New Frontiers in Idiopathic Pulmonary Fibrosis (IPF) Treatment

Overview:
In this video, Dr Elizabeth Volkmann shares her extensive knowledge of IPF, including epidemiology, pathogenesis, current treatment approaches, and therapies in development.

Learning Objectives:

• Review the epidemiology and burden of IPF, including the impact on health-related quality of life and mortality.
• Describe the underlying pathogenesis of IPF, which is characterized by progressive fibrosis.
• Identify current treatment paradigms in IPF and describe the mechanism of action of available therapies.
• Outline new therapies in development for the treatment of IPF.

Presenter:
Elizabeth Volkmann, MD, MS

Dr Elizabeth Volkmann is an Associate Professor in the Division of Rheumatology at the University of California, Los Angeles, where she serves as the Director of the UCLA Scleroderma Program and the founder and Co-Director of the UCLA Connective Tissue Disease-Related Interstitial Lung Disease (CTD-ILD) Program. Her research focuses on the identification of novel biomarkers that predict response to ILD-targeted therapies. Dr Volkmann endeavors to develop personalized treatment algorithms for patients with ILD grounded in solid translational science. She also has an enduring interest in exploring how the gut microbiome contributes to the pathogenesis of ILD and systemic sclerosis.

Transcript:

Presentation Portion:

Moderator: Hello, and welcome to today's First Report Managed Care webinar. My name is Cynthia Cooley-Themm, and it's my pleasure to welcome you to this webinar titled New Frontiers in Idiopathic Pulmonary Fibrosis Treatment. Our speaker for today's session is Elizabeth Volkmann.

Dr Elizabeth Volkmann is an associate professor in the Division of Rheumatology at the University of California, Los Angeles, where she serves as the director of the UCLA Scleroderma Program and the founder and co-director of the UCLA Connective Tissue Disease-Related Interstitial Lung Disease Program. Her research focuses on the discovery of novel biomarkers that predict response to ILD-targeted therapies.

Dr Volkmann endeavors to develop personalized treatment algorithms for patients with ILD grounded in solid translational science. She also has an enduring interest in exploring how the gut microbiome contributes to the pathogenesis of ILD and systemic sclerosis.

During the presentation, you will be prompted with some poll questions to answer in the box to the right of the screen. You can also type your questions for the presenter in the same box. We will try to answer as many questions as we can in the remaining time at the end of the session.

Without further delay, let's get started.

Dr Volkmann: Hi everyone, welcome to this program on New Frontiers in Idiopathic Pulmonary Fibrosis or IPF Treatment. My name is Elizabeth Volkmann, and I am an associate professor in the Division of Rheumatology at the University of California in Los Angeles where I direct our Scleroderma program as well as codirect our CTD ILD program, and my disclosures are listed below.

The learning objectives today are to, first of all, review the epidemiology of IPF and, the burden at the disease, and how it impacts quality of life. Second, we will describe the underlying pathogenesis of IPF, which is characterized predominantly by progressive fibrosis. Third, we will identify the current treatment paradigms for IPF and describe the mechanisms underlying how these drugs work. And finally, we'll outline new therapies in development for IPF. So, to begin, IPF, as many of you know, is a chronic and debilitating disease. It's of unknown origin, but it's characterized by gradual scarring that leads to damage in the lungs.

The clinical presentation of IPF can be nonspecific, particularly in the beginning where patients may notice subtle changes in shortness of breath. They can experience a cough, which could be wet or dry, as well as declining lung function. In terms of the diagnosis, we rely heavily on CT scans, as well as histology evaluation, because we know that diagnostic delays can affect both morbidity and mortality.

The incidence of IPF has been increasing in the United States. So, IPF can actually be diagnosed in up to two-thirds of patients with idiopathic interstitial pneumonia. Currently, there are over 130 000 people in the United States living with IPF.

The annual incidence in adults ranging from age 18 to 64 is six cases per 100 000 per person/year. If a patient is over the age of 65, the incidence is greater: 94 cases. In terms of the prevalence in adults, again, in this younger age group, 18 to 64, there are eight cases per 100 000.

Whereas in patients over the age of 65, there are 495 cases per 100 000. IPF is associated with a number of different other diseases and comorbidities. And there are also risk factors for IPF.

For example, smoking is a known risk factor, and people who have smoked have a 60 % increased risk of developing IPF in the future. There are also known environmental exposures and these can include exposure to silica, wood, metal, and stone dust, as well as occupational exposure to agriculture, farming, and livestock. Again, all of these factors can play a role in the development of IPF.

As we saw in the previous slide, age is also a known risk factor, and IPF generally occurs in patients who are older than the age of 50 years. In addition, male sex is associated with a greater risk of developing IPF. Family history is another important factor and 30 % of patients who have a family history of pulmonary fibrosis have a genetic predisposition to developing idiopathic pulmonary fibrosis.

And then here is a diagram of the comorbid conditions that occur commonly in IPF, and these can include things like lung cancer, COPD, GERD or reflex disease, diabetes, pulmonary tension, coronary artery disease, hypertension, as well as obstructive sleep apnea. And so, when we're managing patients with IPF, we have to not only care for their IPF, but we have to look at these other comorbidities and treat them as well.

In terms of the mortality risk, in terms of respiratory failure, this can occur within 3 to 5 years from the time of diagnosis. This is a debilitating disease that can progress quite quickly, where some patients, again, within this 3-to-5-year range, will develop respiratory failure and are at risk for death, particularly if they don't get a lung transplant. Studies have shown that for patients living with IPF, health-related quality of life is associated with clinical symptoms, duration of disease, physical activity, comorbidities, as well as the severity of the disease. The pathogenesis of IPF is multifactorial.

So, we know that there is some element of epithelial damage that causes destruction to lung tissue. And we also know that there are accelerated aging-associated changes. And with this comes an increased risk of developing fibrosis. This is perpetuated by the constant laying down of the extracellular matrix in areas where it shouldn't proliferate. So, we can see here on this figure on the left side is a normal lung where you have this interstitial layer that's quite thin. And then in a patient on the right side who has IPF where they have damaged alveoli, damaged airwaves, and they have thickened alveolus wall with fibrosis, and this impairs gas transfer and the ability of oxygen to get from the airways into the bloodstream.

In terms of phosphodiesterases or PDEs, these can play a role in the pathogenesis of IPF. So, what are PDEs? They are a group of enzymes that are widely distributed throughout cells and tissues in the body, and they take part in intracellular signaling. So, they play a key role not only in fibrosis but also in inflammation.

PDE4 is a part of lung fibroblast cytokine-induced proliferation, as well as myofibroblast conversion. So, again, in the respiratory tract, in the GI tract, we see PDE4, and it's involved in the perpetuation of not only fibrosis but also inflammation. In terms of the current treatments for IPF, they are somewhat limited.

And when we think about selecting a therapy for the patient, we have to consider the whole patient, including the severity of the IPF. Currently, there are no cures for IPF, but we do have two approved therapies, which include nintedanib and pirfenidone. And these medications have been proven to reduce the number of exacerbations that the patients experience.

However, like all medications, they come with certain side effects and risks. So, for example, possible side effects of nintedanib and pirfenidone should be discussed with patients before you start therapy. Nintedanib can cause diarrhea, and pirfenidone can cause nausea and rash.

But both of these medications can decrease the rate of lung function decline compared with the placebo. However, there have not been any studies demonstrating that they improve overall health-related quality of life. So, when we have these treatment discussions with patients, we heavily weigh the risks and benefits of these therapies when we're choosing which one we want to use in each patient.

The only possible cure for IPF currently is lung transplantation. But this is only considered for selected patients who have advanced IPF. And there could be factors, for example, advanced age, that could preclude someone from getting a transplant.

Supportive care is also a cornerstone of IPF management. And what I mean by this is that we use other modalities to help improve how patients feel and function with this disease. One of the things that can be very helpful for patients is to start oxygen therapy.

Some patients may be reluctant to start oxygen therapy, but once they get used to this concept, they realize that the oxygen allows them to move more in their lives and participate in the activities that they enjoy. Smoking cessation is also important, as well as pulmonary rehabilitation. For those of you unfamiliar with pulmonary rehab, this is a form of supervised exercise for patients.

I find that every patient that I refer for pulmonary rehab enjoys this process because they learn what they can do safely. They learn what their limits are in terms of walking and exercise, and it can give them a lot of confidence in what they can do in their daily life, even if they're on oxygen. Vaccines are also very important because these vaccines, for example, the pneumonia vaccine, can reduce a patient's risk of developing infections.

When a patient has IPF, they have structural changes in their lung that independently will increase the risk of infection. So, as a provider, you want to do everything possible to minimize that risk, and vaccines play a very important role here. The last point I'll mention is about palliative care.

I find palliative care to be so helpful as an adjuvant care team for my patients. Physicians who specialize in palliative care can focus on other topics that maybe we don't have time to address in our busy clinics, whether you're a pulmonologist or a primary care doctor. They can really work with the patient on managing their pain— managing these disruptive symptoms such as cough— and they can often meet with the patient a lot more regularly.

Sometimes, people think that you shouldn't refer a patient for palliative care until they're at the very end stage of their disease. But this is not true. You can include patients getting palliative care very early on in their disease course, and this can tremendously improve their quality of life.

The management of IPF is complex. We have to consider the treatments we give patients, and as we mentioned, nintedanib and pirfenidone are two pharmacological therapies. We also want to consider the management of the comorbidities.

So, things like pulmonary hypertension, reflex disease, OSA, as well as lung cancer. There are nonpharmacological therapies that we discuss, such as oxygen and pulmonary rehab, and then again, incorporating palliative care because this can help with symptom management. In addition, you're going to be giving your patients these treatments, but you also want to be closely monitoring them for the progression of IPF. We do this using objective testing that can be done in your clinics. So, pulmonary function testing and 6-minute walk testing should be done every 4 to 6 months, or even sooner if it's clinically indicated. Doing a CT scan can also give you added insight into the progression of the disease.

I find the CT to be invaluable, particularly in cases where a patient may have other factors that could affect how well they walk. For example, maybe they have arthritis, so they can't walk as far in the clinic, and it's not because of their lung disease; it's because of their arthritis. The CT can give you more direct insight specifically into the ILD and how it's progressed radiologically.

If there's a concern for another pulmonary process, like a pulmonary embolism, then you may need to do a special type of CT, such as a CT angiogram. In terms of treating acute exacerbations, many times, patients might have to be hospitalized, and they may have to be treated with corticosteroids. Throughout this process, you're going to be evaluating the patient to determine whether they need a lung plan, and you'll want to initiate that referral process as soon as it becomes apparent that the patient may need a transplant.

There are novel approaches that can address unmet needs in IPF. So, there were recently eleven European patient advocacy groups that identified five important themes to address unmet needs. One of them was to improve diagnosis and, particularly, the early diagnosis of these patients, to increase the access to a variety of treatments. We've discussed some of those treatments, but even more importantly, to provide emotional support for these patients.

The mortality associated with IPF is really worse than many cancers that we have, but because this is a rare disease, patients don't often get the same type of support from their community—if they would have had a cancer, for example, that more people understand and recognize. We need better informational resources that are reliable and accessible to all patients, even in patients who speak different languages.

And again, we need to offer palliative and end-of-life care. So, I think what's great about this research is that it included the patient perspective, which is really something that we always want to keep in mind when we care for patients. There are a number of new IPF therapies on the horizon, and this is very exciting because, due to the progressive and debilitating nature of this disease, coupled with the poor prognosis and no currently available curative therapies, we need more novel therapies for IPF.

So, the future of IPF treatments is listed here. We have some PDE4 inhibitors that could inhibit both immune or inflammatory, as well as fibrotic processes. We have Pentraxin II, which prevents monocyte differentiation and monocytes are an important component of the immune system that can help perpetuate fibrosis.

Number three—and some of these are difficult to pronounce, like all medications— pamrevlumab, which is an antibody that targets connective tissue growth factor. Growth factors are also fundamental to propagating fibrosis in patients. There are also studies looking at combining pirfenidone with nintedanib to see if you can get added benefits.

And then finally, adding antimicrobial therapy to standard IPF treatment. So, in summary, IPF is a chronic progressive disease of unknown origin, and the incidence of IPF seems to be increasing in the United States. The pathogenesis of IPF is multifactorial and involves an interplay of epithelial damage, lung tissue destruction, as well as accelerated aging-associated changes, including fibrosis.

We do not have a cure yet for IPF, though antifibrotic medications and supportive care can help slow the disease progression and keep patients feeling more comfortable longer. Novel treatment approaches for IPF are currently in development, including new drug combinations and novel mechanisms of action. I want to thank you for your time today. We'll now move into the Q&A portion of this program.

Question and Answer Portion

Moderator: Fantastic! Thank you so much, Dr Volkmann, for such an excellent presentation. Our audience does have some questions for you, so let's get right to them. First question; what is causing the increase in incidence of IPF?

Dr Volkmann: That's a great question, and I wish I had all of the answers to that question. I think there are two possibilities. One, we're probably doing a better job at diagnosing this condition. Previously, patients with this condition were often misdiagnosed with other more common lung diseases, such as COPD, and the diagnosis of ILD was usually missed early on. Secondly, there could be environmental factors that could be contributing to the increased incidence. And this could be related not only to factors in our environment but also in the foods that we eat as well. And hopefully, more research will illuminate the specific environmental factors that are contributing to the increased incidence of IPF.

Moderator: Great! Next question. What treatment options in development are the most promising?

Dr Volkmann: There are a number of clinical trials ongoing for idiopathic pulmonary fibrosis now, and I think that the ones that are very novel, or ones that are looking at targets that are not only involved with fibrosis but also with inflammatory pathways, and even pathways that target vascular factors because this is a disease that is really based on this interplay of inflammation, fibrosis, and vasculopathy like a lot of other ILDs. So, current therapies in development, and we talked about a couple in the talk just now, I think these are among the most promising that we see. I think other strategies could be combining therapies.

So, it could be that maybe not a single therapy is going to be effective for curing this condition, but combining different therapies together that have distinct mechanisms of action could potentially help to further prevent the progression of this disease. And then finally, you know, with fibrosis, if we're truly going to find a cure for fibrosis in the lungs, we need to understand how to reverse fibrosis. So, a lot of the therapies and development are targeting upstream pathways to prevent the development of fibrosis.

I think we have to think about too, when there is fibrosis present, what can we do to potentially promote the degradation of the cellular matrix? We can potentially learn from other diseases, such as post-COVID fibrosis because we know that in a proportion of patients who've got COVID-19 pneumonia, they developed fibrosis. And then, over the course of time, many patients had reversal of fibrosis without any intervention.

Studying this kind of population to understand what are the mechanisms that existed within these patients to reverse fibrosis and then, try to capitalize on that understanding to develop new therapies, that can target this reversal of fibrosis.

Moderator: That's exciting! Let's see, next question. Forgive our pronunciations here; I'll do my darnedest. If a patient is on pirfenidone and demonstrates progression of IPF according to an HRCT scan, is there any role for switching to nintedanib?

Dr Volkmann: That's a great question! I think it stems from the fact that you know, potentially, one patient might respond better to one antifibrotic over the other. So, if a patient fails, you know, either nintedanib or pirfenidone, there could be a benefit of trying the other one.

In this case, the patient was experiencing progression despite pirfenidone. I think it would be reasonable to consider treatment with an intensive. Another time that we switch therapies is also when patients are demonstrating intolerability or toxicity issues. So, we'll have some patients who'll develop, you know, certain symptoms with these medications that become intolerable, and then we will have to switch them to the other antifibrotic. But I'm hopeful that, you know, more drugs come onto the market for idiopathic pulmonary fibrosis will have even more options for patients to switch to.

Moderator: Fantastic! Next question. Is there a relationship between radiation therapy in the distant past—say, over 40 years ago— and the development of IPF later in life?

Dr Volkmann: That's also a great question. There's definitely a relationship between radiation exposure, specifically to the chest area, and the development of fibrosis. Usually, though, this type of fibrosis is distinct from idiopathic pulmonary fibrosis or other forms of ILD, and discerning radiologists and pulmonologists are able to make these distinctions. I'm personally not aware of any relationship between distant radiation exposure and the future development of idiopathic pulmonary fibrosis. But it doesn't mean that there isn't a connection. I just don't think there's much research in this area.

Moderator: That makes sense. Maybe in the future, we'll find out. Next question. For a patient who cannot swallow pills, are there any alternative medications?

Dr Volkmann: That's a great question too. Most of these patients experience reflux disease. And I'll just speak a little bit about this and then I'll get to your question. But patients with IPF can have reflux disease and this may be related to dysfunction of the esophagus.

Many studies have demonstrated that reflux disease can perpetuate the progression of fibrosis in the lungs. And this could be from, you know, the contents that are reflux aspirating into the lungs and causing local inflammation, which can trigger more inflammation. I think the exact mechanisms relating reflux to ILD progression are still under investigation, but it's something to consider in your patients because we typically give our patients proton pump inhibitors, but these really only block acid production and don't prevent aspiration of nonacidic contents into the lung.

We're starting to explore using promotility agents in these patients. But getting back to the original question, and if you could just state it again because I think my tangent got me off track.

Moderator: Sure, no problem. For a patient who cannot swallow pills, are there any alternative medications?

Dr Volkmann: Yeah, so great. I'm not aware of any approved therapies for IPF that aren't properly administered. However, there is a trial looking at inhaled medications such as inhaled pirfenidone and inhaled nintedanib that are currently ongoing. I think inhalation products might be a nice alternative for patients who have a difficult time swallowing pills, but those are not currently on the market.

Moderator: Great! Looking forward to that being available. Next question, why do some patients with IPF have a dry cough and others have a wet cough with copious secretions?

Dr Volkmann: Great, great question! You know, and I think that the type of cough a patient has, no matter whether it's wet or dry, can be very disruptive to their quality of life. Particularly, this happened a lot during the pandemic when people felt embarrassed to go in public and were often humiliated because people thought they were coughing because they were infected with COVID and were irresponsible, you know, infecting other people when, in fact, it was due to their IPF. I don't think we know why some patients experience a dry or wet cough. Certainly, if I have a patient who's experiencing more of a wet cough, I'm always looking for other causes, such as infection.

I don't think whether it's dry or wet, you can completely say what the cause is unrelated to IPF, but infection is a possibility. These patients, like all of us, can get allergies and postnasal drips that can contribute to a wet cough. Then, the reflux disease itself could be a dry or wet cough.

I don't think we know why some patients get a wet or dry cough, but I would say that if you have a patient with a wet cough, look for other causes too, such as infection, postnasal drip, allergies, and reflux disease, because these can also contribute to the quality of the cough that the patient has.

Moderator: That makes sense. Next question, how would someone learn about clinical trials available for IPF patients?

Dr Volkmann: Yeah, and another great question because there's so much exciting drug development in this area. I think it's important that providers understand where to send their patients to learn more about trials because these trials are often done at expert centers where they have interstitial lung disease specialists who are performing these trials.

A good way to learn about these centers is through the Pulmonary Fibrosis Foundation. They have a website, and there's actually a registry that they have called the Pulmonary Fibrosis Registry. The participating sites of these registries are typically ILD centers of excellence, and these are usually the sites where trials are ongoing. So, this is a good starting point, and you can look geographically to see what the closest ILD center is to where you practice that might be feasible for a patient to travel to. Very often, because of the rarity of these diseases and now we're having a number of trials going on at the same time, many sponsors of these trials are willing to pay for a patient's travel.

So, at my center, the sponsors will even cover travel for patients living out of state in states where they don't have trials available. Looking into these options I think is important because many times patients don't know where to look, but the Pulmonary Fibrosis Foundation is a good starting point. Another place is ClinicalTrials.gov.

This would give you a lot of information about trials. But I find that ClinicalTrials.gov is not so easy for patients to navigate unless they have some kind of medical background. So, I think the Pulmonary Fibrosis Foundation might be a better starting point for patients.

But as a provider, you can also visit clinicaltrials.gov. And there you're going to learn a lot of details about the trials. So not only where they're being conducted, who the PIs are, but also what the endpoints, and what are the important inclusion-exclusion criteria so you can determine whether a particular trial is a good fit for your patient.

Moderator: Fantastic. This is a very related question. What are the pros and cons of participating in a clinical trial?

Dr Volkmann: That's another great question, and I think, you know, I do a lot of research, and any time I recommend a trial to a patient, I try to put myself in their shoes and really think about, okay, what would be the benefit for me if I was doing this trial and what would be the downside? So, we'll start with the downsides first.

I think one of the downsides is that many of these trials are placebo-controlled, meaning that you don't know if you're getting the experimental drug or not. For some patients, this can make them feel uncomfortable because even their providers won't know; everyone is typically blinded to their treatment assignment. And so, I think that for patients that really want to know if they're taking a medication or not, it might not be a good choice for them.

But in terms of pros, I think there's a lot of benefits to participating in a trial. Number one, you get seen fairly frequently when you're in a trial, and the visits are typically covered by the sponsor and not billed to your insurance. So, you get, I would say, closer follow-up with your providers. All of the testing is typically covered, as well, by the sponsor. And then, you're getting access to potentially the newest, latest drug for your disease.

It takes a long time to develop a drug. So, for example, if you're participating in a phase two trial and there has to be another trial after it, phase three, it might be years before that trial comes to market. So, you're getting access to it at an earlier stage. But again, for placebo-controlled trials, there's no guarantee that you're going to get the study drug or not.

Again, you have to weigh, kind of, benefits and risks, but these are really personal decisions. And I think if you're considering, you know, putting your patient in a trial, these are great conversations to have to learn about the patient's goals and their interests— what they value—because I have some patients who really value being able to see me more regularly than anything. So, trials are a great option for them. Then, I have others who are so concerned about the placebo that I just know the trial wouldn't be a good fit for them.

Moderator: Very true. Great points. Next question. Are there treatment options other than pharmaceuticals to reduce inflammation and improve quality of life, such as lifestyle changes?

Dr Volkmann: I believe so. I mean, it's hard to study lifestyle changes because many times, when someone modifies their lifestyle, it's done in a very unique way to them. And it's done in a way that makes it hard to do a placebo-controlled lifestyle trial. But I would say in my patients, exercise is very important. And most patients benefit tremendously from doing pulmonary rehabilitation.

So, I think all patients should be referred for pulmonary rehab who have IPF. Another modality that can be helpful that kind of tacks on to pulmonary rehab but maybe takes it a step further is breathwork. And there's all different types of breathwork out there.

But breathwork is any time you do a breathing exercise, where you're doing it in a specific way, and paying attention to the breathing. I've had some patients with very severe lung disease start a breathwork practice, and even experience improvements in their FVC, even patients who aren't receiving therapy. So, I think that there's a lot of power in doing exercise and learning how to control your breathing.

This can also be a form of meditation for patients. I think that stress plays a big role in all diseases we treat, and IPF is no exception. And many patients, when they're diagnosed with this disease, are under extreme stress either related to the diagnosis or related to other issues in their life or just, you know, the stress of getting a diagnosis and knowing that you have a potentially fatal disease. So, doing things to help reduce stress, like meditation and breath work, can be quite helpful. And then I think about the diet is also important. You know, very simply because of the reflux disease and the relationship with ILD progression, you certainly want to coach your patients on avoiding foods that trigger their reflux.

This can be different for different patients, but common triggers of reflux would be things like coffee, caffeine, chocolate, spicy foods, but then beyond that, even the timing of day when patients eat can make a difference. If they eat right before they go to bed and then lie down, that could trigger reflux. And then you can even encourage your patients to start keeping a food diary.

I think, finally, with diet, I would encourage your patients to avoid processed foods. I do a lot of research on the gut microbiome as it relates to interstitial lung diseases and, specifically, systemic sclerosis. And what we find is that the higher consumption of ultra-processed foods leads to more alterations and gut bacteria that can promote inflammation. So, very simply, you can tell your patients to try to avoid foods that have more than five to ten ingredients on the label list.

And so, you know, you're buying a food that comes in a box or in a package, and you read the list, and there's more than five ingredients and some of the ingredients are chemicals and things you are difficult to pronounce. These are typically not the healthiest of foods. These are some things I would consider. Again, there's not a lot of great research or evidence behind these recommendations, but I don't think any of these suggestions could be harmful.

I think breathwork and meditation can have a lot of beneficial effects on how a patient feels and functions in their life.

Moderator: Fantastic! Perhaps on a similar note, the question is what do you know about the use of zinc combined with other supplemental therapy?

Dr Volkmann: Yeah. There is some evidence for zinc therapy with IPF, and there are some well-known practitioners in this field who advocate for using zinc in patients. I typically check zinc levels in my patients. Again, I see a lot of patients who have systemic sclerosis-related ILD, where they also struggle with issues such as malabsorption and have a number of vitamin deficiencies. So, I don't give zinc to all of my patients, but if they have low zinc levels in their blood, then I will definitely prescribe it for them as supplementation. Hopefully, you know, additional clinical trials in this space might support zinc in all patients. But at this time, I just use it in patients who have lower levels of zinc in their blood.

Moderator: Great! Next question. How often should the patients with IPF obtain echocardiograms to assess for pulmonary hypertension?

Dr Volkmann: Another great question. I think, at a minimum, this should be done on an annual basis. Then, it could be done at a sooner time point if there was any concern, you know, that pulmonary hypertension was developing. This could be, let's say when a patient starts to experience a decline in the DLCO disproportionate to declines in FVC. This could be a sign that pulmonary vascular disease is developing.

Also, if you have a patient who has worsening symptoms, such as worsening shortness of breath, and you get a CT scan and everything looks pretty stable to you, then you have to think about other causes of shortness of breath. So, you would get the echocardiogram, and I would just say that, with the echocardiogram, I'm sure most of you know that these are truly estimates. Sometimes, I find the estimates to be unreliable, and at times, they're read as normal when they're really elevated, and the reverse is true, too. So, the more data points you have—the more echoes you have—you're able to establish trends in the estimated pulmonary artery pressure. I would have a low threshold to do a right heart cath in any patient you suspect has pulmonary hypertension.

Moderator: Fantastic! Next question. Is there a method to stop aspiration?

Dr Volkmann: This is a great question. There are a lot of lifestyle recommendations that we give our patients to try to prevent aspiration. And this could be, you know, things as simple as sleeping with the head of the bed elevated. This could be accomplished with, you know, sleeping with a wedge pillow or even, I have some patients put bricks under the head of their bed or get an adjustable bed; many insurances will cover this now. These are simple things that can be done.

Considering, you know, promotility agents can be helpful. We put a lot of our patients on prucalopride, for example, which is an approved medication for chronic constipation but helps with upper GI tract motility as well. And then, you know, coaching patients on how they're eating, when they're eating, to try to avoid these aspiration events.

But gravity is your friend in terms of avoiding aspiration. So, you know, eating, sitting upright, and not lying down right after you eat can be helpful. Eating slowly and mindfully and chewing the food well can also be beneficial here.

Moderator: Great. Next question. How do we decrease the time to diagnosis for IPF?

Dr Volkmann: Yeah, this is hard because many of the patients, as we discussed earlier today, who get IPF are patients who are older. And when they go to their primary care doctors, they are often misdiagnosed or thought, okay, this might be related to deconditioning. You're getting older; this might be related to your underlying coronary artery disease. This could be related to your history of smoking.

So, all of these other more common entities often are at the top of a primary care physician's list of diagnoses, and rightfully so, because these are the most likely explanations. I think to truly improve how quickly we diagnosis disease, we need to do more education among primary care providers because these are typically the first people who are seeing these patients. So, if we can educate them more to look out for IPF and, how to diagnose it and when to consider it, I think this would help improve diagnosis.

I also think that educating patients can be helpful. And certainly, and like I said, in scleroderma, I have some patients who self-diagnosed themselves by reading about their symptoms on the internet and then realizing they have scleroderma. Maybe, you know, they've been misdiagnosed with rheumatoid arthritis or lupus, or maybe someone's told them their symptoms are all in their head. So, I think if we educate patients too, then they become more well-informed and empowered to select doctors that can make these diagnoses and care for them properly.

Moderator: Great. Next question. What treatment options prolong a patient's lifespan?

Dr Volkmann: I don't think we have any current treatments that have been proven to prolong a lifespan. However, we know that both nintedanib and pirfenidone prevent or slow the decline in FVC, and we know that changes in FVC and declines in FVC improve mortality in these patients. So, it's possible they do, but I don't think this has yet been proven in any kind of research study.

Moderator: Got it. Next question. Why is lung transplantation only considered for patients with advanced IPF?

Dr Volkmann: That's a great question. So, you know, lung transplantation is a potentially curative option for patients with IPF. Some might say, well, I've just been diagnosed with IPF. Why wouldn't I just go for the transplant first vs wait till I get really sick? The issue is that transplant is not a benign process. It's a gigantic journey that a patient embarks on. The surgery itself, it can be life-threatening. You have to find a good match for you. And there are people far more advanced in how they feel in their life and how their IPF is that are waiting for transplants.

So, there are currently not enough lung transplants to do them at these early stages of the disease when we have patients much sicker waiting for transplants. But beyond that, once you get the transplant, you have to be on lifelong medications that suppress your immune system, usually two to three medications for the rest of your life. This puts you at greater risk for infections and other complications.

So, really, there has to be this risk-benefit discussion that's made about doing the transplant. I think it's something that when you're diagnosed with IPF, to go to a center that has transplant as an option so that if you get to the point on your journey where a transplant is even a consideration, you have easy access to these doctors that do the transplant. But it's currently not something that's recommended for patients at the early stage of this disease.

I will say that I do care for some patients with IPF who've had it for a decade and are nowhere near needing a transplant. They've been very stable. This isn't the average patient, but this can happen. So, you wouldn't want to subject yourself to a transplant or subject your patient to the transplant if they were going to never need it in the first place.

Moderator: Yeah. Makes sense. Let's see, next question. If a patient has familial IPF, would hot tub usage be contraindicated?

Dr Volkmann: Would what be contraindicated?

Moderator: Hot tub usage.

Dr Volkmann: Oh, hot tub usage. So, if they had familial IPF, I'm not aware that they have to avoid hot tubs. I think that there are certain infections that sometimes patients who are on medications that suppress their immune system can become more susceptible to and using hot tubs. But just having familial IPF alone should not preclude someone from using a hot tub.

Moderator: Great! Well, it looks like we have gotten through all of our questions. Thank you so much, Dr Volkmann, for an excellent discussion and presentation. We want to thank our audience members at home for joining us, and we hope you have a fantastic rest of your day.

Dr Volkmann: Okay, thank you.