Hello, and welcome to the webinar about interstitial lung diseases. It's my hope that by participating in this webinar, you'll learn a little bit more about the general way we think about interstitial lung diseases as an interstitial lung disease physician. Essentially, we're going to be talking about how we identify the presence of an interstitial lung disease, how we classify these and characterize them, and some of the treatment options that we have for patients. So when we think about that term interstitial lung disease, we're really talking about a big category of diseases. Probably over 200 different types have been characterized and named. There's probably even more than that. And so really breaking this down, this big category down into a specific entity is a lot of what we do in an interstitial lung disease clinic. But when we think of the term interstitial lung disease, we're talking about any disease that infiltrates the interstitial compartment or the lung tissue itself and or the alveoli. And they're somewhat confusing. We have to name 200 different ones and some names make some sense and a lot of names are really an alphabet soup terminology that we can find confusing on occasion. And I'll hopefully break some of that down for you. The other thing to understand about interstitial lung diseases and trying to differentiate them is that they oftentimes present very similarly. Patients with lung disease really only have a few ways to manifest that, typically complaining of shortness of breath or a cough. The physiology is similar. Patients with interstitial lung disease typically have restrictive physiology. And the radiology requires expertise to differentiate different patterns, but typically will show some sort of increased markings in the interstitium. So when we start to break down interstitial lung disease, we can categorize these into really some simple compartments. I tell my patients that when I meet them that I'm trying to sort out sort of what category they're in, the questions that I ask them will drive me to understand what type of interstitial lung disease we are thinking about. In broad categories, we have at the top of this graphic the idiopathic interstitial pneumonias, the most common of which is IPF, and I will spend some time speaking to you about IPF and some of the prognoses that go with an IPF diagnosis. But in addition to idiopathic pulmonary fibrosis or IPF, there are other idiopathic interstitial pneumonias, including idiopathic NSIP, unclassifiable idiopathic interstitial pneumonias, which actually make up about 20% of our patients, so 10 to 20%. So oftentimes, despite all our hard work trying to sort out what's going on, the patient ends up being called idiopathic or unclassifiable, excuse me. And then there's other idiopathic patterns that we can see, including the smoking-related diseases, respiratory bronchiolitis, ILD, DIP, and cryptogenic organizing pneumonia. The second big category that we see in our interstitial lung disease patients are autoimmune, and a fair number of our patients have a related connective tissue disease, interstitial lung disease. These include rheumatoid arthritis, scleroderma-related interstitial lung disease, Sjogren's syndrome, mixed connective tissue disease, ILD, and then a lot of patients that seem to have some autoimmune features but don't have a clearly defined autoimmune disease. The third big category are exposure-related interstitial lung diseases, the so-called hypersensitivity pneumonitis, this HP here, and these diseases are related to antigens that we find in our environment. Common types of antigens that cause hypersensitivity pneumonitis include bird-related feathers, such as birds themselves, or down pillows and down comforters, things of that nature. Also molds and mildews. We see this a lot in patients that work in environments where there's a lot of organic antigens, such as farmers and other agricultural-type workers, for example. So our histories are focused quite often on what exposures patients may have had. Another independent interstitial lung disease is sarcoidosis, and then we have a smattering of other rare interstitial lung diseases, sometimes related to occupational exposure, sometimes related to drug-associated reactions, and then the rare entities. And when we think about what an interstitial lung disease physician sees in their practice, this is an approximate distribution of the lung diseases we see. So approximately 20% of patients in any interstitial lung disease clinic would be idiopathic pulmonary fibrosis, or IPF. Another 20% are those chronic hypersensitivity pneumonitis or hypersensitivity pneumonitis patients we discussed. Another 20% connective tissue disease. And then the rest divided between sarcoidosis, pneumoconiosis, and the other rare lung diseases. Now, recognizing interstitial lung disease is an ongoing effort. We are working hard in the interstitial lung disease space to help everyone understand that interstitial lung diseases exist, and that we have to think about this diagnosis earlier so that we can help recognize it and begin treatment. We like to say that time lost is lung loss, so recognizing interstitial lung disease early and beginning treatment can really prevent deterioration of the patient's lung condition. But in its current state, we seem to have difficulty discovering interstitial lung disease, and this happens for a lot of reasons. The patients may not recognize their own symptoms, or providers misdiagnose an onset of a cough or an onset of shortness of breath with more common entities that cause the exact same symptoms, for example, bronchitis, asthma, COPD, heart disease. And we also think that it's related to patients aging or deconditioning. And so in its current state, because of these nonspecific symptoms, because of the subtle onset, because of some providers' sense of futility, and the requirement of special testing, oftentimes it may take us one to two years from the time a patient first notes the symptoms till we actually make a diagnosis of interstitial lung disease. And this is an area that we'd really like to improve to begin to understand how to find this diagnosis earlier. Breaking that down a little bit further, in a study that was published in 2019 for the risk factors for the delay, you can see that general factors include the patient sometimes not recognizing their own symptoms, but also showing up in the setting of a general practitioner or community hospital, this is often the time of delay to making that diagnosis. So how do we begin to think about recognizing interstitial lung disease or idiopathic pulmonary fibrosis? And so again, the key symptoms are either shortness of breath or a nonproductive cough. But breaking that down even further and really thinking about recognizing it, we need to be talking to our patients in a little more detail about their shortness of breath. So for example, the patient may not even recognize their own dyspnea because they forget about it the minute they sit down. But if we ask them, is that same walk that you take getting more difficult, or is it harder for you to climb a flight of stairs, do you find yourself looking for the elevator? Do you have more shortness of breath with your exertion in such a way that you've modified your life? Those are things that we can pick up to say, this is not a short time problem. This is a longer term chronic issue that the patient's been accommodating. Similarly, a cough, while it's very common to have a cough, a short term acute related to a upper respiratory infection, a viral infection, et cetera, a patient that has had a cough for three to six months that isn't going away, that's nonproductive, that's someone that needs to have further evaluation. And so when we hear about a patient with shortness of breath or with exertion or a nonproductive cough, subtle though it may be, we can look for some very specific findings to help us become more suspicious that an interstitial lung disease is present. I would say that the top finding that I think is very helpful for any provider is crackles in the lungs. And this is just a very simple finding that you can discover by doing your physical exam that we're all doing on our patients. The key is to recognize that the crackles are there and to act on them. And the other key is that these crackles frequently start at the very bottom of the lungs. So doing a thorough lung exam and listening to the bottom of the lungs, say the bottom of the rib cage down near the kidneys to pick up those subtle crackles will help us to recognize more patients who have interstitial lung disease as the cause of their symptoms. Other things we can do in the office include an exertional desaturation. So while a patient may look like they have normal saturation sitting in a chair, getting them up out of the chair, walking them around the office with a pulse oximeter can help us detect that a patient is desaturating and alert us to the fact that the patient has a process that is abnormal relating to their shortness of breath. Spirometry and a diffusion capacity, so doing pulmonary function testing can pick up restriction or an abnormal DLCO. And even though a high-resolution CT scan is our favored diagnostic tool, a chest X-ray can be a clue for us. So an abnormal chest X-ray that might have very subtle findings such as readings such as chronic changes or increased or prominent interstitial markings may be the first signal that a patient has an ILD or an IPF. So what are the tools we use? Once we sort of get in that arena that we suspected interstitial lung disease is there, well, I've alluded to some of these as I've been speaking, the first of which is a history. And our history is really focused on what could be that cause of the interstitial lung disease. So we talk to the patient about their family history. Because approximately 10 to 20% of these cases are genetic and the patient's able to identify another family member or two that have had pulmonary fibrosis or interstitial lung diseases. We ask them about their environmental exposures and we try to be relatively thorough about this, you know, asking them about what they do for work, what they do for hobbies, what they do for home. I think questionnaires are very helpful so that we can pick up things that we might forget to ask in our history and physical. So giving a patient a formal questionnaire to fill out can really help us identify environmental exposures. And then we ask them about connective tissue disease associated symptoms. For example, arthritis, dry eyes, dry mouth, looking for Sjogren's symptoms, rain nose, looking for mixed connective tissue disease or scleroderma, rashes, things of that nature. And these can help us identify a concomitant connective tissue disease related to their interstitial lung disease. A thorough physical exam is helpful, really with a focus on the lungs, as we talked about listening for those crackles, but also cardiac findings. Do we hear loud P2? Do we hear murmurs, things that might suspect concomitant pulmonary hypertension or concomitant heart disease? And then also looking at the hands and joints, skin for evidence of connective tissue disease. Radiology is a very key component, and although I won't go into great detail on the high-resolution CT scan findings, I will tell you that the high-resolution CT is the workhorse for the diagnosis of interstitial lung disease. And every patient that we're trying to characterize their interstitial lung disease, we want a high-resolution CT scan so that we can discover the pattern that's there. And that pattern goes into our rubric of understanding which interstitial lung disease is present. We obtain serologies to look for connective tissue disease, although even if we don't find findings of connective tissue disease in the history of the physical exam, oftentimes the lungs are the first manifestation of a connective tissue disease. So we want those serologies to see whether or not the patient has antibodies that would make us suspect that a connective tissue disease is present. And finally, in some cases we need pathology, we need tissue to help us shore up that diagnosis. And that pathology can be a VATS biopsy, a cryobiopsy, or we can even consider transbronchial biopsies for a genomic classifier, all of which are tools that can help us move to getting the correct diagnosis. So the diagnosis is multidisciplinary. We need a team to make that diagnosis. So we have a pulmonologist who is, as we talked about, is taking that history, getting those serologies, looking for medications or other causes of this, looking for environmental exposures to sort of break down where this interstitial lung disease could be coming from. We need a radiologist to review the high-resolution CT scan, which is the gold standard for the diagnosis of interstitial lung disease evaluation. If we see a UIP pattern, that is the hallmark pattern of IPF, but we have to take that into context with the pulmonologist and the history and the patient's story to make a diagnosis of IPF versus another interstitial lung disease. So again, not all UIP is IPF, but in order to have a diagnosis of IPF, a UIP pattern is necessary. And then as mentioned, occasionally we need that surgical lung biopsy that we can take into context with the high-resolution CT scan findings and the history to make a diagnosis. And so the gold standard for making a diagnosis in interstitial lung disease is that multidisciplinary team putting together all their collective knowledge to make a confident diagnosis. And this is reflected in the most common diagnostic algorithm published this past year for our new guidelines for the diagnosis of IPF, is that we look for the potential cause, we use the high-resolution CT scan, and we use this MDD or multidisciplinary discussion at various stages to make our confident diagnosis. So when we think about beyond idiopathic pulmonary fibrosis into all fibrotic lung diseases, we can use different ways to categorize this, including our interstitial lung disease tree here depicted on this slide. And while idiopathic pulmonary fibrosis or IPF is the most common form of idiopathic interstitial pneumonia, it is not the only progressive or fibrotic interstitial lung disease. And so we have to be aware that many of our patients will have a fibrotic lung disease that needs evaluation and treatment, and that will unfortunately progress. And so our work is really in trying to slow down that progression and treat them along the way with their chronic lung disease. And these diseases often have overlapping genetic pathophysiology and clinical features with each other, so that distinguishing them, as we talked about, is helpful, but also understanding that they can progress and we need further intervention. So IPF, as I mentioned, is the most common idiopathic interstitial pneumonia, and it is probably the most severe disease. So it's a chronic progressive fibrosing interstitial lung disease, and it has to be of an unknown cause. The name idiopathic implies unknown. So if we have a known reason for their disease, they don't have IPF, they have a different interstitial lung disease. And it's characterized by always progressive, worsening shortness of breath, worsening lung function over time. And before the arrival of our antifibrotics, which I will discuss, the mean survival is somewhere from three to five years. You can see from this graphic that patients have a variable disease progressive course, and so it's hard to predict for a patient what their specific pattern will be. Patients will sometimes be very rapid progressors, sometimes slow progressors, and frequently progress in steps, as depicted by some of these middle lines that you see here, where they maintain stability for a period of time, and then have these acute exacerbations where their lung function worsens. Despite all the different patterns, as I mentioned, the five-year survival is of somewhere between 20 to 40%. And I think it's important that we put this in perspective. When we think about diseases we fear such as cancers, the survival is actually worse in many of our than breast cancer, for example, very similar to lung cancer and similar to congestive heart failure. So this is a severe disease that is in desperate need of interventions to help improve patient's prognoses. But IPF is not the only interstitial lung disease that is progressive, and this graphic again comes from the guidelines that were published this past year. And you can see that, again, the distribution of interstitial lung diseases from the idiopathic, autoimmune, exposure-related, et cetera, which ones, the blue shading here shows the approximate percentage of patients that will progress with their interstitial lung disease. And as you can see, many, many interstitial lung diseases are fibrotic and are progressive. So we think about interstitial lung disease, IPF, as an incurable chronic progressive disease, but we have to remind ourselves that it's treatable. And we have many, many options of how to treat these patients, a multidisciplinary approach. I will discuss the antifibrotic therapies, perfenadone and Intenadib, but we also help patients by providing oxygen, providing pulmonary rehab, helping them manage other comorbidities such as smoking their weight, keeping them, you know, healthcare maintenance with vaccinations, providing support groups, clinical trials, lung transplant, et cetera. Now the antifibrotics were approved in 2014, and we've been using them since then. And they were approved based on these clinical trials that showed that they slow FEC decline by about 50%. And this is a very significant change for patients. If we think about slowing their FEC decline by 50%, we can think about them feeling better longer, needing, delaying their need for oxygen and being able to do their activities of daily living. So antifibrotics, while they're not curative, and while we don't see that the patient improves and the patients don't feel better, have a significant impact on the patient's disease trajectory. So when appropriate, we try to, we counsel our patients about the use of antifibrotics and employ them in the management of patients with interstitial lung diseases. Now perfenadone and Intenadib are approved for use in patients with IPF, and Intenadib is also approved for patients with progressive pulmonary fibrosis. We also can see that beyond the slowing the progression, we are finding that the use of antifibrotics improve patients' mortality. So in this large study from a US insurance database that included more than 8,000 patients, patients that were treated and that they were equally divided between antifibrotics and not antifibrotics, antifibrotic use was associated with a reduction in all-cause mortality during the first two years and also a decrease in the acute hospitalizations. And importantly, there was not a significant difference between which antifibrotic was used, but just the use of antifibrotics resulted in these impressive changes. So as we think about the management of fibrotic lung diseases, IPF and progressive fibrotic lung diseases, again, this graphic taken from the recent guidelines, we have many considerations, including the pharmacological considerations and Intenadib or perfenadone, the non-pharmacologic interventions, including oxygen and pulmonary rehab, management of comorbidities, many of which have effective interventions, including pulmonary hypertension, reflux, sleep apnea, and then symptom control. And as the patient is followed in our clinic, we have to keep an eye out for their progression. And so it's recommended that we obtain pulmonary function testing about every four to six months or sooner if the patient is experiencing clinical changes, approximately every year to get a high resolution CT scan, or when there's concern of clinical changes, consideration always of intercurrent problems such as pulmonary MLI. At present, we don't have great therapy for acute exacerbations, but corticosteroids are what we use. And then as patients progress, we think about either moving them towards lung transplant and or palliative care. And at all stages of this disease, we find that clinical trials are incredibly important so that we can continue to find new therapies for this disease. And just to finish, I just want to mention, we've been mentioning the comorbidities along the way, and there's many management strategies for the management of these comorbidities in pulmonary fibrosis, including pulmonary hypertension, for which we now have an approved therapy, Tyvazo. So it's important that we screen for pulmonary hypertension with ECHOs, BNP, and other strategies. GERD therapy is a subject of great controversy. There's mixed data on when and how to use antiacid therapy and the consideration of laparoscopic antireflux therapy. In general, if a patient has symptomatic GERD, we want to be treating that. Looking for cardiac disease in all patients with interstitial lung disease, and interestingly, the odds ratio for coronary artery disease is higher than standard mixed or matched populations. So coronary disease is present, and having a high suspicion for patients with dyspnea on exertion for the presence of coronary disease can be very valuable. Anticoagulation when necessary for pulmonary amyloid. Making sure that we're very careful treating patients for concomitant depression and anxiety, so we like to screen these patients, provide support groups, counseling, pulmonary rehab to help manage depression and anxiety, try to avoid deconditioning, again, pulmonary rehab and encouraging patients to be active, referring early for sleep apnea. We know that there's a higher incidence of sleep apnea in patients with interstitial lung diseases, so treating for this is important. We also know that patients have a poor clinical course if they are untreated for their sleep apnea, so we are aggressive about treating sleep apnea, detecting and treating, and then watching for lung cancer. And with that, I'll conclude, and thank you very much for spending your time with me now for this webinar. I'm certainly available to anyone that has questions, and I'm happy to help anytime. Thank you very much.

interstitial lung diseases

lung tissue

diagnosis

treatment

symptoms

clinical trials