Dr. Samuel Brown, Vice President for Research at Intermountain Health in Salt Lake City, talks about understanding A.R.D.S. and how to treat it.
Interview conducted by Ivanhoe Broadcast News in 2023.
Let’s just start with talking about this study that’s going to be going on in next year.
Brown: Yeah, it works. t’s just begun in the planning phases, and will be enrolling the first patients early next year. And it’s really the major work right now in trying to understand these life-threatening syndromes. And the syndromes are ARDS, which is where the lungs fail, suddenly. COVID, when it was life-threatening, it caused ARDS. Pneumonia, which is an infection of the lungs. And sometimes pneumonia leads to ARDS and sometimes it doesn’t. And then sepsis is infection, but it’s infection that’s serious enough that it’s causing your body’s balance to be threatened severely. And ARDS kills as many as 30 or 40% of the people it strikes. Yeah, it’s really serious. Sepsis kills maybe 15-20% of the people that it strikes, depending on its severity. And then pneumonia, overall, is a bit of a milder disease, but by the time it gets you into the hospital, you could be in serious trouble. And the problem is that ARDS particularly can be caused by 35 different things, and it strikes lots of different people. And we’ve been searching for treatments for ARDS for decades. And the main thing we found up until the pandemic was that there are ways to use the ventilator, the lung life support system that are better or worse. So we quit using a worse way and we now use a better way that protects the lungs more. But in terms of specific treatments for it, a medicine, for example, that will take care of your ARDS, we haven’t found it. But then in the COVID pandemic, we had an awful lot of ARDS patients. But they all had one cause, basically, COVID. So they were different themselves, but the cause, there was only one. And for the first time in 50 years, we had clear evidence that there were certain treatments that were benefiting patients with ARDS. We’ve done similar trials before COVID didn’t seem to work. But in COVID where we had that one specific cause, it did work. And that’s caused those of us in the world really, although this grant is based in the United States and is run in the United States, this is a global area of concern. It’s caused us to say maybe we’ve been lumping things together too much. Maybe there’s lots of different things that we’ve been calling ARDS, but they’re different and they have different treatments that may be effective for them. So we’re taking a step back now as a community, and it’s about $51 million from the National Institutes of Health. It’s six centers and a coordinating center. And then within those six centers, there’s a total of 22 hospitals. It’s all across the United States. We are enrolling ethnically and racially representative populations. And we’re trying to answer the question, what do we do now that we realize that one size doesn’t fit all? What’s the right way to make that step forward to more personalized understanding and treatment of people with those diseases? So 5,000 patients we’re anticipating to enroll across the United States and we’re going to gather lots of information about them, where they come from, what medical history they have, what currently is going wrong, what parts of their body are not working well, what are pictures of chest X-rays, for example, to try to understand what’s happening inside the lung and then blood work and where we can other samples that might be available. All trying to understand what makes people different from each other, and what will be the next path to effective treatments for ARDS outside of COVID, where we actually did get some treatments by the end of the pandemic for COVID ARDS.
COVID ARDS – I was reading that everyone’s body is different, they respond different to different kinds of treatment. So for this study, I’ve read about phenotyping. Is that different this time around as opposed to other times that’s been studied? And what is it?
Brown: Yeah. We’re scientists and doctors and those are two groups that make up words and try to sound fancier than they really are. So we use the word phenotype. And what it means is how do you identify a meaningful group of people that are biologically similar to each other, and their disease is biologically similar to the disease in the others? Some people will call it sub-typing or identifying subgroups, or identifying patterns or groups within them. But phenotyping is just a highfalutin word for how do you find the meaningful subgroups of people? The example I use sometimes is that in the past we’ve treated ARDS like a fruit basket where you got apples and oranges, bananas, papayas, guava, mangoes in the fruit basket. And you say, well, this thing I think will work for apples. So let’s do it for the whole fruit basket. But phenotyping is saying, well, no, let’s identify the individual fruits. So there’s apples and oranges and bananas and papayas and mangoes. Let’s figure out how to identify those different types within ARDS. And once we’ve got a sense for their different types, we can start to get treatments that will be relevant specifically to that individual type. And that’s what we mean by phenotyping.
As of right now, you were saying pneumonia even, and I was being like really alters and antibiotics for that. Not a whole lot of understanding is that so?
Brown: Yeah, pneumonia is a tricky thing where a lot of people will get pneumonia. Most people don’t get into trouble with pneumonia. Most people if it’s a virus, you don’t even need antibiotics. You just take a few days off work and try to rest and catch up on Netflix and you know you get better. But then if it’s a bacterial pneumonia, commonly you will need antibiotics. But again, most people, you give them antibiotics, they’ll be okay. What we worry about are the patients who tip over for whatever reason. Is it because they have kidney disease and they’re on dialysis and their body is just a little bit less resilient than it used to be. Is it because they have cancer and they’re under treatment for their cancer and their bodies in a weakened state? Or occasionally you have a situation where the immune system is so strong, but sometimes we’ll see 25-year-olds come in with just a rip-roaring pneumonia and it really looks like their immune system has just gotten so overstimulated. That is almost like it’s gone nuclear. Instead of a surgical strike, like it’s dropping an atom bomb, and that has real problems for the lungs and for the rest of the body. So for people with pneumonia that end up in the hospital, they actually can get into trouble as the pneumonia gets out of control. And we give everybody antibiotics when they’re in the hospital with pneumonia just about. And even so, there are people who don’t get better, so that’s what we need. We need something to do to treat them when they’re not getting better, just with antibiotics. But you’re right for now. We’ve got some guesses from COVID that maybe drugs called steroids might help in pneumonia, but it’s still pretty controversial. And the best guess is that there’s a subset of people who are super inflamed. Their immune system is like wild, too high, too hot, and those are likely to benefit from steroids. And then there are other patients, for example, somebody who’s got really bad lupus and they’re on heavy-duty medicines to drop the immune system. They may not benefit from steroids. They may need something that enhances the immune system. Who knows? That’s part of what we’re trying to answer together is this collaborative group across the United States. What’s the right treatment for this person in front of me?
Given just the scope of this study and all the collaboration that’s being done, do you think that all these questions will be answered?
Brown: As a scientist, you wake up every day and you think, I would love to answer a lots of questions. And you acknowledge that your life was still, your work, our lives are so much more than our work, but that your work life will have meaning if you answer several questions. And so I think that our ambition is to answer all the questions. And we’ll be quite pleased with our work if we answer several of the key questions.
When do you think they’ll start seeing some answers or couple of group?
Brown: It’s a great question. It’s set for five or six years total for the study. And we’ll be enrolling patients all the way through the end of the fifth year of the trial being open for enrollment, or the study, sorry being open for enrollment. And we’re hoping that along the way, we will begin to be able to answer questions even before everything is completed. But of course, science like life takes a little time in the doing. I think most of the big answers that we’ll be getting from this will come after we’ve got the entire group enrolled and then followed up to see how they doing afterwards and then run all the fancy stuff in the science labs and use the artificial intelligence to try to understand what are these patterns. That’s, I think what we’re about.
How is AI being used?
Brown: I think for a lot of people, AI is either some crazy robot from the future that’s trying to kill Arnold Schwarzenegger or something. Or it’s your phone that half the time understands you and half the time doesn’t, or it’s not Chat GPT, which sounds a little bit like your drunk roommate from college rambling on. Yeah, but not quite there. The reality is you strip back the hype. Artificial intelligence says there are some new techniques in math and statistics that let you see patterns that are hard to see otherwise. Basically you get thousands of variables, thousands of details about a person. What’s their kidney function? What’s their lung function? What’s the pattern of inflammation in the lungs? How inflamed is their body by this measurement? What other diseases do they have? Do they have heart disease? How much oxygen are they receiving? Are they requiring adrenaline infusions for their blood pressure? Those are variables and you end up with maybe thousands of variables. We as human beings are really good at certain things we can recognize with people we love immediately. We can do simple math problems immediately. But we’re not really good at taking thousands of variables and summarizing them into meaningful different groups. That’s what AI does. AI takes advantage of certain tricks in certain math calculations to allow patterns to emerge and get identified. What we’ll be doing with AI is using various AI techniques to say so far everything just looks like apples to us, but it’s really a fruit basket with lots of different fruits in it. The AI is the technique that will allow us to say, oh wait a minute, that’s a papaya, that’s not an apple, that’s a papaya. So that’s what we’ll be doing. We gather all the information and then we feed it into these systems that help us to identify patterns that otherwise we just don’t see as human beings.
Fruit basket thing is really good. It makes it easy to understand.
Brown: Sometimes we get so lost in space as scientists, but it’s important to bring it just back down to concrete reality.
Is this something that the doctors are just going to recognize patients that they can enroll with to people? Is there someone who wants to enroll, how are they finding the subject?
Brown: Every hospital that’s part of the study will be screening. They’ll be looking at the patients who are in the hospital and they’ll be looking to identify who has AODS, who has pneumonia, who has sepsis. Then a member of the study team will approach the patient or if they’re not able to think correctly, they’ll approach their next of kin who can decide for them and ask them, would you like to participate in the study and then if they would, they’ll get time to think it through and decide. Then they’ll sign a form that says, yes, I enroll and then after that, they’ll be inside the study. But almost certainly, it’ll be just for patients who are in the hospital at the time. In an individual hospital that’s enrolling and Intermountain Medical Center is the head of the center but this center will include collaborations and enrollments at University Hospital here in Salt Lake and Duke in North Carolina, and Johns Hopkins in Maryland. Then each of the other centers says other hospitals will be enrolling pretty much every day. The teams will be looking and seeing, are there patients you might fit into this study and then they’ll chat with the teams, the treating teams, and also with the patients.
Do you think that this could also shed light on other things?
Brown: Part of what has made us think this will be successful is that there has been work in asthma, that wheezing disorder that makes it hard to breathe and is like an allergy. It turns out they’ve been able to do this phenotyping in asthma where they’ve been able to divide it into apples, oranges, and bananas and get specific treatments for the specific groups. My hope is that what we’ll find from this study is information that will help the study of other syndromes where people get inflamed, the immune systems get activated for some reason, and I think for example, about trauma and about certain forms of cancer, when the body gets just revved up in a way that’s not safe for the body and how do you calm that down? My hunch is the next places we’d be looking based on what we see here would be in trauma, where the body gets beat up by a motor vehicle collision, for example, or in certain kinds of cancer or chemotherapies even where patients just get really revved up and thrown out of balance, biologically.
Can you tell us what this means to the general public?
Brown: I think for most of us, we take our health for granted and most of the time we’re not wrong. Most of the time we’re healthy. What I think it is helpful is knowing that if you do get sick, or if someone you love does get sick suddenly with something really serious, that you’ve got good scientists and clinicians working hard to make sure that if your body falls apart, we’ve got the right answers for you in your time of need. It is something that I hope provides some reassurance as we go about our happy lives God forbid, something terrible happens, we got options. We’ve got people with expertise and understanding, and experience that will be there for us and are continually innovating to understand better how to be of better use.
Is there anything else you want to talk about?
Brown: I’m really proud of the work that’s done here in Intermountain. Intermountain has been working on ARDS since the early 1990s and it has really been a key player in this area and making huge contributions. That’s a big part of why I came to Utah to work. I love working within their system and also being of use to the people in the communities we serve. I really like that.
END OF INTERVIEW
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