Hey, everyone.

Thanks for tuning in today.

For today's podcast, we have a special episode for you.

We were lucky enough to be invited to do a live session at CHEST twenty twenty five.

Unfortunately, I couldn't make it to the conference, but Christina held down the fort and hosted a live session at the conference.

She was joined by associate editors for Poem Peeps, Luke Hedrick, RuPauli Sud and Tom DiVantonio And they were joined by an additional guest, Doreen Adrizo Harris.

The title of this session was widened airways and narrow differentials.

So you may guess it's a great session about bronchiectasis and thinking about the differential of patients who come in with symptoms or signs of this wide spectrum of disease.

It sounded like a great session.

I've listened to the audio and watched the video since, and it's really awesome.

And we wanted to share it with you all.

So without further ado, here's the recording of that episode.

Well, I'm looking at the time.

I see

that we are at 08:02, so we're gonna go ahead and get started.

Good morning, everyone, that is, here live with us in the room today.

I'm Christina Montemayor, the cofounder and half of the Poem Peeps and a chess enthusiast.

We're coming to you live from Chicago in CHESS twenty twenty five.

We'd like to thank CHESS and and specifically doctor Sandy Caruana who asked us to be here today.

And, we know that we have two other critical care podcasts that are going on, so ours is gonna be the great pulmonary focus for you all.

I feel like we all need a little bit more pulmonary, so that's what we're bringing for you today.

We're here in Chicago, the headquarters of CHEST, and I'm really excited to be part of this ninetieth, anniversary celebration.

You may you may notice that, I am missing, one of my other half, David Ferfarro, who's currently in Italy with his family, but he sends his regards.

We've been sending notes to each other about who has the best pizza.

I was like, we've had deep dish, Dave.

You don't have that in Italy.

So, but he, he will be excited to hear this podcast.

And as you can see, we have a fantastic team here today.

If I'm not joined by FIR, very excited to have our associate editor, Doctor.

Luke Hedrick, who is currently a third year fellow at Emory, who is here with us today.

And you may recognize his voice from our rapid bio journal clubs that he does.

Welcome Luke.

Hey Christina.

Thanks for having me.

Maybe just a little bit.

Hey Christina.

Happy to join.

I think it's kind of crazy, but I think this may actually be the first time we've recorded together in person, which is wild given how long it feels like, this has been ongoing, but very happy to be here.

Amazing.

And we're excited to have our, a first time poem peeper to the show, share a warm welcome to doctor Doreen Idriso Harris.

Doreen is a professor of medicine at NYU.

She's currently the associate director of clinical and academic affairs in the division.

In addition to that, she is the director of the bronchiectasis and NTM program and also serves as a program director for the pulmonary and critical care fellowship.

True leader in the field and has a I know definitely has a special place here at CHEST, where in 2023 she served as the eighty fifth CHEST president.

So Doreen, such an honor.

Welcome to Poem Peeps.

Thank you very much.

It's, it's a pleasure to be here today.

I'm very excited to see what this is all about.

I know.

I think I know.

First first time podcaster, Doreen.

We I was just asking too.

I was like, Doreen, how many years have you been the fellowship PD?

And she said twenty five.

So I was like, I'm only 23 behind you.

But a lot to look forward to.

We're also very excited to have two additional members of our Poem Peeps family.

Would like to send a warm welcome to Tom DiVantonio, Roopali Sood.

You both probably have recognized, and have been instrumental in our recent asthma guideline series.

Tom and Roopali are both critical care fellows at Johns Hopkins, and I have the honor to have them as my current co chiefs this year.

So welcome, Tom and Mupali.

Good morning, everyone.

Very excited to be joining y'all here from this awesome CHESS conference, for this, great podcast.

Yeah.

Thank you for having us.

We're very excited to be on stage altogether and in person, because even when we're together in the same place, we're not always in person.

So this is very exciting.

So thanks for having us.

Of course.

Alright.

And so then, just as a reminder, this podcast is not meant to be used for medical advice.

The views we expressed today do not reflect the opinions or policies of our respective employers.

The case we're presenting today is HIPAA compliant and some details may have been changed to protect the privacy of our patient.

And so without further ado, let's get into our case.

The year is 2010 and we have a 60 year old father of two with a history of CLL in remission after three cycles of chemo who presents to pulmonary clinic for recurrent infections.

He describes recurrent respiratory infections about one per year with three hospital admissions for the same.

Most recently he had a right middle lobe pneumonia.

His PFTs are notable for some airflow limitation that corrects with bronchodilators, normal lung volumes, a preserved DLCO and a pheno of 15.

CT chest imaging isn't available for review at this first appointment but there is a report that describes some tree and bud nodularity with bronchial wall thickening and very mild upper lobe bronchialectasis.

And I don't know if you guys feel this way or not, but I feel like this history sometimes is a pretty tricky one to take.

Ref current respiratory infections are so common.

Like, just ask any parent of a daycare aged child, and the vast majority of people in that setting don't have any underlying issue.

But that being said, for our patient, the recurrent pneumonias in particular, I feel like perks my ears up, especially ones that lead to admission.

And so when I think about a patient with recurrent pneumonia, I typically try to approach things geographically, which is to say, are the infections all happening in the same particular region of the lung or not, which may prompt me to think about an anatomic problem, some extrinsic compression, an issue with the airway itself like bronchio bronchiectasis, excuse me, or dependent areas where I worry about recurrent aspiration.

In this case, his infections were diffuse and kind of scattered throughout the lungs, which leads to an entirely different set of differentials about things like underlying systemic issues like cystic fibrosis or immuno deficiencies like HIV or CVID or non infectious mimickers like organizing pneumonia or avasculitis.

And so with our patient, he, as I said, these were not geographically restricted and so labs were sent looking for one of these underlying conditions and he's ultimately diagnosed with CVID or common variable immunodeficiency.

He started on IVIG with improvement until 2014 when he has a STEMI and develops hemoptysis with ticagrelor which leads to a CT chest.

Tom, do you mind just walking us through this picture?

Yeah.

Absolutely.

So here we have five, representative slices of this gentleman's CT chest from 2014 going from the apices of the lungs down to the base.

And I think what really jumps out at me as particularly noticeable is that he has upper lobe predominant bronchial wall thickening, and then some mild bronchiectasis.

And if you look, there's some some mucus impaction as well in some of those, those airways.

And along with those, I think the other notable findings are that there's some scattered central lobular nodules, and patchy upper lobe predominant opacities.

You know, sometimes the term tree and bud gets thrown around with these sorts of findings, and I think it could be applicable here.

Christina, this this term tree and bud, it it's talked about all the time.

And it's really easy just I think a lot of us here at tree and bud equals infection.

Can you talk us through a little bit more what it means pathophysiologically?

Yes.

Absolutely, Tom.

Yeah.

Right.

And I feel like tree and bud, a little hand wavy.

You're, like, reading it and, like, are like, a resident will say, I think there's tree and bud there.

Something looks off like, wrong at the periphery, but totally right.

When I think of tree and bud, it's gonna be the the small airway.

So really, tree and bud associate with small airways, really the bronchioles, for sure.

So right, but something is feeling it, whether it's mucus, pus or something inflammatory.

I definitely, that's what I think of.

So looking on CT, we can see, right, that the those plugged little bronchioles look like nodules connected to branching lines, which I think Luke is pointing out.

I think we're also we're we're coming live, so we're actually, show showcasing some some imaging.

But for those that may be listening after the the conference, we'll definitely make sure that we, have these images for you to review.

But like I said, right, it's I would I don't think of triumvirate as a specific diagnosis.

It's really just pattern.

And I think a lot of what we do in pulmonary critical care, looking at imaging, is going to be pattern recognition.

So something is, obstructing or inflamed in the bronchioles, but that's how do I think about it.

So my mental model for thinking about tree and bud, you know, really focus on what etiologies, you could be thinking about are going to be really favored on distribution and the chronicity.

So I think if it's diffuse and acute, right, infection is going to top the list.

So bacterial, viral or mycobacterial.

If we think it's more dependent and basilar, we're not seeing that in our image today, but I think most of you here in the room will also be thinking about chronic aspiration.

And if it's persistent, if it's nodular and if it's associated with other findings such as bronchiectasis, I know many of you here in the room will also be thinking of NTM.

So tree and bud, small airways, you know, bronchioles, bronchiolitis, pattern recognition.

But the clinical context really matters, right?

So chronic coughs, sputum, weight loss, we're going to be thinking of infection higher on the differential.

But, you know, recurrent aspiration or structural disease can also look similar.

Tom, and I, know that I thank you for pointing that out.

I think, you specifically said, right, the bronchiectasis in our images that we're seeing primarily in the upper lobes.

You know, Roopali, Tom, I know we've talked about bronchiectasis a few times in our fellowship didactics with our radiology rounds already this year.

But we think of bronchiectasis, it's just not a it's not just imaging finding.

It's more of a syndrome that we'll think about.

Symptoms, exacerbations, but we have to have some type of CT findings.

Roopali, do you mind walking us through, when you think of bronchiectasis on CT imaging, what are you looking for?

How are you gonna classify bronchiectasis?

How are we gonna tell Doreen?

Doreen, I really think this is bronchiectasis.

What How is Doreen gonna tell us?

How is Doreen yes.

Exactly.

Yeah.

Great question, Monte.

I think, when we think radiographically looking for bronchiectasis, we usually look for three things.

So the first thing we look for is the bronchoarterial ratio that's greater than one, and all that's really saying is that the airway that's paired next to an artery is greater in diameter or width than the artery that runs next to it.

Sometimes this is called the signet ring sign because the paired artery looks like the ring top and then the airway is larger and looks like the place where the finger goes.

The second sign is a lack of normal tapering of airways.

So usually, airways should narrow as they reach the periphery, however, if they don't, if the bronchi stay open or they remain the same caliber throughout, especially as you go out to the periphery, that's the second sign to look for radiographically.

The third sign is that airways are sometimes visible within one sort of centimetre of the pleura.

Usually, bronchi should tend to disappear before they reach the end of the long edge, so if you see open airway way out until the edge, that's a clue as well.

So, those

three signs: the bronchial arterial ratio, the lack of normal tapering, and then the airways being visible one centimeter from the pleura.

Additionally, those being the three signs for bronchiectasis radiographically, but as, Christina described that this is a clinical syndrome diagnosis, so it's important to consider whether that bronchiectasis pattern that you're seeing, is it focal or is it diffuse, which can often lead to whether this is a local process as mentioned or it's a more systemic process being more diffuse, are there nodules or trans blood, which is something we've been talking about to indicate that there's small active airway disease in addition to the bronchiectasis, which is a structural change, And then third, is there mucus impaction or are there any sort of allergic features which could help us sort of consider other things in the differential that have been mentioned like SCF like process or ABP?

We always talk about bronchiectasis as location, location, location and so also important to consider upper lobe, middle lobe, or lower lobe.

I know we have a good Pompey some demographic on that as well that we can refer to.

Amazing.

Thank you for walking us through that, Rapalje.

I think, sometimes taking a step back and reminding myself what I'm actually looking for instead of just like the alphabet soup of words that get put on radiology reports is really helpful for me keeping some of this straight.

And so for our patient, time advances a few years.

He's seen in clinic where he describes a chronic productive cough and night sweats.

Sputum cultures are obtained, which grow MAC or Mycobacterium avium complex in three separate samples.

And we've all had patients where the sputum grows MAC or some M abscessus, and the big question then becomes, is this real disease, or is this just colonization?

And so, Doreen, I was hoping you could walk us through how you think about when a patient truly meets criteria for having disease.

So based on the guidelines, which we know came out, in 2020, you want to have the clinical radiographic and microbiologic findings in order to make a definite diagnosis.

But that doesn't always apply to every patient.

I mean, this patient's symptomatic is obviously coughing and has sputum.

That's how we got, got the MAC.

So anybody that we're culturing MAC on already, we know probably does have sputum or or cultures.

But we can talk about, you know, radiographic features, which you've all said must be present, whether they're, micro, nodular disease or cavitary disease, and then we like them to have, other symptoms, sometimes fatigue, night sweats, etcetera, to fit the, the best picture.

But there are patients who are totally asymptomatic, and may just be picked up with a cavity or, you know, bronchiectasis on CT.

They don't think they have symptoms of sputum, but they say, sure, I cough up some sputum every morning.

So you really have to ask them.

But those patients that are very asymptomatic, you know, they don't classically fit the definition.

However, they're not people that you would not want to follow, particularly if they have a progressive CAT scan or cavitary disease.

So when, you know, we say who to treat, who not to treat.

That's the big question and often the most difficult question.

So my answer is always, if you decide not to treat, just make sure that you're following the patient closely.

It will become evident to you when that time to treat is.

If you're always if you're on the borderline at the beginning.

Thanks, Doreen, for walking us through that.

For me, you know, I think listening to that, it's a a huge takeaway is that you really need all three of these because so many of all three of these criteria.

So many of our patients are going to come in with one or two, but the decision to treat these people subjects them to long durations of antibiotics, some of which have significant side effects, not always with a chance of cure.

So it's a major decision and it's a big takeaway for me.

And I can see how it could, if we don't adhere to these guidelines, it could lead to us overtreating certain patients, undertreating others.

When as a follow-up question, when you look at a person's CAT scan, are there any particular CT findings that make you more confident that this is actual disease, or is that just part of the overall clinical picture?

Well, your your patient here clearly has diffuse disease and has disease.

You know, if the patient has bronchiectasis and bronchiolitis, they likely have disease.

But again, when to treat, right?

And do you have to treat?

We have plenty of patients who the progression may be stable for many, many years until something then actually happens, whether they have some other comorbidity that occurs or such.

And they may not need treatment for those ten years.

And we know the recurrence and relapse rate reinfection.

And relapse rate is quite high.

In some studies, up to seventy five percent with reinfection within two years after treatment is completed.

So these patients often may need to be treated multiple times.

So, it's not like treatment once is going to, you know, cure them for the rest of their lives in in many cases.

So you wanna be sure.

I do want to point out that sometimes on CT scans, you may not see clear bronchiectasis.

But looking at, first of all, bronchiect mild bronchiectasis, I think, is missed quite a bit by our radiologists.

Particularly, not to fault them, but they're looking for the more acute things.

They're doing PE scans, making sure they don't miss that PE.

And if there's myel bronchiectasis, well that's not high on the list of why the patient came into the ED in the first place.

So they may not even interpret that on the CT.

So it's extremely important, I think, for the pulmonologist to relook at those CTs and say, There really is diffuse bronchiectasis using exactly the criteria you had.

Or just bronchial wall thickening.

We know something must happen before bronchiectasis occurs.

And that's the time we may really want to do something for prevention.

So bronchio wall thickening and this diagnosis of PBB, persistent bronchial bronch persistent, bacterial bronchitis.

Where patients may be very productive and may not yet have bronchiectasis on CT might be the time where we really want to intervene.

So look at those CAT scans that you get on your patients, even if the radiologist did not call bronchiectasis.

That's so so such such great pearls, Doreen.

Just a second follow-up question, you know, and kind of going back.

You mentioned, right, you or you may say that this they they meet criteria, but they don't necessarily, need treatment yet or, you know, you're still wanting to flush things out and have follow-up.

What is your threshold for repeating imaging?

How often do you want to have these patients come in in clinic for surveillance, before you actually say that you need to commit to treatment?

So I think we have to go back again, because we were all assuming treatment means pharmacological treatment, at least I was.

And so I don't we should say all of these patients need full assessment.

As you brought up earlier, all the different etiologies that might so they may not need medications at this point, but they all need a full diagnostic workup.

And I truly believe that we're not doing enough.

The guidelines only give us a few items that we should do on every patient.

And that's just because there's not evidence out there to do more than that yet.

So in a patient who comes to you like this patient, I think a full diagnostic workup, we could talk about what that is later.

And then most patients who are symptomatic, right, we, most of us believe that airway clearance, certainly in the guidelines that came out at ERS recently and the new ones that will be coming out from Jess, are gonna support airway clearance as a mainstay, whether it's exercise with some component or full, you know, airway clearance and other modalities is something that's gonna be treatment Mhmm.

But not pharmacological treatment.

Yeah.

And then I follow them, you know, depending on the patient, but usually every three to six months depending on them.

And I don't wanna be doing CAT scans in patients who have minimal symptoms and are doing very well.

So we will follow pulmonary function test.

We'll follow their sputums if we see the they become smear positive or they're starting to grow other organisms.

Right?

That will trigger us to get a CT scan sooner.

And those who are sick, often annual CTs will be done.

And then those in treatment sometimes as frequently as every six months.

Thank you.

Thank you for highlighting, treatment, pharmacologic, non pharmacologic.

Thank you so much.

Yeah.

Thank you.

And I I really, appreciate the reminder that, there's always more digging to do, which hopefully we can talk about later.

I feel like one of my big takeaways in fellowship has been not just stopping at, you know, ARDS or organizing pneumonia or bronchiectasis, but trying to figure out why that happened in the first place because it often really does affect management.

And so for our patient, he grew the same MAC three separate times and three separate specimens, and I know that pathogenicity varies a lot by the underlying organism.

And so I'm curious, Doreen, would you mind helping us think through which bugs you typically think of as pathogens or which ones you're less worried about, which you tend to think of as colonizers?

How do I guess do you approach the idea of the specific bug that they're growing?

Well, I think you all know the common bugs.

Mac and it's 12 species, depending on what gets reported out from your lab.

So, AVM intracellulara and chimaera are the most common.

But then M abscessus, M.

Zenopi, M.

Kensassai, those are the biggest ones that we'll be seeing in The United States.

There was a paper that came out on m gordonae, which we know is usually a contaminant.

But Chuck Daley and, Mark Petersky along with others just published it, I think, last year.

Looking at what does it signify.

And it actually does signify underlying airways disease even though the gordoni may not be something that you need to treat.

So you should probably be paying attention to a patient who's growing a different mycobacterium, and there are more than a 190 of them in every sputum you send.

We like to say, well, you have to get two.

So I'm waiting for that second one to come, whether it's a bovis or a semia or and then I get a different one every time.

And why is that happening?

So maybe there's some underlying, immunodeficiency in that patient or some exposure environmental exposure.

So further investigation is definitely needed.

But the common ones are the ones that I I listed.

Yeah.

Thank you.

And then I guess just another teaching point to call out here is that, as you mentioned, just because someone meets criteria for NTM pulmonary disease does not necessarily mean that, pharmacologic therapy is indicated for them, in particular the antimicrobials.

These are really long courses with a high treatment burden.

And it's worth considering how robust your patient is or how predisposed to toxicity they may be depending on the agents that you're reaching for, and then again how virulent the bug that you're dealing with is.

That begs a question then of what would be a reasonable first regimen for a patient with MAC and our patient with MAC.

And in general, I think there's a few teaching points that I would I try to remember here.

The first is that your susceptibilities really matter, in particular to macrolides and amikison.

And related to this, it's important that that testing gets done at an experienced lab.

So as an example, ImbObsessus needs to have that testing prolonged over fourteen days because they can have inducible resistance to macrolides, which clinically is really important for those patients.

In terms of a standard regimen for macrolide susceptible mac, ERA or ethambutol, rifampin, and azithromycin is a typical regimen.

Clarithromycin or rifamycin are alternatives, but typically have more side effects or a little less, more poorly tolerated and so aren't quite first line.

This regimen then can get adjusted slightly based on your patient's phenotype.

So if someone has fibro cavitary or, excuse me, nodular bronchiectatic disease, ERA with three times per week dosing is generally appropriate, whereas someone with fibrocavitary or more advanced disease may need daily dosing and you should consider adding an IV immunoglycoside.

It's worth emphasizing here that the macrolide is the workhorse of this treatment regimen.

The other two agents are mostly existing to try to prevent resistance for that macrolide.

Finally, these people need close monitoring, while on therapy.

They need sputum every few months.

You're typically gonna be treating folks for about twelve months past when their culture's clear, and so both monitoring sputum to make sure that it's responding and they're clearing the cultures the way that you hope, but also to keep that clock in your head about how long things may be going.

They'll need lab work with CBCs and CMPs at baseline and then every couple months as well.

Depending on the agents you're using, visual acuity or audiometry testing can be really important.

And then finally, you'll need to consider how frequently you're going to be monitoring your imaging, typically once a year or so or with big clinical changes.

And so for our patient, he has started on ERA.

He's treated for about a year with improvement in symptoms and culture clearance.

Unfortunately, about three years later, he begins having exacerbations again.

First with a viral URI triggered episode and then a few months later, he grows MSSA and MAC in three separate cultures again.

Interestingly enough, he's treated with levofloxacin targeting that MSSA, and his symptoms resolve entirely.

And so at this point, Doreen, I'm curious whether you would you know, you mentioned that sometimes folks need to be treated more than once.

Is this a patient that you think you would initiate MAC directed therapy again?

So I try not to if his symptoms are better by treating the easiest to treat organism like you did, and I would follow him by making sure his CAT scan is not progressing.

So at this point, I think I would just follow him.

Yeah.

And and that makes a lot of sense to me and is similar to what happened with our patient here.

You know, we don't need to go find another problem if we take the easy win sometimes.

And so another round of MAC therapy is opted against, just as you mentioned with his symptoms resolving with the MSSA treatment, the thought being that maybe that was the driver and that the MAC itself wasn't particularly symptomatic.

And so to that point, he gets surveillance cultures over the next four years that grow in Masiliency three times.

I'm sure I've butchered the pronunciation of that particular book.

I was raised by lawyers, so I'm, confidently wrong a lot.

In any case, all of these different isolates have different susceptibility patterns, and he actually has a negative culture in between.

And so kind of corroborating that idea that maybe the NTM wasn't necessarily the thing that was driving his symptoms.

Unfortunately, in parallel over that time, his imaging does slowly progress.

So, Roopali, would you mind helping us think through this scan?

Yeah.

So we'll just take another radiology pause here.

And I think at the beginning when we discussed we talked about the signs of bronchiectasis.

Right?

So I wanna remind you that we have imaging from 2014, now we're flashing forward four years, right, 2018.

And we're seeing a slowly progressive process.

So you can note there in the imaging on the top corner, for those listening, we will post the slides, but you can see that bronchiectasis is progressing.

You can see again that thickened enlarged airway, we can see signs of that signet sign, down at the bottom there, and there's the mucus impaction that is slowly progressing.

So we see progressive upper lobe predominant bronchiectasis with mucus impaction as well as increasing nodularity.

This patient, I believe, Luke also had some scans done subsequently after 2018, 2019, and then following a few years later in 2022, and they continued to show a slow progressive story of mild progression of this upper lobe predominant bronchiectasis, as well as this waxing and waning nodular pattern that we're starting to see with very evident mucus impaction, which you can see here too with some of the airways actually impacted, specifically with mucus, in those settings.

So I'm curious, Doreen, given these findings, symptoms, the recent cultures that we heard about with the negative culture and then the positive cultures, how confident are you at this point that what we're seeing right now is NTM and possibly what we've mentioned before, before, common variable immunodeficiency related bronchiectasis, that we are currently treating this patient for.

Yeah.

So I'm concerned about him.

I forget how old he is, but, he's progressing.

He still has persistent symptoms.

I don't know how many exacerbations.

I'm not too excited about one M.

Abscessus macilians per year.

So I would automatically be getting sputums on him several times a month, probably.

Because I want to see what's that pathogen that's going to be growing the most.

And we haven't really done anything, I don't know about his airway clearance regimen, if he's compliant or if he's on anything, but that would be something I'd wanna make sure we maximize.

Because believe it or not, I can show you many cases that you have dramatic improvement in CTs just after doing.

And I tell my parent patients before you go for your CAT scan, I don't care if you haven't done your airway clearance for six months.

The month before your CAT scan, please make sure you're doing it regularly.

Because I really do think it makes a big impact.

And, so if he is doing airway clearance, let's assume he's doing it and he's compliant, then we have to think about anti inflammatory modulation somewhere here.

And he hasn't been growing Pseudomonas or repeated staph, it seems like.

So, you know, what about macrolide therapy for, anti inflammatory effects?

And the problems we have that in with him is that he's got the Mac from before or I I know how recently.

And now if he actually had a, a, M abscessus that was resistant to macrolides, we could use and no Mac.

We could use azithromycin, because then we wouldn't have to worry about him becoming resistant.

But you have an, macrolide sensitive m abscessus.

So I would start thinking about if he grows another, you know, get a few.

And if the mycelians is still growing, start treatment for myceliancy.

Yeah.

Thank you.

That that makes a lot of sense.

I think, we also shared some questions about, what was happening to him at the time.

He's, just for reference, in his sixties.

We've advanced over the years now, so kind of in his mid to late sixties at this point.

He's on a little bit of airway clearance with some exercise and an aerobica that he uses, maybe not as often as we've requested, but he does have one.

So time moves forward.

He establishes with a new pulmonologist in 2022, and unfortunately his clinical trajectory changes.

He has recurrent exacerbations over the 2022 and then into early spring twenty twenty three.

So in September, he has hemoptysis while he's out of state with some stable imaging.

He's given PO antibiotics of some kind.

The records aren't quite available.

In December into January, he gets COVID, then has purulent sinus drainage.

His sputum grows MRSA this time.

He goes to an urgent care where he's given doxycycline and prednisone.

In March, he has a recurrent productive cough with more purulent sinus drainage, worsening fatigue and dyspnea.

His PFTs now show a new airflow limitation.

Cultures grow MRSA and MAC again.

He's finally started on some 7% saline for airway clearance and is given amoxicillin clavulanate for an antimicrobial.

Fortunately, he keeps getting worse and is admitted at an outside hospital not long after where he gets a little over a week in total of a combination of levofloxacin, vancomycin, l levofloxacin, vancomycin, lonazolid, and bactrim kind of at various times in various combinations.

There was a lot of issues with his insurance improving various antibiotics, and so his outpatient plan kept changing and then leading to different regimens.

It seemed like every thirty six hours for him.

And then a week later, his symptoms recur, and he's directly admitted to the hospital again.

Thanks, Luke.

Yeah.

I think I think we could probably all agree, like, the patient is not thriving, right?

Something is not happening.

How can we best, treat the patient?

And I think just show of hands in the room since we have this opportunity to do this.

Do we think this is just CVID and NTM?

Does anyone else in the room think that maybe something else is going on?

Great.

Yeah.

So I think at least half of you are thinking, right, some other process is going on.

I think some important things that Doreen mentioned, right, looking at what microorganisms is a patient growing.

You mentioned not Pseudomonas.

We usually think of Pseudomonas with cystic fibrosis, but, you know, someone growing, you know, MAC, MRSA, MSSA, Right?

You know, is something else happening?

The patient's now admitted.

And I think many of us here in the room as as trainees or faculty, when someone comes in for the inpatient admission, you get to think of this patient in a homey way.

And I feel like it's the trainee sometimes that are really like, you know what?

I don't I think something else is going on, and you're right.

So please continue to think that.

And I think I'm thinking now.

Right?

He's admitted, Luke, what you know, diagnostic pause.

We've done radiology pauses today.

But let's do a diagnostic pause.

Right?

Because I think a lot of times, you know, along the course, it's it's easy to look back now and just be like, woah.

They're anchoring bias.

Someone was like, oh, this is this is only CVID and NTM.

He's not getting better.

We're just giving him the wrong antibiotics.

Maybe he's not doing airway clearance.

But, Luke, diagnostic pause.

What what framework do you like to to think about when you're doing a diagnostic pause in a patient?

Yeah.

Definitely.

And I will say too, I was, fortunate to meet Dave very early in my residency, so I think he actually is the one who taught me the, like, idea of the diagnostic time out.

And so I have cribbed some of this from him, shamelessly since he's not here to claim credit for himself.

In general, I think my goal when taking a a time out or a pause like this is to deliberately work through in a system one kind of explicit way what the current diagnosis is.

And so first, I like to name that working diagnosis, which I call that a working diagnosis because, again, if we felt really confident about it and the patient was doing well, we wouldn't be doing this in the first place.

Right?

And so there's some degree of uncertainty around whether we've gotten this correct.

Then I like to identify what fits and, more importantly, what doesn't about our case and our history with that working diagnosis.

Are there things that are inconsistent with it?

What does seem consistent with it?

Hopefully, there's some of those consistencies that led us to that working diagnosis in the first place.

Then I try to think about whether this could just be an atypical presentation of a common disease, you know, common things being common, whether the patient has multiple diagnoses, you know, that kind of inverse of, Occam's razor that people can have as many illnesses as they please, and then whether we've truly ruled out any can't miss diagnosis.

Is there something big and scary that's kind of lurking in the margin that either we're worried about or the patient and their family are worried about?

And do we feel like we've truly given that a good look?

If I'm still unsure at that point, I like to load the boat, which that is, like, ask for help.

So either another attending, a more senior colleague, whether that's a formal consult to, you know, ID in a lot of these tricky cases, etcetera.

But I don't like to worry alone.

And then lastly, I just wanna make sure that I've communicated that uncertainty to the patient and their family, just to make sure that they're where everybody is kind of on the same page about what exactly it is we're dealing with.

And, you know, I feel like I've I've seen a couple times where someone feels very blindsided later when a diagnosis changes, even though ultimately that is helpful for them clinically and they improve this idea that they've kind of had anchored in their mind for some period of time, that can be a real shock to folks.

And so just making sure that I'm being transparent with patients about that.

And so for our patient, some potential considerations that when I kinda think through things for him, and please feel free, everyone to add any others as they occur to you is, one, whether he just needs IV therapy.

Is oral antibiotics inadequate for him for some reason?

Whether there's been an incomplete duration of antibiotics, so his courses were typically somewhere in that seven to ten day range, and sometimes these folks just need two weeks.

Whether the staph isn't his major pathogen, you know, is it that Mac is one of the various MTMs that he's grown over the years?

And then finally, I do wonder about whether there's an underlying process that we're missing.

Yeah.

Thanks, Luke.

Yeah.

And I I think just maybe a few minor things to add or as you're thinking about this and how I would be if I was seeing the patient for the very first time, in the hospital, many of you may also be thinking, you know, what, right, this could be this could be CBID.

We have pulmonary.

We have sinus disease.

But I think there's other conditions that we haven't talked about yet that we can also think of both pulmonary and sinus disease, you know, specifically cystic fibrosis, primary ciliary dyskinesia.

So thinking about does this patient have a genetic defect that we should be thinking about?

But also we haven't necessarily talked about are there allergic or inflammatory etiologies as well, including ABPA or EGPA?

So I think that this would be an important time to, like, expand or broaden our differential.

And I I think as you mentioned too, right, I do agree with some patients, I do adult cystic fibrosis.

So my typical duration for patients is about fourteen days of IV treatment.

During for for NTM bronchiectasis, do you are you usually doing seven to ten days or do you expand on that?

For bacterial infections, for usually, if it's, depending on the pathogen, but usually fourteen days.

If it's a very sensitive organism, then we'll reduce it to seven.

Okay.

Yeah.

So but I think to your to your point, Luke, are we treating the right organism and is the patient getting the right antibiotic?

I would be curious, and I'm sure that you do have this too, but he's grown MRSA, MSSA multiple times.

Is he getting some type of resistance to the typical antibiotics that we think of as well to consider?

And then one one thing too, I would also think about at this point, Roopali, you mentioned earlier, the bronchi bronchiectasis that we're seeing, you know, you said location, location, location.

I feel like I'm gonna Tom and Rupali, we we've had three radiology conferences so far.

When we thought when we think of location, and or I'm gonna ask I'm gonna ask y'all.

Thinking about location, how do you how do you divide it up?

What are y'all thinking?

What should we be thinking about?

Yeah.

That's a great question.

This is a I know, an impromptu retention retention knowledge question.

Yeah.

So I think of when we think about location, we're trying to sort of geographically think about the bronchiectasis in our mind.

Mind.

And I think we had mentioned, right, when we think about lower lobe predominant bronchiectasis, right, we're thinking about things that can commonly affect the lower lobe.

So I think aspiration has been mentioned many times, and that just logically makes sense to us is where you would see bronchiectasis associated with chronic aspiration.

But CVID has also come up as a potential etiology, and that can either be more of a diffuse or in the lower lobes, sometimes more.

Although, I will note in this patient, we noted upper lobe predominance, in the first sort of time.

And then I know in the upper lobes, Doctor.

Montemiro is a CF doctor, so we often talk about genetic defects and how CF can often be seen in an upper lobes.

There can also be infectious ideologies like HIV, that can sometimes be seen and then the great mimicker of everything.

Right?

I think we talk about sarcoidosis as being the mimic disease that mimics everything, but can often be seen in sort of the upper lobes as well.

Tom, you have anything to add?

Yeah.

I think the, you know, we've addressed the upper lobes, we've addressed the middle, the lower lobes.

The only other place to really look is the, the middle lobe.

And when I think about middle lobe bronchiectasis, I'm usually, you know, the classic thing that's gonna jump out as like, NTM disease.

But also if you have the patient with the right clinical history, you know, whether they have asthma or they have cystic fibrosis, maybe they have some very central bronchiectasis, you're gonna think about things like ABPA.

And if you're studying for the pulmonary boards, maybe you're gonna come across a Mounier Coon syndrome or something a little bit more esoteric.

But I think when, you know, when you are faced with someone with bronchiectasis, thinking about where is it is a really good place to start.

Amazing.

I feel y'all have been definitely have been paying attention over our last few conferences, so appreciate that.

Yeah.

And I think it looks like Luke has pulled up a fabulous, infographic that we can definitely share and we'll just mention to summarize, right, we said upper lobes, we had sarcoidosis, CF, we often think about we've listed radiation TB here, and the central lobes, we have AVPA, some CTDs as mentioned, and then our lower lobes are aspirate duration.

We I think Christina had mentioned, ciliary dysfunction as well, which we think about in our lower lobes and then the immunodeficiencies like CDID in the lower lobes that we had mentioned.

Yeah.

Thank you for that.

That kind of tore through the lungs.

I think, the way that I remember at least the lower lobe things, or it's either something that gravity has dragged down there, like an aspiration or the ciliary dyskinesia is where you just can't clear your airways or there's more perfusion in the lower lobes.

And so that's how I remember that, you know, IBD and RA, I'm I'm sure this is not physiologically how this happens and everywhere rheumatologists just shuddered hearing me talk about this.

But that's how I remember that the stuff with positive serologies often affects the lower lobes.

And so for our patient, here is his CT from this admission.

He has notably progression of his bronchiectasis again, his nodularity, and now with pretty extensive mucus impaction, pretty impressively here in one of these slices.

And so thinking about what you just shared, I wonder about why our patient has bronchiectasis in the first place.

You know, it is possible that it's from his NTM, but that's can be a tricky chicken and egg question.

You know, do they have NTM because of the or did the NTM give them bronchiectasis?

And in our case, I remember that his initial CTE did have some upper lobe bronchiectasis, and so that feels less likely here.

Even though I'm sure it has played a role in his progression over the years, it maybe doesn't feel like, you know, the smoking gun that started things.

He does also have CVID, which could explain things, but like y'all just discussed, that is typically either more diffuse or lower lobe predominant, and so our patient doesn't quite fit that pattern either.

And so, Doreen, I'm sure you have had experiences where you need to go back to the patient and review or rereview a history.

And so I'm curious if there are particular things that you would ask this patient to try to target your testing and workup.

Yeah.

So I think we sometimes get stuck in.

A patient comes to us already with a diagnosis of NTM related bronchiectasis, and then we forget about really looking at all of the other etiologies, and they're doing okay.

And then this is what happens.

They start to fall off the cliff, and we're saying, did I I look back.

Oh my god.

Did I do that work up?

Did I check for their, you know, IGE levels, etcetera, etcetera.

So I do think, you need to go back.

Like you said, take a pause.

You talked a lot about recurrent sinus and, GI issues.

We know that these patients, particularly those with NTM, have a very high percentage of esophageal, dysmotility, and many of them have aspiration, that is asymptomatic.

So we pretty much study everybody who comes in.

But there's really almost no lower lobe disease in this patient, so that's not very high among those.

I like that that CT with that glove like mucus plugging there is making me more worried about, you know, ABPA.

I'm always worried about in patients who aren't responding, not having picked up some genetic disorder for either PCD and even and I'm not a PCD expert, but even genetic screening for PCD misses patients who have milder disease, in into their adult life.

So the new guidelines just came out, actually, I think, two weeks ago with ERS and ATS together, showing that you have to use multiple, exhaled nasal nit nitric oxide.

You can use genetic testing, or if, immunofluorescence, so spectra spectrometry.

So you have to use multiple things in order to be able to pick that up.

So it's being at a center where they can do that is important.

And then CFTR testing is gonna be very important because, we don't typically do that in our NTM patients, and we're finding that there are patients who have CFTR mutations.

So I'm though I'm gonna start thinking about that, making sure I did my room basic serologies, and unlikely, he has no other symptoms, but to test that.

And you said he's getting IVIG supplementation?

Yes, ma'am.

He's still getting that.

So it's unlikely that we're gonna uncover a bigger, immunodeficiency since you've already given him replacement therapy.

So that's where I would start.

Yeah.

Thank you.

And that's that's all really helpful.

In our case, when you go back to ask our patient, he shares that while he does have children, he's a father of two, they were conceived via sperm aspiration and IVF as he has a congenital absence of the vas deferens.

And so history, a nice reminder of how important it is, in our patients.

And that's so it's really important to think about too, Luke.

Right?

Because as I'm seeing this scan, I'm thinking, right, CF until proven otherwise.

I know I'm coming in with my own bias, though.

But, right, going back to the patient and just, right, look, not only physical exam, but really history because, right, as we all say, the patients are gonna tell you what's wrong with them.

So but there's a lot of testing to think about.

You know, during and thank you for kinda going down your review of history.

But then how does that lead us to think about what type of diagnostics we're gonna do?

Right?

There's so many things that we can, try to order, and we wanna be, you know, we wanna be thoughtful, but we also don't wanna send the entire list of things and and, charge a great bill if it's not gonna be clinically relevant for our patients.

So, Rupali, Tom, hoping that you can walk us through, how you know, it could be really overwhelming to think about working up bronchiectasis.

What is a good framework that y'all try to do when when seeing patients in clinic?

Yeah.

Definitely.

And I think, as Doreen has mentioned, we have some guidelines and hopefully some new and upcoming guidelines that can help guide us.

But for what we have right now, we had do have some available ERS and BTS guidelines that help serve as an initial way for us to think about diagnostic work out through these patients.

So when I think about these patients and I'm seeing that clinical syndrome of bronchiectasis, I usually start with a basic workup.

And these are recommended by those ERS BTS bundles.

So the first thing is a CBC with a DIF.

That's to assess for any of those hematologic abnormalities as well as eosinophilia.

The second thing is a quantitative immunoglobulin workup, as we've mentioned, that IgA, IgM, IgG serologies.

That screens for primary or secondary immunodeficiencies, such as CVID as this patient had initially had.

The third thing to think about is ABPA testing.

So that includes a total IgE as well as an Aspergillus specific IgE IgG.

This allows us to test for AVPA as a treatable cause for what this patient might have.

Next is sputum.

I think Nori mentioned the importance of the sputum.

And in terms of sputum cultures, we can order to stand out bacterial cultures, special fungal cultures, as well as AFB stain cultures, which may take more time, but are helpful to have at that first visit, if the patient is able to have, produce that much sputum, and that's to identify chronic pathogens, as we mentioned, guide antimicrobial therapy, as well as detect atypical infections, such as NTM, which we've been discussing.

And then the last thing, which hopefully all our patients have when they're coming to clinic, although in practice, it doesn't always happen, PFTs.

Right?

So we always would like to establish baseline what the patient's lung function is.

So that that's something we can clinically follow over time as well as airflow obstruction can be helpful in sort of confirming some of those bronchiectasis, obstructive like symptoms and allows us to monitor it over time.

And I think starting with those as a baseline bundle is helpful to identify any initial treatable causes for bronchiectasis and reversible things as well that can help our patients.

But, Tom, there are further testing that we can order.

And how can we think about some of that additional testing that we can do?

As has been really, I think, appropriately driven home here, you're going to use your history to guide your additional testing, because a shotgun approach sometimes works, but it's it's better to be targeted and actually think about what your pretest probability is for a condition so that you can better interpret what the test result is when it comes back.

CFTR testing, like Doreen mentioned, sweat chloride testing is the other way we test for cystic fibrosis, particularly if there's a history of upper lobe predominant, bronchiectasis, nasal polyps, chronic rate rhino sinusitis, pancreatitis, infertility, malabsorption problems, all of those are gonna clue us in that, maybe maybe this is all tied together with cystic fibrosis.

I think it's important to remember too that, you know, patients don't like being tested with needles and needle sticks.

Sweat chloride testing does not involve needles, but it does require that you have that test done at a center that is specialized and familiar with doing this testing.

Other things I think about, again, based on history, particularly if there's a family history of liver or lung disease, if there's lots of emphysema in someone who is a never smoker, I'm gonna think about alpha one antitrypsin testing.

In the right context, you'll think about, primary ciliary dyskinesia testing.

That could be genetic.

It could be nasal nitric oxide testing, connective tissue disease serologies.

Doreen mentioned that aspiration and GI pathologies are very common and often missed, so a upper GI evaluation, particularly when the bronchiectasis is lower lobe predominant.

And then when you're going down the road of thinking, does this person have CVID, often you will see patients get pneumococcal vaccination antibodies, and then you assess their response to vaccination, to help you guide your understanding if it's if this person indeed does have CVID and is in need of treatment.

Yeah.

That was great.

Thanks for walking us through that.

I feel like, trying to remember some of the those things, like, why I'm doing the testing and, like, when to think about particular conditions helps me keep this, like, laundry list of potential orders that could be put into an order set, but maybe shouldn't be put into one giant order set straight.

And so on that note, our patient has a battery of tests sent.

His sputum grows MRSA.

He has a specific, IgE testing done for aspergillus that is negative.

His ANA and rheumatoid factor are negative and his immunoglobulins and alpha one antitrypsin testing are unrevealing.

However, on CFTR mutation analysis he is found to have two pathogenic mutations.

He has a F delta five zero eight and then a, and I'm gonna probably butcher this so please don't judge me too hard, Monty, but the thirty one forty twenty six a greater than g mutation, which as I understand it is also pathogenic for cystic fibrosis.

And so clinically, he gets better with a fourteen day course of anti MRSA antibiotics.

He's discharged and started on Trikafta and Dornase, and he's referred to the adult CF clinic for further care.

At follow-up, he has no constitutional symptoms, very mild ongoing cough, and he's back in the gym several times per week with no fevers and night sweats.

Luca, you, that rolled off the tip of your tongue like a like a natural CF doctor.

But yeah.

So I think I mean, I think this is really important.

Right?

We, you know, we CBID, NTM, patients not getting better, maybe some anchoring bias along the way, saw a lot of different positions over over, you know, five, ten years.

But coming up with with the right diagnosis for this patient, I think was really important.

And it's you may be asking, well, starting Trikafta, for those of you who may not have heard Trikafta, it's a CFTR modulator, so a tablet that patients take, three different components that really help restore the genetic defect in CF.

But it's pretty remarkable.

The, you know, patients will start this and within a week or within two weeks, their symptoms, like, almost completely resolved.

Pretty remarkable.

I know that this was, that this patient had the case, you know, a few years ago, and, when he started on Trikafta.

There is a new modulator though now is approved actually between, Christmas and New Year's of this past year.

So the newest modulator is called the Liftrec.

So a lot of patients may be on that.

So you may be see be seeing both Trikafta a LiftTrack in CF patients.

A LiftTrack's once a day medication.

Trikafta's twice a day medication.

But I think it's truly is remarkable how fast and, their symptoms improve, not only subjectively, but objectively as well.

So I I this is exciting, exciting when I see patients who, are on modulators and can and can be helpful.

You're also probably thinking, well, I mean, this patient 60, you know, what am I missing CF in a lot of different patients?

But you can see this is a great example for you to be thinking about it.

You know, we brought up again, like, is something still not fitting?

But he doesn't have Pseudomonas.

But actually now that the current guidelines within CF, MSSA is actually, the most common organism now that's grown in patients with CF followed by Pseudomonas and then followed by MRSA.

That was another teaching point I just wanted to make sure that we came to.

But, Luke, fantastic case.

Thank you for bringing this.

It went through so many, I think, different things.

This is our first time about talking about NTM on Home Peeps, and couldn't be more excited to have, the, OG expert, Doreen, being able to provide some teaching points today.

I know we usually end with a teaching point from the case, but since we're at CHESS, I thought we could just, each say CHESS is such a fantastic organization.

I thought we could each, end with what what are we looking forward to the most at CHESS and, how has this conference been for you so far?

So, Luke, I'll start with you.

That may be an unfair question because you just got here yesterday.

But in your in your the the the twelve hours that you've been here, what has been the best thing for you so far?

So I'll take the best part of Chicago so far and the best part of CHEST maybe separately.

The deep dish pizza we had last night, truly life changing.

I probably don't need to eat for the rest of the week, but that's okay.

In terms of CHEST, I think I really appreciate the conference's focus on medical education, both in terms of education, both in terms of those in attendance, but also in the development of people's skills as educators.

There's some really exciting sessions that are on the docket over the course of the week, with everything from, like, gamification, of learning to some of the more practical logistical steps of building a career as an educator.

So that's, I think, what I'm looking forward to a lot.

I'll say for me, this is my my second time attending CHEST in person.

And I really think especially for any trainees in the room or trainees who might be listening on, you know, asynchronously and wondering, hey.

Should I go to CHEST next year?

It's in Arizona, so it'll be warm this time of year.

But, you know, it CHEST is an incredibly trainee friendly, trainee focused conference.

I'm really grateful to be a member of the trainee work group, which is part of the training and transitions committee.

And through that committee, we've had the opportunity to organize a lot of trainee specific, excellent programming related to the needs of trainees.

You can come to the trainee lounge, throughout the week.

It's a dedicated space for trainees to learn.

We go over things like how to study for the boards, how to negotiate your first contract, how do you how do you find your niche, medical education.

The list goes on and on.

There's a lot of really great stuff in there, and it's also a great opportunity to network.

These are the people that are gonna be our colleagues, coming to CHEST, go into national meetings throughout our career, and CHEST is a great place to meet people.

Yeah.

I totally agree, Tom.

It's also my second time at CHEST this year, and I wanted was fortunate enough to take advantage of the CHESS fellows course last year, and it was a fantastic course for any of our trainees listening, really covers a large gamut of things.

And, Christina and, other people have have taught there, and that's been really excellent.

I also wanted to highlight some of the other awards, trainees can apply for.

I was a fortunate recipient of a CHESS travel grant this year.

That's a wonderful opportunity for any trainees seeking to come to the conference.

And also wanted to know that there are a lot of other opportunities for trainees to be involved.

There are the various networks with, I believe, meetings, ongoing throughout the week as well as the matched mentorship program that I'm a part of this year and really excited, to see where that takes us.

So lots of amazing opportunities, and I've loved the experience here so far.

I feel like we could probably have a whole, separate podcast on what Doreen loves about chess.

But Doreen, any any final words for those that may be here in the room and those that may be listening today about what you love about this organization?

I love everything about CHESTA as you probably could imagine.

But, I think the best thing is that you can go up to anybody that you pass.

You may know them.

You may have, you know, read an article and tell them who you are.

Tell them you wanna get involved, and it will happen.

I really do think, all of the leadership and faculty here are really willing to help you get started, particularly if you know the area that you wanna be in.

I wanna highlight, we usually always have a grant through chest philanthropy on NTM or bronchiectasis every year.

So, we love to give those grants to fellows and junior faculty.

So please apply for the grants.

They come out, usually, announcements around February, every year.

And, don't forget to go to the chess challenge.

It's really a great way to meet people and get to know, everybody at chess.

So, yeah.

Just, immerse yourself in it for three days.

Yes.

So amazing.

I know.

And I think one of my favorite things was was doing the fellows course.

I'm, fortunate to be on the CHESS t and t committee as a faculty member, and everything we do is for trainees.

So we do a lot of programming.

So, again, yeah, definitely, take take advantage of the trainee, training lounge.

I hear there's free coffee for you all.

So, maybe make your way to there right after this.

And as Doreen said,

chess challenge is gonna be tomorrow night, 05:00 reception, is gonna be there, and then the challenge starts at 6PM.

So come on come cheer on.

There's three teams.

The three finalists are coming from Marshall University, University of Buffalo, as well as University of Colorado.

But great, such a great morning to start off, Chess on this Monday morning in Chicago.

This, case was edited or was written by Luke, edited by myself, and our, original music is, by Eric Rogers.

Have a great day, everyone.

And, any any trainees or fellows on the course as well, we love we love working with you.

So email myself, and Dave or come after come up to me afterwards and love to try to collaborate with you.

Thanks, everyone, for your time.