EDAC and TBM Diagnosing and Treating Airway Collapse Diseases

Podcast Transcript

Raed Dweik, MD:

Hello, and welcome to the Respiratory Exchange Podcast. I'm Raed Dweik, chairman of the Respiratory Institute at Cleveland Clinic. This podcast series of short, digestible episodes is intended for healthcare providers and covers topics related to respiratory health and disease.

My colleagues and I will be interviewing experts about timely and timeless topics in the areas of pulmonary, critical care, sleep, infectious disease, and related disciplines. We will share information that will help you take better care of your patients today, as well as the patients of tomorrow. I hope you enjoy today's episode.

Dan Culver, DO:

Hi, my name is Dan Culver. I'm the chair of the Department of Pulmonary Medicine at Cleveland Clinic. Welcome to another episode of Respiratory Exchange. I have with me today Dr. Tom Gildea. Dr. Gildea is the section head of Interventional Pulmonary and Bronchoscopy, as well as the Innovations Lead for the Respiratory Institute. Welcome Dr. Gildea.

Tom Gildea, MD:

Thank you, Dan.

Dan Culver, DO:

Today, we're going to talk about something that many of us didn't learn about too much in medical school, excessive dynamic airways collapse, which is really part of an umbrella of collapse of the large airways. We all remember tracheobronchomalacia, but excessive dynamic airways collapse, which I won't say anymore. I'm going to call it EDAC, is something that is relatively newly recognized. And we now have a program here at Cleveland Clinic focusing on these entities led by Dr. Gildea. So we're here to talk more and learn about where we are with it. Welcome, Tom.

Tom Gildea, MD:

Thank you, Dan.

Dan Culver, DO:

So we all remember tracheobronchomalacia, collapsing of the airways. What's the difference between EDAC and TBM?

Tom Gildea, MD:

That's a great question. And it turns out that anytime you have to change the definitions of words and definitions of diseases, you know that we have a problem. The general gist is that tracheobronchomalacia, as a term, is really focused on the destruction or failure of the tracheal cartilages. And so the structural integrity of the airway is lost because of the anterior support structures are failing.

Excessive dynamic airway collapse, on the other hand, would presume that the cartilages are intact, but there is a hypermobility or collapsing segments of the posterior wall that cause obstructive symptoms. And so we clump them all together now with several other diseases that cause expiratory or even focal obstructive symptoms under the category of excessive central airway collapse.

So there are two parts of the same puzzle in terms of diseases that cause dynamic airway problems and symptoms, but we think of them as a larger cluster of diseases that we manage in similar ways.

Dan Culver, DO:

So you manage these in collaboration with ENT colleagues and thoracic surgery colleagues as part of the Center for Major Airways Disease?

Tom Gildea, MD:

In fact, most of the management is done just by pulmonologists because it falls under the category of people who have diseases related to COPD or asthma or cough where this is just a subcomponent of a much larger problem.

Dan Culver, DO:

So talk to me a little bit about the presentation and overlaps with small airways disease. I bet you've never seen a patient with one of these syndromes that didn't have a diagnosis of COPD or asthma.

Tom Gildea, MD:

Yeah. In fact, there are so many other diseases that overlap with this. It becomes one of the biggest challenges to sorting this out and that, frankly, you have to be thinking about it to look for it. So, in general, we're looking for patients who have symptoms that seem to be more pronounced than what would be expected for their level of disease that you would see clinically. So they're more dysthymic or they have a cough that is something that they can't clear secretions or an intractable cough. And some patients, it's dyspnea that's out of proportion to their symptoms. And other folks, it's problems with recurrent infections where they just can't seem to get better.

And so anytime that there is a challenge where the disease seems to be discordant from the pulmonary function or from the general management, it's time to start thinking about this particularly being a problem underneath.

Dan Culver, DO:

So when patients have small airways disease like asthma and COPD, the physiology is such that there's wider swings in the intrapleural pressure, and that leads to more stress on the larger airways as well.

Tom Gildea, MD:

Yes.

Dan Culver, DO:

So do you ever see this without patients who have underlying asthma or COPD, or is it just misdiagnosed asthma and COPD?

Tom Gildea, MD:

It can be both frankly. There are patients in some studies up to 20% or more patients have completely normal PFTs. And so you could argue that perhaps that is small airway disease that has not yet shown its way to be abnormal in the PFTs or could just be a central disease all by itself where there is a mixture of just malacia syndrome or something along the line of a posterior airway membranous problem. Again, some of the diseases in this category are things like relapsing polychondritis, Ehlers-Danlos where they may not have peripheral lung disease, but it may be co-existent with central airway or peripheral airway disease.

Dan Culver, DO:

Right. We think a lot about malacia either due to trauma to the cartilage, ischemia to the cartilage or connective tissue disease. But that's not necessarily the main risk factors or the pathogenesis of what we call EDAC. Is that right?

Tom Gildea, MD:

That's correct. Yeah. EDAC is a separate grouping within there, and that's really in some people's minds purely physiologic, but there's probably also some focal issues within the posterior airway itself. There are some pathologic studies that have shown that in patients with EDAC. There's complete loss of elastin in the posterior membrane as well as a whole lot of other inflammatory markers seen in some of these conditions.

Dan Culver, DO:

Is that due to inhaled steroids or is that just because patients get treated with that so it's a confounder?

Tom Gildea, MD:

It's a confounder, nobody knows for sure, but there are papers mechanistically written about the possible impact of inhaled corticosteroids on cartilage or the posterior airway muscle. There's an ischemic component. There seems to be a problem with smooth muscle atrophy that occurs in the context of inhaled corticosteroids. So it's kind of a chicken and egg phenomena, you can't quite separate them based on what we know so far.

Dan Culver, DO:

And is obesity and the changes that brings into the physiology of the large airways a main contributor? Do you see this getting better, for example, after weight loss surgery or other major weight loss?

Tom Gildea, MD:

Yes. So it is not only a primary problem where super obese patients with very high BMIs can have mediastinal fat that contributes to the airways, but it also becomes a sort of a second hit phenomena. So as you mentioned with increasing intrathoracic pressures related to, say, a primary lung disease add to it mediastinal pressure from the obesity, both contribute to the physiologic phenomena that we see.

As noted, you say that when patients do lose significant weight, you can get better. Conversely also, Dr. [Atul] Mehta has published a paper in Transplant, patients who had EDAC going into transplant after the lung has been replaced, it has been resolved. So both of those are true. They're components to the same problem. It's kind of like a two-hit phenomena with obesity. And certainly, obesity management will contribute to the improvement of these patients.

Dan Culver, DO:

So this is really bringing it all back to physiology and medical school and the pulmonary and extra pulmonary contributors to intrapleural pressure during the phases of respiration and how that impacts this mobile part of the trachea which is the posterior wall.

Tom Gildea, MD:

Yes, that's true. And in fact, what the challenge for these diseases is that it goes above and beyond. So not only is there a physiologic component to these factors where the central airway becomes the choke point. But when it goes beyond that where it becomes a disease itself is the challenge. And these patients do occasionally benefit from airway stabilization in and above the physiologic components that led to this problem.

Dan Culver, DO:

So if somebody suspects EDAC or even malacia, talk to me about how do you suspect the diagnosis. What's the initial evaluation? And then how do you confirm it. I know that quite often, we look at flow volume loops. Sometimes, we look at tracheal CTs with reconstructions during the phases of breathing. And sometimes, you even have to do a bronchoscopy. And I think there are some thresholds. So how should a general practicing physician approach either suspecting it or confirming it?

Tom Gildea, MD:

So as you point out, the first thing is to suspect it. So patients who do not seem to be doing as well as they should for what you're treating them for, that's usually the first clue. You can see some hints of it in the, in the peak flow as you mentioned. Again, 21% of patients have normal peak flows and normal spirometry. But you can see some problems in there where you can see a decrease in the peak expiratory flow with some coving. You can see some fluttering in there in severe cases.

You can see restriction. You can see all sorts of different patterns. But if you start to sense anything there that is unexpected, you could look to the next step. Really, it comes down to the dynamic CT scan, so you can see it sometimes in free breathing CT scans in severe disease. But the best sort of non-invasive assessment is a what we call dynamic CT which is really just an inspiratory and expiratory CT where we can look at the central airway. And there are some calculations where you can measure how much airway volume change and how much movement of the posterior airway can be seen.

Traditionally, it used to be described as a 50% collapse. Right now, we don't really think of this problematically until you get into the 70% or higher level. But really, the CT is not the pace to measure that so much all by itself, but it is a great place to start to see at least the sense of it. And you could also get a sense of the morphology from there and look at other diseases where you can, you know, get a handle on this being particularly a problem.

As you mentioned, the bronchoscopy sort of is still the gold standard. We do a dedicated bronchoscopy with a patient under absolute minimal sedation with a very small bronchoscope. And the intent here is to try to do a series of forced expiratory maneuvers to see if we could identify not only the segments or where the abnormality is, but also the extent of it and see if it extends beyond the central airway and the peripheral airways.

In that same procedure, we can do some airway biopsies. We can do a BAL or some cultures. And then, if we do find significant disease, we can do a CPAP titration to see if we can find a pressure at which we can reduce that, that collapse to some degree.

So, the bronchoscopy is the mainstay of assessment, but we do have some mobility there to also stage and grade it. There's some classification systems. And then from there, we can go on to what the rest of the evaluation may be.

Dan Culver, DO:

This sounds like a complex business for interventional pulmonary. If you come back to somebody like me who doesn't do that sort of thing, the question I would have is with a reassuring CT scan, can I just stop?

Tom Gildea, MD:

Short answer is no. Patients, just like in a bronchoscopy, if you can't get the breathing mechanism just right, there is technique involved, certainly the CT has to be done in a place that does this study well. There is some technique to it. So in and of itself, it is not a perfect test, a CT alone. It's a good screening test if you are suspicious and you see it, that moves the ball. However, if it's something you're still not sure about, the bronchoscopy is the gold standard.

Dan Culver, DO:

And do you find that other kinds of physiologic testing is helpful? I'm thinking about some patients I've seen where MVV is markedly reduced, maximal voluntary ventilation, or even some patients who have had CPAP at times, sometimes, that's been helpful to pick this up. Has that been useful?

Tom Gildea, MD:

Not in and of itself. Again, sensitivity and specificity of these tests are not so clear for this particular phenomena. But if you do see abnormalities that are unexplainable, you should be thinking or at least you can be thinking about the central airways at least some component of that. It's helpful to sort of see that perhaps those abnormalities are indicative of another problem that is not as easily identified.

Dan Culver, DO:

Gotcha. We've thought about malacia a lot of times, and there are a number of ways to approach that. When we think about something that's more a pure EDAC, is this typically a fairly focal phenomenon or does this usually involve the trachea, the mainstem bronchi, even the segmental bronchi? And, and does that matter for how you approach it?

Tom Gildea, MD:

So it can affect all the above. It really can affect starting at the cricoid cartilage and all the way down into the lower and segmental airways. We do have a grading system where we look to see if it is focal or if it is multifocal or is it global. Certainly, the findings of it in multiple locations tells us that sort of a central airway approach only is not gonna be sufficient if you see the disease in other places, and you have to think about the things we mentioned before obesity, other diseases, a severe peripheral lung disease, stuff that, that is not simply managed just with the central airway but with global management.

So yeah. We do look to see if it's in more than one place, and that weighs into severity. There are a couple of different rating systems. There was one just published a few months ago that looked at multiple segments mixed with severity can be more indicative of than just one severe segment in one airway. So it's still evolving science, uh, to understand these things. But it is true that there's variants.

Dan Culver, DO:

So you mentioned earlier that when you see this, one of the first things you do is a trial of CPAP. And I suppose that some people can just stop there. So how well does CPAP work, and how do you do the titration?

Tom Gildea, MD:

So it's a great question. So in addition to all the other things that we sorta do with the low-hanging fruit, managing obesity, doing the best you can with the asthma, COPD, looking for vocal cord dysfunction, reflux disease, we'll talk about that a little differently. But CPAP titration in this context, it seems to help a lot of people. There's not a lot of great outcomes data with regard to exactly how they improve. But the process of doing some component of pneumatic splinting does seem to improve symptoms significantly.

For some people, that's all that is necessary. So when the mild to moderate reforms of the disease, that's really all that's necessary. In fact, some people just need it as needed. So in the context of, say, an exacerbation where the disease is bad or if they're having an illness where they're flared up, it does seem to have value.

There are a number of papers that describe how you do this. Some of them really just simply pick a pressure and see how patients feel. In the bronch suite, we have the ability to titrate by ramping up the inspiratory pressures or putting a CPAP mask on the patient. And we look to see if we can see a pressure at which there's a 50% reduction in the floppiness as it were.

And in those cases we would simply prescribe CPAP to be used at nighttime and as needed during the daytime to ameliorate the symptoms. Again, a lot of patients do well with that as primary therapy or at least I should say secondary therapy in addition to what they're already getting. And it can be very effective at some patients.

Dan Culver, DO:

I've always thought that some of the people who describe coughing so badly that they're unable to ventilate are ones who are really having EDAC rather than other problems. Is that something that you've also observed in your practice?

Tom Gildea, MD:

Yeah. There are phenotypes, to be sure. And I'm starting to learn a little bit more about all the different phenotypes. The cough variant phenotype, I think, is one of the most challenging frankly because if the cough and the nature of the chronic cough is driving the disease, and so there are some theories that the severity and hackingness of the cough is causing the loss of elastin and, and almost basically permanent trachea failure.

Those patients are very difficult. So if you can support the airway, you can then sometimes improve the dyspnea, but you can't always fix the cough. And in fact, when you hear these patients, they have a very characteristic cough. It's called seal-barking cough. It's this sort of grunty low level rumble when the airway is going on. And that seems to be a much more severe end-stage form of the disease. But the cough variant patients are very difficult particularly because the cough itself may be driving this and not necessarily underneath and the cause of it.

Dan Culver, DO:

So CPAP can really help for patients with mild to moderate disease and perhaps for most people, that should be the initial therapeutic trial. There will then be some people who just don't get enough benefit and who perhaps have exacerbations of symptoms. Maybe, they get hospitalized periodically or show up in the ED or come back to the clinic with ongoing symptoms. And that may be really when you're thinking about some other sorts of modalities.

One of the things that I've really taken from many exposures I've had to bronchoscopy is to be very cautious about the idea of stent placement. And it makes me remember the cardiology practice of stenting lesions. So I thought you might get into an oculomalacic reflex here. And I suppose we wanna avoid that.

Tom Gildea, MD:

Yeah, that's true. Stents as much as I am a proponent of stents, they are really a last ditch option. So, we talk about this in two different forms and two different steps really. The first is if you find severe disease and severe disease is defined currently as patients with more than 90% collapse in more than one segment typically, is when you start thinking about the possibility of surgical stabilization.

For those patients, we can sort of break them into folks who have a response to a stent trial. So there are some controversies about what stent to use and in what duration, et cetera. But for the most part, there are papers that say that if you put a stent in and you can show demonstrable subjective and objective improvement by several measures, then, those patients may be good candidates for surgical stabilization, and that would be a trickier bronchoplasty. These days, it's done robotically, and we can talk about that in more detail.

For patients who are not surgical candidates and are very symptomatic, you can use a stent as destination therapy. And in that context, there are some papers that say that long-term stenting is basically a challenge. It's a problem, and it will always be. And so, you have to choose those patients very carefully, full well aware that the stents are gonna be long-term maintenance problems. Stents have complications. Forty to 100% of stents are gonna have some complications. And so, you just have to go into that very wide-eyed with what that looks like.

The patients in the stent trials, they can be very short just a few days, or they can be up to two weeks. You know, there are studies using metal stents that you can place pretty much at the time of the bronchoscopy, and they have to be removed within a few weeks before they begin to granulate. You can use silicone stenting, put those in pretty quickly. They can mucus plug. So you have to be careful of that.

So again, how you do that and, and how you do the stent trial is kind of center dependent and depending on the patient. But of those patients, 60 to 80% of patients who do undergo a stent trial have improvements, demonstrable improvement. And those are the patients in whom we select for surgical or long-term therapy.

Dan Culver, DO:

So the trachea bronchoplasty, tell me a little bit more about that. How morbid of a surgery is that? I imagine that if it's a longer segment of the airway, that there's higher stakes and it's more challenging. And just maybe describe a little bit about what's exactly done to the trachea during that surgery.

Tom Gildea, MD:

Sure. Dr. [Sudish] Murthy is the surgeon that does it here, and he can go into a lot of details in the technical parts. It used to be done with a thoracotomy, and we'd go in or the surgeons would go in, and they would take mesh and then sew it to the back of the airway. They would treat everything that they could reach from the intrathoracic trachea down into the bronchus intermedius. So that would be the... It's basically treat all of the central airway if possible.

They don't do that anymore, mostly... Or at least we don't do it anymore here because the morbidity is what's quite high. There was a 1% mortality. There was 40 to 50% morbidity associated with long-term hospital stays, chest infections, tracheostomy, you know, all sorts of problems with respiratory failure. So it was a good surgery that 80% of the patients who got it and did well did very well. But there was quite a bit of mortality, or I should say morbidity associated with that particular surgery, and patients who are in the hospital for about a week because of the nature of the surgery.

The new surgery now was pioneered by a physician, Dr. Lazaro. And I think he's in New York and New Jersey now. And that's done robotically. So it's the same concept. You do a robotically-assisted minimally invasive surgery, and you stitch the mesh to the back of the airway in all the same locations. That seems to have significantly reduced hospitalization down to about three days.

Morbidity is pretty much zero in the very first trials -- very small, small trials. And the long-term outcomes look pretty good. So it's a much better surgery from an overall morbidity in that the early data seems to be positive. So it's still early.

Dan Culver, DO:

Is it a widespread procedure? Are there very many centers that can do it?

Tom Gildea, MD:

Very, very few, in fact. There are a number of centers around the country, large centers that do this. There seems to be movement toward more of the robotic procedure as opposed to the thoracotomy procedure because of the operative times. But it's still pretty fancy. It's still pretty high end, and it does take some significant skill to do it well. So I don't know exactly how many. But certainly, it is a higher end, more complex procedure.

Dan Culver, DO:

So you've started a program for you and some of your colleagues really focusing on these issues of airways collapse, whether malacia or EDAC. Tell me a little bit about how a program like that provides value. And what's the structure like for a patient?

Tom Gildea, MD:

Our program basically exists at the juncture of all the other pulmonary sections, frankly. So we do know this exists in asthma. It's COPD. It can happen in a whole lot of other lung diseases. So if someone suspects this or they happen to pick something up on a CT scan, we're happy to get involved with the patient's care to try to figure it out.

At the end of the day, we have the ability to perform the bronchoscopy and do the stent trial and go down that pathway. But in the early phase, it's really just a matter of focusing on this problem and trying to determine whether or not it is a driver of the symptoms or it is not a driver of the symptoms. And so, we sort of have an algorithmic sort of structured approach to looking at these patients, which includes looking at the, you know, vocal cords, doing a good assessment for the reflux, talking about the obesity management of these patients, referring them on to the bariatric medicine. There's lots of stuff going on in that world, calling in the other colleagues related to, say, asthma care or the COPD group or something to see if we can make sure that all of the things that are low-hanging fruit can be addressed within our group.

And as they progress down the pathway toward the bronchoscopy, we often pick up things that are, you know, low-hanging fruit and fixes. By the time we get to the bronchoscopy, we've pretty much figured out that probably there is something there. Now, it's just a matter of gradation and to decide if they're gonna be moving on toward advanced therapy or not. And if they don't end up on advanced therapy, meaning they're not heading towards surgery or stenting, then we work with the physicians that refer to them to us and we help manage them longitudinally with sort of CPAP management, helping arrange that. Sometimes, that's difficult, and sort of just working through what it takes to take care of these patients in the long run as they have exacerbations of flare-ups of their disease.

In the program, if they are advancing down toward the bronchoscopy and stent trial, then we'll sort of take over their care at that point to make sure that that phase of their care is managed. And we just make sure that the patients get through that system. And then, we, you know, put them on pathways of treatment, be it CPAP and standard management of their underlying comorbidities or if they move down the surgical pathway or long-term stenting pathway, we'll basically take care of them in that phase.

Dan Culver, DO:

So it sounds like there's a pretty comprehensive approach. There's a lot of things to offer, sometimes not the majority. But in some cases, you end up with an airway stent in place. And I wonder, as a last question, if you can just share a little bit about the experience here with stents. What sort of stents, what's the durability of those, how's the complication rate been? And you have a 3D-printed stent that you've developed and invented, in fact. Is something like that part of the algorithm here?

Tom Gildea, MD:

It is. And, you know, full disclosure, as the inventor, I do have a possible equity stake in this company if it ever goes anywhere. So, yes, I am the inventor and there is a potential conflict of interest. So I'll say that openly. We do use this stent in our stent trial. We use it because we find that it matches exactly what the surgical zone would be. So we can design, de novo exactly where the treatment area should be.

So again, if the surgery covers the intrathoracic trachea, the entire left main stem, and then down to at least the right main stem, we can design a stent that actually perfectly fits that. And for the patients in whom we're gonna do this, that's exactly what we do. We would design the stent that would match the surgical treatment.

And in that context, that gives us, we believe, the best assessment of whether or not they're gonna have stabilization. This hasn't been proved in an open trials yet, but it is certainly on the horizon and then stuff we're thinking about actively with some other centers. We also use these stents because, you know, in our post-experience and with some of the studies we've written before, it is very well tolerated for the most part.

The timing is short that we're not expecting significant granulation, although do we do see some. The biggest challenge is mucus plugging. It happens to 40% of the patients around, maybe a little bit more depending on what symptoms they have. If they're a big mucus producer, you see a bit more often. It's challenging in the cough variant patients. They cough hard with or without the stent. So it's difficult in those patients.

And so, that's the general approach to stenting in these patients. As a long-term option, again, if they tolerate the stent and they're never gonna be a surgical candidate, then, sometimes it is a destination therapy, again, with the idea that all the stents are gonna require management. They're all gonna have granulation tissue. They're all gonna have some mucus plugging.

With the 3D printed stent, the VisionAir stent, it's less common. We see a whole lot less granulation tissue, a whole lot less mucus plugging, but it, but it still exists. It's just something you have to manage.

Dan Culver, DO:

Well, a lot's going on there, and certainly good job security for all of you by reworking the acronyms and coming up-

Tom Gildea, MD:

(laughs)

Dan Culver, DO:

... with new terminology and things for us to learn about. So that's exciting. Any parting thoughts about tracheobronchomalacia or EDAC? Anything else that you think we missed today?

Tom Gildea, MD:

I don't know if we missed it. I mean, you know, we're learning a lot. If you just look at populations and how common this is, you know, depending on how you define it, it's 5 to 10% of the normal population has malacia. You can question whether or not that's even real. I should say they have EDAC. So you could question whether that's real. It's up to 37% of patients with COPD. So you wonder, "You know, is it something really worth treating? Is that really the barrier?"

We find it in 25% of patients with just bronchoscopy for other reasons. So it's a very common phenomena. I understand the controversy here and that trying to figure out in whom the stent is best used. And so, we have to be very, very circumspect in what we're doing. That's a very common phenomena. We're not so sure it's always purely physiologic or it's disease.

And so, we're learning. We're trying very hard to not intro- instrument these people. But just being aware of it, I think, is the key. And I think the beauty of this podcast is to sort of say, "Think about these patients. They're very interesting. They're complicated." And sometimes, we have ways to help them.

Dan Culver, DO:

Well, that's wonderful. We'll leave this today on awareness and circumspection. I think that's a good way to wrap up. I wanna thank you for visiting with us today, Tom. And it's been my pleasure to host this episode of Respiratory Exchange. Thank you all for joining.

Tom Gildea, MD:

Thank you, Dan.

Raed Dweik:

Thank you for listening to this episode of the Respiratory Exchange Podcast. For more stories and information from the Cleveland Clinic Respiratory Institute, you can follow me on Twitter @RaedDweikMD.