All right, so I have announcements to make before we get into it. First of all, just so everyone knows where they are, you should be at Sarcoidosis, Diagnosing, and Managing Pulmonary, Endobronchial, and Cardiac Manifestations. This is a reminder that all sessions can be evaluated through the mobile app and or the online program. Don't forget to evaluate the section, course, and faculty when it's done. We are required to verbally disclose any or no financial relationships relevant to our presentation. All rights are reserved. Please assist chest staff by keeping the aisles and the exits clear. Please silence all cell phones and pagers during the presentations. Please make room for attendees to have a seat by moving forward toward the center of the rows and leaving empty seats in the aisle of late comers. We're really at tables, so that doesn't really apply. CME claiming will be open Wednesday, October 11th at noon. And then we do have some audio response, so please keep your phone handy for that. So, again, you should be at Sarcoidosis, Diagnosing, and Managing Pulmonary, Endobronchial, and Cardiac Manifestations. Today's session will be in four parts, and I am gonna be touching on diagnosis and management of pulmonary sarcoidosis. What do the guidelines say? My name is Carrie Henna. I'm Assistant Professor of Medicine at NYU School of Medicine in the Division of Pulmonary Critical Care and Sleep Medicine. I work primarily at Bellevue Hospital Center. I'm the Associate Director of the Medical ICU, the Medical Director of Respiratory Therapy, and the Director of Bronchoscopy. I have nothing to disclose. So, after participating in my part of the session, I hope the audience will be able to evaluate which signs or symptoms should lead to further studies, including the appropriate imaging and biopsies needed to facilitate diagnosis as far as pulmonary disease. And then we're really gonna review the 2020 ATS Clinical Practice Guidelines and the 2021 ERS Clinical Practice Guidelines on the treatment of sarcoidosis. So, the ATS Guidelines are diagnosis, and the ERS Guidelines are gonna be on treatment. All right, so let's talk about diagnosis. Unfortunately, there's not a specific diagnostic test for pulmonary sarcoidosis. Instead, and really sarcoidosis in general, instead we follow diagnostic algorithms. So, the algorithms really have three scenarios. One, specifical clinical syndromes in which you may or may not need tissue diagnosis, and then a biopsy showing non-caseating granulomas. However, that's not enough. You also need to exclude other causes. So, first, just to review some of the specific clinical syndromes that you actually do not require a diagnosis. First, we have Lofgren syndrome. So, you're gonna have bilateral hyaluronidine lymphadenopathy, erythema nodosum, which is sort of these painful papules, nodular lesions, oftentimes on the shins, migratory polyarthralgias, and fever, and this is primarily seen in young women. That does not require diagnosis. Slam dunk sarcoidosis. Sometimes treatment is required based on severity of symptoms, but again, sarcoidosis, you're done. Second one is Hereford syndrome, which you don't see, I've never seen, but it does exist out there. So, I like to think of this from the pneumonic puff. So, parotid gland enlargement, uveitis, fever, and then facial nerve palsy from the parotid gland enlargement. Same thing with that, you do not need a tissue diagnosis. And then this third one is lupus perneum, which are these violacious plaques or nodules that oftentimes are on the nose, cheeks, and ears of sarcoidosis patients, and again, does not require tissue diagnosis. I also have here just essentially a stage one chest x-ray. We'll go into stages in the next slide, but this is asymptomatic bilateral hyaluronidinopathy on the chest x-ray. The guidelines, which I will review, do not make a recommendation for or against diagnosis. They leave it up to the clinical provider in that case, and the patient. And then we have the good old gallium scan, which some of us still have access to, and you would have, again, the lambda sign, which is the mediastinal and hyaluronidinopathy in the formation of the Greek letter lambda, and the panda sign, which is bilateral sacrumal and lacrimal gland enlargement. Important to note, when you do have the panda sign, a differential does also include irradiated lymphoma, Sjogren's disease, and HIV AIDS. Okay, so those scenarios, you either do not need a tissue diagnosis, as I showed with the two clinical syndromes, with the x-ray, may or may not, and then the lambda panda sign, there's no recommendation in the ATS guidelines, because many of us do not still use that. Then we have our biopsy. If you do require tissue diagnosis, that must show non-caseating granulomas. And then again, I said it's important to exclude other granulomatous processes. These are other inflammatory granulomatous processes and other infectious granulomatous processes. And then finally, sarcoidosis often doesn't just affect one organ. Sometimes it does, but oftentimes it does not. So you need to document systemic involvement and clinical evidence of other organ involvement. And a lot of times we can use the VASOG organ assessment tool, and the ATS guidelines also has an assessment tool that they use as well, that essentially gives you the probability of extra thoracic organ involvement. Okay, so to stage or not to stage. SCADding came up with the stages back in 1970, and we still do typically use them. So what are they? Stage zero is a normal chest X-ray, so no pulmonary involvement of sarcoids. Stage one, as I mentioned before, is gonna be your bilateral hiler lymphadenopathy. Stage two, in addition to the hiler lymphadenopathy, you start to develop some sort of pulmonary involvement, parenchymal involvement, infiltrates. In this image, reticular nodule infiltrates bilaterally. Third, you start to lose your lymphadenopathy and you're left with your pulmonary parenchymal involvement. Again, some infiltrated process. And then stage four, what we hope our patients don't develop, is gonna be your pulmonary fibrosis. If I were to poll the audience, I think the majority of the people would say we don't stop at chest X-ray. Many of our sarcoidosis patients, if not all of them, get a contrast, excuse me, a non-contrast CT of their chest. So, there really is some push to say maybe we should ditch scatting staging and go to a more evolved CT staging, which can also be used as a radiographic biomarker. In this review by Dr. Meyer and her colleagues, she highlights some patterns of CT abnormalities that are predictive of pulmonary impairment and even treatment response. So perhaps the future will go away from scatting stage and go into a chest CT form of staging and prognostication. So what do we see on our high-res CTs? Again, you don't necessarily need contrast. Sometimes contrast does help you see vascular structures and lymphadenopathy, but oftentimes, we're doing high-res non-contrast. And you're gonna look for hyaluramidostinal lymphadenopathy. Perilymphatic nodules, this is important. They're along the bronchi, vessels, and subplural regions. This is in contrast to the central lobular nodules that we see in hypersensitivity and pneumonitis, which is another granulomas process. You can see bronchial wall thickening, ground glass opacities, parenchial masses or nodular consolidation, sometimes even cavitating disease, fibrosis and traction bronchiectasis in our stage four disease. And then the key here is you're gonna get a mid to upper zone predominance. I also show here a galaxy sign, which is large nodules arising from the coalescence of small granulomas, stimulating the appearance of the galaxy. So what do we do for diagnosis? I'm not gonna go too much into this because we do have our interventionalists who will touch on a lot of this. But essentially this is from the ATS guidelines, comparing EVS versus metastinoscopy, and looking at a total of 703 articles, of which they actually selected 29 to make up their recommendations for whether or not you do EVS versus metastinoscopy. So essentially with EVS, we're gonna get a diagnostic yield of 87%. It's less invasive. Combined with standard bronchoscopic techniques, transbronchial or endobronchial biopsy, you can get to up to 100% diagnostic yield. And that's typically with EVS plus transbronchial biopsy, which again, you're gonna have if there's parenchymal abnormalities. There's no difference with rapid onsite evaluation. And the yield is associated with stage, which makes sense, right? Because our EVS is going after our lymph nodes, so higher yield with stage one as compared to stage two, and two or more lymph node stations. No difference in 21 versus 22-gauge needles, but the 19-gauge needle did show the highest sensitivity. And then comparing to metastinoscopy, the diagnostic yield is higher, 98%, but higher complication rate, extrapolating from lung cancer and metastinal staging data. So what about standard conventional bronchoscopy? And again, just to kind of gloss over this a little bit, transbronchial biopsy does give you a yield of 37 to 90%, higher with stage, which makes sense because you're getting your parenchymal abnormalities, and higher yield with number of passes. And a bronchial biopsy, again, we'll go over that a little bit later, but the yield's variable, higher when you have cobblestoneane, which is granulomatous involvement of the mucosa. And then the BAL CD4 to CD8. You're in there, you might as well. A value of greater or equal to 3.5 is indicative of sarcoid, but again, low sensitivity, high specificity, and the key to know is it's often higher with flow cytometry, and exclude, and you also are able with the BAL to exclude other granulomatous infections such as fungal or mycobacterial processes with your staining. And then whether or not there's a role for navigational robotic bronchoscopy for some of those peripheral nodules remains to be seen and evaluated. So what do we see? We're gonna see our non-necrotizing or non-caseating granulomas that are well-formed. In this image, you can see G is the macrophage aggregates, the arrows are the multinucleated giant cells, and you'll see that although granulomas in sarcoid are along a lymphatic distribution, they are usually associated with a relatively low amount of lymphocytic infiltration, which is the L. This is in comparison to non-necrotizing, poorly-formed granulomas. Again, the macrophage aggregates are there, and the lymphocytic infiltration is more pronounced, and you're gonna see that in your hypersensitivity pneumonitis and then our large necrotizing granulomas, which are typically infection. This is actually a histoplasma, and they're acellular cavities that you're gonna see on your histopathology. Okay, so what does the ATS practical guideline tell us about diagnosis? To summarize, so in patients in whom there's high clinical suspicion for sarcoid, think Lofgren's, think Hereford's, lupus perneo, no sampling of lymph nodes is required. For patients presenting with asymptomatic bilateral lymphadenopathy, no recommendations for or against obtaining a lymph node sample is made. So up to, again, provider and patient discussion. For patients with suspected sarcoid and midiastinal and or hyalolymphadenopathy for whom it has been determined that tissue sampling is necessary, we suggest endobronchial ultrasound-guided lymph node sampling rather than midiastinoscopy as the initial procedure. This is important because as we'll hear from our cardiologist, oftentimes we do need to make a diagnosis, even if our patients are asymptomatic, to prove extra thoracic involvement. So EVIS would be the diagnostic modality of choice. So what about treatment? We will talk about second and third-line agents later in the talk, but I'm just gonna give a brief overview of the European Respiratory Society Task Force. This committee, it was very interesting. It was clinicians, methodologists, and patients. And they made recommendations based on grades, so grading of recommendations, assessment, development, and evaluations methodology. And they asked PICO questions, so patients, intervention, comparisons, outcomes. And I'm gonna go over the ones that covered pulmonary. So question one, in patients with pulmonary sarcoidosis, should glucocorticoid treatment be used versus no immunosuppressive treatment? And question two will be in patients with pulmonary sarcoidosis, should one add immunosuppressive treatment or remain on glucocorticoid treatment alone? So how do we decide to treat in pulmonary sarcoid? We wanna look at three things, both for the indications to start and potential end points of treatment. And this is a slide from Dr. Judson. So essentially, looking at granulomatous activity as indicated by ACE levels, BAL cell count, radiographic imaging, PET scans, physiologic impact, looking at lung function, cardiac function, kidney function, and then functional impact. And you can argue maybe this is the most important of all, patients' health-related quality of life, the symptoms that are debilitating their day-to-day activities. All of these need to come into play. This is a busy slide, but essentially, this is what the ERS came up with. And in blue, you're gonna see, essentially, strong recommendations based on low-quality evidence. In purple, you're gonna see a conditional recommendation based on very low-quality evidence. And then in orange, you're gonna see a conditional recommendation based on low-quality evidence. Clearly, we need more research in sarcoid. Okay, but first off, you have your patient who is low-risk. You could probably observe. And then you're gonna be assessing those patients more often than not, at least every six to 12 months, and deciding whether or not they do develop symptoms that require glucocorticoids. Intermediate risk, but impaired quality of life, you're gonna probably start glucocorticoids. The white boxes, just to say, are actually just anecdotal what the physicians and part of the committee do in their practice. And then if there's good clinical response, you're just going to taper. If not, you're gonna move on to your second line. And if not, you're gonna move on to your third line. What I wanna highlight here is your high-risk patients, which they, sorry, which they define, oh my gosh. That's not staying up there for some reason. Anyway, I will just tell you. As impaired lung function, as reduced FEC or DLCO, and then essentially stage four fibrotic lung disease was their high-risk patients. They went right to glucocorticoids, and then sometimes, some of the authors suggested actually doing a combination of glucocorticoid and an antamytopolyte, given the severity of disease, and whether or not there was relapse or inability to taper steroids, or inadequate response based on imaging or granulominous activity, they would go to infliximab. Okay, so here is another slide that's a little bit more readable that shows you the stepwise approach. So again, patients who are entirely asymptomatic, we can probably just observe them without systemic therapy. Step one is prednisone. We used to think .3 mg per kg, however, more and more studies have shown that 20 milligrams is probably more than enough steroid. Step two, our patients are on steroids, they're having side effects, or they're having worsening of symptoms or functional and physiologic impairments, you're gonna go to methotrexate as your antimetabolite of choice, best study. There's actually a retrospective study that showed that 2 3rds of patients actually had reduction or cessation of their steroids after six months of therapy on methotrexate. So that's the best studied antimetabolite we have. Then we have infliximab as our step three. So again, our patients are now on methotrexate, maybe a reduced dose of steroid, but still having symptoms, we may switch them to infliximab. And this is based on studies that have shown improvement in chronic pulmonary sarcoidosis with infliximab. The thing with infliximab is the side effects, and those are allergic reaction and infection, particularly tuberculosis. At Bellevue, we have a lot of patients who have risk factors for tuberculosis, so it's important that you exclude granulomas infection when you're putting your patients on infliximab. And then additional, you have rituximab, repository corticotrophin injections, and then sort of what's been new is JAK inhibitors, which has been studied well in cutaneous sarcoid. And then maybe or maybe not, there's a potential for antifibrotic. So again, just to highlight, prednisone initial 20 milligrams, following up with five to 10 milligrams once a day to once every other day as a taper that suggested. We all know the side effects of prednisone. They're not so great. Methotrexate, typical dosing would be 10 to 15 milligrams once a week. Looking for leukopenia, hepatotoxicity, as we all know, so monitoring with CBC and a CMP. And then we have our TNF inhibitor of choice, which oftentimes is infliximab, being concerned for allergic reaction, infections, and screening appropriately for TB beforehand. And then this question of whether or not we use an antifibrotic. There is some concern that fibrotic sarcoid actually isn't completely burnt out. So there's a suggestion that maybe we should be getting PET scans on these patients who have stage four disease, and we'll find smoldering disease that actually may be more responsive to increasing immunosuppression as opposed to an antifibrotic. But, as you can see in this ATS report, we do see patients with sarcoidosis who have progressive pulmonary fibrosis. So potentially they would be targets for antifibrotic agents, such as nifatinib. This sort of shaded area is just a rough estimation of the amount of patients with those disease states that develop progressive pulmonary fibrosis. So, to summarize the ERS guidelines, in patients with pulmonary sarcoidosis, should glucocorticoid treatment be used versus no immunosuppressive treatment? So the answer is, for patients with major involvement from pulmonary sarcoidosis, believe that higher risk of future mortality or permanent disability, so think reduced FEC, reduced DLCO. The other actually high risk I failed to mention before would be also pulmonary hypertension in addition to stage four fibrotic disease. Those are all high risk. Introduction of glucocorticoid treatment, no more than 20 milligrams, to improve and preserve FEC and quality of life is recommended. And that's strong recommendation, although there's not a lot of studies, so they qualify it with a low quality of evidence. For patients with worsening quality of life from pulmonary disease, a consideration of initial low to medium dose glucocorticoid treatment with a dose and duration of maintenance treatment based on efficacy side effect balance. So these are patients that are not high risk, that are either low or typically intermediate risk, which they don't define quite clearly, but are having some worsening quality of life. You can do low dose, potentially even lower than your typical 20. And then patients not felt to be at risk for morbidity or mortality or having no significant impairment. So again, our three caveats we wanna look at, granulomas activity, physiological impairment, functional impairment. If patients have none of those, we do not need to treat them. Okay, so question two. In patients with pulmonary sarcoidosis, should one add immunosuppressive treatment or remain on glucocorticoid treatment alone? So for patients with symptomatic pulmonary sarcoidosis at higher risk, the task force recommended treating with glucocorticoids and having continued disease or unacceptable side effects from glucocorticoids at the addition of methotrexate to improve or preserve efficacy and quality of life as suggested. Again, conditional recommendation and low quality of evidence. For those patients who are having continued symptoms or adverse side effects from other step-down therapies, the addition of infliximab is recommended to improve, again, the efficacy and preserve quality of life. Okay, conditional recommendation, very low quality of evidence. All right, and these. So every year we have an annual sarcoidosis symposium at NYU, and I make my kids take a picture with me afterwards, which you can see there. Our next symposium is gonna be March 7th at 2024 on Thursday, and that's a QR code if anyone is interested in signing up. So I'll leave that up momentarily. And then, I'm a little behind, sorry. We're gonna move on to our next speaker, and we'll do questions at the end. Good morning, everybody, or good afternoon if you're still in a different time zone like me. And I'll dive a little deeper now on second- and third-line therapy for sarcoidosis. So I think a perfect follow-up to this great lecture on the guidelines, and the main area from the Cleveland Clinic, nothing to disclose related to this topic. And again, 15 minutes, I wouldn't have time to review the whole evidence on this. I'll show you what I think is the best available evidence to guide practice when you're seeing those patients, taking care of those patients in clinic. So a few things on second-line agents, a few things on third-line agents. And starting with a question to warm up, and starting with a why. So why should we even talk about this, second-line agents in sarcoidosis? Why don't we just use prednisone? So I hope you know already how to use your audience response system. This is a question, why should we consider second-line agents in pulmonary sarcoidosis? A, prednisone is not effective, and many RCTs have shown the benefits of second-line agents. B, prednisone is effective, but many RCTs have shown that second-line agents are better. C, prednisone is effective, but can cause significant side effects. So second-line agents have a steroid-spiraling effect and may improve outcome. Or D, I couldn't care less about methotrexate or azathioprine, I'm gonna give prednisone and that's it. So I'll give you, okay, we have 54 votes already, so I think we are pretty good to go to the answer. I'll give you maybe five more seconds, maybe six. Okay, 74, 76, very good, perfect. So most of you answered C, and that's what I think is right as well. And this is why, right? So we know already from the guidelines that steroids are effective. This is just one example, this is a meta-analysis that showed that in one outcome, for example, chest x-ray or two years, there's a good response when we use steroids in those patients. Risk difference at 21%, the number needed to treat four. So we can use prednisone and we do it all the time, but this is the problem, right? We all see those patients in clinic coming with the steroid-induced diabetes, hypertension, obesity, hyperlipidemia, osteoporosis, sometimes osteoporotic fractures already. So that's why I think we definitely need to talk about second-line agents. So we'll do that now, but we'll go straight to our second question. So which second-line agent is the most prescribed in the U.S.? And there's a recent study in the annals of ETS showing this. So take a look at your response system here. We have a lot of votes already. Try to get to that 76. Okay, there we go, more people voting now, this is good. So the answer is, there we go, methotrexate, absolutely. And as you saw, methotrexate is recommended in the guidelines as well as the agent of choice for second-line agents, so that's perfect. Now, here's the key, right? So this is not because there are a lot of high-quality studies convincing us of that. This is mainly based on expert opinion and years of experience in some centers and cohort studies, but there is actually one RCT for methotrexate. So that's why, even though it's a very small RCT, 24 patients enrolled, I definitely wanted to show you that. This is from Dr. Boffman and his group. 24 patients with pulmonary sarcoidosis were enrolled. The idea was to give one year of methotrexate versus placebo. Of course, both groups got steroids. Only 15 patients completed more than six months of methotrexate, so those are the 15 patients that he analyzed. And even though, again, small study, big number of loss of follow-ups or high risk of bias, but I think the main lesson is they were able to show a steroid-sparing effect, as you can see in this graph here. This is the prednisone dose, and in the methotrexate group, this first column here is the steroid dose in the first six months of methotrexate therapy, and in the second column, you have the second six months of methotrexate therapy. It went down to eight milligrams per day, the dose of steroids, and if you look at the placebo arm, that dose after six months of placebo wasn't 60 milligrams daily. So this was statistically significant, and again, there are other cohort studies that we can take a look, guidelines, systematic reviews, but this is the only one really with an RCT guiding our practice. So methotrexate, great option as a second-line agent. Interesting study, very nice study comparing methotrexate directly to azathioprine, but this was not a randomized control trial. This was done in Europe, and all of the patients on methotrexate were from the Netherlands. All of the patients on AZA were from Belgium, so they compared those two groups. Very tough to compare by those two groups, because again, a lot of other differences that you can imagine from being, you know, from different countries and all of those things, but important points, I think. This is the main one, again, the steroid-spirin effect that we know that methotrexate has, the same steroid-spirin effect was seen in AZA as well. And one additional important point, in patients with pulmonary sarcoidosis, which are the two, you know, those bottom lines here, they saw some significant improvement in the LCO, in both groups, methotrexate and azathioprine. So again, not an RCT, but maybe some data suggesting that not only there is a steroid-spirin effect, you also can improve a little bit of lung function in those patients. Another great drug for a second line therapy in sarcoidosis, I think, Liflunomide. This is a paper from Saho and his colleagues, and this is the largest retrospective cohort in Liflunomide, 76 patients. Most of them had pulmonary sarcoidosis, 92%. Those are patients with refractory pulmonary sarcoidosis, so they were on prednisone, they were on methotrexate, they were not getting better, and Liflunomide was either added on, or they replaced methotrexate for Liflunomide. They saw that steroid-spirin effect again before the Liflunomide, 10 milligrams per day, average of prednisone. After Liflunomide, very, you know, zero milligrams, this was the medium, so significant decrease there. And they saw similar things that they saw with AZA and methotrexate as well. At least FPC, after the initiation of Liflunomide, you can see this top graph here on the right-hand side, there was a positive change in the FPC. So some signs that maybe this improves lung function. There was a trend in the LCO, but that was not clinically significant, statistically significant, sorry. Now, the other second-line agent that we use, mycophenolate, but completely honest, we don't use it as much as the other three, and methotrexate, AZA, and Liflunomide, those are the ones that we use most of the time. But it's definitely a possibility, but probably we, in our center, don't use it that often because of data like this, showing that maybe it's not as good as the other three, but again, a good option. This study specifically from the National Jewish, they included 37 patients in this retrospective cohort. They had, they found a good steroid-spirin effect, as you see here, from 14 to eight milligrams daily after the addition of MMF. But this graph, I think, tells a nice story. If you look at, you know, focus on the left one, and focus on the bottom line first, those were patients that had intolerance to methotrexate. They wore methotrexate, had a lot of side effects, then you switch that patient to mycophenolate. In those patients, they saw a trend towards improvement in their lung function. It was not statistically significant, but it was a trend if they were intolerant to methotrexate. If they had failed methotrexate, this is the bottom line, this dotted line, their lung function kept getting worse. So this is, you know, one thing to remember. Maybe if they already tried methotrexate, hazel, ethylamide, it wouldn't, you know, and they didn't work, you wouldn't help probably to move to MMF. In that case, you definitely need to think about a third-line agent that we'll talk in a little bit. Actually, we'll talk about third-line agents right now. So this is the final question, and moving into the third-line agents. Which biologic agent has shown to be effective in pulmonary and extrapulmonary sarcoidosis in NRCT with more than 100 patients, which for sarcoidosis, as you all know, this is great, right, we really get those large studies like this. So take a few seconds to answer that. Let's try to beat those 80 votes that we got in the second question, there we go. 76, 77, 81, nice, good. So the answer is infliximab, there we go. So it is infliximab, and we'll review that study in a little bit more detail, just two slides for that study, you know, they deserve a little credit here. So this was a phase two trial, including 34 centers in the US and Europe, 138 patients with pulmonary sarcoid. They tried two doses of infliximab, three or five migs per kg, and placebo as well, and this was their regimen, week zero to six, 12, 18, and 24, they did do a follow-up until week 52. So patients, after they had stopped infliximab, what happened to them? Primary endpoint change in baseline to week 24 in lung function, but they checked for a lot of other important endpoints, for example, chest x-ray scoring system, dyspnea scale, which is probably, you know, the most important one to patients, and this is what they found. So those, I think, are the two most important graphs from that study. This publication here was the first one on pulmonary sarcoid, they have a second one looking at the data on extra-pulmonary sarcoid, but we'll focus on this one now. In the graph here to your left side, you'll see that, regardless of the dose, there was an improvement in the lung function after the 24 weeks. Not that great, right? So 2.5% improvement in FVC, but it was a positive study for that outcome. And they also found some improvement in some secondary outcomes, such as the chest x-ray scoring, the scoring decreased or improved by 26%. Interesting finding here in the right-hand side, you see this graph, all the way up to week 24, you know, especially in the infliximab group, of course, they improved their lung function. As soon as they stopped the infliximab, there was this trend downwards. I showed you the regimen that they use. Of course, since then, we have more cohort studies, we have more experience on this, we have studies coming from other diseases like rheumatoid arthritis, for example, and we use a different regimen. We start with five mgs per kg, weeks zero, two, and then every four weeks. Sometimes insurance only approves every six, every eight weeks, that's okay, you know, you gotta use that, and then later try to increase the frequency if needed. And you can actually go up on the dose as well. Start with five, and then after six months or something, if patient is not getting better, you can go to 7.5 or even 10 mgs per kg. Again, when you try to get those things approved with insurance, it gets a little tougher, but for some patients, you definitely need to pick that better. And then I think this is the last slide, Adalimumab. There is one RCT, small one, for Adalimumab, but that's for cutaneous sarcoidosis. There's no one for pulmonary sarcoid. This is a case series, 11 patients with refractory pulmonary sarcoid, and they used Adalimumab 40 mg weekly, which is the same dose that I use most of the time for pulmonary sarcoid. And interesting things that they found, so some patients, in the left-hand side, you can see here, some patients improved FPC, not all of them, some patients improved the six-meter walk distance in the middle graph, and some patients improved their global assessment score. And then they came up with this composite outcome of if you improved at least one, we consider you as having a good response. So with that analysis, they actually found nine out of the 11 patients having a good response to Adalimumab. And it's a small series, but that kind of fits with what we see in our clinic as well. We certainly use Adalimumab for pulmonary sarcoid. And then that's it. So take-home points, steroids can cause significant morbidity. Second-line agents, I think all of those are reasonable, methotrexate, azoliflunomide. Methotrexate should be, I think, the agent of choice, and I agree, of course, with what they said in the guidelines, there's more data on it. Mycophenolate, also an option, but probably only if they don't tolerate the first three. Due to side effects, third-line agents, infliximab and adalimumab, I think with all of those important things that Dr. Hanna mentioned, risk of side effects and infection like TB or reactivation of hepatitis. As we exclude those things, as we test patients for that, those, I think, are great options for patients with sarcoidosis. But without a doubt, the last thing to say is we definitely need more RCTs, even if it is just to look at what is the best first-line, second-line. We need to find new drugs as well, of course, but organizing that workflow, I think, is important as well. And I think we'll leave questions for Dan. Thank you very much. Well, thanks for inviting me to Hawaii. HFSA is in Cleveland right now, and no offense to Cleveland, but happy to be here in Hawaii. So we're gonna be talking about cardiac sarcoidosis, diagnosis, and management. I'm an advanced heart failure and transplant cardiologist at NYU, but I'm here with my cardiac sarcoid hat, and I'm the co-director of the Cardiac Sarcoid Program. So I have no financial disclosures, but I think it is important to note that, as a cardiologist, I stick out a little bit in this room. And I think it can be helpful. We sometimes see the same thing a little bit differently, so I'll give you perspective, as a cardiologist, how I think about cardiac sarcoidosis. So we'll talk about the epidemiology quickly, manifestation, screening, diagnosis, and treatment. In cardiac sarcoid, clinical cardiac involvement is about 5% of patients with extra-cardiac sarcoid. 25% of patients with extra-cardiac sarcoid will have asymptomatic involvement, and that can be seen on a post-mortem autopsy. Isolated cardiac sarcoid is about a third of patients with cardiac sarcoid, although that number is disagreed upon, depending on the studies and the groups that have looked at it. And full-body FDG PET can often pick up small amount of disease in the outside of the heart. And you can have a high morbidity and mortality from this disease, both from arrhythmic complications, and then about one out of 200 patients who go on a cardiac transplantation are repeatedly shown to have cardiac sarcoidosis, and those patients are only seen if they're at a transplant center referred appropriately. So I think thinking about screening these patients. In this group, given we have a lot of pulmonologists, or predominantly pulmonologists here, we're only talking about the patients with extra-cardiac sarcoidosis who are gonna look for cardiac involvement. And to think about who has cardiac involvement, you have to understand the manifestations of the disease. So the typical manifestations we think about are ventricular tachycardia, conduction abnormalities, and advanced heart block, and then heart failure. This schematic from Dr. Burney looks at scar at different areas and how you can have reentrant arrhythmias causing ventricular tachycardia, although you can also have polymorphic PT in the setting of just overall inflammation. Conduction abnormalities, particularly when the septum is involved in the Purkinje fibers, and heart failure, we think about an overall large burden of fibrosis. So the questions you need to ask, and this is because patients often don't associate certain symptoms with their disease. They're seeing a pulmonologist, why am I gonna talk about my palpitations, my lightheadedness, but I think it's really important with this disease that we're assessing for that thing about PT or heart block. Dysmyone exertion's really tough in your clinic. I'm sure how to separate that out, but I think what's very helpful from the pulmonologists I work with is when they recognize that their dyspnea is out of proportion to their PFTs or their PFT chain. Like something else is going on, let's make sure we have an appropriate cardiac involvement and assessment. Orthopnea and P and D might be more specific for heart failure, so those are gonna be beyond just the standard dyspnea you might see in your clinic. So we have to consider cardiac sarcoid in a whole host of patients, and outside of extracardiac sarcoid, really think about young patients with idiopathic heart block. About 30% of these patients under 65 will have cardiac sarcoidosis. Young patients with idiopathic ventricular arrhythmias, ruling out coronary heart disease, having sustained VT, and then as I mentioned, extracardiac sarcoid, you really have to screen with any possible cardiac involvement. So where do I start with? Detailed cardiac history in our groups when we work together, it's really nice hearing from patients from the pulmonary side, from the cutaneous side where they elicited symptoms that they wanna send someone my way. So orthopnea, P and D, syncope, palpitations, those latter two being very concerning because rhythmic death is something that's I think scary for all of us. Initial screening with EKG and yearly thereafter, you're looking for multivocal PVCs, conduction disease, any degree of heart block, first degree AV block in a young patient is not normal, and then more advanced heart block as well. I put a question, a baseline alter. I know a lot of people, and probably in this room, don't believe in the evidence, I think, for ambulatory rhythm monitoring. I think as a cardiologist, I find it very helpful, and we are more and more getting PDFs of Apple Watches sent to us in our inboxes, and I think we have to be able to understand what to look for in ambulatory rhythm monitoring, but I think for every extracardiac sarcoid patient that sees me, I get a baseline one-week event monitor. Same thing with the baseline echo. These are cheap and readily available, although the screening characteristics are not very high, but I think it's a good place to start. And if you look at some of these studies that looked at the sensitivity and specificity for individual screening tests, none of them are good. Electrocardiogram, Holter, echocardiogram, but in combined, you approach in this study by Dr. Mehta, you approached 100% sensitivity. You know, this is sacrificing some specificity as you add them all together, but I think any good screening test, you're gonna really try not to miss the people who potentially could die from a sudden death prior to being evaluated. And of note in the most recent HRS working group guidelines, 10 out of 14 members voted to have ambulatory rhythm monitoring in the guidelines. That did not meet the pre-specified threshold for adding it in, and so that was tabled, and the current guidelines that are being developed in the next few months are gonna be started, and that will probably be reconsidered, and we'll see what is suggested at that time point. Dr. Judson looked at these two studies from Dr. Mehta and Dr. Kouranos, and looked at the different screening tests, and I'm outlining here, this is the, any of the Holter EKG or echocardiogram, and looking at the increased sensitivity and the specificity that's seen there. And then here, in Dr. Kouranos, the sensitivity increases when you have any of these abnormal width of sacrifice and specificity. You know, if you have a high suspicion for cardiac involvement, do we need to think about histologic sampling for these patients? I mean, it is one of the ways to make a diagnosis from the HRS consensus. However, cardiac biopsy has increased risk in experience centers, about 1% yield of cardiac perforation. We do it quite well, but 1% is not trivial. But the more important thing is, this is a very patchy process in the heart, and the yield that we see on endomyoparty biopsy is nowhere near what Dr. Hennig quoted in the pulmonary world, typically seeing about 20, 30% yield. Potentially able to increase that sensitivity with electroendotomic mapping and guided biopsy, but that's not the standard. Some centers are doing that, you know, more under experimental or center-specific. But I will also say, if something tells me electroendotomically I should go to the RV free wall, I'm not gonna do it because of the increased risk of perforation, so it still has to be on the RV septum for me to feel comfortable going after it. So we like to look elsewhere, skin, the lymph nodes, the eyes, and we often work closely with our pulmonary team. If I see someone first, maybe sending them back to their pulmonary, can you guys make a histologic diagnosis? So what we typically work with in the HRS consensus is that middle aspect, with a clinical diagnosis. You can make, with a histologic diagnosis of extracardiac sarcoid, and then idiopathic, low EF, VT, advanced heart block, and then imaging findings consistent with sarcoid. That's kind of the bread and butter to move away from the right-sided, which is a clinical diagnosis of cardiac sarcoid, may be considered. See if we can get extracardiac diagnosis. A little bit about echo, since I mentioned it before, what we're looking for. You can have a dilated cardiomyopathy, you can have diastolic dysfunction. You can have septal thinning, and you can also have LVH, wall motion abnormalities, valvular disease. You can have aneurysms and not be from coronary artery disease so we can have a whole host. But a normal echo does not rule out cardiac sarcoid. An abnormal echo does not mean that they have sarcoid. You have to use more advanced imaging. I like this screening for extracardiac sarcoid algorithm. I added into that top box, that Holter monitor. That was not in the initial publication. I added what I choose to do. We're looking at EKG, echo, and Holter. And if they're abnormal, go into cardiac MRI, which has much greater sensitivity and specificity. And then if that's abnormal, go into cardiac PET scan to look for active inflammation. And cardiac MRI and PET scan, it's not one or the other, they're complementary. So if you look at the left side, the left two black and white images, those are cardiac MRI. And the blue arrows are pointing to late gadolinium enhancement. And that correlates with scar. And this is a young gentleman who has a lot of scar in the septum. He presented with asymptomatic complete heart block to his rheumatologist for a non-sarcoid rheumatologic disease. And this is his PET scan, where the yellow arrows are pointing out FDG avid segments that were active inflammation. And he had some septum involvement inflammation, but he had a lot of inflammation outside that. And so the FDG, looking at glucose uptake, is active inflammation. The way I explain it to patients is if you've ever had poison ivy, you have this red itchy rash, that's what someone's gonna put cream on or in bad cases give you steroids. But if you scratch it and it goes away eventually and you're left with scar, you're not treating that. The scar is the late gadolinium enhancement. The PET is looking at the active inflammation. So these are the patients that benefit from steroids. And I think that's a key point. With the caveat being MRI can also look at edema with T2 imaging, but that's much less sensitive than PET scans. So for typical late gadolinium enhancement, that all MRIs will look for, is really looking at scar. The treatment, I won't belabor, everybody mentioned, the level of evidence continues to be a level of evidence C with the highest evidence being in steroids and thinking about other agents afterwards. And what do we look for for steroids? We keep talking about non-clinical endpoints and I'll show you some great non-clinical endpoints here, but you're looking for that inflammation to go away. And this study looked at, retrospectively, a follow-up of 88 months, looked at changing in volume of the left ventricle and also ejection fraction. So if you look at the bottom left, increased volume of LV is bad, and the bottom right, lower EF is bad. And so if you started, the black is before steroid treatment, the white is afterwards, and on the x-axis, the groups are by different EF to start. So just breaking it down, group A, if you started with a normal EF and you were treated with steroids, the EF did not get worse in follow-up. In group B, if you had a mildly reduced EF and you started on steroids, your volumes decreased, which is good, your EF improved, which is good. And in group C, if your EF was severely reduced and you put on steroids, things did not get better. And so I think this is suggestive, although not in a randomized fashion, but this is suggestive, that starting patients on steroids can prevent some of the progression. If you wait too long, you might not be able to reverse it at all. What do we do at NYU? We look at if you have active cardiac sarcoid by pet, we start you on prednisone 30, and this is different than what was mentioned as far as 20 milligrams in the pulmonary. I think in general, historically, cardiac sarcoid was treated with 0.5 mgs per kg and 30 milligrams was found not to be inferior to that with the benefit in steroid side effects. So we treat for three months and repeat a PET scan. If you have improvement in the PET scan, we will wean steroids slowly, typically over three months, and repeat that PET scan. But if you still have a positive PET scan or you have recurrent PET scan after weaning, then we start methotrexate with this. And I start at 10 and increase every two weeks up to 20 to 25 milligrams with folic acid daily, and then I'm trying to get off the steroids and repeat the PET scan. If it's negative, weaning, and if it's positive, talking about the third-line agents. And typically, the best evidence, as mentioned, is for infliximab, there are other immunosuppressive agents, but insurance doesn't often want to cover adalimumab for some of the studies that they're in, and I know some of the rheumatologists really like to go to that for patient convenience. I try to start with infliximab, also the benefit, as mentioned, increasing dosing and administration rates, whereas adalimumab is kind of a one-size-fits-all. You also have to really think about adjunct management in cardiac sarcoid, you're not done with treating the inflammation. Always, everybody should be considering whether they need an ICD. Not that everyone needs an ICD, but if you see them two years later, and things change, you should always reconsider, is the conduction disease changing, are their symptoms changing, is the EF lower? So there's the standard class one indications, EF less than 35%, prior sustained VT, but there are other high-risk individuals and should work closely with a cardiologist, electrophysiologist, to think about them. In high-degree AV block, and I'll show you why I never do a pacemaker, they all get an ICD because the risk is different than in other high-degree heart block. And then heart failure, there's no randomized trials of cardiac sarcoid with heart failure, but it's thought that standard GDMT is helpful with the added understanding that if you're adding Bactrim for PGP prophylaxis, think about potassium, might have to intervene on valves, someone has severe MR that doesn't get better with kind of resolved inflammation, whether that has standard indications for correcting that. This looked at a risk of sudden cardiac death if presenting with AV block. On the left side, they separated it out by class one indication, that's the red group, so either prior sustained VT or EF less than 35%, green was mildly reduced EF, and blue was if you just had a normally F but advanced AV block. And I outline here, at five years, the people with VT or low EF, 30% risk of sudden death. But on the right side, normally EF, no VT, 90 patients with just complete heart block in five years and 9% risk of sudden death. And I think in most other trials, we would think about implanting people with that with a 9% five year risk of sudden death, and these are patients that are already getting a device. So I think they benefit, you have already done the procedural risk, it's a slightly bigger device, maybe a slightly increased risk of complications, very small, and I think they benefit, personally I think they benefit, and you are guideline supported, although not class one, but any sarcoid patient who's getting a pacemaker, you have guideline support to put an ICD in them. A lot of patients will read Google before coming in and they're terrified when they come in to talk about cardiac sarcoid. And so what is the prognosis? I think if you look at the left side, transplant-free cardiac survival. You know, if you have a very reduced EF, you're about a 50% 10 year transplant-free survival, so it is not a death sentence, but this is making sure you treat people appropriately, prevent sudden cardiac death, better obviously with a normal EF. And on the right side, it's survival, free of transplant, and free of transplant or ventricular arrhythmias, that's all comers. Again, this is at, the x-axis is in years follow up. So it's not a death sentence, people do quite well, but I think we have to treat them appropriately using GDMT as appropriate for heart failure, preventing sudden cardiac death, and making sure to follow them, and if they are someone that is going to progress, that needs consideration for a transplant, understanding how to refer them. So our take home here, about 5% of patients with systemic sarcoid will have manifest cardiac involvement, really screening is important. EKG, history and physical is paramount. Echo and halter, I think there's some individual aspects to that, but I personally advocate for them. And then advanced imaging, if something is, does not look right. Steroids, but may need second line agents. Don't treat the MRI, treat inflammation. The initial EF correlates with outcomes, and you can have a decent overall prognosis, but have to make sure we treat them appropriately to prevent sudden cardiac death. And that's it for me. Thank you very much. Thank you. Good morning, everyone. Thank you for all these great talks. It's really a pleasure, a pressure to be here in this panel. My task is to talk about endobronchial abnormalities and management in sarcoidosis. These are my disclosures. I want to ask the audience, if you can raise your hand, if you have seen and or treated a patient with bronchial stenosis related to sarcoid, if you can please raise your hand. Great, great. So really today, I want to show you the different manifestations of airway sarcoid and discuss the approach. I may touch base again on diagnosis, biopsying, and everything else, PFTs, bronchoscopy. And then later at the very end, talk about some of the interventions that can be made for the management of these. So this is my first question. Which of the following is more common in endobronchial sarcoidosis? Thickening, multilevel airway stenosis, plaque, or increased vascularity? We have 50 votes. Let's get up to 90, oh, okay. Great, okay, yep. So I'm glad I'm gonna be able to show you some of the things I found in terms of data. So out of all these options, plaque is the more common one, okay? So thickening is common. Out of all these options, plaque is more common. So sarcoidosis has a number of airway abnormalities from nodules, cobalt stoning, which are the more common ones, plaques, and then followed by increased vascularity from left to right. Oftentimes, these are missed. So either because they're very subtle, or we just, you know, there may be in the segmental airways, so deep into the lungs, and not necessarily in the central airways. This is a study that was recently published in CHEST where they used high-definition bronchoscopy. This is nothing different than what you guys are probably doing. So most bronchoscopes nowadays are high-definition. So what they looked at is at 130-plus patients with suspected sarcoidosis. They went on and did a thorough exam, and this is how they found. This is of note, this patient population is of white Europeans, and that's what they found. So it may be different than African Americans, maybe different manifestations, so we're gonna talk about those. It's good to know that airway involvement in sarcoidosis is actually associated with increased morbidity and mortality. What are some of those manifestations? So in the bronchial granulomas, you're probably very familiar with them. Bronchial stenosis is not as common. Bronchiolitis, so sarcoidosis can really affect anywhere from the nasal passage all the way to the terminal bronchioles. In fact, there was a recent study in the Blue Journal, it was a case report, by the way, of somebody performing a navigational bronchoscopy and actually seeing all the way out some evidence of nodules. They took biopsies, and those were, they found non-necrotizing granulomas. Airway distortion, as noted on CT scans, narrowing, traction bronchiectasis, in the late stage of fibrosis. Airway hyperactivity can be seen in up to 20% of patients. And obviously, this can lead to airflow limitations. So on the pictures you see, this is a classic bronchial stenosis related to sarcoidosis down here at the bottom. My cursor isn't showing, but the one here in the right upper lobe is showing some bronchial stenosis. Granulomas or nodules. So well, the classic endobronchial sarcoid is characterized by mucosal islands of waxy yellow nodules that measure two to four millimeters in diameter. They're usually diffused, but they're not, and they're usually in the segmental airways or lower airways. Typically, when you have endobronchial sarcoid, there's always parenchymal disease. On CT scan, as they mentioned earlier, the classic is bilateral and symmetrical adenopathy, hylar and mediastinal, but sometimes can be asymmetric. And if the clinical picture fits and you have other findings like traction bronchiectasis, then there's very likely that the sarcoidosis is there. As with every other diagnosis, this sarcoidosis should be of exclusion. You need to rule out other granulomatous disease as it was mentioned earlier. PET scan is useful. I'm not going to get into detail, but PET scan can be useful in guiding therapy to look at areas that are active that have disease activity, or also it will guide you to get a biopsy. Bronchial stenosis is not as common. Can be solitary or multiple, lower or segmental. It's very common to see it in the right middle lobe or the right upper lobe, in that order. Sometimes you can have, like the bottom right picture, some web-like stenosis. And these are commonly and easily picked up on CT scan, even though CT scans don't typically report airway abnormalities if they're subtle. If you pay close attention, you may find those at the level of the segmental airways. Where you see the classic right middle lobe anelectasis, you cannot explain why that's happening. Patient comes with frequent post-obstructive pneumonias, and then you'll see this if you do a bronchoscopy. Bronchiolitis is also common. So in a study of 21 patients with sarcoid, 95% had evidence of air trapping and small airways disease, like shown here. And the CT scan shows mosaicism, like seen here, air trapping. BFTs, x-rays or radiological imaging, bronchoscopy, they're all three play an important role in diagnosing sarcoidosis that is involved in the airways. Bronchiolar involvement from sarcoid can also occur in early stage of disease as well. So how do we approach this? So the question is, which patient needs a bronch if it's not a diagnostic bronchoscopy? So you have your sarcoid patient you're treating for years, but then all of a sudden they come with new symptoms or maybe there's progression of disease. So really the question is, who needs a bronchoscopy? Well, you have to make use of the tools that you have, your PFTs, your imaging, and at the end, endoscopy. So restrictive lung disease is by far the more common finding in sarcoid, but obstruction can also happen, you all know that. So just obstructive disease pattern is more common in African Americans, up to 60% of them. What are the mechanisms of airway obstruction in sarcoid? Well, you have the accumulation of endobronchial granulomas and you can rarely have extrinsic compression for very large lymph nodes. That's not very common, but that's the mechanism for airway obstruction. You can have bronchiolar disease as well, as we said earlier. It can involve any part of the respiratory tract, so you have to really pay attention of what symptoms the patient is presenting with. You know, the common ones when sarcoid is involved in the airway is cough, dyspnea, wheezing, but if you have upper airway or supraglottic involvement, you may have dysphonia, dyspnea stridor, dysphagia as well. This leads to my next question. Mucosal abnormalities seen in sarcoidosis are more common in the lower and segmental airways. True or false? All right. We have 72 votes. Great. Yes. So I was just saying lower and segmental airways are more frequently affected. Central airway involvement related to SARCOID is not as common as lower involvement. So this leads me to talking a little bit about diagnosis like we heard about it earlier. So the gold standard has been transbronchial lung biopsies. The yield is 50 to 90 percent depending on what you're reading. And it's also dependent on the procedural list. It's also dependent on whether the patient has evidence of parenchymal disease or not. Now positive in the bronchial biopsies, they do correlate with bronchial symptoms in SARCOID. That's important to know. But if you don't have any airway symptoms related to SARCOID, you may find it in lomas. That's why we suggest doing the bronchial biopsies even though you don't have airway involvement that is evident at bronchoscopy. The combination of transbronchial lung biopsy and eBBX increase your yield. But eBST-TVNA has a higher yield compared to that. And that was shown in the granuloma trial in the Netherlands. This is an old study. The one on the right is showing that they saw like a very few patients, like 18 patients that suspected to have SARCOIDosis. They found that SARCOIDosis was more common on the right bronchial tree. And they took biopsies from all those main carinas, secondary carinas on both sides. And what's important to notice here, if you see in a fine print, and I'm sorry for the font size, but even in those patients who had normal mucosa, they did find up to seven patients had positive granulomas on biopsies. And of those who had no bronchial symptoms, up to 15% of them also show evidence of endobronchial granulomas. If you're doing a transbronchial lung biopsy, then it is recommended that you take at least six samples. And it doesn't matter if it is a small forceps, a big forceps. It doesn't matter if it's floating on your container where you think there may be alveolar parenchyma involved, or is it sinking down to the bottom. Because even if you have bronchial tissue, that may show granulomas. So it is recommended that you do at least six transbronchial biopsies. I found this, there's the algorithms that you see in ATS guidelines, but I found that this algorithm is very simple. It really simplifies what to do when considering tissue diagnosis for sarcoid, and I really want you to focus on the bottom part of it. So, if you have stage 1 and 2, EBUS-TBNA plus minus BAL, if you have only parenchymal disease and the bronchial biopsies, transbronchial biopsies, and I would say for sure do a BAL, because you also want to rule out other granulomatous diseases. If you have mixed nodal and parenchymal disease, then EBUS-TBNA is the first line, as opposed to mediastinoscopy, plus BAL and plus EBVX. So you would do biopsies if you don't have abnormal airways, main carina, two there, two on the secondary carinas, and go from there. What is the management? So the management starts by first identifying that you have, you know, involvement that is leading to new symptoms or symptoms that are debilitating, but really the cornerstone of treatment continues to be systemic. So if you have evidence of that, then you have to start steroids or whatever steroid spirit agents you want to use. If we start from the top, laryngeal sarcoidosis is the least common, it's about 1 percent, but in order of affection, arytenoids are epiglottic, false epiglottis, and false vocal cords, those are the more common sites. The pictures on the right, this was a study by ENT folks in the U.K. where they had the classic appearance of laryngeal sarcoidosis. What they treated these patients is with laser and instead of injection, and they did this pot pepper application to reduce the bulk of disease, and these patients did it well. Ideally, these patients were the least common ones of having sarcoidosis in the larynx. This is a classic appearance of nasopharyngeal sarcoidosis, so waxy and yellow plaques. By far the best treatment for bronchial stenosis related to sarcoidosis is balloon bronchoplasty, so balloon dilation. Do you need to do it if you see it? What I'm trying to say is probably not. You just have to make sure that the patient is getting the right treatment systemic, but if you have significant and multi-level airway stenosis, perhaps you need to try balloon dilation. This was proven in the past to be the more effective treatment for sarcoid in the airways. Standard injections have different outcomes in different small studies. It can be tried. What's in the literature is usually catalog 10 or 40, and the dose could range from 20 to 50 milligrams per injection. The patients who've had laryngeal sarcoidosis in the ENT literature have a significant response of standard injection in that area, but it's not as commonly used in the bronchi. CO2 and endiac laser plus minus. Airway stenting is not very commonly used in sarcoidosis management when it's involving the airway. Airway stenting has complications, and there's contraindications if you use metal ones in benign disease, but these are cases that were reported in the literature where they used the small ICAS stents in lower airways that have a good outcome and good opening of the airways, so those should be avoided unless it's last resort. My summary slide, cobblestone mucosa nodularity are the more common findings. Up to two-thirds of patients will have it, and it's often missed. If you have parenchymal disease, then it's likely that you have airway involvement, and combination of TBVX with EVX increase the yield, and bronchoscopic interventions only in addition to systemic therapy. Out of all those I mentioned, balloon dilation is the most effective, and if you have airway stenosis, that doesn't necessarily mean that you need to treat it endoscopically. Thank you.

pulmonary sarcoidosis

airway sarcoidosis

inflammation

granuloma formation

diagnostic test

glucocorticoids

methotrexate

biologic agents

nodules

mucosal changes