Dr Kershaw: So what we are going to talk about here at the end is the message here is going to be, this requires a small village to manage these patients. And certainly you may be that way where you are doing a lot of this on your own, but there are ways to get help.

[01:26:27]

Multidisciplinary Discussion of ILD Is the Gold Standard

So I have mentioned in the diagnostic part of this session about the multidisciplinary discussion. This really has become the gold standard for diagnosing interstitial lung disease.

So there are multiple guidelines all over the world that have recommended this as part of the management of patients with ILD. The core members of a multidisciplinary discussion conference, you have a pulmonologist or more than one pulmonologist, a radiologist who at least has an interest or specialty in thoracic radiology, ideally a thoracic-centered pathologist, any other members of your care team that take care of these patients. You can bring in additional personnel as needed. This could be a thoracic surgeon if you are trying to decide, should we biopsy someone or not? Because a thoracic surgeon is always going to have insight into someone's candidacy that we do not. They may say the scan, no, that looks like a hostile plural space to me. I do not think I can do a good biopsy. There are things that as pulmonologists, non-surgeons, we do not think about. A rheumatologist can be very helpful to help with the diagnosis if we are considering the patient may have an autoimmune disease.

And why is this important? Because it allows us all to put everything on the table. All our cards are out. We can review all the data in one session. We will hear the history as one team, look over the CT scans and be able to ask questions of the radiologist while they are there, look at the pathologist, and be able to ask questions of the pathologist sitting in the room by themselves that they have not considered.

And the greatest benefit to the MDD is when you are not suspecting IPF. If the diagnosis is very straightforward, you have a 70-year-old man, former smoker, no connective tissue diseases, he has never taken any medicines, he has been coughing and short of breath for two years, definite UIP on CT scan. That is a straightforward case of IPF. The MDD is not that it is not a bad thing. It is just not going to enhance your diagnostic accuracy because you are already well over 90%.

It is those difficult cases where the CT scan is not straightforward. The story is a bit muddled. There may be some exposures. The patient had a water leak in a closet. And by the way, I am thinking of patients of mine. It was in a closet that was down the hall. We never go in that closet, but I found water moisture in there a year ago. I do not know what to think of that. These are things that can be helpful to discuss together.

How can we do this? It does not necessarily mean that everyone has to gather in a room. Those of us that work and all of you that have very busy practices, it is difficult to stop your day for an hour, travel someplace in your building or on campus somewhere, and sit down for an hour and look at this.

I will speak anecdotally. We used to do this in my medical center and COVID changed that. When COVID happened, suddenly we had to start doing everything virtually. And when the pandemic ended, where it was safe to be in person again, we did not go back to being in person because we realized our attendance was much better if I could do MDD from my office. And that is what we do now.

We have a multidisciplinary discussion at UT Southwestern every Monday at 13.30. And that is just set in stone where we all sit down and we bring cases. We discuss them all as a team and decide what we are going to do.

[01:29:38]

Common Barriers and Alternatives to Multidisciplinary Discussion

Barriers to this. As I said before, if you are by yourself and you do not have a thoracic-interested radiologist or a pathologist, it does not necessarily mean that you need to have somebody who has done a formal fellowship in thoracic radiology. Great if you have it, but you want to try to find those people that are especially interested in those things.

It is the time that is required to do this. As I mentioned, geographic location. Perhaps you practice in an area where there is no one around. Your radiologist is in another city. You do not have a pathologist. You have to send all your pathology to a reference center. That makes it a bit more challenging.

We do not get paid for MDD. I cannot sit down and take a bunch of notes and render some decisions and then get reimbursed from someone's insurance for doing that. This is donated time. You have to have people willing to accept that for the good of the patient care.

What are some ways you can do this? It may be challenging for a patient to have multiple appointments across several days. I practice in the Dallas-Fort Worth area. You may think, oh, that is great. You have got this giant metroplex. People that live in Fort Worth do not want to come to Dallas. It is 30 minutes away. You think that is not a big deal. I am not going to Dallas. It is very difficult. If you do get them to Dallas, you want to try to get it all done at one time.

There was at one time, we do not do this anymore, but perhaps, have combination clinics. Have a combined pulmonary-rheumatology clinic. Have the rheumatologist and the pulmonologist be in the clinic together. Then, goes into a room, and the doctors rotate in. You can do the same thing with infectious diseases. You can do the same thing with any of these specialties. You can do this. It is something to explore to get more bang for your buck, so to speak, and make it easier for the patient.

There is lots of really interesting data about regional MDDs or referral MDDs where some medical centers have set up a situation where instead of referring the patient to be seen at this medical center, you refer the case. You send them the data. You send them the history, the CT scans, the pathology, and then you have the experts wherever that is discuss it and render a MDD-based assessment, recommendations, diagnosis virtually that way.

A lot of centers can do this where the referring provider can attend even. Even though they are not on faculty at your medical center, they can attend also. These are things that are emerging now. There is a study in Canada that I quoted here that 40% of the patients that did this, their diagnosis was changed. Even 45% of the time, the treatment plan was changed. That is a lot. It shows you the value of having multiple people discuss these things together.

[01:32:37]

Diagnostic Considerations for Multidisciplinary Discussion

Some very specific things where the MDD is very helpful. There is this phenomenon of unclassifiable ILDs. If you go back to the slide that I showed in the beginning that had all the squares and the myriad types of ILD, there is a specific category of unclassifiable ILD. The CT scan just does not fit any pattern. Even if you have a biopsy, it does not fit a pattern. That is a real diagnosis of unclassifiable ILD.

There are even some studies that will enroll patients with unclassifiable ILD. There is a study that I refer to at the time of pirfenidone with progressive unclassifiable ILD. There were some issues with the way the test performed in that study, but there is a signal there perhaps that pirfenidone might be helpful for those patients. You really cannot make an unclassifiable ILD diagnosis without an MDD. That is one example of that.

The value of cryobiopsy. Cryobiopsy should never be used as a primary diagnostic modality without an MDD. Any cryobiopsy study you see, the real way it moves the needle in terms of diagnostic and therapeutic implications is sending the biopsy to an MDD to discuss everything together. There is a cryobiopsy society guideline, I think it is an ATS guideline that actually says this is how you need to do it with an MDD.

Then if there is discordance, I mentioned the diagnostic rubric. If you have somebody with definite, let us say they have indeterminate UIP on CT scan, but you do the biopsy and the pathologist comes back and says, oh, this is clearly UIP. That does not mean that that is what the diagnosis is. You need to get together and figure out, okay, what is the real diagnosis here? Because one piece of data does not trump everything else.

This is something that we used to think. I think patients sometimes get this message that a biopsy is going to be the trump card. It is going to overrule everything else. I have got to do a surgical lung biopsy. That is not true. You have to put all the pieces together and have the conversation under a multidisciplinary discussion conference.

I have a case right now that I am really struggling with of someone who is like this. Her CT scan is not in the universe of UIP and did not get better in spite of therapy, went to transplant. Now I have got two lungs in the pathology department. My pathologist can see everything that he needs to see. He is trying to tell me it is UIP. We have discussed this patient twice in MDD because we are like, there is no way this is IPF. No way.

She has already had a transplant. It does not matter. That is an example that one thing does not trump the other. You have to look at this as a composite.

[01:35:20]

Developing the Multidisciplinary Discussion for IPF

The more pieces of data you have, the better your agreement becomes. Stepwise along the way, I am by myself. I get a CT scan. Well, now I am going to discuss the CT and the data together. Now I am going to get a group of friends together, and we discuss the CT and data together, and so on and so forth.

Every time you add more to the discussion at one time, whether it is more data at one time, plus or minus more people at one time, and you agree that we are going to have a consensus diagnosis, you do a much better job at that, as this graph shows here.

[01:35:52]

The Optimal Structure for Multidisciplinary Discussion Is Being Refined

We are constantly refining this structure. What is the best way to do this? As I said, RMDD is pulmonologists, pathologists, radiologists. We have all of our APPs come to that clinic. We will rotate in a rheumatologist as necessary. Rheumatologists bring us cases and we will discuss them together, but there is no right or wrong way to do this. It is whatever works for you and whatever, because I really believe that the more people you have discussing and you want to reach a consensus and look at things together, you are going to do a better job at this.

[01:36:26]

Multidisciplinary Management of ILD

Finally, before I pass it over to Fernando to talk about shared decision-making, I want to just make a brief comment about the multidisciplinary management of these diseases.

Not only are there comorbidities to consider in order to help the patient's quality-of-life, you know, their sleep is bad, they have got symptomatic acid reflux, they are more bothered by cough, so let us try to help your cough. That is great, but there also could be direct implications on the disease itself. This is a slide that I like to use in different formats because not only does it show that there is a quality-of-life impact on comorbidity management, but it also could indirectly or even directly affect the disease itself.

Someone who is coughing that multiple times increasing in coughing could cause stretch injury and could perpetuate the pathophysiology of the ILD. Somebody who has nighttime hypoxemia from sleep apnea, that could lead to more progression of the ILD. The patient who Fernando talked about, the RAP-IPF study he mentioned before about using surgical treatment for acid reflux, well, you know, yes, that is great, we are going to help the patient's reflux, but it actually may treat their disease, the IPF itself, because I have gotten rid of the acid and the regurgitation impact on the lungs themselves, perhaps slowing progression of the ILD.

Do not just necessarily think, you know, I am going to work on giving the patient antifibrotics and they are going to be fine after that. You need to think about all these other things because not only will it maybe help the patient's quality-of-life, but you could also affect the disease process itself.

I will turn it over to you, Fernando, to finish up with the rest of our session today.

Dr Martinez: Yes, given that we are sort of tight on time here, I am going to try to go through this next component just in a little bit more straightforward fashion here.

[01:38:17]

Real-World Evidence on ILD Patient Pathway

This actually is a paper that we just published. That is actually from the Respiratory Effectiveness Group, the REG, and it is a global group.

This was looking at ILD patient pathways globally, meaning all regions of the world, areas where there is very little resourcing to areas which is very well resourced. And so, it was in part of what you referenced, Corey, and that is we were asking people from multiple countries what the structure was for their MDD, particularly in some countries where there may be one or two ILD specialty centers, and everything was being remote.

All of this changed with the pandemic, and what you actually see now is that most of the MDDs, most of these multidisciplinary discussions that are taking place are remote, and I think that is what all of us have done. We have transitioned to remote components, which allows greater access. Some of these things are not surprising. ILD specialty centers have a bit more resource availability than non-ILD.

And so, Tyler, there are some questions already here regarding how to get some of these antifibrotics approved. That actually is easier to do in a specialty center because you have people dedicated to doing that. It is more of a challenge if you are on your own. Those are some of the questions that we will need to address as we get to this last Q&A.

[01:39:31]

Conscious Awareness: Optimizing Health Equity in ILD

There are also some really challenging components that I realize are challenging to speak about in the current political climate, but the idea of ensuring that there is equal access. This is, again, some of the questions that are being asked.

Karen just asked a great question regarding this, and that is how can we optimize the management of individuals to allow them some reasonable access to diagnostic pathways, Corey, like an MDD, and to ensure that there is access to pulmonary rehab. For those of you that live in rural communities, you realize what a challenge that is, and whether tele works in that setting is being tested right now. And then trying to provide a system so that there is at least equivalent access to some of these medications that, unfortunately, are very, very expensive.

And so, we cannot overlook the fact that this is a challenge now. It is likely to be more of a challenge next year. Sorry, guys, just facts of life.

[01:40:36]

Optimizing Shared Decision-making in ILD Care

Given what I have told you earlier and what Corey has described, we now have multiple therapeutic strategies, all of which have their own toxicities, tolerability issues, expenses. We need to ensure that our patients and their caregivers are actively engaged at every step because these decisions are very, very difficult to make, and you need to really take into account what the patient wants, what the patient views in terms of whether they want to do something oral or inhaled, for example, what kind of side effects they are willing to tolerate because all of these drugs have their own components.

That requires you to be able to support the patient and say, what do you want? Here are the options. The discussions, Corey, which used to take about 10-15 minutes, now are 45 minutes to an hour when you are dealing with these because there are just so many options that you need to discuss, and this is really the epitome of where shared decision-making takes place that is now ILD care.

[01:41:39]

Communicating Disease Progression and Supporting Acceptance of Palliative Care Needs

So, I will leave you with the last two slides. So, Michael Kreuter wrote this about 7-8 years ago, and as you can now tell, if you look at this, some of this is out of date.

Assessing the patient remains the same. Incorporating the patient's desires, regular follow-up, those components remain the same. From a comorbidity space point of view, pulmonary hypertension has a therapeutic alternative. The sleep apnea component Corey just highlighted. Lung cancer screening, particularly relevant in this population. Reflux we have talked about.

All of that middle bucket there has a greater role. Disease-modifying treatments are now changed because now it is not just two, but there is three, likely four and five next year. And end-of-life care always, in all of these components, remains something that needs to be discussed, as is palliation of symptoms is the other component.

[01:42:29]

Key Takeaways

Tyler, I will leave folks with the thought that IPF is a progressive disease, but its management is much better now than it was even 5-10 years ago. There are a whole series of non-IPF ILDs that can progress. Making a diagnosis is important because their therapeutic options are also quite complex and beneficial. And earlier diagnosis, to me, is one of the key components.

That is several of the questions that I have been asked. And I think antifibrotic therapy now, with three agents soon, four or five, and five, is where we are.

Tyler, back to you.

[01:43:07]

Skill Building and Feedback

Tyler Kuhk: Guys, what a great talk. I think, just given that I practice in a community setting, I think just the different experiences we all have, I think a lot of really great information. We have a lot of really great questions.

And so, I want to just get through this case study as quickly as we can. And then we are going to get to some of the questions. We have another about 15-20 minutes here.

Let us talk about Mrs. Rogers real quick. A 62-year-old woman with IPF visits her pulmonologist for follow-up, and her diagnosis was based on clinical presentation and an HRCT that was showing UIP. Mrs. Rogers mentions that she has been more fatigued lately, has had some worsening dyspnea. She has a past medical history of GERD. Current therapy is omeprazole. pirfenidone was also started at diagnosis. And she has bibasilar inspiratory crackles on examination, no digital clubbing. You can see her PFTs there, FEV1 76%, FVC 65%. Her ratio is 94%. And her total lung capacity is 85%. DLCO is at 57% predicted.

[01:44:10]

Skill Building and Feedback: Follow-up

She is evaluated for sleep apnea with a sleep study, which demonstrates moderate disease. And she started on CPAP. And she is also referred to pulmonary rehabilitation to help with her dyspnea and fatigue. And her clinic's ILD nurse specialist calls Mrs. Rogers to discuss her fatigue further. She reports feeling well before starting pirfenidone at the 801 mg TID dosing. Now she feels tired all day. So, her dose was reduced to the 267 mg TID. And her symptoms improved in a few days. And now we have restarted titration back up to that 801 mg with frequent monitoring.

[01:44:48]

Poll 9: Mrs. Rogers has had relatively slow disease progression. Her recent visit describes increasing dyspnea over the past 4-6 wk. What is your differential diagnosis for her worsening dyspnea?

Mrs. Rogers has had relatively slow disease progression. And her recent visit describes increasing dyspnea over the past 4-6 weeks. What is your differential diagnosis for her worsening dyspnea?

1. Progression of her IPF;
2. Development of a secondary pulmonary hypertension;
3. Coronary artery disease;
4. Deconditioning; or
5. All of the above.

We will just wait for some of those results to come in. So, 60% of you said all of the above. And that is the correct answer.

[01:45:34]

I do not know if Dr Martinez or Dr Kershaw, if you want to just to quickly comment on the answer there.

Dr Kershaw: I mean, yes. Exactly, all of the above. Yes. I mean, and frankly, you can probably throw some others in there too, that you have to guess medication side effects. Sometimes people just do not feel good on these medicines you have to, at least with the pirfenidone and nintedanib, you know, we will learn more about how people feel on nerandomilast. But, you know, it is one of the things you have to warn. And I think that is, if I could, as an aside of the medicines, these medicines do not necessarily show quality-of-life improvement.

That is why all these other things are so important, because we have got disease-specific therapies, but you may have to do some other things for patient-specific therapies. And I would not discount that, you know, some of this could be due to the pirfenidone itself, that she just does not feel good on it.

[01:46:28]

Poll 10: How frequently do you assess rheumatic comorbidities in patients with IPF?

Tyler Kuhk: And so just a quick poll question, and this is more for demographic data or data collections. How frequently do you assess rheumatic comorbidities in patients with IPF?

1. Never;
2. Rarely;
3. Sometimes;
4. Frequently; or
5. Always.

I will just wait for the answers to come in on that and then move along.

[01:47:00]

Faculty Discussion

I think we have already had a great discussion on how we collaborate with other health care professionals on this, so I do not think there is much to add there.

[01:47:06]

Posttest 3: A 70-yr-old man with IPF returns to clinic for a follow-up. Which of the following best reflects a patient-centered approach to monitoring disease progression in fibrosing ILDs?

We will just get quickly to our posttest questions, and then we will get to answering some of your great questions. So we have this 70-year-old man with IPF that returns to clinic for a follow-up. Which of the following best reflects a patient-centered approach to monitoring disease progression in fibrosing ILDs?

1. Scheduling further follow-up based on patient-reported symptoms;
2. Minimize patient burden by performing pulmonary function tests every two years;
3. Developing a plan that includes home monitoring and quality-of-life assessments; or
4. Scheduling follow-up based on changes in the patient's HRCT findings.
5.  

And so we will give you a couple seconds to answer that.

Good. So the pretest here, most people answered C, and then most people also answered C in the posttest.

[01:48:06]

So the correct answer is C, to develop that plan. So a comprehensive patient-centered monitoring strategy involves regular assessment of symptoms, looking at lung function testing, and then impact on daily life, and then using home spirometry, quality-of-life questionnaires, and enabled proactive management. And while the CT plays a role, it is not sufficient by itself.

Dr Kershaw: Yes, and I think the message for that question is that the other three answers are just much more wrong than the others. You are not going to do PFTs in two years for these patients. You would never do that. That is way too long.

Tyler Kuhk: Great point.

[01:48:40]

Posttest 4: How confident are you in your ability to integrate shared decision-making for ILD management strategies into patient care?

And then we just want to know, how confident are you in your ability to integrate shared decision-making for ILD management strategies into patient care? Again, data collection.

1. Not confident;
2. Somewhat not confident;
3. Somewhat confident;
4. Confident; or
5. Very confident.

Great. Okay, and then the last little thing here, just leave this open because we are going to get into questions because we have about 10-15 minutes.

[01:49:17]

Poll 11: How can you improve shared decision-making in your management of patients with IPF?

But how can you improve shared decision-making in your of patients with IPF? So go ahead and feel free to enter that answer.

Q&A

Tyler Kuhk: And then I am going to jump into questions and answers here with our awesome faculty. We have some fantastic questions. I had a hard time picking all of these.

I just saw one pop in that I thought we should probably, I would ask right away to Dr Martinez, Dr Kershaw from Justine, and she is asking, how are you billing for these complex patients for these therapeutic intervention conversations with patient and family as well as advanced care planning discussions and how to best take credit for those lengthy discussions? I think that would actually be really helpful for our APP audience to hear how you guys are managing that in your practice.

Dr Kershaw: I mean, I can speak to that. Yes. You can bill for time. So there are allowances for the length of time that you spend. You could easily bill a level 5 E&M visit and do nothing but have a conversation. And I do that not infrequently at all. I may bring someone back who is struggling with some decision-making and now granted you are taking up time in your clinic for that, but I mean, there are ways to do that where you are having that conversation and base your billing E&M-wise on the time. And I think for a level 5 follow-up visit, 40 minutes, that will get you a level 5 billing if you do 40 minutes or more. That is a lot.

I think there are also some codes that you can use. Palliative care does this a lot where you are having like end-of-life discussions and you can bill for those based on time. But that is one thing I do all the time. I actually have a sort of a template in my EPIC templates about time-based discussions where I drop that in and I can actually say, our EPIC is built in a way where it actually will keep track of the time you are in the chart too. So you can use those numbers. I do that a lot.

Dr Martinez: Yes, I mean, I think that is the optimal approach. And I will tell you, Tyler, one of the interesting things that happened here in Massachusetts recently is a series of very heated discussions with several insurers over the amount of reimbursement for APP time versus physician time. It was really quite heated.

The health system eventually won in that interaction because a lot of this discussion takes place by our APPs. Our clinic spends a lot of time with patients discussing all this.

Tyler Kuhk: That is actually a really good talk. And I know that there are some states that are working on legislation for that, including my own state in Washington, and it has been a challenge. But yes, I agree. I think with so many APPs doing those kinds of conversations, it is appropriate to make sure that we are getting the proper reimbursement and things like that.

So there is a really good question here. I think either of you probably be great to answer. Is this from Carolyn? And she is asking, when do you recommend starting patients with IPF slow progression on, and I am going to say it wrong, that nerandomilast, the new drug. Do you plan to wait and monitor for progression or go ahead and use it prophylactically? Is the current mindset it is never too early or is the drug too new for this?

Dr Martinez: So this actually is a really, it is a really good question that has been in our field since antifibrotics came to be. And there was a lot of disagreement earlier on with regards to how to answer this question. And that reflects the following.

In IPF, IPF is a progressive disorder, and it is the prototypical progressive pulmonary fibrosis disorder. And so it is expected that every patient will progress, as Corey highlighted, at different rates of progression. When the antifibrotics came out, it was clear that the first two antifibrotics, pirfenidone and nintedanib, could attenuate lung function decline.

Corey, you pointed out this early ILD nintedanib study that you were referring to, suggesting that you could also document treatment effects in that population. But those drugs are difficult to take, and they were very challenging from a tolerability profile. So I think most of us made the argument, as part of shared decision-making, we would tell the patients, you know what, it is probably better to treat as soon as a diagnosis of IPF is made. But you need to decide, given the tolerability profile and the expense of that timing.

My own personal thinking, Corey, is I think nerandomilast may change that, given its tolerability profile, with the caveat, because another person asked this great question, and that is, what is the tolerability of nerandomilast in the real world? We do not know.

The drug just got approved. The first series of prescriptions that I have prescribed over the last two weeks has just taken place. So I am hopeful, based on the clinical trial data, that it will be much better tolerated. And that is certainly what the clinical trial data suggests. But Corey, we will see how that takes place.

Dr Kershaw: Yes, I 100% agree with everything you just said. It is, you know, with pirfenidone and nintedanib, you present the drugs to them, you tell them the pros and cons. I tell them, you know, and realize that just because you were stable for the first year does not mean you are going to be stable for the second year and the third year. Past performance does not predict future performance. That is why we want to preserve as much as we can upfront. But you are absolutely right, you know, because there are some tolerance issues.

Some patients opt to just follow me for now. And that is what you are going to do. Again, you are not going to send them off. I will see you back in a year. You are going to watch them every three months, every four months, you know, some, some, you know, I certainly do not think you should ever see someone earlier than three months for routine things, because the PFT changes just get lost in the noise, I think, if you see them back too soon.

But, you know, nerandomilast absolutely is going to change that, because the tolerance seems to be so much better. You know, the top-end endpoint was 40%, right, diarrhea, but when you looked at, as Fernando pointed out, when you look to the patients who were taking nothing, that 30-or-so percent of patients who were not taking anything, it was 20%. So that it is really going to be a game-changer.

I think nerandomilast, we will not see that as often, but I do the same thing. I tell them what I think, I tell them the data, we make a shared decision, and I am there to support them no matter what, but I will keep following you closely in case something changes.

Dr Martinez: So one of the questions, Corey, that I posed to you, because we have been trying to arrange some of these clinical trials and this comparative effectiveness stuff, is what do you think the insurers will do once you have generic versions of nintedanib next year, and if they significantly undercut the price, do you have any idea, have you gotten a sense of that in Texas?

Dr Kershaw: So I have a patient right now who is going to help me answer that question. So nintedanib is going to be generic. Pirfenidone is already generic. So you can get the cost-plus drugs pharmacy, I am not advertising for that pharmacy, but I am advocating that you can get drugs inexpensively than going through your regular pharmacy through that.

And, you know, pirfenidone will cost a patient $150 a month. And so I have a patient who is taking pirfenidone that he gets, that he pays out-of-pocket. And he is asking me that question. He is like, why do not we start nerandomilast now, and let me take both drugs, and let my insurance pay for nerandomilast, and I will pay for pirfenidone out-of-pocket. Yes, so we may start, because I do not think insurances are going to cover both of them. I do not see that happening.

And I am probably going to do it, you know, as my own little end of one, let us see how this goes situation. But you will start seeing this more and more. And I am looking forward to it, because the FIBRONEER study, I was not blown away at all by combination therapy, there just was not a difference in people taking combination therapy.

But, I do not know if you talked about this, those were patients who had been taking antifibrotics for three years. On average, before they went in the studies, these are people that had already been treated, and we would have already seen what happened in year two and three. But what if we do two drugs upfront? I do not know, let us see what happens. And I think generics are going to make that a lot easier in the future.

Dr Martinez: I agree. Well, you know, that is actually what has happened in the PH world. So the PH world has gone to upfront combination therapy.

Corey Kershaw: Absolutely, yes.

Dr Martinez: And these are studies that we are trying to design right now, Corey. The problem is, Tyler, sorry, because it has just been something I have been immersed in the last 2-3 weeks.

Corey Kershaw: And we love this stuff, as you can tell, so we can do this.

Dr Martinez: And so the challenge to these components has been the cost. Because when I have approached the NIH or Corey, these are $200,000-a-year drugs. And so there is no way that the insurance companies are going to easily allow us to just give $400,000 worth of drugs upfront without data. And the companies, Corey, will not give us the drugs for these. They have not been willing to do that, right?

Corey Kershaw: Yes, they do not want to know.

Dr Martinez: The one thing I will say, Corey, about the FIBRONEER studies, I agree with you. I mean, there was benefit when you added them, and it was not like you completely negated. What you did see is you saw more diarrhea.

Dr Kershaw: Well, yes, you are just adding side effects. Yes, so, again, we will see.

Dr Martinez: Sorry, Tyler.

Tyler Kuhk: But that does address some of the questions people asked here. Yes, I was going to say, there were so many questions about resources and insurance and, you know, all this kind of stuff. And I think, yes, it is great. And I think, you know, to be determined on a lot of these things, too, right? But it does not sound like we are showing up with a copay card for a $200,000 medication, right? It is a challenge. And so it will be interesting to see where that goes.

There are just so many good questions here. I am just trying to go back to some of the earlier questions, because we kind of really started talking about this stuff.

Amy had asked, are you seeing early detection of possible ILD findings with low-dose CTs? And do you see that has helped with changing life expectancy in IPF patients?

Corey Kershaw: Oh, what a good question that is.

Tyler Kuhk: That is a Dr Kershaw question for sure.

Dr Kershaw: So yes, so you are describing what we call an interstitial lung abnormality, right? I have picked up some abnormality in the CT scan that I was not looking for. And you are absolutely right. We are 100% seeing early detection from low-dose CT scans, coronary CT scans, abdominal CT scans, where you get lung cuts, and what to do with those patients.

And so there is an excellent guideline that was a primary author by one of Dr Martinez's mentees, Anna Podolanczuk, you know, who we have done a lot of sessions together, Anna's great, who gave us guidance on what to do with these patients, when you pick up these ILAs, what, and how to follow them.

And it is too early to say, are we changing mean life expectancy, because there is this, you know, there is this diagnostic bias idea, lead time bias. Does it really change the life expectancy if you diagnose it early if it is going to progress no matter what? I do not necessarily believe that is true, because if you detect something early, and it really is a real ILD, or develops an ILD, you have now diagnosed them earlier radiographically, and so it is someone you are going to watch. You do not necessarily treat those patients based on the CT alone, but if they develop symptoms where it falls into the ILD category, as opposed to an ILA category, if you start slowing their progression earlier than if you picked it up later, I do believe you are going to improve survival, but we just do not know that yet, because this is a phenomenon.

Tyler Kuhk: Great question. Becky asked, when working in the pediatrics world, I think this could apply to anybody, though, but if a patient reports mold exposure, so they have a humidifier, wet basement, etc., what additional testing might you do for that patient? And I think that would be a really good question here, you guys, how you would deal with that situation.

Dr Kershaw: I mean, Fernando, there are industrial hygienists, if you have access to one of those, there are also these mold detection companies that will come out and survey your home. I tell patients to have your eyes open with that, because they are in the business to find mold. And if you call them in, they are probably going to find something usually.

And so you just need to be aware of that. But I think if you, it depends on what your pretest probability is. So in this setting, if someone has an ILD, the ILD has features suggestive of an exposure, they have got mosaicism, someone asked how to explain mosaicism, and I can do that if we have more time, but they have air trapping on CT scan, upper low predominant fibrosis, they do not have IPF because their age is wrong. That could be helpful, because then you are adding more data in someone that has a high pretest probability for an exposure-related ILD to begin with. So that is a place to start. And I certainly have done that in my practice before.

Dr Martinez: Agree.

Tyler Kuhk: And just seeing here, so many good questions. Somebody was actually asking about mosaic pattern. Can you explain mosaic pattern too, please? I do not know if you had a couple of points to add on to that, but I think you covered some of the things.

Dr Kershaw: The part of being an ILD pulmonologist is you have to be an amateur radiologist. This is what we do. So mosaicism refers to, I think of it like from an architecture standpoint, it is light and dark patterns next to each other.

So if you have somebody with, let us say, a normal CT scan, and you have these areas where you have got light and dark gray in spots next to each other, that is called mosaicism, mosaic pattern. Now it does not tell you what it is. This is why you have to do the expiratory CT scans to find out does the darker area get relatively darker relative to the lighter areas that should get more white when you exhale?

Because we exhale air out, everything should get more toward white because I have emptied the air out. So if all the air empties out, that does not tell you that the dark area is air trapping. You just have mosaicism and you have to decide, is it a vascular phenomenon? Is it somebody who has more of an upper airway problem? We see this sometimes in pulmonary hypertension because vascular disease, you can also get hypoperfusion changes that will show up as mosaicism. So this is why you need to do both things, both the inspiratory and expiratory are used to determine, is that mosaic pattern due to hypoperfusion or is it hypoventilation causing the attenuation?

There is just some nuance to it, but seeing mosaicism on the scan should prompt a further look to figure out what is happening there.