our group case-based discussions this morning. Myself, I'm Uzma Siddiqui from the University of Chicago. We have Dr. Falk from UPenn and Dr. Hirano from Northwestern. We're gonna kind of be the overall moderators, but we'll have different presenters and panels for each case, about 20 minutes per case, and please ask questions. This is only as good as the audience in the audience, so we'll start with Dr. Falk. And then you can use the mic to the first one. Okay. Okay, so we'll keep this informal, and I was asked to give a couple of cases, and let's start here. This is a case of cough. Typical person who comes into my office. 42-year-old woman who was referred by our PCP for chronic cough, several years. Definitely impact your quality of life. She says it's making her miserable. There are no triggers. Importantly, there is no history ever of heartburn or acid regurgitation, even when you put the words in her mouth. She says, I've never had it even during pregnancy. No dysphagia, no post-nasal drip, no sinus issues, no asthma, no GI symptoms at all. Current medications are here listed. Notice there's no PPIs. The past surgical history is negative. Past medical history of anxiety and fibrocystic breast disease, the physical examination is negative. Any missing in the history? This is not, we're among friends here. Anything else people wanna know? No smoking history, thanks, thanks, Iko. Well, you know, this is a classic situation. It comes, and so here are your choices. So, hands by show of hands, who would, you're the gastroenterologist, the patient's seeing you. Primary care referral? By show of hands, empiric BIDPPI trial? An EGD? Bravo. We got one bravo, kind of hand going up a little bit. I wanna go back, I'd do an EGD, but. You'd do an EGD, okay. Impedance off therapy? Impedance on therapy? Pulmonary referral? ENT referral? And would anybody do more than one thing? You don't have to tell me what, but would anybody do multiple things at once? So, this is a classic situation. We'll turn to the panel and get some insights here. Why don't we start with you, Dr. Siddiqui? I was gonna say, this is why I don't do general GI, but. This is not general GI, this is topogology, please. I know, well, again, the patient's coming to you for a complaint, so I probably would do an EGD just to document that there's no obvious erosive esophagitis, or I still look for Barrett's, or any other mucosal changes, and potentially an ENT referral. And then I'd send it to my esophagology colleague for further workup for acid reflux and pH testing. So, you do an EGD, so let's go from the south side of Chicago to the north side of Chicago. Iko? So, I do think, as a gastroenterologist, we need to know about the other causes of chronic cough, because these patients get tossed around a lot, and bounce around a lot of specialists, and get a lot of unnecessary tests. So, I do see patients like this, and you pick up the history of the ACE inhibitor, you pick up a cough-errant asthma without any reason. So, I think it's good that we're aware of those things, and go through that systematic checklist, which I'm sure you'll go through. Chest x-ray, environmental exposures, including tobacco. And when that list comes all out negative, then I think it's reasonable to consider GERD. Usually, I'll just go to the PPI. Even with minimal reflux symptoms, I'll just do that, because I don't want to go through testing yet. And when they fail that, that's when I'll consider doing an operonidoscopy, off therapy, and then do a bravo off therapy. And somebody like this, with no pre-test probability for GERD, I would do an off-PPI test. But before I put them through that expensive evaluation, I want to make sure that I've at least gone through that checklist of things that can cause chronic cough. And I'll order the chest x-ray. That's what I was going to ask you. You're going to do all of that workup beforehand. Yeah, because they have to go back, and they have to find a pulmonary, or they go to a primary. I don't think it's too hard for us. I'm sure that's a style and preference of what you want to get, hassle of ordering tests and looking up results and things like that. But I do do that, and sometimes I will prescribe. Sometimes I have prescribed nasal, if they have post-nasal drip syndrome, and also even a trial of a bronchodilator. If they're frustrated, and they've gone through a lot of rounds of this, and not getting a lot of answers. I was going to say, a lot of the time, the patient's already had that respiratory workup, so by the time they come to you, if you want to add something additional. I would say the post-nasal drip, that is a very common cause. That's the one thing that I probably would advise the patient on, and a lot of times that will resolve the cough. But I'm usually talking to them about that at the time of the EGD, when it's normal. Let's switch Great Lakes now to Lake Ontario, to the southern shores of Lake Ontario and Rochester. How would you handle this? I agree that a lot of times when they're sent to me, they've already had their basic pulmonary. I'm not the first pick for the primary care for cough, so they've had their basic evaluations, and we do see a lot of undiagnosed post-nasal drips, but if they've not seen ENT, then I do refer them and a trial of PPI to start with, and see if that helps. Any comments from the audience? How are you all handling this? Other than either shrugging your shoulders or cowering in fear and saying, oh no, not again. Yes. I'm still a fellow, but most of the patients I've seen, they usually come as a referral from ENT, and they already have some nonspecific findings. The physicians tell them that this is good, so they're already fixated. So even if I've tried to give them just PPI or something, they want more definitive evaluation. Someone's put in their head already that they need an EGD or something. So it becomes tough to just do like a diagnostic therapeutic trial, and their expectations, too, are kind of high, so eventually end up giving to an EGD, or eventually, if that's normal, then a pH testing. Well, you know, I think it's interesting what you mentioned about patient expectations, and again, we do have to factor that in, but I think that one of the things that all of us have the advantage of, a lot of us have the advantage of, is having the institutional logo behind us, which gives us a certain amount of gravitas, whether it's merit or not. So, you know, in a situation like this, and I admit, I kind of fudge this a little bit, because usually they're not coming from the primary care physician, but a lot depends on what's already happened, but just because somebody wants a test doesn't mean they should get a test. And for example, if you're gonna do an EGD, do you wanna be thinking ahead? Do you wanna do an EGD with prolonged pH monitoring versus having that repeated again? So I think all of that factors in, but I think, you know, my approach in situations like this is, you know, I don't have ECO's broad suite of capabilities, and I usually have a team of people, I'm kind of a big believer in a multidisciplinary approach to this, because I know my track record in this area is usually pretty abysmal. So I think that these are your various options. I think that, and we'll go through a little bit more what is recommended. So we've talked a little bit about this, and we'll just kind of, I'm gonna just hit the panel quickly here. You can all choose one thing only here. So we'll start, we'll go from left to right this time, and Shivangi, what would you do here? One choice, including none of the above. Well, I would say empiric PPI trial. Iko? I would do the same. We heard about EGD, but I didn't give that to you as a choice. You have upfront testing, so it could be EGD. Absence of GERD. Fine, I'll go with the PPI trial too. Okay. How about for the audience, we'll just, I just gotta speak up a little bit. Upfront testing. So we've got upfront testing. Any other takers for upfront testing? I'll take it. All right, we knew that's what you wanted. Any empiric BID PPI trial? Yeah, of course, yeah. All right, multidisciplinary referrals? None of the above? You didn't put all of the above. Not putting up your hand is not an option here. Oh, that's too far, I'll do it again. So this is what, let me go through a couple of guidelines, what they're telling us to do here. So this is from the 2022 ACG GERD guideline. And they recommend evaluation for non-GERD causes. So as Iko was mentioning too, post-nasal drip, asthma, other pulmonary issues. And if no typical accompanying GERD symptoms, reflux testing should be done prior to PPI therapy. And this is not the only guideline that suggests doing that at this point. However, if there are typical accompanying GERD symptoms, such as heartburn, acid regurgitation, it's perfectly reasonable at that point to consider BID PPI prior to additional testing. And surgical or endoscopic approaches are best reserved for patients with objective measures of reflux. So here's the CHESS guidelines. This is from now several years ago. Peter Kirillis was part of this as well in 2016. So a chronic cough, which is what we're talking about here, is defined as greater than eight weeks. And this gets into what Iko was saying. What are the most common causes? Rhinosinusitis, asthma, GERD, non-asthmatic eosinophilic bronchitis, something that none of us can diagnose. Combinations of the above and miscellaneous causes. And the one thing I always tell patients with cough is that it's one of the few examples of one symptom, multiple causes. It can be one of these, it can be two of these, it could be multiple of these. So there can be more than one thing's operative at the same time here. And in patients with suspected cough due to reflux cough syndrome, without heartburn or regurgitation, recommend against PPI therapy alone, unlikely to be effective. So Iko, that's kind of how I've evolved here is that, I don't know about you, but I've just become so inured with the fact that in the absence of symptoms, PPIs aren't gonna work. Is it reasonable as long as there's follow-up, despite what the guidelines say? I think yes, but it's really not with any great gusto that I'm doing it. Iko, so I know you wanted to do a BID-PPI trial. Your upfront thought of success with this? It is low. I mean, the reality is most patients that I'm seeing are already been on it. They've already seen ENT or pulmonary or their primary already tried it. So then the likelihood is very low. But I just think to go right to testing, and we can have a debate about this, but that's an expensive proposition for a cheap, over-the-counter medication. You could try it for a couple months. I don't think you lose anything. You lose a couple months, maybe. If they've already been on a BID-PPI, correct. The Irwin study that people quote about the top six causes of cough, once you've excluded that list that you have there, they included a chest X-ray on there to make sure there wasn't some pulmonary process. But once you've done that and tried treatment, the pure treatment for asthma and rhinosinusitis, then the probability of GERD went up higher, even in the absence of GERD symptoms. So, yeah, I'd probably differ a little bit from what the recommendation is here, to just, I don't think you lose anything by a couple months of a PPI. But expectation's low, that's gonna work. And also, if you do an endoscopy, the expectation's very low you're gonna see anything in the absence of symptoms. So we're not gonna discuss this article, but I have to tell you that this article changed my understanding of chronic cough. This is from the New England Journal from 2016. And it's a wonderful review on chronic cough that kind of walks you through how best to approach the problem. And again, it's a little bit dated right now, but step one is exactly what Iko was talking about, the medical history, underlying diseases, red flags, chest X-ray, spirometry. Again, spirometry's not on our checklist. And then seeing what that has to say, then focus testing and treatment for asthma, reflux, and rhinosinusitis. But you'll see here consideration of monitoring a pH or impedance, here it says patients with symptoms of heartburn or acid regurgitation. Consideration of empirical treatment, although in the article, body, it basically recommends against using PPIs in the absence of symptoms. And then investigation to exclude rare causes. Excuse me, that doesn't play to our strength. And then consideration of neuromodular treatment for idiopathic or refractory chronic cough. So here's what happened in this patient, a BIDPPI trial, did nothing. She was seen by a pulmonary colleague who was concerned that she had interstitial lung disease causing the cough and abnormal PFTs and chest imaging. She had a CT of the chest with stable pulmonary nodules, diffuse airway inflammation, band-like opacity. She had a CT of the sinuses with chronic mucosal disease. She had a bariomesophagram with mild reflux, whatever that means, a small hernia and normal motility. Here's her EGD. I put the arrow there to show you that the GE junction is not entirely normal. And we'll see how that plays in, but everything else was okay. And here's her 96-hour Bravo off of therapy. So she has a total acid exposure time of 6.3%, that's pathologic, and it was greater than 6% on three out of four days. That gives you some information as well. 68 reports of cough, and then as usually is the case, there's a lack of concordance between the symptom index and the symptom association probability. So she has objective evidence of reflux. She has an abnormal hill classification. And here's where she is at most recent follow-up. She's vomiting because she can't stop coughing. She's going up the stairs and feels tightness in her throat and then coughing. She lies on her side and feels her throat tighten, caused her to cough. She's had Botox injections of her vocal cord. That hasn't helped. She's tried multiple inhalers. That hasn't helped. She still has absolutely not a whiff of heartburn or acid regurgitation. Dr. Hirano. Why are you picking on me here? You're definitely the expert. I mean, the pH study, it showed a nice upright reflux pattern almost all the episodes were occurring when she was awake and there was almost nothing happening at night, which is interesting. But she did not respond to your PPI trial. Even though there's evidence of acid exposure, would you still try something like a nasal steroid spray or something? Again, looking for... Yeah, that's a good point. I mean, a lot of these patients, as you know, we end up coming up with these multifactorial. Yeah. Because you find a little bit of this, you find a little bit of that, and you end up trying to shotgun them sometimes just to see if you can get them better because she's got some evidence, subjective evidence now, GERD, but it's not causality. It's just that there's GERD. You don't know whether the GERD is causal in her cough, but it sounds like she's been to the ringer with the other therapies. These patients, often they tell you they get a little bit better with something. So sometimes I will try multimodal treatment. The other thing to consider here would be doing another pH study on PPI therapy this time to see if you're radically suppressing the acid reflux and then looking at the impedance, the non-acid reflux events and weekly acid reflux events to see if that's ongoing on a, I would put her on a high-dose PPI to see if you can just abolish this and see what happens to symptoms and see what happens to your reflux test and if everything else has been exhausted. But these are people, again, I'd go back through that same list again and make sure that you've addressed all, because there were some abnormalities on that CT scan. I'm not sure what inflammation of the lung meant. Was that aspiration? Was it thought to be some individual lung disease? I'm not exactly sure how that was interpreted. Vani, there's a question from the virtual audience. Oh, okay. I was, you know, I think this is a very interesting case, and just looking at that laundry list of things that she'd already gone through, I just wanted to share, you know, I actually am lucky enough to have the laryngologist and I, we decided to move into offices together, and so they're next door, and we have a lot of multidisciplinary and multi-step approaches. And so sometimes in this kind of case, we tag team and they're like, okay, I tried this. I tried one Botox, but we got nothing. I think maybe you should address the reflux first and, you know, maybe do the pH impedance or do a little bit more before I sit there and exhaust everything when we haven't dealt with the triggers. Because some of these things with the eye-opening cough experience that I've had is how bad irritable larynx syndrome or sort of these neurogenic coughs can play a role. And so even though there might be triggers and you fix the triggers, that's still there, or if the laryngologist fixes that, there's still the triggers and we haven't really helped the patient unless we've done it together. And sometimes it does take a little bit of communication and tag team approach. And I will say sometimes I actually ask these patients because I'm not sure, I'll go through the pH impedance testing, but I will ask them to go on a three-day trial of a very strict diet and really, especially if they have more nocturnal or early morning symptoms, literally ask them to just step down to full liquids after a period of time, just to see if the cough gets better and really focus on some of the non-PPI managements of reflux and be really strict for three days just to see if I'm heading in the right direction. And I found that that helps because if they tell me the cough is better when they like step, they went down to a smoothie dinner for three days and I'm like, okay, let's keep going. Whereas if it was no difference, I might not be as reflux oriented. Uzma, I know you said that you basically go Olay and send these to your colleagues, but you're the only person to see right now, so. I mean, I would still try going down the inflammatory route, Flonase, histamine blocker, repeat the pH testing on the PPI and go from there. Shivangi? Yeah, I agree. I would repeat the pH on the PPI and assuming the endoscopy and everything is good. You know, Gary, again, you've given us some other things that were not normal. So I think with that would have to be discussed that CT scan finding. And then just going back to that pH tracing, it is interesting. I look at it a little more closely now. There are some events happening right when she's going to bed, which is interesting. And those were the prolonged acid exposure times, which is what you expect for supine reflux. And it's goes to Vani's point is that there could be a post-parendial component here where she's eating dinner and going to bed. And Vani's idea is interesting to put them on a liquid diet or just making sure she is following that three hour window between dinner, she eating late and then going to bed because there are some prolonged acid exposure times that are happening on that pH tracing right when she's going to sleep and then it's quiet through the night. So I think it's worth exploring lifestyle, making sure the timing of the PPI, before you go further with further testing. So, you know, we've talked about some, as would be expected, we get through one of the two cases, which is fine. But these are then at the end of the day with what I've shown you, these are the things that start going through one's head. We've talked about it. Do you based on the endoscopic findings of an abnormal hill, an abnormal Bravo go with a mechanical fix, like a TIF or anti-reflux surgery or magnetic sphincter augmentation? You can argue, she's got abnormal anatomy, she's got abnormal pH, let's do it. Or she's desperate. People are desperate when they see us for this. Would you do pH testing on therapy? Would you go with a gabapentin trial to modify the neural arc here? Or would you have further multidisciplinary discussion recognizing none of these are mutually exclusive? So, these are the things that I start thinking about. I didn't say, I didn't show my hand yet. So, by a show of hands here, who would recommend any of these mechanical fixes at this point? This includes everybody. pH testing on therapy? Gabapentin trial? Got a couple for that. More further multidisciplinary discussion? Yeah, and that's kind of my sentiments as well. We'll turn for one last word. John, you've been listening to this a little bit. Any words of wisdom from the back there? Positive. Three out of four. Three out of four and it was total 6.7. A little over six, yeah. 6.7, yeah. I mean, she's got reflux. It is abnormal. Whether or not that's contributing to her symptoms is very unclear. I think before I send someone for an anatomical fix, even if it's quite positive, I still tell them 50-50 chance it's gonna help you. I think that you'll see that over and over. So in this person, I might not try a Gabapentin trial. If her MIPH came back on therapy abnormal, then I would probably try Baclofen. I've had pretty decent success with Baclofen with cough. It's got a little bit of an antitussive effect to it as opposed to just being a reflux inhibitor. Gabapentin I've had very little success with. I do not believe that randomized control trial that was published because I've not seen a single person get better on Neurontin. So I think that that had been greatly exaggerated. So yeah, I want really definitive evidence that they're breaking through PPI therapy, which is a safe and effective therapy. If they do have abnormal reflux events and abnormal ass exposure on pH impedance on medicine, I will probably add Baclofen to that. If that doesn't work and they're pushing, I'll send them to a surgeon that I know will be very conservative. So we have a surgeon who rarely operates that I'll send them to. And he'll talk them out of it usually. And they'll just kind of go back to allergy and pulmonary and try to figure out something else. Any takers for a TIF in a situation like this as kind of a intermediate approach? Bonnie, I saw you shaking your head. I do think TIF works. I mean, it's an effective treatment. And if I was going to do something and the hill grade was one or two, and this was really a reflux mechanism, then I think TIF could be something that I would offer. I've had two people that have had primary reflux event, like abnormal reflux event that have gone for TIFs that have done quite well. But still, I think this is always going to be one of the most difficult problems we deal with. And people don't get better. Yeah, I think that the trap you could fall into is just this true, true and unrelated that you've documented GERD and that you've got a patient with a symptom and you're going to link them. And you could fall into the trap of going with, therefore they need treatment for the GERD. And every Tuesday we have this conference at Northwestern where we bring in all the surgeons and everyone talks. And a lot of them are these surgical mishaps where patients had good intention, but they just went down this algorithm saying, well, the next thing to do is to treat your reflux more aggressively. And they got a front application and they end up with some other complication from the front end. So I think one important teaching point is that just because you're showing GERD doesn't mean the GERD is causal in the patient's ENT symptom. And don't fall into that trap. And you have to go through that other list of all the other things three times before you make the recommendation to treat it. And look for other evidence. If you can find the corroborative evidence on a pH impedance testing, at least gives you more likelihood of having GERD as a cause, that's great. But I think you just have to be really careful about recommending invasive therapies here. Yeah, the other thing too is, when people come in with this cough and you look at their pH impedance study, sometimes they don't cough at all during the entire study. But yet this is something that made them come in and get two, three manometry sometimes, reflux testing. And I always question, what's really driving this? And that's where we've had the luxury of having five psychologists at Northwestern and our GI division. There's a lot to this acceptance, commitment therapy, where people kind of accept that this is kind of how their life's gonna be. And they really talk them down from going after these solutions that can be life-altering. And I think it puts them in a better perspective. So when you look at these patients, I think it's always important to, I mean, is this really destroying your life? And you'll get the people who say, who catastrophize, and maybe those people will benefit from a little bit of psychotherapy. Yeah, I mean, I think, again, for the audience, you feel pressure from a referring doctor or from a patient to do something. And it's our obligation to do the right thing. Forget about, again, you think about, oh, I'm not gonna get another referral. Do no harm. Do no harm. Yeah, yeah, I mean, you gotta do the right thing. What would you want if it was you or your family member? And you've gotta resist the pressure. The patients sometimes are the ones exerting the pressure, fix this problem. I've seen a million people. I'm now at University of X, where you are the maven. And these are challenging patients. So these are my take-home points here. And then we'll turn things over to Shivangi. GERD is one of multiple potential causes of unexplained chronic cough. In the absence of typical GERD symptoms, upfront testing, off-therapy is indicated. And I think that multidisciplinary evaluation is critical for management. I think you've heard that here. We've heard a little bit of different nuances on how to do it. But I think that if you have an organized approach, you can make these patients, you can make it work all the way around. And don't submit yourself to pressure here, okay? So Shivangi, I'm gonna step off and let you proceed.

chronic cough

42-year-old woman

heartburn

acid regurgitation

diagnose

treat