Intro: Welcome to UAB MedCast, a continuing education podcast for medical professionals, providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie Cole, MS (Host): Welcome to UAB MedCast. I'm Melanie Cole. And today, we're highlighting idiopathic pulmonary fibrosis. Joining me is Dr. Mridul Gupta. He's a pulmonologist with the Interstitial Lung Disease Program and an Assistant Professor of Medicine at UAB Medicine. Dr. Gupta, it's a pleasure to have you join us today. And for other providers who may not live in interstitial lung disease every day as you do, how do you frame idiopathic pulmonary fibrosis as a disease entity? What makes this so challenging to manage?

Dr. Mridul Gupta: Hi, Melanie. Glad to be here. And certainly, idiopathic pulmonary fibrosis, it's a challenging disease. I would frame it as a progressive fibrotic lung disease, which is driven by epithelial lung injury and dysregulated repair. This disease is most commonly seen in about the sixth decade of life. It's more common in Caucasians. And we would see like more the males getting affected by this.

The challenge is a lot of times there are delays in diagnosis. A lot of times, the patients get labeled as recurrent pneumonias and asthma and other diagnosis. And it may be like several months to years before a patient gets an accurate diagnosis, and they don't get started on appropriate treatment, which makes a difference to their long-term prognosis and treatment.

Melanie Cole, MS: Well then, Dr. Gupta, based on that, how can we shorten that time to an accurate diagnosis? Where do you feel that they get tripped up in that diagnosis as they're thinking pneumonia or multiple conditions? What do you feel we could do to speed that up a little bit in diagnosis?

Dr. Mridul Gupta: There are certain things when our providers, whether they are like general pulmonologist or primary care physicians, if they're seeing any factors which would put patients at high risk of having IPF or any of the other ILDs, they should have high index of suspicion. A lot of times, especially in our elderly patients in which we're seeing some reticulations on their CT scans, again, those findings can be non-specific, but we need to have high index of suspicions. Also, when we are examining our patients, when we are listening to like crackles, a lot of times they get attributed to heart failure. At bedside, we need to make a differentiation between like the velcro crackles, which are more associated with ILDs compared to more course crackles, which would be present in a heart failure patient. So if we have any clinical findings or other signs which would be suggestive of IPF, then these patients need to be referred to get pulmonary function testing and high resolution CT scans, which would be the diagnostic testing to get an accurate diagnosis.

Also, in most of the patients, and especially like more complex patients, having an expertise of a tertiary center with an interstitial lung diseases program becomes very important, because we have access to multidisciplinary discussions in which we can review patients with our group of ILD pulmonologists along with radiologists and pathologists and come to an accurate and confident diagnosis for our patients.

Melanie Cole, MS: That's great information, Dr. Gupta, for other providers and as far as pharmacologic courses of treatment, once we know what's going on, antifibrotic therapy has changed the natural history of IPF, but not necessarily cured it. I'd like you to speak about expectations for patients. And as I understand it, you have some updates from recent positive phase III clinical trials that you'd like to discuss. So, please tell us about that.

Dr. Mridul Gupta: So, the cornerstone of treatment of IPF has been antifibrotic medications. We've had two antifibrotic medications, pirfenidone and nintedanib, which were approved back in October 2014. They've been around for 12 years. The challenge with these medications is expecting. A lot of times when we are starting our patients on certain treatments, the expectation is they're going to feel better from this. Unfortunately, these medications, what they do is they slow down the decline in lung function. They slow down the process of fibrosis in their lungs. They don't get immediate symptom benefit. Instead, what they're doing is preserving lung function and improving long-term outcomes instead.

The biggest news in the IPF world from the last year is FDA has approved a third antifibrotic medication, which is the new medicine which we have after 12 years. So, it absolutely adds an extra therapeutic target that we can use for our patients. The biggest challenges of these medications have been their side effects. About at least half of the patients who get started on antifibrotic medications, they would get certain side effects. Certainly, our older patients would have disproportionately more side effects. So, we always have to balance out the risk and benefits in these patients.

Another additional benefit that we have with approval of nerandomilast or Jascayd is it is approved by FDA to be used as an add-ON therapy so the patients can be on background nintedanib or pirfenidone, and it can be used as an add-on treatment. One thing to keep in mind is the patients who've been on the combination therapy in the clinical trials had slightly higher rates of side effects. So, we always have to balance out the benefit from a combination therapy from the additional side effects which our patients may get.

Melanie Cole, MS: This is so interesting. And you're giving great information. Now, what about non-pharmacologic management? Based on some current guidelines, are there surgical treatments that you would look to and when do those come into play?

Dr. Mridul Gupta: So, the biggest benefit of the non-pharmacological treatments that we have, like the first one I would highlight is supplemental oxygen. A lot of our patients may need it even in earlier phases, because at rest they would be fine, but they have exertional dyspnea. So, our practices for all new evaluations, and at least once a year, we would do six-minute walk test in our patients to establish if they need supplemental oxygen.

The second thing would be referral to cardiopulmonary rehab programs. They are very, important for our patients. Our patients, when they go through a pulmonary rehab program, they notice improvement in their symptoms, improvement in their quality of life. And what I emphasize to my patients is when you are in the rehab program, you're working with our physical therapist and exercise physiologists. So, the things that you learn in that program, keep on doing them even after you finish that structured program at a rehab place.

Melanie Cole, MS: Well, along those lines then, Dr. Gupta, you mentioned a multidisciplinary team. So, tell us a little bit about what that looks like for these patients. I mean, there's many different clinicians involved. Tell us a little bit about some of the other specialist consultations that are indicated for treatment of IPF.

Dr. Mridul Gupta: IPF, it's a complex disease process. There are certainly other comorbidities we have to rule out. Certainly, there are some autoimmune conditions which can look very closely to IPF, and that actually leads to a diagnostic dilemma. For example, rheumatoid arthritis can look very much similar based on the CT scan like presentation on HRCT. So, getting input from rheumatologists from some of our patients is helpful. In very selected patients, we do have to get surgical lung biopsies. Again, we have gone away from doing surgical lung biopsies for IPF for the most part. But in rare cases where we have atypical-like presentations, we need expertise of our thoracic surgeons to get that diagnostic procedure for our patients.

In our multidisciplinary discussions, we have a group of ILD pulmonologists, along with thoracic radiologists and thoracic pathologists. So, getting expertise from various facets of ILD world helps in getting accurate diagnosis for our patients. And also, in some of our patients, they would eventually have progression, like most of these patients would have progression. Some of these patients can be a candidate for lung transplantation, which can be the only therapeutic or curative way of managing our patients.

Unfortunately, as I said, all the antifibrotic medications can do is slow down the progression. It doesn't reverse the fibrosis that has already happened. So, we do work very closely with our lung transplantation program. We do have a lung transplant program at UAB. And it becomes very helpful to work with them for the patients who can be an appropriate candidate for lung transplantation.

It's good to get patients plugged in into lung transplant program early in their disease course, as IPF can be highly variable. Some patients can have slow progression. But on the other side, others can have a rapidly progressive disease course or they can have episodic rapid decline in their lung function. So, having already being established and having that initial workup done in lung transplant program can help getting expedited listing to get a lung transplant.

In very selected patients, if they're presenting with an exacerbation and they are not doing well and if we are trying to bridge them to a lung transplant, we do have an option of getting them on ECMO. That is extracorporeal support for oxygenation.

Melanie Cole, MS: It's very comprehensive. And as we think of the patients and whether they're on bridge to transplant, working with this multi-D team, how do you integrate quality of life, Dr. Gupta, conversations into this routine care? What do you feel patients and families underestimate about living with IPF and clinicians sometimes? And while you're managing those comorbid conditions, what else are you working on, whether it's weight loss or smoking cessation with these patients?

Dr. Mridul Gupta: So certainly, for everything that we are managing medicine, the quality of life comes before anything else. So certainly, that's a discussion that we have with our patients very early in their disease course. Mostly in our first or second clinic visits, those discussions come in even before starting antifibrotic medications. Because as I said, a lot of these medications can have a heavy side effect burden. So, we always have to weigh out how much side effects the patients are getting and how much benefits the patients are getting.

Few of our patients, after hearing all the discussions, they like not to go on those medications to have a better quality of life. And that is very much reasonable. Same goes for the patients undergoing lung transplantations. It is a very complex surgery, and it can be several months of recovery after the process. So, trying to talk to the transplant team in advance, trying to talk to other patients who might have gone through lung transplantation, understanding what the quality of life would look during the transplant evaluation, after the transplant evaluation. All those things come very handy.

There are certainly other things that we can do. As you had said, if the patients have been smokers, trying to achieve smoking cessation comes in handy. Because if they continue to smoke, they would have more rapid decline in their lung function. So if you are able to help them with appropriate resources and to achieve smoking cessation and able to get to a cardiopulmonary rehab program, that would make sure that they get a good quality of life.

Unfortunately, some of our patients do get into acute exacerbations and they can like progress and invariably they can die from idiopathic pulmonary fibrosis. So, having those conversations early enough, it helps. We do have palliative care, palliative care teams at UAB that we can engage for our patients. And just discussing or talking to palliative care does not mean like end-of-life care. It is to focus on their symptoms and making sure that they have a better quality of life while they are living with IPF.

Melanie Cole, MS: Great information, Dr. Gupta. As we wrap up, are we moving toward a future of disease phenotyping, personalized therapy in IPF? Tell us a little bit about what you hope to see in the next bunch of years and why it's so important that physicians look to such an experienced team as you have at UAB.

Dr. Mridul Gupta: We do have a lot of promising research that has been going on for the past few years. 2025 was a great year with having some positive clinical trials. We are looking into like evaluating specific gene mutations, which can help us stratify how our patients are going to behave. We are seeing more AI and machine learning-based tools in which we can evaluate the CT scans and other information from the patients to predict which patients are more likely to progress. All these things can help us focus our efforts on the patients who can get like most benefit from our medications.

We have some early phase II clinical trials, which I'm very excited about. We are now evaluating antifibrotic medications as an inhalation therapy. We are hopeful that when we are using that way of medication delivery, we'll be able to achieve like similar treatment benefits with a lot fewer side effects.

Nerandomilast or Jascayd is like the first treatment that we are able to use as an add-on therapy. This, as I said, is the new medication that has been approved in October 2025. Hopefully, we are looking into more medications, which can be used as a combination therapy, which are hopefully going to be with lesser side effects and better tolerability.

One of those medications which we have completed phase III clinical trials out of Europe as inhaled treprostinil. We are still waiting for the North America Clinical Trial of TETON to finalize their data collection and to come up with the results. And hopefully, that would be another, treatment option that we can use as a combination therapy for our patients.

Melanie Cole, MS: Thank you so much, Dr. Gupta, for joining us today and really sharing your incredible expertise in this area. Thank you again. And for more information, please visit our website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole.