, the lowest threshold? Yeah. And [00:10:00] what I didn't realize with the FEV one Q that she pointed out is that that has actually been shown to be.
More predictive of mortality mm-hmm. In patients with COPD and sort of outperforms even Z-score. Mm-hmm. In this sense. So I think we'll start to see more and more of this and sort of more validations across other studies and other constructs.
Dr. Amy: Yeah. Yeah, I think, I mean, when I think of my COPD patients, like they seem, some of them kind of follow a trajectory where they seem to do okay and then they just really decompensate.
And I think that that makes a lot of sense with the survi having that lower limit and that survivable, lower limit FEV one Q. So so again, really, really exciting to kind of see that field grow and kind of looking at things a little a different way. And so sleep again, I think was also kind of a similar con concept, but moving beyond CPAP, I guess, for obstructive sleep apnea.
Thinking about other ways to treat obstructive sleep apnea or [00:11:00] have more tools in your toolkit. I think that was one of the things I noticed in the sleep. Topics presented,
Sara: right? Yeah. Yeah. Luciana Paulini, who's from the institute, Sao Brazil, reviewed the sleep topic really nicely. And I think, like you said, she talked about some of the data behind, um mandibular the mandibular advancement devices and.
The hypoglossal nerve stimulation. And really, I think framing particularly the mandibular devices as sort of an adjunct, potentially A-C-P-A-P, and that using this together with CCP a p will probably improve adherence. That even if someone's not perfectly adherent to one or the other, that there might be some synergy of combining them more.
Sort of the mm-hmm. Sum is greater than. The parts on their own. Mm-hmm. Yeah. Yeah.
Dr. Amy: I, and I noticed the hypoglossal nerve stimulation. So again, looking at that and seeing, seeing it validated in the literature and then also the GLP one, right? Yes. The GLP one agonists, which, yes,
Sara: [00:12:00] those are just everywhere, right?
Yeah. They feel like they're gonna put them in the water before you know it. But yeah, the I think it was great to see that even independent of changes in weight that those were, mm-hmm. Improving. The apnea hypopnea index and the parameters around oxygenation for these patients. And this was for people who had been on CPAP and also for those who were naive.
Mm-hmm. And so I think again, as we've seen for so much around the Ggl PB one agents broadening indications and realizing that there will be these probably pleotropic benefits mm-hmm. Beyond what we might expect mm-hmm. From sort of the weight loss, um aspects, effects alone. Yeah.
Dr. Amy: Yeah. Yeah. No, I think it's really fascinating.
All the. All the GLP one can affect so many organs of the body. And then we're kind of seeing all these studies coming out. So so I think the kind of moving to interstitial lung disease, I think it was a lot. My, my takeaway was a lot of endot typing, molecular endot typing and precision [00:13:00] medicine, I think.
So kind of trying to, phenotype, the ILD patients and kind of look at them with using molecular tools. I think that was one of my takeaways.
Sara: Yeah, absolutely. This topic was covered by Dei er, he's one of the clinical year interview co-chairs along with Arun Kon from Arun from Colorado Desi's from University of Chicago, and.
I think the, the first study really highlighted there around the molecular endot typing. They've really sort of recapitulated some elegant work that's been done in a RDS historically where they've defined the sub phenotypes of A RDS. And those were based on a statistical tool called latent class analysis that now they've brought into this ILD world, as you said.
And so instead of looking at some of the inflammatory biomarkers that have been associated with these A RDS subgroups, historically, they looked at. Markers more associated with fibrogenesis. Mm-hmm. And they were able to identify these sort of two distinct molecular [00:14:00] endotype groups within these larger cohorts with ILD.
Mm-hmm. And not only did the biomarkers segregate, but as has been seen with a RDS, it was associated with clinical outcomes. And so one of the groups had higher mortality, faster progression and whatnot.
Dr. Amy: Mm-hmm.
Sara: And, you know, I think we don't, we won't yet have the ability to sort of do this molecular genotyping at the bedside per se, or in the clinic.
But certainly this is gonna help us move the field towards subgroup driven medicine, if not personalized medicine. Mm-hmm. Quite yet.
Dr. Amy: Yeah. Kind of a similar concept with like testing for telomeres, right? Because they thought that it might the telomere group. Seemed to suggest, like it was the way to guide therapy.
Right. Immunosuppressive versus non. Right.
Sara: Yeah. And this was a study that Desi was actually involved in. Mm-hmm. Which is great to have him be able to talk about his own work during the clinical year in review. And so short telomeres have been associated with. Fibrotic lung disease historically. And what they found here, you know, they had a [00:15:00] cohort it was just over a hundred patients who had fibrotic ILD.
This is now a CLIA certified test. They were using, looking at the telomere length, and they found that almost half the patients who were clinically identified as having fibrotic ILD had short telomeres, which sort of confirms and emphasizes that this is linked so common to the disease. Yeah. Right, right.
And I think what was really exciting was that. Once they got those results back, it actually changed clinical care for around a third of patients. Mm-hmm. In terms of adjustments to their immunosuppression regimen. Mm-hmm. And that's because as I, as I myself learned apparently patients who have short telomeres actually do worse with higher immunosuppression regimens.
Mm-hmm. So you, you would be peeling back and potentially sort of tapping the brakes on immunosuppression for folks who have those short telomeres, whereas those who would have normal telomere length, you might feel, more at liberty. Yeah. To proceed with your suppression strategy. Yeah.
Dr. Amy: Yeah, yeah.
Yeah. That's really fascinating. So again, I think ILDA lot more to [00:16:00] show, oh, there was also the study like environmental exposures in interstitial lung disease also, so that was associated with increased methylation and linked to senescence. So again,
Sara: yeah. Yeah. No, I mean I, I, I love this. I think.
Epigenetics has just been blowing up. Mm-hmm. You know, all these sort of methylation changes that are happening to all of our genomes all the time. Right. And epigenetic age has been sort of a hot field lately. Mm-hmm. And this is one where they looked at this epigenetic age in the construct of fibrotic ILD again.
Mm-hmm. Mm-hmm. And they found that patients with fibrotic ILD had a much higher epigenetic age mm-hmm. Than match controls. And that those when looking at epigenetic age is sort of a more continuous variable that it was associated with earlier age of onset of disease faster declines in lung function and worse survival without transplant.
So I think I. Again, you can imagine looking ahead that there might be a time where we could measure the epigenetic age and that would help us with decisions on when to refer to transplant. Mm-hmm. [00:17:00] Or sort of whom to be more aggressive with on some of those measures.
Dr. Amy: Yeah. Yeah. There actually, there's a lot of interesting studies happening in the COP world as well, so there's like, I think that's, there's more to come just to think about the, how many of these diseases are associated with this, like premature kind of molecular aging, which I think is fascinating.
Sara: So, yeah, and I love the way also that it's. Tied to clinical outcomes. Mm-hmm. Because I think there's so much going on in the omic space and it can feel overwhelming in this sort of omics alphabet soup, but it's when you are bringing that back to patients and how it can potentially impact care. Yeah.
Yeah. It really underscores the importance of it. And I think emphasizes particularly in these days when it can feel like biomedical research and science are a bit under threat. It highlights the importance of this work that this can impact. Patient lives and decisions. Absolutely. And it's not just sort of discovery for discovery's sake.
Dr. Amy: Right. Right. I mean, so it's clinical year in review, right? Absolutely. So now we're moving, we realize that translation is such an important part, like of how we treat our patients clinically. Mm-hmm. So, definitely. [00:18:00] So I think we've, we talked a lot about a lot of the great topics today in the clinical year in review, but I would just love to kind of hear how you.
Became involved in ATS and so now you're actually organizing the clinical year in review. Do you have a
Sara: Yeah, I think it's one of those stories where. You know, chance favors the prepared maybe. And so I had a colleague who, when I was a fellow, encouraged me to get involved in the early career working group for the pulmonary infections TB assembly, which I'm a member of.
And so I got involved in the working group and then did the apprentice program through there. And then just sort of kept having opportunities come up and taking advantage of those. And I think what I've certainly come to appreciate around ATS is that. It really provides such a wonderful opportunity for networking and getting outside of your own institution and finding sort of mentors and then peer mentors really around the country and around the world.
For clinical year interview in [00:19:00] particular, I. This came about. I had a faculty mentor at Emory who suggested I do an ATS based webinar during COVID. And this was with Jose Gomez, who is an asthma mm-hmm. Provider at Yale. And we did this webinar together. And it was, you know, sort of a one-off experience that I didn't think about again until about a year later when he reached out and said, I'm the outgoing chair for the clinical year in review.
Would you be interested in, you know. Stepping in and I hadn't ever really thought about it before, but it's a really great opportunity. It's a three year role and so there's sort of three co-chairs at a time and one person's, you know, cycling in and out each year. I. And so this is my third year doing it, and it's a lot of fun because you get to brainstorm with the two other co-chairs about who not only what topics you wanna have featured each year and some show up every year, but some sort of cycle in and out depending on [00:20:00] what's going on.
PTs, for example, is one that we brought back this year because there's been so much happening in the space. But then you also get to tap into your own networks that you've created and reach out to, you know, people, you know, to say, Hey, do you know anyone who would be great to sort of highlight and feature mm-hmm.
As a clinical year interview speaker. And it's, it's been a lot of fun. I'll uh. Fee. I'll be sorry to move on when this, when this year's done. Mm-hmm. But it mm-hmm. It will be time to turn over the reins too. Mm-hmm.
Dr. Amy: Yeah. So it sounds like you, so you had your advocates who know what great work you do, so they kind of, they know where, when there's an open space, they advocate for you and then you kind of get to move.
You kind of get to think about that in the future for you mentees, right?
Sara: Yeah, yeah, yeah. Absolutely. That's wonderful. You know, that sort of sponsor role when put forward for those opportunities and whatnot. And then I think it's nice because as a clinical year in review co-chair, that's essentially what the entire experience is.
Mm-hmm. Is you're sponsoring people for these talks. Yeah. Yeah. So it's a lot of fun. So you're [00:21:00] moving it forward for other people. Yeah. So that's great.
Dr. Amy: Well, congratulations. I on, you know, your time in doing the clinical year in review and I think this year is. So much exciting topics and wish you just told us so elegantly about.
So thank you again for participating in the podcast. Yeah, it's such a pleasure. Thanks for having me. Thank you. Thank you so much.
non: Thank you for joining us today. To learn more, visit our website, thoracic.org. Find more ATS Breathe Easy podcasts on transistor, YouTube, apple podcasts and Spotify. Don't forget to like, comment, and subscribe so you never miss a show.