Chapters Transcript Sarcoidosis, Interstitial lung disease and progressive pulmonary fibrosis in WTC-exposed FDNY responders Course: Advances in Home Mechanical Ventilation: From the Iron to Artificial Lung This sets the scene for what we're gonna come back and talk about when we bring back those two cases, which is what do we do now? All right, they're on prednisone, low dose taper, they're on methotrexate. What do we do? The CAT scans are worsening, their breathing tests are worsening. So let's talk a little bit first about sarcoidosis in firefighters exposed to the World Trade Center and then talk a little bit about pulmonary fibrosis and see what you would all think that we should do afterwards. Uh, so, uh, I also don't have any financial disclosures. I, I do get a tremendous amount of, uh, financial support, the World Trade Center Health Program from each and every one of your taxes. So thank you very much, much appreciated. Uh, the millions of people that have helped, uh, with everything that I'm gonna show you today, uh, and of course all of our FDNY patients, it's, uh, I'm like a small town doctor for the fire department, it's great, it's absolutely fantastic. I've got the greatest job in the world. So right after 9/11 we realized that our firefighters and EMS workers uh exposed would need long term medical monitoring uh and treatment programs, uh, and we knew that there were gonna be three areas that we would, uh, have problems with and that we would concentrate on and of course the main area was respiratory disease, but we also knew about mental health issues which I won't talk about today and about emerging diseases cancer which I won't talk about today and sarcoidosis. Uh, we have a wealth of data, so we're the only group with pre-9/11 data, uh, as you could hear from Crystal's presentation pre-9/11, their PFTs were normal pre-9/11, their chest X-ray was normal. They did not have sarcoid. We're the only group with that, uh, and we collect a tremendous amount of data on annual medical monitoring and on their treatment visits, uh, and you can see all the data that we, we collect here which is then funneled into our, uh, uh, uh, data center. And our data center has all access to this data and then uh analyzes it. Prior to 9/11 we demonstrated in a paper in chest that sarcoidosis was increased in firefighters, all right, and that increase was compared to a control group of EMS workers, uh, in the fire department now. The access study with Doctor Judson had talked about earlier, uh, I believe had missed statistical significance for firefighting. It had it for wood exposure but missed it for for firefighting, but there was at least a signal, uh, in there, so we showed that that was true, uh, compared to a control group of EMS workers. Now after 9/11 there was a tremendous increase in sarcoidosis, uh, in our rates internally, but now we had a much larger epidemiologic group, so we're able to compare this to general population and there is no really great data on sarcoidosis in the general population, but there is the Westchester the, the Rockchester Epidemiologic Project that has a lot of data on incidence and prevalence rates, uh, from the Mayo Clinic and from that area. And the ethnicity of that area is very similar to the fire department, so it's the best control group we can get, and you could see that the age adjusted rate for sarcoidosis, new new cases of sarcoidosis in the fire department after 9/11 was about 26. Uh, per 100,000 males, uh, compared to the Rochester study which, uh, showed it was about 10 per 100,000 males, so definite substantial increase in sarcoidosis, uh, after 9/11 in the fire department. Uh, also, uh, there was, uh, a World Trade Center exposure gradient, so there was a greater, uh, incidence rates if you arrived, uh, on the morning of 9/11, which we call Group one, and, uh, great. Incidence rates if you were down there for at least 3 months uh and if we combine early arrival plus duration that's our high exposure index and you can see that there's uh an increased incidence rates there. Now this uh has been substantiated in other cohorts including the cohort here, the health and hospitals Bellevue Environmental Health Center, including the World Trade Center Health registry, uh, and including, uh, the non-FDNY rescue recovery workers, uh, which is called the general responder group and their data center is at Mount Sinai. There are of course some cohort differences compared to FDNY, uh, and FDNY is the only one of these cohorts, like I said, with pre-World Trade Center data. Uh, the other cohorts have greater diversity, the other cohorts have different exposures. Uh, with both Crystal and Carrie's help, uh, we did a study in 2016, uh, looking at 59 cases to see what the clinical course of their sarcoidosis was. Most of these patients had now had sarcoidosis for about 8 to 10 years, and we wanted to see what was happening over that time. Again, because it was the FDNY, uh, essentially it's all male and all white, uh, and 69%, uh, had retired by the time we, uh, brought them back for a full evaluation. This full evaluation included everything eyes, lungs, methylcholine challenge test, PFTs, cardiogram, echo, all right, included everything, all right, and a full physical examination, full PFTs, the whole bit. Uh, median age was 43, 90% were never smokers, uh, and only 1 person of the 59, uh, had a family history of sarcoid. And this demonstrates the clinical course and Uh, you can see the count, yeah, great. So, uh, all of these patients, uh, except I think one had, uh, intrathoracic sarcoid, so they had for the most part all of them had both enlarged lymph nodes and, uh, infiltrates, in other words, scatting stage one. A few of them had scatting stage 2. None of them had scatting stage 3 or 4, and, uh, I'll show you their PFTs in just a moment, but they were essentially normal. But over the course of time, all right, on average about 8 years, some longer than that, uh, but all these are post 9/11 sarcoid patients, uh, over the course of time you could see that as it's shown, been shown in the literature, uh, there was a substantial resolution of intrathoracic sarcoid. It went from 98% down to 54%. So, down to, yeah, down to 54%, so about 46%, uh, wind up resolving, all right? Uh, but using Wassa criteria that Doctor Judson had already discussed with you, uh, there was, uh, an increase in extrapulmonary sarcoidosis. Uh, and the extrapulmonary sarcoidosis, there was no cardiac disease at. Uh, entry into the study at diagnosis, uh, there was a few patients who, uh, complained of joint disease, uh, arthropathies, uh, but, uh, when you look at the end of the study in 2016, uh, that 7% with joint disease had increased to, uh, to 15%, and the 0% with cardiac disease had increased to 16%. Uh, now I've updated these, uh, with our sarcoid, uh, as of 2025. So what I just showed you before was published, but this is now an update. We now have 119 cases of sarcoidosis post 9/11, and cardiac sarcoid, uh, has increased to 20%, and joint sarcoid has increased to 22%, and I'll show you later that we have a few cases of progressive pulmonary fibrosis. Now this compares to the access study that looked at uh at diagnosis and then at a follow-up time period they had 4% with cardiac increasing to 6%, they had 1% uh increasing uh and not increasing at all with, with joint disease over their time period. Now, I grant you there, there are differences in how aggressive cardiac sarcoid was diagnosed over this time period. So, uh, in the access study they did not do cardiac MRIs. Not quite certain if they did echoes. Did they do echoes on, on all these people? Just 2 year follow up, OK. Very important, but they, they didn't do echoes, they didn't do cardiac MRI's in our study at entry, we did, uh, uh, EKGs and echoes in most of these patients at the time of their diagnosis that we did not do cardiac MRI's at the follow up time period we were now starting to do cardiac MRI's on every one of these patients. So there is a difference in how aggressive the diagnosis is being made, but nevertheless, the percentage has increased substantially. Uh, so cardiac sarcoid, uh, has already been discussed today. No gold standard. We now rely on cardiac MRI for the diagnosis. All of our responders are getting cardiac MRI for diagnosis and if positive, they're moving on to cardiac PET scan. Uh, and you know it's certainly a question that maybe we've over diagnosed this because we're doing cardiac MRI's on everybody, but I would say that we haven't because we've had a substantial percentage of these people with active, uh, cardiac sarcoid in terms of active inflammation by PET scan, and we've had a substantial number of these people that have qualified for, uh, uh, auto defibrillator placement, all right. Uh, so this higher prevalence may certainly be due to the fact that we're more aggressive at diagnosis, but also possibly due to a shared exposure, the World Trade Center and firefighting and possibly an underlying genotype, uh, so we believe that. Everyone should be moving towards cardiac MRI, but certainly in, uh, first responders where, uh, like autopilots, uh, you don't want them to fail while they're rescuing you, all right, uh, our treatment's already been discussed here and, and we follow that recommendation starting with prednisone, going to methotrexate and then to TNF blockers. We've had great results with, uh, adalimamide, Humira. Uh, we use Remicade only if they're very severely reduced, uh, problems. All right, so moving on now, uh, to pulmonary sarcoidosis, uh, we have, uh, very few patients that have gone on to progressive pulmonary fibrosis. Uh, as I said to you, we, the vast majority of our patients, 46% of them have actually had resolution of their intrathoracic sarcoid over time. But a small number have uh moved on both in terms of scatting stage CAT scans to show interstitial lung disease and then progressive pulmonary fibrosis, so you've got the access study in the middle uh with uh 735 patients and then you have FDNY, uh, with at the time of our study in 2016, 5555 patients, it wound up that there were, uh, 4 patients, uh, with, uh. Uh, stage three, all right, but as of 2025, we've had one additional case, and these cases have moved on, uh, by scatting stage to be stage 4, and I'll show you, uh, that by CAT scan they've shown both interstitial lung disease and, uh, uh. Uh, 2 of them are progressive pulmonary fibrosis. I'm sorry, 3 of them progressive pulmonary fibrosis. So when they don't develop pulmonary progrosis, their pulmonary function tests have remained normal and uh have remained stable. They have not required treatment, so you can see here, uh, over time period, uh, at diagnosis and then at follow up they're essentially in the 80 to 90% range, uh, including their DLCO. But once they develop interstitial lung disease and pulmonary, uh, fibrosis, it's a different story. So we decided to look at all of our patients to see how many were developing interstitial lung disease and pulmonary fibrosis. Uh, so we looked at the literature to see what, what should we be comparing to and interestingly, uh, the literature is, is absolutely terrible, uh, on, uh, showing incidence rates or or prevalence rates for interstitial lung disease. Vast differences in cohorts, and how aggressive they are at how they're defining it, vast differences in, uh, uh, uh, in the statistical approaches to, to doing it. I'm not talking about the studies where they're looking at, at drug interventions. I'm talking about studies where they're just looking at determining what the incidence and prevalence rates are in the United States or any country. Now the largest study, all right, of 37 million patients in the United States, huge, right, uh, is based on healthcare claims, all right, and they did an age and sex standardized incidence and prevalence rates based on the US 2014 population, so that's what we decided to repeat. But, uh, as you said for the Invo study, all right, there are sarcoidosis patients hidden in this, so they just took all of these patients based on health claims and just shoved them all together, right, and they don't provide you as with the invo study, they don't even show you other and and the other groups, they just put them all together and you never know. They admit that there are sarcoidosis patients in there, but that you never know how many there are, all right, uh, in addition, because they used health claims. Their health claim data was based on sarcoidosis with lung involvement, but they're not able to tell how many had progressive pulmonary fibrosis. So, uh, we repeated that study, uh, but we don't have 37 million claims. We have 15,000 firefighters, but we do know who actually has interstitial lung disease and we do know actually how many have progressive pulmonary fibrosis based on PFTs and CAT scans, so we don't have a bias based on, on health claims. Uh, to make our study as rigorous as possible, we required, uh, that the diagnosis, the criteria for ILD, uh, and for progressive pulmonary fibrosis had to be confirmed on at least 2 CAT scans, uh, 1 year apart, all right? We excluded, uh, unilateral disease. We excluded ILD diagnosed prior to 9/11. We excluded. Fibrosis or ILD that might have been radiation induced and to eliminate the potential for COVID-19 poisoning our numbers, we ended the study at 3-1-2022 before there could be uh COVID ILD or COVID uh progressive pulmonary fibrosis and in fact there was a lot in our group there was 26 uh that did have COVID issues and we excluded them all all right by ending the study at 3-1-2022. Uh, for the difference between ILD and progressive pulmonary fibrosis was based on ATS criteria, uh, which required two of the following physiologic evidence decline in forced vital capacity or DLCO CT evidence of, of progression, and you could see that there was progression in those cases that were just ILD. 20% had traction bronchiectasis, 0% had honeycombing. In those patients that had progressive pulmonary fibrosis, traction bronchiectasis went up from 20% to 60%. And honeycombing, which had been 0%, went up to 48%. Uh, so this is, uh, it includes sarcoidosis and non-sarcoidosis patients. It's a prospective study. It's two decades of follow-up, so it gave them enough time to develop these conditions. It's the only study with pre 9/11 and also pre-diagnosis, uh, lung function and, and. And the reason why that's so so important is because we hypothesized prior to doing the analysis one of our main, we had two main purposes one was what's the incidence and and prevalence rate, but the other one was would pre-diagnosis force vital capacity predict who developed ILD or predict who developed a progressive pulmonary fibrosis. Because that would be great because then we would be able to really develop a phenotype for more aggressive uh monitoring, diagnosis and, and early treatment. So those were our two, hypotheses or goals, all right, uh, and, uh, we knew who had sarcoidosis. They were of this group, there were 99 patients with pulmonary sarcoidosis. There were 5 with ILD and there were 3 of the 5 had progressive pulmonary fibrosis so we did a separate analysis without the sarcoidosis patients and then we did a separate analysis adding in the sarcoidosis patients. This we can skip. You can see here that uh as they developed ILD in the top line, sort of the grayish line, uh, their lung function declined, but in the bottom line, which is sort of orangeish, uh, their lung function declined even further, even more rapidly if they developed, uh, progressive pulmonary fibrosis, and this is from time of diagnosis. So our results uh was that uh the predictors of ILD uh were what has been known in the past age, smoking, and GERD, uh, but unfortunately we were not able to show that force vital capacity either pre-9/11 or post 9/11 or pre-diagnosis or at the time of diagnosis or any way we cut it, uh, the force vital capacity was not predictive of who developed ILD. We did those same prediction, uh, models for PPF, uh, progressive pulmonary fibrosis, but we had too few cases in the total group, we had only 40 cases, uh, and only 3 of those were sarcoid cases, so, uh, we were not able to find anything. Uh, predicted for pulmonary progressive fibrosis, but that was uh a power issue, all right, but what we did show was that of the 80 ILD cases, 40 developed progressive pulmonary fibrosis, which means 50% went on to develop that and. Uh, that is a, a huge percentage, much greater than in the literature, even though the literature is, is terrible on this subject, but it seems that the literature says that of ILD cases, about a third at max will go on to progressive pulmonary fibrosis. Here with these strict definitions, uh, by CAT scan and PFT, half went on to do that. All right. Uh, and the average lifespan was about 8.5 years and. Most of those deaths were due to the ones in progressive pulmonary fibrosis. Uh, this is just showing what I already showed you. Uh, so in terms of the numbers, uh, we had a twofold increase compared to the general population of ILD. Uh, we had a substantial increase, uh, in pulmonary progressive fibrosis, and if we added in the sarcoid cases, uh, these numbers were even more dramatic, uh, an additional twofold increase in the ILD cases. So conclusion before we get back to our cases, uh, at least in the FDNY cohort for sarcoidosis, we had a substantial resolution of intrathoracic involvement. I say greater here really I, I should say about the same as what's expected from the access study. We had less ocular disease almost. Very few ocular cases, no hypercalcemia. We had a lot more arthritis and for a topic of a totally different, uh, talk, they don't respond to hydroxychloroquine and they barely respond to, to steroids. They really needed aggressive therapy, but that's a different topic. We had more cardiac disease. Uh, and, uh, we have, uh, uh, a, a small number of cases that have progressed on to ILD and then to progressive pulmonary fibrosis. Published March 26, 2025 Created by
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