Podcasts about fev1

On this episode of JHLT: The Podcast, the Digital Media Editors invite lead author Chung-Wai Chow, MD, PhD, FRCPC, to discuss the paper, “Pollution exposure in the first 3 months post transplant is associated with lower baseline FEV1 and higher CLAD risk.” Dr. Chow is a transplant pulmonologist and clinician scientist at the University of Toronto, with work focusing on investigating air pollution's impact on chronic lung diseases and developing improved methods to assess lung function. The episode explores: Measurement methods for home and personal air pollution exposures Specific pollutants like black carbon and their effects on patients after lung transplant Practical advice for mitigating these effects For the latest studies from JHLT, visit www.jhltonline.org/current, or, if you're an ISHLT member, access your Journal membership at www.ishlt.org/jhlt. Those on heart transplant teams should tune in again later this month for a Scandinavian study that performs long-term follow ups with patients on the nephrotoxic effects of CNIs. Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.

Hannah Went, a pioneer in epigenetics, is the co-founder of TruDiagnostic and founder of Everything Epigentics. She shares her journey from the early days of TruDiagnostic to its burgeoning role in healthcare. She reflects on the rapid evolution of epigenetics, the challenges of making groundbreaking science accessible, and the gratifying shift towards mainstream acceptance. Hannah also delves into her personal growth, emphasizing the transformative impact of "The 15 Commitments of Conscious Leadership" and her desire to be remembered as loving and impactful.  Guest links: trudiagnostic.com | everythingepigenetics.com Charity supported: Equal Justice Initiative Interested in being a guest on the show or have feedback to share? Email us at podcast@velentium.com.  PRODUCTION CREDITS Host: Lindsey Dinneen Editing: Marketing Wise Producer: Velentium   EPISODE TRANSCRIPT Episode 041 - Hannah Went [00:00:00] Lindsey Dinneen: Hi, I'm Lindsey and I'm talking with MedTech industry leaders on how they change lives for a better world. [00:00:09] Diane Bouis: The inventions and technologies are fascinating and so are the people who work with them. [00:00:15] Frank Jaskulke: There was a period of time where I realized, fundamentally, my job was to go hang out with really smart people that are saving lives and then do work that would help them save more lives. [00:00:28] Diane Bouis: I got into the business to save lives and it is incredibly motivating to work with people who are in that same business, saving or improving lives. [00:00:38] Duane Mancini: What better industry than where I get to wake up every day and just save people's lives. [00:00:42] Lindsey Dinneen: These are extraordinary people doing extraordinary work, and this is The Leading Difference. Hello, and welcome back to another episode of The Leading Difference podcast. I'm your host, Lindsey, and I am so excited to introduce you to my guest today, Hannah Went. Hannah has a lifelong passion for longevity and breakthrough disruptive technologies that drive radical improvement to the human condition. She attended the University of Kentucky and graduated with a degree in biology. During that time, she had multiple research internships studying cell signaling and cell biology. After graduation, she worked for the International Peptide Society as their Director of Research and Content. Through work in the integrative medicine industry, Hannah saw an opportunity for a methylation based age diagnostics and started TruDiagnostics in 2020. TruDiagnostic is a company focused on array based methylation diagnostics for life extension and preventative healthcare serving functional medicine providers. TruDiagnostic has a commitment to research with over 30 approved clinical trials investigating the epigenetic methylation changes of longevity and health interventions. Since TruDiagnostics' inception, they have created one of the world's largest private epigenetic health databases with over 75, 000 patients tested to date. Hannah has since created Everything Epigenetics, where she shares insights on how DNA regulation has an impact on your health. All right, well, welcome to the show, Hannah. I'm so excited to talk with you today. Thanks for taking some time. [00:02:14] Hannah Went: Thanks, Lindsey. I'm excited to speak with you. [00:02:17] Lindsey Dinneen: Awesome. Well, would you mind starting off by sharing a little bit about yourself and your background and what led you to MedTech? [00:02:25] Hannah Went: Yes, absolutely. I've known since I was a little girl that I've always been interested in science, how the world works, how the body works. I remember being a little girl and going in our backyard, lifting up rocks, finding roly-polies and worms and getting all down and dirty. I was definitely a tom girl, if you will, growing up. I love sports. I loved connecting with people. So I also loved the social aspect of understanding how the body works as well. And I was very athletic growing up. So I played track soccer, basketball, sports all year round, essentially. I knew I wasn't good enough though, to go to like a D1 or probably even D2 college for sports. So I was like, "All right, well, I'll just go to a larger university, maybe play some club soccer and really focus on my academic route." And I ended up going to University of Kentucky. It wasn't too far from me. I'm just from Ohio, north of Dayton, a small town called Piqua. And I did end up playing soccer, club soccer there, got involved in a lot of other activities. Ended up actually going into veterinary work, animal science. UK has a really good program for that. They have a really good agriculture department. I ended up shadowing a vet one summer and I hated it. It was one veterinarian clinic. So a lot of work, a lot of late hours. And I knew I wanted to have a family growing up. So I was like, "Eh, let me just switch to general biology. Let me just open my doors." And fast forward to senior year. I was really interested in genetics and you know, how do we have these predispositions that are passed on throughout our family? How does that affect our health outcomes essentially? So I applied to genetic counseling school, which is a very new program. It's a master's program. It is where you get your master's essentially in genetics and counseling. So it's like the best of both worlds, exactly what I loved growing up. You have the science aspect, but you're sitting down and helping people actually understand their risk. Applied to school, Lindsey, and didn't end up getting in. So I was like, "Oh, I'm heartbroken. I'm still super young. My life's over!" type of deal, a big eye roll ,and thought it was the end of the world. But really where my career took a huge turning point was at that failure point. I took a job, my best friend got me a position at a compounding pharmacy in Nicholasville, Kentucky, which is just a little bit South of Lexington. And that was when I was opened up into this entire medtech space of healthcare providers and the integrative functional medicine journey who were focusing on healthcare, like true healthcare, not sick care, not taking care of sick people when they're already sick, they're already doomed and just trying to bill them for all of these medications through insurance. So that's really how I've gotten to where I am today. [00:05:23] Lindsey Dinneen: Oh, that is so cool. Well, first of all, thank you for sharing a little bit about your background. It was fun to even hear about your childhood and how that theme of interest in all those different aspects has woven its way through your story. And I would love to hear a little bit more then about, okay, so what does present day look like and how did you end up where you are? [00:05:43] Hannah Went: Yes, so I'll try and keep it short and concise. So this pharmacy was very innovative. It was the fourth fastest growing healthcare company in the nation in 2019. And it's really focused on the unique peptide products. It was again a compounding pharmacy by trade, meaning you can compound anything in all different dosing as long as you have a prescription from a healthcare provider by it. They grew really fast. So, you know, we always had regulatory agencies come check in, make sure we were doing everything correctly, which we absolutely were. But there was always this worry that these products made people feel better, but there wasn't a lot of quantitative data behind it. So we were like, "All right. Well, what can we measure in clinical trials and institution review boards to really prove to people out there, 'Hey, these are having a massive underlying biological effect on people.' They don't just feel better." We used to joke and say, "People can become tan, they can become skinny, they can increase their libido from these products, but they also actually save people's life." They stabilize insulin sensitivity. They can help people lose weight who have metabolic disease. They can mediate a lot of the effects of specific autoimmune diseases. So there are massive impacts that these products had. And we're like, "All right, well, if you had one test, like if you could measure one thing that really relates to all of those items I just mentioned, it's aging," right? These age related diseases. So, "how do you even measure age" is the follow up question and you can do that in all sorts of different ways. But there are actually these DNA regulation markers, like these on and off switches, called your epigenetics that seems to be the best way to measure aging. So we really started measuring and doing clinical trials with these epigenetic aging biomarkers to prove the efficacy of these products. And what we ended up doing is just selling the pharmacy in 2019. It became-- oh-- pretty boring, I guess, for lack of a better word, because there were new rules and regulations in place by regulators on what you can and cannot compound. And then you have built my company now, TruDiagnostic, from the ground up. We have our laboratory in Lexington, Kentucky, and we started out with one goal, which was essentially to offer the best age testing. And now we're doing a lot of different things. So that's what I'm really involved in now on a day to day basis. [00:08:10] Lindsey Dinneen: Wow. Well, thank you for sharing about that. And okay, so, so you embrace this entrepreneurial endeavor, which is a whole second set of-- I mean, obviously you have all the skills from your experience and your education and whatnot, but then to compound that with owning your own business and then setting up a brick and mortar, it's an actual lab and whatnot. How was that transition? Did you feel prepared for it? Did it catch you off guard? What was that like? [00:08:38] Hannah Went: We were kind of creating TruDiagnostic behind the scene when we had the pharmacy. So like end of 2019, we were really creating it. But I do think it caught me off guard looking back where it was like, "Okay, pharmacy sold, full time TruDiagnostic. How the heck do we set up this lab at the beginning of 2020?" It was go mode. So we bought a building in Lexington. It was an old insurance building. We completely knocked out the top floor, which was offices, carpeted, not usable lab space and built the lab again, like I mentioned, from the ground up. So I joke and say, "I'm a construction worker. I was an interior designer." I was doing all of these other things. And of course I had a lot of amazing people helping me all throughout the way, but testing SOPs for standard operating procedures, creating those. I remember the first day we were running samples in like trialing the protocol. I was here till 5am because we were thawing things and freezing things as part of the protocol and didn't even realize that was part of the step once we started to get into it. So yeah, it definitely took me off guard. And I think furthermore, we launched right before COVID 19. So it was the worst timing in history to launch. And you know, we did it anyways. And then the first year and a half, two years, it was a lot of follow up. It was a lot of cold calling. It was chasing or following up with these healthcare providers to use these kits that we sent out because we did a really nice promotion to get the product out there, but it was hard to balance because when COVID 19, this nasty pandemic, came into the U. S., you almost felt guilty asking the healthcare providers to focus on anything else, right? You're like, "That is not what you should be worrying about right now." So it was definitely hard to balance. [00:10:23] Lindsey Dinneen: And yeah, my goodness. And honestly what resonated with me too is, you know, you're talking about, you've worn so many hats, obviously, as a business owner and setting this up. And I used to joke that, when I had a brick and mortar business and I was like, "On any given day, I'm everything from the CEO to the janitor." [00:10:40] Hannah Went: I can relate. I can definitely relate to that. I remember we needed some kind of-- I don't even know what we need this for-- it was like some type of part that had to regulate water temperature or something like that. So a traditional thermometer wouldn't work. I remember I drove across the street to a pet store and I got something that belonged in a fish tank. And I'm like, " I don't even know if this will, will work." But I mean, we are just piecing everything together. It was like you were doing yet literally everything and anything that you could just because you wanted it to work so bad. You had that passion, that, that push. And you realized that the end goal in mind, which for us, it's really just to help our people, you know, people who are working with us, and our clients, whether that's anyone from now a healthcare provider offering our services or a researcher or academic collaboration, it's someone doing third party processing at our lab or even down to the end consumer client patient, whatever you'd like to call them that come directly to our website and do our testing. [00:11:40] Lindsey Dinneen: Yeah. Great. And that actually addresses my next question, which was going to be, so do you only work with healthcare providers? Is it a B2B enterprise? But it sounds like you also do the B2C and you can sell directly to them, to people who are interested. [00:11:55] Hannah Went: Definitely. Yeah. When we opened, we had that one goal in mind, which is what we knew, which were our healthcare providers that we really transitioned from the pharmacy over to TruDiagnostic. So that was like our main customer at the time. And I think we completed that goal of offering the best aging diagnostic tools at the end of last year with a large study we did with Harvard. But now what we've noticed and, of course-- we kind of got lucky in this sense, we would have never imagined where we are now-- is that epigenetics, these DNA markers, these on and off switches are really great for creating new and novel biomarkers. So you can predict almost anything with them. You can predict even how much you've smoked across your entire lifetime, how much alcohol you've consumed, your zip code based on where you live, just because of the environment you're exposed to and your behaviors in that environment. So it's pretty crazy, obviously we, we didn't expect that and I mean it's just being really blown up and everywhere you, you look, I mean it's related to every aspect of life and of course changeable as well. So even, providers who are using this test on a patient once, they'll retest them every 6 to 12 months. And then of course people coming from our website, we just released actually a subscription model a couple days ago so people can start to retest this in more of a hands off fashion. even every three to four months if they wanted to. [00:13:19] Lindsey Dinneen: Wow. So when somebody does your test and they get the results, is this something that you walk them through and say, okay "Here's where things stand now. If you make these tweaks, here's how things could stand?" Or how does it work from that perspective? [00:13:34] Hannah Went: Definitely. So just to walk you through the process, you would get your kit, we'd ship it to you, you would prick your finger. So just a little blood spot card about the size of a quarter, you ship that sample back to our lab in Lexington and we get results back to you in about two to three weeks from the time we receive it. Then you would get all these different age related reports, some of those characteristic and trait based reports I mentioned, like this smoking and alcohol. And we, we do, so we can project you out saying, "Hey, if you still stay on this trend, whether it's aging faster or aging younger, here's where you're, where you'll be in six months, 12 months." So it may be exciting to some, it may be scary to some, depending on where they are. Regardless, it's changeable. So if anyone's listening and they're like, "Oh my gosh, I don't want to know that. I'm so scared." If you've tested your genetics, that's in my opinion, even scarier. That doesn't change, right? You know your risk, you know your predisposition. So, this can all be mitigated through lifestyle factors, through supplements, medications, procedural based therapies as well. So we do give you recommendations on the report on what to do. You can absolutely again take it by yourself, but we can always help you and connect you with a healthcare provider if you're really wanting to go on this journey. But I always say, Lindsey, the first test is really fun. It's sexy. It's really trendy right now. But it doesn't mean much. It's just a baseline. It's telling you where you are, just like your hormones and your CBC panel, your second test is more important than your first third, more than the second fourth, more than the third. And so on and so forth. [00:15:09] Lindsey Dinneen: Okay. Yeah. And you addressed something else that I was going to ask. So when people are interested, they'd like to do it, but they have this like, "Ooh, I don't know if I really want to know," how do you help overcome that? Is it because things are changeable? Like everything can be changed? [00:15:26] Hannah Went: Yeah. Yeah. I'll even give you to an extent, I would say most of it, right. For the purpose of this conversation, yes. There are of course some exceptions, but my grandmother, for example, passed away from Alzheimer's when I was senior in high school. Right after that happened and what started some of my interest in genetics is I went and got my genes tested. I'm like, "Oh my gosh, that was awful to watch her go through. Am I doomed, right? Am I going to have that same risk?" And my results came back. Well, I have this specific snip. It's a single nucleotide polymorphism. So this specific variant on my genes that's APOE 3-4. So this means I'm at a more increased risk to have Alzheimer's, and even at a younger age as well. I would say you have an even further increased risk if you're at APOE 4/4. So I'm not the worst, but I'm the second worst, essentially, and I'm like, "Well, this obviously isn't good. But this can't be it, right? This can't be the end of this story." And you hear a lot of people say that too, people with metabolic disease or diabetes in their family. And, they may shrug and just say, "Oh, well, you know, I can eat whatever I want, right? I don't have to work out, like I'm doomed anyways, type of thing." And we know now that's not true, right? You're no longer really the victim of your genetic predisposition that we may have thought due to these epigenetic changes or the fact that it's changeable. So there are even peer reviewed published papers that come out showing estrogen, so optimizing your hormone levels can actually reduce your risk of Alzheimer's from an epigenetic standpoint along with everything else, exercising, eating very healthy, no artificial foods, flavoring. So you're, of course, always going to have that genetic risk, but you also have all of these other types of risks and you have this epigenetic risk, which should really be the main focus, because you're in the driver's seat again. You're no longer in the passenger seat. And that's really empowering to have all of that knowledge. [00:17:22] Lindsey Dinneen: Yeah. Yeah, absolutely. I know that the test is really important in terms of telling an individual exactly what's going on and how things can change, but in doing all this research and data collection, are there certain lifestyle things that pretty much everybody regardless should pay attention to. Is that a thing? [00:17:45] Hannah Went: Of course, that's the multimillion dollar question and a very frequent one that we get. And the answer is, "Sure, yes and no, kind of, maybe so." And what I mean by that is you can look at all of these general population studies that come out, right? These clinical trials and look at what really moved the needle. But again, those are populational trials, so you really need to find out what works for you. I can tell you what works for me. There is a study on this, which is why I wanted to try it first. So again, you can start to maybe trial some things based on results that are already out there, but I've tested my aging before and what I've noticed that really slows it down is caloric restriction. So it's not necessarily intermittent fasting or time restricted feeding or skipping an entire meal, it's just continual, 10 percent caloric restriction. So if you're on a 2000 caloric based diet, take out about 200 calories, which if you're eating healthier anyways, you may not even be hitting your intake of calories based on your metabolic rate and what your specific goals are. And I've noticed that helps slow down my aging. I've also noticed that I need to do more aerobic based exercises. So things like VO2 max, increasing FEV1, we can actually quantify those on our test. So really VO2 max is your oxygen uptake, so how much oxygen you can get into the body. Your FEV1 is your forced expiratory volume, so how much oxygen you can get out in and out of your lungs. Swimmers have a really good VO2 max and FEV1. So I noticed I was doing maybe too much like weightlifting, too much HIIT type of workouts. So you can get a lot of feedback from those reports. So for me, personally, that's what works. [00:19:30] Lindsey Dinneen: Wow. That's great. That is amazing what you can test and gain knowledge about and then make those changes based off of. So on your LinkedIn profile, something that I was really intrigued by is you are a founding member of an organization, I believe, called Opscotch. Did I get that right? Okay. And one thing that really stood out to me, and I'd love to just hear your take on the organization as a whole, but you said part of your mission is to make biohacking accessible to everyone. And I really appreciated that. And I'm curious if you would share a little bit maybe more about that. [00:20:05] Hannah Went: Yeah. Obscotch is a really cool community. So it is really democratizing the way healthcare I think has been viewed, even healthcare, like the model where we should go towards rather than that sick care. So it's making it a lot less scary. And I know that the founders of Obscotch, Spencer Coppin and Matt Christensen, and they're amazing people. They really set up this community as a way for people to have a support system. I think it can be really scary when you're entering really optimizing your overall health, what do you do? You see all of these ads, what protein should you take? What supplements should you take? They're just everywhere. Whose supplements really match the label? There are a lot of studies that show, that they don't even have promised ingredients on the label included in the supplement itself. So it's really confusing. And then you go down these rabbit holes and after a while, you don't know what you're looking at. So if you're part of this community, you can choose to get a Whoop and to start tracking a lot of these markers. You probably know the quote by Peter Drucker, "You can't manage what you're not measuring," so they measure a lot of things. They do the biological age testing through TruDiagnostic, and then they do some other laboratory based testing as well. So there's different levels of the membership that you can actually get depending on how involved you want to be, but they also do these monthly quarterly type of challenges. So it could be to get your Whoop fitness score above 12 for 15 days of the month. So again, it really encourages people to come together and I love that community aspect of it. They've done a really nice job. And again, are just amazing people there. They're located in Canada too. [00:21:46] Lindsey Dinneen: Oh, nice. Yeah. So taking ownership of your health, but within a community, which makes it a lot, well, more fun, at least. [00:21:54] Hannah Went: Yeah. And the community is awesome. That's probably a really good group for you to even look into, Lindsey. It's a lot of founders and entrepreneurs and people who have like wild backgrounds. And they're from all over the world too. So it's not just like, oh, you have to be in Canada. They do have a lot of like local meetups in Canada, which is really cool for things like cold plunging or running or, you know, scheduling dinners or seeing like Andrew Huberman, he was in town like a couple of months ago or something. So they put together the events and they also send you even like recommended podcast or YouTube videos to watch. So it's really curated health information if you're looking to optimize your own health. [00:22:35] Lindsey Dinneen: Wow. Amazing. Yeah. And then, so another thing that I really enjoyed reading about you and your experience is, you mentioned that you appreciate taking complex scientific ideas and translating them into narratives that resonate with the intended audience. And I love that, and I think that's really important, but I'm wondering if you could tell us a little bit about your process in doing that, translating very technical engineering science speak into maybe what other people who aren't in that world could relate to. [00:23:14] Hannah Went: Yeah, definitely. So I have my personal company too, called Everything Epigenetics. So this is a, something TruDiagnostic wanted to do for a while is just educate others on epigenetics and what that means because there's a lot of education lacking out there. There's not much you can find. With all things that kind of got pushed under the rug in our early days, but I was just, " Screw it. I'll just make it mine." And I set up all of the social, the website domain and didn't do much with it for the first couple of months. And I was like, "Okay, I really want to get into this." And I think I started it at the end of 2022, so almost two years, which is crazy to say. And, I used it as a way to really keep myself honest and involved in the research. So I'm not as involved in our research on a day to day. So I work with a lot of postdocs or PhDs who have created epigenetic algorithms or interpretations. And basically, hopefully break those conversations down for people to easily understand. It's still very high science and not as applicable, so it can be tough sometimes. But my real goal is just educating those on this massive paradigm shift we're seeing with epigenetics in terms of not only taking over traditional lab testing, but just medicine in general. I mean, it's causing a massive wave and really, I think, flipping our understanding of how this field works, how even really the body works. So I don't monetize that at all. It's just something I do on the side. I have a podcast that runs every other week. And then I also am pretty active on Instagram doing these Journal Club Friday kind of spiels. That's where it's usually a video that's anywhere, I think, they're at least 90 seconds, but 90 seconds to four minutes long, just highlighting some type of research paper in the space and trying to do it in really simple terms that way people can understand it. So it's not maybe always going to be applicable to everyday life. I think it's absolutely going to get there where we are able to measure epigenetics, see our exact plan, have everything served us on a silver platter. But we're a little bit far away from that now. And I think that's can be really frustrating to some people, but I think it's also as equally as exciting. And you have to keep in mind that this came out after the iPhone, after the first iPhone. So it only came out about, or I would say only became popularized about 10 years ago, which is very new. So we just have to be a little bit patient. [00:25:51] Lindsey Dinneen: Yeah, that's fair. Well, thank you for helping translate some of these crazy things into more digestible pieces of information for those of us who maybe don't have that same background. So I do appreciate that. [00:26:05] Hannah Went: Yeah, of course. It's really fun to just continue the conversation and start to break these complex ideas down. [00:26:12] Lindsey Dinneen: Yeah, absolutely. Yeah. So, within your journey you know, as a scientist and researcher and entrepreneur and everything else, are there any moments that stand out to you that, that really affirm to you that you were in the right place at the right time in the right industry? [00:26:34] Hannah Went: Ooh, that's a good question. I, I think yeah, I think probably a couple months ago, three months ago. So, we've actually joined with some other clinics on really pushing forward epigenetics. And I think we're starting to see everything coming together. So I think it is hopefully becoming mainstream. And that is just huge, because the vision for epigenetic testing is to be able to use one blood spot card, so really simple, easy collection method at a really cheap cost and getting every single biomarker back that you could possibly imagine: clinical lab values, hormones, inflammatory markers, vitamin levels, minerals, proteins, metabolites. And I think, I remember just a couple months ago, when we really started to get an increased volume and testing, more healthcare providers just saying yes and super open to this idea. So I usually spend my day to day on calls with healthcare providers or our partnerships that we have with, whether it be wholesale or like resellers of these kits. And people are just starting to get it more. Like I remember at the beginning of TruDiagnostic, we always had to set up a call with every single account. It was, Hey, start from the top. What is epigenetics? Even before epigenetics, what is aging? How do you measure this? This is a really weird idea. And now we're starting to see where people set up accounts with us and they don't even set up a call and they just start ordering, right? Or they set up a call and they're like, "Hey, I know what aging is. I know what epigenetics is. Help me market this to my patients. How do I sell this?" So, so we're starting to see that change and that's definitely not been overnight. To answer your question, right time, right room with the right people. But I think probably at the beginning of this year is when we started to really see that change, which has been super exciting. [00:28:35] Lindsey Dinneen: Yeah, that is. It is because it's hard to-- it's great to educate-- but it is hard when that is your entire job day in and day out. And eventually maybe the science will catch up or the understanding of the science will catch up so that you finally get to this, you know, "we're getting there" stage. [00:28:54] Hannah Went: I think it's hard, yeah, because you know, with us we speak with the healthcare providers. We speak with the academics, but we may not actually be seeing the end user, the end patient. So sometimes it can be hard. It's like, "Hey, what difference are we actually making?" And that can be a little bit of a pain point or a struggle. I think not so much anymore because our providers will come back and give us case studies or, you know, talk to us about some of their findings, which is really exciting. And that, continues to expand as we do these clinical trials and dive deeper into the research. But I think we're TruDiagnostics sits right now is just an awesome opportunity because we are in between collaborators in terms of universities and academics and healthcare providers and patients. So we really bridge that gap as new algorithms, as new research is happening. We really do feel like we're at the centerfold and it's our responsibility to push that out to healthcare providers because there's no one really there to merge the two. So we'll start to see our type of healthcare providers we work with are willing to try anything, and willing to want the newest, latest, and greatest information as well to test on their patients. So they make for a really great group. [00:30:04] Lindsey Dinneen: Yeah, that's incredible. And it's so great to hear about the ability to bridge the gap between an individual being able to take ownership of their own health versus-- doctors are amazing. I'm so thankful for every medical person-- but also it's nice to be able to feel a little bit empowered to take ownership as well. So I appreciate that you're able to start bridging the gap and, and help them make be more accessible. So that's great. [00:30:30] Hannah Went: Yeah. Yeah. Definitely. [00:30:32] Lindsey Dinneen: Yeah, so, pivoting the conversation just for fun, imagine that you were to be offered a million dollars to teach your masterclass on anything you want. It can be in your industry, but it doesn't have to be. What would you choose to teach and why? [00:30:47] Hannah Went: Ooh. What would I choose to teach and why? I think the ,there's a book that's really good that I think everyone should read and it's called "The 15 Commitments of Conscious Leadership." And have you ever heard of it before, Lindsey? [00:31:00] Lindsey Dinneen: Nope, but I'm writing it down. [00:31:02] Hannah Went: Yeah. It's awesome. So there, there are a couple of authors on the book, but yeah, Jim Dethmer, he would previously go to all of these companies and understand how their leadership worked. And it's a super readable book, super short, breaks it down in all of these chunks, depending on what you want to really focus on. He actually came and spoke to our company and it was really cool to learn from him about this. He doesn't do it much anymore. So, we felt very special to, to be able to have him. And It can act in all areas of your life. So it's not necessarily just leadership . It really extrapolates out to relationships, whether it be a romantic one, or not, or kind of a family one. It is really I think changed my outlook on a lot of things in life. So I think I would want to teach something that has to do with that, that book. Jim's wife actually does a lot of the Enneagram work too. So the Enneagram test and understanding really your, kind of, why you're wired the way you are almost. Everyone has this conception of life. And you get to learn more about the way people think and how they work and why they do the things they do. So everyone did that test, the Enneagram test, in our company, and you can start to see these patterns and things. And it's just very useful information and it just makes everyone, I think, work together and flow together a little bit better too, which is awesome. [00:32:25] Lindsey Dinneen: Yeah. It sounds like a great masterclass and I have it written down. I'm going to, I'm going to look it up right after so I can secure my copy. Yeah. So, and then how do you wish to be remembered after you leave this world? . [00:32:39] Hannah Went: Oh, how do I wish to be remembered? Hopefully as someone who is loving and fun and taught the world something. Doesn't necessarily have to be epigenetics related, but I think people probably see me right now as someone who is like very busy running around all of the time, going from place to place, and I don't think I like that. That's just what I think my interpretation of me maybe would be from the outside. But it doesn't feel like I'm busy, right? It feels like I'm doing the things that I want to do right now and I don't think I necessarily even like the word busy, right? What does that mean? Everyone's busy. Everyone's doing something to a degree. So, yeah, I just want to be remembered as fun, loving you know, I think would also be remembered, though, just as hardworking, determined and yeah, willing to work hard to reach specific goals. [00:33:32] Lindsey Dinneen: I love that. Yeah. And then final question. What is one thing that makes you smile every time you see or think about it? [00:33:41] Hannah Went: Just my family, my husband, my sisters, my mom, my stepdad, everyone. So I get to hang out with them next weekend. I'm super, super excited. We'll be with them at their lake house. So I'm excited to be with the family. [00:33:55] Lindsey Dinneen: Nice. Oh yeah. That's going to be wonderful. Well, Hannah, this has been such a great conversation and I so appreciate your spending some time with me today and sharing about your incredible journey and everything that's coming up too. And I'm so excited for you and for this mission and to see the company continue to grow and expand, so I do really appreciate you. being here. And we are so honored to be making a donation on your behalf as a thank you for your time today to the Equal Justice Initiative, which provides legal representation to prisoners who may have been wrongly convicted of crimes, poor prisoners without effective representation, and others who may have been denied a fair trial. So thank you for choosing that organization to support and we just wish you the most continued success as you work to change lives for a better world. [00:34:49] Hannah Went: Awesome. Thank you, Lindsey. I appreciate your time. [00:34:51] Lindsey Dinneen: Absolutely, you too. And thank you also to our listeners for tuning in and if you're feeling as inspired as I am right now, I would love it if you would share this episode with a colleague or two and we will catch you next time. [00:35:06] Ben Trombold: The Leading Difference is brought to you by Velentium. Velentium is a full-service CDMO with 100% in-house capability to design, develop, and manufacture medical devices from class two wearables to class three active implantable medical devices. Velentium specializes in active implantables, leads, programmers, and accessories across a wide range of indications, such as neuromodulation, deep brain stimulation, cardiac management, and diabetes management. Velentium's core competencies include electrical, firmware, and mechanical design, mobile apps, embedded cybersecurity, human factors and usability, automated test systems, systems engineering, and contract manufacturing. Velentium works with clients worldwide, from startups seeking funding to established Fortune 100 companies. Visit velentium.com to explore your next step in medical device development.

We're in Canada for this podcast. Canadian Advocate Beth Vanstone has two daughters, one with CF and she's hosting this podcast with Laura Bonnell.Beth is introducing us to 32-year-old To Touraj Dehghan Manshadi who has a CF mutation that is common to Iran, but rare in Canada where he lives. You may be surprised to learn Canada does not have a rare disease strategy. We know American's thinking that medically everything is better in Canada, but that's not true. Many countries around the globe are struggling with the high cost of drugs for Rare Diseases, Canada is no exception. However, while we see industrialized countries around world looking at solutions to get rare therapies to patients quickly in an effort to maintain, improve and save lives, Canada remains stuck relying on a drug system designed to handle aspirin. Canada is the only country in the G7 without a national approach to rare diseases.In February 2023 the Federal government announced a Rare Disease Drug Strategy with a 1.4 billion budget over three yrs to support it. The expectation was that drugs for rare diseases would have a quicker pathway and that it would address the specific challenges of the rare community and fill some of the many gaps to access. Sadly, that has not been the case thus far. Beth says, “There are a lot of challenges for patients, it's very timely, there are a lot of gaps that will potentially harm patients.”  Touraj is one of the patients falling through the gaps.Touraj says his FEV1 is 35 percent, which means he is potentially looking at a double lung transplant. “It is shocking that in the next two to three years I might be getting to the point of needing a transplant. We're sad about it. My girlfriend is sadder about it than I am right now. I think of it as more of a reality.”  The hope would be access to a drug, despite his rare mutation, but the ability to try it.To connect with TourajInstagram: https://www.instagram.com/tojyla/Facebook: https://www.facebook.com/touraj.dehghan/Linkedin:  https://www.linkedin.com/in/touraj-manshadi Please like, subscribe, and comment on our podcasts!Please consider making a donation: https://thebonnellfoundation.org/donate/The Bonnell Foundation website:https://thebonnellfoundation.orgEmail us at: thebonnellfoundation@gmail.com Thanks to our sponsors:Vertex: https://www.vrtx.comViatris: https://www.viatris.com/en

GİRİŞ GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease) İnsiyatifi, eldeki en iyi bilimsel verilerle KOAH için yönetim önerileri sunma amacıyla 1998 yılında kurulmuştu. İlk GOLD Raporu, 2001 yılında yayınlandı. Bunu 2006 ve 2011 yıllarında yayınlanan raporlar takip etti. Geçtiğimiz günlerde yayınlanan GOLD 2024 Kılavuzu, Revize Edilmiş 2023 Kılavuzunun bir güncellemesi. GOLD'un ana kılavuzları bu şekilde aralıklarla güncelleme adeti var: 2011 Kılavuzunu sonraki 4 yıl boyunca her yıl güncellemiş, 2017 Kılavuzunu ise sonraki 5 yıl boyunca her yıl yenilemişti (Sitemizdeki ilgili yazılar: 2013 - 2015 - 2017 - 2018 - 2020 - 2022). Bu yazı dizimizde işte bu 2024 Güncellemesini (sade haliyle) 4 bölüm halinde Türkçeye kazandırmaya çalışacağız. Klinik pratiğimize doğrudan etki etmesini beklemediğimiz akademik bölümleri çevirilerimizde kapsam dışı tutacağız. Kılavuzun orijinaline buradan ulaşabilirsiniz: 2024 GOLD Report. KANIT DÜZEYLERİ Kanıt temelli önerilere yer verildiğinde, bu önerilerin kanıt düzeyleri parantez içinde şu şekilde sunulmuştur: (Kanıt Düzeyi A). Aşağıdaki tabloda Kanıt Düzeyleri ve anlamları yer almaktadır: Kanıt KategorisiKanıt KaynağıARandomize Kontrollü ÇalışmalarABelirgin sınırlılık veya taraflılık içermeyen yüksek kaliteli zengin kanıtlarBÖnemli sınırlılıkları olan randomize kontrollü çalışmalarBSınırlı kanıtlarCRandomize olmayan çalışmalarGözlemsel çalışmalarDPanel konsensus değerlendirmesi KOAH NEDİR? Tanım Kronik Obstrüktif Akciğer Hastalığı (KOAH); hava yollarındaki (bronşit, bronşiyolit) ve/veya alveollerdeki (amfizem) anormalliklere bağlı kronik solunum semptomları (nefes darlığı, öksürük, balgam üretimi ve/veya alevlenmeler) ile karakterize, genellikle ilerleyici kalıcı hava akımı obstrüksiyonuna yol açan heterojen bir akciğer rahatsızlığıdır. Nedenler ve Risk Faktörleri KOAH, bireyin yaşamı (T) boyunca meydana gelen gen(G)-çevre(E) etkileşimlerine bağlı olarak akciğerlerin zarar görmesi ve/veya normal gelişim/yaşlanma süreçlerinin değişmesinden kaynaklanır (GETomics). KOAH'a yol açan temel çevresel maruziyetler, tütün içimi ve evdeki ve dış ortamdaki hava kirliliğinden kaynaklanan zehirli parçacıkların ve gazların solunmasıdır; ancak diğer çevresel ve konakçı faktörler de (anormal akciğer gelişimi ve hızlanmışış akciğer yaşlanması dahil) katkıda bulunabilir. Bugüne kadar tanımlanan KOAH için en alakalı (epidemiyolojik olarak nadir olsa da) genetik risk faktörü SERPINA1 genindeki mutasyonlardır ve α1-antitripsin eksikliğine yol açar, ancak bireysel etki büyüklüğü düşük olan diğer genetik varyantlar akciğer fonksiyonunda azalma ve KOAH riskinde artışla ilişkilidir. Tanı Kriterleri Uygun klinik bağlamda (bkz. yukarıdaki 'Tanım' ve 'Nedenler ve Risk Faktörleri'), spirometri ile ölçülen, tamamen geri döndürülemez hava akışı kısıtlılığı (Bronkodilatasyon sonrası FEV1/FVC < 0,7) varlığı, KOAH teşhisini doğrular. Ancak bazı bireylerde; hava akımı obstrüksiyonu (Bronkodilatasyon sonrası FEV1/FVC ≥ 0,7) olmaksızın yapısal akciğer lezyonları (örn. amfizem) ve/veya fizyolojik anormallikler (düşük-normal FEV1, gaz hapsi, hiperinflasyon, azalmış akciğer difüzyon kapasitesi ve/veya hızlı FEV1 düşüşü dahil) ile ortaya çıkabilir. Bu konular 'Pre-KOAH' olarak etiketlenmiştir. 'PRISm' (Korunmuş Oran Bozulmuş Spirometri) terimi normal oranlı ancak anormal spirometriye sahip olanları tanımlamak için önerilmiştir. Pre-KOAH veya PRISm'li kişiler zaman içinde hava akımı obstrüksiyonu geliştirme riski altındadır, ancak hepsinde bu durum söz konusu değildir. Bu kişiler için (sigarayı bırakmanın ötesinde) en iyi tedavinin ne olduğunu belirlemek için araştırmaya ihtiyaç vardır. Klinik Prezentasyon KOAH'lı hastalar tipik olarak nefes darlığı, hırıltı, göğüste sıkışma, yorgunluk, aktivite kısıtlılığı ve/veya balgamlı veya balgamsız öksürükten şikayetçidir ve alevlenmeler olarak adlandırılan, sağlık durumlarını ve prognozunu etkileyen ve spesifik önleyici ve tedav...

En este episodio nos sumergimos en el mundo de las pruebas de función respiratoria. Comenzamos con una revisión detallada de los conceptos básicos, asegurándonos de que todos los fundamentos estén claros y bien entendidos. A continuación, exploramos los diferentes tipos de pruebas, como la espirometría, la capacidad vital forzada (FVC), el volumen espiratorio máximo en el primer segundo (FEV1) y la relación FEV1/FVC. Explicamos cómo interpretar estos resultados y su relevancia clínica en diversas condiciones pulmonares. Para asegurarnos de que estés completamente preparado para el ENARM, incluimos consejos sobre cómo abordar preguntas relacionadas con este tema en el examen, destacando trampas comunes y estrategias para elegir la mejor respuesta. Este episodio es una herramienta indispensable para cualquier médico que se prepare para el ENARM y busque dominar las pruebas de función respiratoria, un área fundamental en la medicina respiratoria. ¡Asegúrate de escucharlo y estar un paso más cerca de alcanzar tus metas profesionales!

Dr. John Fleetham chats with Dr. Surya Bhatt about his article, “FEV1/FVC Severity Stages for Chronic Obstructive Pulmonary Disease.”

As we age, physical fitness tends to decline. This decline can be attributed to various factors such as changes in body composition, reduced muscle mass and strength, decreased flexibility, and diminished cardiovascular endurance. Additionally, the body's ability to recover from physical exertion also tends to slow down with age.It has been well validated that the rate at which this decline occurs varies among individuals. However, those who maintain their physical fitness as they age experience a lower risk of various diseases and tend to enjoy longer lives. At the molecular level, changes in fitness and related indicators of functional capacity coincide with molecular markers of decline, which are believed to reflect underlying biological aging processes. Therefore, measurements of fitness offer a novel perspective on biological aging. Nevertheless, the measurement of fitness parameters presents challenges due to the need for in-person data collection by skilled experts utilizing specialized equipment. Moreover, remote data collection or studies involving stored biospecimens do not facilitate direct assessments of fitness. To overcome this limitation and facilitate the evaluation of fitness in such scenarios, Kristen Mcgreevy has developed blood-based DNAm biomarkers that encompass various aspects of fitness, including mobility (gait speed), strength (grip strength), lung function (forced expiratory volume in one second), and cardiovascular fitness (VO2 max). These biomarkers form the basis of a groundbreaking indicator known as DNAmFitAge, which quantifies biological age based on fitness levels. This research also highlights the influence lifestyle has on the aging methylome.In this week's Everything Epigenetics podcast, Kristen and I chat about the importance of physical fitness as we age, how she developed blood DNAm biomarkers for four fitness parameters, and how she created DNAmFitAge. We also focus on FitAgeAcceleration in age-related conditions and DNAmFitAge relationship to physical activity and body builders. Kristen is in the final year of her PhD, studying biostatistics at UCLA.In this episode of Everything Epigenetics, you'll learn about: Kristen McGreevy's interest in biostatistics and epigeneticsWhy Kristen made the decision to get her PhDThe definition of strength training Why physical  fitness is important for agingWhich aspect of physical activity is the most important for longevity and healthWhat prompted Kristen to create DNAm estimators of fitness parameters Gait speed (walking speed)Handgrip strengthForced expiratory volume in 1 second (FEV1; an index of lung function)Maximal oxygen uptake (VO2max; a measure of cardiorespiratory fitnessWhy Kristen chose gait speed, grip strength, FEV1, and VO2max for her predictorOther biomarkers Kristen considered for her studyWhat makes these biomarkers different from other DNAm biomarkersHow Kristen created DNAmFitAgeThe population used to create DNAmFitAgeThe application of DNAmFitAge How DNAmFitAge is related to athletes, physical activity, and age-related phenotypesWhat these biomarkers contribute to the field of aging and EpigeneticsEpigenetic memory How we can trust that the DNAmFitAge is a biomarker of agingWhat these biomarkers don't they tell usKristen's focus now and her future workSupport the showThank you for joining us at the Everything Epigenetics Podcast and remember you have control over your Epigenetics, so tune in next time to learn more about how.

On the June episode of JHLT: The Podcast, the Digital Media Editors explore two manuscripts from the June issue of The Journal of Heart and Lung Transplantation, with authors from the US and Denmark.   First, hear from senior author Steven R. Hays, MD, on his team's study “Design and implementation of a digital health home spirometry intervention for remote monitoring of lung transplant function,” which explores digital health and comes out of UCSF. In the study, the authors developed an automated digital health intervention using Bluetooth-enabled home spirometers to monitor for complications after lung transplantation. Using a chat-based application, patients could perform home spirometry, answer symptom queries, and receive patient education. The program could also alert both the patient and center providers to substantial decreases in FEV1 from baseline—and any other concerning symptoms.   Dr. Hays and Digital Media Editors Erika Lease, MD, and Van-Khue Ton, MD, PhD, discuss how COVID-19 created a serendipitous moment to fund the study, and some of the most valuable lessons from the rollout of the program, including creating efficiencies among the transplant team, proper resourcing, and next steps for perfecting the program.   Next, the editors welcome first author Niels Moeslund, MD, PhD, from Aarhus University in Denmark, to discuss the paper, “Ex-situ oxygenated hypothermic machine perfusion in donation after circulatory death heart transplantation following either direct procurement or in-situ normothermic regional perfusion.” In the study, authors set out to explore the use of oxygenated hypothermic machine perfusion as an alternative to in-situ normothermic regional perfusion or ex-situ normothermic machine perfusion of DCD hearts. They used a porcine model to simulate a DCD setting, and performed either normothermic regional perfusion and static cold storage; normothermic regional perfusion with hypothermic machine perfusion with the XVIVO heart preservation system; or direct procurement with hypothermic machine perfusion—all before heart transplantation was performed.   Digital Media Editor David Schibilsky, MD, digs in with Dr. Moeslund on the main findings of the study, in which HMP hearts showed better contractility after transplantation despite significantly lower inotropic support. Why? Dr. Moeslund shares that the hypothermia of HMP keeps metabolic activity low while myocytes are being replenished, creating maximum potential for energy restoration.   Follow along at www.jhltonline.org/current, or, if you're an ISHLT member, log in at ishlt.org/journal-of-heart-lung-transplantation.  Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.

A new research paper was published in Aging (Aging-US) Volume 15, Issue 10, entitled, “DNAmFitAge: biological age indicator incorporating physical fitness.” Physical fitness is a well-known correlate of health and the aging process and DNA methylation (DNAm) data can capture aging via epigenetic clocks. However, current epigenetic clocks did not yet use measures of mobility, strength, lung, or endurance fitness in their construction. In this new study, researchers develop blood-based DNAm biomarkers for fitness parameters including gait speed (walking speed), maximum handgrip strength, forced expiratory volume in one second (FEV1), and maximal oxygen uptake (VO2max) which have modest correlation with fitness parameters in five large-scale validation datasets (average r between 0.16–0.48). “These parameters were chosen because handgrip strength and VO2max provide insight into the two main categories of fitness: strength and endurance [23], and gait speed and FEV1 provide insight into fitness-related organ function: mobility and lung function [8, 24].” The researchers then used these DNAm fitness parameter biomarkers with DNAmGrimAge, a DNAm mortality risk estimate, to construct DNAmFitAge, a new biological age indicator that incorporates physical fitness. DNAmFitAge was associated with low-intermediate physical activity levels across validation datasets (p = 6.4E-13), and younger/fitter DNAmFitAge corresponds to stronger DNAm fitness parameters in both males and females. DNAmFitAge was lower (p = 0.046) and DNAmVO2max is higher (p = 0.023) in male body builders compared to controls. Physically fit people had a younger DNAmFitAge and experienced better age-related outcomes: lower mortality risk (p = 7.2E-51), coronary heart disease risk (p = 2.6E-8), and increased disease-free status (p = 1.1E-7). These new DNAm biomarkers provide researchers a new method to incorporate physical fitness into epigenetic clocks. “Our newly constructed DNAm biomarkers and DNAmFitAge provide researchers and physicians a new method to incorporate physical fitness into epigenetic clocks and emphasizes the effect lifestyle has on the aging methylome.” DOI - https://doi.org/10.18632/aging.204538 Corresponding authors - Kristen M. McGreevy - kristenmae@ucla.edu, Zsolt Radak - radak.zsolt@tf.hu, and Steve Horvath - shorvath@mednet.ucla.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204538 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, epigenetics, physical fitness, biological age, DNA methylation About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (listed as “Aging (Albany NY)” by MEDLINE/PubMed and “Aging-US” by Web of Science) Volume 14, Issue 23, entitled, “DNA methylation GrimAge version 2.” Researchers Ake T. Lu, Alexandra M. Binder, Joshua Zhang, Qi Yan, Alex P. Reiner, Simon R. Cox, Janie Corley, Sarah E. Harris, Pei-Lun Kuo, Ann Z. Moore, Stefania Bandinelli, James D. Stewart, Cuicui Wang, Elissa J. Hamlat, Elissa S. Epel, Joel D. Schwartz, Eric A. Whitsel, Adolfo Correa, Luigi Ferrucci, Riccardo E. Marioni, and Steve Horvath from the University of California Los Angeles, Altos Labs, University of Hawaii at Manoa, Fred Hutchinson Cancer Research Center, University of Edinburgh, National Institute on Aging, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Harvard T.H. Chan School of Public Health, University of California – San Francisco, and the University of Mississippi Medical Center previously described a DNA methylation (DNAm) based biomarker of human mortality risk DNAm GrimAge. In their current study, the researchers describe version 2 of GrimAge (trained on individuals aged between 40 and 92) which leverages two new DNAm based estimators of (log transformed) plasma proteins: high sensitivity C-reactive protein (logCRP) and hemoglobin A1C (logA1C). “To arrive at version 2 of GrimAge, we developed two additional DNAm based surrogates for plasma proteins that are widely used in the clinic (DNAm logCRP and DNAm logA1C).” The team evaluated GrimAge2 in 13,399 blood samples across nine study cohorts. After adjustment for age and sex, GrimAge2 outperforms GrimAge in predicting mortality across multiple racial/ethnic groups (meta P=3.6×10-167 versus P=2.6×10-144) and in terms of associations with age related conditions such as coronary heart disease, lung function measurement FEV1 (correlation= -0.31, P=1.1×10-136), computed tomography based measurements of fatty liver disease. The researchers presented evidence that GrimAge version 2 also applies to younger individuals and to saliva samples where it tracks markers of metabolic syndrome. DNAm logCRP is positively correlated with morbidity count (P=1.3×10-54). DNAm logA1C is highly associated with type 2 diabetes (P=5.8×10-155). DNAm PAI-1 outperforms the other age-adjusted DNAm biomarkers including GrimAge2 in correlating with triglyceride (cor=0.34, P=9.6×10-267) and visceral fat (cor=0.41, P=4.7×10-41). Overall, the team demonstrated that GrimAge version 2 is an attractive epigenetic biomarker of human mortality and morbidity risk. “GrimAge2 will not replace existing clinical biomarkers. Rather, GrimAge2 complements existing clinical biomarkers when evaluating an individual's aging rate.” DOI: https://doi.org/10.18632/aging.204434 Corresponding Author: Steve Horvath - shorvath@mednet.ucla.edu About Aging-US: Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com.

VIDEOS: Unpayable Debt & Deadly Vax Causing Hell on Earth – Ed Dowd – start 6:30 -20:00 What Greta Thunberg does not understand about climate change | Jordan Peterson – 7:09 Gary Null – Speaks to U.N. on Earth Day (Part 2 of 2) – 9:30 Neil Oliver: ‘By taking back control of the money we can begin regaining control of our world'  Breast health linked to eating peanut butter and nuts Washington University School of Medicine, September 27, 2022 By eating more peanut butter during their high school years, girls could be improving their breast health in adulthood, according to a US study published recently in the journal Breast Cancer Research and Treatment. Dr. Graham Colditz, of Washington University School of Medicine in St. Louis, and colleagues found that girls aged 9 to 15 who ate peanut butter and nuts twice a week were 39% less likely to develop benign breast disease by the age of 30 than girls who did not. Benign breast disease includes lumps or tender spots that turn out to be fibrous tissue and/or cysts, as well as other conditions like hyperplasia, an overgrowth of the cells that line the ducts in the glandular breast tissue. Although benign breast disease is not cancerous, it can raise the risk of developing breast cancer later in life. For their study, he and his colleagues looked at health data on over 9,000 American schoolgirls recruited to The Growing Up Today Study.  The data also included reports from the girls between when they were 18 to 30 years old, that indicated whether they had ever been diagnosed with biopsy-confirmed benign breast disease. When they compared the two sets of data, the researchers found that participants who had eaten peanut butter or nuts twice a week were 39% less likely than peers who never ate those foods to receive a diagnosis for benign breast disease. The data suggest pulse foods – soy and other beans and lentils – and corn may also be linked to reduced risk of benign breast disease, but because they did not feature as much in the diets of these girls, the evidence was not so strong.And they concluded that “consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD [benign breast disease] as young women.” Pine bark extracts may help curb age-related muscle loss; Study D'Annunzio University (Italy), September 28, 2022 Supplements containing the French maritime pine bark extract Pycnogenol may help stabilize muscle loss, support muscular function, and boosts daily muscle endurance, says a new study. Data from a study with 64 healthy seniors aged 70-78 indicated that 150 mg per day of Pycnogenol may improve muscle function and endurance in a range of everyday activities, from carrying items to climbing stairs and walking. Results published in Minerva Ortopedica e Traumatologica also indicated that supplementation with the pine bark was associated with a reduction in oxidative stress of 14%. Oxidative stress is reportedly a common measurement of sarcopenia which prevents the body from normal detoxifying and repair. “Supplementation with Pycnogenol – suppressing the excess in oxidative stress and controlling muscular pain and fatigue – possibly in association with some specific protein and vitamins supplementation, may produce faster muscular replacement and muscular remodeling improving physical functions and fitness. In this study, muscle loss appeared to be controlled and reduced,” wrote the authors from Irvine3 Labs and D'Annunzio University in Italy. Sarcopenia Muscle loss is a natural part of aging, and researchers have estimated that, after the age of 50, we lose 1-2% of our muscles each year. Strength declines as well, at a rate of 1.5% per year beginning at 50 years and accelerating to 3% after the age of 60. Results showed that the pine bark group experienced greater muscular function and endurance in daily tasks such as carrying items (4-5 lbs) (71% improvement versus 23% in the control group), climbing stairs (52 % improvement versus 20% in the control ground) and distance walked (38% improvement versus 17% in the control group). Supplementation with Pycnogenol was also associated with reduced proteinuria – the presence of protein in urine which, with normal kidney function, can indicate waste from muscle erosion – by 40%. In addition, individuals who took the pine bark extract supplements demonstrated improved general fitness scores by more than 46% in comparison with the control group. Study links prenatal phthalate exposure to reduced childhood lung function Barcelona Institute for Global Health, October 3, 2022 A study led by the Barcelona Institute for Global Health (ISGlobal) has found that exposure to phthalates in the womb is associated with reduced lung function during childhood. The findings of the study, published in Environmental Pollution, support the European Union's current restrictions on the use of these substances Phthalates are chemical compounds that are widely used as plasticizers, as well as in lacquers and varnishes. They are found in a wide variety of consumer products, ranging from toys to food packaging, clothing, detergents, cosmetics, solvents, etc. Over time, phthalates in these products leach into the surrounding environment—for example, into the air, dust and food—making them virtually ubiquitous. Moreover, human exposure to phthalates starts as early as in utero, given that these compounds are able to cross the placental barrier. Phthalates act as endocrine disruptors and have been associated with numerous developmental and reproductive health problems. “Research has consistently found that gestational phthalate exposure is associated with increased risk of childhood asthma, but the evidence on its possible association with lung function is scarce and unclear,” explained ISGlobal researcher Magda Bosch de Basea, lead author of the study. The study included 641 mother-child pairs from the INMA Project birth cohorts in Sabadell and Gipuzkoa. Gestational phthalate exposure was analyzed using urine samples collected from the mothers during pregnancy. The children's lung function was assessed by spirometry at various stages of development between the ages of four and eleven years. As an indication of the ubiquity of these compounds, laboratory analyses detected all nine of the studied phthalate metabolites—i.e., substances into which phthalates are transformed once metabolized by the human body—in nearly 100% of the urine samples examined. At all stages of development, the studied metabolites were associated with decreases in two lung function parameters: forced vital capacity (FVC), which measures the maximum volume of air a person is able to exhale, and forced expiratory volume in 1 second (FEV1), which measures the maximum exhaled volume in the first second of exhalation. T The researchers found that the associations between certain metabolites (e.g. MiBP and MBzP) and decreased lung function were generally statistically significant at younger ages, but not in spirometries performed in later years. This pattern is consistent with the findings of studies in animal models suggesting that the possible effects of these compounds on lung function revert over time. Eating late increases hunger, decreases calories burned, and changes fat tissue Brigham and Women's Hospital, October 4, 2022 A new study by investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, found that when we eat significantly impacts our energy expenditure, appetite, and molecular pathways in adipose tissue. Their results are published in Cell Metabolism. “In this study, we asked, ‘Does the time that we eat matter when everything else is kept consistent?'” said first author Nina Vujović, Ph.D. “And we found that eating four hours later makes a significant difference for our hunger levels, the way we burn calories after we eat, and the way we store fat.” Vujović, Scheer and their team studied 16 patients with a body mass index (BMI) in the overweight or obese range. Each participant completed two laboratory protocols: one with a strictly scheduled early meal schedule, and the other with the exact same meals, each scheduled about four hours later in the day. In the last two to three weeks before starting each of the in-laboratory protocols, participants maintained fixed sleep and wake schedules, and in the final three days before entering the laboratory, they strictly followed identical diets and meal schedules at home. In the lab, participants regularly documented their hunger and appetite, provided frequent small blood samples throughout the day, and had their body temperature and energy expenditure measured. To measure how eating time affected molecular pathways involved in adipogenesis, or how the body stores fat, investigators collected biopsies of adipose tissue from a subset of participants during laboratory testing in both the early and late eating protocols, to enable comparison of gene expression patterns/levels between these two eating conditions. Results revealed that eating later had profound effects on hunger and appetite-regulating hormones leptin and ghrelin, which influence our drive to eat. Specifically, levels of the hormone leptin, which signals satiety, were decreased across the 24 hours in the late eating condition compared to the early eating conditions. When participants ate later, they also burned calories at a slower rate and exhibited adipose tissue gene expression towards increased adipogenesis and decreased lipolysis, which promote fat growth. Notably, these findings convey converging physiological and molecular mechanisms underlying the correlation between late eating and increased obesity risk. “This study shows the impact of late versus early eating. Here, we isolated these effects by controlling for confounding variables like caloric intake, physical activity, sleep, and light exposure, but in real life, many of these factors may themselves be influenced by meal timing,” said Scheer.  The immune system benefits from life in the countrysideAarhus University (Denmark), September 30, 2022Research from Aarhus University has demonstrated that exposure to a farming environment may prevent or dampen hypersensitivities and allergies — even in adultsAdults who move to farming areas where they experience a wider range of environmental exposures than in cities may reduce the symptoms of their hypersensitivities and allergies considerably. This is the result of new research from Aarhus University.This pioneering result was published online in the esteemed periodical, The Journal of Allergy and Clinical ImmunologyThe immune systems of people who work in farming are frequently exposed to a wide range of bacteria, fungi, pollen and other irritants which may trigger a response that protects them against hypersensitivity. Working in a farming environment may therefore serve to prevent or dampen hypersensitivity to the most widespread plant allergens: grass and birch pollen.Surprisingly, the positive effect on the immune system is seen both in people who have lived in urban environments and in adults who were born and raised in farming areas. But the real surprise is that the effect is not only seen in children:”Previously, the assumption was that only persons who had lived in farming areas while growing up would benefit from the environment's protective effect on the immune system. But now we can demonstrate that it's not too late simply because you are an adult,” says postdoc Grethe Elholm.It is, in other words, possible to affect the immune system and thereby the hypersensitivity which may cause allergy and allergic asthma − and what is more, this can be done at a much later point in life than previously assumed. High Blood Pressure Linked To Faster Cognitive Decline, Dementia Risk   University of Michigan, October 1, 2022 High blood pressure, or hypertension, often causes people to feel perpetually stressed out or angry. Now, researchers from the University of Michigan say people with hypertension may also experience a faster deterioration in their cognitive abilities (thinking skills, decision making, memory) in comparison to those with normal blood pressure. The team performed a “study of studies” focusing on high blood pressure's association with declining brain function over a period of several years. They gathered and analyzed datasets collected for six large prior studies. Originally, researchers set out to determine if fluctuations in long-term blood pressure control may somewhat explain why Hispanic Americans experience a 50-percent higher risk of developing dementia by the end of their lives in comparison to non-Hispanic white people living in the United States. Somewhat surprisingly, that study failed to produce a clear answer, as blood pressure-related cognitive decline appears to occur at about the same pace among Hispanics and Caucasians. Study authors conclude their work suggests other factors are at play regarding why Hispanics are generally more at risk of dementia. Still, these findings make a strong case that blood pressure has a connection to cognitive outcomes later in life. Maintaining a healthy blood pressure level looks to protect thinking skills, study authors say. “Our findings suggest that high blood pressure causes faster cognitive decline, and that taking hypertension medication slows the pace of that decline,” says lead study author Deborah Levine, M.D., M.P.H., director of the University of Michigan's Cognitive Health Services Research Program and a professor of internal medicine at the U-M's academic medical center, in a media release. Researchers examined changes in the thinking and memory abilities among a group of adults (18+) who took part in six long-term studies conducted over the past five decades. Study authors enjoyed access to an average of eight years' worth of data for each participant, including systolic blood pressure (the top number in any blood pressure reading). The  data encompassed 22,095 non-Hispanic white adults and 2,475 Hispanic adults. None of the participants had any documented history of stroke or dementia at the time of enrollment. To start, average systolic blood pressure was lower among Hispanic adults in comparison to non-Hispanic white adults (132.5 mmHg compared with 134 mmHg). This is especially notable considering Hispanic adults in the study displayed an older average age than non-Hispanic adults (62 versus 54 years-old). Blood pressure readings tend to increase with age. Among both Hispanics and non-Hispanics, the team observed the same pace of deteriorating thinking skills and memory linked to high blood pressure. However, when researchers focused solely on the two studies that had deliberately recruited Hispanics, they noted an undeniably faster decline in overall cognitive performance among Hispanics in comparison to the non-Hispanic white group. Importantly, though, blood pressure differences between those two groups didn't appear to explain this cognitive decline difference. This may be due to Hispanic participants having lower blood pressure than non-Hispanic whites in these studies, researchers speculate.The study is published in the Journal of Alzheimer s Disease.

Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. This week, we sit down with Thoracic Surgeon, Dr. Jane Yanagawa to discuss surgical considerations in treatment of NSCLC. * How do you choose what type of surgical resection to do?- Considerations: --Lung anatomy --Location of the nodule within lung--Lymph node involvement-Options: --Pneumonectomy: removal of whole lung --Lobectomy: remove a whole lobe--Segmentectomy/sublobar resection: part of a lobe* What does “adequate margins” mean? And how do you know if it's enough?- If you're removing the whole lobe, it does not matter as much - If you're doing a segmentectomy, you want to have samples evaluated while in the OR because if there is signs of more disease that initially thought, you would take this one step further and do a lobectomy. - Need to consider the patient's situation - how good is their status * Why does preoperative workup matter?- Pulmonary function tests: Surgeons are looking at the %FEV1 and %DLCO to then predict what their function would be AFTER surgery. After surgery, they want to ensure patient has %FEV1 or %DLCO >40%. - Lung anatomy: In patients with COPD and endobronchial lesions, sometimes they also get V/Q scans to evaluate ratio- Cardiac echo: Important in pneumonectomy where removal of lung tissue will also remove a significant amount of blood vessels. Want to rule out pulmonary hypertension pre-operatively. - Pulmonary hypertension can also affect someone's survival while they're ventilating with only one lung during the procedure (“single lung ventilation”). - Smoking status: Smoking can increase complications by ~60%. - Pre-habilitation: Encouraging patients to be fit prior to surgery with walking, nutrition, +/- pulmonary rehabilitation* What is “VATS”?- VATS stands for video-assisted thoracoscopic surgery; it is not, in itself, a procedure. But a VATS allows for minimally invasive surgery through the use of a camera. - It involves three incisions (axilla, lowest part of mid-axillary line, one posterior)* In what scenario is a mediastinoscopy warranted? - Needed after EBUS if there is still high index of suspicion for cancer involvement in lymph nodes, even if lymph nodes are negative from EBUS* What is “systematic lymph node sampling”?- An organized way to sample lymph nodes, including all lymph nodes that are along the way, not just the ones that may be involved * As a surgeon, how do you determine if a patient is okay for surgery if the mass is invading another structure?- Need to take the anatomy into consideration - are there major blood vessels or nerves there, for instance, which can impact outcome and recovery.* When should we consider induction chemotherapy from a surgeon's perspective?- Lots of changes in this sphere coming; lots of discrepancy between institutions when there is N2 disease - In Dr. Yanagawa's opinion, anyone with N2 disease should get neoadjuvant therapy * If there is neoadjuvant chemoradiation given, how does that effect your surgery?- Radiation increases scar tissue in the lung tissue. But what is worse is that radiation neoadjuvantly may make wound healing more difficult. She does not prefer radiation pre-operatively- Chemotherapy also adds scar tissue*How does neoadjuvant IO therapy affect scar tissue formation?- The hilum and lymph nodes are more swollen, but does not translate to more complications - She has even seen patients who had gotten IO for another cancer and then get lung cancer, she can still appreciate swollen nodes!* How long after surgery is it safe to start adjuvant therapy?- If patient has a complication from surgery, would not start right away. It is important to discuss with the surgeon about when it is okay to proceed with adjuvant therapy. - If patient has good recovery/without complications, okay to start about 4 weeks after- There is no good guidance yet about when it is safe to start IO after surgery About our guest: Jane Yanagawa, MD is an Assistant Professor of Thoracic Surgery at the UCLA David Geffen School of Medicine and the UCLA Jonsson Comprehensive Cancer Center. She completed medical school at Baylor College of Medicine, after which she went to UCLA for her surgical residency. She went onto Memorial Sloan-Kettering for her Thoracic Surgery Fellowship. In addition to her practice as a thoracic surgeon at UCLA, Dr. Yanagawa also sits on the NCCN NSCLC guidelines committee! We are so grateful she was able to join us despite her very busy schedule! Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast

Videos : Those who speak out are shouted down until they are proved right, says Neil Oliver – 10:06 Gad Saad: Why Rational People Fall for ‘Parasitic' Ideas | American Thought Leaders CLIP – 9:11 Scientist Carl Sagan testifying to the U.S. Senate in 1985 on the greenhouse effect: – 2:44 Parent Eviscerates School Board Over Censorship– 4:59 Vitamin C supplementation associated with improved lung function in COPD Medical College of Lanzhou University (China), September 23 2022. The International Journal of Chronic Obstructive Pulmonary Disease published a systematic review and meta-analysis of clinical trials that found improvement in lung function among chronic obstructive pulmonary disease (COPD) patients who received vitamin C. The disease is characterized by airflow limitation and persistent respiratory symptoms. Ting Lei of Medical College of Lanzhou University in Lanzhou, China and associates identified 10 randomized, controlled trials that included a total of 487 adults with COPD for the meta-analysis. The trials compared lung function and/or antioxidant enzyme or nutrient levels of COPD patients who received vitamin C to a placebo or control group. The meta-analysis found improvement in forced expiratory volume in one second as a percentage (FEV1%, a measure of lung function) in association with vitamin C supplementation. When dosage was analyzed, it was determined that consuming more than 400 milligrams vitamin C per day was needed experience a significant benefit. The ratio of FEV1 to forced vital capacity (another lung function assessment), and levels of vitamin C and glutathione, both of which are antioxidants, also improved among participants who received vitamin C supplements. The authors remarked that oxidative stress, which is a disturbance of the oxidant to antioxidant balance, has been suggested as playing a role in the development of COPD. The current investigation is the first systematic review and meta-analysis to assess the effect of vitamin C supplementation in people with COPD. “We found that supplementing vitamin C to patients with COPD demonstrated vital clinical significance,” Lei and associates concluded. “Vitamin C supplementation could increase the levels of antioxidation in serum (vitamin C and glutathione) and improve lung function (FEV1% and FEV1/FVC), especially in patients treated with vitamin C supplementation greater than 400 mg/day.” Single Flavanoid (Found in 6 Foods) Reduces Cognitive Impairment Drastically Fourth Military Medical University (China), September 19, 2022 A singular flavanoid can protect the brain against cognitive deficit and other cellular damage, according to studies from the Fourth Military Medical University. The news comes from Xi'an, People's Republic of China, and shows great promise for those suffering from mental impairment due to Alzheimer's disease, vascular dementia, and other debilitating cognitive conditions. The study abstract concludes: “Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease.” Rutin is a biologically active flavonoid found in the following foods:  Buckwheat – Possibly the best source of rutin, and much better than boiled oats, uncooked buckwheat leaf flower offers about 675 mg in a 1.1 cup serving. Uncooked buckwheat groats contain 230 mg of rutin per 1 kg, dark buckwheat flour has 218 mg per 1 kg and buckwheat noodles provide 78 mg. Elderflower Tea – When dried, the white flowers of the elderflower make a delicious and rutin-filled tea. According to the Czech Journal of Food Science, elderflower tea contains approximately 10.9g/kg of rutin per brewed cup. Amaranth Leaves – In Western cultures, most people are familiar with the edible seeds of amaranth, though in Chinese and Southeast Asian cooking the leaves are also gaining traction, partly due to their high rutin content. You can expect around 24.5g/kg from the dried leaves. Seeds only contain trace amounts of the important nutrient. Unpeeled Apples – Keep the peel on your apples to enjoy lots of rutin. Just be sure that they are organic, since apple peels are especially prone to pesticide build-up. Apple skins are 6x as powerful as the flesh at preventing high blood pressure due to this flavanoid, too. • Unfermented Rooibos Tea – While rooibos tea contains fewer antioxidants than black or green teas, it is a good source of rutin, providing around 1.69 mg/g. • Figs – These little gems contain about the same amount of rutin as apples, so be sure to add them to your diet. The scientists found that rutin works primarily through anti-inflammatory mechanisms, and reducing hypofusion in the brain. Resistance-breathing training found to lower blood pressure University of Colorado and University of Arizona, September 23, 2022 A team of researchers with members from the University of Colorado, the University of Arizona and Alma College, has found that resistance-breathing training can lower blood pressure as much as some medicines and/or exercises. The study is published in the Journal of Applied Physiology. Hypertension, also known as chronic high blood pressure, can lead to a wide variety of health problems, from loss of vision to strokes and heart attacks. For that reason, doctors take it seriously. Typically, patients are directed to modify their diet and to exercise more. If that does not fix the problem, medications are prescribed. In this new effort, the researchers looked into a new type of therapy to reduce blood pressure levels—resistance-breathing training. Resistance-breathing training involves breathing in and out of a small device, called, quite naturally, a POWERbreathe, every day for several minutes. The device forces the patient to use their breathing muscles to push and pull air through it, making them stronger. And that, the researchers found, also reduces blood pressure. The device has been in use for several years as a means to assist athletes, singers and people with weak lung muscles. Several groups of healthy volunteers practiced the training for a few minutes every day for six weeks. Each was breathed in and out with the device 30 times each session. Each of the volunteers had their blood pressure measured before and after the training. The researchers found a sustained average drop of 9 mmHg in systolic blood pressure (the top number in blood pressure readings)—normal pressure is defined as 120/80. They describe the change as significant, as much as some patients see with medication. They also note that it is similar to changes in many patients who begin an aerobic exercise regimen, such as walking, cycling or running. They suggest such training could be used by patients of all ages who are unable to exercise to lower their blood pressure. How To Maintain Peak Brain Health: Scientists Say It Comes Down To These 3 Factors Norwegian University of Science and Technology, September 23, 2022 What's the best way to maintain peak brain health as we age? There are countless studies detailing ways to prevent cognitive decline, so scientists in Norway sought to simplify the science of managing strong brain health to three recommendations. This report is something of a summation covering modern science's current understanding of how best to cultivate robust brain health. The team at NTNU cite 101 references to prior articles in this latest theoretical perspective paper. “Three factors stand out if you want to keep your brain at its best,” Prof. Sigmundsson adds. The three identified keys to strong brain health are: Physical exercise Social activity Strong, passionate interests and hobbies It's common knowledge that spending all day on the couch isn't healthy for the body, but physical activity is also key to brain health. “An active lifestyle helps to develop the central nervous system and to counteract the aging of the brain,” according to study authors. Researchers add that consistency is essential. Do your best to get in at least a little movement each and every day. Even if you work a sedentary job that requires lots of sitting, get moving every hour or so for just a few minutes at the very least. Some people are naturally more social than others, but researchers stress that no one is an island. Even if you prefer a quiet night in to attending a party, make an effort to stay in touch with the people who matter to you. Our brains thrive on social interactions and connections. “Relationships with other people, and interacting with them, contribute to a number of complex biological factors that can prevent the brain from slowing down,” Prof. Sigmundsson explains. Just like bicep curls help us build muscle, keeping the brain active promotes strong lifelong cognition. Consider taking up a new hobby, or learning a new skill. Perhaps most importantly, though, don't force it; find something you're actually passionate about. It's never too late in life to learn something new! “Passion, or having a strong interest in something, can be the decisive, driving factor that leads us to learn new things. Over time, this impacts the development and maintenance of our neural networks,” Prof. Sigmundsson says. “Brain development is closely linked to lifestyle. Physical exercise, relationships and passion help to develop and maintain the basic structures of our brain as we get older,” Prof. Sigmundsson concludes. Calcium supplements may support a healthy colon: Harvard study Harvard School of Public Health, September 18, 2022 Supplements of calcium or non-dairy products fortified with the mineral may reduce the risk of colorectal cancer, according to meta-analysis of prospective observational studies by researchers at Harvard School of Public Health. For every 300 mg increase in calcium from supplements was associated with a 9% reduction in risk, wrote NaNa Keum and her co-authors in the International Journal of Cancer . Every 300 mg increase in total calcium was associated with a similar reduction in risk (8%), they added. “Our findings have several important clinical and public health implications,” they explained. “First, according to the 2003 to 2006 National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey in the U.S., median total calcium intake of adults aged over 50 years was approximately 650 mg/day for no calcium-supplement users and 1,000 mg/day for calcium-supplement users. “As the benefit of calcium intake on CRC is expected to continue beyond 1,000 mg/day, not only non-supplement users but also supplement users may further reduce their CRC risk through additional calcium intake.” “Second, while dairy products, especially milk, are the major sources of calcium in many countries, they are a substantial source of calories and contain potentially harmful factors such as saturated fat, hormones, and casein proteins. Since our analyses provide evidence for an equivalent benefit of dietary and supplementary calcium, the benefit of calcium on CRC risk may be obtained through supplements and non-dairy products fortified with calcium.” The Boston-based scientists conducted dose-response meta-analyses of 15 studies involving 12,305 cases of colorectal cancer and calcium intakes ranging from 250-1,900 mg/day. The studies varied in duration from 3.3 to 16 years. The data indicated that both total and supplemental calcium were associated with reductions in the risk of colorectal cancer. “In conclusion, both dietary and supplementary calcium intake may continue to decrease colorectal cancer risk beyond 1,000 mg/day,” wrote Keum and her co-authors. Yoga's Age-Defying Effects Confirmed by Science Defence Institute of Physiology and Allied Sciences (India), September 21st 2022 While yoga's longevity promoting effects have been the subject of legend for millennia, increasingly modern science is confirming this ancient technology for spiritual and physical well-being actually can slow aging and stimulate our regenerative potential. One particularly powerful study published lin the journal Age titled, “Age-related changes in cardiovascular system, autonomic functions, and levels of BDNF of healthy active males: role of yogic practice”, found that a brief yoga intervention (3 months) resulted in widespread improvements in cardiovascular and neurological function. Indian researchers studied healthy active males of three age groups (20-29, 30-39, and 40-49 years) by randomly assigning them to practice one hour of yoga daily for 3 months. The observed significant differences between the younger and older participants in the study, specifically: “Significantly higher values of heart rate (HR), blood pressure (BP), load in heart (DoP), myocardial oxygen consumption (RPP), and total cholesterol (TC) were noted in senior age group.” The yogic practice resulted in significant reductions in all of these parameters (HR, BP, DoP, RPP and TC). Also observed in the older participants were decreases in high frequency (HF), total power (TP), all time domain variables of heart rate variability (HRV), and skin conductance (SC) — all of which increased following yogic practice. Higher levels of catecholamines (“stress hormones”) and low frequency (LF) power of HRV were noted in advancement of age, both of which decreased following yogic practice. Additionally, the senior age group had highest levels of cortisol and adrenocorticotrophic hormone (ACTH), both of which decreased following yogic practice. Finally, brain-derived neurotropic factor (BDNF), serotonin, and dopamine were low in higher age group, but these increased following yogic practice; an indication of improved brain function and cognition. The researchers concluded: ‘This study revealed that yogic practices might help in the prevention of age-related degeneration by changing cardiometabolic risk factors, autonomic function, and BDNF in healthy male.” There are a number of promising studies revealing the age-defying potential of this ancient practice. Here are some additional benefits confirmed in 2014 alone: Age-Related Respiratory Problems: A 2014 study from the journal of Human Kinetics found that a 3 month yoga intervention in 36 elderly women (average age 63.1) significantly improved pulmonary (respiratory) function. Age-Related Brain Cognitive Decline: A review in the Journals of Gerontology, involving a two month Hatha yoga intervention in the elderly (average age 62.0) resulted in significant improvements in “executive function measures of working memory capacity and efficiency of mental set shifting and flexibility compared with their stretching-strengthening counterparts.” Age-Related Hormone Insufficiency: A study published in Evidence Based Complementary and Alternative Medicine found that a 3 month yogic intervention in men (average age 42.8) and women (average age 44.75) resulted in improvements in the level of growth hormone and DHEAS, two essential hormones that drop off precipitously as we age. Age-Related Sleep Problems: Astudy published in Alternatives Therapies in Health and Medicine found a 12 week yogic intervention (yoga 2x a week) resulted in significant improvements in the quality of sleep in older individuals (average age 60). Age-Related Depression: From the Chinese Journal of Nursing found that not only did yoga improve sleep as found in the study above but also significantly reduced the depressive symptoms of elderly participants…after 6 months. “ This is just a small sampling of the literature. There is older research revealing that yoga has even more benefits for aging populations.

The following question refers to Section 3.4 of the 2021 ESC CV Prevention Guidelines. The question is asked by student Dr. Adriana Mares, answered first by early career preventive cardiologist Dr. Dipika Gopal, and then by expert faculty Dr. Michael Wesley Milks. Dr. Milks is a staff cardiologist and assistant professor of clinical medicine at the Ohio State University Wexner Medical Center where he serves as the Director of Cardiac Rehabilitation and an associate program director of the cardiovascular fellowship. He specializes in preventive cardiology and is a member of the American College of Cardiology's Cardiovascular Disease Prevention Leadership Council. The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association. Question #7 While you are on holiday break visiting your family, your aunt pulls you aside during the family gathering to ask a few questions about your 70-year-old uncle. He has hypertension, hyperlipidemia, type 2 diabetes mellitus, and moderate chronic obstructive pulmonary disease. His medications include Fluticasone/Salmeterol, Tiotropium, Albuterol, Lisinopril, Simvastatin, and Metformin. She is very concerned about his risk for heart disease as he has never had his “heart checked out.” She asks if the presence of COPD increases his chance of having heart disease. Which of the following statements would best answer her question? A. Systemic inflammation and oxidative stress caused by COPD promote vascular remodeling and a paradoxical ‘anticoagulant' state affecting all vasculature types. B. Although chronic COPD is associated with increased cardiovascular events, individual exacerbations have no impact on risk of cardiovascular events. C. Patients with mild-moderate COPD are 8-10x more likely to die from atherosclerotic cardiovascular disease than respiratory failure. D. Cardiovascular mortality increases proportionally with an increase in forced expiratory volume in 1 second (FEV1) Answer #7 The correct answer is C. Patients with mild-moderate COPD are 8-10x more likely to die from atherosclerotic cardiovascular disease than respiratory failure. Patients with COPD have a 2-3-fold increased risk of CV events compared to age-matched controls even when adjusted for tobacco smoking, a shared risk factor. This can be partly explained by other common risk factors including aging, hypertension, hyperlipidemia, and low physical activity. Interestingly, CVD mortality increases proportionally with a decrease (rather than increase) in FEV1, making answer choice D wrong (28% increase CVD mortality for every 10% decrease in FEV1). Additionally, COPD exacerbations and related infections are associated with a 4x increase in CVD events, making answer choice B incorrect. COPD has several effects on the vasculature which creates a ‘procoagulant' not ‘anticoagulant' effect on all vascular beds. This is associated with increased risk of cognitive impairment due to cerebral microvascular damage as well as increased risk of ischemic and hemorrhagic stroke. Main Takeaway The presence of COPD (even mild to moderate) has a significant impact on the incidence of non-fatal coronary events, stroke, and cardiovascular mortality mediated by inherent disease process and progression, risk factors (smoking, aging, hypertension, and hyperlipidemia), and systemic inflammation altering vasculature creating a ‘procoagulant' effect. The ESC gives a Class I indication (LOE C) to investigate for ASCVD and ASCVD risk factors in patients with COPD. Guideline Location 3.4.5, Page 3264. CardioNerds Decipher the Guidelines - 2021 ESC Prevention Series CardioNerds Episode Page CardioNerds Academy Cardionerds Healy Honor Roll CardioNerds Journal Club Subscribe to The Heartbeat Newsletter! Check out CardioNerds SWAG! Become a CardioNerds Patron!

Dünya Sağlık Örgütü'ne (DSÖ) göre, KOAH 2019'da 3,23 milyon ölüm ile dünya çapında üçüncü en sık ölüm nedeni haline geldi. KOAH ve komplikasyonları artık her nöbette karşımıza çıkmakta. Peki; sık karşılaştığımız bu hasta popülasyonunu ne kadar tanımaktayız? Bu yazımızda KOAH hakkında yedi soruda, doğru sanılan yanlışlara odaklanacağız. 1)KOAH tanısının yeri acil servis değildir? YANLIŞ ! Çoğu otör KOAH hastaları ile ilgili "milyonlarca kişiye henüz teşhis konmamış olabilir." görüşündedir.Türk Toraks Derneği “KOAH çok sık görülen bir hastalık olmasına rağmen hastaların doktora başvuruda gecikmesi, doktorların spirometreye ulaşma ve yorumlama güçlükleri nedeniyle, KOAH'lı hastaların ancak 1/3 -1/10'u KOAH tanısı almaktadır” diye belirtir.Bu nedenle, daha önceden tanısı olmayan birçok hasta KOAH ve komplikasyonlarına bağlı şikayetler ile acil serviste karşımıza çıkabilmektedir. 2)KOAH ve Astım aynıdır? YANLIŞ! Bu iki hastalık halk arasında birbirine çok karıştırılır. Dolayısıyla hastayı iyi sorgulamaz isek, hasta söylemi bizi yanıltabilir. Oysa ki bu iki klinik durum birbirinden oldukça farklıdır. Kabaca değinecek olursak: Astım, çok sayıda uyarana bağlı olarak gelişen havayollarının artmış inflamatuar yanıtı ile karakterize kronik inflamatuar bir bozukluktur. Hastalarda, inflamasyon özellikle geceleri veya sabahın erken saatlerinde tekrarlayan hırıltı, nefes darlığı, göğüste sıkışma ve öksürük nöbetlerine neden olur. Astım vakalarının yaklaşık yarısı 10 yaşından önce, üçte biri ise 40 yaşına kadar tanı alır. Patofizyolojisinde solunum yollarında anormal eozinofil, lenfosit, makrofaj ve mast hücresi birikimi vardır. Akut astım özellikle en sık viral akut solunum yolu enfeksiyonları, hava kirliliği, aspirin ve diğer NSAİİ'lerin kullanımı gibi tetikleyicilerle agreve olur. Klinikte akut bronkospazmdan kalıcı havayolu remodellingine ilerleyen bir spektrum izler. Bu remodelling sürecinde subbazal membran kalınlaşması, havayolu düz kas hipertrofisi ve hiperplazisi, anjiogenez, mukus bezlerinin hiperplazisi ve hipersekresyonu görülür ve akciğer fonksiyonlarında geri dönüşsüz kayıp gelişir. Astım ciddiyetinin sınıflanmasında FEV1 (bir saniyedeki zorlu ekspiratuar hacim) ve PEF(tepe ekspiratuar hızı) değerleri kullanılır. KOAH ise; zararlı partiküller veya gazlara ciddi derecede maruziyetten kaynaklanan havayolu ve/veya alveoler anormalliklere bağlı gelişen inatçı solunumsal semptomlar ve hava akımı kısıtlılığı ile karakterize, yaygın, önlenebilir ve tedavi edilebilir bir hastalıktır. İrritanlara bağlı hava yollarının kronik inflamasyonu patogenezin başlatıcı faktörüdür. İnflamatuar hücre infiltrasyonu , mediatörler, oksidatif stres, proteaz antiproteaz dengesizliği mekanizmaları ile parankim destrüksiyonu oluşur. Kronik inflamasyonun onarım mekanizmalarında bozulma doku hasarı, peribronşiyal ve interstisyel fibrozise yol açar. Oluşan amfizem hava akımı kısıtlanmasına ve azalmış gaz transferine neden olur. Sonuç FEV1de azalma, hipoksemi ve hiperkapnidir. Ayrıca kronik irritanlara ve bronşite bağlı olarak mukus hipersekresyonu da görülür. Hipoksik vasokonstrüksiyona bağlı ilerleyen dönemde pulmoner hipertansiyon gelişebilir. Bu da sağ kalp yetmezliğine yol açar. Tanıda FEV1/FVC oranının

Good morning and welcome to your Wednesday dose of Your Daily Meds.Bonus Review: Where does Vitamin K come from? Where is it absorbed? Why is it called Vitamin K?Answer: We need dietary Vitamin K. We get most of our dietary Vitamin K from leafy green vegetables and meats. Large amounts of menaquinone (Vitamin K2) is produced by bacterial action in the colon - unfortunately Vitamin K absorption does not occur in the colon. Some of the bacterially-produced Vitamin K is absorbed in the terminal ileum where there are some bile salts present. But, again, we need dietary Vitamin K.The absorption of dietary Vitamin K is from the small intestine. Remember that Vitamin K is fat soluble and so needs bile salts so that it can initially be solubilised into micelles which facilitates absorption into the circulation (via chylomicron form in the lymphatics).So, in patients with obstructive jaundice and an absence of bile salts in the small intestine, Vitamin K absorption will be impaired. They might even need some intravenous Vitamin K.Or what about the intubated malnourished patient with terminal ileitis from Crohn’s Disease. He has normal small bowel bile salts but no dietary Vitamin K? And naturally that little bit of bacterially produced Vitamin K are not going to be absorbed in the terminal ileum…let’s watch his INR go up…Also the ‘K’ in Vitamin K comes from the German ‘Koagulation’…Case:Consider the following ECG:What is the correct rate, axis and interpretation, respectively?100/min; normal axis; left bundle branch block120/min; normal axis; atrial flutter120/min; left axis deviation; atrial flutter with ectopic beats120/min; normal axis; atrial fibrillation with rapid ventricular rate100/min; right axis deviation; sinus rhythmHave a think.Count some little squares and look at the squiggles.Scroll for the chat.Investigation:A 25-year-old male is being worked up for an obstructive respiratory condition. Which of the following respiratory function test results would be most indicative of asthma.(FEV1 = forced expiratory volume in 1 second; VC = vital capacity; TLCO = carbon monoxide transfer factor; KCO = carbon monoxide transfer factor per unit lung volume; TLC = total lung capacity; RV = residual volume) FEV1 ↓↓; VC ↓; FEV1/VC ↓; TLCO →; KCO →/↑; TLC →/↑; RV →/↑ FEV1 ↓↓; VC ↓; FEV1/VC ↓; TLCO →; KCO →; TLC ↑; RV ↑FEV1 →; VC →; FEV1/VC →; TLCO →; KCO →; TLC →; RV →FEV1 ↓↓; VC ↓; FEV1/VC ↓; TLCO ↓↓; KCO ↓; TLC ↑↑; RV ↑↑FEV1↓; VC ↓↓; FEV1/VC →/↑; TLCO↓↓; KCO→/↓; TLC ↓; RV ↓(And where down arrow means decreased, sideways arrow means normal/stable etc…)Have a think.Remember those flow-volume curve/loop things.More scroll for more chat.Rapidamente:This ECG shows atrial fibrillation with rapid ventricular rate. The rate is approximately 120/min and with clear atrial fibrillation as P waves are not seen. The QRS complex is narrow at approximately 80ms. The axis is normal. Note there is mild horizontal ST depression in V4, V5 and V6 which is likely rate-related, not due to ischaemia.Vitality:Answer a) is most suggestive of asthma. The greatly reduced FEV1 is suggestive of airflow obstruction, as in asthma and COPD. To differentiate asthma from chronic bronchitis and emphysema, it is important to note the carbon monoxide transfer capacity, greatly reduced in emphysema, and the TLC and RV, which is not necessarily increased in asthma, unlike chronic bronchitis.Thus, answer a) is most suggestive of asthma;answer b) most suggestive of chronic bronchitis, answer c) is most likely a normal respiratory function test result; answer d) is suggestive of emphysema; and answer e) is suggestive of pulmonary fibrosis.In the case of asthma, lung function tests should be repeated after administration of a short-acting beta-2-adrenoreceptor agonist, such as salbutamol, to observe for any reversibility, such as a large improvement in FEV1 (eg 400mL). Bonus: Why are newborn infants susceptible to Vitamin K deficiency?Answer in tomorrow’s dose.Closing:Thank you for taking your Meds and we will see you tomorrow for your MANE dose. As always, please contact us with any questions, concerns, tips or suggestions. Have a great day!Luke.Remember, you are free to rip these questions and answers and use them for your own flashcards, study and question banks. Just credit us where credit is due. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit yourdailymeds.substack.com

Join moderators Viren Kaul, MD, and Divya Patel, DO, and journal CHEST® authors Spyridon Fortis, MD, and Igor Barjaktarevic, MD, PhD, as they discuss the article, "Ratio of FEV1 to Slow Vital Capacity of < 0.7 Is Associated With Clinical, Functional, and Radiologic Features of Obstructive Lung Disease in Smokers With Preserved Lung Function," which will be published in the July issue. DOI: https://doi.org/10.1016/j.chest.2021.01.067

Sunflower peptide as 'template' for potential analgesic Medical University of Vienna (Austria), June 28, 2021 A naturally occurring peptide in sunflower seeds was synthetically optimised and has now been identified as a potential drug for treating abdominal pain or inflammation (in the gastrointestinal tract, abdominal area and/or internal organs). That is the finding of an international study led by Christian Gruber from MedUni Vienna's Institute of Pharmacology (Center for Physiology and Pharmacology), which was conducted jointly with the University of Queensland and Flinders University in Australia and has now been published. The scientific aim of the study is to find analgesics that are only active in the periphery and do not cross the blood-brain barrier, as an alternative to commonly used synthetic opioids. Gruber explains the background: "Morphine was one of the first plant-based medicines and was isolated from the dried latex of poppies more than 200 years ago. It binds to opioid receptors in the brain and is still regarded as the main pillar of pain therapy. However, there is a high risk of opioid addiction, and an overdose - as a result of this strong dependency - inhibits the breathing centre in the brain, which can result in respiratory depression and, in the worst case, in death." For this reason, researchers throughout the world are trying to make analgesics safer and to find active drug molecules that do not have the typical opioid side-effects.  Sunflower extracts were to some extent used in traditional medicine for their anti-inflammatory and analgesic properties. In the current study, the scientists from Austria and Australia, primarily PhD student Edin Muratspahi?, isolated the plant molecule that may be responsible for this effect. Medicinal chemistry methods were then used to optimise the so-called sunflower trypsin inhibitor-1 (SFTI-1), one of the smallest naturally occurring cyclic peptides, by 'grafting' an endogenous opioid peptide into its scaffold.  A total of 19 peptides were chemically synthesized based on the original SFTI-1 blueprint and pharmacologically tested. "One of these variants turned out to be our lead candidate for as potential innovative analgesic molecule, especially for pain in the gastrointestinal tract or in the peripheral organs. This peptide is extremely stable, highly potent and its action is restricted to the body's periphery. Its use is therefore expected to produce fewer of the typical side-effects associated with opioids," point out Gruber and Muratspahi?.  The mode-of-action of the peptide is via the so-called kappa opioid receptor; this cellular protein is a drug target for pain relief, but is often associated with mood disorders and depression. The sunflower peptide does not act in the brain, hence there is much less risk of dependency or addiction. Furthermore, it selectively activates only the molecular signalling pathway that influences pain transmission but does not cause the typical opioid side-effects. The data of the animal model in the current study are very promising: the scientists see great potential for using this peptide in the future to develop a safe medication - which could be administered orally in tablet form - to treat pain in the gastrointestinal tract, and this drug could potentially also be used for related painful conditions, e.g. for inflammatory bowel disease.  Using Nature's blueprint The research of this MedUni Vienna laboratory led by Christian Gruber exploits the concept of using Nature's blueprint to develop optimised drugs. "We are searching through large databases containing genetic information of plants and animals, decoding new types of peptide molecules and studying their structure, with a view to testing them pharmacologically on enzymes or membrane receptors and ultimately utilizing them in the disease model," explains Gruber. Finally, potential drug candidates are chemically synthesised in a slightly modified form based on the natural blueprint, to obtain optimised pharmacological properties.   Study associates organic food intake in childhood with better cognitive development Analysis of multiple prenatal and childhood environmental risk factors suggests that poor nutrition, house crowding and indoor air pollution are associated with poorer cognitive function Barcelona Institute for Global Health (Spain), July 1, 2021 A study analysing the association between a wide variety of prenatal and childhood exposures and neuropsychological development in school-age children has found that organic food intake is associated with better scores on tests of fluid intelligence (ability to solve novel reasoning problems) and working memory (ability of the brain to retain new information while it is needed in the short term). The study, published in Environmental Pollution, was conceived and designed by researchers at the Barcelona Institute for Global Health (ISGlobal)--a centre supported by the "la Caixa" Foundation--and the Pere Virgili Health Research Institute (IISPV-CERCA).  The explanation for this association may be that "healthy diets, including organic diets, are richer than fast food diets in nutrients necessary for the brain, such as fatty acids, vitamins and antioxidants, which together may enhance cognitive function in childhood," commented lead author Jordi Júlvez, a researcher at IISPV-CERCA who works closely with ISGlobal.  The study also found that fast food intake, house crowding and environmental tobacco smoke during childhood were associated with lower fluid intelligence scores. In addition, exposure to fine particulate matter (PM2.5) indoors was associated with lower working memory scores.  The study, titled "Early life multiple exposures and child cognitive function: A multi-centric birth cohort study in six European countries", used data on 1,298 children aged 6-11 years from six European country-specific birth cohorts (United Kingdom, France, Spain, Greece, Lithuania and Norway). The researchers looked at 87 environmental factors the children were exposed to in utero (air pollution, traffic, noise, various chemicals and lifestyle factors) and another 122 factors they were exposed to during childhood. A Pioneering Study The aim of the study was to analyse the influence of these exposures on the development and maturation of the human brain, since during childhood the brain is not yet fully developed for efficient defence against environmental chemicals and is particularly sensitive to toxicity, even at low levels that do not necessarily pose a risk to a healthy mature brain.  The originality of the study lies in its use of an exposome approach, i.e. the fact that it takes into account the totality of exposures rather than focusing on a single one. This approach aims to achieve a better understanding of the complexity of multiple environmental exposures and their simultaneous effect on children's neurodevelopment.  Another strength of the study, which analyses cohorts from six European countries, is its diversity, although this factor also poses the additional challenge of cultural differences, which can influence exposure levels and cognitive outcomes. Notable Associations The study found that the main determinants of fluid intelligence and working memory in children are organic diet, fast food diet, crowdedness of the family home, indoor air pollution and tobacco smoke. To date, there has been little research on the relationship between type of diet and cognitive function, but fast food intake has been associated with lower academic development success and some studies have also reported positive associations between organic diets and executive function scores. "In our study," explained Júlvez, "we found better scores in fluid intelligence and working memory with higher organic food intake and lower fast food intake."  In contrast, exposure to tobacco smoke and indoor PM2.5 during childhood may negatively affect cognitive function by enhancing pro-inflammatory reactions in the brain. Still, according to Júlvez, it is worth bearing in mind that "the number of people living together in a home is often an indicator of the family's economic status, and that contexts of poverty favour less healthy lifestyles, which in turn may affect children's cognitive test scores".  Some Surprising Findings  The study also found some unexpected associations, which could be explained by confounding and reverse causality. For example, a positive association was found between childhood exposure to perfluorooctane sulfonic acid (PFOS) and cognitive function, even though PFOS is considered an endocrine disruptor that may alter thyroid function and negatively influence cognitive development.  The study forms part of the large European project Human Early-Life Exposome (HELIX), as does another recent paper that used the same exposome and the same participants but looked at symptoms of attention deficit hyperactivity disorder (ADHD) and childhood behavioural problems. "We observed that several prenatal environmental pollutants (indoor air pollution and tobacco smoke) and lifestyle habits during childhood (diet, sleep and family social capital) were associated with behavioural problems in children," explained Martine Vrijheid, last author of the study and head of ISGlobal's Childhood and Environment programme. "One of the strengths of this study on cognition and the earlier study on behavioural problems is that we systematically analysed a much wider range of exposure biomarkers in blood and urine to determine the internal levels in the model and that we analysed both prenatal and childhood exposure variables," concluded Vrijheid.     Extract of mulberry leaves partially restores the composition of intestinal microbiota and strengthens liver glycogen fragility in diabetic rats Macau University of Science and Technology (China), June 28, 2021 According to news reporting out of Macau, People's Republic of China, research stated, “Mulberry leaf as a traditional Chinese medicine is able to treat obesity, diabetes, and dyslipidemia. It is well known that diabetes leads to intestinal microbiota dysbiosis.” Our news journalists obtained a quote from the research from the Macau University of Science and Technology, “It is also recently discovered that liver glycogen structure is impaired in diabetic animals. Since mulberry leaves are able to improve the diabetic conditions through reducing blood glucose level, it would be interesting to investigate whether they have any positive effects on intestinal microbiota and liver glycogen structure. In this study, we first determined the bioactive components of ethanol extract of mulberry leaves via high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS). Murine animal models were divided into three groups, normal Sprague-Dawley (SD) rats, high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic rats, and HFD/STZ-induced rats administered with ethanol extract of mulberry leaves (200 mg/kg/day). Composition of intestinal microbiota was analyzed via metagenomics by sequencing the V3-V4 region of 16S rDNAs. Liver glycogen structure was characterized through size exclusion chromatography (SEC). Both Student's t-test and Tukey's test were used for statistical analysis. A group of type 2 diabetic rat models were successfully established. Intestinal microbiota analysis showed that ethanol extract of mulberry leaves could partially change intestinal microbiota back to normal conditions. In addition, liver glycogen was restored from fragile state to stable state through administration of ethanol extract of mulberry leaves. This study confirms that the ethanol extract of mulberry leaves (MLE) ameliorates intestinal microbiota dysbiosis and strengthens liver glycogen fragility in diabetic rats.” According to the news editors, the research concluded: “These finding can be helpful in discovering the novel therapeutic targets with the help of further investigations.”     Supplemental antioxidants may reduce exacerbations in cystic fibrosis     University of Colorado, July 2, 2021 An antioxidant-enriched vitamin may decrease respiratory exacerbations in people with cystic fibrosis(CF), according to new research published online iin the American Journal of Respiratory and Critical Care Medicine. In "Effects of an Antioxidant-Enriched Multivitamin in Cystic Fibrosis: Randomized, Controlled, Multicenter Trial," Scott D. Sagel, MD, PhD, a professor of pediatrics at Children's Hospital Colorado and director of the University of Colorado Cystic Fibrosis Center, and coauthors report a 50 percent reduced risk of time to the first exacerbation requiring antibiotics in those receiving the supplemental antioxidants. During the 16-week study of 73 patients (36 received supplemental antioxidants), 53 percent of the antioxidant-treated group experienced 28 exacerbations, compared to 68 percent of the control group who experienced 39 exacerbations. The researchers also found that supplemental antioxidants increased circulating antioxidant concentrations of beta-carotene, coenzyme Q10, gamma-tocopherol (a form of vitamin E) and lutein and transiently decreased inflammation (at 4 weeks, but not 16 weeks) as measured by two blood-based biomarkers of inflammation, calprotectin and myeloperoxidase (MPO). People with CF typically experience chronic bacterial infections, which lead to inflammation and the release of "vast amounts of reactive oxygen species in the airways," the authors wrote. Normally, they added, the body would marshal an antioxidant defense to neutralize this oxidant stress, but CF is characterized by dietary antioxidant deficiencies. This contributes to an oxidant-antioxidant imbalance and more inflammation, which leads to lung damage and a progressive loss of lung function. "Improving antioxidant status in CF is an important clinical goal and may have a positive effect on health," Dr. Sagel said. "Oral antioxidant formulations had been tested in CF with mixed results. However, there had not been a well-designed randomized controlled trial of an antioxidant 'cocktail' that included multiple antioxidants in a single formulation." This phase 2 trial, conducted at 15 CF centers affiliated with the CF Foundation Therapeutics Development Network, enrolled patients who were 10 years and older (average age 22 years), with pancreatic insufficiency, which causes malabsorption of antioxidants. Participants had an FEV1, the measure of how much air can be forcefully exhaled in one second, between 40 and 100 percent of what would be predicted, based on age, gender, height and a range of other characteristics. Patients in the control group received a multivitamin without antioxidant enrichment. The two groups tolerated their vitamins equally well, and there were no differences in adverse events between the two groups. The study did not meet its primary endpoint: change in sputum MPO concentration over 16 weeks. The authors chose sputum MPO "rather than another marker of airway inflammation such as neutrophil elastase because MPO generates reactive oxidant species as part of its function in innate host defense mechanisms, and is considered by many a marker of oxidative stress." "While the antioxidant supplement did not appear to exert sustained anti-inflammatory effects, we believe its effect on time to first pulmonary exacerbation was significant and clinically meaningful," Dr. Sagel said, adding that the improvement in antioxidant status alone may justify its use. "Developing safe and effective anti-inflammatory treatments remains a key priority of the CF community."   Maternal diets rich in Omega-3 fatty acids may protect offspring from breast cancer Marshall University School of Medicine, June 28, 2021 According to researchers at Marshall University, a maternal diet rich in Omega-3 fatty acids protects from breast cancer development in offspring. In a new studyrecently published by Frontiers in Cell and Developmental Biology, researchers noted a significant difference in mice from mothers that were fed a diet rich in canola oil, compared with mothers fed a diet rich in corn oil. A maternal Omega 3-rich diet affected genome-wide epigenetic landscape changes in offspring and potentially modulated gene expression patterns. Dr. Ata Abbas, a former postdoctoral research fellow in Marshall's Department of Biological Sciences, headed a research team under the leadership of Dr. Philippe Georgel in the College of Science. Research was done in the Cell Differentiation and Development Center at Marshall as part of a collaborative effort with the Joan C. Edwards School of Medicine's Department of Biochemistry and Microbiology, under the leadership of Dr. W. Elaine Hardman. Researchers noticed a three-week delay in mortality in mice whose mothers were fed canola oil versus corn oil. The early delay in mortality was significantly different, but the ultimate overall survival rate was not. Eventually, all the mice developed tumors, but the ones fed canola oil had tumors that were slower-growing and smaller than the mice fed corn oil. Translated to human time scale, the duration of the protective effect linked to the maternal diet would be equivalent to several months (Sengupta et al., 2016). This study is among a body of work done by Marshall University scientists and others looking at the link between Omega-3 fatty acids and reduced incidence of various types of cancer including, but not restricted to, Chronic Lymphocytic Leukemia and Diffuse Large B-Cell Lymphoma. "The issue of parental diet and inter-generational transmission has become an important field of research; however, the mode of action often remains partially elusive," said Georgel, a professor in the Department of Biological Sciences at Marshall. "The MU research group focused on 'epigenetic' aspects of trans-generational transmission to explain the reported role of Omega-3 fatty acids. Epigenetics involves changes in gene expression which are not linked to changes in genetic sequences. These results have the potential to promote the design of simple changes in diet which would allow for reduced onset of various types of cancer, not only for the individuals using that diet but also for their offspring."     Compounds found in green tea and wine may block formation of toxic metabolites Tel Aviv University (Israel), July 2, 2021 A new Tel Aviv University study suggests there is hope of treating certain inborn congenital metabolic diseases -- a hope found in green tea and in red wine. Most people with inherited metabolic disorders are born with a defective gene that results in a critical enzyme deficiency. In the absence of a cure, many patients with inborn congenital metabolic disorders must adhere to a strict and demanding diet their entire lives. This new research finds that certain compounds found naturally in green tea and red wine may block the formation of toxic metabolites. The research was led by Prof. Ehud Gazit of TAU's Faculty of Life Sciences and his doctoral student Shira Shaham-Niv. It was published in the Nature group journal Communications Chemistry. The researchers considered two compounds: (1) epigallocatechin gallate, known as EGCG, found naturally in green tea, which has attracted attention within the medical community for its potential health benefits; and (2) tannic acid, found in red wine, which is known to prevent the formation of toxic amyloid structures that cause neurodegenerative disorders such as Alzheimer's and Parkinson's disease. "In the case of inborn congenital metabolic diseases, the body does not produce a vital metabolic enzyme," Shaham-Niv said. "As a result, metabolites -- substances that are, among other things, the building blocks of DNA and proteins -- accumulate in the body. Such uncontrolled accumulation is toxic and can cause severe developmental and mental disorders. "Our new study demonstrates once again the ability of nature to produce the best candidate of drugs to treat some of the worst human maladies." Collectively, this group of disorders constitutes a significant portion of pediatric genetic diseases. The disease phenylketonuria (PKU), which produces the aggregation of the metabolite phenylalanine, is one common inborn metabolic disease. Infants with PKU must adhere to a strict diet free of phenylalanine for the rest of their lives. If they don't, they may face severe debilitating developmental problems. "But this is an incredibly difficult task, since phenylalanine is found in most of the food products that we consume," Shaham-Niv said. "The avoidance of certain substances is the only way to prevent the debilitating long-term effects of inborn congenital metabolic disorders. We hope that our new approach will facilitate the development of new drugs to treat these disorders." The new research is based on two previous studies conducted at Prof. Gazit's TAU laboratory. In the first study, phenylalanine was shown to be capable of self-assembly and of forming amyloid structures like those seen in Alzheimer's, Parkinson's and other neurodegenerative diseases. In the second study, by Shaham-Niv, other metabolites that accumulate in other inborn congenital metabolic diseases were also shown to undergo self-assembly processes and form toxic amyloid aggregates. "Both studies led to an overhaul in the research community's understanding of metabolic diseases," Shaham-Niv said. "In our new study, we examined whether the molecules identified in past studies on Alzheimer's disease and other amyloid diseases, which are known to inhibit the formation of amyloid aggregates, could also help counteract the amyloid formation process of metabolites in metabolic diseases." The new research focused on EGCG and tannic acid using test tubes and culture cell systems. The two substances were tested on three metabolites related to three innate metabolic diseases: adenine, cumulative tyrosine and phenylalanine. The results were promising. Both tannic acid and EGCG were effective in blocking the formation of toxic amyloid structures. The researchers also used computer simulations to verify the mechanism driving the compounds. "We are entering a new era of understanding the role and the importance of metabolites in various diseases, including metabolic diseases, neurodegenerative diseases and even cancer," Shaham-Niv concluded. "The tools we have developed are ground-breaking and have tremendous potential to help a wide range of patients in the future."       People with fibromyalgia are substituting CBD for opioids to manage pain University of Michigan, June 24, 2021 Fibromyalgia is one of many chronic pain conditions that remains stubbornly difficult to treat.  As the ravages of the opioid epidemic lead many to avoid these powerful painkillers, a significant number of people with fibromyalgia are finding an effective replacement in CBD-containing products, finds a new Michigan Medicine study.  CBD, short for cannabidiol, is the second most common cannabinoid in the cannabis plant, and has been marketed for everything from mood stabilization to pain relief, without the intoxicating effects produced by the most common cannabinoid, THC. THC, which stands for delta-9-tetrahydrocannabinol, is the ingredient in marijuana that causes people to feel high. The cannabis industry has exploded, aided by the legalization of medical and recreational marijuana in states around the United States and the removal of hemp-derived CBD from Schedule 1 status--reserved for drugs with no currently accepted medical use and a high potential for abuse--at the federal level.  Previous research shows that some people substitute medical cannabis (often with high concentrations of THC) for opioids and other pain medications, reporting that cannabis provides better pain relief and fewer side effects. However, there is far less data on CBD use. "CBD is less harmful than THC, as it is non-intoxicating and has less potential for abuse," said Kevin Boehnke, Ph.D., a research investigator in the Department of Anesthesiology and the Chronic Pain and Fatigue Research Center. "If people can find the same relief without THC's side effects, CBD may represent a useful as a harm reduction strategy." Boehnke and his team surveyed people with fibromyalgia about their use of CBD for treatment of chronic pain.  "Fibromyalgia is not easy to treat, often involving several medications with significant side effects and modest benefits," Boehnke explained. "Further, many alternative therapies, like acupuncture and massage, are not covered by insurance." For this study, the team focused on 878 people with fibromyalgia who said they used CBD to get more insight into how they used CBD products.  The U-M team found that more than 70% of people with fibromyalgia who used CBD substituted CBD for opioids or other pain medications. Of these participants, many reported that they either decreased use or stopped taking opioids and other pain medications as a result.  "I was not expecting that level of substitution," said Boehnke, noting that the rate is quite similar to the substitution rate reported in the medical cannabis literature. People who said they used CBD products that also contained THC had higher odds of substitution and reported greater symptom relief. Yet the finding that products containing only CBD also provided pain relief and were substituted for pain medications is promising and merits future study, noted Boehnke.  The team noted that much of the widespread use of CBD is occurring without physician guidance and in the absence of relevant clinical trials. "Even with that lack of evidence, people are using CBD, substituting it for medication and doing so saying it's less harmful and more effective," he said.  Boehnke stressed the need for more controlled research into how CBD may provide these benefits, as well as whether these benefits may be due to the placebo effect.  Clinically, opening up lines of discussion around CBD use for chronic pain is imperative, said Boehnke, for medication safety reasons as well as for "enhancing the therapeutic alliance and improving patient care."

From 1961 to 1970, healthy U.S. males between the ages of 21 and 81 enrolled in the ongoing Veterans Affairs Normative Aging Study. One of the objectives of the study is to characterize the biomedical and psychosocial parameters of normal aging (distinct from the development of disease). There are a total of 2,280 participants in the Normative Aging Study (NAS). In the current Aging study, researchers included 696 elderly men from the NAS. “The present study included 696 elderly men with 1,070 visits during years of 1999-2013.” In search of associations between biomarkers of aging and lung function, the researchers first collected the study participants' personal characteristics, including age, smoking history, height, weight, BMI, education, blood work, and other measures. They then analyzed lung function using three tests: forced expiratory volume in one second (FEV1), forced expiratory volume in one second / forced vital capacity (FEV1/FVC), and maximum mid-expiratory flow (MMEF). Next, the team analyzed the participants' epigenetic biomarkers of age; including GrimAgeAccel, PhenoAgeAccel, intrinsic epigenetic age acceleration (IEAA), extrinsic epigenetic age acceleration (EEAA), and Zhang's DNAmRiskScore; as well as non-epigenetic biomarkers of age, including telomere length and mitochondrial DNA copy number (mtDNA-CN). They then assessed for associations between these biomarkers and the three measures of lung function. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.103363 DOI - https://doi.org/10.18632/aging.103363 Full text - https://www.aging-us.com/article/103363/text Correspondence to: Cuicui Wang email: cuicuiwang@hsph.harvard.edu Keywords: pulmonary health, DNA methylation, biological clock, aging About Aging Launched in 2009, Aging publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com​​ or connect with us on: Twitter - https://twitter.com/AgingJrnl​ Facebook - https://www.facebook.com/AgingUS/​ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Aging is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Representative Mike Mueller's older sister was diagnosed with cystic fibrosis (CF) at four years old. Growing up with a sister having CF gave Rep. Mueller a lot of compassion for people living life with a health challenge, and impacted his life of public service.  The two have a strong bond of love and understanding. It's a heartfelt story about the fear about what CF does to his sister, his fears, pushing through it. Rep. Mueller also is the co-author of the resolution to make May, CF Awareness month (Rep. Jim Ellison is the other).  Rep. Mueller is also the co-author, (along with Rep. Care Clemente and Rep.Jim Ellison) for the Rare Disease Advisory Council.For more information on The Bonnell Foundation find us at https://thebonnellfoundation.org/Vertex Pharma - the science of possibility.  https://www.vrtx.comTo contact Rep. Mueller: https://www.facebook.com/MichiganHouseRepublicans/The original music in this podcast is performed by Kevin Allan, who happens to have Cystic Fibrosis.  You can find him on Facebook here: https://www.facebook.com/KevinAllanMusicThis podcast was produced by JAG in Detroit Podcasts. https://jagindetroit.com/

Written/Researched By: Khash Farzam Peer Review By: Caleb Dusdal Objective One: In all patients presenting with symptoms of prolonged or recurrent cough, dyspnea, or decreased exercise tolerance, especially those who also have a significant smoking history, suspect the diagnosis of chronic obstructive pulmonary disease (COPD). Objective Two: When the diagnosis of COPD is suspected, seek confirmation with pulmonary function studies (e.g., FEV1). Objective Three: In patients with COPD, use pulmonary function tests periodically to document disease progression. Objective Four: Encourage smoking cessation in all patients diagnosed with COPD. Objective Five: Offer appropriate vaccinations to patients diagnosed with COPD (e.g., influenza/pneumococcal vaccination). Objective Six: In an apparently stable patient with COPD, offer appropriate inhaled medication for treatment (e.g., anticholinergics/bronchodilators if condition is reversible, steroid trial). Objective Seven: Refer appropriate patients with COPD to other health professionals (e.g., a respiratory technician or pulmonary rehabilitation personnel) to enhance quality of life. Objective Eight: When treating patients with acute exacerbations of COPD, rule out co-morbidities (e.g., myocardial infarction, congestive heart failure, systemic infections, anemia). Objective Nine: In patients with end-stage COPD, especially those who are currently stable, discuss, document, and periodically re-evaluate wishes about aggressive treatment interventions.

Albuterol is a bronchodialating beta-2 adrenergic agonist. Common brand names are ProAir, Ventolin, and Proventil. The most common use is for treating and preventing bronchospasms in patients with obstructive airway diseases. There are several dosage forms with the most common being metered dose inhalers (MDI) and dry powdered inhalers (DPI). Albuterol is generally considered a quick relief or rescue inhaler with dosing being 2 puffs by mouth every 4-6 hours as needed. Since albuterol specifically targets the beta-2 adrenergic receptor in bronchial smooth muscle there is little to no effect on heart rate. Although the drug is targeted it is still wise to monitor patients with heart issues. Common monitoring parameters are FEV1, peak flow, blood pressure, and heart rate. Go to DrugCardsDaily.com for episode show notes which consist of the drug summary, quiz, and link to the drug card for FREE! Please SUBSCRIBE, FOLLOW, and RATE on Spotify, Apple Podcasts, or wherever your favorite place to listen to podcasts are. The main goal is to go over the Top 200 Drugs with the occasional drug of interest. Also, if you'd like to say hello, suggest a drug, or leave some feedback I'd really appreciate hearing from you! Leave a voice message at anchor.fm/drugcardsdaily or find me on twitter @drugcardsdaily --- Send in a voice message: https://anchor.fm/drugcardsdaily/message

FDA 批准RET选择性抑制剂治疗RET基因驱动的非小细胞肺癌JAMA 慢性阻塞性肺病患者出院后肺康复训练可以显著降低1年生存率Cell 超级抗生素的研制塞帕替尼（selpercatinib）RET基因融合是1%～2%非小细胞肺癌的致癌驱动基因，2020年5月，RET选择性抑制剂塞帕替尼（selpercatinib）同时被FDA批准用于治疗RET驱动的肺癌和甲状腺癌。本期节目首先介绍塞帕替尼在非小细胞肺癌中的临床研究，周五的内分泌科专题当中，会和大家讨论一下塞帕替尼在甲状腺癌中的应用。《LIBRETTO-001研究：塞帕替尼对RET融合阳性非小细胞肺癌的疗效的1/2临床研究》New England Journal of Medicine，2020年8月 (1)研究纳入接受过铂类化疗的和未接受过治疗的RET基因融合阳性的、晚期非小细胞肺癌患者共105例。中位随访12.1个月时，接受过铂类化疗的患者，客观缓解率64%；未接受过治疗的患者，客观缓解率85%；6个月时，90%的缓解仍持续。中枢神经系统转移的11例患者中，颅内缓解率91%。最常见严重不良事件包括高血压、谷丙转氨酶升高、谷草转氨酶升高、低钠血症和淋巴细胞减少，仅2%的患者因不良事件停药。结论：在RET融合阳性的、非小细胞肺癌患者中，塞帕替尼具有持久疗效。慢性阻塞性肺病 - 吸入剂治疗慢性阻塞性肺病（COPD）患者中使用吸入的支气管扩张剂，可以改善症状、运动能力。常用药物包括：快速起效的短效β受体激动剂吸入剂（SABA，如沙丁胺醇）；快速起效的长效β受体激动剂吸入剂（LABA，如沙美特罗、福莫特罗、阿福特罗、茚达特罗、维兰特罗、奥达特罗），长效抗毒蕈碱受体阻滞剂（LAMA，噻托嗅铵、阿地溴铵、芜地溴铵、格隆溴铵）；糖皮质激素吸入剂（ICS，布地奈德、倍氯米松、莫米松）。对于单用长效支气管扩张剂效果不好的患者，可以考虑联合方案，比如：LAMA联合LABA，LABA联合ICS。重症患者可以使用LAMA-LABA-ICS三联治疗。《IMPACT研究：使用氟替卡松/芜地溴铵/维兰特罗三联治疗方案降低COPD患者的全因死亡率》American Journal of Respiratory and Critical Medicine，2020年6月 (2)该研究纳入10355例、有未来恶化风险的COPD患者，随机给予ICS-LAMA-LABA三联吸入治疗方案（氟替卡松/芜地溴铵/维兰特罗），或者LAMA-LABA二联治疗方案（芜地溴铵/维兰特罗），或者ICS-LABA二联治疗方案（氟替卡松/维兰特罗）治疗。在三联治疗组和两个二联治疗组中，分别记录了2.36%、2.64%和3.19%的患者死亡。与二联治疗组相比，三联治疗组的患者死亡风险更低，风险比分别为0.72和0.89。结论：IMPACT研究证明，每日一次吸入氟替卡松/芜地溴铵/维兰特罗三联疗法，可以降低了有症状且有加重史的COPD患者的全因死亡率。《真实世界的队列研究：LAMA-LABA-ICS三联吸入方案和LAMA-LABA二联吸入方案对COPD的临床治疗比较效果》Chest，2020年4月 (3)研究者从英国临床实践研究数据链中确定了一组2002年至2015年间使用LAMA、LABA治疗方案或LAMA-LABA-ICS治疗方案的、≥55岁的、近2700例COPD患者，随访1年，观察中重度COPD加重和严重肺炎的发生情况。在COPD急性加重的发生率上来看，三联吸入疗法与LAMA-LABA二联疗法相比，风险比为0.97，没有统计学意义的降低。对于嗜酸性粒细胞计数>6%的患者，三联疗法可以显著降低COPD急性加重的风险，风险比0.66。对于反复因COPD急性加重住院的患者而言，三联疗法也可以显著降低COPD急性加重的风险，风险比0.83。但是在三联疗法组中，需要住院治疗的重症肺炎的发生率显著升高，风险比 1.46。结论：真实世界中，在预防COPD加重方面，LAMA-LABA-ICS三联吸入疗法与LAMA-LABA二联吸入疗法同样有效。但是在嗜酸性粒细胞增多、或频繁急性加重的患者中，三联治疗方案获益更多。除此之外，二联治疗方案可能更为可取，因为它与重症肺炎发生率较低相关。《系统综述和荟萃分析：布地奈德/格隆溴铵/福莫特罗三联吸入疗法和其他LAMA-LABA-ICS三联吸入疗法的疗效比较》Advances in Therapy，2020年6月 (4)这篇荟萃分析纳入了18项研究，29,232例患者的资料。在减轻中重度COPD患者病情加重、改善肺功能和症状方面，布地奈德/格隆溴铵/福莫特罗和其他三联吸入的固定剂量组合（氟替卡松/芜地溴铵/维兰特罗、倍氯米松/格隆溴铵/福莫特罗）没有统计学差异；和其他开放联合用药之间也没有统计学显著差异。敏感性分析和元回归分析的结果与基本情况一致。结论：在减轻中重度COPD患者病情加重、改善肺功能和症状方面，可布地奈德/格隆溴铵/福莫特罗与其他LAMA-LABA-ICS固定剂量三联疗法的疗效相似。小羽点评：从随机临床研究的角度看，固定剂量的三联吸入疗法在减少COPD患者病情加重方面的疗效是相似的，并且优于二联吸入疗法；然而，在真实世界中，三联吸入疗法的优势则不那么明显了，甚至还有可能增加重症肺炎的发生率。《IMPACT研究亚组分析：吸入糖皮质激素停用和基线吸入治疗对病情加重的影响》American Journal of Respiratory and Critical Care Medicine，2020年11月 (5)IMPACT研究证明，每日一次吸入氟替卡松/芜地溴铵/维兰特罗三联疗法，可以降低了有症状且有加重史的COPD患者的全因死亡率。这项亚组分析的目的是了解吸入糖皮质类固醇停药是否影响影响结果。与芜地溴铵/维兰特罗二联治疗方案相比，氟替卡松/芜地溴铵/维兰特罗三联治疗方案显著降低了以前使用糖皮质激素的患者中，COPD中重度急性的发生率显著降低29%（P < 0.001），但在先前不使用糖皮质激素的患者中这种获益并不显著（降低12%，P = 0.115）。无论先前是否使用过糖皮质激素，三联吸入治疗方案均可以降低重度急性发作达35%、持续改善第一秒用力呼气量谷值和圣乔治呼吸问卷评分（SGRQ）。结论：这些数据支持了三联治疗在减轻病情恶化、肺功能和生活质量方面的重要作用，而这些作用似乎与ICS的突然停用无关。《ISOLDE研究：吸入糖皮质激素治疗后血液嗜酸性粒细胞的变化可能预测慢性阻塞性肺病的长期临床反应》European Respiratory Journal，2020年5月 (6)此研究的目的是评价吸入糖皮质激素后，血液嗜酸性粒细胞的变化可以预测长期治疗结果。这项为期3年的双盲试验中，对751名中-重度COPD患者随机分入氟替卡松组和安慰剂组。研究发现，1年内的嗜酸性粒细胞的减少与治疗效果相关，而且是治疗反应的强预测因子。在嗜酸性粒细胞下降≥200/μL时，吸入糖皮质激素可降低第一秒用力呼气量（FEV1）下降率达32mL/年，恶化率降低30%。相反，在嗜酸性粒细胞升高≥200/μL时，吸入糖皮质激素可加速第一秒用力呼气量下降，下降速度为37mL/年，恶化率增加80% （P4年的患者患肺癌的风险比为0.92，无统计学意义。平均每日吸入糖皮质激素较高的患者肺癌的风险比为1.36（95% CI 1.03-1.81）。结论：在COPD患者中，吸入糖皮质激素与肺癌发病率的降低无关。《欧洲呼吸协会指南：慢性阻塞性肺病患者何时停用吸入糖皮质激素》European Respiratory Journal，2020年6月 (8)吸入糖皮质激素联合支气管扩张剂，可降低慢性阻塞性肺病患者病情加重的频率，但是糖皮质激素经常被用于疗效不确定的患者。因此文章建议对于下列情况停用吸入糖皮质激素：（1）若COPD患者没有频繁发作的病史，指南认为停用活继续糖皮质激素吸入治疗的获益风险比存在不确定性，需要充分告知和与患者讨论；（2）若血液嗜酸性粒细胞计数≥300/µl，指南强烈建议不要停用吸入糖皮质激素；（3）若准备停用吸入糖皮质激素，指南强烈建议使用一个或两个长效支气管扩张剂。COPD患者肺康复训练肺康复可以改善慢性呼吸系统疾病患者的症状、生存质量和肺功能。肺康复包括运动训练、促进将康的行为（比如戒烟、锻炼、营养支持、恰当用药和自我管理）和心理支持。运动训练可以采用下肢训练（如，固定式脚踏车、跑步机或自由行走）、上肢训练（如手臂训练）、间歇运动训练、抗阻力/力量训练和呼吸再训练。《回顾性队列研究：COPD出院后开始肺康复1年生存率的影响》JAMA，2020年5月 (9)肺康复训练与慢性阻塞性肺病患者生存率提高相关，但相关研究的患者数量少且异质性高。研究的目的时确定慢性阻塞性肺病患者出院后90天内开始肺部康复与1年生存率之间的关系。研究纳入197 376例患者、平均年龄76.9岁，1.5%的患者在出院后90天内开始肺康复。出院1年内死亡率19.4%，其中进行肺康复训练者死亡率7.3%，没有进行康复训练者死亡率19.6%。进行肺康复训练者绝对死亡风险下降6.7%，风险比 0.63。结论：慢性阻塞性肺病病人，出院后3个月内开始肺部康复1年死亡率显著降低。《随机对照研究：下坡行走对COPD患者肺部康复的影响》European Respiratory Journal，2020年5月 (10)收缩性肌肉疲劳影响COPD患者的训练反应。下坡步行诱发收缩肌疲劳、呼吸困难和疲劳程度较平地步行低。本研究比较了下坡步行训练和平地步行训练的方式进行肺康复对COPD患者的影响。在这项随机对照试验中，35例患者，平均年龄62岁，第一秒最大呼气量（FEV1）平均50%，随机分为下坡步行组或平地步行组。两组间，6分钟步行试验结果和肌肉活检没有差异（p=0.45）；但是94%的进行下坡行走锻炼的患者进步了，平地行走组仅为65%（p=0.03）。在其他方面，下坡行走组也有更大的改善。结论：在慢性阻塞性肺病患者中，结合下坡行走与常规步行在肺康复临床疗效上具有相似的效果；但是锻炼耐受性更好。《ON-EPIC研究：口服硝酸盐补充剂增强慢性阻塞性肺病肺部康复》Thorax 2020年7月 (11)研究的目的是评估口服硝酸盐是否能增强慢性阻塞性肺病患者的肺康复效果。这项双盲、安慰剂对照、平行组、随机对照研究在四个英国中心进行，登记了患有GOLD分级II-IV级的、医学研究委员会（Medical Research Council）呼吸困难评分3-5分或功能受限的COPD成年患者，进行每周两次、为期8周的肺康复训练计划。他们被随机分配到140ml富含硝酸盐的甜菜汁组（含12.9 mmol硝酸盐），或安慰剂组，服用前3小时进行肺康复训练治疗。积极治疗组(57例)的运动能力比安慰剂组(65例)提高更多;ISWT距离+60 m (10,85) vs +30 m(0,70)中值(IQR)变化，估计处理效果30 m (95% CI 10 ~ 40);p = 0.027。积极治疗对收缩压也有影响:治疗组-5.0 mm Hg (-5.0， -3.0) vs对照组+6.0 mm Hg(-1.0, 15.5)，估计治疗效果-7 mm Hg (95% CI 7 ~ -20) (p

FDA 批准RET选择性抑制剂治疗RET基因驱动的非小细胞肺癌JAMA 慢性阻塞性肺病患者出院后肺康复训练可以显著降低1年生存率Cell 超级抗生素的研制塞帕替尼（selpercatinib）RET基因融合是1%～2%非小细胞肺癌的致癌驱动基因，2020年5月，RET选择性抑制剂塞帕替尼（selpercatinib）同时被FDA批准用于治疗RET驱动的肺癌和甲状腺癌。本期节目首先介绍塞帕替尼在非小细胞肺癌中的临床研究，周五的内分泌科专题当中，会和大家讨论一下塞帕替尼在甲状腺癌中的应用。《LIBRETTO-001研究：塞帕替尼对RET融合阳性非小细胞肺癌的疗效的1/2临床研究》New England Journal of Medicine，2020年8月 (1)研究纳入接受过铂类化疗的和未接受过治疗的RET基因融合阳性的、晚期非小细胞肺癌患者共105例。中位随访12.1个月时，接受过铂类化疗的患者，客观缓解率64%；未接受过治疗的患者，客观缓解率85%；6个月时，90%的缓解仍持续。中枢神经系统转移的11例患者中，颅内缓解率91%。最常见严重不良事件包括高血压、谷丙转氨酶升高、谷草转氨酶升高、低钠血症和淋巴细胞减少，仅2%的患者因不良事件停药。结论：在RET融合阳性的、非小细胞肺癌患者中，塞帕替尼具有持久疗效。慢性阻塞性肺病 - 吸入剂治疗慢性阻塞性肺病（COPD）患者中使用吸入的支气管扩张剂，可以改善症状、运动能力。常用药物包括：快速起效的短效β受体激动剂吸入剂（SABA，如沙丁胺醇）；快速起效的长效β受体激动剂吸入剂（LABA，如沙美特罗、福莫特罗、阿福特罗、茚达特罗、维兰特罗、奥达特罗），长效抗毒蕈碱受体阻滞剂（LAMA，噻托嗅铵、阿地溴铵、芜地溴铵、格隆溴铵）；糖皮质激素吸入剂（ICS，布地奈德、倍氯米松、莫米松）。对于单用长效支气管扩张剂效果不好的患者，可以考虑联合方案，比如：LAMA联合LABA，LABA联合ICS。重症患者可以使用LAMA-LABA-ICS三联治疗。《IMPACT研究：使用氟替卡松/芜地溴铵/维兰特罗三联治疗方案降低COPD患者的全因死亡率》American Journal of Respiratory and Critical Medicine，2020年6月 (2)该研究纳入10355例、有未来恶化风险的COPD患者，随机给予ICS-LAMA-LABA三联吸入治疗方案（氟替卡松/芜地溴铵/维兰特罗），或者LAMA-LABA二联治疗方案（芜地溴铵/维兰特罗），或者ICS-LABA二联治疗方案（氟替卡松/维兰特罗）治疗。在三联治疗组和两个二联治疗组中，分别记录了2.36%、2.64%和3.19%的患者死亡。与二联治疗组相比，三联治疗组的患者死亡风险更低，风险比分别为0.72和0.89。结论：IMPACT研究证明，每日一次吸入氟替卡松/芜地溴铵/维兰特罗三联疗法，可以降低了有症状且有加重史的COPD患者的全因死亡率。《真实世界的队列研究：LAMA-LABA-ICS三联吸入方案和LAMA-LABA二联吸入方案对COPD的临床治疗比较效果》Chest，2020年4月 (3)研究者从英国临床实践研究数据链中确定了一组2002年至2015年间使用LAMA、LABA治疗方案或LAMA-LABA-ICS治疗方案的、≥55岁的、近2700例COPD患者，随访1年，观察中重度COPD加重和严重肺炎的发生情况。在COPD急性加重的发生率上来看，三联吸入疗法与LAMA-LABA二联疗法相比，风险比为0.97，没有统计学意义的降低。对于嗜酸性粒细胞计数>6%的患者，三联疗法可以显著降低COPD急性加重的风险，风险比0.66。对于反复因COPD急性加重住院的患者而言，三联疗法也可以显著降低COPD急性加重的风险，风险比0.83。但是在三联疗法组中，需要住院治疗的重症肺炎的发生率显著升高，风险比 1.46。结论：真实世界中，在预防COPD加重方面，LAMA-LABA-ICS三联吸入疗法与LAMA-LABA二联吸入疗法同样有效。但是在嗜酸性粒细胞增多、或频繁急性加重的患者中，三联治疗方案获益更多。除此之外，二联治疗方案可能更为可取，因为它与重症肺炎发生率较低相关。《系统综述和荟萃分析：布地奈德/格隆溴铵/福莫特罗三联吸入疗法和其他LAMA-LABA-ICS三联吸入疗法的疗效比较》Advances in Therapy，2020年6月 (4)这篇荟萃分析纳入了18项研究，29,232例患者的资料。在减轻中重度COPD患者病情加重、改善肺功能和症状方面，布地奈德/格隆溴铵/福莫特罗和其他三联吸入的固定剂量组合（氟替卡松/芜地溴铵/维兰特罗、倍氯米松/格隆溴铵/福莫特罗）没有统计学差异；和其他开放联合用药之间也没有统计学显著差异。敏感性分析和元回归分析的结果与基本情况一致。结论：在减轻中重度COPD患者病情加重、改善肺功能和症状方面，可布地奈德/格隆溴铵/福莫特罗与其他LAMA-LABA-ICS固定剂量三联疗法的疗效相似。小羽点评：从随机临床研究的角度看，固定剂量的三联吸入疗法在减少COPD患者病情加重方面的疗效是相似的，并且优于二联吸入疗法；然而，在真实世界中，三联吸入疗法的优势则不那么明显了，甚至还有可能增加重症肺炎的发生率。《IMPACT研究亚组分析：吸入糖皮质激素停用和基线吸入治疗对病情加重的影响》American Journal of Respiratory and Critical Care Medicine，2020年11月 (5)IMPACT研究证明，每日一次吸入氟替卡松/芜地溴铵/维兰特罗三联疗法，可以降低了有症状且有加重史的COPD患者的全因死亡率。这项亚组分析的目的是了解吸入糖皮质类固醇停药是否影响影响结果。与芜地溴铵/维兰特罗二联治疗方案相比，氟替卡松/芜地溴铵/维兰特罗三联治疗方案显著降低了以前使用糖皮质激素的患者中，COPD中重度急性的发生率显著降低29%（P < 0.001），但在先前不使用糖皮质激素的患者中这种获益并不显著（降低12%，P = 0.115）。无论先前是否使用过糖皮质激素，三联吸入治疗方案均可以降低重度急性发作达35%、持续改善第一秒用力呼气量谷值和圣乔治呼吸问卷评分（SGRQ）。结论：这些数据支持了三联治疗在减轻病情恶化、肺功能和生活质量方面的重要作用，而这些作用似乎与ICS的突然停用无关。《ISOLDE研究：吸入糖皮质激素治疗后血液嗜酸性粒细胞的变化可能预测慢性阻塞性肺病的长期临床反应》European Respiratory Journal，2020年5月 (6)此研究的目的是评价吸入糖皮质激素后，血液嗜酸性粒细胞的变化可以预测长期治疗结果。这项为期3年的双盲试验中，对751名中-重度COPD患者随机分入氟替卡松组和安慰剂组。研究发现，1年内的嗜酸性粒细胞的减少与治疗效果相关，而且是治疗反应的强预测因子。在嗜酸性粒细胞下降≥200/μL时，吸入糖皮质激素可降低第一秒用力呼气量（FEV1）下降率达32mL/年，恶化率降低30%。相反，在嗜酸性粒细胞升高≥200/μL时，吸入糖皮质激素可加速第一秒用力呼气量下降，下降速度为37mL/年，恶化率增加80% （P4年的患者患肺癌的风险比为0.92，无统计学意义。平均每日吸入糖皮质激素较高的患者肺癌的风险比为1.36（95% CI 1.03-1.81）。结论：在COPD患者中，吸入糖皮质激素与肺癌发病率的降低无关。《欧洲呼吸协会指南：慢性阻塞性肺病患者何时停用吸入糖皮质激素》European Respiratory Journal，2020年6月 (8)吸入糖皮质激素联合支气管扩张剂，可降低慢性阻塞性肺病患者病情加重的频率，但是糖皮质激素经常被用于疗效不确定的患者。因此文章建议对于下列情况停用吸入糖皮质激素：（1）若COPD患者没有频繁发作的病史，指南认为停用活继续糖皮质激素吸入治疗的获益风险比存在不确定性，需要充分告知和与患者讨论；（2）若血液嗜酸性粒细胞计数≥300/µl，指南强烈建议不要停用吸入糖皮质激素；（3）若准备停用吸入糖皮质激素，指南强烈建议使用一个或两个长效支气管扩张剂。COPD患者肺康复训练肺康复可以改善慢性呼吸系统疾病患者的症状、生存质量和肺功能。肺康复包括运动训练、促进将康的行为（比如戒烟、锻炼、营养支持、恰当用药和自我管理）和心理支持。运动训练可以采用下肢训练（如，固定式脚踏车、跑步机或自由行走）、上肢训练（如手臂训练）、间歇运动训练、抗阻力/力量训练和呼吸再训练。《回顾性队列研究：COPD出院后开始肺康复1年生存率的影响》JAMA，2020年5月 (9)肺康复训练与慢性阻塞性肺病患者生存率提高相关，但相关研究的患者数量少且异质性高。研究的目的时确定慢性阻塞性肺病患者出院后90天内开始肺部康复与1年生存率之间的关系。研究纳入197 376例患者、平均年龄76.9岁，1.5%的患者在出院后90天内开始肺康复。出院1年内死亡率19.4%，其中进行肺康复训练者死亡率7.3%，没有进行康复训练者死亡率19.6%。进行肺康复训练者绝对死亡风险下降6.7%，风险比 0.63。结论：慢性阻塞性肺病病人，出院后3个月内开始肺部康复1年死亡率显著降低。《随机对照研究：下坡行走对COPD患者肺部康复的影响》European Respiratory Journal，2020年5月 (10)收缩性肌肉疲劳影响COPD患者的训练反应。下坡步行诱发收缩肌疲劳、呼吸困难和疲劳程度较平地步行低。本研究比较了下坡步行训练和平地步行训练的方式进行肺康复对COPD患者的影响。在这项随机对照试验中，35例患者，平均年龄62岁，第一秒最大呼气量（FEV1）平均50%，随机分为下坡步行组或平地步行组。两组间，6分钟步行试验结果和肌肉活检没有差异（p=0.45）；但是94%的进行下坡行走锻炼的患者进步了，平地行走组仅为65%（p=0.03）。在其他方面，下坡行走组也有更大的改善。结论：在慢性阻塞性肺病患者中，结合下坡行走与常规步行在肺康复临床疗效上具有相似的效果；但是锻炼耐受性更好。《ON-EPIC研究：口服硝酸盐补充剂增强慢性阻塞性肺病肺部康复》Thorax 2020年7月 (11)研究的目的是评估口服硝酸盐是否能增强慢性阻塞性肺病患者的肺康复效果。这项双盲、安慰剂对照、平行组、随机对照研究在四个英国中心进行，登记了患有GOLD分级II-IV级的、医学研究委员会（Medical Research Council）呼吸困难评分3-5分或功能受限的COPD成年患者，进行每周两次、为期8周的肺康复训练计划。他们被随机分配到140ml富含硝酸盐的甜菜汁组（含12.9 mmol硝酸盐），或安慰剂组，服用前3小时进行肺康复训练治疗。积极治疗组(57例)的运动能力比安慰剂组(65例)提高更多;ISWT距离+60 m (10,85) vs +30 m(0,70)中值(IQR)变化，估计处理效果30 m (95% CI 10 ~ 40);p = 0.027。积极治疗对收缩压也有影响:治疗组-5.0 mm Hg (-5.0， -3.0) vs对照组+6.0 mm Hg(-1.0, 15.5)，估计治疗效果-7 mm Hg (95% CI 7 ~ -20) (p

FDA 治疗高度耐药肺结核的新药NEJM 巴罗萨韦对流感家庭接触者的流感预防效果医学前沿 支气管低温冷冻术和支气管流变成形术治疗慢性支气管炎普托马尼（pretomanid）普托马尼（pretomanid）是一种新型的口服硝基咪唑嗪类抗菌药。2019年8月，普托马尼被批准作为BPaL方案（贝达喹啉、 普托马尼和利奈唑胺）和BPaMZ（贝达喹啉、 普托马尼、莫西沙星和吡嗪酰胺）方案的一部分用于治疗耐药性肺结核。《开放标签单组研究：高度耐药肺结核的治疗》New England Journal of Medicine，2020年3月 (1)这项开放标签、单组研究的目的是评价贝达喹啉、普托马尼和利奈唑胺联合26周治疗广泛耐药结核病患者、以及治疗无效或因副作用而停用二线治疗方案的多药耐药结核病患者的安全性和疗效。共计109例患者被纳入本研究，治疗结束后6个月时，90%的患者结局良好。11例不良结局包括：7例死亡，2例在随访期间复发。利奈唑胺的预期毒性作用包括周围神经病（81%）和骨髓抑制（48%），这些毒性作用虽然常见，但可以控制，常导致利奈唑胺减量或中断用药。结论：在高度耐药结核病患者中，在治疗结束后6个月时，贝达喹啉、普托马尼和利奈唑胺联合治疗使高比例的患者有良好结局。流行性感冒流行性感冒是甲型或乙型流感病毒导致的急性呼吸道疾病，在世界范围内引起爆发和流行，主要发生在冬季。患者出现上呼吸道和/或下呼吸道受累的症状，伴有全身症状，如发热（37.8°C-40.0°C）、头痛、肌痛和无力。一般人群中流感属于自限性疾病，高危人群中并发症和死亡率增加。流感通过大颗粒飞沫和小颗粒气溶胶传播，潜伏期1-4天，无并发症的患者病程持续1周左右，病毒排出时间为病毒暴露后0.5天到7天，病毒排出的高峰在第2天。高危人群包括：年龄≥65岁，妊娠或产后2周，住在长期护理机构，美国印第安人和阿拉斯加原住民，极端肥胖者（BMI≥40kg/m2)，慢性疾病患者，糖皮质激素或免疫抑制治疗的患者。《回顾观察性研究：老年人流感疫苗接种对住院和死亡率的影响》Annual of Internal Medicine，2020年4月 (2)65岁以上的老年人接种疫苗有临床获益的证据非常缺乏，研究者设计了一项“断点回归”分析，他们通过英国7个大型临床数据库分析了疫苗接种率和流感相关疾病。研究发现成人疫苗接种率在65岁这一年，从34%提高至57%。重度呼吸系统疾病均随着年龄的增长而升高，平滑地通过了65岁这一门槛，没有出现急剧下降。假如每年接种流感疫苗的确能给65岁以上的老年人带来明显临床益处的话，预期应出现急剧下降。结论：老年人接种流感疫苗充其量只有很小的直接获益。《双盲随机对照研究：巴罗萨韦对流感家庭接触者的流感预防效果》New England Journal of Medicine，2020年7月 (3)巴罗萨韦在家庭环境中的暴露后预防效果尚不明确。这项多中心、双盲、随机、安慰剂对照试验，在确诊流感病例的545个家庭的752个接触者中，将参与者随机分为两组，分别接受巴罗萨韦或安慰剂单剂给药。巴罗萨韦预防组患临床流感显著低于安慰剂组（1.9% vs. 13.6%；P＜0.001）。巴罗萨韦在高危、儿童和未接种疫苗的参与者的亚组中有效。两组的不良事件发生率相似（巴洛沙韦组22.2%和安慰剂组20.5%）。结论：单剂巴罗萨韦显示出显著的流感病毒暴露后预防效果。流行性感冒的治疗抗病毒治疗包括：神经氨酸酶抑制剂（奥司他韦、扎那米韦和帕拉米韦），流感病毒cap-依赖性核酸内切酶选择性抑制剂巴罗萨韦（baloxavir），金刚烷胺类（金刚烷胺和金刚乙胺）。《开放标签随机对照研究：流感样疾病的治疗中加用奥司他韦的疗效研究》Lancet，2020年1月 (4)研究目的是确定流感样疾病患者在常规初级护理中加入奥司他韦抗病毒治疗是否会缩短康复时间。这项开放标签的、实用的、适应性的、随机对照试验中，将奥司他韦添加到常规治疗中。研究纳入3266名参与者，其中52%经证实感染了流感。总体而言，奥司他韦组的患者恢复时间较短，绝对缩短1.20天。对于没有合并症的、

FDA 治疗高度耐药肺结核的新药NEJM 巴罗萨韦对流感家庭接触者的流感预防效果医学前沿 支气管低温冷冻术和支气管流变成形术治疗慢性支气管炎普托马尼（pretomanid）普托马尼（pretomanid）是一种新型的口服硝基咪唑嗪类抗菌药。2019年8月，普托马尼被批准作为BPaL方案（贝达喹啉、 普托马尼和利奈唑胺）和BPaMZ（贝达喹啉、 普托马尼、莫西沙星和吡嗪酰胺）方案的一部分用于治疗耐药性肺结核。《开放标签单组研究：高度耐药肺结核的治疗》New England Journal of Medicine，2020年3月 (1)这项开放标签、单组研究的目的是评价贝达喹啉、普托马尼和利奈唑胺联合26周治疗广泛耐药结核病患者、以及治疗无效或因副作用而停用二线治疗方案的多药耐药结核病患者的安全性和疗效。共计109例患者被纳入本研究，治疗结束后6个月时，90%的患者结局良好。11例不良结局包括：7例死亡，2例在随访期间复发。利奈唑胺的预期毒性作用包括周围神经病（81%）和骨髓抑制（48%），这些毒性作用虽然常见，但可以控制，常导致利奈唑胺减量或中断用药。结论：在高度耐药结核病患者中，在治疗结束后6个月时，贝达喹啉、普托马尼和利奈唑胺联合治疗使高比例的患者有良好结局。流行性感冒流行性感冒是甲型或乙型流感病毒导致的急性呼吸道疾病，在世界范围内引起爆发和流行，主要发生在冬季。患者出现上呼吸道和/或下呼吸道受累的症状，伴有全身症状，如发热（37.8°C-40.0°C）、头痛、肌痛和无力。一般人群中流感属于自限性疾病，高危人群中并发症和死亡率增加。流感通过大颗粒飞沫和小颗粒气溶胶传播，潜伏期1-4天，无并发症的患者病程持续1周左右，病毒排出时间为病毒暴露后0.5天到7天，病毒排出的高峰在第2天。高危人群包括：年龄≥65岁，妊娠或产后2周，住在长期护理机构，美国印第安人和阿拉斯加原住民，极端肥胖者（BMI≥40kg/m2)，慢性疾病患者，糖皮质激素或免疫抑制治疗的患者。《回顾观察性研究：老年人流感疫苗接种对住院和死亡率的影响》Annual of Internal Medicine，2020年4月 (2)65岁以上的老年人接种疫苗有临床获益的证据非常缺乏，研究者设计了一项“断点回归”分析，他们通过英国7个大型临床数据库分析了疫苗接种率和流感相关疾病。研究发现成人疫苗接种率在65岁这一年，从34%提高至57%。重度呼吸系统疾病均随着年龄的增长而升高，平滑地通过了65岁这一门槛，没有出现急剧下降。假如每年接种流感疫苗的确能给65岁以上的老年人带来明显临床益处的话，预期应出现急剧下降。结论：老年人接种流感疫苗充其量只有很小的直接获益。《双盲随机对照研究：巴罗萨韦对流感家庭接触者的流感预防效果》New England Journal of Medicine，2020年7月 (3)巴罗萨韦在家庭环境中的暴露后预防效果尚不明确。这项多中心、双盲、随机、安慰剂对照试验，在确诊流感病例的545个家庭的752个接触者中，将参与者随机分为两组，分别接受巴罗萨韦或安慰剂单剂给药。巴罗萨韦预防组患临床流感显著低于安慰剂组（1.9% vs. 13.6%；P＜0.001）。巴罗萨韦在高危、儿童和未接种疫苗的参与者的亚组中有效。两组的不良事件发生率相似（巴洛沙韦组22.2%和安慰剂组20.5%）。结论：单剂巴罗萨韦显示出显著的流感病毒暴露后预防效果。流行性感冒的治疗抗病毒治疗包括：神经氨酸酶抑制剂（奥司他韦、扎那米韦和帕拉米韦），流感病毒cap-依赖性核酸内切酶选择性抑制剂巴罗萨韦（baloxavir），金刚烷胺类（金刚烷胺和金刚乙胺）。《开放标签随机对照研究：流感样疾病的治疗中加用奥司他韦的疗效研究》Lancet，2020年1月 (4)研究目的是确定流感样疾病患者在常规初级护理中加入奥司他韦抗病毒治疗是否会缩短康复时间。这项开放标签的、实用的、适应性的、随机对照试验中，将奥司他韦添加到常规治疗中。研究纳入3266名参与者，其中52%经证实感染了流感。总体而言，奥司他韦组的患者恢复时间较短，绝对缩短1.20天。对于没有合并症的、

Fev1 etc.

IntroDawn Patterson, ERT Director of Respiratory Solutions, is joined by Kevin McCarthy, ERT Clinical Overread Specialist and member of the ATS/ERS 2019 Spirometry Update Task Force. They’ll explore the implications of the October 2019 ATS/ERS update to their pulmonary function testing guidance. ERT was the only data and technology vendor involved in the update.What are the ATS/ERS guidelines?These guidelines represent what can be considered as worldwide standards that ensure the quality of pulmonary function measurements. This type of measurement is somewhat unique in that it requires a high degree of patient understanding and cooperation.When were the ATS/ERS guidelines last updated?Spirometry standards were first published 40 years ago, and updated approximately every 10-15 years since. The last time they were updated prior to 2019 was 2005.How did you get involved in the task force that was responsible for updating the guidelines?I was approached by the ATS/ERS to participate on a committee to develop an accreditation for pulmonary function laboratories. While working on that project, I was asked if I’d be interested in participating on the update task force.How is this guidance used in clinical research?Typically, ATS/ERS guidelines are incorporated in testing protocol for clinical trials. This is important in guaranteeing comparability of tests obtained from multiple global testing sites. In the 2019 guidelines, it’s specified that these standards represent the minimum criteria that must be met for clinical spirometry only - not necessarily for research or occupational surveillance. In clinical trials, sometimes the bar should be set higher.What are the most important changes in the new spirometry guidelines?One of the most important changes involves the recognition that the forced exhalation could be performed perfectly but still give erroneously low results. The new standards emphasize the need to look at the subject for feedback, and gives detailed guidance to site operators on how to vigorously coach patients to full inflation.The new standards also stipulate that the procedure does not end with the forced exhalation. At the end of the forced exhalation, the subject is again vigorously coached to full inflation, allowing for a comparison to the FVC that allows operators to verify the forced exhalation started from full inflation.In recognition that pediatric patients and patients with interstitial lung disease had difficulty in meeting end-of-test acceptability criteria, these acceptability criteria were redefined in a manner that accommodates the lung physiology of these groups.Finally, the updated standards provide a new letter grading standard for acceptability based on the two main forced spirometry parameters. In the old standards, if an effort failed to meet the start of test criteria, the effort was considered to be unusable for reporting. In the new standards, an effort that is unusable for FEV1 may be acceptable for FVC and vice versa.Are there any minor changes to the guidance that people need to look out for?This document makes recommendations to the manufacturers about features that they should provide for the users of their testing equipment. One of the recommendations made was that the manufacturers provide standard lists of operator comments. These lists allow the operator to quickly select a comment from a list (in addition to adding free text) to provide insight and context about quality issues for study teams or physicians.How will this new guidance impact sites and patients in respiratory clinical trials?This new update of the spirometry standards will likely reduce the number of times a patient will have to perform the forced expiratory maneuver to achieve acceptability, improve data repeatability and improve data quality by verifying all efforts start from full inflation. This should result in a big win for sponsors, especially in studies involving pediatric patients and patients with interstitial lung disease.Final thoughts:There was an increased recognition of the importance of the operator administering the test in getting quality results. Operator training and the attainment and maintenance of competency must be integrated in any spirometry testing service.    

> Restrictive Pulmonary Disease Idiopathic pulmonary fibrosis The development of scar tissue within the lungs Clinical presentation Dyspnea Dry cough Chest discomfort Labs, Studies and Physical Exam Findings Fine crackles at the bases may be present FEV1 is reduced FVC […] The post S2 E053 Restrictive Lung Diseases and what to avoid on your breaks. appeared first on Physician Assistant Exam Review.

Ha ottenuto risultati "eclatanti" il seminario tenuto dal dottor Franco Berrino e da Daniel Lumera e organizzato dall'associazione La Grande Via lo scorso giugno. Si è trattato - spiega il sito Terranuova.it - "di un ritiro scientifico esperienziale di riattivazione del corpo, della mente e dell’anima, della durata di due settimane presso La Villa La Mausolea (Soci, Arezzo), in cui sono state fornite istruzioni precise e dettagliate per poter proseguire il percorso per un’ulteriore settimana di mantenimento a casa propria, in autonomia". Gli esami medici eseguiti prima e dopo le due settimane hanno dimostrato un netto miglioramento a livello fisiologico nei 33 partecipanti, di età compresa tra i 39 e i 75 anni. Dall'associazione La Grande Via hanno fatto sapere: «Ogni partecipante ha ottenuto risultati evidenti anche sul proprio fisico: in media sono stati persi 4 kg di peso corporeo e 4 cm di circonferenza addominale, che possono essere tradotti in termini di benefici in un 30% in meno di rischio cardiovascolare. Nei partecipanti che hanno sperimentato le attivazioni bioenergetiche svolgendo test pre e post pratica, i valori FEV1 e FVC sono risultati aumentati riscontrando un’aumentata capacità vitale e del volume espiratorio».

Editor's Summary by Howard Bauchner, MD, Editor in Chief of JAMA, the Journal of the American Medical Association, for the June 25, 2019 issue

In this episode I cover lung function tests, spirometry and peak flow assessment.If you want to follow along with written notes on lung function tests go to https://zerotofinals.com/lungfunctiontests or find the respiratory section in the Zero to Finals medicine book.This episode covers the obstructive and restrictive lung disease, spirometry FEV1, FVC, FEV1:FVC ratio, peak flow and the findings that you would find in various conditions.The audio in the episode was expertly edited by Harry Watchman.

Rapid declines in spirometric measures of lung function were associated with higher risks of cardiovascular disease today, risankizumab provides more effect in psoriasis that ustekinumamb, there is no link between screening and liver cancer mortality, and eosinophils are a possible marker for nonceliac gluten or wheat sensitivity.

Have we lost sight of the adult patients in the cystic fibrosis community? The trio responds to Gunnar's blog about what seems to be the prioritization of pediatric patients over the adults who have fought through CF for decades. Do adults feel forgotten? Tiffany talks about some of the frustrations she feels in having just missed out on the drug development boom by virtue of being post transplant, Lea shares her frustrations with falling just below the FEV1 cut off for different trials, and Gunnar pleads for more to be done for adults in the here and now.

Future Landscape of CFTR Modulators

A phase 3, multi-center, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin inhalation solution (APT-1026) in stable cystic fibrosis patients. Flume PA, VanDevanter DR, Morgan EE, Dudley MN, Loutit JS, Bell SC, Kerem E, Fischer R, Smyth AR, Aaron SD, Conrad D, Geller DE,Elborn JS. J Cyst Fibros. 2016 Jul;15(4):495-502. doi: 10.1016/j.jcf.2015.12.004. Epub 2016 Feb 4. Abstract RATIONALE: For patients with cystic fibrosis (CF), the use of inhaled antibiotics has become standard of care to suppress chronic Pseudomonas airways infection. There are limited antibiotic options formulated and approved for inhaled use and antibiotic efficacies attenuate over time, making additional inhaled antibiotic classes desirable. APT-1026 (levofloxacin inhalation solution, LIS) is a fluoroquinolone in development for management of chronic P. aeruginosa airways infection in patients with CF. OBJECTIVES: To compare the safety and efficacy of a 28-day course of treatment with LIS 240mg or placebo BID in persons ≥12years old with CF and chronic P. aeruginosa infection. METHODS: A multinational, randomized (2:1), double-blinded study of LIS and placebo over 28days in CF patients ≥12years with chronic P. aeruginosa infection. Time to exacerbation was the primary endpoint. FEV1 (% predicted) and patient-reported ...

A phase 3, multi-center, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin inhalation solution (APT-1026) in stable cystic fibrosis patients. Flume PA, VanDevanter DR, Morgan EE, Dudley MN, Loutit JS, Bell SC, Kerem E, Fischer R, Smyth AR, Aaron SD, Conrad D, Geller DE,Elborn JS. J Cyst Fibros. 2016 Jul;15(4):495-502. doi: 10.1016/j.jcf.2015.12.004. Epub 2016 Feb 4. Abstract RATIONALE: For patients with cystic fibrosis (CF), the use of inhaled antibiotics has become standard of care to suppress chronic Pseudomonas airways infection. There are limited antibiotic options formulated and approved for inhaled use and antibiotic efficacies attenuate over time, making additional inhaled antibiotic classes desirable. APT-1026 (levofloxacin inhalation solution, LIS) is a fluoroquinolone in development for management of chronic P. aeruginosa airways infection in patients with CF. OBJECTIVES: To compare the safety and efficacy of a 28-day course of treatment with LIS 240mg or placebo BID in persons ≥12years old with CF and chronic P. aeruginosa infection. METHODS: A multinational, randomized (2:1), double-blinded study of LIS and placebo over 28days in CF patients ≥12years with chronic P. aeruginosa infection. Time to exacerbation was the primary endpoint. FEV1 (% predicted) and patient-reported ...

A phase 3, multi-center, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin inhalation solution (APT-1026) in stable cystic fibrosis patients. Flume PA, VanDevanter DR, Morgan EE, Dudley MN, Loutit JS, Bell SC, Kerem E, Fischer R, Smyth AR, Aaron SD, Conrad D, Geller DE,Elborn JS. J Cyst Fibros. 2016 Jul;15(4):495-502. doi: 10.1016/j.jcf.2015.12.004. Epub 2016 Feb 4. Abstract RATIONALE: For patients with cystic fibrosis (CF), the use of inhaled antibiotics has become standard of care to suppress chronic Pseudomonas airways infection. There are limited antibiotic options formulated and approved for inhaled use and antibiotic efficacies attenuate over time, making additional inhaled antibiotic classes desirable. APT-1026 (levofloxacin inhalation solution, LIS) is a fluoroquinolone in development for management of chronic P. aeruginosa airways infection in patients with CF. OBJECTIVES: To compare the safety and efficacy of a 28-day course of treatment with LIS 240mg or placebo BID in persons ≥12years old with CF and chronic P. aeruginosa infection. METHODS: A multinational, randomized (2:1), double-blinded study of LIS and placebo over 28days in CF patients ≥12years with chronic P. aeruginosa infection. Time to exacerbation was the primary endpoint. FEV1 (% predicted) and patient-reported ...

A phase 3, multi-center, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin inhalation solution (APT-1026) in stable cystic fibrosis patients. Flume PA, VanDevanter DR, Morgan EE, Dudley MN, Loutit JS, Bell SC, Kerem E, Fischer R, Smyth AR, Aaron SD, Conrad D, Geller DE,Elborn JS. J Cyst Fibros. 2016 Jul;15(4):495-502. doi: 10.1016/j.jcf.2015.12.004. Epub 2016 Feb 4. Abstract RATIONALE: For patients with cystic fibrosis (CF), the use of inhaled antibiotics has become standard of care to suppress chronic Pseudomonas airways infection. There are limited antibiotic options formulated and approved for inhaled use and antibiotic efficacies attenuate over time, making additional inhaled antibiotic classes desirable. APT-1026 (levofloxacin inhalation solution, LIS) is a fluoroquinolone in development for management of chronic P. aeruginosa airways infection in patients with CF. OBJECTIVES: To compare the safety and efficacy of a 28-day course of treatment with LIS 240mg or placebo BID in persons ≥12years old with CF and chronic P. aeruginosa infection. METHODS: A multinational, randomized (2:1), double-blinded study of LIS and placebo over 28days in CF patients ≥12years with chronic P. aeruginosa infection. Time to exacerbation was the primary endpoint. FEV1 (% predicted) and patient-reported ...

Volume 5, Issue 12.In this issue of eCysticfibrosis Review Dr. Chris Goss of the University of Washington Medical Center. Dr. Goss discusses the benefits of CFTR modification beyond Fev1 improvement through the use of patient-cases.The post Benefits of CFTR Modification Beyond FEV1 Improvement appeared first on DKBmed Radio. Hosted on Acast. See acast.com/privacy for more information.

Originally presented at the 2013 North American Cystic Fibrosis Conference, this program covers differentiation of CF classes and current/potential therapies and using the CFTR2 database.

Learn about the 5 classes of CFTR mutations, the latest research on emerging therapies for each mutation class and follow four individuals with CF. These case-based modules were presented at the 36th European Cystic Fibrosis Society Conference in Lisbon, Portugal.

Background: The diagnostic use of lung function using spirometry dependson the validity of reference equations. A multitude of spirometricprediction values have been published, but in most of these studiesolder age groups are underrepresented. Objectives: The aim of thepresent study was to establish new spirometric reference values foradvanced age and to compare these to recent prediction equations frompopulation-based studies. Methods: In the present study spirometry wasperformed in a population-based sample from the KORA-F4 and KORA-Agecohorts (2006-2009, Augsburg, Germany) comprising 592 never-smokingsubjects aged 42-89 years and with no history of respiratory disease.Using quantile regression analysis, equations for the median and lowerlimit of normal were derived for indices characterizing the expiratoryflow-volume curve: forced expiratory volume in 1 s (FEV1), forced vitalcapacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forcedexpiratory flow rates at 25, 50 and 75% of exhaled FVC (FEF25, FEF50and FEF75). Results: FEV1 and FVC were slightly higher, and PEF waslower compared to recently published equations. Importantly, forcedexpiratory flow rates at middle and low lung volume, as putativeindicators of small airway disease, were in good agreement with recentdata, especially for older age. Conclusion: Our study providesup-to-date reference equations for all major indices of flow-volumecurves in middle and advanced age in a South German population. Thesmall deviations from published equations indicate that there might besome regional differences of lung function within the Caucasianpopulation of advanced age in Europe.

Background: The relevance of Trichosporon species for cystic fibrosis (CF) patients has not yet been extensively investigated. Methods: The clinical course of CF patients with Trichosporon spp. in their respiratory secretions was analysed between 2003 and 2010 in the Munich CF center. All respiratory samples of 360 CF patients (0 - 52.4 years; mean FEV1 2010 81.4% pred) were investigated. Results: In 8 patients (2.2%, 3 male, mean age 21.8 years) Trichosporon was detected at least once. One patient carried T. asahii. One patient carried T. mycotoxinivorans and one patient T. inkin as determined by DNA sequencing. As potential risk factors for Trichosporon colonization steroid treatment, allergic bronchopulmonary aspergillosis (ABPA) and CF associated diabetes were identified in 6, 5, and 2 patients respectively. For one patient, the observation period was not long enough to determine the clinical course. One patient had only a single positive specimen and exhibited a stable clinical course determined by change in forced expiratory volume in one second (FEV1), body-mass-index (BMI), C-reactive protein (CRP) and immunoglobulin G (IgG). Of 6 patients with repeatedly positive specimen (mean detection period 4.5 years), 4 patients had a greater decline in FEV1 than expected, 2 of these a decline in BMI and 1 an increase in IgG above the reference range. 2 patients received antimycotic treatment: one patient with a tormenting dry cough subjectively improved under Amphotericin B inhalation; one patient with a severe exacerbation due to T. inkin was treated with i.v. Amphotericin B, oral Voriconazole and Posaconazole which stabilized the clinical condition. Conclusions: This study demonstrates the potential association of Trichosporon spp. with severe exacerbations in CF patients.

In Anbetracht der hohen Prävalenz an Atemwegs- und Lungenerkrankungen gewinnt deren Diagnostik und Therapie zunehmend an Bedeutung. Eine klinisch etablierte Methode zur Lungenfunktionsprüfung stellt die nicht-invasive Messung der Diffusionskapazität für Kohlenmonoxid (DLCO) dar, die Rückschluss auf die Gasaustauschfähigkeit der Lunge gibt. Welche Komponenten der Lunge- die Perfusion bzw. das Parenchym - bei reduzierter Diffusionskapazität konkret von pathologischen Veränderungen betroffen sind, lässt sich mittels des neuen Messverfahrens der kombinierten Diffusionskapazität für Kohlenmonoxid und Stickstoffmonoxid (DLNO) eruieren. Die vorliegende Untersuchung hat sich zum Ziel gesetzt, die Abhängigkeit des viel versprechenden Verfahrens von den Messbedingungen sowie die Aussagekraft der Messergebnisse bezüglich pathologischer Lungenveränderungen unter Hinzunahme bildgebender Verfahren zu prüfen. Bei Variation der Atemanhaltezeit von 4 s, 6 s, 8 s und 10 s differierten bei gesunden (n=10; Mittelwert +/- SD Alter 31 +/- 9 a; FEV(1) 108 +/- 8% Soll) und lungenkranken Probanden (n=10; Alter 33 +/- 9 a; FEV(1) 69 +/- 28% Soll) DLCO und DLNO signifikant (jeweils p < 0.05). Bei 6 s und 8 s waren jedoch für beide Studiengruppen vergleichbare Messwerte zu erheben, so dass eine standardisierte Messung der kombinierten Diffusionskapazität für CO und NO bei 6 s Atemanhaltezeit bzw. bei 8 s entsprechend den derzeit geltenden Empfehlungen zur Messung der Standard DLCO bei 10±2 s Atemanhaltezeit (MacIntyre et al., 2005) durch die Daten aktueller Untersuchung zu empfehlen ist. Der Vergleich der Messungen der kombinierten Diffusionskapazität sowie der Spirometrie und Ganzkörperplethysmographie von lungenkranken Probanden (n=21; Mittelwert +/- SD Alter 34 +/- 8 a; FEV(1) 59 +/- 13% Soll) mit deren hochauflösenden Thorax-Computertomograhien zeigte eine stärkere Korrelation mit DLCO und DLNO als mit den Messgrößen konventioneller Messmethoden, FEV1 als Standardgröße inbegriffen. Die CT Scores korrelierten am engsten mit DLNO (rS = -0.83; p < 0.001). Ferner ließ sich eine signifikante Beziehung zu DLCO (rS = -0.79; p < 0.001) und dem volumenspezifischen Transferkoeffizienten KNO (rS = -0.63; p < 0.01) nachweisen. Demnach erlaubt das neue Messverfahren der kombinierten Diffusionskapazität für CO und NO den Schweregrad struktureller Lungenalterationen nicht-invasiv zu quantifizieren. Um den Zusatznutzen vorgestellter Methode abschließend zu beurteilen, bedarf es weiterer prospektiver Longitudinalstudien.

eCystic Fibrosis Review: Featured Cases: Emerging Pathogens in Cystic Fibrosis

Surfactant associated protein-A (SP-A) is the most abundant pulmonary surfactant protein and belongs to the family of innate host defence proteins termed collectins. The aim of the study was to elucidate the role of SP-A in human lung disease. This study was designed to analyze the relation between genetics, structure and function of SP-A in a CF, chronic bronchitis and asthma and healthy control population ex vivo. Beginning with the analysis of SP-A oligomeric forms, there were no correlations between serum and BAL SP-A distribution forms. The forms showed only a significantly different distribution comparing serum samples from bronchitis patients and controls. In serum and BAL of CF patients the forms containing the first peak were correlated with a better lung function (Fev1 (% pred.)age20). Also higher relative SP-A amount in the first peak is associated with a milder lung disease and a better course of lung disease. Additionally, SP-A self-agglutination is dependent on the amount of particular SP-A oligomers present in a sample, i.e. the relative strength of SP-A molecular forms in a sample. All SP-A structures self-agglutinate in serum better than in BAL in samples of the patients groups while in control samples BAL and serum SP-A showed the same abilities. There was also a difference between the self-agglutination ability of BAL samples from CF, Bro and control derived SP-A, but none in serum. SP-A from control BAL agglutinated better than from bronchitis BAL and this better than from CF BAL. These results are also supported by the fact that a better agglutination ability of SP-A was significantly associated with lung function. Therefore the degree of the presence of active oligomeric forms within a BAL or serum sample seems to be important for a better lung function outcome. The SP-A oligomerization is associated with one SFTPA1 rs1136451 and one SFTPA2 SNP rs17881665 which are coupled, while the mutated allele seems to cause a lack of complex oligomers. The wildtype alleles of the SP-A2 SNPs rs1965708 and rs1975006 were associated with CF compared to the bronchitis and control group. There was a significant association between the mean ∆ Fev1 (%pred.) / year and V50L a SNP in the SFTPA1 gene (p = 0.0038) while the mutated allele was associated with a worse course of lung disease. The SP-A BAL level was significantly associated with the SP-A1 SNP rs1136451 (p = 0.002) and the SP-A2 SNP rs17881665r (p = 0.002). The SP-A serum level was significantly associated with SP-A1 N9T (p = 0.028). In addition in the CF study population there was a significant association between the SP-A level in BAL and the Fev1 (% pred.) estimated for age 20 (p = 0.009). The higher the SP-A levels were in BAL the bigger were the values of the Fev1 (% pred.) estimated for age 20. There was no correlation between the SP-A BAL or serum level and any other clinical characteristic such as BMI, age, gender, IgG or IgE in serum. In conclusion, these results indicate a very important role for SP-A in human lung immunity. Future areas for clinical research include disease specific SP-A expression pattern and their functional consequences, the differential roles of SP-A1 and SP-A2 in human lung diseases, and therapeutic approaches to correct altered SP-A levels.

Presented at NACFC Anaheim 2011 this symposium presentation offers information on the current treatment options for patients with cystic fibrosis. Mike Boyle, MD, from Johns Hopkins University School of Medicine offers a 25-minute look at the basics of CF, then describes genotype and CF phenotype relationships. The presentation includes a review the influences of severity of lung disease and outcomes in CF, followed up by issues related to adherence.

Presented at NACFC Anaheim 2011 this symposium presentation offers information on the current treatment options for patients with cystic fibrosis. Mike Boyle, MD, from Johns Hopkins University School of Medicine offers a 25-minute look at the basics of CF, then describes genotype and CF phenotype relationships. The presentation includes a review the influences of severity of lung disease and outcomes in CF, followed up by issues related to adherence.

Presented at NACFC Anaheim 2011 this symposium presentation offers information on the current treatment options for patients with cystic fibrosis. Mike Boyle, MD, from Johns Hopkins University School of Medicine offers a 25-minute look at the basics of CF, then describes genotype and CF phenotype relationships. The presentation includes a review the influences of severity of lung disease and outcomes in CF, followed up by issues related to adherence.

Aufgrund der steigenden Lebenserwartung von Patienten mit cystischer Fibrose (CF) nimmt die Prävalenz einer gestörte Glukosetoleranz (IGT) und eines CF-assoziierten Diabetes mellitus (CFRD)kontinuierlich zu. In der vorliegenden Arbeit wurde die Prävalenz von Glukosestoffwechselstörungen und deren Einfluss auf den klinischen Status in einer nicht vorselektionierten Gruppe von erwachsenen CF Patienten (n=34) im Vergleich zu neu-diagnostizierten Patienten mit Typ 2 Diabetes (n=9) und gesunden Kontrollpersonen (n=10) mittels oGTT untersucht. Desweiteren wurde durch Messung von Insulin, intaktem Proinsulin, intaktem GLP1 und der Bestimmung verschiedener Indices für die ß-Zellfunktion und die Insulinresistenz mögliche pathophysiologische Mechanismen in verschiedenen Stadien der Glukosetoleranzstörung untersucht. Bei den CF Patienten (Alter 30,2±8 Jahre, BMI 20,9 ±2,5 kg/m2) zeigten 50% der Patienten eine gestörten Glukosetoleranz (12% IFG, 23% IGT, 15% neu diagnostizierter CFRD). Im oGTT war der maximale Insulinpeak und die totale Insulinsekretionskapazität nicht unterschiedlich in den CF-Gruppen (AUCinsulin0-120min NGT: 3296±547 μU/ml, IFG: 3694±809 μU/ml, IGT: 3337±535 μU/ml, CFRD: 2387±318 μU/ml) und den Kontrollpersonen(3704±335 μU/ml). Bei CF-Patienten war ähnlich wie bei DM2 Patienten eine verminderte erste Phase der Insulinsekretion und eine zeitliche Verschiebung des Insulinpeaks nachweisbar, die mit der Verschlechterung der Glukosetoleranz assoziiert war (Stumvoll-FPIR NGT:450±291; IFG:252±203; IGT:309±254; CFRD:18±41; Kontrollen:950±388). Die Insulinsekretion korrelierte invers mit dem Glukoseprofil, so dass bei IFG und IGT hohe postprandiale Glukosespiegel innerhalb der ersten 60 Minuten und ein Blutzuckerabfall nach 120-180 min zu beobachten waren. Die Proinsulinspiegel und die GLP-1 Spiegel im oGTT waren nicht unterschiedlich im Vergleich zu den gesunden Kontrollen. Im Gegensatz zu den DM2 Patienten konnte bei CF Patienten keine deutliche Insulinresistenz festgestellt werden. Bei den CF Patienten war eine Verschlechterung der Lungenfunktion und des Ernährungszustandes mit zunehmender Glukoseintoleranz zu sehen. Hohe maximale Glukosespiegel(rs=-0,50, p=0,002), der Insulinogenic Index (rs = 0,36, p

Background: Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM. Methods: Sirolimus (trough level 5 - 10 ng/ml) was administered to ten female patients (42.4 +/- 11.9 years) with documented progression. Serial pulmonary function tests and six-minute-walk-distance (6-MWD) assessments were performed. Results: The mean loss of FEV(1) was - 2.30 +/- 0.52 ml/day before therapy and a significant mean gain of FEV(1) of 1.19 +/- 0.26 ml/day was detected during treatment (p = 0.001). Mean FEV(1) and FVC at baseline were 1.12 +/- 0.15 l (36.1 +/- 4.5%pred.) and 2.47 +/- 0.25 l (69.2 +/- 6.5% pred.), respectively. At three and six months during follow-up a significant increase of FEV1 and FVC was demonstrated (3 months Delta FEV(1): 220 +/- 82 ml, p = 0.024; 6 months Delta FEV(1): 345 +/- 58 ml, p = 0.001); (3 months Delta FVC: 360 +/- 141 ml, p = 0.031; 6 months Delta FVC: 488 +/- 138 ml, p = 0.006). Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy. Conclusions: Our data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.

Featured Cases: Allergic Bronchopulmonary Aspergillosis (ABPA)

eCystic Fibrosis Review:Featured Cases: Allergic Bronchopulmonary Aspergillosis (ABPA)

Background: Little is known about the influencing potential of specific characteristics on lung function in different populations. The aim of this analysis was to determine whether lung function determinants differ between subpopulations within Germany and whether prediction equations developed for one subpopulation are also adequate for another subpopulation. Methods: Within three studies (KORA C, SHIP-I, ECRHS-I) in different areas of Germany 4059 adults performed lung function tests. The available data consisted of forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. For each study multivariate regression models were developed to predict lung function and Bland-Altman plots were established to evaluate the agreement between predicted and measured values. Results: The final regression equations for FEV(1) and FVC showed adjusted r-square values between 0.65 and 0.75, and for PEF they were between 0.46 and 0.61. In all studies gender, age, height and pack-years were significant determinants, each with a similar effect size. Regarding other predictors there were some, although not statistically significant, differences between the studies. Bland-Altman plots indicated that the regression models for each individual study adequately predict medium (i.e. normal) but not extremely high or low lung function values in the whole study population. Conclusions: Simple models with gender, age and height explain a substantial part of lung function variance whereas further determinants add less than 5% to the total explained r-squared, at least for FEV1 and FVC. Thus, for different adult subpopulations of Germany one simple model for each lung function measures is still sufficient.

Transcript -- A look at the two tests available for examining COPD.

A look at the two tests available for examining COPD.

Transcript -- A look at the two tests available for examining COPD.

A look at the two tests available for examining COPD.

Background Due to large-scale destruction, changes in membrane diffusion (Dm) may occur in cystic fibrosis (CF), in correspondence to alterations observed by computed tomography (CT). Dm can be easily quantified via the diffusing capacity for nitric oxide (DLNO), as opposed to the conventional diffusing capacity for carbon monoxide (DLCO). We thus studied the relationship between DLNO as well as DLCO and a CF-specific CT score in patients with stable CF. Methods Simultaneous single-breath determinations of DLNO and DLCO were performed in 21 CF patients (mean ± SD age 35 ± 9 y, FEV1 66 ± 28%pred). Patients also underwent spirometry and bodyplethysmography. CT scans were evaluated via the Brody score and rank correlations (rS) with z-scores of functional measures were computed. Results CT scores correlated best with DLNO (rS = -0.83; p < 0.001). Scores were also related to the volume-specific NO transfer coefficient (KNO; rS = -0.63; p < 0.01) and to DLCO (rS = -0.79; p < 0.001) but not KCO. Z-scores for DLNO were significantly lower than for DLCO (p < 0.001). Correlations with spirometric (e.g., FEV1, IVC) or bodyplethysmographic (e.g., SRaw, RV/TLC) indices were weaker than for DLNO or DLCO but most of them were also significant (p < 0.05 each). Conclusion In this cross sectional study in patients with CF, DLNO and DLCO reflected CT-morphological alterations of the lung better than other measures. Thus the combined diffusing capacity for NO and CO may play a future role for the non-invasive, functional assessment of structural alterations of the lung in CF.

C. Wenzel1, P. Brand2, C. Herpich2, S. Häußermann2, T. Meyer2, B. Müllinger3, G. Scheuch3, K. Häußinger1 1 Asklepios Fachkliniken München-Gauting, Gauting 2 Inamed Research GmbH & Co. KG, Gauting 3 Activaero GmbH, Gemünden Abstract Einleitung: Die Verwendung von kontrollierten Atemmanövern bei der Inhalation von Medikamenten zeichnet sich durch eine hohe Dosis-Reproduzierbarkeit aus, die auch bei der Durchführung von bronchialen Provokationstests von Vorteil sein kann. Material und Methodik: In der vorliegenden Studie wurde bei 30 Probanden mit Atopie-Anamnese in einem cross-over Design je ein bronchialer Provokationstest mit Methacholin und dem Viasys-Jäger-APS sowie mit kontrollierter Inhalation (AKITA-System) (vorgegebenes Inhalationsvolumen und -fluss) durchgeführt. Gemessen wurde die Häufigkeit positiver Befunde im Studienkollektiv, wobei „positiv” entweder als 20 %-iger Abfall des FEV1, oder als 100 %-Anstieg des sRaw definiert war. Ergebnisse: Es zeigten sich keine signifikanten Unterschiede in der Prävalenz positiver Testergebnisse zwischen beiden Methoden: APS-FEV1 : 8, AKITA-FEV1 : 9; APS-sRaw: 18, AKITA-sRaw: 17. Es reagierten also erheblich mehr Personen mit einem 100 %-igen Anstieg des sRaw, als mit einem Abfall des FEV1. Allerdings hat sich gezeigt, dass zwischen den Ergebnissen der beiden Methoden Diskrepanzen bestehen. Nur in 25 (sRaw: 21) von 30 Fällen stimmte das Ergebnis (positiv oder negativ) zwischen beiden Methoden tatsächlich überein. Zusammenfassung: Trotz dieser Diskrepanzen kann gefolgert werden, dass das AKITA-System mit kontrollierter Inhalation von Methacholin eine Alternative zum APS-System darstellt.

Landwirte sind durch ihr Arbeitsumfeld einer erhöhten Konzentration von organischem Staub, insbesondere Endotoxinen im Stall, bei erhöhtem Lungenminutenvolumen durch körperliche Arbeit ausgesetzt. Ziel der vorliegenden Untersuchung war es, unter Berücksichtigung der Endotoxinkonzentrationen das broncho-pulmonale System auf Entzündungsreaktionen zu untersuchen. Insbesondere war hier die nasale Lavage von Interesse, da hierbei durch eine nicht-invasive Untersuchungstechnik Rückschlüsse auf den Zustand des Respirationstraktes gezogen werden können. Zum Vergleich und um Aussagen über systemische Entzündungsreaktionen zu erhalten, wurden ausgewählte Entzündungsparameter im peripheren, venösen Blut quantitativ bestimmt. Die Untersuchung erfolgte an zwei Kollektiven gesunder Probanden. Es wurden 21 Landwirte mit 24 nicht beruflich exponierten Personen verglichen und das Auftreten von respiratorischen und allergischen Symptomen nach Exposition erfasst. Des Weiteren wurden eine Lungenfunktionsuntersuchung, eine Blutabnahme und eine Nasallavage zur Evaluierung der häufigsten Blut- und Entzündungsparameter durchgeführt. Im Plasma wurden die proinflammatorischen Zytokine TNF-, IL-6 und ENA-78 bestimmt. Zusätzlich wurde Endotoxin personenbezogen gemessen sowie die Kohlendioxid- und Ammoniakkonzentrationen im Stall ortsfest bestimmt. Temperatur, Luftfeuchtigkeit und Windgeschwindigkeit im Stall wurden vor Ort am Expositionstag ermittelt. Die gemessenen Endotoxin Konzentrationen lagen im Bereich von 0,9 EU/m3 bis 20816,3 EU/m3. Die Lungenfunktionswerte zeigten eine signifikante Erhöhung über die Stallarbeit. VCinsp (vor Expo: 107,7 ± 3,7 %; nach Expo: 112,4 ± 3,7 %; pw=0,039), FEV1 (vor Expo:111,2 ± 4,0 %; nach Expo: 114,6 ± 3,8 %; pw=0,042), und MEF50 (vor Expo: 82,0 ± 7,5 %; nach Expo: 88,1 ± 6,2 %; pw=0,044) stiegen signifikant an. Die Analyse des Differentialblutbildes zeigte das Bild einer Entzündungsreaktion nach Exposition. Es erhöhte sich signifikant der Anteil der neutrophilen Granulozyten an den Leukozyten (vor Expo: 52,7 ± 1,6 %; nach Expo: 62,9 ± 1,6 %; pw=0,003). Lymphozyten fielen von 35 ± 1,56 % auf 27,5 ± 1,3 % ab (pw=0,003), eosinophile Granulozyten fielen von 3,5 ± 0,4 % auf 7,3 ± 0,3 % (pw=0,013), Monozyten von 8,4 ± 0,5 % auf 7,3 ± 0,3 % (pw=0,012), CRP von 0,2 ± 0,04 mg/dl auf 0,15 ± 0,04 mg/dl (pw=0,011). Auch in der Kontrollgruppe kam es zu einer ähnlichen, ebenfalls signifikanten Veränderung, diese war jedoch geringer ausgeprägt. Für die Zytokine im Serum zeigte sich keine statistisch signifikante Veränderung über die Exposition. Jedoch ergab sich ein positiver Zusammenhang zwischen der IL-6 Konzentration im Serum und der Höhe der Endotoxinbelastung im Stall. Dieser Zusammenhang war allerdings nicht statistisch signifikant (p=0,056). Bei Betrachtung der Zelldifferenzierung der Nasallavage konnte ein geringer, aber signifikanter Abfall der Anteile der neutrophilen Granulozyten (vor Expo: 88 ± 5,7 %; nach Expo: 77 ± 8,7 %; pw=0,047) festgestellt werden. Außerdem ergab sich ein hochsignifikanter Zusammenhang zwischen der Höhe der Endotoxinkonzentration und der nasalen Makrophagen (psp=0,0001), sowie der nasalen Epithelzellen (psp=0,022). Im Hinblick auf unsere Anfangs gewählte Fragestellung deutet unser Ergebnis an, dass eine Exposition gegenüber organischem Staub, insbesondere Endotoxin, zu einer Neutrophilie im Serum führen kann und bei hohen inhalierten Endotoxinkonzentrationen auch vermehrt Makrophagen in der Nasenschleimhaut rekrutiert werden. Da sowohl die Lungenfunktionsparameter, als auch die systemischen (Serum) und lokalen (Nasallavage) Entzündungszeichen das Bild einer Entzündungsreaktion zeigen, kann davon ausgegangen werden, dass die Lungenfunktion, sowie die systemischen und lokalen Messmethoden über ausreichende Sensitivität verfügen, um in diesem Studiendesign Entzündungsreaktionen nachzuweisen. Die Nasallavage konnte im Feldversuch als eine objektive, kostengünstige, schnelle und gut tolerable Messmethode zur Darstellung von nasalen Entzündungsreaktionen etabliert werden.

Background: There is growing epidemiological evidence that short-term and long-term exposure to high levels of air pollution may increase cardiovascular morbidity and mortality. In addition, epidemiological studies have shown an association between air pollution exposure and respiratory health. To what extent the association between cardiovascular mortality and air pollution is driven by the impact of air pollution on respiratory health is unknown. The aim of this study was to investigate whether respiratory health at baseline contributes to the effects of long-term exposure to high levels of air pollution on cardiovascular mortality in a cohort of elderly women. Method: We analyzed data from 4750 women, aged 55 at the baseline investigation in the years 1985 - 1994. 2593 of these women had their lung function tested by spirometry. Respiratory diseases and symptoms were asked by questionnaire. Ambient air pollution exposure was assessed by the concentrations of NO2 and total suspended particles at fixed monitoring sites and by the distance of residency to a major road. A mortality follow-up of these women was conducted between 2001 and 2003. For the statistical analysis, Cox' regression was used. Results: Women with impaired lung function or pre-existing respiratory diseases had a higher risk of dying from cardiovascular causes. The impact of impaired lung function declined over time. The risk ratio (RR) of women with forced expiratory volume in one second (FEV1) of less than 80% predicted to die from cardiovascular causes was RR = 3.79 (95% CI: 1.64 - 8.74) at 5 years survival time and RR = 1.35 ( 95% CI: 0.66 - 2.77) at 12 years. The association between air pollution levels and cardiovascular death rate was strong and statistically significant. However, this association did only change marginally when including indicators of respiratory health into the regression analysis. Furthermore, no interaction between air pollution and respiratory health on cardiovascular mortality indicating a higher risk of those with impaired respiratory health could be detected. Conclusion: Respiratory health is a predictor for cardiovascular mortality. In women followed about 15 years after the baseline investigation at age 55 years long-term air pollution exposure and impaired respiratory health were independently associated with increased cardiovascular mortality.

BACKGROUND: Eradication of Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is possible if initiated early in the course of colonisation. To detect P aeruginosa as early as possible is therefore a major goal. This study was undertaken to validate a commercialised test for the detection of serum Pseudomonas antibodies in patients with CF. METHODS: A representative cross sectional analysis of serum antibodies against three Pseudomonas antigens (alkaline protease, elastase, and exotoxin A) was performed in 183 patients with CF of mean age 16.7 years and FEV1 85.9% predicted. The results were correlated with microbiological results from the previous 2 years to calculate sensitivity, specificity, positive and negative predictive values. The following 2 years were assessed to determine prognostic predictive values. RESULTS: A combination of all three tested antibodies yielded the best results with a sensitivity of 86%, specificity of 96%, and a positive predictive value of 97%. These values were higher if only patients in whom sputum cultures were available were considered (n = 76, sensitivity 95%, specificity 100%, positive predictive value 100%). The prognostic positive predictive value was high in intermittently infected patients (83%) but low in patients free of infection (33%), whereas the prognostic negative predictive value was high in patients free of infection (78%) and low in intermittently infected patients (58%). CONCLUSIONS: Regular determination of serum antibodies may be useful in CF patients with negative or intermittent but not with positive P aeruginosa status. A rise in antibody titres indicates probable infection and eradication treatment may be initiated even in the absence of microbiological detection of P aeruginosa.

Background: Eradication of Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is possible if initiated early in the course of colonisation. To detect P aeruginosa as early as possible is therefore a major goal. This study was undertaken to validate a commercialised test for the detection of serum Pseudomonas antibodies in patients with CF.Methods: A representative cross sectional analysis of serum antibodies against three Pseudomonas antigens (alkaline protease, elastase, and exotoxin A) was performed in 183 patients with CF of mean age 16.7 years and FEV1 85.9% predicted. The results were correlated with microbiological results from the previous 2 years to calculate sensitivity, specificity, positive and negative predictive values. The following 2 years were assessed to determine prognostic predictive values.Results: A combination of all three tested antibodies yielded the best results with a sensitivity of 86%, specificity of 96%, and a positive predictive value of 97%. These values were higher if only patients in whom sputum cultures were available were considered (n = 76, sensitivity 95%, specificity 100%, positive predictive value 100%). The prognostic positive predictive value was high in intermittently infected patients (83%) but low in patients free of infection (33%), whereas the prognostic negative predictive value was high in patients free of infection (78%) and low in intermittently infected patients (58%).Conclusions: Regular determination of serum antibodies may be useful in CF patients with negative or intermittent but not with positive P aeruginosa status. A rise in antibody titres indicates probable infection and eradication treatment may be initiated even in the absence of microbiological detection of P aeruginosa.

Background: Lung function and exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with short-term exposure to air pollution. However, the effect of long-term exposure to particulate matter from industry and traffic on COPD as defined by lung function has not been evaluated so far. Our study was designed to investigate the influence of long-term exposure to air pollution on respiratory symptoms and pulmonary function in 55-year-old women. We especially focused on COPD as defined by GOLD criteria and additionally compared the effects of air pollution on respiratory symptoms by questionnaire data and by lung function measurements. Methods: In consecutive cross sectional studies conducted between 1985-1994, we investigated 4757 women living in the Rhine-Ruhr Basin of Germany. NO2 and PM10 exposure was assessed by measurements done in an 8 km grid, and traffic exposure by distance from the residential address to the nearest major road using Geographic Information System data. Lung function was determined and COPD was defined by using the GOLD criteria. Chronic respiratory symptoms and possible confounders were defined by questionnaire data. Linear and logistic regressions, including random effects were used to account for confounding and clustering on city level. Results: The prevalence of COPD (GOLD stages 1-4) was 4.5%. COPD and pulmonary function were strongest affected by PM10 and traffic related exposure. A 7 mu g/m(3) increase in five year means of PM10 (interquartile range) was associated with a 5.1% (95% CI 2.5%-7.7%) decrease in FEV1, a 3.7% (95% CI 1.8%-5.5%) decrease in FVC and an odds ratio (OR) of 1.33 (95% CI 1.03-1.72) for COPD. Women living less than 100 m from a busy road also had a significantly decreased lung function and COPD was 1.79 times more likely (95% CI 1.06-3.02) than for those living farther away. Chronic symptoms as based on questionnaire information showed effects in the same direction, but less pronounced. Conclusion: Chronic exposure to PM10, NO2 and living near a major road might increase the risk of developing COPD and can have a detrimental effect on lung function.

Background: In a cross-sectional analysis of cystic fibrosis (CF) patients with mild lung disease, reduced surfactant activity was correlated to increased neutrophilic airway inflammation, but not to lung function. So far, longitudinal measurements of surfactant function in CF patients are lacking and it remains unclear how these alterations relate to the progression of airway inflammation as well as decline in pulmonary function over time. Methods: As part of the BEAT trial, a longitudinal study to assess the course of airway inflammation in CF, we studied lung function, surfactant function and endobronchial inflammation using bronchoalveolar lavage fluid from 20 CF patients with normal pulmonary function ( median FEV1 94% of predicted) at three times over a three year period. Results: There was a progressive loss of surfactant function, assessed as minimal surface tension. The decline in surfactant function was negatively correlated to an increase in neutrophilic inflammation and a decrease in lung function, assessed by FEV1, MEF75/25%VC, and MEF25%VC. The concentrations of the surfactant specific proteins A, C and D did not change, whereas SP-B increased during this time period. Conclusion: Our findings suggest a link between loss of surfactant function driven by progressive airway inflammation and loss of small airway function in CF patients with limited lung disease.

Background: Workers on dredgers and lighters on rivers are exposed to the inhalation of aerosols and dusts. Objective: The aim of this study was to investigate effects of river silt aerosol and dust exposure on the respiratory health of dredging employees. Methods: Six era mi nations were performed over a period of 2 years at 4-monthly intervals in 54 seamen with higher silt aerosol exposure and 36 controls of the same employer. Results: No significant differences could be observed between the groups at any time of the study but there was an unexpected significant decrease in the age-corrected expiratory vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and midexpiratory flow rate (MMEF25/75) over the six series in both groups. This may indicate a loss of effort of the participants in re-examinations since biological and technical influences were highly unlikely to be the cause of these findings. Conclusions: Ignoring this possible decline of effort in frequently repeated measurements may result in overestimating potential effects of occupational exposure. Copyright (C) 2000 S. Karger AG, Basel.

Featured Cases: Emerging Pathogens in Cystic Fibrosis

Presented at NACFC Anaheim 2011 this symposium presentation offers information on the current treatment options for patients with cystic fibrosis. Mike Boyle, MD, from Johns Hopkins University School of Medicine offers a 25-minute look at the basics of CF, then describes genotype and CF phenotype relationships. The presentation includes a review the influences of severity of lung disease and outcomes in CF, followed up by issues related to adherence.

Presented at NACFC Anaheim 2011 this symposium presentation offers information on the current treatment options for patients with cystic fibrosis. Mike Boyle, MD, from Johns Hopkins University School of Medicine offers a 25-minute look at the basics of CF, then describes genotype and CF phenotype relationships. The presentation includes a review the influences of severity of lung disease and outcomes in CF, followed up by issues related to adherence.

Presented at NACFC Anaheim 2011 this symposium presentation offers information on the current treatment options for patients with cystic fibrosis. Mike Boyle, MD, from Johns Hopkins University School of Medicine offers a 25-minute look at the basics of CF, then describes genotype and CF phenotype relationships. The presentation includes a review the influences of severity of lung disease and outcomes in CF, followed up by issues related to adherence.