#306 Bronchiectasis and NTM: You can’t get enough sputum!

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Pretty much we are responsible if you screw up. You should always do your own homework and let us know when we're wrong. Paul. It's been quite a journey, as you said. This is The Curbsiders. I'm Dr. Matthew Waddo. Paul is speechless. Tonight, we're going to be talking about... bronchiectasis, non-TB mycobacteria. We had a great guest, Dr. PJ McShane, who you will be hearing shortly. And with us, we have another fantastic co-host who Paul will tell you about.

Paul, before you say your part, I should tell the audience that this and most episodes are available for CME and mock credit. Actually, Paul, you know what? I don't like this. You're not saying anything. Say something, Paul. How are you feeling? I wish... For the audience at home, I don't know if there's a way that we can capture probably my favorite part of recording, and it's been, what, two hours now? It's just watching you...

try to work up and figure out how and what kind of energy you're going to bring as you open like there's like a two to five second moment where I just kind of see you kind of work on how you're going to present yourself and it is my favorite thing about the entire recording process and I just I wish our audience could see it Well, audience, maybe someday. Next live show, Paul. It's got to be video for the audience and they can see it happen in real time.

But Paul, I hope you're doing well. And this is a topic that I was excited to do because I didn't know much about either bronchiectasis or non-TB mycobacterium. And now I feel like I really have a pretty good handle on it.

Yeah, I at least feel that I can better prep my patient and the pulmonologist I may be referring them to and just have them teed up a little bit more for success as opposed to knee-jerk referring just because I don't know what to do with a radiographic finding. So I feel like this really...

brought my understanding of the disease process and sort of what management might look like for our patients. I found this extraordinarily helpful. And Paul, before we get to your part... A reminder for the audience that this and most of our episodes are available for free CME credit through VCU at curbsiders.vcuhealth.org.

I wanted to let the audience know that our guest for this episode did mention that she's been a speaker and an advisory board member for InsMed. They do make some products related to non-TB mycobacteria. but we didn't discuss them with her on the show. And we'll have some other audio patched in at that point. So with that, Paul, can you tell the audience, what is it that we do on the curbsiders? Sure. And this is the part they've really been waiting for.

We are the internal medicine podcast. We use expert interviews to bring you clinical pearls and practice changing knowledge. And we have a fantastic guest tonight that we'll talk more about. But before we get to discussing our guest.

As we build things up even more to a fever pitch, you did allude that we have another co-host with us. We had the great Dr. Cyrus Askin with us who helped produce this episode and then also was one of the co-hosts with us. So Cyrus, let me start by asking how you're doing tonight. Oh, I'm great. It's good to be back. It's like home cooking. Good home cooking. I hope you'll specify. It is what it is.

Why don't you tell us a little bit about the episode and then we'll let you transition seamlessly into telling us about our guest as well. uh sure absolutely so very exciting uh episode as far as i'm concerned dr mcshay you know really talked about what bronchiectasis is gave us kind of a little bit of a framework in terms of how we would work it up

We then talked about some of the treatment strategies to include airway clearance and antibiotics and all aspects of therapy that can be kind of confusing. She did a great job of, I think, composing it.

And then finally, we spent the last portion of our discussion talking about non-tuberculoid mycobacterium, or NTM, which is another sort of mystifying aspect of all of this. And I think she did a great job of giving us some of the basics and equipping us with the knowledge we need to go forward and work with our colleagues. in internal medicine and pulmonary and beyond.

So I'll tell you a little bit about Dr. PJ McShane. She is a world-renowned bronchiectasis expert. She's a pulmonary critical care physician. She has a clinical and academic focus in bronchiectasis and non-tuberculous. mycobacterial pulmonary infections. She's done fellowship training at University of Chicago. She did four years active duty in the US Air Force as an internal medicine physician.

And despite being a loyal Chicagoan and a cold weather enthusiast, she is currently working at the University of Texas Health Sciences Center at Tyler, Texas, which is a nationally renowned mycobacterial lab and clinical reference center. And you're going to hear a lot more cool stuff about her coming up right now. PJ, we've been through a lot together already, but the audience...

The audience doesn't know any of this. Can you tell them a little bit about yourself and maybe a hobby or interest outside of medicine? I was interested in how hard it was to answer this question, even in like prep. Because it's, you know, it's hard to capsulize yourself in a couple of words. I don't know. I really like being a physician. I'm pretty enthusiastic about it.

try to have fun throughout my day and probably am the person who sticks their foot in their mouth most often at any institution where I've been. And then when I'm not working, I'm trying to...

have fun with my dogs and go hiking. That sounds wonderful. And you're in Texas, so please watch out for rattlesnakes. We can't afford to lose you, okay? Hey. Some of these mosquitoes are as big as rattlesnakes. That sounds great. Basically, one of my new hobbies... while being in Texas is scratching all of my mosquito bites. I have about seven to eight going at any one time. Well, you know. The price of admission for hiking probably.

Probably. Those things get in your house too, you know, those snakes that have legs. I think you call them skints or skis or... Something like that. Texas is a terrifying place to live. A lot of wildlife. They're going to get in your business. And Godspeed. That's all I can say. Thank you for that. So good. This fuels my absolute absence of desire to be outside in general. It's certainly not outside in Texas, but...

So that being the case, I am now mostly caught up with books. So I will cheerfully take any book recommendation. It does not have to be medical. Just something to distract myself from myself would be great. Yeah, I love this recommendation because... I have one that I think is really good for physicians and it's called The Millionaire Next Door. Yeah.

kind of about, I mean, this isn't like a good, you know, page turner fiction novel, but, and, and probably for you guys who have been in the military, you learned about good savings and things like that, which is where I kind of started learning about it. Basically, it's a book that, you know, talks about how prodigious accumulators of wealth get there.

And it's all about how they live kind of modest lifestyles and do a lot of savings. And that for the most part, a lot of physicians are the type of people because of their delayed. income, they're sort of eager to buy really nice blingy things. And then it turns out that physicians are the worst as far as savers. So I liked that book a lot. Yeah, I've heard of that book. I haven't read it. I feel like there's a handful of really good personal finance books that...

If people just read one of them and just follow the basic principles, it really sets you up. And the earlier you read them, the better. And that one sounds great. Maybe even rereading, like I read it maybe 10 years ago and then I read it again last month and I was really surprised at how much.

Like I thought, well, this is good that I hear this again, like each decade in your life because you have different priorities and different, you know, goals, especially the older you get, the closer retirement comes. So it's really important. I'll give a quick pick here. It's very related. There's a podcast. I think I sent it to Paul. I'm not sure if he's checked it out yet, but it's called Money Meets Medicine. And it's an anesthesiologist and a financial advisor who's married to a...

physician who's a pediatrician. And they just talk about like, here's a checklist of like what you should do to get yourself set up and you should have this type of insurance and you should do this type of saving and Uh, it's, it's, it's pretty good if you're like into this kind of thing, or you're thinking about this kind of thing, it's a good, it would be a good supplement to that, that book. Um, that sounds great.

What's the title again? It's called Money Meets Medicine. And for the audience, we'll, of course, put that in the show notes. Paul, what else should we ask about before we get on to the topic here? Let's skip failures. I like, what best advice have you received as a learner, I think is a good one. So as you, before you became a preeminent expert in the field, what advice was given to you early on that you took to heart and sort of helped you develop and grow?

I thought you were going to ask about my failures. I mean, I can. I'm happy to ask about failures. That one just always seems to trust people out a lot. If you had one ready to go, then... Yeah, if you have one locked and loaded, by all means, I would love to hear about your favorite failure. Well, I was going to say, ironically, is the times that I have not adequately prepared for something.

are the times that it really comes back to bite me, whether it's for a test or the times that I get, on the other hand, the times that I get really stressed out and I... you know, over-prepare for something that goes great. So it, but I say ironically, because we had trouble with the mic today and now I feel like maybe I should have put more time into the mic.

I think that was an equipment fail. I don't think that was your failure at all. Cause, cause we couldn't, usually we can troubleshoot things like that. And, uh, I think, I think that was an equipment issue. So anyway. But what about advice? Like, did you receive any favorite advice as you were going along? It could be when you were a learner or it could be now that you've been on and going on in your career.

Yeah, I mean, it was that you really cannot listen to the outside influences about what career you pick. Like, what... superficial things matter or come along with that career choice. Because when it comes down to it at nine o'clock at night, If you have to go put a central line in someone when you could be home with your family or your dog or whatever.

you really had better at least a little bit enjoy that. I'm not saying that we all love to be at the hospital at 9 or 10 o'clock at night putting a central line in, but there has to be a little bit of joy there still. even though I didn't necessarily choose a career that was particularly fancy or glamorous to someone else.

really did interest me. That has kind of come back in spades because it is every single day I'm enjoying what I do and thinking about it and the patients become more interesting then. So, you know, it wasn't the shortest route to get there. biggest moneymaker that I could have picked. It wasn't, you know, the most glamorous. I have this memory of talking to a colleague of mine during internal medicine residency. And I said, I think I'm going to go with pulmonary. And he went.

Oh, God, that's sputum. And I had a little moment of like, what did I do? But truly, sputum actually doesn't bother me.

And so it's turned out okay because I kind of thought I liked it. Paul, is this the best segue we've ever had on the show? So time for Picks of the Week. You just can't get enough sputum and bronchiectasis. Paul, did you want to give a pick of the week related to sputum before we get onto the case, which is going to involve lots of sputum? I could not. I mean, actually, I probably could come up with a sputum-centric pick of the week, but I will not, I don't think. Why don't we...

Why don't we move on if there's nothing else? Okay. All right. Hey, curbsiders. If you're like me, you like to think of yourself as somewhat of an athlete. Although, okay. Maybe athlete is a stretch, but I like to move my body. I like to work out. I go to the gym. I do some running. And that's why I'm excited to tell you about our sponsor today, 10,000.

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That is a great design and great fit. Right now, 10,000 is offering our listeners 15% off their purchase. Go to 10,000.cc and enter the code CURB. to receive 15% off your purchase. That is 10,000.cc and enter the code CURB. So Cyrus, how about you give us a case from CashLack that we can talk through with PJ? My pleasure. So we do have a... A case this evening to discuss. So Nina T. McKenzie, her family calls her Mac.

which is extremely humorous, so that was well done there, Clea. Very well done. Is a 62-year-old woman who just transferred to your primary care clinic at Cashlack Southwest. Mac is pretty healthy, except for this nagging cough she's had for years. She's been told she has COPD, but that bothers her because she's only smoked for a few years in her 20s. She does have mild obstruction on her PFTs. She's mildly short of breath.

but still able to swim several times a week. After swimming, she does note that she often coughs up white and occasionally yellow phlegm. So you decide to start from scratch and you order a chest x-ray. It isn't resoundingly abnormal, but there is some right lower lung field.

atelectasis versus aspiration. So you decide to go for it and you order a chest CT. After all, she's had this cough for years. On the chest CT, the report says right middle lobe and lingular bronchiectasis with mucus impaction. and diffuse central lobular nodules. You are starting to think COPD isn't the issue after all, but need an urgent Dr. McShane consult. So, PJ, before we get too deep into the woods here...

What is bronchiectasis in terms of its definition, and how do you go about diagnosing bronchiectasis? So, bronchiectasis is rooted in that bronchi is the airway, of course, and ectasis is the word for wide. Gosh, is that Greek or Latin? I'm sorry. I took Spanish in college. Same. So I think we get a pass on that one. The wide airway. And really, it is a radiographic definition in combination with symptoms.

a lot of us bronchiectasis folks who get together and sort of this may just be a syndrome rather than a disease but whether you're going to argue that a disease or syndrome it is a constellation of the patient's symptoms with these wide airways that are noted on radiographic imaging. Really, a CT scan is the diagnostic imaging of choice. And the airway should be on cross-section greater than one times the accompanying vessel.

Now, there's a little bit of wiggle room there based on the patient's age because just when you get long in the tooth, so to speak, you get a little wide in the airway. So older people tend to have a little bit wider airway than their accompanying vessel. And I'm talking about when you see that airway on axial cross-section. And then when a patient has... COPD emphysema, the airways tend to be a little wider also. So that ratio should be like more like 1.5 times.

the size of the vessel on cross-section if you're going to call bronchiectasis in COPD. COPD, when I say that word, I'm talking about emphysema. So really, it's a width of the airway. And then it's also a similar, a different way of saying the same thing, but a lack of tapering. The airway does not taper as it goes out to the periphery. So you can see these larger airways out in the periphery on an axial cut of the CT scan. And then in combination, they tend to produce purulent sputum.

Which is your favorite, which is perfect. I can see how you chose your career field. I wanted to ask when you explain it to a patient, like we understand that as physicians, but do you have like a way that you explain this to a patient? Like what's your spiel to them? I do. And so now I have three people here who can tell me if this sounds terrible, because this is how I've started to describe it. So first of all, I just want to go off on a tangent for those of us who...

spend our days thinking about sputum. Mucus is this wonderfully healthy, slimy, see-through stuff that actually has antimicrobial properties. You know, we love mucus. We need mucus. Any woman with Sjogren's will tell you mucus is great, right? But when mucus gets combined with bacteria, it becomes sputum. So I'm very specific about the difference between mucus and sputum. Because sputum then has these very heavy properties, influx of proteins and enzymes from the broken up neutrophil.

bogs down the cilia. And so the cilia can't move and sweep the mucus forward. So that's sort of a thing I like to discuss because a lot of people say, you know, my mucus is this, but it's really their speech. And they don't want to drink milk because they are concerned that that increases mucus. Well, we don't worry about mucus. We just don't like sputum. So the way I describe it to my patients and.

You know, I explain that these airways are, even though they're wide, which seems like it would be a good thing, they don't work as well when they're wide and they don't move the sputum. or the mucus out and that mucus can pool there and sit in their airways and become infected. And sometimes when they want to know why they have to do airway clearance every day, I'll explain that.

And I'll preface it with, although it's not always a perfect analogy, if a building were a little bit broken down and not in perfect repair. you might get bad guys coming to live in that building and take up shop in that older building. And doing airway clearance and keeping the airways clear is sort of like sending the police through a building that's kind of broken down.

So sometimes they seem like they get that. And then other times I feel bad because I'm comparing their airways to a broken down building squatters. All right. Well, I don't know. Did it sound bad? No, that's perfect.

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ACP 20. I like this case a lot, though, because I feel like this is fairly typical where you have symptoms that don't quite align. So you check the CT scan. And then at least for me, because I'm not smart. You get this reading of bronchiectasis and you're like, oh, bronchiectasis. That sounds bad. So I guess this is all, I guess, preface what.

So what I would like to do is be smarter. And so I'm wondering what symptoms should prompt me to think about bronchiectasis rather than sort of discovering it on CT scan. Is there any historical features or anything?

that the way a patient presents that might make you think this is an issue even before you start getting the imaging? How can we have a higher suspicion for it? Yeah. So that case was spot on. It described my, you know, my two o'clock and my three o'clock and my 10 o'clock last Wednesday. I mean, it was. Perfect. I would say that if you prescribe an antibiotic for a respiratory infection more than two times in a six-month period, I would go digging.

And then anyone who has airflow obstruction who doesn't have a history of smoking needs to get a CT scan. I mean, if you're pretty sure it's not asthma, you know, based on your clinical history. Okay. So in her, she's got this mild shortness of breath and the sputum, and we found mild obstruction on the PFTs. It doesn't quite make sense because it's been like 40 plus years and she never really smoked that heavily anyway.

It's so common for me to see a patient who's never smoked and has been diagnosed with COPD. And I'm sure it's just because, you know. I have this luxury of sitting there for 40 minutes with a new patient or something, you know, like I have all this time as a more academic focused physician to sit there and talk with a patient. But I mean, the way.

internists have to see people at such a fast rate, I think probably it's really hard to get all the history down. And so I think that's probably some of what happens. And then the other thing is, I'm sure you notice when you've, you know, just living your life, to cough up a glob of sputum is just not normal. Anyone who coughs up sputum like that deserves, I think.

a workout. It sounds like this is a diagnosis that is sometimes missed or sometimes delayed because, because of like what you're saying, like we. We sort of take for granted COPD. Oh, probably this person smoked enough that that's what they have. And that's, that's common for us. But like, what's the.

burden of this, I guess, in the US or if it's different internationally. We do have some international listeners. Can you talk a little bit about that? This is not a rare diagnosis that we're talking about. This is something that people should be on the lookout for.

It's true. I mean, it's much more rare than, of course, diabetes or heart disease, but it's much more common than we previously thought. It is much more common in the elderly. So the numbers... at age 70 and above can be as high as six, you know, 600 per hundred thousand people in. much younger ages, it's much, much less common. Maybe, you know, 50, like for the age of 20 to 30, it might be 50 per 100,000. But on the other hand,

That 20-year-old patient has so long to go with that bronchiectasis that it's still very important to take them seriously, even though they're such a much more rare condition. In the UK... Their numbers are much, much higher. They're about five all comers. They're about 500 per 100,000 persons. And if you took all ages in the United States, it would be more like 120 per 100,000 persons. But we're getting our data in different ways. So in the UK, they get that data from primary care.

databases and just like, I think, coding data from their primary care, whether that patient has received care for their bronchiectasis or not. In the United States, we get that data from the United States. bronchiectasis and NTM research registry. And that is a registry, a centralized registry of only 17 centers from the United States. So it's really a much more specialized referral.

database. So maybe that's why the numbers are smaller. Europe as a whole, I mean, it's harder to say those numbers, but like, for example, Germany. reported some numbers that were somewhere in between UK and United States. So the common theme that United States has with the other areas of the world is that in all cases or in all locations,

the prevalence of bronchiectasis is increasing steadily per year. And maybe that's because we're getting more CT scans, getting better at recognizing it. I don't know.

all areas of the world, it's increasing steadily. I found that fascinating in the pre-reading because that was not the expectation, right? We thought this was sort of a tail-end pathway of infectious disease once we had great... antimicrobial therapy. You're like, we did it, we fixed bronchiectasis, but instead the prevalence is going up, which I just, I find, I'm sure we'll get into more why the reasons why that might be. I did want to ask for our patient here for Mac.

Have we made the diagnosis? So we have radiographic findings consistent with bronchiectasis. We have some with cough and sputum. Are we done? Is it time for management or is there more work to do in terms of workup and evaluation for this particular patient? Yeah, there is more to do. And that's kind of what makes it fun. So, you know, for anyone who's getting frequent infections throughout their last, you know, years, it's important to look at immune globulin.

as well as a strep pneumo 23 serotypes. That gets a little cumbersome because if they're low, and generally the strep pneumo 23 serotypes look a little low in people who may not have been vaccinated. Then you need to immunize them and then look at the strep pneumo 23 serotypes four weeks later. The Pandora's box that you open up by immune globulin workup is quite large.

If you think of any disease with a big etiology, I mean, I think immune deficiencies win that one. If you've had any recent experience with reading their most recent. guidelines, and I regret that I don't have the exact name of their recent, one of their recent guidelines is there's like hundreds and hundreds of immune deficiencies. And so it's...

worthwhile if something's not right in that initial workup to send them to an immunologist because that really gets into the weeds. But that's important because that's one of the things that you can fix in some of these people if you put them on immune globulin replacement. Just to clarify, that was an IgG, like a total IgG, and they look at the different subtypes of IgG. Yes. And then the other one was a – I know there's the –

pneumococcal vaccine with the 23, like the PPSV 23 vaccine. So you're essentially just checking for the antibodies that someone would have if they had gotten that vaccine. That's right. So, and then to be clear, I do the total G, the A and M. In rare cases, there are A deficiencies and M deficiencies, which have been associated with bronchiectasis. And then the G...

could be kind of normal-ish. If it is normal-ish, that doesn't mean that they're going to mount a normal response when you get the strep pneumo 23 serotypes. So that's...

where, you know, a little bit here, I'm speaking outside my area of expertise, other than knowing that it needs to be worked up and addressed, but I don't claim to be an immunologist. And then you... immunize them with the strep 23 after you get their first panel of the strep pneumo 23 serotypes, and they should increase by a set amount that's in the guidelines for immune.

competency. And actually, that is a paper that this is stated very clearly that I should be able to get to you so that you can refer your audience to. you know, the right resource. Yeah, because this is a totally new practice for me. I'm excited. I have not heard of that practice before. Paul? No, I've not been – this is not something I've been ordering. I just – I just published a chapter in the seminars of critical care medicine that was a whole chapter on this.

It should just roll right off my tongue. But I did sort of list a consolidated workup in there more for the pulmonologist rather than the immunologist. But all I can say is this immunology deficiency thing has grown exponentially with their ability to work up these cases genetically. It's something that none of us should really be playing in without, you know, a curbside. And maybe you're, hopefully you'll have an episode with an immunologist because it's, it's really taken off.

Okay. So I think the point here is that someone with bronchiectasis, infection is one of the common cause, especially recurrent infections, right? So we're checking to make sure there's no immune deficiency. And then what else are we, what else do you think in that? Like if you're just like a pulmonologist or a primary care who's not as specialized, but you want to get the ball rolling on this testing.

Absolutely. Okay. So that's exactly great. So you want to get the ball rolling. It's the immune globulins and the strep pneumo 23 serotypes. So that whole thing. would be even more the signal that should inspire you to do that is that your patient's getting frequent infections. And a lot of times these people have sinus stuff going on too.

So that would even more push me toward the immune globulin workup. In addition, it's really important to ask these people about any other... systemic symptoms that they're having that may go along with diseases that sort of associate with bronchiectasis. And those are the connective tissue diseases. So rheumatoid arthritis is well described to be associated with bronchiectasis. Sjogren's well described as associated with bronchiectasis.

So if they have any of those features, I don't hesitate to order the serologies that go along with each one of those diseases, you know, SSA, SSB, if it's a Sjogren's type sounding patient. the rheumatoid factor, if it's, you know, if they've got joint issues, if they're very asthma-like in their history.

And you think that bronchiectasis may not be the whole pulmonary story, that there is a association with asthma symptoms, then I would not hesitate to get an immune globulin E. And then if they have any other family history of lung disease, and even if they don't, an alpha-1 antitrypsin is always probably a good idea to get going because...

You know, guidelines are always changing about whether these people should be replaced if they're borderline in their alpha-1 antitrypsin level. So at least if you have that data, you can... push it toward the pulmonologist and say, hey, what do you think? Should this patient be replaced with alpha-1 antitrypsin? And how are we from the imaging standpoint? Because probably for me, I would not have fired this patient off for a high-res CT initially. It would have been just sort of a standard CT.

Again, not being smart, I didn't really have a good idea what was going on. So do we have to then reset them back for a high res or is this sufficient now that we already know there's bronchiectasis there? Is there anything else from an imaging standpoint that we need to do to get the patient teed up for? for your expertise? I think the high resolution CT is always valuable. It, that those thicker cuts, those five millimeter cuts can really miss some important details, especially those.

tree in bud opacities that kind of go along with bronchiectasis when NTM is present, those can get kind of blurred or missed.

in a thicker cut. So the high resolution CT, I think is always money well spent. And there are a few nuances with the CT scan. The right middle lobe and the lingula is a very common place for bronchiectasis to appear. Predominantly, upper lobe bronchiectasis tends to be present in cystic fibrosis. And so it's not a bad idea to get their, their fertility history. You probably know that adult CF is often diagnosed in infertility clinics.

pulmonologist, we must be missing some, you know, and I'm sure, you know, so many astute internists could, would pick up on this also if they notice this patient has had difficulty conceiving children and then they... Lo and behold, they have upper lobe bronchiectasis. And on the other hand, lower lobe bronchiectasis is more common in primary ciliary dyskinesia. And so primary ciliary dyskinesia is a...

type of bronchiectasis that's caused by a genetic abnormality that causes the cilia not to work. And it happens from birth. And most of the time, these patients have really dramatic symptoms at birth. But if they have a less intense... less intense penetration of the disease, they may make it to adulthood and not have yet received a diagnosis. So people who had lots of respiratory infections as a kid.

sinus infections, ear infections, and they have bronchiectasis, and you notice it's mostly in the lower lobes, those patients should probably be, you know, primary ciliary dyskinesia should be kind of ringing around in your head. In our patient here, I mean, her initials are NTM, but she's 62. We don't get that history of as a child that she was having lots of infections. So she's not necessarily someone we have to do genetic testing for PC.

the primary ciliary dyskinesia, and the chloride sweat test, we don't think for her that would be maybe not high yield? Probably not. high yield because she really didn't have other symptoms that went along with suggesting those two diseases were present. But academically, once she gets to maybe... an academic center where some of these things kind of make a difference in terms of registries and writing papers. Many of these women have a partially abnormal CFTR. Got it.

And that's kind of cool. So a lot of these NTM women are kind of partially down the path of CF. Oh, interesting. Well, what about, we mentioned non-TB mycobacteria a little bit here. And we, in the initial testing so far, we've talked about, you know, trying to recognize. Immune deficiencies, make sure we attack the sinuses and try to treat that. Looking for connective tissue disease, asthma symptoms, thinking about a family history with alpha-1 antitrypsin.

And then of course, we're getting our favorite, Paul, high res CT to make sure we don't miss any of the smaller stuff like tree and bud things. And then fertility history is going to definitely make us think CF and the recurrent childhood stuff. primary ciliary. What about just good old fashioned sputum culture? Are we inducing sputum in all these people and do they all need like three AFB smears and cultures? So great question.

The more sputum, the better. I mean, diagnostically, you mean, for the patient. I'm thinking about how we can incorporate that into the title of this episode, Paul. Well, it'll be gross. I feel like t-shirts, I think there's going to be swag. You just, you can't get enough sputum. That's my motto. Sputum junkie t-shirts, Paul, maybe.

So I just, I'm not, so yes, the, the idea should be that really the more sputum, the better, but I just think that that's a lot of burden to put on the internist because frankly. You know, many of the pulmonologists who send me patients at Tyler, I mean, they don't get as many sputums as I would hope. It's a lot because a lot of these patients, yes, they can get some sputum out, but to expect an internist to do sputum induction, I mean, my goodness, that's just a lot to ask. If you are...

have the luxury of a place where they can go to have their sputum induced, or if you're practicing in such a place like that, then yeah, right on, you know, send them down and get that done. But the reason why... it's really important to get the sputum is for a couple of reasons is one is most of them are going to grow these pathogenic gram negative

infections. They kind of start out with H. influenzae, and as they get worse, they get like Pseudomonas, Denetrophomonas, Acinetobacter, all these scary bugs. And the literature is such that most of these patients who have pseudomonas and stenotrophomonas have worse disease. They have more exacerbations. And so...

that's when you should probably pull the trigger on sending them to a pulmonologist and trying to get them on some maintenance inhaled antibiotic therapy. However, and this is a huge however, is that in the field of pulmonary medicine, bronchiectasis medicine, we've studied inhaled tobermycin, Toby. We've studied... As Trianam, we've studied two different types of ciprofloxacin. We've studied colistin and gentamicin. And none of these...

except for the case of gentamicin, which was studied at a single center in the UK. None of these have universally reached the endpoint of reducing exacerbations. That gets you all of nowhere, really, because none of these inhaled antibiotics are FDA approved because the trials haven't met their outcomes.

There are so many reasons why we think they haven't reached their outcomes of reducing exacerbations. And most of these reasons are because it's such a heterogeneous disease. It's so hard to study these patients in multi-centered trials. But so the bottom line on inhaled antibiotic is they probably help some people. They help people who have really high burden of organisms. They're not always the easiest to tolerate. They're very difficult to get from insurance.

Many times they have to be ordered in the IV form and then compounded by the patient at home. So there's all sorts of nuances to prescribing them for the potential benefit. And that's certainly something that should be tried in the patient, but it's definitely worth getting the pulmonologist involved for that. So that's why one reason, it's just a long-winded answer to why should you get sputum. That's one reason. And then, of course, the other reason is to find acid-fast bacilli or...

non-tuberculous mycobacteria. So that's super important. I'm a little worried I'm talking too long. Is this one of those times? No, no, you're doing great. You're doing great. Okay. So. It's really, if you do get sputum and you're sitting there with a sputum cup of, you know, five mls of a really good loogie, you definitely...

have to send that for not just the regular bacteria, but the acid fast bacilli. And the reason why it's so important to know that your patient may or may not have MAC or... M. abscessus or M. cansaceae is that because the inhaled antibiotics for the other bugs have not been a panacea, we have... Three studies that show that just azithromycin helps these people and works to reduce exacerbations. It's a little bit of a mystery. Why? Because it's not.

azithromycin is not treating their stenotrophomonas or their pseudomonas, but nevertheless, the studies show that that macrolide helps reduce exacerbations. So it would be very... potentially harmful to the patient to start a macrolide monotherapy if you don't know if they're growing mac. Because as you know, the macrolide is one of the three very important drugs for non-tuberculous mycobacteria, specifically MAC. And I can't even think of two drugs.

that would replace or substitute for MAC for, I'm sorry, I can't think of even two drugs that would be good substitute for azithromycin or clarithromycin. if the Mac becomes resistant to it. I'm just going to jump in real quick because that's such a huge point, I think, because as you know, I did primary care for a little while, albeit a year, but still, you know.

We see plenty of patients with upper respiratory infections. The ED sees plenty of patients with these, and it's very easy to knee-jerk that Z-Pak. And if you do that several times and you're treating the wrong thing and you're treating the wrong patient, you can really be doing them a disservice. So I'm really glad you mentioned that.

The thing is, is it is an anti-inflammatory. So it's remarkable how much better your patient feels when they go on the azithromycin. It really helps. And it's partially why I think they feel... Ultimately, they feel better when you put them on three drugs. It's the azithromycin. But boy, to watch the progression of a patient who has macrolide. resistant mycobacterium avium infection. It's a, it's a really, it's a horror show. You just don't have any drugs.

to treat them if they're resistant. Well, let's back, let's, let's not make her quite that sick yet. And let's take, let's take Nina. back. So Nina is our patient we've been talking about, member audience. She's 62. She was the one that had this like, curiously, she didn't have a big history of smoking, but she had some airway obstruction, the sputum. We've been working her up.

And we're starting to talk to her about how we're going to treat her going forward. We've identified she has bronchiectasis. How do you initially talk to patients? Let's say she's on the spectrum where she's not yet growing resistant organisms, like her culture is normal flora. And she hasn't had any exacerbations yet. So like, what's the initial like starter therapy that maybe Paul or myself might feel comfortable starting? Because certainly once they get to like...

macrolide resistant, you know, they're definitely coming your way for sure. So regardless of how extensive their bronchiectasis is, I always start airway clearance. So airway clearance.

is the collection of a few different modalities. It's typically a nebulized drug. And when I say drug, we're talking drug loosely. So it's a nebulized... 7% sodium chloride, breathing maneuvers that are called active cycle of breathing, and then typically some sort of positive expiratory pressure device with oscillation. One of those is the one that looks like the sea cucumber. It's like the green one that you...

Yeah, and then there's one that looks like a white pipe. Can I say the names? I think so, if we're using multiple names. I don't know what the generic name is, to be honest. I only know it by the trade. I'm sure they don't exist, actually. I think that's fine. There's several available and I'll be equal. There's a aerobica or some people call it aerobica. It's easy to clean. Then there's the acapella.

And there's like six different kinds of acapellas. Some are blue, some are green. Some are easy to take apart to clean, some are not. Then there's the flutter valve, which is my personal favorite. It looks like a little white pipe. And then there's like something that almost looks like a banana that has almost like a really great whoopee cushion noise that gets points just because it sounds like a whoopee cushion.

So those three things. Now, there's a paper out there that talks about mucomist, which I... Is that N-acetylcysteine? Yeah, I was just going to say, which is N-acetylcysteine. And I was trying to figure out whether I said it wrong because I said the commercial name first. But that has... been noted in the literature to be abrasive and potentially harmful to the mucus layer of the airways. So I don't typically use that. It also has a foul smell.

And then, of course, there's that DNase that the cystic fibrosis patient population can use, but the DNase or pulmazyme. can't be used by non-CF bronchiectasis. It has not been approved for them. And actually, it was shown to cause harm in the study. So really, all you have is these hypertonic salines.

The other thing, I guess, I don't know if you do this in your practice, but I've always prescribed them with either albuterol or levalbuterol. Excellent point. So I was going to say, you know, a lot of these patients, because they don't have a history of smoking. And if you think after talking to them, they don't have reactive airways, you don't need the albuterol.

I typically give it to them in the clinic to make sure they tolerate it okay. And I go in and I listen to their lungs afterwards. And I would say 95% of my patients tolerate the hypertonic saline, no problem. But there is that. small percentage of patients who get a little tight from it. And in those people, you need to use the albuterol. And then there's some smaller percentage that really, it goes really wrong after they get that 7%, like they go into a full-on.

bronchospasm, very small amount, but it's happened to me twice. So I always make sure they do the first time in the clinic. If they don't tolerate the 7% sodium chloride, then you can use 3%. Or you can even, believe it or not, sometimes I go to 0.9% because there was a study that was done in the UK that compared 0.9% nebulizing to 6%. sodium chloride. And the 0.9 was just like their placebo group. And both cohorts after a year had improved quality of life scores.

And they also improved their bacterial load, which is really cool. And they had lower inflammatory markers. So that gives me sort of the juice to prescribe people 0.9%. If they don't tolerate the 7%. So normal saline. And we think this works by at least to some extent by bringing extra water into the mucus, kind of hydrating it or in the sputum, thinning it out. So it's more like mucus consistency. They cough it up.

can get it out easier to cough up. Exactly. Right. And also that saltiness provides like a hostile environment for the, um, And that's where I get into my analogy of the cops going through the broken down building. And can I ask, and this may sound like a dumb or basic question, but I feel like that's kind of my role here is what are.

What are we hoping to accomplish with this? Like, I guess, are we modifying disease progression? Are we preventing exacerbations? Are we improving day-to-day quality of life, all of the above, some of the above? So what is it that we're getting at with sort of just this, the airway clearance versus some of the other treatments that we're doing?

Yeah, good question, because why the heck are we doing it? I mean, I wish we had, you know, 20-year longitudinal studies to show that it reduces progression of airways, but I don't think we have that. But we definitely have improved quality of life, reduced cough. So anecdotally, I for sure can say it reduces cough, but there is a study that was, I want to say.

Ashwin Basavaraj from New York published something on NTM patients who were not treated with antibiotics, but were just treated with airway clearance and it improved their cough. So that's more than just, you know, PJ's noticing her patients cough less, but, you know, like it's actually in the literature. One thing I really want to emphasize and. I don't want to claim that our bronchiectasis patients are the same as CF. Certainly, they're not.

But when hypertonic saline airway clearance was introduced into the CF population, it literally changed their survival curves, dramatically reduced mortality. We think we have a lot of faith, these bronchiectasis folks, we have a lot of faith in this airway clearance.

I wanted to recap just the basic therapies, and I do want to go on and talk about an exacerbation. So the recap, what we talked about so far, bronchodilators, not necessarily needed for everyone, but if we think they have a component... of like reactive airways, especially after they get the saline challenge, then they may need that. Hypertonic saline or maybe even just normal saline, but that seems like a big part of this.

some sort of positive end expiratory pressure device, like a flutter valve or acapella valve to help, help with clearance. And with the airway clearance, you mentioned there's some breathing techniques and we can link to some of this stuff. that uh leah and cyrus had sent out like there's some um from ats there's some patient handouts that were really good talk about huff breathing and uh positioning and yes

Nice recap. I want to make two extra points, and that's that the hypertonic saline is available on GoodRx.com. As long as the patient scrolls down and picks the four mLs of the 7% sodium chloride, and they can usually get 100 vials for like $18 or $20. And then the... Active cycle of breathing is, I tell my patients, this is a sport. You don't get good at this the first day I teach this to you. You have to practice it.

So I direct them to the bronchiectasis toolbox. It's an Australian website. So you get to hear the cool accent. Oh, I love it. And it's a great, great, great website because they show videos of people doing the active cycle of breathing. And then the last thing I tell them is, how long do I have to do airway clearance? You have to do airway clearance until you die. That's so depressing. Because they're never going to get rid of their bronchiectasis. It's an irreversible condition.

They get going at me. When can I stop? Never. Yeah. We did an episode on cystic fibrosis and... She, our expert was telling us that one of her patients wears that battery powered vest and he like drives to work and he's able to, one of the reasons he's still able to work is because that saves him time, you know, because the clearance is such a burdensome thing that patient.

have to do. It absolutely is. It's the biggest complaint I hear. And I frequently tell people to do things while they drive. And I'm thinking, God, I wonder if the sheriff is going to... come show up at my clinic one day and give me the ticket. They were trying to drink their coffee in their vest and they spilled and crashed their car.

You know, but one question I had about this, the airway clearance stuff, because she's 62. She's starting to have sputum. I feel like I do see some patients where they have bronchiectasis noted. but they don't seem to have this syndrome where it's like to the point where I feel like they would need to do it. Is that pretty common where there's like a period where they're just kind of in this in-between land where you can see it, but you don't really have this?

need to do all this stuff we were just talking about? Yes. I mean, I think there is so much unknown about this because we don't see people when the bronchiectasis happened. I mean, I see these people who present to me with raging. bronchiectasis. And I have to know, based on looking at the CT scan, it's been there for a decade, but they haven't always been symptomatic that long. So I think there's...

So much we have to learn about the pathophysiology of what ultimately starts the avalanche of these people feeling sick. How to, how to. recognize them earlier because as you said, it's irreversible and they don't want to do airway clearance for the rest of their lives. We want to avoid getting to that point. Paul, I don't know. It sounds awful.

I feel like we should just recontextualize that. As long as you're using your lungs might be how I would frame it, as opposed to until you're dead. Until you die? As long as you're using your lungs. It just feels slightly cheerier. And listen, for me to be the positive one is weird. You're really... really putting some perspective as to why they look at me with such a shocked face when I say that.

Hey, we will punch up any of your stuff if you want to just send us. Paul, maybe this is new business for us. We'll punch up physicians. Send us what you say to patients. We'll punch it up for you.

I like it. Cyrus, let's get on with the case because I want to talk about exacerbations here. So why don't we make her a little bit sick? All right. So about six weeks later, since your initial appointment, Matt gives you a call. And she says that several of her family members have had a cold. But for her, the symptoms are kind of worse than theirs.

Her cough has increased. She's coughing up some greenish yellow sputum and she just feels exhausted. So she's just not not doing so great. So, you know, based on that, what do you think is going on with her? this may or may not be a bronchiectasis exacerbation. So if it were a bronchiectasis exacerbation, how would you define it? What would you be looking for?

So I love that you're calling it an exacerbation because it's so important that the patients understand what an exacerbation is. The COPD patients seem to really get this, but it's... This whole thing with bronchiectasis, it's new to them. So an exacerbation has a formal definition for clinical academic.

type trials, but nevertheless, we use it clinically. And it was published, I think, in the European Respiratory Journal. And I think we'll have to put a link in because I forget the first author on that. But basically, it's... three or more of the constellation of symptoms that you would think of for your COPD patient. Increased cough, worsened sputum, fever, chest discomfort, hemoptysis, fatigue, and I think, did I say fever already?

for 48 hours, and then it's marked by the physician prescribing an antibiotic. So the reason that this is important is because... Most of the trials for bronchiectasis require patients to have two or more exacerbations in the last year. And if the patients don't understand what an exacerbation is, they don't, they just feel like they're feeling crummy.

Maybe they don't always call you, and then it goes unrecognized. More exacerbations lead to worse lung function. Not getting enrolled in trials means that we'll never have an FDA-approved drug. So lots of consequences from not really marking these exacerbations. And then if I didn't already tell you how much I love sputum before, I'm going to say another good reason to have sputum in the bank.

sort of in the, you know, in your lab is that when that patient gets sick and calls you and says, oh, I feel terrible, you look back to their past sputum culture. And if it's H. influenzae, awesome. You can give them some Augmentin or... of your choice. But if it's pseudomonas, then you kind of have to pull the trigger on a fluoroquinolone. So it's sort of like you need that exacerbation and then it doesn't hurt to kind of put in their chart, you know, exacerbated, you know, April 20th.

and was given ciprofloxacin. And then when she gets referred to pulmonary, I can look back at that and say, oh, she qualifies for this trial. So because she's earlier on in her disease course, and this is her first exacerbation. we we had the culture and remember we said she's like

more to the early end of the spectrum. She isn't yet growing anything resistant. And let's say she has some H flu. You mentioned amoxicillin. How long would we do it? And then is doxycycline? I mean, we love doxycycline on the show. another option for her at this stage? I like doxycycline too. I think that's a nice drug to give someone who's growing.

you know, not non-pseudomonas bacteria. There is no formal, the length of time has not been set in stone. Typically we give for more simple cases like the one you're describing. a week, but there is some expert opinion that supports longer courses for those pseudomonas patients. They may get two or sometimes even three weeks in a more chronic pseudomonas.

patient. Kind of similar to CF. So we sort of, the duration may be shorter on the end of a week for less severe disease, less resistance, and then as they gain resistance and more big time bad... bugs, they get longer courses and probably, and fluoroquinolones and more complicated antibiotic regimens, I imagine. Right. And definitely this is not a steroid group, so they probably should not get...

corticosteroids unless there's additional asthma present. Right. So they would continue all their baseline stuff, the airway clearance things that we talked about, the hypertonic saline. you add this antibiotic and then is there anything else for an exacerbation as primary care that you would want us to know or pitfalls that you see?

Well, I usually tell them to increase the airway clearance, but the other thing that can be dicey is when hemoptysis is involved. For one, it really scares the patient, and especially it's a first time. And so, of course, as I feel almost silly saying this, because I'm sure everyone out there knows it, but a teaspoon here, a teaspoon there, sometimes even a clotted, you know, a big hunk of clot.

a tablespoon, okay. But if it slowly starts to increase, of course, they need to go to the ER. And to keep in mind that it only takes one angry vessel near one bronchiectatic airway to hemopticize or to bleed. So it doesn't matter if they have mild bronchiectasis, they could still bleed a lot.

The other thing that's kind of confusing about hemoptysis is hemoptysis can be a symptom of an infection but it can also be sort of like an airway that's kind of irritated because there's been a lot of airway clearance.

So sometimes, depending on the other symptoms, I might tell the patient to back off airway clearance for two or three days, take a break from that, let the hemoptysis go away, or... you know if i think it's an infection then i'll go with a antibiotic and increased airway clearance okay

All right. So we've talked a little bit about what an exacerbation looks like. And fortunately, we were able to get Mac through her little exacerbation. However, about a month later, when she's feeling well, she happens to go online and look at some of her results. And she sees that a sputum sample from, you know, previously when she had called you. actually grew something called Mycobacterium avium complex. And so, of course, she starts Googling this, understandably, and gets...

pretty concerned and calls you worried that she has TB and she's not sure what to do. And so she's pretty worked up and wants to know, you know, is our family at risk, friends at risk? So lots and lots of questions. So maybe in the time we have left, you could talk. to us a little bit about what is kind of NTM and how it relates to bronchiectasis, and then we'll kind of take it from there. Nice. So non-tuberculous mycobacteria are environmental organisms.

There are over 250 different species of them. And the ones that we see most commonly when your patient coughs up a sample that's... positive for NTM is Mycobacterium avium complex, Mycobacterium abscessus, and Mycobacterium cansaceae. Mycobacterium avium complex is the most common. It's 80% of all NTM. And there are actually 12 different species within Mycobacterium avium complex.

The most common are Mycobacterium avium and Mycobacterium intracellulare. We also see a fair bit of Mycobacterium chimera, which is now known to be a subspecies of intracellulare. There is quite a range of disease severity with Mycobacterium avium complex. So there are people that feel very nonchalant about this. And then there are people who take it. life-threateningly seriously, and frankly, they're both right. Because it's really about sort of the host.

and the burden of the culture. And so some of the nuances of why some cases are worse and some cases are bad become really interesting. And we could kind of hang out all day and talk about, but I guess what I would like to see. on behalf of the internists is to recognize that

pulmonary and ID physicians who are really into this, there's just so much more to learn. And the more patients who we can get to these specialized centers who are studying it, I think the more chances we have to learn about it. So the other thing is, is that so many physicians are so handicapped by the fact that many labs don't really adequately test for these bacteria. And for the most part, an internist is going to get a report that says Mac.

And you have no idea what subspecies and you might not even know whether it was smear positive or whether it would grew in the broth or it grew in the agar and how much it grew. And, you know, so there's all these nuances that can be. become much more clear at centers that have microbiology labs that focus on this.

There are a few in the country. So there's, of course, University of Texas at Tyler is a big one. National Jewish in Denver, Colorado is another big center for this. The Mayo Clinic does a lot. I believe Johns Hopkins is pretty specific about their identification. So there are little hubs throughout the country, but obviously it's really tough for someone if they're not close to one of those centers.

I get phone calls all the time from people who want just a little bit of advice about how to approach something. And I'm always more than happy to do that. Paul and I were talking about a little bit off air here, but when we, as primary care. It's pretty common for us to like maybe on an imaging report or a culture or something and they're like, oh, this could be non-TB mycobacterium based on the imaging findings. And then it always seems a little confusing to me about like...

where to go from there and when do they decide to treat and not treat. And that's just like, so as primary care, when we see this, especially if it's just like on an imaging study and we don't even have sputum yet. Like, where would you recommend we go from there to get them into, because it sounds like this gets pretty specialized pretty quickly. It really does. I can't imagine having to think about, you know.

their blood pressure and their screening and their, you know, they all have back pain too. Yeah. They all want our back pain and the knee pain. Right. Um, so I think the main thing is to keep in mind. One is that the patient needs three criteria to be called. you know, MAC lung disease. Let's just take MAC, for example, because if you're going to, if you find Kinsassii in abscessus, just, you know, send them on to ID or pulmonary. But MAC, you know, potentially, you know. May not be.

disease that needs to be treated. So they have to have the radiographic criteria. And you were talking about probably when the radiologist sees the tree and bud opacities, those really kind of smack of MAC lung infection. So they have to have the radiographic criteria. They have to have two MACs in a sputum. So it can't just be one because, as you know, it's environmental. So it's possible that we can all cough up a MAC once in a while.

And then three, you know, you're never alone. And three, they have to be sick. And that's where sort of the art of the physician comes in is, are they kind of sick because their bronchiectasis is not optimized or are they sick because they've got MAC lung disease? And there are a few symptoms which really go well with MAC lung disease.

And that is they have trouble keeping weight on, they don't have an appetite, and they're really fatigued. And obviously, you don't want it to get this far, but a lot of these people have to take a nap. I mean, they're really fatigued. So, but the weight thing is really, is really interesting. I mean, you can recognize a MAC lung disease from the door because their BMI is like 18 or less.

hot tips, I would say, because that is making things a bit more clear. Paul, what else do we want to know about this? Because I know we have limited time left and I want to use it wisely. I think we talked about a new guideline, so that might be a direction to go. But was there anything else? I always forget things, Paul. I jump too far ahead.

No, no, you're doing great. In fact, I think that was sort of the next thing. I think we were talking about which patients would actually merit treatment. So this sounds like a basic question, but what would that look like? And has that changed recently? I guess it'd be the questions I might ask about Mac. Yeah. And then I, without being politically incorrect, I don't want to, I just need to hammer this. When I have never once treated a patient who was overweight for Mac.

I mean, the weight thing is really, if they are overweight. I'm probably not going to treat them. That's what a strong correlate that weight is for treatment. Okay. So, um, I got so excited about that point now. That's a really good point. Yeah. So. just like you have to have the three symptoms or the, you know, radiographic symptoms and sputum cultures, you got to have three things to treat them. The guidelines recommend a macrolide.

ethambutol, and erifamycin. The guidelines specifically, and when I say guidelines, I'm referring to the 2020 ones that just came out that are like... 38 pages long and totally seemingly unorganized and difficult to read. So I'm just going to tell you. Did you have involvement with them or are you just like throwing your colleagues? I am. I was just going to say.

Chuck Daly at Denver, who's the first author and someone who I respect tremendously, is probably like, what the hell? Come on, Chuck. Get it together. Get your guidelines organized. Yeah, I mean, once you read through them, you can kind of tackle them. But really, it's like chewing on a piece of tough steak. You want us to keep this in or cut this? It's up to you. Honestly, I don't think anybody would disagree. And I just, as long as you include the part that I tremendously respect Chuck Daly.

And it probably was really hard to get those written because it's not just ATS-IDSA guidelines anymore. It's ATS-IDSA. ERS, and then another long acronym. So they had to get together with many different countries to make a consensus on this. So it probably was really hard to write, but they're not user-friendly and I'm sure they would agree.

but I really respect Chuck Daly. Okay. So the thing is, you got to have three drugs at this time, macrolide, ethambutol, and rifamycin. The guidelines put their penny down and say, of the macrolides choose azithromycin because it's easier to tolerate. They stress the importance of... using all three of these drugs. So the azithromycin acts intracellularly. The ethambutol attacks the cell membrane so that the azithromycin can get in and work.

And then the rifamycin is there to make the patient sick. so that they can say that this treatment plan is dreadful. No, I'm just kidding. The guidelines also recommend that your patient can be on three times a week treatment. if they just have nodular bronchiectasis. So unless they have this raging, big, I have emphysema in a huge, scary cavity in their upper lobe, you can treat them with three times weekly. So that's... Azithromycin 500 milligrams, Monday, Wednesday, Friday.

Iffambutol is 25 milligrams per kilogram Monday, Wednesday, Friday. And the rifampin, if you use that one, is 600 milligrams on Monday, Wednesday, Friday. So that's your regimen. The gigantic... Oh, and then you should be testing their CBC and CMP once a month. And they have to go to an eye doctor and they probably should go to a hearing doctor so that they get their hearing check too on the azithromycin.

Now, there is one other very exciting update in the world of Mac therapy. In the 2020 guidelines, Liposomal inhaled amikacin is referenced as a therapy that can be used in patients who are unable to clear their MAC from their sputum after six months of appropriate triple drug therapy. Liposomal inhaled amikacin was studied in the CONVERT trial.

In that study, 330 patients were examined, and roughly half of those patients received standard triple drug therapy and then received inhaled liposomal amikacin. In addition to that...

in order to attempt to clear their sputum. In those patients in the treatment arm, they did have a statistically significant clearance of their sputum in regards to MAC without an increase in adverse events. So this is very exciting in that this makes... liposomal inhaled amikacin, the first FDA-approved drug specifically for MAC therapy, and it gives clinicians an opportunity to actually achieve sputum clearance in patients who may otherwise.

not achieve sputum clearance. So to recap, MAC is about 80% of the, if people have this non-TB mycobacterium on imaging. if they have the weight loss we can think about this most likely this would be mac 80 of the time would be mac we just went through the three drug regimen We're going to be monitoring CBC, audiology, ophthalmology. We're going to get monthly sputum cultures, make sure that they're trying to clear them.

we would be potentially adding on this liposomal amikacin inhaled if they don't clear within six months' time. And I think...

I understand this about as much as I ever have, Paul. So do you think this is a time for take home points now? It feels right. So PJ, this has been so much fun, but. at some point we have to let you go. So can you give us like a couple of take home points that you want the audience to remember about this giant topic that we just covered? You just can't have enough. Great.

A sputum is a vital sign. It's keeping your finger on the pulse of what's going on in your patient. Airway clearance all day long. And don't use azithromycin alone. And please let us get involved if you have a patient with MAC lung disease so that we can increase our numbers in trials and get more drugs that are FDA approved. I have six clinical trials going on right now for MAC lung disease. But the problem is they all want treatment-naive patients.

They don't want the patients who have been treated six times before out in the community and are now finally making it to the specialized referral center. They want treatment naive. Please send us your patients so that we can get more drugs available for you. Well, we will certainly our audience can can help you out with that. We can we can. We will be better about doing the referrals. So thank you so much for all of this. This was fantastic. And we will fade into the outro.

This has been another episode of The Curbsiders, bringing you a little knowledge food for your brain hole. Delicious. I still don't like it. Get your show notes at thecurbsiders.com. And while you're there, sign up for our mailing list to get our weekly show notes in your inbox. You can also be signed up for our...

twice-monthly newsletter, the Curbsiders Digest, which will update you on all of the exciting things happening in internal medicine. And we're committed to providing you with high-value practice-changing knowledge, so we want your feedback. Please subscribe, rate, and review to the show on Apple Podcasts. You can send us an email to thecurbsiders at gmail.com. Special thanks to our producers for this episode, Drs. Leah Witt and Cyrus Askin.

And to our social media team, Beth Garbs Garbatelli on Twitter, Maddie Mad Dog Morgan on Instagram, Tima Karganov is on the website, and Chris DeChumanchu is on Facebook. Also, Paul, this and most of our episodes are available for free CME credit for all healthcare professionals through VCU at curbsiders.vcuhealth.org. So finally, Paul, until next time, I've been Dr. Matthew Frank Watto.

And I've been Dr. Cyrus Askin. This outro has been a real journey, and we have to thank the great Dr. Stuart Brigham, who composed the theme music you are hearing behind us. We should also thank the amazing Claire Morgan of Notterley, who edits our audio. And as always, I remain Dr. Paul Nelson-Williams. Thank you and goodbye.