Presented by Jonathan M. Bock, MD, FACS, Medical College of Wisconsin, Milwaukee, WI.
good afternoon, everybody, and welcome to another in the series of diverse Attack Healthcare's Webinars. I'm very happy to introduce today that the Jonathan Bach, MD. Fellow American College of Surgeons who is an associate professor in the division of Lauren geology and professional voice in the Department of Otolaryngology and Communication Sciences at the Medical College of Wisconsin in Milwaukee, Wisconsin. He also serves a ZA consultant, otolaryngologist for the Children's Hospital, Wisconsin, and the Clement JSA Blocky Veterans Administration Hospital in Milwaukee, Wisconsin. Um, I could go through quite a bit of Dr Box Bio, and I'm sure he may mention a couple of these things during his talk. But I don't want to take too much time away from this excellent conversation today about LPR. So with that, I'd like to turn it over to Dr Bach. Thank you. Still, can you guys hear me? Okay. I've seen good signal there on my microphone. I'm assuming you can hear me. Let me know if there's any problems. Eso Thank you. Once again, stew, I'm Dr Jonathan Bacchus. He said I'm here in Milwaukee, Wisconsin, and I'm speaking you from my office here, Just finishing clinic this afternoon. actually talked to a couple of patients just this afternoon about LPR. So this is a very, um, controversial and hot topic in our specialty. And I know that having spoken with my G i colleagues here in Milwaukee, we see a ton of patients together with them to try to figure out how to help these patients. I do have a couple disclosures to make to you. One is that I am, ah, paid speaker and consultant for diverse a tech three other is that I'm gonna be showing you some research data here. That's on some ongoing research products that we have here at the medical college. And these are being funded by the, um but I'm not speaking on their behalf. Eso The objectives of this talk today are to describe the current state, as I would describe it, of LPR diagnosis and treatment, the modern LPR testing options that we have and the pros and cons of all those. And then I want to speak at length about the role for dual Ph impedance testing in order their ideology and then, lastly, kind of as a Larry oncologist and someone that takes care of a lot of throat complaints and symptoms. How I approach treatment of the patient with quote LPR symptoms. So this is a really great quote that came out from my friend Dr Francis and his group at Vanderbilt. Uh, Dave is actually recently moved over to University Wisconsin Madison here, but he trained at Vanderbilt University and they're learning geology department and then stayed on a spatula there for some time, where he worked with Mike Daisey. Many of you guys may know the Doctor visit is a very of smart area that speaker on reflux topics, But they have this quote from a review article that they wrote about LPR last year. I wanted to read this year to date. Now, the clinical trials and comparative observational studies have been able to demonstrate a strong dose response relationship between reflux and voice disorders. There's no proof of temporal ality and that reflux proceeds hoarseness or throat issues. There's no consistent treatment, effects or strength of association between anti reflux treatment and improved voicing among patients with presumed letting go Frenzel reflux and no note the word presumed there nonetheless. Ah, relationship does exist between LPR and voice, and it deserves careful consideration. The strength and nature of that association remain unclear. This is from 2016, and the thing that is most challenging about this is that we do know that there are patients that respond and improve to reflux treatment when they have the panoply of vague, reflux related symptoms. The Fantastic Four, as it were, of reflux symptoms in the throat, those being hoarseness, throat clearing, cough and global's. I see tons of patients with these concerns, and we're constantly trying to figure out whether or not they're related to actual anatomical issues or whether they're reflux. This algorithm here was published by Dr Chuck Ford, who's a friend. He also is just down the street at UW Madison and Charlie Ford. It was the chairman at UW Madison for many years. This article was published in 2005. You see that on the bottom there? This is the journal American Medical Association, and what they described here was an algorithm to treat patients with LPR. This became widely popularized in the otolaryngology literature and really became one of the main approaches by which patients were treated and you notice the top. You see a patient with possible LPR. We're using the reflux symptoms in next, which is a quality of life type survey and the reflux finding score, which is based on Larry Endoscopy scores to diagnosis. And then, based on that, we immediately would recommend if they were over 13 and seven on those which I could go into more detail about those later on if we need to. In any case, if they scored more than that and they had symptoms that were consistent without obvious other physical findings, thes patients were placed on empirical B I. D p p I trials that could go on for a very, very long time. And then we they recommend here in this talk Ah, three month follow up assessment. The problem, of course, as many of you in the audience may know, and I know from my own practice we see patients that have been put on PP ice for these circumstances and stay on them forever. And there's never been any offers. Objective testing to see whether or not they really do have reflects whether this was entirely a placebo effect or whether they would even be a candidate for funding application procedures or other things that could stop there reflects from happening. So I wanted to also mention the hoarseness guidelines. This is from the American Academy of Otolaryngology had next surgery. I got a few friends that are on this list over here, and I've spoken with many of them at length. This initially came out in 2000 and nine, and there was quite a bit of controversy about this because they mentioned that there was a statement that they could consider as an option anti reflux medication treatment for chronic laryngitis without any obvious evidence beforehand to prove that there was reflux in place again. This was support for possible long term imperial treatment protocols, and we found in our practice and many others and my colleagues around the country that this idea of giving these long PP I trials without proving that there is direct evidence of reflux can sometimes be a detriment to the patient. I want to stay show here, though they do say there's a substantial role for shared decision making these patients and what we have found in our practice is that if we offer these patients objective testing for reflux early on in this discussion, many of them will choose to pursue that. We find the data to be useful and interesting. One last thing that came out off this opinion article in JAMA surgery Regarding the use of PPE, ice and reflux treatment studies have shown that the important aspects of the diagnosis and treatment of chronic cough specifically and reflects of unknown to origin, and many of these patients have abnormal proximal reflects of gastric contents. If you test them, you can see this is where patients that have no long ideology, they're not on Ace's inhibitors. They're not smokers, and they have chronic cough for many of these patients cough maybe their primary symptoms. But they do not have typical symptoms of GERD. Therefore, testing for reflux and these patients maybe a paramount importance. And then they make some very strong statements in this opinion article that conventional pH testing may fail to detect proximal extensive reflux when it's weakly acidic or not acidic. This would also include things such as Bravo testing, which are really only looking at the lower esophageal sphincter area and not assessing whether there's abnormal amounts of reflux, that air coming up into the throat. Many of the patients that I evaluate for these issues here in Milwaukee will have normal Bravo studies because they have normal physiologic amounts of reflux. But when you include differential probe testing as part of the dual ph. Impedance it array, you can see that most of the events that are happening, even though there's a normal number of them, are going up into the pharynx. Once that cause and effect relationship between reflux and respiratory symptoms such as cough has been established, the Onley good treatment for these patients may be anti reflux surgery because the majority of the events that they're having by the time they get to the proximal sensors are non acidic. This is our reflux symptom index. Uh, this is the questions that we asked to try toe determine whether patients have reflux. This has been shown in many studies to correlate well with reflux testing. In fact, it's even been shown in our patients. We've looked at this ourselves, and we've seen positive pH probe studies. There is good statistically, a significant association of patients having elevated reflects symptomatic next scores and ph positive impede studies. The things that's concerning here, though, is if you look at this. Hoarseness clearing your throat, excessive mucus, some coughing after you know, lying down breathing difficulties. Cough here, since they sensation of something sticking a global sensation. Many of these have overlaps with traditional allergy symptoms. So what we find in our practice is that a lot of these patients can have allergies and have very highly elevated RSC when they really don't have reflux. Excuse me, the reflux finding score but also published around the same time in the early two thousands. This is something where we can put a scope in the nose. We take a look at the lengths, and we're looking for these different parameters here. If a patient scores mawr than a seven on this, it's supposed to be suggestive of reflux. Unfortunately, there's been many, many studies that have been done that show that this reflux finding score may not really be very good at predicting reflux. And in fact, this may be one of the things that has been to the detriment of the otolaryngology community at large. Many of my colleagues around the country diagnosis reflux based on the fact that the original it took a little bit red. There's a little bit of a Dema underneath the vocal chords. Uh, maybe a small amount of regulation in the post cried coId segment and they will say, Well, that's obviously reflects we need to treat with the I D p. P. I s What we found with our studies as well as many other colleagues around the country now have shown that not only is this a poor predictor of positive pH probes on reflux testing, it's also not a very positive predictor of response to treatment. And there's very poor intra and inter rater reliability for the studies. You can take the same blinded pictures, show them to the same person at different times, and they will rank them differently. So there's a lot of gray area. Or maybe I should say pink area regarding the amount of red nous that's going on between normal and abnormal. The thing that I say to my patients when we have this discussion about looking at their larynx and telling them if they have reflux is that that is way more art than science. One of the last caveat that many of you in the community may already know there are obviously increasing risks that are being associated with P. P. I use I know my own clinic. I'm finding more and more that patients, especially younger patients, are pretty ambivalent about going on toe heartburn medications. And we were seeing in the literature continuously developing new concerns with long term PP. I use BA 12 deficiency hospital acquired pneumonia, malabsorption syndromes, electrolyte abnormalities. There's actually 70% increase in coronary events that we think may be due to interactions with warfarin and Plavix. Chronic kidney disease farmer can academic farmer called dynamic interactions between clopidogrel, warfarin, Fenton, hyper gastronomy, a etcetera, etcetera, etcetera. So the list goes on and on. There are reasons then you consider not putting patients on PP I if we think that it's not going to help them. One of the other concerns that we have with P p I is that my community colleagues often will be treating patients with Cem readiness and swelling in their throat. And if they come in with hoarseness, they'll just immediately put them on PP ice and not look closely what's going on. This is the patient that I cared for last year. He's a 32 year old gospel singer. He's got a loss of singing range. He's got significant hoarseness when you listen to him, and he has bilateral hemorrhagic polyps that are very, very large now. In addition, yes, he does have some readiness in his lyrics is what records look a little beat up, a little bit swollen. This guy probably does have reflux, but guess what? That reflux is not the cause of his hoarseness. It's these polyps on his vocal cords. These were removed surgically in his voice, improved almost immediately to normal. So the traditional LPR exam findings are this constellation of non specific torrential inflammatory science original. Dema Aaron Thema Nukus Collection granule ation package Hermia. This is a patient that actually does have significant oedema, their vocal participation with Yankees oedema we call it, which is inflammation and fluid and rank e space, which has caused their vocal chords to become basically large balloons. These patients do have a large history of reflux, but unfortunately, that also won't improve just with reflux treatment. That's a surgical disease. So I would like to suggest, and what we do here in Milwaukee is early on. If we have a suspicion that reflects maybe a play as part of their issue, and the patient has no physical findings that suggest an an atomic cause off their hoarseness or other symptoms that if we're going to consider doing a P p I try ALS. I offer a pH impedance testing very early on in this process, and I found that my younger patients, uh, will consider this much more readily, basically any patient well, especially if they have other co morbidity is or things that could cause it to be, uh, complicated for them to be on a P p I, for instance, if they're on some of those blood centers or other agents that interact with proton pump inhibitors, so why do we do reflects testing in our clinic? We do it because patients will ask for it. If you give them the option, we use it for proof of reflux or LPR and patients that are not responding to treatment. And I would say even mawr, so we use it to prove to patients that they do not have reflex. I spend much more time in my clinic, taking patients off of PP ice and convincing them they don't have reflects than we do having them get actual positive testing. What we found is that the one of the rial powers of this dual pH impedance technology and the LPR patient is the negative study. A negative study will basically rule out any significant reflux component to what's going on for the patient. And I found that a lot of times these patients have been on heartburn medicines already for six months a year, two years. I had somebody come into my clinic that was on Ph Probe P on PP ice for nearly 10 years. Yeah, when we tested them, guess what? They had no abnormal reflux. It's also incredibly useful, though, if they do have reflux because you could do some of the symptom association, which can be challenging. But it does sometimes help to support further progressive treatment and also to determine how severe their reflects really is. So we're able to get that to Mr Score when we do our probes off of therapy so that we can one determine if there is an elevated amount of distal reflux. Get that total ph time under four to see if that's ah person that may be able to be considered for fund application, and it allows us to get good symptom association so that as much as there is a gray area with that, I'm sure many people in the audience that may have done those things studies. They know there are some that are very positive, but most of them are somewhere in that gray area. But it's a negative study that is very helpful, and I find that my patients find that this data is interesting and important, and I personally find it fun and relatively interesting to do so. There's a long list of different things that can be done to test for reflux, barium, swallow stop program. The Billet Tech detector, which has never really gotten into any sort of clinical use, at least in order their technology. The wireless Ph probe, the Bravo System, which many of my colleagues and G I use around the country. And for understandable reasons. The D X pH rest tech device, which is the nasal foreign JAL sensor for acid Onley. Single probes, perhaps in testing, which we do a lot of here in Milwaukee, and I could speak a little bit about that if people have further questions and then obviously dual pH within multi generational in peace. A couple of words about Barry massage programs. So barium SAF programs, actually, for LPR type symptoms can have relatively good specificity, but they have poor sensitivity. I have found that if you see um, reflux up to the Jurassic Inlet on a, uh, SAF program, if you do a pH probe on that patient, you will see that they do have elevated numbers, approximate impedance events and are much more likely to have torrential pH events. So studies have shown that really it only works about 35% of the time to distract to demonstrate reflux. If you have provocative maneuvers in the hands of someone who is a well trained radiologists in this regard, you can get increases up to 70%. But it still does not give you the power that a dual Ph probe P and study would do a few words about how Bravo could be used. So bravo, obviously, I'm sure the giant colleagues that are listening to this, uh, they used this extensively. It's well tolerated by the patients. They enjoy it. AST faras. It's much more tolerable than having a wire in the nose, I think. But the problem is that, um it does not allow you to assess anything going on in the upper esophageal area. And there have been papers, including one from might raise this group at Vanderbilt, But they attempted to do a dual Bravo study, but they put a bridle sensor in the upper esophagus. Lower esophagus patients did not tolerate that upper one for a while. All in fact, many of the patients had asked to have it removed because it was so uncomfortable. Okay, so it's a good product that allows you to certainly determine whether patients candidate for fun duplication. But it won't tell you if a patient has abnormal numbers. A proximal reflux despite normal lower esophageal exposure, a couple words about the rest tech device, The rest tech devices also well tolerated. It's something that sits in the back of the nose, and the nasal cavity actually usually hangs just below the edge of the palette on ditz. Well tolerated, and you can supposedly detect pH events with this with this apparatus and the nose. Unfortunately, the normative data for this has not been well vetted, and studies have shown that There is very poor correlation between impedance peps in and rest tech data so impedance and peps and data seem to correlate together fairly well. But, uh, the rest tech data does not seem to correlate well with that in my, um regard. I'm not sure exactly what rest Tech is showing us as clinicians. This has become fairly popular among some of my otolaryngology colleagues and has been the basis again for a lot of patients to be treated with p p I medications. Interestingly, this put this paper here by Mazzoleni at all from 2014, and Euro gastroenterology showed that Onley upto a maximum of 17% off. All rest tech events were temporally associating with lower probe reflux events when they tested both at the same time, meaning that there was a ton of reflux events that were happening, that this technology is missing. And in fact, many of the events that it was picking up weren't associated with direct reflux events as measured by dual Ph and PCO technology. Things is a sort of layout. You get a print out, you get on it. I have done a few these myself. They are fairly easy to interpret because it is only Ph data that shows you the sensor staying in the back of the pharynx. And it is easy to interpret. However again, I'm not 100% sure what that data is showing us testing Testing may be the next wave. Um, there are certainly centers. Ours included that air using Pepsi in, uh, to determine whether there's gastric enzymes in the oral pharynx in the middle ear mucosa in the nasal secretions. Uh, it is a highly specific sensor for reflux going on. We know from our research we have done here that Pepsi can be incorporated into the tissues in the endurance and in the nasal cavity, and it stays there for at least 12 hours. And one of the concerns there is once that Pepsi has taken up into the cells, it could be reactivated by the drop in ph as it enters the Golgi apparatus. So we've seen using scanning electron microscopy cells that literally blow up from inside. If you expose them to peps in, they don't get digested by. And this is Pepsi at neutral pH at seven. So it's not activated when it's on the cells But once it's taken in, it gets reactivated by the acidic pH in the end, acidic vesicles within the cell. So we've shown that Pepsi can actually stimulate cancer cell growth. It can stimulate normal cell growth. And it seems to help augment proliferation, proliferation rates in the mucosa. This maybe something as well regarding, uh, maybe part of the background as to why non acidic reflux into the larynx may be contributing to some of the symptoms that patients have. So the rest of time that I'm gonna be speaking here, we'll be talking more about the LP. Hmm. Multi channel Luminal impedance technology. But I will come back to some more peps and data and help Epson and impedance data seem to be thinking in both our hands in the hands of others around the world. I would say that dual ph multi channel into aluminum impedance technology is the gold standard for LPR detection. Um, it as the impedance that allows you to detect not only a liquid reflux, but also non acid reflux or low acidic reflux. You can measure liquid vapor and mixed phases. You can speak easily, distinguish between answer grade and retrograde events and the new probes that are available, including the comfort tech LPR probe is available from sandhill allows you to do this with a single wire and gives you really quite a bit of information about what's going on in the pharynx relative to lower esophageal reflux and relative to the patient's symptoms. And I find it again fun and relatively easy to do. So. These are the sensors that we're using in our clinic thes total LPR come protect LPR probes that are now being marketed by a diverse tech previously sandhill. So we actually spoke with the folks at Sandhill many years ago about developing this product, and what we wanted was we wanted a sensor here at the top that included a ph probe sensor that was, uh, overridden by an impedance sensor. So we know that when we look at our tracings, if this upper impedance array is being triggered, that that event actually got all the way into the pharynx, we'll show you in a minute how we place these. So we based the choice of which one of these we use on the size of the patient. We generally use out of the short or the medium length, and if they are over 6 ft tall, they get a medium length probe. If they're less than 6 ft tall, we give them the short life and really for us, we aren't as concerned about where this lower array sits. We just want this to be somewhere lower in their esophagus that's above at or above five centimeters above the lower esophageal sphincter. So if anything usually are placement technique, we'll have this place somewhere between five and 10 centimeters above the lower esophageal sphincter. So if anything, we're gonna be under calling the amount of distal reflex and a domestic score will be slightly decreased compared to what you might see if you had that sensor a little bit lower. But really, what we're looking for in our patients is one how much reflects their having it that lower sensor, but really to how many of those lower sensor events are getting all the way up to the top sensors? So what we do is we actually placed this just like we would place the feeding tube. We put it through the nose, we advance it down in to the post, cried, cried region and into the stomach. We detect the pH. Drop the lower sensor just to confirm that were in the stomach. We then put a nasal or endoscope into the nasal cavity and this gently pull this back until we see the upper arrays. So here's Europeans to raise and the Ph sensor right there. And then this is dunk down in gently. So here's that back down into the post quite good segment and that way basically, place these until there be closely covered and then advance it about one centimeter more so that the entire thing stays in the upper esophageal sphincter area. By doing this, we're probably placing that array right at or just above the upper esophageal sphincter. We have published a series of our patients now in this paper and order. Their ideology had next surgery in 2016, and what we've shown is in the 1st 140 of the patients that we had come into our clinic. A very significant distribution of positive, negative and equivocal studies we are using right now is our parameters. Using this specific probe now a single PH event in the pharynx we consider to be abnormal on. We use 40 impedance events at that proximal sensor. This is something that's been an area off significant debate amongst myself and my colleagues around the country were basing that on a lot of data that's come out of some Chinese groups, where they've done a lot of volunteers 70 to 100 each paper where they've shown that he 95th percentile for asymptomatic, normal young patients for proximal impedance events in the upper esophagus, Pharynx is around 30 to 32. So we decided to use 40 as a marker for elevated a proximal impedance. Based on that eso here in our first patient, Siri's that we published. Fully 47% of our studies were found to be positive. However, 39% were negative. So this speaks to the power off this technology where we're able to tell over a third of our patients that we test with this. You actually don't have reflux. You don't need to have any further work upper evaluation for this. We need to find other ways to treat your problem is equivocal. Studies have gone down a bit over time as we've been doing more and more than, but they still do happen. And they tend to be patients where there is just a borderline amount of abnormal reflux and poor symptom association. So for those patients, really, sometimes there's much greater questions there was before you started. But notice that's Onley around 10 to 12% of the patients that we evaluate with this and again, as we've gotten on and had further confidence in what our parameters are for abnormal and normal, we have been ableto decrease that number of equivocal studies. These are the reasons why we're doing our dual pH impedance probes and our click. The vast majority are for throat clearing, throat irritation, cough, post nasal drip sensation, heartburn and globus. There's a few other ones here for dysphonia, subotic stenosis or otherwise patients that just came in with an exam that looked really inflamed or red and swollen consistent with possible LPR. This is the distribution of those diagnoses for which the papers patients were referred, and how many of the studies we called positive or negative or equivocal, so positive is blue. Negative is red and equivocal. Is the green studies here, So first thing I want to point out and this has continued to bear. True in my practice, patients do not seem to get throat pain from LPR or reflex every study we've done to date for patients with throat pain or even nasal pain. Upper airway pain They have not had reflex now. It's not to say that it couldn't happen. But, man, it's much less common than a lot of people think. Also, patients with non specific dysplasia or sinusitis, much less likely to have reflects how we do see some patients that have significant reflects. That has some contribution to the sinusitis because we're able to see Pepsi in in their nasal secretions. We're not sure what the contribution that directly is we're doing. Evaluations and research on that topic right now here at the Medical College of Wisconsin are more common reasons, including dysphonia, heartburn, Globus cough. You expect patients that common with heartburn to have more commonly positive studies, but interesting A lot of the heart burn patients, as you may know, from doing normal probable studies or other evaluations such as that many of them have normal amounts of reflux. They just have more sensitive esophagus symptoms, so they may not have a pathologic amount of reflux, but they could still have heartburn. Um, we've also found that there is some variance between myself and my partners. We do these and again over time, we've gotten better at establishing what are cut offs are. But what's interesting here is even amongst our positive studies, there are some where there was negative ph and impedance. But the symptom association was so strong for their global sensation with, uh, the A normal amount of reflux. But the symptom association was quite strong. Those air patients where we'll consider doing prolonged medical treatment or even non acid reflux treatments like Gascon, advance from the UK, which has an alternate formulation in it that allows a lipid basically a raft sort of blockage of gastric reflux. Eight. So we see that there's some that are ph positive pieces positive or both positive here. But again, there are some where we see that there are basically no significant amounts of reflux. But the studies returned positive based on their symptoms association. In addition, you look at these borderline studies there some here where most of these were negative. But then that borderline amount comes from the fact that their system association was stronger, and there's even one here that had, ah, highly positive study. But their symptoms did not associate at all on this study, and so they were considered to be borderline. So I wanted to show you an example of patient, for which we found this technology to be incredibly useful in our hands. So we're using now things new LPR specific probe that comfort LPR probe that's available from diverse attack to do these types of studies. We evolved initially from doing two probes, one in the upper esophagus and one of the lower esophagus patients tolerated that, but it was a little bit uncomfortable for them. These new sensors were much more tolerated, much more easily tolerated Referral patterns for me, by the way, our patients that have non PPE responsive cough, throat clearing, hoarseness, Clovis or their patients that have not been on meds and they're coming to see me primarily. I see the non p p i responsive patients more from my G I colleagues. That's probably only about a third of the patients that I see with these issues. So the patient that I'm gonna show you right now is a sample patient. The 46 year old male financial analyst. He's got many, many years of allergy and cough symptoms and some of his interesting history factors. He's had allergy treatments in the past. He's had pulmonary function. Tests that show some variable in Pretoria phase blunting, meaning his vocal cords maybe are closing a little bit as he's taking depressed him. I could also be seen with things like paradox with vocal full motion disorder. Or it could be seen with Lauren. Just as, UM, he's had longstanding spells of sudden shortness of breath with exertion. Specifically, when he would be biking or running, he would get sudden spells where he would feel like his vocal cords, which closes Shut off. Hey, Cough, Throat Clearing and Globus but specifically on Lee. Shortly after we eat meals, he had no hoarseness noticed Asia and no complaints of heartburn or previous reflux. So we used this technology to do a Ph probe study on him. I'll show you some of the data that we got from his study next, but his Dmitry score was nine, which is a normal day, Mr Score, but when you look at how much reflux he was having. He had 98 proximal reflux events on impedance testing. Two of those two of those 98 where Ph below four. So that goes to show you that you can have a lot of proximal reflux but not have proximal pH changes. That's due to two reasons. One is the fact that are swallowing obviously keeps, uh, these events from getting all the way up into the pharynx, but also the amount of reflux that you have to have to get up to that area. That has to be a very high volume that additionally, our South saliva has a lot of bicarbonate in it. So at the same time that you're swallowing that reflects event down, which is a normal reflex, it reflects reflects, um you also will be buffering it at the same time. So in order for that reflux events ding the Ph. Bell in the pharynx, it's gotta be a heroic reflux event. So this is a great example. Patient had 98 impedance events that were detected by the technology, but only two of those for Ph. Positive. And this is a patient that if he had had a Bravo study would not have had an abnormal finding on it would have been right out as a normal amount of reflux. So this patient was eventually referred for a links funding application procedure, and he's now doing incredibly well after that. So here's his tracing 24 hours looking at what's going on for him. So toe orient. Those of you that may not have seen one of these before. The top line here is the upper pH. Tracing the lower line here is the lower pH tracing. And then there's three paired sets of impedance arrays thes with lower esophageal arrays, thes air, the upper esophageal raise. And these were the fair and deal arrays. Sorry, they picked up the upper esophageal sphincter array, and the first thing you notice in this gentleman is he has a ton of coughing. He had over 100 coughing stalls during the day, so that is a lot of coughing. And then you can also get a gestalt. Look, just by looking at this, he is having a lot of distal reflux events that are very short, and he's having some of these that seem to be getting up to the upper ph sensors. So here's what the technology can show you what we've done now back up here, we've done now is using this. Bought in here on the technology, you can spread the tracing out to multiple different times times. So we've now look at this. This is a four minute window and you can see each one of these swallowing episodes that he's having during the tracing. Here's a couple cough episodes that he had that are associated with no reflex thes spells. By the way, we do all of our studies here for the most part, off of P P I on day one. I find them easier to read with that because you can obviously see the pH events more easily with that. But in addition, we want to really get a symptom association based on acid and non acid reflux, as well as domestic score for our patients off of therapy. So, here again, you see, uh, to coughing spells patient had, which you can maybe see a little bit of a squeeze of the impedance technology there with that, but you don't see any reflux events. This is a lower esophageal reflux event. So here's the ph Tracing going below four. Here is the beginning of what I like to call the pyramid of rising impedance change. So the P the impedance is dropping as the liquid is crossing these rays and you see here then that there is a change of the lower esophageal sensors, the opera savage it'll spend centers did not get triggered, and the torrential ones did not notice here again. Reflux event immediately the patient swallow so the reflux starts and it triggers a reflex of swallowing to push that reflects. But that reflects event back down. Now we're showing an acid reflux event that's actually gotten with all the way up to the upper sensors. So this is a acid reflux that has upper, uh, proximal extent penetration, but no ph change in the pharynx. So this would be one of those 98 proximal impedance events that was detected by the reflux LPR technology. This here shows a full column impedance event with an acid reflux events. So this is a longer one again. We have three minute window here roughly the same time frame assed faras the distance here and we see this rising pyramid of narrowing impedance change all the way across, up to here, up into the pharynx. And then here is the fragile pH. Drop for this patient and then again right away. What does he have? Three. Clearing swallows in a row to try to push that reflects event back down. Ah, couple other interesting things that you can see with this technology that we find of interest here, that we're doing some research on here at the Medical College of Wisconsin. We see this sawtooth respiratory rate pattern on this again is something that's basically being caused by the increased parasitic pressure during inspiration. It's squeezing the impedance arrays a little bit in the esophagus and causes the slight changes in the impedance technology detection. So what we can do with this? We can actually see if the patient stops breathing. So here's ah, patient that has a penetration with differential uh, impedance, um, a drop all the way into the pharynx with the acid reflux event during their sleep. And here's a patient that actually had a arousal from sleep from hypothermia and apnea. I want to back up to one of the things along those lines. I'm gonna go back here to this slide. Last thing I want to show you. Here. This is an L. P. R. Patient. I would describe this gentleman here as a fairly classic patient with LPR. Look, this is when he's laying down at night notice that there is no reflux whatsoever when this man is laying down again. One of the traditional teachings about GERD is that it's worse at night. Patients have more irritation, more heartburn symptoms when they lay down. As a gentleman who has had reflects in my own life, I can tell you in the past, when I've had it for me, it was worse when I was laying down our LPR Patients have almost no reflects the once they're laying down. They may have one or two spells right after when they lay down, and then the rest of the night they are quiet, as faras reflects is concerned. So again, this is our patient here, sleeping at night has a arousal where they stop breathing briefly and then they swallow several times. We're looking at this technology to see if we can use this to measure swallowing episodes during sleep as a marker for possible obstructive sleep apnea. So how do we interpret these? Where did we come up with these numbers? I'll show you a few of the papers that we're using to get our standard data. How we use that cut off of 40 proximal impedance and one proximal ph event as being abnormal many of you here. Probably no other Dimitra score is developed in 19 eighties is a overall index of extent of lower esophageal reflux. Our system, the way that we're doing this, if anything is going toe under, call the dmitri score because we're placing that lower pH sensor a little higher than the normal convention of five centimeters above the L E s, which is probably where most patients were most G. I doctors, I should say, are placing their Bravo's. They usually don't place them at five. They play some somewhere further down, further above in that area, roughly where we're putting our sensor, at least in my experience here in Milwaukee. That's the case. In any case, most of our G I surgical colleagues require having that to Mr Score in order to make a rationalization for referral for fund implication. So we need to get that data for them. But data on forensic impedance is a bit more Graeme. And this is something where we here in Milwaukee are probably one of the leading centers in the world. Honestly, and evaluating this. And it's the reason why I'm being asked to China and talking a lot of meetings not only in America, but now around the world on what we consider normal and having this discussion on, I have discussed this at length here in Milwaukee with my G I colleagues, including Dr Benson Massey, who's a good friend of mine here. In any case, studies have shown that as faras pH events are concerned in the pharynx, you do not typically see pH change reflux events in the pharynx in normal volunteers. So and this paper here hop Oh, they used a similar type of product. Although a different probe from diverse tech on day showed that LPR events are rare and the asymptomatic population and that the 95th percentile for, uh, impedance detected pH events. No. So this, uh, answer retrograde Sorry. PH drops below four. The pharynx was one event. So they said that the 95th percentile was at one event in their studies. There's several Chinese papers that have come out this being one of them where they looked at the number of proximal impedance events. And this is actually the upper esophagus, not the upper esophageal sphincter. So just below this would basically be full column esophageal reflux. So they looked at 70 healthy volunteers without symptoms. They found their that their 95th percentile for a civic events in the upper esophagus was 32. And they found that the cut off for weakly acidic and all these other ones was much lower. So total was 32 weakly acidic. 13 acidic. 27. Here. The total on this is upright. Re comment again noticed and recumbent position. Normal people do not have significant reflex. Another study from our Chinese colleagues. So they found in this one that the number of ph of this was to and that that that was the 95th percentile for abnormal was too. And they also had impedance data with this that correlated fairly well with the other discussion. No, hold on a second. Sorry about that. So what we found was that in this study also corroborated fairly well with the impedance data. was from the other papers. We have now looked at our patients, and we found on bats in the paper that I referenced before from us that came out in 2016. We found that the positive studies that we were looking at, we called them positive. The average number approximate impedance events was over 40 on those pages. So it's roughly in the low forties, like 44 the normal studies patients that did not have have symptoms or in what we're doing right now in a controlled population, we see that numbers around 30 to 32. So it really does correlate fairly well with what our Chinese colleagues have done. So this is another interesting paper this is looking at. How does Pepsi in correlate with rest tech data correlate with impedance data? So here they're using a bifurcated probes. It's a little bit different than the one that we're using, but they're using some sparely similar parameters for detecting what they call abnormal LPR. They looked at a controlled population. They looked at 21 patients that had LPR type symptoms. Interestingly, again noticed that when they tested, these patients again have over half less than half of them, I should say, had evidence of reflux, but they found on their testing. In addition, was that the rest text these patients that had a rest tech device and one side of their nose. They had a pH probe on the other side of the nose, a dual ph and peace toe, a probe. And then they collected celebrate peps and from them for 24 hours. And what they found was that the Pepes and data actually correlate, correlated and supported well with the positive pH studies. Uh, there were a few patients that had any peps and positivity. If they're impeding, studies were negative. Um, and they were much more likely to have one or even more than one Pepsi celebrate Pepsi tests that were positive. So this suggests if they had a positive impedance studies. So this suggests that impedance and Pepsi in which I think peps and perhaps maybe the most sensitive test for LPR. They correlate fairly well and we've seen this in our testing. We're doing a study right now in the same regard. So this is our protocol that we're doing right now here in Milwaukee. We've been recruiting now for almost two years or with our goal to do a 50 patients and 10 controls. We're using those probes. They're the ones we showed you before. We're also collecting them five daily sputum tests for Pepsi in a swell as a scientist aspiration at the time of placement and then are borderline here for a positive impeded study is these parameters. This just shows you a western blot that we've used to confirm our lives of testing for person showing that you can actually see, uh, this is the first, uh, sputum upon awakening. So our patients, as I mentioned that have LPR tend to not reflects much at night, but then the minute they wake up, they usually have a massive reflux event. So this is the Pepes in equivalent of that. So you're showing things patient. The sputum four is the one that we collect first upon waking in the morning. And that was very positive in this patient. So so far today, we've had 13 controls in 26 patients and are due ph. Pro Data is showing again that we can really show whether or not these patients have LPR or abnormal amounts of Lauren go for NGO reflex. What we're trying to show that is the actual outcome. So whether or not once we detect these patients having that abnormal amount just treatment, then does this predict response to treatment? We've only had four of our control patients that have had positive studies, and 19 of the patients in the population have had positive studies with the day Mr Score that's still considered to be in the normal range. They've had an average number of proximal pH events of 1.42 We found that Peps in tends to correlate well with the positive studies, and we're still working this out. We found this sputum upon waking interestingly again, seems to be the one that has the most peps and positivity, and we're doing ongoing work with that in our clinic right now. We're also looking at testing these. There's a test that's come out of England, called the PAP test that's available from Peter Debt, Mars Group, and that's now available worldwide. It could be purchased and used in any clinic, and it's something where you collect a salary specimens, spin them down with centrifuge in your office, and then do a lateral flow type device like a pregnancy test test. That then gives you a band that's positive. There's Peps and detected. We're gonna be repeating our specimen tests, using that as well to see if that may be a better way to look than the ELISA tests that we're doing. So far, stuff studies are showing that Pepsi correlates more with typical gastroesophageal reflux disease, not some of our LPR patients, but we're looking at that further with more testing, and we're continuing to analyze and recruit more patients in this regard. But so far we can tell you that Waking Pepcid and the longest Bullis recumbent acid Exposure and the Reflects Symptom Index do seem to correlate. Well, statistically, I'm gonna skip over this paper just to spice it to say that studies have shown that if you have patients that you select carefully using some of these dual P H and PS parameters that that study does predict response to treatment, However, we need more studies like this. And it's one that things type of studies, one that we're hoping to continue to do here at the Medical College of Wisconsin. So this study well shows that if you carefully screen patients with these parameters that you can actually predict response to misinformed application. So we have seen in our study Siri's Here, the previous patients series that we showed you. There were nine patients out of roughly 50 that were positive for LPR that went on to have a misinformed application, and all nine of those patients expressed benefit. Unfortunately, we have. We don't have post testing pH in peace raised on these patients, but it's something that at least we can show that their symptoms have improved. There's a serious that came out of Pittsburgh from hop, uh, Blair job. And they additionally, using again some of these standard type technologies with dual pH impedance have shown that 15 of 16 patients with cough that referred to them improved after funding application again, many of these patients have tested with standard Bravo technology would not have abnormal findings, and you would not know that you could help them with this type of type of surgical intervention. So what this has led me to do then is think very carefully and critically about the symptoms for which these patients are coming to see me so again. Here's what I call my fantastic four of LPR symptoms hoarseness, chronic cough, global sensation, throat clearing and you'll notice for many of these now I have dual pH MPs fairly high in the evaluation. Global sensation is one where we definitely think of it higher up because we know that global is a very hard problem to treat. And one of the only things that can be done to help with global in my experience is treating for reflux issues. Additionally, Manama tree, I think, is used for those patients. A lot of our patients that have throat clearing or hoarseness. If you look closely and see what's going on with their glass closure, they often have a logic insufficiency, and you need to do something to bulk up their vocal chords is a trial to see if it will improve their voicing and we'll get their throat clearing to go away if they don't respond to that? Or they appear to have normal closure that I'm fairly quick to offer or at least discuss ph emptiness pro testing. So for hoarseness. Specifically, I highly recommend that you look as close as possible at the vocal chords before you consider reflux treatment or trials. Studies from colleagues like my friend Dr Lucien Silica at Cornell have shown that patients that are referred to him for reflux often have subtle vocal cord pathology that can really only be seen with videos. Jarvis copy, which is something that we in learning biology do all the time. But it's not something that maybe in the standard armamentarium of your average otolaryngologist, they could be seen to have. Subtle paralysis. Saul Kosor Scar Decreased Mucosal wave or most commonly, vocal cord atrophy where they seem to not have as much bulk on their vocal cords. This is then felt as if there's something stuck in their throat all the time. Their voices never quite right. It's not resilient. Those patients could benefit from either vocal cord augmentation. Or they could benefit from referral for speech therapy and often will try therapy First, a trial injection next, and then we'll consider objective testing for reflux or, if they don't want that, that's when we do give them a trial of Imperial P P. I. This is just a word about what injection lowering, lowering a plastic. Is this a manuscript that we did a unfortunate young man that had some neurologic cause of his vocal cord atrophy. But here you see this bode very thin vocal chords. With this zero degree scope, you can see the Boeing with a 70 degree telescopes looking in the operative. You can see how incredibly thin these vocal cords are. So this is one of vocal cord looks like after we've both it up and you can see how much thicker, fatter and more vibrant those vocal cords look. So if patients respond to this, um, they often will notice at the same time that they're reflects symptom. The next score gets way better once you bulk up their vocal chords. So for patients that we see in our clinic, this is a major consideration. Are chronic cough patients. I have a very standard algorithm for how I approach them. I try to have one. At least that could be very challenging. But a couple quick words about them asking them what their cough is like. Is it wet, dry, thick, productive? Is it coming from? Their lands were coming from their chest. Have they had all the pulmonary screening that they need to have every patient that has chronic cough for more than a month is to have a chest X ray or chest CT. If they're an active smoker, should they should have pulmonary function test with mythically challenge and if they're on a nation, have nothing to stop it. A 12% of all patients honest inhibitors could have chronic cough issues, then consider stopping their ace. We do test for pertussis a lot in my office. It's much more common than people realize, and I have here some of the questions that I ask patients to determine whether I think they may have had prosthesis were very quick to recommend speech therapy referrals. And then, if all this is negative, then the last few things that we think of our behavioral issues reflux upper airway cost syndrome, which is an alert allergy issue or upper airway inflammation and then pull spiral Fagel neuropathy, which is a sensory nerve injury to the throat. That's a diagnosis of exclusion. I could do a whole talk on just that, but in addition, this is something that will work out quite well. Okay, Global sensation we talked about already. Very, um, South Graham could be useful for these patients, I do often recommend pH probe testing for these patients. Early on, throat clearing you overlap here is again very similar to what we do for patients with hoarseness. Often again, it's two o'clock gap. We offered speech therapy, injection rhinoplasty and then again often will consider doing reflex testing. Or that's our program early on. So combining all those things together, this is what I consider to be the 1st 2nd 3rd tier for LPR treatment. The first year is almost always good. An atomic evaluation. What's going on in lyrics? Because there's a lot of things that get missed and a lot of things that are overlooked. Dual pH impedance testing in my mind comes in at the bottom of that first year of the very top of the second here. That's something that I recommend, quite often conclusions. Here I recommend judicious use of Imperial PP ice with a distinct plan for end point and weaning ID like pieces to consider the option off early objective testing. And we'll consider that they may have LPR type symptoms, and then if they conduct you meant that they have it consideration for referral for fund implication because As we all know, the P p. I is not going to stop them from reflux. And it's only going to stop the reflexive from being acidic. And then I recommend to my otolaryngology colleagues that may be listening to follow that type of symptom based algorithm that I just gave you for evaluating LPR type symptoms. With that, I think I'll stop and I'll be able to take any questions that you guys might have for me. Thank you very much, Dr Bock. That was nicely done. Appreciate all that information. We do have a number of questions here. Um, what is your experience with Issac for LPR treatment? E s o x X or Issac one? Have you heard of them? I have no experience with that. Okay, Um, do you find a correlation between post coal assist ectomy or gall bladder stones, post bariatric patients and L P R. Well, so patients that air bariatric patients, if they've had a ruin, why they should not be able to really have any significant reflux as's faras the amount of extensive reflexive because they shouldn't have, they could have obvious they can have some Pepsi in, but usually there's not much of an issue for them. I can't say that. I've had ah, lot of patients that have come into me with that specific complaint spectrum. Obviously, in my experience, patients that have had their ah, cold suspected me. They can have chronic diarrhea, chronic issues with other mild gastrointestinal distress. Uh, but I can't say that I've had a lot of patients referred to me specifically with those concerns. So it's not something that's come up often, although, to be honest, I can't say that I looked at it that closely either. So I don't know if I really have enough data to make a strong statement about that. Okay. Thank you. Um, how long do you leave them off? A P p i before testing. You may have mentioned that, but I mean, so what we dio generally in our clinic is we leave them off for one week. So all PP ice. We allow them to use H two blockers up to 24 hours before the study, the last 24 hours before the study. They could only use Tom's. And then after that's done that morning of the study, basically after midnight, they can use nothing, so we want them off of everything. So one week off PP ice one day off of H two blockers and then that morning off of Tom's. Very good. Um, do you think that weakening hearing enlarged tonsils may be due to LPR? Uh, there is no data is just that council enlargement is related to LPR. There has been, um, kind of cloak, really some suggested association with tongue based hypertrophy and LPR, certainly patients that have a lot of active regurgitation reflex. We do see that some of them come in and have massive post cry coid. You know, Heiple, Frenzel, oedema, tonsils Swelling, however I don't think is nearly as is common. Those are almost always related to chronic infectious issues. Um, the other question was about hearing loss. Uh, hearing loss is not associated with LPR. Specifically, however, there's a lot of patients that come in with subtle hoarseness complaints or throat clearing, where they actually may have as part of their problems from hearing loss because they are hearing their voice the same way. And so when you don't hear your voice the same way in your head many times, the first thing they assume is, well, I'm horse, but it's actually not that their voices. The problem is that they're not hearing themselves the same way. So it's not a direct and they may think, Well, maybe I'm horse because I have LPR But there's not any direct correlations there that I can speak Thio. Okay, what are your thoughts on manna metric placement of LPR probes versus your described technique of direct visualization and withdrawal with respect to accuracy and reliability? Well, I don't have a problem with that approach for placing them. In fact, you know r g I colleagues, but they also use the same probe for some of their patients. Um, we, uh, don't really see much need to do it. We don't have the technology in our clinic right now to be able to do that, but it hasn't seem to make much difference. Uh, generally, what we're doing is I said when we play stars were placing that upper sensor right at or just above the upper esophageal sphincter and the lower sensor in our hands. We don't care as much about exactly where that is. I can understand why, by convention RG colleagues have been placing Amanda Metric Lee to have that lower sensor beam or correctly placed. That's always kind of bothered me in my mind regarding that is the fact that that the Bravo sensors don't seem to be placed that low many times when I see them. Or somewhere around 7 to 10 centimeters above, which is kind of where we place ours. Um, however, I thought, you know, patients are clinicians have the ability or interest in placing it mathematically, I think that that can Onley probably improve the reliability of it. Um, so far for us, because it's so easy for us to do it this way. This is how we've done it as little immunologists. Okay, Thank you. Uh, the pH impedance probes will detect liquid mixed liquid and gas as well as gas reflux events. Do you consider the gas reflux events in Europe Your studies? We have looked at that data. It hasn't seemed to really to have much correlation in our hands. But we're trying to get more, um, in depth on that, Um, it's not something that's been, um, written about much in our literature and the otolaryngology literature. Um, but we have looked at it, But it's so far we haven't seen that. That has been Ah, very important parameter. Really. What we're looking at is just how many of these events are getting up to the proximal sensors. Okay, I have a few peps and questions. There are fight. There are five types of human peps, an enzyme. Which type did you examine? The Pepsi in that we're looking for is e believe the standard one that's made in the chief cells in the stomach. My colleague, Dr Nikki Johnson, is the one that runs the research lab in that regard. Um, what we found is that the antibodies that she has designed is one that reacts toe all known types of human Pepsi so they could design that antibody to react to any specific part of the protein. So, as far as we know, that enzyme, the antibody that we're using to detect person is one that works for every known type of human person. Okay, uh, you focused on Pepsi in, but what about bile acids and, um, trips in? Well, that's a good question. So Pepsi is only one component of all of these different things. We use Patteson just as a marker of reflux state. But there's no reason you couldn't look at any of these other parameters. That's what some of the other technologies ability, for instance, had looked at. We don't have any specific research expertise with those, but it's an excellent point. You could look at any of these things honestly to see whether they're good market. Very good. Well, that brings us Thio the five o'clock hour in Central time. So that completes our our webinar. We do appreciate your offering and all of the great information you've shared with us. Do you have any other closing thoughts for us? No, I would just say for specifically for my colleagues. There may be listening to this that are ordinary oncologists. I find that this adds a lot of clarity's is very challenging patient treatment issue in our clinic, mainly again, the power being ruling out reflux for patients that have some of these bags, throat complaints that may be convinced that that's their problem. Unfortunately, the longer retreated the water we're putting off coming up with the right answer for these patients. So that's really the power of technology I would encourage. So my G I colleagues as well to think more carefully about how much reflexes, normal and abnormal as far as it concerns the proximal measurement of these things. And that's what I think. A lot of the patients that I'm seeing that air coming into me have had rabble type studies where they're on Lee looking at that, this little amounts of reflux. And this is certainly a technology that allows you to look at that upper extent of reflux A in a much more elegant way. Thank you very much for your time, Dr Bach. And thank you to all the attendees for joining us. This will be recorded and loaded onto our website. So please encourage your colleagues to go there if they were not able to attend live. Thank you very much. Thank you.