In this podcast recorded by the American Association of Bronchology and Interventional Pulmonology, Gerard J. Criner, MD discusses patient selection for Bronchoscopic Lung Volume Reduction.
Hello everyone and welcome to what promises to be another exciting and educational episode of the podcast. This is your host and podcast editor Utakata. And on this podcast, it is my honor to introduce to all of you. Our new associate podcast editor Abby Navigable. Our topic for today is bronchus, coptic lung volume reduction and our guest is arguably the global leading authority on this topic. Dr Gerard Criner is the chair and professor of thoracic medicine and surgery at Temple University. Dr Criner, thank you so much for joining us. Happy to be here. Thanks for asking me. Before we get started. You have any relevant conflicts of interest to disclose? I was the principal investigator for the pivotal trials for both harmonics, deliberate study as well as for inspiration. Olympus With the improved study and I've um received consulting and travel funds for both Olympus and harmonics for presentations and educational seminars. Perfect. Thank you so much. So, all right, but let's get started. Thank you for the kind introduction and welcome Dr Criner. So we're going to talk about microscopic lung volume reduction today and let me just start off with a brief introduction. Patient selection for lung volume reduction surgery as we know, is limited due to a high postoperative nonfatal pulmonary complications and also a short term mortality of 7.9% At night at the 90 day mark. This is particularly relevant in patients with the lower Phoebe one of less than 20% and homogeneous Emphysema or DLC Oh, less than 20%. The surgical intervention is also largely limited as we know to being performed at centers of excellence in which the surgery could be performed as in those that were part of the net trial broncos capital and volume reduction of Bl VR. Was described in 2000 and three. Has now evolved to encompass various techniques aimed at causing targeted low collapse through in the bronco valves or coils or by bypassing abnormal airways with stents or inducing are targeted love destruction and remodeling through ceilings of thermal of a population. These techniques unfortunately have had available success and require larger and more robust studies before the widespread use can be recommended. So we know that within the last two years to in the bronchial valves that zephyr and the bronchial valve and desperation intra bronchial valve have obtained FDA approval after multiple studies for B. L. V. R. So Dr Crane, I would want to start off by asking you what patients should we be considering for broncos coptic lung volume reduction. Using these in the bronchial valves. A very good question. Um Overall patients that have been maximized on optimal medical therapy and continue to be breathless and have emphysema as a major phenotype of their disease and um have evidence of complete fissures or um fisher assessment by physiologic technique with endoscopy showing that they have no evidence of collateral ventilation. Those people that have those features could be considered. Her bronchus. Ka pik long going reduction with an end of bronchial valve. Some of the physiologic parameters that go along with that. Our patients that have really gold three to gold for severity of airflow obstruction with F. U. B. Ones between 15 to 45% of predicted and have residual volumes that are at least 150% of predicted and higher if patients have homogeneous disease. The only prospective randomized controlled trial that was done with bronchus topic uh lung volume reduction using in the bronco valve was the impact trial. And those patients had a floor of entry criteria of an R. V. Of 200% of predicted One should know that in the pivotal trials itself. The mean residual volumes were 225% of predicted or greater and deliberate study and more than 250% of predicted in the impact studies. So the degrees of hyperinflation in the trials themselves or usually hire the mean data compared to what was seen as far as entry criteria. Then six minute walk distance being in the swath of patients 100 m for a threshold up to 500 m as a ceiling over all. Those are the general ranges of patients that are too sick are too well to be considered for an intervention even though it's minimally invasive and then not being active smokers for at least four months overall. But I think one of the things that consider overall when you consider any type of lung boy reduction procedure, whether it's surgery or bronchus coptic approach regardless of the method is that this cut type of intervention does not significantly improve gas exchange overall the mean improvements in pho to about 2 to 3 tour and I mean reductions in PCO two or 2 to 3 tour. So these procedures should not be used to get patients off supplemental oxygen or decrease severe or moderately severe hyper cappy overall. So it's an adjunctive treatment and patients optimally medically treated the decreased significant air trapping that's due to emphysema and a case of an end of bronco valve. These patients must have structurally intact or physiologically intact fishers to work correctly. Thank you so much for summarizing that. So Well We know that for patients who have official completeness score of 80-95%. Intra procedural confirmation of the absence of collateral ventilation can be done using charters Dr Greiner, what do you do for those patients who have a fisher completeness score of less than 80%. And a second part of that question is what about those patients who have official completeness score Using this modality of greater than 95%. You automatically select those patients for health placement. Yeah, great question. So overall this becomes a very important sort of feature of selection for patients to consider friend of bronco valve treatment. And I think it's important to step back for a second, I realized what we're looking at with cat scans. Looking for structural integrity of the fisher versus physiologic intact. MS of the fissure by using the chartists. So overall with looking at um the computer programs that are being generated those are reports. But really the inspection of fisher completeness is done qualitatively. There's no automatic computational assessment of fisher integrity occurs at this time. This is done by labs by qualitative assessment overall by the vendors that are subcontracted by the companies to look at fisher completeness. So your own eye or your thoracic radiologists. I can help you to complement that. The physiologic uh intact. This of the fissure by the chartists is looking at float across the fissure that you're looking at to treat the patient at the time of assessment and are really somewhat similar but somewhat dissimilar and that one's structural integrity versus physiologic integrity. So you can really um logically conclude from that. Some patients may not have a a fissure that structurally intact but could be official physiologically intact or vice versa that could be present. So what this means from the literature is that if you have a fissure that's less than 80% complete the likelihood of physiologically. Uh and tactics of that fisher is less than 15%. If you have a fisher it's 95% structurally intact By looking at H. R. C. T. The likelihood of that being physiologically intact is going to be 15%. So you have like some indication of the correlation of both of these measures for patients that are very open by fisher and tactics by looking at H. R. C. T. And very complete on the opposite and overall. But they're not always the same. The best patients to treat our patients that have complete fisher shown by H. R. C. T. And physiologically intact. As shown by the chartist. Those patients are much more likely to be intact overall and if you fell with getting volume reduction, those cases it's related to improper selection, replacement of the valve or patients that overall have problems with pleural adhesions that you can't see by H. R. C. T. That's not letting the low come down overall. So you have a good sense of knowing that those lobes should come down with a proper valve placement and if they don't have any pleural adhesions this group in between 80-95% or more problematic. Those patients should not have valves placed by themselves with fisher and tactics by itself at least greater than 90% in those cases. And those who are between 80 to 90% they really need to have a collateral ventilation assessed by a chartist physiologic assessment if they don't exist. The likelihood of treatment effect in those cases is less than 30% overall. So I think this gives us some clue. But one should acknowledge that these data actually are limited in amount overall. These are studies that have looked at retrospective performance of Chartres assessment mainly in patients that had H. R. C. T. And four clinical trials. So I think we need much more data to show exactly the fidelity of either treatment in those cases. Thank you so much for summarizing that. So to your point the patients with both structural integrity of the fisher and physiological integrity would be the best candidates. Perfect patients in the impact trial. As we had talked about homogeneous emphysema. And some in the Stelvio trial had homogeneous emphysema which was defined as Less than 15% difference in emphysema destruction scores between the target and the absa lateral lobes. So can you explain how you go about selecting these patients with homogeneous emphysema for bronchoscopy, clang volume reduction. And what is your opinion on the role of the profusion scan? Yeah that's also a very good question overall. And and as you gave him the kind of like introductions that has questioned the amount of data that we have for bronchus ka pik lung reduction effects in patients with homogeneous disease is minimal number and short on scope for duration of effect. So you remember from the lung volume reduction surgery, the net trial, we had data that went out to seven years for these patients overall physiologic assessment and important pivotal clinical outcomes. The impact study was a three month study and the Stelvio study was a six month study and in the impact study was only 50 patients And I think it is 60 patients in the Stelvio study Only 15 were homogeneous disease. So the numbers of patients from these two pooled studies is low in number and shortened duration. Overall, that being bite said there is significant clinical improvements that you can demonstrate the endpoint of those studies and improving F. E. V. One overall. Now, how durable is it and how how great magnitude is the benefit overall? Well, if you look from any form of a lung reduction procedure, whether that surgery or bronchus ka pik, whether it's valve or steam or coil or glue, the magnitude and duration of the improvement of the decrease in air trapping is not as robust as what you see with heterogeneous disease. And if someone can be a logical conclusion, because patients with homogeneous disease don't really have any significant less impaired tissue, whereas patients with homogeneous disease have diffuse disease overall. So I think one of the important things when you discuss a lung reduction procedure in patients with homogeneous disease is you tell them that the degree of improvement and the magnitude of the improvement that they may see maybe limited overall compared to patients with heterogeneous disease, but maybe better than just optimal medical treatment by itself. So in this patient group, it's very important to choose the lobe that's most affected by the disease and the patient that's most affected by hyper inflation. So it's very key in this patient population homogeneous disease. Even more than Heterogeneous the patients that are most hyper inflated by itself or more likely to respond And that the lobe that should be targeted for treatment for to be the one that's most impaired by a lack of profusion. If the profusion is more than 20% less than the other lobes And the patient is very hyper inflated as I told you before and the impact study those patients had a mean RV 250% of predicted or greater. Those patients are more likely to see a clinical benefit that's going to be meaningful as well is going to be um more durable. So I think it's the key is to look at profusion less than 20% of globe and a patient group that's really affected by hyperinflation for it to be a successful intervention. Dr chrono do you use the spect ct scan at all? Yes. I think you know not everybody has a spect ct to use. Some patients will uh some providers will just have a plane R. C. T. D. U. S. And that can give you a clue as to how the patient will do. That's what we had in the metro overall. And that showed really robust results in using the the profusion scan overlay with the C. T. Scan to show what patients magnitude and duration of treatment will be. But if you have a spec uh C. T. To use or nuclear medicine scan to use which is the overlay of a low dose ct scan. A title ventilation with profusion data that can give you a fidelity down to the low bar level. And that ends up being important for those middle zones that along where you don't know if it's part of the upper lobe or the superior segment of the lower lobes and can tell or the middle lobe over on the right side to be able to tell you what is the most all academic load to check. So I would recommend if you have a spec C. T. Use it. If you don't you can still use a plane our nuclear medicine scan. But you need to keep in the back of your mind. What is the middle low versus superior segment or the lingua versus the spirit segment on the left side? Thank you so much for that. So moving on to how I should be following these patients? So we should be following these patients. Let's say I have a patient who is CV negative and replaced in the bronchial valves and we have seen no reduction In the target lobe during the three days of hospitalization discharge him or her for our patient follow up. How long should I be waiting before I call this? A failure and in case these patients do not achieve target low production. What is your approach? Do you get a ct scan? Do you re bringing them to make sure that the valves have not moved. And when would you consider removing valves and calling them in the bronco valve failure? Yeah, that's actually a question that we did not address into the clinical trials, but in clinical practice is a terrific question. So you can tell the patient what the next steps will be. So we just constructed an abstract and submitted to the 80 S, the 80 S. That actually did not happen. I was looking at the time point or the temporal change in looking at low bar volume reduction by chest x rays that we get daily in our patients overall and measured the amount of volume reduction. And what we reported it is that if you don't usually have it by four days, you're likely not going to get it. Um except for rare circumstances at six weeks or 45 days, you can in about 15% of subjects. But in 80, of subjects, most of what you're gonna see for volume reduction, you're going to see within the 1st 96 hours. And that tends to make sense because that's the height of the time where patients develop a pneumothorax, which is really related to wreak or really related to expansion above which the non targeted gypsy lateral lobe can handle in terms of volume shifts overall. So that tends to make physiologic sense overall. Well in some cases, 15% of the cases thereabouts, the valves were settled over time and you might get further lung reduction. So while we wait is day 45 or about six weeks after the valves are placed. So we can basically see how much targeted low reduction that they have and if they don't have targeted low reduction, it's probably related to one or two factors. One is that the valves are not placed properly or the valves may have shifted or moved over time. And also if the patient has pleural adhesions that you didn't see before, Like I mentioned that even with proper valve places the other thing is we wait that long because with valve or with low bar shifts over time, there might be some valve movement in terms of not only approximate movement but might be related to valve rotations. Then they let some of the sub segments that are really at the area where the bell was placed become not a pacified and really lead to re expansion of the lobe. So we wait to a period of time to develop, settle overall and then decide if we need to replace the valve. How often do we do that? That's about 15% of patients overall. Do we see valve rotation and then we need to do replacement and what do we do for replacement over time at that time? What we might choose depending on what the nature of the valve changes to go more distal and place more valves or you might place a different type of valve especially if there's grant regulation tissue that might have developed, that actually have pushed develop and rotated developed out of time. So at the point of contact with the airway wall is a little bit different. So dr kleiner, you mentioned the pneumothorax and for our audience, you know, usually due to unilateral non targeted lobe expansion, it can occur in these patients with the rate of azaleas up to 30%. In the studies it was anywhere between 2.1 to 33.2%. Dr crane, are you seeing such high rates of pneumothorax in your patient population? Yeah, we've treated about 225 patients within the bronchial valves since commercial approach approval of temple. And you know, we tell patients that it's going to happen. You know, we give them about one in three patients is going to be the quote overall. And we'll see about 20-30% of our patient cohort. I think it's the last That we looked at it and analyzed. It was about 26.6% of the patient population. And we'll see runs of where we'll see no pneumothorax. And in the last four patients, I placed three out of the four patients that developed a pneumothorax overall. So I think it's, you know, in a specific patient overall. That's what one of the challenges is, is being able to predict for that individual patient what their risk of pneumothorax is. And I think the complication is it's really not well defined as yet. Is it related to the degree of volume shift? We tend to see that the patients that have greater success in volume reduction, that those patients have a greater likelihood of a pneumothorax developing and people with less volume change. So patients that have 1.7 liter reduction in residual volume, we see a greater risk of pneumothorax and those with a 700 to 800 ml. Of of uh RV reduction overall, but tissue integrity. The rate of change that depends upon elastic recoil the lung, which you can't really measure is probably a factor and also the number and the degree of adhesions that patients have. So you know, overall it ends up being a range overall. But what we tell patients is that pneumothorax is a necessary consequence of effective treatment and that we prepare every patient to develop a pneumothorax and at every point in time we have a patient that is uh in a location, has prepared to recognize and treat a pneumothorax. So we do imaging four times in the first day that we do um a valve placement and then daily there After all the patients are followed with a chest to cart that's based for needle decompression, down to a pig tail that can be placed or an open thoracotomy at the time of the procedure. And as we uh modify the protocol and liberate study if a patient has more than 50% volume reduction estimated by chest x ray within the 1st 24 hours they get H. R. C. T. To look for early findings of a pneumothorax. Overall that maybe a minimal to to placement overall. So it's a high surveillance, a high threshold that we have for the detection of a pneumothorax in early treatment of that. Thank you so much. That is very helpful in terms of having informed discussion with our patients and for patient safety for most builders are studies the Zephyr and the bronco valves were used for the inspiration into bronco valves were used in the improved reach and ibV trial desperation valves have a size 56 and seven and nine millimeter. While the Zephyr has a four size four BV which covers the every diameters from 4 to 7 millimeters and a size 5.5 V. DV. Which covers the every diameters from 5.5 to 8.5 millimeters, both in the regular and the shorter length. Which is also known as the LP. So doctor coroner, do you have a valve of preference between two And I know this could be a leading question. And is there any specific characteristic of one val versus the other that you personally like? Yeah I appreciate the question and you know being a investigator in both studies overall, I know both products very well and I feel very comfortable in using them for any patient overall um One of the important issues to try to answer this question is, is there any head to head studies that look at one veil versus the other one in terms of um ease of or successive placement and patient outcomes and the short answer to that is no, there is not overall and I doubt that there will ever be for the reason that there really is rarely any head to head comparisons of looking at commercially approved products, whether it's an inhaler or whether it's any type of device including the valve. So I don't think we'll ever see that overall that being said, you know, you've outlined with the valve ranges are but you know, the airway walls also change and if you go more distantly you can put a velvet in any location that you want because obviously the airway size will be smaller and will accommodate any valve dimension. The more difficult issue is will the valbe ultimately placed based on what the nature of the valve is? So, you know that the zephyr valve was one that fits best when it's placed on a karina. So there's not distal movement because there's not distal anchoring and that serves best when you can actually see that distal karina and you could do a partial deployment and place that valve and you know the valves are going to move any further compared it to desperation veil which has distal anchors overall that you can place that. Now. One of the challenges is is when you have more regulated valves where you can't see the distal karina where inspiration valve you don't, since it has distal feet that can anchor the valve, you don't need to place it on the Christina. However, it's more difficult to regulate the expiration valve system into an area where it's around the corner bend that you can't see overall and it may not allow you to place the bill. There's some special techniques that you can use such as breath hold, head rotation, um do it at residual volume, pull the endotracheal tube back to allow to get that degree of flexion that may allow you to accommodate. But with the uh with the zephyr valve system to actually have some j catheters that can allow you to make the bend and do the deployment. So as you can see from what I'm saying, there's pluses and minuses from both devices. Overall there may be better in one circumstance and the other one or when patients like I mentioned before have one valve place that they have an optimal placement that might be related degranulation tissue, then I treat degranulation tissue and I place the opposite valve mainly to see if that will mitigate against further graduation tissue development. But overall I think that both bells could work on almost any circumstances or some nuances that make make one a better option than the other one. But really it's not ever been shown by any evidence based medicine. I think one of the things are these are two great products that have just been FDA approved. Both, both of them could have further modifications to improve their efficacy overall. And that 15-20% of patients that have rotation available or movement of elves to make sure that that's not the case and we get more durable um effectiveness over time. So on that thought, do you have any experience or comments about what advantages some other non valve based technologies to achieve this lung volume reduction may provide. So all of the time that was spent talking so far has been on people, patients that can meet the criteria of no evidence of collateral ventilation, whether it's fisher integrity or lack of collateral ventilation, measured physiologically. That's 30% of the population, 70% of the population with patients with severe hyperinflation from emphysema were not able to treat right now. But these other technologies that have been studied, none of them um FDA approved in the United States, none of them are undergoing current study in the United States. Could address this problem. Such as use of lung coils which are part of a phase two trial now being done in europe right now but not um not approved for use of clinically by the FDA in the US and not undergoing clinical trial in the U. S. Uh thermal ablation which is approved in some parts of the world for treatment of lung reduction could be a viable option because not only is it effective in cV positive or non fisher intact patients but also since it's slower over time it has a less uh rate, incidents of pneumothorax overall. Um same thing for biological lung volume reduction. Its rate of pneumothorax is low and a global technology may allow us to get those more difficult to angle it. A pickle segments of the upper lobe or the lower lobe. And both of them could be used to treat on a segmental, not a low bar fashion. So we could sculpt around the heterogeneity of emphysema. This involvement at the low bar level which we can't achieve within the bronco valve treatment. And then finally, I think one of the things that it's done in europe but not so much in the United States is using lung reduction to sculpt lobes at a low bar level. That's done by walter Vader very well in and uh in Switzerland but not many have adopted that technology outside the US. So I think there's a wide range of bronchus coptic technology needs to be developed using the bronchus scope to address this issue of collateral ventilation patients that we haven't really tapped into yet. And we need to do a lot of work to push that to get that approved in the US and do the research that needs to be done? Thank you. I mean I'm sure you'll be leading some of those trials. Do you envision any of them coming to the United States sooner. We still have a lot of work from that perspective. Well we still have a lot of work. We're pushing pretty hard to get this done. We're looking for some of the trials to be done in the US at least as uh an early study overall because of the high unmet need that occurs. And some of these options, as you well know really patients with diffuse disease who have collateral or heterogeneous disease for collateral ventilation positive, who aren't candidates for lung transplantation is really an extreme unmet need at this time. Thank you so much. This has been great and I'm sure this will be very helpful for our listeners and as informative as it has been for us. Any closing comments, Dr Criner Now it's a dynamic field. It's I think one thing is bronchus topic, lung reduction is really the thing that I think will drive to the forefront the advantages that interventional pulmonologist brings the therapeutic applications for patients with a variety of lung diseases, not only asthma, but now emphysema and different forms of emphysema and hopefully uh chronic bronchitis and lung cancer treatment in the future in the future. Thank you so much. Dr granados has been fantastic. We've totally enjoyed hosting this. Uh thanks for the privilege of representing. 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