Interstitial Lung Disease and Esophageal Disorders: When Specialties Work Together

In this special podcast Dr Rita Knotts and Dr Elizabeth Volkmann discuss the intersection of their specialities in the care of patients with scleroderma, interstitial lung disease, and esophageal conditions such as reflux.

Rita Knotts, MD, is a specialist in neurogastroenterology and motility at with the Center for Esophageal Health at NYU-Langone Health in New York City. Elizabeth Volkmann, MD, is founder and codirector of the Connective Tissue Disease-Related Interstitial Lung Disease at the University of California Los Angeles.

TRANSCRIPT:

Any views and opinions expressed are those of the authors and or participants, and do not necessarily reflect the views, policy, or position of the Gastroenterology Learning Network or HMP Global its employees and affiliates.

Welcome to this podcast, which comes to you today from both the Gastroenterology Learning Network and the Rheumatology and Arthritis Learning Network. I'm your moderator, Rebecca Shaw. And today this cross-disciplinary podcast features two outstanding contributors, Dr. Elizabeth Volkmann, who is the founder and director of the Connective Tissue Disease- interstitial Lung Disease Integrative Clinic Program and director of the Scleroderma Program at the University of California Los Angeles. And Dr. Rita Knott, a specialist at the Center for Esophageal Health at NYU Langone Health in New York City. Today, doctors Volkmann and Knotts are going to discuss a study that Dr. Volkmann was involved in on the association of symptoms of GERD, esophageal dilation, and the progression of systemic sclerosis-ILD, which is what inspired this podcast. So thanks to both of you for taking the time to talk about this very interesting topic. And with that, I'm going to hand it over to Dr. Knotts who's going to lead us off.

Dr Knotts:

Hi. Hello, Dr. Volkmann. I thank you for writing such an interesting paper. I was wondering if you could walk us through a little bit about the patient population you explored and some of your findings.

Dr Volkmann:

Yeah, thank you so much. It's really a pleasure to be here, and I think it's wonderful to have a dialogue between a rheumatologist and gastroenterologist on a disease like scleroderma that affects so many different parts of the body, including the GI tract. But this was a study where we looked at a unique patient population. These were patients with scleroderma-related ILD who participated in a large clinical trial called the Scleroderma Lung Study 2. And this was an NIH-sponsored trial that compared oral cyclophosphamide that was given for 12 months, followed by 12 months of placebo versus mycophenolate for 24 months. And the primary endpoint in this study was looking at the forced vital capacity. And in this study, many patients experienced an improvement in their FVC with these treatments, but there were some patients who continued to have progression. And so the motivation for doing this research was to try to understand what are the factors that might predict someone experiencing ILD progression despite therapy, and one of those issues could be the severity of their esophageal disease.

Dr Knotts:

That's awesome. Thank you so much. So can you tell us a little bit about your findings, especially with reflux testing and how that relates to disease severity?

Dr Volkmann:

Yeah, so one of the things, and this is something I know you're very familiar with as a gastroenterologist, but we don't have a lot of different ways to objectively measure the severity of reflux disease in scleroderma. So we rely a lot on patient reported symptoms. And so there is a valid questionnaire called the UCLA GIT 2.0, and this has a domain specifically for esophageal symptoms. And we looked at patients' responses on this domain and they basically were given a score. And so we used this score to then look at the relationship between the severity of their self-reported reflux disease and then their radiological progression of ILD. We also looked at their CT scan and we at UCLA use a special computer algorithm for quantifying the extent of ILD, the extent of fibrosis, and we were able to use this algorithm to also quantify the area of maximum dilation in the esophagus, which we thought might be a surrogate for severity of reflux disease. So interestingly, we did find that the patient-reported symptoms were associated with patients having more progression of their ILD over the course of the study. But looking at the radiological measurement, which was again that area of maximum dilation, it didn't correlate with progression. And it could be—and I'd love your thoughts on this—that maybe just looking at the esophagus at one point in time and looking at dilation might not be as meaningful as looking at something like motility. What do you think about that?

Dr Knotts:

Absolutely think that there is likely a temporal factor associated with this. And typically at our center, we do study a lot of these patients with manometry and pH impedance testing. And that really helps, gives us a sense of how well, it helps to give us a sense of the patient's overall motility. And it also helps us to understand their disease severity as well with regards to reflux, how well they're responding to PPIs. We tend to do a lot of these patients, to study a lot of these patients on PPI, particularly our pulmonary patients. And while there's no distinct guideline for that, we do see that PPI use doesn't necessarily or response to PPI doesn't necessarily alter their underlying pulmonary function. And that may be because there's micro aspiration and the fact that dysmotility is largely associated with non-acid reflux events. So we know that PPIs only change pH, but it's not necessarily, it only changes the pH of a regurgitant, not necessarily what the patient is bringing up, which is likely correlated with their pulmonary function as well. Do you guys typically study your patients? I know that your study largely focused on symptoms, but how often are you guys sending your patients for testing? And at one point do you decide to do that?

Dr Volkmann:

Yeah, so because this was a clinical trial and the focus was on lung disease, we didn't perform manometry in these patients. But in clinical practices it is something that we routinely do for, I would say all of our patients when they're diagnosed get a upper endoscopy, and then we typically do some type of motility testing in these patients as well, for the upper GI tract; the lower GI tract I think is a whole other story and maybe not so clear what to do at baseline. But certainly in patients with early scleroderma, even before the patient even experiences reflux disease, they can have, as you probably know, changes in these objective tests. So we try to do this early on to help establish a baseline so that we can use it to kind of monitor progression over time. But you brought up a great point about the proton pump inhibitor use in our multi-variable model.

In this paper, we controlled for a treatment arm baseline ILD disease severity and also PPI use, and it really didn't alter the relationship between severity of reflux disease at baseline and radiological progression. So I agree that there's probably other factors that might be important in terms of perpetuating this process in the lungs besides the acid contents that we're trying to eliminate with the PPI use. Another question I wanted to ask you, and it's a little bit outside of this paper, but something that I face a lot in my practice now, is that many patients are reluctant now to use PPIs. They have concerns about lots of issues like osteoporosis, dementia, SIBO, and SIBO is something that affects scleroderma patients. So how do you approach this discussion with your patients in your practice?

Dr Knotts:

I think that's a great question. I think that's something that many gastroenterologists are facing right now because patients are being taken off PPIs, patients are afraid to take PPIs. So I really try and focus on concrete data and the data showing the long-term effects of PPIs. And really what we know about that is that PPIs are certainly associated with enteric infections, and that appears to be very robust in current literature. But a lot of the other things and a lot of the other data is not quite as robust, especially with risk factors for dementia and cardiovascular disease. And so I really try and center it on a number of factors. The most important being the need for a PPI: have we studied the patient, are we certain that they have reflux? And do those patients certainly need a PPI to improve their symptoms or for some other cause, if you don't necessarily have reflux or you're not necessarily responding to PPIs, maybe you're not a good candidate for PPIs.

So when we're looking at risks and benefits, perhaps the benefits don't outweigh the risks in those situations. But there are a number of patients that have erosive disease that certainly need to be on PPI or erosive esophagitis that need to be on PPI. So I really center the conversation on the need for PPIs if the risks outweigh the benefits and the fact that the data is not as robust for many of the factors that patients are mainly concerned about. For example, we know that there has been a link with long bone fractures, but when we look at changes over time and bone mineral density, the data's not as robust for that. So I try and really focus on the things that have a significant odds ratio in these studies, the things that we know may concretely be associated with PPIs. And I frequently say an association is not a causation, but there are some people that don't need to be on PPIs, and at that point, their risks, the concerns are valid and I'm happy to take patients off those drugs.

Dr Volkmann:

Right. Yeah. So I think same here. I think it's a very individual patient decision and you really have to take into account the whole patient. If we have a lot of patients with scleroderma that have difficulty sleeping because of the reflux symptoms being worse at night, if someone's not sleeping through the night, that has its own deleterious effects on their health, not just the next day, but if cumulative, they're losing sleep, this can really affect their health and their autoimmune disease. So I think that's a really important point and something that we're all going to continue to face. The more that these risks are put out into the lay literature, we have to have more communication with patients for how they can interpret these articles that they read online.

Dr Knotts:

I think that it's really powerful that you’re a rheumatologist discussing many of the gastrointestinal factors that are associated with scleroderma at your center. I know you're at a large tertiary care center. Can you tell us a little bit about the multidisciplinary model that you may work under and how that may be helpful in patients with scleroderma?

Dr Volkmann:

Yeah, no, absolutely. So I direct our CTD-ILD program, and this is a multidisciplinary team that's comprised of a core group of specialists. So the core group is rheumatology, pulmonary, radiology, and pathology. So any patient who comes to our center who has interstitial lung disease undergoes a multidisciplinary review where we present their clinical case and history, go over their labs or pulmonary function tests, and then review their radiology and then when available, their pathology. And then we come up with a diagnosis based on consensus and then develop a treatment plan. And patients can be subsequently entered to our group if they, for example, experience ILD progression despite initial therapy. But then we also have other members of the group that come into play when we feel like it would be helpful. And so that includes gastroenterologists, and we are fortunate to have a few at UCLA that focus on motility, and we're very grateful for their help because as you know, there's not a lot of gastroenterologists that focus in this area like you do. Sometimes we bring in oncologists because these patients have a higher risk of lung cancer, and we'll have patients with scleroderma ILD who have lung cancer. But I think the multidisciplinary team is really essential for caring for these patients because they do have this systemic disease and there's no way to just look only at their lungs. You have to look at the whole patient when you're coming up with these treatment plans.

Dr Knotts:

That's wonderful. I think you mentioned that there were surgeons and some gastroenterologists and how your study looked at esophageal dilation and the radiographic correlation with it among any of those patients or in your clinical practice, we know that a lot of these patients also have reflux and likely worsening reflux disease. How and when do you as a team decide to refer someone for an antireflux surgery? Do you make that decision? Does your gastroenterologist lead that decision? Does your group lead that decision? And do you ever notice whether or not that has changed any of your long-term outcomes in any of these patients?

Dr Volkmann:

That's a great question, and I typically will defer to the gastroenterologist to make that decision because I feel like they're more access to this area than me. But we certainly do. And one area where we probably do it more is in patients being evaluated for lung transplantation. These are patients where if they have very refractory reflux disease, it could affect their eligibility. And we've done surgery in these patients and it's actually really benefited the patients, made them eligible for a transplant, and then ultimately they got a transplant and did very well. So speaking about lung transplantation, but we've even done it in other patients who aren't even at the point where they need a lung transplantation when they're not responding to medical therapy. So I know that surgery isn't done necessarily in the general population as maybe it once was many years ago, but certainly in scleroderma, I think there's a time and place for it. Is this how you approach it or?

Dr Knotts:

Absolutely. We actually also have a multidisciplinary team where we work with surgeons, our lung transplant team, our pulmonologist, and we try and make these decisions very thoughtfully and carefully. We are very concerned about patients, particularly in the posttransplant setting, as we know that reflux can affect transplant outcomes, the risk of bronchiolitis and rejection. And so we try and be very diligent within the first 90 days, including mainly in our transplant patients and our post-transplant patients about reassessing these patients, evaluating them, and bringing them in for surgery so that we can maintain their allograft function. But we're very, very careful and thoughtful in our scleroderma patients as well, because the decision is never taken lightly.

Dr Volkmann:

So one of the interesting things, and I'm involved in a lot of drug development in scleroderma, and largely it's focused on lung disease and skin disease, and many companies have been reluctant to develop drugs for GI disease and scleroderma because we do lack objective measures of GI disease activity in scleroderma. We mostly rely on these patient-reported measures. And I think this paper highlights that looking at something at one point in time, like esophageal dilation on HRCT, might not be the best way to look at severity of esophageal disease and looking at maybe motility measures might be better. But in the future, what do you see as a way to improve how we clinically not only monitor patients with esophageal disease and scleroderma, but maybe how we can apply that to future research studies?

Dr Knotts:

So I don't think there is going to be, at this point in time anyway, any perfect means of testing, but certainly the addition of higher resolution esophagal manometry, as well as pH testing, whether that be pH impedance testing or wireless pH testing, can be helpful in a useful adjunct in these patients to be able to assess their esophageal disease or the degree of esophageal dysfunction, whether or not they have an alternative motility disorder like gastroparesis or small bowel dysmotility. So the use of a gastric emptying study or some other means of testing could be helpful. And I paused on that a little bit because up until recently, a wireless motility capsule was a useful agent to assess a degree of gastric small bowel and chronic dysmotility. But that's being phased out at this point. So we do have a sort of limited tool set in our armamentarium at this point, but it can be useful to have objective data with the use of manometry and pH testing, particularly to quantify the degree of reflux to further assess these patients and how well they respond to therapies.

What an incredible discussion. Thank you so much, Dr. Volkmann, for sharing your research and your patient experience. This has been truly enlightening for all of us. We look forward to further reading about your research in the future and hope that we can learn from how you build upon this for such a complex patient population. Thank you.

Dr Volkmann:

Thank you so much.

Rebecca Mashaw:

Thank you both for coming on today to have this really interesting discussion. Again, you've been listening to Dr. Elizabeth Volkmann from UCLA and Dr Rita Knotts from NYU Langone talk about the intersection of gastroenterology, and specifically esophageal study of the needs of the patient with systemic sclerosis and interstitial lung disease. I hope you've enjoyed this and you found it very helpful and interesting. Thanks.