Dr Corey Kershaw (University of Texas Southwestern Medical Center): I am going to speak to you all this morning for the first part of our session about increasing and improving your awareness about interstitial lung diseases in order to make a timely diagnosis. And we will talk about why that is so important.

[00:08:58]

What Is ILD?

First of all, what is an interstitial lung disease? So, the simplest way that I explain this to patients is that these are diseases that cause combinations of scarring or inflammation in the lungs. Usually, there is more of one versus the other, but that is a simple way to think about it. They are characterized by proliferation and fibrosis within the alveolar wall. And although you can have similar scan patterns and symptoms from malignancy or infection, an interstitial lung disease implies that what you are seeing on the scan and in evaluating the patient's symptoms is that the scarring and/or inflammation is not due to malignancy or infection.

[00:09:40]

Classification of ILD

This is a conceptual diagram that shows, first of all, the myriad types of interstitial lung disease there are. I encounter this a lot in my practice, that when a lot of providers think about an interstitial lung disease, they generally think of maybe one diagnosis, maybe two. But in fact, there are several different flavors of interstitial lung disease.

There are ILDs of known cause, there are ILDs of no cause, and then there are some rare categories, including granulomatous interstitial lung diseases, and then another category that includes some really rare things. But what we are really going to focus on primarily are the first two categories, ILD of known cause, and the three most common causes would be connected tissue or autoimmune diseases, exposure-related ILD, and then medication complications or pulmonary toxicity from medications.

There are smoking-related ILDs that we would not say this is exactly ILD of known cause, but it has a category in and of itself. There are acute ILDs and then fibrosing ILDs. Once again, you do not need to know every single one of these small categories, but the message here is that there are many different possibilities when you encounter a with an interstitial lung disease.

[00:11:00]

Estimated Relative Distribution of ILD Types

And in fact, these are the most common ILDs that you may encounter in your practice.

First of all, certainly in older patients, the most common diagnosis you will see is idiopathic pulmonary fibrosis. And we are going to talk a lot about idiopathic pulmonary fibrosis or IPF today. It accounts for about 20% of ILD cases in the United States, but it is not the only one.

You will see chronic hypersensitivity pneumonitis, connective tissue-related ILD. Sarcoidosis accounts for a substantial portion of the types of ILD that you will probably see in your practice. Chronic hypersensitivity pneumonitis, this is the exposure-related ILD, usually from organic or living antigens. Pneumoconiosis, that is something that is usually caused by inorganic dust. And then the other ILDs encompass all those other categories we showed on the previous slide.

[00:11:51]

Overview of Idiopathic Pulmonary Fibrosis

So again, let us talk about IPF specifically.

So idiopathic pulmonary fibrosis is an interstitial lung disease where you have either radiologic or histologic findings consistent with a usual interstitial pneumonia pattern. I will talk to you about what an interstitial, what a usual interstitial pneumonia pattern is. And that UIP pattern is not caused by environmental factors, autoimmune diseases, or any known cause. So it is UIP without a cause.

The risk factors for idiopathic pulmonary fibrosis, older age, being a man, having a history of smoking, even though it is not directly a smoking-related ILD. We do know that patients who smoke have a higher risk to develop IPF later in life. Idiopathic pulmonary fibrosis is a disease of older patients.

We do not start seeing IPF until about the age of 55. So one thing to keep in mind is that if you encounter a patient in your practice that is younger than 55, but they seem to have an interstitial lung disease, IPF is likely not the diagnosis. They could have some genetic predisposition. However, if you have a patient in their 30s, 40s, clearly has an inflammatory or scarring ILD on their CT scan, IPF should not necessarily be at the top of your list. This is a disease of older patients, certainly in the 60s, 70s, even 80s decade of life.

The incidence is anywhere from 1-13 patients per 100,000 people. The highest prevalence, this is probably a reporting bias, but Korea, United States, and Canada. And I will talk about a little bit of the pathophysiology on the next slide, but essentially this is a disease of injury, improper or aberrant healing leading to fibrosis. We tend to think of IPF as a progressive disease, but there is much more to the story than just saying IPF is an interstitial lung disease that progresses.

The pace of that progression is incredibly variable. No two IPF patients behave the same. Some could progress slow and steady. Some could be stable for a long time and then progress. Some patients, unfortunately, progress very rapidly and expire from their disease within a few years of diagnosis. And to make it even more complicated, someone can be progressing perhaps slowly, but they may have these acute incidences of what we call an exacerbation.

It is an acute worsening of the disease in which lung function decreases rapidly in association with relatively acute onset of symptoms, shortness of breath or new cough within 30 days. And should patients recover from their exacerbation, they generally do not recover their lung function back to where they were before. We are not going to talk more about exacerbations, but you should be aware that this is a well-known phenomenon in really all fibrosing ILDs where they could be doing fine for a while, either on treatment or with monitoring, and they could have a sudden worsening exemplified by an exacerbation of the disease.

[00:14:52]

Pathophysiology of Fibrosing ILDs

As I mentioned earlier, these are diseases in which the lung is assailed by something causing an injury. This injury could be caused by unknown factors, which is probably what happens in IPF. It could be the autoimmunity in a connective tissue disease-related ILD, the exposures from environmental antigens. We see sometimes the exposures, there is something about the medications. We see this a lot in chemotherapy medications. There are some antibiotics that can do this. Whatever the source of the damage is, the lung then is required to undergo repair.

Most of the time, and for most of us, we are going to repair normally. We are going to repair back to normal. We never know anything happened at the alveolar level. However, some patients, and why this happens to some patients and not to others, is a relatively unknown concept. However, you can see there are some risk factors for aberrant healing.

Again, cigarette smoking, telomere biology disorders in which their telomeres on the tops of their chromosomes are shortened. This predisposes them to early and more progressive ILD. Then there are some other genetic things, like the MUC5B promoter variant on chromosome 5. This can also lead to patients being more susceptible to ILD. Regardless of the susceptibility, the patients heal aberrantly and begin to go down a more fibrosing pathway rather than a normal healing pathway. There are multiple pro-inflammatory and pro-fibrotic cytokines implicated.

As you will hear from Dr Martinez later in our session, most of these mechanisms are targets for new and emerging therapies. If we can arrest the fibrosing process, perhaps we can slow the progression and perhaps even reverse it. All of these pathways eventually run through TGF-beta, which is an important cell marker to cause migration and proliferation of fibroblasts into the alveolar space, leading to something called a mesenchymal transformation in which the fibroblasts turn into myofibroblasts. We get the laying down of mature collagen and more fibrosis. This process, unfortunately, the fibrosis itself also calls out for more fibroblasts and mesenchymal transformation, which is why sometimes this progresses more quickly because the process itself leads to more fibrosis.

So lots of targets for therapy, but this is the general mechanism we see really in all fibrosing ILDs, not just IPF.

[00:17:23]

Burden of Delayed Diagnosis

The importance of diagnosing these diseases early is so important because we know that a delay in diagnosis leads to worsening prognosis and perhaps a window closing to treat patients early. Almost all patients who are diagnosed with idiopathic pulmonary fibrosis are usually diagnosed with one or even more than one respiratory diagnosis before they finally arrive at their ultimate diagnosis of IPF.

The average diagnostic delay is 2.7 years. To take this even further, many of these patients are even hospitalized for a respiratory-related diagnosis before the diagnosis is made. Two or more respiratory diagnoses before someone realizes perhaps there is a chronic disease here driving this. 2.2 years on average from the time of first hospitalization until the IPF diagnosis is made.

The median survival if a disease is progressive is poor, 2.8 years. This is a graph that I have on the right side of your screen that sometimes patients are even starting on oxygen for years before someone makes the diagnosis of IPF. 26.7% of patients in this Medicare database study were placed on oxygen before they actually had a diagnosis of IPF.

Once again, it is very important to have a low threshold of consideration for IPF, especially if the diagnosis fits the demographic: an older patient, a male patient, and has symptoms of slowly worsening cough and shortness of breath. We will discuss this more in some detail.

[00:19:02]

Disease Burden and Impact on QoL

As I mentioned before, a delay in diagnosis could result in irreversible damage and a missed therapeutic window. And frankly the diagnosis itself has a significant impact on quality-of-life and leads to the burden of more comorbidities. Common comorbidities in patients with fibrosing ILD include gastroesophageal reflux disease. They are predisposed perhaps to more infections because of a susceptibility with chronic lung disease. More psychological conditions, such as depression. Some patients, because of the cough itself, leads to perhaps wanting to stay home and not go out because they are embarrassed by their cough. It keeps them up at night. They feel tired all the time, leading to poor personal and social life interactions, impaired productivity, and not being able to work and loss of income.

Delaying the diagnosis and the diagnosis itself has a significant impact on quality-of-life that we should all be aware of.

[00:20:04]

Risk Factors for Non-IPF ILDs

What about some of the other ILDs? Talking a lot about IPF, but what are the risk factors for some of these non-IPF ILDs? Well, I have mentioned before the three most common causes to think of are autoimmune-related ILD, exposure-related ILD, and then medication-associated ILD.

The common autoimmune diseases that can cause an interstitial lung disease, rheumatoid arthritis is very common. 10% or more of patients who have rheumatoid arthritis will have an interstitial lung disease condition related to the arthritis. The other common ones are inflammatory myositis, systemic sclerosis or scleroderma, mixed connective tissue disease, and Sjogren's syndrome.

Other autoimmune diseases to consider that could cause ILDs, similar syndromes, a vasculitis, microscopic polyangiitis is a known cause of a fibrosing ILD. About 5% of those patients will develop a lung fibrosis condition. Lupus is not a common cause of ILD. There is an acute condition called acute lupus pneumonitis that is a rapidly progressive ILD, but as far as causing some of the more typical progressive, slowly progressive ILDs, that would not be a common consideration there.

Some of the causes of hypersensitivity pneumonitis or exposure-related ILD, I mentioned organic antigens. Mold is a big one. We always ask questions about plumbing in the home and potential mold exposures. Feathers of any kind, we always ask about birds in the home, birds in cages, but it is more than just birds. It is feathers in pillows and bedding.

You would ask if the patient has a hot tub or uses a humidifier they do not clean, because this is a place where mold or fibrogenic bacteria could grow. And then the common medications. We always ask about amiodarone, nitrofurantoin, because chronic use of these medications could cause lung fibrosis.

There are numerous chemotherapy medications that can cause lung toxicities, and I, myself, have to always sit down and look up the medication and see what the incidence is of pulmonary toxicity. A good resource to look for medications that could cause lung toxicity is pneumotox.com. I urge you to keep track of that website. It is a wonderful resource that collates case reports and research about lung toxicity from medications.

[00:22:26]

When to Suspect ILD?

So when should you suspect an ILD? There is history, there are exam findings on lung function tests or on chest radiography.

So patients with chronic exertional shortness of breath, dry cough or fatigue. We think of other things first. I think that is typical. Cardiology conditions, allergy conditions, but please add interstitial lung disease as one of your high differential diagnoses to consider if a patient has some of these symptoms. You hear dry crackles on exam, they may have clubbing of their fingernails, that is widened fingernail nail beds on the tips of their fingers, that is clubbing. If you happen to get lung function tests, a low diffusion capacity can precede changes in the lung volume.

So an isolated diffusion capacity defect of normal lung volume should raise your concern for an early ILD. Patients that have exertional hypoxemia on walking tests, that should be a signal that there is something wrong, perhaps an ILD. And then if you get a chest X-ray, which should be part of the workup for someone with shortness of breath, if the radiologist or you see basilar reticular infiltrate, so extra lines in places where they should not be, think about an ILD.

Our approach to these diseases is one of, if I am thinking of an ILD, I have to first figure out, do they have IPF or something else? And that really drives the diagnostic algorithm is making that determination because of the progressive nature of IPF and the diagnostic and prognostic implications of delaying that diagnosis.

[00:23:58]

Clinical Approach to Evaluating Patients With ILD

So this is what we do in clinic every day when we see these patients.

If I suspect an ILD, I want to ask about the tempo of their shortness of breath, what kind of cough they have, if they have a cough at all, what is the timing? Has this been going on for days or has it been weeks or months? Getting collateral history is very helpful.

It is not uncommon at all for a spouse or living partner shaking their head behind them and saying, no, you have been coughing actually for a couple of years, you just did not realize it. That is a very common history that we receive in clinic.

Ask about jobs and hobbies. Did they work with asbestos? Do they keep a farm where they make their own hay? Ask about the storage of the hay because wet hay leads to mold and can cause a fibrosing ILD. Do they work with woods or metals? Have they worked in an industry where they use beryllium? Berylliosis causes a sarcoidosis-like syndrome.

Asking about some of these inorganic dusts that could lead to pneumoconiosis, patients who are involved in stone cutting or sandblasting in the oil industry in Texas. We see a couple of these a year where patients are involved in the oil industry in West Texas and they have developed silicosis because of the sand-like material that they use to clean the drilling pipes out. Hot tub use. Wind instruments. So patients who play reed instruments, if they do not keep their reeds dry or change their reeds, mold can grow in a wet reed. That can lead to ILD. Asking about smoking history, not just as a predisposition to IPF, but also the smoking-related ILDs.

A full medication history. I have this happen a couple of times a year where a patient, I am taking a history, and they failed to mention that they had Hodgkin's disease 10 years before because they are cured from it. It is not on their radar, but they may have taken bleomycin as one of their Hodgkin's disease medications that could lead to a lung fibrosis condition.

Ask about their environment. You know, the most common places that you are exposed to something leading to an exposure-related ILD or hypersensitivity pneumonitis, work and home. Ask about their work environment. Is there water damage? Is the plumbing old? Do you smell some musty odors when it rains?

Asking about birds. I ask about taxidermy. People do not think about that. You know, they have got pheasants in their home that they shot on a hunting trip five or six years ago, and those are feathers that could still have fibrogenic antigens in them.

We ask about their foundation. Do they have a pier and beam home, and what is their crawl space like? Does it get wet and musty when it rains? Always ask about humidifiers. Do they clean it? How often do they use it? Do they use distilled water? All things that could lead to mold.

Associated symptoms. These are screening symptoms for possible autoimmune diseases. Difficulty swallowing, joint swelling or redness, unexpected weight loss, unexplained fever, skin rashes, whiteness or blueness of the fingertips when it gets cold. Not diagnostic, but at least raising your concern that perhaps there is an ILD.

[00:27:02]

Connective Tissue Disease Serologies

Perhaps as part of the workup, you could send a panel of connective tissue disease serologies. This is certainly practice-dependent. Most people would send these if they do not have a clear idea of why the patient may have an ILD. They are not diagnostic in and of themselves.

I am not going to read this slide to you, but you can see the antibodies and the disease associations. The reason these are not diagnostic is because you can have false positives with some of these antibodies, and so you want to see the antibodies be associated with typical symptoms of the autoimmune disease. Rheumatologists will not diagnose rheumatoid arthritis just based on an elevated rheumatoid factor, nor should they, because that is a common false positive.

However, if someone has one of these antibodies that is just sky-high through the roof, it is possible that the full disease has not developed yet. That is a whole other phenomenon of connective tissue disease with lung-only symptoms or preclinical connective tissue disease. We see this a lot, but it is a good idea to have it on your radar if you are suspicious of an autoimmune disease causing the ILD.

[00:28:08]

2023 ACR/CHEST Guideline: Screening for and Monitoring of ILD in Patients With SARD

In patients who already have an established diagnosis of an autoimmune disease or a systemic autoimmune-related disease, this is new terminology from a guideline in 2023, and that guideline stated that any patient that you are seeing who has one of these common systemic autoimmune-related diseases, this is rheumatoid arthritis, Sjogren's syndrome, scleroderma, and inflammatory myositis, or mixed connective tissue disease, all of those patients should have screening PFTs and a high-resolution CT scan to assess that they have ILD.

So if you have one of those patients, and for whatever reason the rheumatologist has not, it certainly would be appropriate for you to do that as part of the screening for ILD in a high-risk condition.

[00:28:49]

ATS/ERS/JRS/ALAT Diagnostic Algorithm for IPF

This is the ATS and other society diagnostic algorithm for IPF, and you will notice that it is step-wise. We have talked about many of these steps already.

We suspect IPF, we evaluate them both with history and exam for potential causes, and then we move on to the chest CT. The high-resolution chest CT is after the history, if not the same as the history, the most important part of the diagnostic algorithm, and frankly, we can often make the diagnosis of what type of ILD the patient has with history and CT alone.

[00:29:22]

ATS/ERS/JRS/ALAT Guidelines: Role of HRCT in Diagnosing IPF

So what are the ILD patterns to look for on an HRCT?

As I mentioned before, we are thinking about, is this IPF, or not IPF? And what the pattern we are looking for is that UIP pattern, the usual interstitial pneumonia pattern. The terminology that the radiologist should use is, is the pattern typical for UIP, is it probable for UIP, indeterminate for UIP, or is it not in the universe of UIP and considered an alternate diagnosis? These are really the four categories that when a radiologist is reading the chest CT, they should use these terms.

I am not going to read this slide, but we are going to go through the typical and probable UIP patterns directly.

[00:30:04]

UIP Pattern on HRCT

So what is a UIP pattern on HRCT? These are some examples you will see on the right of the slide of a very good UIP pattern with honeycombing.

A UIP pattern is one of scarring that is more common on the edges and at the bottom. So a subpleural or basilar predominant ILD pattern. We refer to that as an apical-to-basilar gradient. So if the fibrosis is more common at the bottom of the lungs than the top, that is something that goes along with the UIP pattern. They should actually have scarring, reticular abnormality or extra lines.

So if you see the term reticulations in a radiology report, that is the radiologist telling you that there is scarring present. They should have honeycombing fibrosis. It is just what it sounds like, honeycomb cysts stacked on top of each other looking like a beehive honeycomb. This is the essential finding on an HRCT to establish a UIP pattern. They may or may not have traction bronchiectasis. This is dilated airways caused by traction from microscopic fibrosis around the airways.

And then the fourth feature is an absence of inconsistent things. So extensive ground-glass opacities argue strongly against a UIP pattern. Do they have a bunch of nodules, a bunch of cysts not consistent with honeycombing?

If a patient's CT scan has all four of these features, subpleural and basilar predominant, scarring or reticulations, honeycombing, and an absence of inconsistent features, you can be very confident that this is UIP if you were to take them to biopsy and have a surgeon get you a sample to take to the pathologist. Up to 96% concordance with a surgical lung biopsy. The message here is if someone has a UIP pattern on CT scan, do not do a lung biopsy. It will not add anything to your diagnostic weight, and you only put the patient at risk for perioperative morbidity and mortality.

[00:32:06]

Probable UIP Pattern on HRCT

So a probable UIP pattern is the other one to know and is the same thing as a definite UIP pattern except you do not have honeycombing. So apical-to-basilar gradient with scarring in an absence or relative absence of those confounding factors.

You are allowed to have a little bit of ground-glass, a few nodules, but if it is diffuse and widespread, that is inconsistent. So if you have those three factors, relative absence of confounders, scarring that in an apical to basilar gradient distribution, they will also very likely have UIP on surgical lung biopsy. Up to 85% concordance.

Do not biopsy these patients either because you very likely have UIP. And in fact, this data is so strong that when we are enrolling patients in clinical trials for IPF, if they have a definite or a probable UIP pattern, that is acceptable. So those are the two patterns to know, and if you have one of those two patterns, you have UIP.

[00:33:08]

When UIP Isn’t IPF: Alternative Diagnoses

But you do not necessarily have IPF because UIP can occur in many other conditions. Asbestos exposure, some of these drug toxicities I have talked about, exposure-related ILDs. So even though I have talked about that is not IPF, you can also have UIP.

Radiation exposure, so someone who has had radiation for cancer treatment and the lungs are in the radiation field and they get fibrosis from that, these autoimmune diseases, or in fact, IPF.

[00:33:34]

Is UIP a Diagnosis or a “Pattern”?

So stated another way, IPF means that there is a UIP pattern, but UIP does not mean it is IPF. This is the answer to the question some of you may have, well, why not just do the CT scan right away? It is because the history is as important, if not a little more important, because just because you have UIP does not mean you have IPF. That is a pathological diagnosis. IPF is a clinical diagnosis.

[00:33:59]

Other Diagnostic Procedures

And finally, what are the other things that we can do diagnostically? Well, there are times when you do need to get some sort of tissue or other sample from inside the lungs. People ask, should I do a bronchoalveolar lavage? Well, if you have a UIP pattern or probable UIP pattern, it is not necessary. But if you have one of these other patterns, you may do that. Having a high lymphocyte count on the fluid could be helpful to support a hypersensitivity pneumonia diagnosis.

Sarcoidosis being granulomatous, a transbronchial biopsy showing granulomas could be very helpful there, but it does not really help support an IPF diagnosis. We do not do a lot of surgical lung biopsies anymore. Transbronchial lung cryobiopsy is really starting to take the place of that because you get a pretty good sample of tissue, but you have to use it in conjunction with a multidisciplinary discussion conference. We will discuss this a little bit later. But having a little bit of tissue from a cryobiopsy and then discussing it with under an MDD can be very helpful in helping with a diagnosis. But once again, it is for these alternative patterns, not necessarily for an IPF diagnosis.

Thank you very much for your attention. And I believe we have some skill building discussions coming next.

[00:35:14]]

Skill Building and Feedback

Tyler Kuhk: Thanks, Dr Kershaw. Great introduction there to ILD. I think it was very insightful, and we will get to some questions. I believe we are having some running in, but we are going to talk about a little case here, get into some polling questions, and then have a brief discussion for the next 15 minutes with Dr Kershaw and Dr Martinez.

So let us talk about Mr. Smith. He is a 65-year-old lawyer who reports at least a two-year history of daily dry cough. Also complaining of dyspnea with physical exertion, which recently has worsened. He has hypertension, he is pre-diabetic, he has GERD, and he has a smoking history of 30 pack-years, and he quit 10 years ago.

And so this patient that comes in was initially treated by his primary care provider for seasonal allergies. He was given some intranasal corticosteroids. This obviously did not help him. And when his symptoms persisted, he was referred to cardiology six months ago, given his history of smoking and hypertension, had a little bit of a workup at cardiology, stress testing was negative. And now he is in our office in pulmonology expressing frustration about kind of constant coughing.

So I guess to kind of kick off the discussion here, start thinking about what factors might be contributing to Mr. Smith's persistent dry cough. I do not know if Dr Kershaw, if you have any kind of insights that you want to share here when you are seeing this case.

Dr Kershaw: Well, I mean, certainly, you know, having a patient who is of this age with a longstanding cough, those are things you should consider. Now, you know, you always want to think about the common causes of cough. That is always the message.

So if you have someone with a two-year history of cough who is 65, I do not think we necessarily should jump right to, oh, this patient has fibrosing ILD because maybe they have acid reflux, maybe they have allergies, maybe they have cough variant asthma. So you still should consider the most common causes of cough. But I think the message is that if you do pursue that, do not then see the patient back in six months.

You know, this is something we really need to be on top of. And he just has a lot of other concerning things. You know, he has the smoking history talked about. So is there a smoking-related ILD or is he at increased risk for IPF? His age alone does that for him. And the story, once again, is common.

You know, the doctor, his PCP, did treat him for allergies, and it did not help. Same to a cardiologist. That is super common, and where, because you are thinking about those things first: he is a smoker, he is hypertensive, he is 65. Of course, coronary disease would be something you would think about. So I do not think this is necessarily unusual or wrong. It is just that you do not want to delay too much once you have ruled those things out. And perhaps pursue them at the same time. You know, there is no rule that says, well, let me rule out all the cardiology stuff first before I pursue it.

So this is one that has all the important features to consider an ILD diagnosis. His age, long-standing cough, did not get better by treating some of the common things. You have ruled out cardiac things. ILD should jump way up on your list, if not being hot on your list from the very beginning.

Tyler Kuhk: Yes, thanks. As someone who sees a lot of chronic cough consults, I am reading this case too and seeing all the red flags here. And I think when you do this a lot, you start to kind of go in certain directions when you are kind of considering that.

[00:38:30]

Skill Building and Feedback: How Did We Get Here?

So how do we get here? So just kind of advancing the case here. Obviously, he is referred to pulmonology due to his shortness of breath and his cough. And this is about three years of clinical visits. And I think you had talked about how sometimes that delay of 2.7 years, right? We are sitting at the three-year mark.

He has ruled out environmental exposures of concerns. We do a thorough history. There is no mold or history of water damage in the home. He does not have any pets or birds. No family history of interstitial lung disease. And his serologies for connective tissue disease are negative. And his examined past medical history are not suggestive of an underlying kind of connective tissue disease.

[00:39:08]

Poll 3: Which of the following is the next best step in evaluation?

So we are going to get to some polling questions here for the audience. So the question is, which of the following is the next best step in evaluation?

Dr Fernando Martinez (University of Massachusetts Chan): Tyler, can I interrupt you?

Tyler Kuhk: Oh yes, Dr Martinez, yes.

Dr Martinez: Let me just make one interesting comment regarding this particular case. You will remember, you and I have talked about this before. Two of my favorite studies addressing the issue of delay and diagnosis were actually studies that were published by a group in the UK.

And they did a very thorough assessment of large data sets and identified that the most common missed clinical scenario for ILD, IPF in particular, is what they were looking for, were a long history of recurrent visits for cough in an older person. And the older you were by five years, 65, 70, 75, the greater the likelihood that you had a person with IPF that had been missed. If you added dyspnea to that, everything ratcheted up.

So when you think about this guy who has had three years of recurrent visits for cough at 65, that is already a very high predictor that there is likely an interstitial process.

Tyler Kuhk: Actually a really, really good clinical pearl. Thanks for that, Dr Martinez. Just back to the poll, I believe it is on the screen here.

So I think everybody's had enough time to address the next best step in evaluation. And so we had a pretty good spread here, about 27% chest X-ray, 25% PFTs, 0% for the empiric trial of PPI therapy, and then D wanted a high-resolution CT of the chest.

In this case, correct answer is chest. I actually do not think that PFTs and high-resolution CT testing might come a little bit later, but I think the initial thing for a patient like this that has no chest imaging would be to get that chest X-ray. So that is why that is the correct answer.

Dr Martinez: As you know, Tyler, in the chronic cough world, a cough for more than three weeks buys you a chest X-ray.

Tyler Kuhk: Of course, I tell everybody that. And it is amazing is how many patients get referred to us that have no history of chest imaging or something from like 10 years ago. So always get that chest X-ray because that is going to be the first step and really going to the next step.

[00:41:21]

Poll 4: What is the next step for a patient with symptoms consistent with IPF and an HRCT pattern of probable UIP in whom potential possibilities have been ruled out?

So what would be the next step for a patient with symptoms consistent with IPF and a high-resolution CAT scan pattern and probable UIP in whom potential possibilities have been ruled out?

1. Bronchial alveolar lavage and histology;
2. Biomarker testing;
3. Lung biopsy and histology; or
4. Multidisciplinary discussion.

I will give you a few moments to answer that one.

Good. So pretty good spread on this, but most of you agree that multidisciplinary discussion would be a priority here. Anybody have anything that they want to add to that, Dr Martinez or Dr Kershaw?

Dr Kershaw: I mean, biomarker testing if you are thinking about connective tissue disease serologies, for example, but it is not, you have got probable UIP. And, you know, those of us who see this a lot, yes, it can be helpful there, but you need to start thinking about the diagnosis already, and the MDD is really the next step after you have the CT scan to determine is there anything more we need to do then.

Dr Martinez: So Tyler, one of the things that comes up in this kind of a question is for those of us that have actually been involved in writing board questions, you always be really careful in terms of how you write a question, because if you think about the way you have asked that question, you have said in whom possibilities have been ruled out, that already tells you that you have gone through that initial process. If you hadn't put that line, those words in, then if somebody answered biomarker testing, I could say, okay, you know what, I could see why you would come up with that component.

So you sort of loaded the question already by saying, come on, we have excluded other things. You have got probable UIP. Corey already told you what that is.

Tyler Kuhk: Good, good points.

[00:43:20]

Mr. Smith’s PFTs and Imaging

So here are Mr. Smith's PFTs and imaging. So he’s got an FVC of 69%. His FEV1 is 72% and his ratio is 79%. And there is his CT imaging on the right.

And so I will let Dr Kershaw talk about the PFTs and any kind of pearls of wisdom for the imaging here.

Dr Kershaw: Yes. So I mean, these are not normal PFTs. So the first thing we do reading PFTs is you are going to look at the ratio of FEV1 to FVC. This is 79%. So that is normal. It is actually a little high. You see that sometimes with fibrosing ILDs when the FEV1-FVC is a bit above normal because of increased elasticity. You get a pretty high FEV1 relative to FVC. Not obstructed. And then we have a vital capacity, which I go to next, and someone not obstructed. And that is lower than normal.

That is moderately impaired, 69% of predicted. And this is a patient who clearly has some fibrosis. We have got extra lines along a subpleural surface. It is subpleural predominant. We have only got one slice here. So we are kind of into the lower lobes and lingula middle lobe here. So we have some honeycombing changes in the right lung base there. There is a little bit of fibrosis in the lingula also. You have got some excellent traction bronchiectasis that I can see there in the lower lobe pretty well.

This is not a normal CT scan. This is somebody who has got a fibrosing ILD something. I know we have a question next. I do not want to give it away.

[00:44:57]

Poll 5: What is the imaging diagnosis?

Tyler Kuhk: So what does the audience think? What is the imaging diagnosis?

1. Definite UIP;
2. Probable UIP;
3. Something that is indeterminate;
4. Fibrotic HP; or
5. NSIP.

Tyler Kuhk: All right. So 50% definite UIP, 34% probable UIP.

Dr Kershaw: And if I could just comment on that, the definite versus probable. Remember that definite and probable look the same with one exception. Definite UIP has honeycombing. Probable UIP does not. This patient has honeycombing. That is why it is definite.

Tyler Kuhk: Thank you for that clarification.

[00:45:50]

Faculty Discussion

So we have about five minutes to kind of have a little discussion here about how radiographic patterns guide your diagnosis and treatment decisions. So I just want to open it up here.

And I am kind of just looking through some of the questions here. So if we could maybe answer one question right now.

Dr Martinez: So you know what, Tyler, there is a question from Ludmilla, regarding, which actually is a very good question, Ludmilla, and she poses: is UIP then a radiological finding, Corey? And so how would you interpret that?

Dr Kershaw: Yes. So I love the history of medicine. And UIP was named by pathologists. And the reason they called this usual interstitial pneumonia, because when they looked at a series of biopsies, this was what they saw most commonly. So it is the usual pattern you would see in a fibrosing ILD. So, they called it that.

And so, first and foremost, UIP was a histopathological finding. But it only became later that these concordance studies were developed, showing that patients who had these specific patterns on their CT scan, with these criteria, they always had the same thing on biopsy. So over time, we have determined that there is also a UIP pattern on CT scan.

So the answer to your question is yes. And yes, radiological. It is also a histopathological finding. And there are similar criteria that we have not talked about here that go through the same thing. You have four of these, you have three of these things, and they have the same terminology, definite, probable, indeterminate. And we have a wonderful rubric that has been published in the most recent diagnostic guidelines for IPF that shows you when you have the radiology and the pathology together, how that fits.

If I have got indeterminate on radiology, but I have got definite on biopsy, what does that mean? And I go to that all the time. I show it to patients. I put it in talks. It really helps a lot. So the answer to your question is yes, it is a radiological finding. It is also a histopathological finding, also.

Dr Martinez: That is a great answer.

Tyler Kuhk: Great answer.

[00:48:01]

Posttest 1: Which of the following CT findings would argue against a diagnosis of idiopathic pulmonary fibrosis with a usual interstitial pneumonia pattern?

So I think just in the interest of time, we have some great questions. We will have time at the end, but we are going to get to the posttest question here before we kind of break into the next section.

So remember back to which of the following CT findings would argue against a diagnosis of idiopathic pulmonary fibrosis with a usual interstitial pneumonia pattern?

1. Honeycombing and subpleural basal distribution;
2. Traction bronchiectasis;
3. Extensive ground-glass opacities without reticulation; or
4. Reticular opacities and minimal fibrosis at the lung basis.

Dr Martinez: And remember, Tyler says against a diagnosis. So read that carefully.

Dr Kershaw: Way to go, guys.

Tyler Kuhk: Good. Yes, you did great. So 51% in the pre and 70% in the post. So good work, everybody. And that was correct.

[00:49:06]

So again, UIP is characterized by reticulation, honeycombing, and traction bronchiectasis, often without prominent ground-glass opacities. Predominant ground-glass opacities without fibrosis suggest other interstitial lung diseases like NSIP, organizing pneumonia, or hypersensitivity pneumonitis. So good work on that.

Dr Kershaw: Remember, you are allowed a little ground-glass. The term is extensive. If it is the dominant pattern, because it is not unusual at all, because this is part of the pathophysiology of this, is that there is some inflammatory process in the beginning, but it turns into fibrosis.

So I always find it really fascinating when you see in the bed of the fibrosis a little ground-glass. This is like a really active area of mesenchymal transplantation that you can see actually on the CT scan. So you are allowed a bit. You just cannot be the dominant pattern overall.