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Hello, everyone. Today, I will be speaking to you about emerging therapies in pulmonary fibrosis care for 2025. Um, these are my disclosures available to you. And this is our assignment today, our learning objectives, and I'll leave those up for just a second. OK. Our patient asked, I would say the most important question of all this. We spent a lot of time talking about pulmonary fib, you know, pulmonary function testing changes. Uh, we're gonna make the, uh, vital capacity look better and the doctor, um, Mr. Rice is very appreciative of all this. Thanks so much for giving me all this information. I'm really encouraged and I'm gonna feel better, right? I mean, you know, my cough, my shortness of breath, all that's gonna get better, right? These medications are gonna make me feel better. Well, maybe, maybe not. Um, anytime we discuss treatment of these diseases with our patients, an important part of that educational process when we're telling them about the options to treat, we have to tell them what the downsides are. These medications carry side effects. This is prophenidone. Um, the most common side effects of prophenidone are nausea. Um, I would say the dyspepsia, acid reflux is also fairly common. And there's also this issue with a sun sensitive rash. This is unique to prophenidone. So you have to tell patients who that you prescribe prophenidone to, they have got to cover all their skin when they go outside. That includes sunscreen, covering exposed skin with sleeves, pants, etc. because Um, a sensitive rash is very common, as you can see here, and this is the original prophenidone study, 28% of the patients had a rash versus only 8.7% of patients not taking prophenidone. I also counsel patients about the anorexia and weight loss. This is not unique to prophenidone. In tentative also has this, um, this side effect, and it can be really disconcerting for patients. You know what, I'm just not hungry anymore. Uh, I'm losing weight and I'm not trying to. These are known side effects of these medications. So, We have to counsel patients about this and tell them to be very conscious of their diet because they may lose weight and we need to start looking for alternatives to help them hold on to weight if this is something um alarming for them. Um, another thing that's a little bit problematic when prescribing prophenidone is the, is the pill count. Um, the top dose of prophenidone is 3 tablets 3 times per day, so 9 pills per day. That's how you get to the total dose of 801 mg 3 times per day. There is a single 3 tablet to 1 tablet conversion available. So the small tablets are 267 mg. They, they, uh, there is a single 801 mg tablet. So if patients do get to the top dose, you can convert them to the single tablet, but it's still 3 times per day. So, often when, um, we're discussing prophenidone with patients, this can be a bit of a turnoff for them to have to take a medicine 3 times per day. Um, and that's, that's just the way prophenidone is. So I find that in my own practice, just to speak anecdotally, this, if people are not willing to try prophenidone, it's usually one of two things. They're not willing to wear sunscreen. They don't want to take a pill 3 times per day. So, it's important that they know that upfront. In tentative, uh, one of the interesting things about the pulmonary fibrosis patient population is that these are, um, often well-educated patients, meaning well educated about their disease. Um, when they come, they at least have done some research if they're concerned about this, and patients who read about nintenative, they're going to know about diarrhea. The diarrhea of ninentative is very common. It's well over 60% of patients who take nintendib will have some change in their bowel habits. Um, they also can have the anorexia and weight loss because of the mechanism of action of nintentinib. Uh, bleeding is a side effect, potentially the most common bleeding side effect in the Impulsive trial was nosebleed, um, thought to be due to the dryness that patients get if they're on oxygen predisposing to bleeding from the nose there. Um, so you should have at least a little caution if patients are already predisposed to bleeding either because of a bleeding diathesis or because they're taking systemic anticoagulation. Once again, anecdotally, I have not found this to be an absolute contraindication to taking nititinib if they're on, uh, some sort of uh anticoagulant, but it should be part of the, um, Discussion and shared decision making with a patient so they're aware of this side effect. Um, what can you do to mitigate the diarrhea? Well, one of the absolute requirements of that natentative is you have to take it with a full meal, twice, you know, so if your twice per day dosing of natentative must be taken with a full meal and that meal must include protein. So if you have a patient who their breakfast is A piece of toast, a cup of coffee, they take them in tentative, they will have diarrhea. So that, that, that requires some education, perhaps a visit with the dietitian to discuss how can I help with um eating properly to help with the diarrhea side effect of this new medication my doctor put me on. Um, loperamide can be helpful if patients are really struggling with the diarrhea. Um, taking loperamide is, is an option. And also holidays. So what does that mean? That means just taking a break, you know, maybe. Taking a weekend off, maybe taking a week off. This is a common thing to do to help mitigate the side effects of, of nitinib, just resetting the bowel, so to speak. Um, so once again, this is an ongoing process. We have to talk to our patients about this every time we see them, how they're doing with the medication, and what can we do to help them so that they continue to benefit from the medication and not have the side effects be so outweighed. Narrandomala has some advantages. Nearindomala seems to be much better tolerated than intenib and prophenidone, um. So diarrhea, again, the most common side effect and you'll notice that the first panel is all patients. So 41% of the patients taking top dose of ninten of neuronommoast had diarrhea, but you'll recall that this include included patients that were taking antifibrotics. 77% of patients were taking antifibrotics and that includes nintentinib. So if you look at the patients who were not taking any background therapy or were taking prophenidone, so meaning not taking nintentinib, the diarrhea incidence was, was much, much less, you know, 20, 23%, 26%. So I, I don't think that the diarrhea with neuronomelas. If you take it by itself, is as severe as the 41%. It's just that that was the primary outcome to look at was all patients. So if you have a little, you know, deep dive look at the subgroup analysis here, you'll see that if you're starting someone on an antifibrotic who have never taken one before, during Domolas's diarrhea count actually may be quite less than the 41% from the primary group. But the patient's main question for us today was, am I going to feel better? And the reality is, is that, you know, when, when you study these medications, patients really don't report that they feel better, that their shortness of breath is better, their cough is better. So part of the management of these diseases goes beyond just prescribing an antifibrotic and sending them on their way. We have to first of all, do a, do a screen for other comorbidities associated with the pulmonary fibrosis. This includes pulmonary hypertension. Acid reflux that could be also contributing to shortness of breath or cough. Is their sleep disturbed? Do they need oxygen at night? Do they need to have a formal sleep study because they have undiagnosed sleep apnea, uh, that's just happens to be along with their pulmonary fibrosis. What can I do for the cough itself? This is a very active area of research. This cough is such a challenge for these patients. And I will tell you, you know, from an anecdotal standpoint, I spend so much time talking about cough that, you know, that may be the bulk of the visit because we've got their vital capacity loss slowed down, but they're more bothered by their cough. They can't go to a restaurant. They can't go to their spiritual services because they're coughing all the time and they're a little embarrassed by it. So, we really must look at some of the other things. This could be cough suppressant. This could be other causes. It would be a shame that we're working on trying to treat their cough if the patient's taking an ACE inhibitor, for example, that might be causing their cough. There are neuromodulators um that we can try for this, seeing a speech language pathologist for some, uh, biofeedback mechanisms to help with your cough. Lots of options. To do to help with cough that go beyond just treating the fibrosis. Um, shortness of breath could be helped with pulmonary rehab, perhaps a visit to see palliative care to help with some symptomatic therapies for shortness of breath. These diseases are often associated with, you know, anxiety, depression because we've told them they, they have a disease that probably will progress. We're gonna try to slow the progression down and that could affect their quality of life just because of having that hanging over their head. So seeing a psychologist, perhaps even a psychiatrist to help with some Antidepressants or anti-anxiety medicines and also referral to support groups. Um, there's a lot of them out there. I often encourage patients to join a support group because they can often find their people that way and they often get tips of how to manage some of these things that even I haven't thought about before. So I learned a lot from patients because they learn from other patients and we all share strategies to help, um, this side effect or this comorbidity. Um. And even beyond managing the comorbidities from symptoms, it's possible that these comorbidities may even affect the disease themselves, and this is just a slide that I often use in presentations from 2016 that show the interdependence of some of the things like sleep apnea, cough, as. Reflux. They all could feed on each other and actually make the other comorbidities worse. So why we need to address all of these because helping the sleep apnea, for example, may help the patient's cough, helping the reflux may help the ILD. That's a bit of an area of controversy, but it's a simple thing to do. So don't ignore the other.