Melanie Cole (Host): Recent guidelines have been released, defining clinical criteria for progressive pulmonary fibrosis and optimal management. And we're here today to illustrate a summary of the key points from these guidelines. Welcome to UAB Med Cast. I'm Melanie Cole, and joining me is Dr. Teja Kulkarni. She's a pulmonologist in critical care medicine and an associate professor at UAB. Dr. Kulkarni, thank you so much for being with us today. There's increasing recognition that certain interstitial lung diseases behave similar to idiopathic pulmonary fibrosis with development of a progressive fibrotic phenotype.

Can you tell us about the scope of the issue that we're discussing here today and what's previously been the thought about the pathophysiology and have there been sort of different definitions of progressive pulmonary fibrosis? Can you explain a little bit about that to us?

Dr Teja Kulkarni: Thank you, Melanie, for having me. And absolutely. So when we talk about fibrotic lung diseases, it is a group of almost 200 entities. they're characterized by heterogeneity in the extent of inflammation and or fibrosis. As we talked about, idiopathic pulmonary fibrosis is the most common form. When we talk about the fibrotic lung diseases, but there's been more and more evidence of the last few years that there's a similar progressive phenotype in a proportion of non IPF fibrosing lung diseases.

They share overlapping genetic pathophysiological and some clinical features with IPF. This understanding has evolved over time and how we defined a progressive phenotype has certainly changed over the last few years. This entity or progressive Fibrosing interstitial lung disease or PFILD was initially termed with the first clinical trial that looked at patients with this phenotype and with the new recent guidelines, we now define it a little differently in terms of the symptoms, the physiological findings, and the CT findings.

Melanie Cole (Host): Well, thank you for that. So previously there had been no consensus on how to clinically define these patients nor to manage them. So why don't you tell us about those recent guidelines and really about the clinical criteria and optimal managements. Give us some of those key points.

Dr Teja Kulkarni: So, progressive pulmonary fibrosis is now defined as either symptomatic or physiologic or radiological evidence of progression. These are patients with non IPF diagnosis of interstitial lung disease. So the patients have to meet at least two out of the three criteria. The first criteria is worsening respiratory symptoms. The second criteria is physiological evidence of disease progression, either by showing that there is an absolute decline in force, vital capacity of greater than or equal to 5% predicted within one year of follow up, or an absolute decline in diffusion capacity. Greater than or equal to 10% predicted within one year of follow up.

And then the third criteria is radiological evidence of disease progression. So either there is an increased extent or severity of traction bronchiectasis, there's new ground glass opacity with traction bronchiectasis, new fine radiation, increased extent or increased coarseness of regulations that were previously present, new or increased honeycomb changes or increased low bar volume loss. So if the patient meets two out of these three criteria within the past year, with no alternative explanation, this patient is now told to have progressive pulmonary fibrosis. Remember, it's not a diagnosis, but it's more of an entity to define how the patient is doing.

Melanie Cole (Host): So as it's not a diagnosis and an entity to sort of stage the patient, then how important is that early staging or assessment as being crucial to improve outcome prediction? And as we're discussing the diagnosis and challenge with this, tell us about the clinical experience, the importance of that multidisciplinary group of experts. Because with patients with these types of challenges, Getting that group together would seem to be really the most expeditious approach to getting them the treatment that they need.

Dr Teja Kulkarni: Absolutely. When we talk about management of progressive pulmonary fibrosis, I mean there is a pre and a post right, before the progression happens. How do we recognize these patients? And so for that, it's very important to understand what are the risk factors for progression. So you recognize some of the different types of pulmonary fibrosis that have a higher tendency to progress further. So, among the connective tissue disease related, ILD, scleroderma and rheumatoid arthritis tend to have a higher predilection towards progression. And if The CT actually shows more fibrosis than inflammation. Those patients tend to have, progression much quicker.

You see the progression much earlier and they progress faster. So recognizing those signs are very important. Now, if you take a patient with hypersensitivity pneumonitis, if they present early in their disease, they may have more inflammation, but they present later in their disease, then they have a more fibrotic phenotype and if they show usual interstitial pneumonia pattern, those patients have a higher tendency to progress as well. So before the progression happens, recognizing the risk factors are very important.

So you can actually, treat the patient appropriately as well as, monitor them at least every three to six months to look for progression once the progression has already occurred. Now, if the patient meets the phenotype, the criteria for progressive pulmonary fibrosis then comes the next question of how do we change the management? What do I change in terms of the patient's treatment? So clinically it's very important to recognize the risk factors before the progression happens, and then understand how do we treat these patients after the progression happens as well?

Melanie Cole (Host): So then speak about that. What happens next?

Dr Teja Kulkarni: When we talk about management before progression already happens in connective tissue disease related ILD patients. Mycophenolate [inaudible] is the first line of therapy, typically along with varying doses of glucocorticoid. But if you do see progression in spite of treatment with these medications, we have to think about whether this progression is related to a more inflammatory phenotype or is it more fibrosis that has now ensued. So there's this gray zone when we talk about the treatment, but you could think about escalating immunosuppression to maybe rituximab.

Now, there are newer trials which have shown the benefit of rituximab in this patient population and or they have a more fibrotic phenotype you could consider adding nintedanib, and that is based on the in bill trial which is what I was talking about earlier in the in bill trial. The term PFILD was initially termed, and the way progression was defined was slightly different. But overall though, it is disease progression. And so if the patient has a more fibrotic phenotype, more fibrosis seen on the CT scan, then you add an antifibrotic therapy as well in addition to escalating immunosuppression for these patients.

Similarly, for a patient who has chronic hyper sensetive pneumonitis once the antigen has been removed and you've considered maybe immunosuppression in some of the patients, if they continue to have progression, could add nintedanib, for more fibrotic phenotype. And this would apply for the varying other, ILDs that are also present.

Melanie Cole (Host): . Well then Dr. Kalkarni, would you please speak about comprehensive management and what's involved in that aspect?

Dr Teja Kulkarni: Absolutely. I think, you have to see the patient as a whole. It's not just about one medication that you're trying to treat the patient with or looking at numbers that you're getting from pulmonary function tests or changes seen on CT scan. For a more holistic, comprehensive management, it involves more than just pharmacological therapy. Important non-pharmacological therapies are, supplemental oxygen pulmonary rehabilitation. These are very important, to try to help improve patients functionality. We do try to have our patients, Attend pulmonary rehabilitation if feasible, at least on an annual basis.

We also do six minute walk tests on an animal basis to look for the need for supplemental oxygen. Another important factor we focus on is comorbidities. A lot of these patients have other comorbidities like reflux disease. they develop pulmonary hypertension. They have obstructive sleep apnea and recognizing or asking questions to recognize these comorbidities as well as evaluating further and treating is equally important as we talk about a comprehensive management of these patients.

When the patients have a progressive disease, we have to think about is lung transplant appropriate for this patient? And if they are, Potentially a candidate for lung transplantation early refer to the transplant program is equally crucial and important, to give the patient the best chance there is at success with the lung transplant. And ultimately if all else fails, think about more Involvement of support systems, focusing on the patient's symptoms and comfort and not just trying to treat the disease itself. Early recognition of that and involvement of the palliative team, in the management of our patients is also very important.

Melanie Cole (Host): So please speak as we wrap up about the unique areas that set you apart and why it's so important. You just mentioned early referral for lung transplant. Tell other providers why it's so important to refer to the specialists at UAB Medicine and if someone wants to refer a patient, when is the best time to do that?

Dr Teja Kulkarni: Yeah, so UAB has a large interstitial lung disease program, which not only encompasses clinical care of these patients and management, but also the ability to refer to lung transplant program and work with our lung transplant team. We also have an excellent clinical trial program here, and that is an additional opportunity for patients to not only be on the current FDA approved treatment, but also participate in clinical trials. The earlier the patient has referred to us for additional recommendations or management, the higher the, chances of success or better outcomes.

What I would recommend is that we can definitely help with early diagnosis of the specific type of interstitial lung disease for your patients and continue for the co-management of the patients. With, few visits at UAB and a few visits, with their providers early referral. Two lung transplant program, which is extremely crucial if the patient is eligible and participation in clinical trials.

Melanie Cole (Host): Such an interesting topic, and thank you for joining us today and sharing your expertise in those recently reviewed guidelines. Thank you again, and a physician can refer a patient to UAB Medicine by calling the MIST line at 1-800-UAB-MIST by calling our website at uabmedicine.org/physician. That concludes this episode of UAB Med Cast. I'm Melanie Cole.