Okay, the next lecture is on Berlin sensitivity and chronic brilliant disease. I'm very pleased to present John O'Neill MD MPH. F. A. C. O. E. M. Dr. O'Neill graduated from University of Kansas with a degree of degree in history of art and received an M. D. From the University of Kansas School of Medicine. He completed an M. P. H. and residency in occupational and environmental medicine at Harvard and later completed a masters of fine art in screenwriting at UCLA. That's pretty cool. He recently retired as a lieutenant colonel and senior flight surgeon from the Air Force, having served 10 years on active duty and in the Kansas Air National Guard. He has consulted or worked for major corporations, including Boston Gas, Polaroid, Boeing, Rocketdyne, BNSF, and Union Pacific Railroads, the USAF, Army, VA, and Navy. He is the author of the textbook, the bloodborne pathogens standard of pragmatic approach and is the writer, director and producer of an introduction to occupational environmental medicine video. He is currently the civilian consultant and occupational medicine for the Navy Bureau of Medicine and surgery based out of Falls Church VA. Welcome Dr. O'Neill. Thank you. Great. Thanks to be back. I guess my take home lesson from the last lecture was pro football players cannot be pilots. If you own that going to start off, see a couple of familiar faces from yesterday. So I'm going to ask a couple of questions from my lecture. Why am I not a vegan? Yes, something sucks. Try this a little harder one. Anyone remember any of the three movies I recommend you watch? Forks Over Knives, What the Health, and for performance, The Game Changers. The Game Changers is absolutely phenomenal. So you can watch that I think on networks or Amazon Prime, particularly when you're talking about performance. The first two were about cardiac, but the other one is about performance. So it's something called The Game Changers with elite athletes saying why their body heals up better on a plant based diet. And another thing, let's see, the last question was Bill Self, the KU basketball coach, could not coach yesterday. He's just released from the hospital for what routine procedure? I was going to say stats, but I was going to ask what the two was. There we go. And KU did play yesterday and beat Howard University. I'm from D.C. Sad about that, but it's number one for the 16. So we're going to talk a little bit about beryllium sensitivity. I'm going to first ask, do any of you all have worked with beryllium or work with beryllium exposed workers? Anybody in the room? OK, so a couple, obviously, probably aerospace or something like that. So this one, this lecture then will not specifically relate to a lot of you. But I want you to look at it as sort of like a case study in chemicals and exposures and and how to do and not to do maybe some screening examination. So I want you to think about that. You may not be dealing with beryllium itself, but you'll get a little bit of knowledge about that. But also look at what the risks are sometimes when you do screening programs with relatively inaccurate tests and with things that are legislated versus stuff based on reality. I don't know if you know about this, but we're going to go through a lot of stuff with PFAS quote forever chemicals. The military is now under the National Defense Authorization Act as of last year. We are required to offer that to our firefighters, and we don't really know what low levels mean. It's a very, we don't know where the threshold is, but we're going to end up spending hundreds of millions of dollars of testing this. It's now even going out. Basically, people are some of the researchers are saying, well, there's no safe level. That's a whole other thing. So let's talk a little bit about beryllium, beryllium sensitivity, and how I got involved with this was when I was actually in film school. I started in 2000. I was there for two years. I was the, I sort of needed some fun money to be able to eat and go. So I took a part time consulting position for Boeing Rocketdyne, and they, at the time, made the space shuttle engines. We were still having space shuttles and repairs, and beryllium was used as a composite in the engines. And I'll talk a little bit about that, but they had had somebody in one of their plants. Rocketdyne had been bought by a couple of different people. It's no longer with Boeing. I think it's somebody else's asset. But they were, they had done some screening. The test had just come out, and they actually had somebody that had died of chronic beryllium disease. And Boeing was very aggressive. They were not required to do this, but they went ahead and said, we are going to do a screening program and try to do that. So they looked very closely. They also put a circle around where they were drilling and sanding on the engines, and said they then administratively controlled who could go inside the stuff. So that was the first thing that they did. This was sort of retroactive. But I came in, and then we had just tested over 400. I'll go over those results in just a bit. And then I'll go over how we had to deal with some of that stuff, but I'll give a general overview of beryllium. I have no disclosures on this. Beryllium, it's a light, it's a very light metal, atomic weight of nine. It has a very high melting point, which, of course, makes it perfect to put in space shuttles and aircraft and stuff. It's very hot and very light, high tensile strength. It's very strong. And it's actually got really good electrical and thermal conductivity. It's corrosion-resistant, improves metals when it's alloyed, which is what happens. It's alloyed with other stuff. And it's ubiquitous in the environment, i.e., it's around naturally. So we all have a small amount but very low exposure to this. And this comes into play because it's actually a sensitizer. Occupations with beryllium exposure, we talked about aerospace, some in ceramics. I'm not going to go over all of these, but it has been used a lot in high-tech industries. And for a while, it was used in dental amalgams. That had created some problems, particularly if it's a sensitivity thing. Beryllium timeline, it was discovered in 1798. In the 1930s, and this is really typical for a lot of our exposures, were first discovered and looked at in Europe. And we were a decade or two behind in really following some of this stuff in the 40s. And that's when we really looked at the problems. 1949, the U.S. Atomic Energy Commission set an occupational exposure limit at 2 micrograms per meter cubed. That stayed that way until a few years ago at the 2.0. And basically what happened was they had really high exposures. And the OSHA, and this is what happened. When OSHA came in in the 70s, they just point blank adopted all the exposure limits that had been set by ACGIH, adopted in blanket. Once OSHA got started, to change any of those limits, you have to go through the complete OSHA rulemaking process, which takes years. They're now looking at that for the asbestos, the lead levels, because we're way behind where the science is on the level of lead. But they didn't adopt one for beryllium. Well, they adopted beryllium, but they didn't have a separate standard on it. So they just adopted all these permissible things, but there was no really beryllium standard. So in the 1970s, when OSHA was created, and OSHA was actually created, anyone know who the president was when this happened? It was Nixon. And I highly doubt there would be a Republican president today that would put in anything that would put limitations on industry. That's a whole other political discussion. In the 1980s, we actually found sensitivity testing, and I'll talk some about the beryllium lymphocyte proliferation test in just a bit. And in the 1990s, we found out there is some genetic susceptibility. And guess what that means, that we cannot ask for, for workers. Under GINA, the Genetic Information Non-Discrimination Act, we can't ask for some of those things. But it's a small part, but it is there. And this played into one of the reasons why there was concerns about genetic information. The big thing about driving GINA, some might remember one of the major railroads, I was peripherally involved as a consultant, found out that carpal tunnel syndrome may have some genetic component to it. And one of the railroads was going to test the railroad workers for this. Guess what? It's a very litigious thing. They went to Congress, and it basically came down, not only no, but hell no, we do not want employers doing genetic testing on any of us. Now, what's happened is the genetic testing under GINA has been defined as asking any family history, which basically means when you do a pre-placement examination, you cannot ask any questions about your family history. I'm now trying to get the DOD to understand they cannot use generic forms right out of their personal history online about that. And it's a long, complicated story, but the DOD has been doing stuff for a long time. That's a whole other discussion. I'm sort of bringing in some of these other things just to make it interesting because you're probably not going to be dealing with brillium. But that's something that's really important for us to know. We cannot ask about family history. So if you're working in a family practice, internal medicine clinic, and you give a routine new patient exam, illegal. It's actually the findings that now come out from ADA and EEOC that you cannot even request to have access to their personal medical records because not only is it illegal to get them, but it's illegal to ask for family history. And if you sign a release, that's what the DOD has been doing, is having people sign a general release to look at your medical records. You can't even ask that because those medical records may contain that. Okay, I will get off of my—I guess I am on, so I'll be up here for a while. Brillium-related diseases. First off is acute brillium disease, chronic brillium disease, brillium sensitization, skin disease related to brillium exposure, and cancer. Acute brillium disease, World War II, we greatly increased the use in aircraft and aerospace and other things. And the people that had high-level exposures, and this pretty much came from people that are grinding and grounding, putting stuff together. Those high-level exposures caused a chemical pneumonitis, pulmonary edema, and some cases of death. But these are very high doses. And the people that survived some of those, some of them went on to progress to chronic brillium disease. And in those studies with the very high doses, they found later that only about 17 percent of people that had high enough exposures to have some symptoms for acute brillium disease then went on to develop chronic brillium disease. It was extraction and production plants, extremely high concentrations, much more higher than we do. And this is sort of the same thing that happened in World War II with Navy and asbestos. And one can argue that the creation of the specialty of occupational medicine really in the 70s came about by all the people exposed to asbestos in the 40s and started then having symptoms 20 or 30 years later. The first people that really were doing occupational medicine were pretty much pulmonologists, dealing with asbestos, some with brillium, and coal miners disease, black lung disease, and I guess cotton disease. Anyways, so what happened was they said, okay, we're no longer going to have these very high doses, exposures, and we no longer see high-dose exposures in the United States. Chronic brillium disease, and where it comes from, are low-dose exposures in the 1940s. Brillium was used in fluorescent lamp workers, and they were developing symptoms. And basically, they looked at it, and in 1940, the lamp industry decided to discontinue the use on it. They realized its exposures. They were looking at the stuff, and so they no longer used brillium. Anybody know the other chemical that's still used in fluorescent? Mercury. So there's still some mercury stuff. There is a plant, one of the few remaining fluorescent light bulb plants in the country, in Salina, Kansas, and I actually consulted with them and had some cases of some mercury exposure. They did a stupid thing. They hired some people, had them work there, and didn't do the preplacement baseline test until four or five months later, and they developed some symptoms. And it was a really complicated case to try to say, well, you know, maybe she's got a lot of fillings and stuff like that. But we look at that. We're still using mercury in one small area in this plant. Chronic brillium disease, old. We used to call it brilliosis. We no longer use the term brilliosis. So now we're looking at chronic brillium disease. You'll see it referenced as brilliosis. It's probably okay, but the real term now is chronic brillium disease because that's to discern it from acute sensitization. Symptoms, dyspnea, cough, chest pain, fatigue, weight loss, and some dermatitis if you have exposure on your hands or face. X-rays showed diffuse infiltrates, small random opacities, hyaluronidinopathy, and pulmonary function tests showed both restrictive and obstructive defects with interstitial findings. I don't know how well you can see this, but this is pretty much typical. We don't see a lot of that now, again, because we don't have really high, high, high levels of exposure. Here's another one. It shows a little bit more of the interstitial. See how that's a little fluffier than other parts? We're not really seeing a real definition there. Okay, and so 1972, OSHA creates the permissible exposure limit of 2 micrograms per meter cubed, and the OSHA regulates… Interesting thing to know about OSHA, they regulate on symptoms and irritation. OSHA does not really regulate based on sensitivity or hypersensitivity, and the reason that is is OSHA had standards set on hypersensitivity. Most exposures would be so low, they wouldn't be able to obtain that. We couldn't work with a lot of chemicals. So, OSHA doesn't really look in setting their levels at sensitivity or certainly hypersensitivity. They're sort of set on basically symptoms of irritation. They do take… The other… NIOSH in other places take into effect the cancer-causing effect, but most of the initial OSHA stuff was for sensitization. 1979, we had the beryllium sensitivity test. I'll talk about that in a bit. By 1983, the incidence of chronic beryllium disease decreased, and that's because they stopped having the high-dose exposure. And as much as people think OSHA is a four-letter word, the fact that they came in and we decreased, you know, high-level exposures to a lot of different things… Chat question. Okay, I'm not used to looking at chat questions. No, I'm going to answer these after. How's that? Is that okay? So, OSHA… OSHA said… So, they… What OSHA did when they came in the 70s, still allowed exposures, but we no longer had really great exposure, really high-level exposure, and this would happen with beryllium. So, we stopped really having a lot of chronic beryllium disease or berylliosis. In 2002, OSHA put out a beryllium request for information. This is the start of the process to do standard formation. You put out a request for information. You get that in. Then you put out what's called an advance notice of proposed rulemaking. Then you get other information back, and then you put that together, and then you do a notice of proposed rulemaking. And then, once you have the notice of proposed rulemaking, you have people that send in testimony, or they actually have hearings in person around the country, and they send a lot of information in from all sorts of different stuff. OSHA doesn't just listen to NIOSH, to the doctors. They listen to the employers. They listen to the employees. They listen to lawyers. So, it's not just medical. The medical branch from the OSHA Act was NIOSH. Created separately, OSHA was put under the Department of Labor. NIOSH was put under the Department of Health and Human Services. They have different functions. OSHA does not have to listen to NIOSH, and that's very important for people to understand. So, NIOSH had a relative exposure limit set of—ACGIH at the time was 0.05. This is in 2007. We learned enough about it based on sensitivity and other types of stuff. NIOSH, their recommended exposure limit was 0.05, which is a fourth. The ACGIH was 0.05, so significantly lower, and that was for their acute threshold limit. And a short-term exposure limit of 0.2, which is still one-tenth of what it had been. 2017, finally, finally, OSHA got through. They did do a standard, and they created a standard on beryllium exposure. Anybody remember when that happened or not? It happened in 2017, but the reason it got through is it got through because there was eight years of the Obama administration. This process took so long. It took eight years, so the process finally got through, and it was approved and published. And then the new—the following administration came in in January, and it was too late to shut this down. And, again, it's political, but if you look at what the influences are on OSHA, certainly somewhat on NIOSH, and certainly in the last few years on CDC. But the reason the beryllium standard got through because there was eight years of one administration that was long enough to go through. If you look at admins that are only there for four years, a lot of this stuff has killed. There had been—they spent years trying to get an OSHA ergonomic standard. That got killed. People tried to spend years getting an indoor air quality standard. That got killed. I actually testified at OSHA hearings for two and a half hours as the DOD representative because I was doing indoor air quality exams for the Air Force. I got grilled by the tobacco community. And I said, well, it doesn't affect me. We're not smoking in military buildings. But we really had great data on that. But the interesting thing is the politics of stuff getting done. So there is no definition of acceptable air quality in this country, which means we have no definition of poor air quality. And the tobacco lobby was upset about it. They didn't want to not only said, stop, you're not going to do it. They went to Congress said no, but not hell no. Because if we regulate it on particular matter, you wouldn't be allowed to smoke in any workplace in the country. That was what the tobacco lobby concern was. So anyways, I'll get down off of my soapbox. But I'm trying to give you some understanding about how long it takes to get this. So here we now have a NIOSH recommended exposure level, which is 0.05. And the current OSHA one was 2.0. Pretty significant differences in this. Chronic beryllium disease new. So now we have new chronic beryllium disease diagnostic criteria. I'm sorry, go back one slide there for a second. Let me see if I got us 2017. I see 0.2. Is that a typo? No, no, that 0.2. That's the new standard. That's when the standard came out. Right. Okay. So the standard got more. The standard got 10 times more restrictive. Correct. You said the new administration did away with it. No, it was too late. It came into being. It already had gone through the whole federal system. And you can't stop it once it's gone past a certain level. That is the level. It was published in the Federal Register. Once it's published in the Federal Register, it becomes sort of, a standard is not a law, but it basically is what we have to comply with. Okay. So yes, in the 2017 was when it came through. So they started this process in 2002. That's how long it takes to get this stuff through. But the other thing is industry and people realizing this is a big enough problem that we need to have a standard on it. Okay. New diagnosis, confirmation of beryllium sensitization. I'll talk about that. Pulmonary granulomas on biopsy. So now you can have chronic beryllium disease without having symptoms, having a normal chest x-ray and normal lung function tests. That sort of creates some problems when you're testing for a population because we're now telling you you have some type of disease or something without symptoms. Do you think that creates problems in the medical legal system? Absolutely it does. It also creates problems where people that have no symptoms are going in to get lung biopsies that prove that their lungs have some inflammation to get diagnosed with this. I'll talk about that in just a bit. So the new definition, there's really no definitive medical criteria for chronic beryllium disease. You consider chronic beryllium disease if they have a history of beryllium exposure, a positive blood or BAL, bronchial alveolar lavage, lymphocyte proliferation test, non-casein granulomas for mononuclear cell infiltrates for lung biopsy. So guess what? There were a lot of lung biopsies done. And there were at the time some take-home cases where people at home, part of the beryllium dust and stuff was taken home and people actually developed, again, no symptoms, but they were found to be sensitized. Some other family members found to be sensitized. Negative tests on PFTs and x-rays, but they did do a lavage and found some inflammation of the lymphocytes on that. Treatment for chronic beryllium disease, there's really no cure. I am not actually doing treatment. Really, there are only a couple of places in the country that do treatments. The main one is in Denver with a national Jewish. It's basically the world leaders on this. So I pretty much send people to them because they're the ones that look at it. The only thing that we know has worked pretty well is putting people on steroids. It reduces the symptoms, improves lung function, and the side effect is you get a lot of muscles from it. Lifelong treatment, you're supposed to, like, realize this is a dry humor and not just take that seriously, okay? I put the slides in so people will at least look and keep you sharp on this stuff. At higher levels, I've never done it, but it's reported that people may use some methotrexate on some of it. Beryllium sensitization, and this gets complicated also. So there is a skin patch test you can do for beryllium sensitization. The problem is we don't use it now much because guess what it can do? It can sensitize you, your whole body to the beryllium. So we're not really doing that anymore. There is a blood test, a beryllium lymphocyte proliferation test. There's a lung wash test. We use the same thing I'll talk about in a bit, but not everybody that's sensitized will go on to develop chronic beryllium disease. It's a pretty good marker, and the vast majority of people that have chronic beryllium disease will test positive, but there's some that don't. And it's believed, though not completely proven, it's really believed that sensitization precedes development of disease, and we actually have people evaluate it every one to two years. Chronic skin disease, contact dermatitis, I don't know if you can see this right here, but it's direct irritation, skin sensitization, also nodular skin lesions, granuloma, and has occurred in chronic beryllium disease patients with inhalation exposure only, which means that somehow it gets out into the skin through the body in different places. It's rare. I've never seen a case. Again, we're not really having high levels of exposures like this anymore, but it is something that has occurred. There were two cases of gingivitis that occurred from dental alloys, and these were workers that were mixing up dental alloys to put in fillings, and they then developed some skin disease from that. Again, not a lot of stuff lately. Beryllium in cancer, this is actually pretty controversial. We know it's a known animal carcinogen, but as you may know, when we work with animal studies, we expose people at very high levels, sometimes 100 or 1,000 times what the regular level is for other stuff. So, when we look at it, we know it's a known animal carcinogen at very high levels, and the studies that have been done on cancer in human beings, guess what? We're done on the people in the 40s and 50s and 60s with very high-level exposures. So, we don't know where the threshold is. Data suggests there's a lung cancer link, but low potency, we don't know. So, high-level exposures to animals and to people with high-level exposures, yes, or something. The debate is whether it's ever caused cancer in humans. There have been some studies done. There's one main Beryllium manufacturer. It used to be called Brushwellman, and now they were sold as now called Materion Wellman, yeah. So, and the study—so, they did a study. They sponsored the study, but here's the deal is that, yes, it was sponsored by the end of the company that makes it, but they're the only ones that make it. They would want to have this information. So, here's a study that came out recently. This was—what was the date on it? Relatively recent, 2016, and it was done by someone at Mount Sinai, but it was also funded by them. But basically, it said there's no difference for low-dose exposures. We don't find anything. So, there is one study, and you have to look at that. That's why they hired a center at Mount Sinai. If you know the history of the Mount Sinai Occupational Medicine Program, this was the one that had represented workers for years, the unions for years, and really did the stuff with asbestos and got the program really started. So, the mortality study or current exposure limits really shows no excess excess cancer. So, now if you look at—I'm going to say then, which is back in the 40s, which is high-dose exposures. I'm going to say now, where we have relatively—we still have exposure, but they're relatively low-dose. Acute disease, then, we had a lot of it. Now, don't have really acute disease. Chronic brilliant disease, then, we had a lot of it. Now, we have a little, but it's still present. Dermatitis had some, now none. Sensitization, we didn't really know about sensitization back then because we didn't have the test to find that. Now, we have some. And cancer, questionable with high-dose exposures back then. And now, we really don't know, have evidence of that. And the problem is, is when you start regulating based on exposures, when we don't really have proof that this level caused stuff, it's a lot of money that could be wasted that people look at. Okay, current. So, now let's talk about what we're looking at currently. The current problems with brillium deal with chronic brillium disease and sensitization. And I'll spend the rest of time talking about brillium screening. In 1999, the Department of Energy started a chronic brillium disease prevention program, and their goals were to reduce the number of exposed workers, minimize the level of exposures, and detect disease earlier and improve knowledge about this. They also, the U.S. government also created what was called the Energy Employees Occupational Illness Compensation Program Act. We called it EIOIU. What's the song? I forgot. EIOIU. We called it, because we couldn't get all the stuff. But it was basically, the Department of Energy wanted to look at compensation for stuff. Act of Congress, again, political, in 2000, and they had a part, it came into, and basically what it said is anyone that worked for the Department of Labor that had exposure to radiation, to brillium, or chronic silica, or silica, got a check for $150,000. And what that meant was, it is the first part of this, paid out over a billion dollars for this compensation program. What that meant, you know, for radiation, again, you're going to have to have a cancer. For silica, you're going to have to have silicosis. But guess what? For brillium, do you need to have symptoms? No. On biopsy. That's where they're good. So, you're getting a lung biopsy, or taking a chance to get a check for $150,000. Do you think a lot of these were done? Oh, yeah. Yeah. Okay. Then, that was so successful. That one. Then, they had a Part D that opened it up for any illness, or any toxic substance exposure. And they said, oh, this is so good. We'll do this. So, again, this was for Department of Energy employees only. The politics was pretty strong. And I actually did some consulting at this time, at Part D. I was living in Kansas, and they flew me back to D.C. one week a month to look over this. And we were looking at stuff that's, they were flying stuff for breast cancer, and prostate cancer, and all sorts of different cancers about these exposures. And that's where I really became sort of an expert in what's called causation determination. Does this exposure cause that? And, again, we cannot absolutely, we cannot prove something. We have to disprove the null. And it's a long, complicated exposure. But it was a really great experience for me. I think I did this for six months, and then I got tired of flying back to D.C. But it was really, really great fun to look at that. But we had all of these people saying, oh, here are the radiation exposures, the silica, the beryllium exposure, recalling all these different things. And that's where I became very acutely aware of the difference between medical causation and legal causation. And a couple of you may have heard my causation determination lecture in Boston and talked about that. So, that was Part II. It was switched over later to the Department of Labor. They tried to simplify and expedite this. And they actually had some other non-physicians doing the review. That's also another reason I've been doing it. Yes. Where did they file their claim with? Straight to, or is it FTC? It would be under the Department of Energy. So, you just get online and look at it. I haven't worked with the program for a couple of years. I assume it still may be there, but they may have run out of the funds for this. I haven't seen them lately. And it's now under the Department of Labor. So, yeah. So, I haven't worked with it for a couple of years. There's two of these programs. One is under the Department of Labor, and one is under the Department of Justice. That's where I was wondering, because I know we, and I have to go into litigation on these. No, but the Department of Justice, we had to teach the Department of Justice how to look at spirometry results. Like, we did that. I was at the university. So, there's two different programs. And I know NIOSH still does the x-rays for these programs. They still used to be reading stuff on it. NIOSH, that's for that. It's for contracts. I think there's one kind you can file. Yeah. My two programs, it's very complex. What you want to do is, if you're doing that, talk to a lawyer that's in that world. Because there's two programs, and it depends on whether you're working, whose stuff you're working with. Because DOE owns some of it, and contractors own some of it, and the Department of Defense owns some of it. It depends on, it's the same stuff. It depends on who you work for, which program you're on. And it continues to go on, because- It's time limited, too. Yeah. And the states can file for that, if somebody dies. So, again, look, I would just Google EEOICP, and look at that. Okay, good. It's very interesting. Really, in medical surveillance. And so, this is what we did before the standard came out. And this is a company I worked for that wanted to do the right thing. It was pretty aggressive, wanted to do some surveillance. So, they did a blood test. I'll talk about that. And it was required for all employees that had beryllium exposure. And it was offered to all employees with historical beryllium exposure, even if they've retired. The company wanted to do the right thing and look at it. It was given to former employees as requested and warranted, and they did periodic testing to people who had exposure levels above 0.1. So, sensitivity-confirmed positives were offered pulmonary function testing, chest CT scan, bronchoscopy. And basically, you can take the white cells in blood, but you can do a bronchoalveolar lavage and get those white cells. Those probably are a little better, because those are the white cells right there where the exposure happens. And then you can do a lung biopsy and continued follow-up as indicated. They also did high-resolution computed tomography. And even people with diagnosed chronic beryllium disease on the high-res HRCT, 25 percent had normal. So, it's not a really precise test. So, let's talk now about the beryllium lymphocyte proliferation test. And you're really looking at the beryllium-specific immune response and beryllium-reactive. So, what happens is, to simplify it, you have lymphocytes, you're exposed to beryllium, the beryllium gets into lymphocytes, they recognize it. If they're re-exposed to beryllium, these lymphocytes grow, proliferate, and that means they have prior been exposed to the beryllium. What does this mean? We are using live human cells. What does that mean? The test must be done within 24 hours of being drawn. What does that mean? There may be three places in the whole country that do this test. And you have a question? So, not done very much. Do you think there might be some problems with the test? Oh, yeah. So, we're looking at the, do they proliferate to beryllium in vitro? Cultured blood with and without. So, what you do is culture blood with and without the beryllium and assess what's called a stimulation index. That's the term they use, the SI. Stimulation index is how much they proliferate, how much they're stimulated if they are re-exposed. If they're stimulated, the assumption is they have been sensitized. And it can be used, again, on lung cells, and that's a secondary thing because those may be more sensitized because they're getting the, most of the exposure in the lungs, not through the skin anymore. The stimulation index is less than three. It's considered normal. I won't go into this whole bunch. They're abnormal tests, and it's, again, something. What's normal? What's abnormal? They do it, they repeat it again. A borderline test, border, if it's a borderline or abnormal test, will repeat at the same lab. The interesting thing is there's huge inter-lab variabilities, huge intra-lab variabilities, okay? It's a difficult test. Borderline, or they're often borderline or uninterpretable results, and inter-laboratory disagreements. Same sample, split and sent to other places. 30% to 60% disagreement, which is huge, huge, because, guess what? The cells may have died. They're not going to proliferate. They have to have live cells. There's a lot of stuff. It takes at least seven days to get the results back. They look at it at different days. They have little vials. I think there's three different concentrations that they do, and they look at them over a couple of different days. And it, again, does not discriminate between chronic beryllium disease and beryllium sensitivity. You still need to have the bronchoscopy, because that's going to help with the diagnosis if you actually show inflammation. Individual disagreement, there's a waxing and waning of the immune system. Believe it or not, our immune system does change as we have different exposures and things. On one study of new employees, 18% of the people exposed had tested sensitive, and the same people tested two years later, only 6%. So, it sort of comes and goes pretty imprecise. There's a lot of false negatives, maybe up to 30%, and there are also people that are symptomatic that actually have chronic beryllium disease that test negative on the test. Sensitivity and specificity, we really don't know as it relates to how hypersensitivity goes in. The hypersensitivity means it doesn't matter what level you're exposed to. If you're exposed, you're going to develop some sensitivity to it. We're guesstimating the sensitivity. It's really hard to get sensitivity and specificity, because it's a test and a disease. In this, we're doing a test and a sensitivity, and a sensitivity is not a disease. Do you understand how that may confuse? And we're sort of tossing this around, but it certainly has great specificity. If you test negative on it, you probably don't have chronic brain disease. If you test positive, we don't know. False positive rate is unknown. We assume, in most of the studies, that false positive rate is 1 to 3%. Why is that, even for people that are not exposed? Because it exists in the environment at very low doses. At low doses, there may be some people that are hypersensitized to it. I just guesstimate about 2% people that may not have exposure. But how do you find out when you test stuff? We are now doing this testing at one of our naval facilities at Pearl Harbor. There are about 300 workers there that work with some brilliant parts, amalgams, in some of their ship and subparts. And there are 300. I've been after them since I took the job a year ago. You've got to follow this standard. Well, the baseline blood test, we worked on it, could be shipped, had to be AeroVac'd. It's sent overnight from Honolulu to Denver to be put in the lab. The test alone costs $300. It's about $100 a test to get it overnight to Denver. Well, that's $400 a pop times 300 people. It's $120,000. And now the medical and military has gone under the Defense Health Agencies for the MTFs. But this is really part of the employer, part of the fleet. And do you think the fleet wants to pay $120,000 for something that they think is a medical test? And I'm sort of saying, wait a minute. This is a federal regulation. It's a standard. And guess what else the Navy is dealing with at Pearl Harbor now? Red Hill, which is the fuel tank leak. That's going to cost billions of dollars. I'm trying now to tell people, maybe you should be compliant with the OSHA regulation, because if this gets out publicly, all hell is going to break loose. Imagine if a company did not follow an asbestos standard. It's not about the fine. It's not going to be very much. It's going to be that. Luckily, it took a while. They have started being compliant and doing the testing. It's up in the air what's going to happen. We're going to have of those 300 people, we're going to have a percentage of those that are going to test positive. We're then going to send them to Denver. We just had one at another Navy base that tested positive, sent it to Denver and had that work up. And it costs a lot of money. Guess what? It's the right thing to do. Are there any conditions like chronic granulomatous disease or medication that you're on that can be more or less likely to test? I can't answer that. You know why? Because I don't treat this clinically. Those discussions, you can ask of the people in Denver at National Jewish, because they're the ones that are actually doing treatment. I have not, in the screening, even the people I did with Boeing Rocketdyne, we didn't have anybody sick enough to be treated. Again, the levels are pretty low, but they're enough to cause some problems. So I can't ask questions like that. They become more and more vague. But they'll be happy to take in $300 for the test and they'll let you know when the test shows. And I was a little concerned because I had been doing this for a while, sitting in there. They want to buy off everybody. Guess what? They want to have the denominator of the people they're sending. They need the denominator for the study. So it's a lot. Are they great people? Absolutely. Are they the leaders in the world in this? Absolutely. But part of it is research, but that's who I'm sending to. I'm just saying this is who I'm going to send to. This is who knows what's going on. They're the world experts in this. Hypersensitization, abnormal beryllium lymphocyte proliferation test, a positive skin patch test, we're not really doing that much, may have no evidence of chronic beryllium disease, no granulomas, can develop within nine weeks of exposure and can develop years after exposure. We don't know what the timeframe. We don't know the timeframe for a lot of hypersensitivities, and that's the same way we work with human beings. Hypersensitivity may not be dose-dependent. One company's results. So I've already told you the company is, and I'm not working for them anymore, but they were doing it really right. They did a great job. So we tested about 400 workers at three different sites. We had 14 that tested positive and two that were borderline. And, again, if we – what happened now? It went all the way to the end. Okay. I don't know how to get back. Screen sharing has stopped. Could somebody come in? So I hit something. It doesn't say forward or backward, and I lost everything. I'm going to have you do that. Sorry. Thanks. I need something very simple. It says next slide versus that. So what the company had done is they looked at – so we had these people. They had a couple of people that tested positive. And what they did was they tested positive for sensitivity. They got online and read about beryllium disease, and they read the data that 10% of people die every year if they have this disease. Well, they were getting online and reading about chronic beryllium disease, not sensitization. So a couple of these employees – I had to send to psychiatry to get evaluated, and I had one of them that would not go on the base. They were actually working at a federal facility where they launched the space shuttles, would not go on base. And this person did not even work in the area where they had beryllium but was working in that same building and became pretty much paranoid schizophrenic. I had to meet and do the evaluation with this family lawyer off the federal property. It should be set, sir. And then I need to get back to – Your clicker's up here. How do I do it? This is back. There we go. Here we go. There we go. So then we had two of the five. So we had 14 of them, and only five wanted to do the workup. They had read enough. And I had done some lectures, explained to them. And it was so – they actually flew me. It would have been to Kennedy Space Center. It was Cape Canaveral. And I did three sets of lectures for all of their employees because we had so many that tested positive, didn't even work in that area. Come to find out when I reviewed the medical records, the guy that was the administrative worker had majored in metallurgy in college. But I couldn't use that in part of the legal proceedings because we don't – no one had tested him before. All I can say is in college he was exposed to metals, and in his workplace he wouldn't work in a room where the metal was. Does not matter. The company bought this case. May have also bought the psychological implications of it. So a couple of them got that. So two of the five had psych problems, online information. They thought they had a 10% chance of dying. None of them were diagnosed with chronic beryllium disease. They had become sensitized. And very few experienced occupational pulmonologists. I've actually given this lecture at a couple major medical centers to pulmonologists because for this – this is a great zebra example about stuff. It's a really interesting zebra thing, but it does exist. So summary. Chronic beryllium disease and sensitivity are real problems. Difficult screening and surveillance. But at least we have something. At least we have this beryllium lymphocyte proliferation test we can do. It's not perfect, but it helps us. And there's also – we can use – I won't go into that. But hypersensitivity, not dose-dependent. That creates other problems. Beryllium sensitivity testing, not real accurate. Unknown progression. Misinformation on the Internet. And refer to the few expert witnesses. Now, let's talk about the rulemaking process. Got a couple more minutes. The notice of proposed rulemaking was published in 2015. Remember, they put out in, what, 2002 a request for information? Took to 2015. They had public hearings in 2016, final briefs, and the Department of Energy proposed a level of 0.05. The Department of Energy themselves proposed a lower level. But what OSHA found out is at this point it's not practical or pragmatic or cost-effective. We cannot get those levels down that low. So OSHA looked and said, okay, we're not – you know, you can't meet the statutory requirements. So they put it – what they said is you could reach this level of 0.5. And that's what they basically said. It may not be the most protective, but remember, OSHA does not have to regulate based on hypersensitivity. They're going to regulate on something that is practical and pragmatically that they can measure. And the 0.05, to get lower than that, that was lower than the level of detections of some of the tests, the industrial hygiene tests. You see how that creates a problem? You're not going to set a level lower than what the standard test can test for. Make sense? So the new PEL is 0.2 micrograms per meter squared. Eight-hour time weighted average is back to the two, the regular two, for eight-hour one-time exposure. This is done short-term exposure for a 15-minute exposure. And what they state is the final permissible exposure limits are technologically feasible and the compliance is economically feasible. So OSHA looks not only at the medical recommendations. They say, is it technical – again, can we afford to do this? And that's the way OSHA is. The final rule found that employees exposed to beryllium are at the preceding permissible exposure limits are at increased risk of developing chronic beryllium disease and lung cancer. OSHA considers a new level in risk to still be significant. However, they could not demonstrate technological feasibility of lower time-weighted average permissible exposure limits. The rule – final rule published January 9, 2017, and I think that was about the time of the inauguration of the following president. The final rule completely – they publish stuff in advance. They give companies six months to a year to get prepared for this. So during that preparation period, there was some stuff. They extended it because there are, again, compliance dates. The company said we cannot comply with this. It's going to be extremely expensive to do it. And it finally became effective December 12, 2018. So now we do actually have this beryllium standard. And it's the most recent standard. I think it's the only one we've had now in the past 10 or 15 years. They're trying now – they've started now, they've done it, put out a notice of proposed rulemaking to reevaluate the lead standard. There's enough data out there right now for the lead standard. Yes? Since the NIOSH 12 was higher than the Bell, will the automatic exchange prove out? I don't know. I'm not a NIOSH expert. So this is – this gets confusing. Remember, I think you started with just there's two risks. There's the toxicity of beryllium, and then there's client relations needs. And NIOSH has all sorts of stuff with way lower recommendations for us. Absolutely, way lower. Beryllium, because of the Congress-derived definition of toxicity, is based on metal toxicity and not sensitization. It's going to be based on irritation and symptoms versus hypersensitivity. Correct. Sensitivity is not – It's not – But there are many NIOSH publications that recommend a much lower – I get that the rel is even lower. It's just like rel is higher. But the rel is – I lost the question. Hold on to it for me. It's right here in the little chat window. Sensitization. It's not allowed up there. And you can scroll up and down here. I'm going to look at some of the questions. What Congress says you can do, and they define a rel, based on the toxicity, not on long-term effects. It's very confusing. It's medical-legal stuff. And I'm not an industrial hygienist. But, again, I'm giving an OSHA perspective. We're going to do stuff that's practical, that's enforceable, that's technologically feasible. And that can override everything. A question, very general question, are you allowed to ask family history and workers' comp setting? For example, worker alleges an injury in examination and actually showed changes consistent with rheumatoid arthritis. No, you're not allowed to ask about a family history of rheumatoid arthritis. Now, the provider may – well, here's the deal. Okay, let's reverse this. What workplace exposure is known to cause rheumatoid arthritis? I don't know. I don't know any myself. It's very complicated. Now, it's really difficult. This is a really difficult medical-legal issue to look at because, again, we're talking about workplace exposures. And if someone is trying to prove that it was not the exposure, you have to be able to – it's difficult. In general, in cases like this, it costs more to defend the legal case than it does just to settle it or put someone in an alternative job or restricted duty. Yes? When I have a guilty physical or an FAA physical, I haven't signed a lease and I don't have an available medical record. For the last six months, I had one truck driver forget and tell me that he had a heart attack. Another truck driver didn't tell me that he was on insulin. I had a pilot. He didn't tell me that he was on two FSAs. How did he tell me that I'm not allowed? You're allowed to get those. But you can only request the records that relate to the heart or that relates to the stuff. You cannot just say, send me all your medical records. I'm not. That's going to be in the encounter. We're going to have an amnesia. You cannot get that. Well, the key thing here is family history versus personal history. Correct. And you just separate those. You have to separate those. Family history gets you into GINA, and you're really stuck, whereas personal history of the disease is a – You can ask anything you want about personal history of disease, but you cannot ask, did your parents have this disease? What I do is I have a release. I have Epic. If they're in Epic, I take a look. Current medications. It's like, God, it's insulin. I take a look at the EKG. I just want to see, do they – They say my history is completely negative. I just want to – It's a tough case, and there's a lot of legal liability that goes on. What's my liability if I have access to it and I don't look at it? Well, your liability is going to be if you make a poor determination based on information that you should not have had access to. That's where your liability is, okay? And you're probably not going to do that. The problem is if you get online and somebody says, oh, they're on insulin and you're a DOT exam, and they fail to disclose that they use insulin, that's not admissible. It would not be admissible in a court of law because you did not have right to get access to that information. It's the same way for legal. If someone stops a car, it's – You're all off. You're all off. I'm sorry. Yeah. GINA allows you, as an attorney, GINA allows you to ask a family medical history. You cannot use it to discriminate in the decision. You cannot report it on a medical exam. Right. Unless there's six limited conditions that are allowed by EEOC where you can ask about the family history. Those are very limited. Wellness and FMLA. Okay. So it gets a lot more complicated. It's very complicated. As a general rule – Don't write it down. Don't write it down. Family history. And I'm doing policy based on DOD trying to get access to their whole health history in the military and same stuff. GINA does allow you to ask work-related questions to get access to information if it relates to the job. What you cannot ask for is information that does not relate to the job. And I think you agree with that. Is that correct? When you get some personal history, then you're getting into the ADA problem. I got two hours of lecture. Right. And ADA will allow it if it relates to the job. So obviously very controversial stuff. But the concern is, you know, try not to ask some of this stuff. I brought it up because there may be some genetic component. I understand. Yeah. I have a pilot in two antipsychotic medications. He doesn't tell me about that. I mean, I've got a safety obligation. You have an obligation to do that. Okay. What you probably cannot do is ask, are your parents schizophrenic? Yeah. Great. Okay. And I lost the other questions. So anyways, I'm happy to talk about stuff. Obviously some controversial things. What I want you to get out of it, again, maybe not all of you will have brillium, but maybe have a little better understanding of how difficult at a high level these issues are. So thank you very much. So I'm going to have a suggestion. I'm going to ask Dr. O'Neill if he's okay with this. While y'all are serving yourself, I'll pull up Dr. Campbell's module and whatnot. And if you have any further questions or want clarifications, Dr. O'Neill, he'll be here. And then what we'll do for our virtual participants is we'll set him up in the lobby with Bridget. And if there's any chat questions we missed, you can talk to them via chat. Okay? Absolutely. All right.

beryllium sensitivity

chronic beryllium disease

occupational exposure

OSHA standards

beryllium lymphocyte proliferation test

aerospace industry

screening challenges

regulatory compliance

occupational health